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Sample records for base tumors analysis

  1. A survey of MRI-based medical image analysis for brain tumor studies

    Science.gov (United States)

    Bauer, Stefan; Wiest, Roland; Nolte, Lutz-P.; Reyes, Mauricio

    2013-07-01

    MRI-based medical image analysis for brain tumor studies is gaining attention in recent times due to an increased need for efficient and objective evaluation of large amounts of data. While the pioneering approaches applying automated methods for the analysis of brain tumor images date back almost two decades, the current methods are becoming more mature and coming closer to routine clinical application. This review aims to provide a comprehensive overview by giving a brief introduction to brain tumors and imaging of brain tumors first. Then, we review the state of the art in segmentation, registration and modeling related to tumor-bearing brain images with a focus on gliomas. The objective in the segmentation is outlining the tumor including its sub-compartments and surrounding tissues, while the main challenge in registration and modeling is the handling of morphological changes caused by the tumor. The qualities of different approaches are discussed with a focus on methods that can be applied on standard clinical imaging protocols. Finally, a critical assessment of the current state is performed and future developments and trends are addressed, giving special attention to recent developments in radiological tumor assessment guidelines.

  2. A survey of MRI-based medical image analysis for brain tumor studies

    International Nuclear Information System (INIS)

    Bauer, Stefan; Nolte, Lutz-P; Reyes, Mauricio; Wiest, Roland

    2013-01-01

    MRI-based medical image analysis for brain tumor studies is gaining attention in recent times due to an increased need for efficient and objective evaluation of large amounts of data. While the pioneering approaches applying automated methods for the analysis of brain tumor images date back almost two decades, the current methods are becoming more mature and coming closer to routine clinical application. This review aims to provide a comprehensive overview by giving a brief introduction to brain tumors and imaging of brain tumors first. Then, we review the state of the art in segmentation, registration and modeling related to tumor-bearing brain images with a focus on gliomas. The objective in the segmentation is outlining the tumor including its sub-compartments and surrounding tissues, while the main challenge in registration and modeling is the handling of morphological changes caused by the tumor. The qualities of different approaches are discussed with a focus on methods that can be applied on standard clinical imaging protocols. Finally, a critical assessment of the current state is performed and future developments and trends are addressed, giving special attention to recent developments in radiological tumor assessment guidelines. (topical review)

  3. Statistics-Based Prediction Analysis for Head and Neck Cancer Tumor Deformation

    Directory of Open Access Journals (Sweden)

    Maryam Azimi

    2012-01-01

    Full Text Available Most of the current radiation therapy planning systems, which are based on pre-treatment Computer Tomography (CT images, assume that the tumor geometry does not change during the course of treatment. However, tumor geometry is shown to be changing over time. We propose a methodology to monitor and predict daily size changes of head and neck cancer tumors during the entire radiation therapy period. Using collected patients' CT scan data, MATLAB routines are developed to quantify the progressive geometric changes occurring in patients during radiation therapy. Regression analysis is implemented to develop predictive models for tumor size changes through entire period. The generated models are validated using leave-one-out cross validation. The proposed method will increase the accuracy of therapy and improve patient's safety and quality of life by reducing the number of harmful unnecessary CT scans.

  4. Partial least squares based gene expression analysis in estrogen receptor positive and negative breast tumors.

    Science.gov (United States)

    Ma, W; Zhang, T-F; Lu, P; Lu, S H

    2014-01-01

    Breast cancer is categorized into two broad groups: estrogen receptor positive (ER+) and ER negative (ER-) groups. Previous study proposed that under trastuzumab-based neoadjuvant chemotherapy, tumor initiating cell (TIC) featured ER- tumors response better than ER+ tumors. Exploration of the molecular difference of these two groups may help developing new therapeutic strategies, especially for ER- patients. With gene expression profile from the Gene Expression Omnibus (GEO) database, we performed partial least squares (PLS) based analysis, which is more sensitive than common variance/regression analysis. We acquired 512 differentially expressed genes. Four pathways were found to be enriched with differentially expressed genes, involving immune system, metabolism and genetic information processing process. Network analysis identified five hub genes with degrees higher than 10, including APP, ESR1, SMAD3, HDAC2, and PRKAA1. Our findings provide new understanding for the molecular difference between TIC featured ER- and ER+ breast tumors with the hope offer supports for therapeutic studies.

  5. Facilitating in vivo tumor localization by principal component analysis based on dynamic fluorescence molecular imaging

    Science.gov (United States)

    Gao, Yang; Chen, Maomao; Wu, Junyu; Zhou, Yuan; Cai, Chuangjian; Wang, Daliang; Luo, Jianwen

    2017-09-01

    Fluorescence molecular imaging has been used to target tumors in mice with xenograft tumors. However, tumor imaging is largely distorted by the aggregation of fluorescent probes in the liver. A principal component analysis (PCA)-based strategy was applied on the in vivo dynamic fluorescence imaging results of three mice with xenograft tumors to facilitate tumor imaging, with the help of a tumor-specific fluorescent probe. Tumor-relevant features were extracted from the original images by PCA and represented by the principal component (PC) maps. The second principal component (PC2) map represented the tumor-related features, and the first principal component (PC1) map retained the original pharmacokinetic profiles, especially of the liver. The distribution patterns of the PC2 map of the tumor-bearing mice were in good agreement with the actual tumor location. The tumor-to-liver ratio and contrast-to-noise ratio were significantly higher on the PC2 map than on the original images, thus distinguishing the tumor from its nearby fluorescence noise of liver. The results suggest that the PC2 map could serve as a bioimaging marker to facilitate in vivo tumor localization, and dynamic fluorescence molecular imaging with PCA could be a valuable tool for future studies of in vivo tumor metabolism and progression.

  6. Skull base tumors

    International Nuclear Information System (INIS)

    Kikinis, R.; Matsumae, M.; Jolesz, F.A.; Black, P.M.; Cline, H.E.; Lorenson, W.E.

    1991-01-01

    This paper reports on an image processing procedure for the planning of surgery of skull base tumors that can extract bone, vessels, tumor, and brain parenchyma and that permits resolution of cranial nerves. Three-dimensional (3D) reconstructions were generated from double-echo long TR interleaved conventional spin-echo and fast-spin-echo MR imaging data. Sixteen cases have been analyzed preoperatively. Image processing consisted of a multistep procedure combining a supervised multivariate analysis with neighborhood operations such as connectivity and erosion/dilation. 3D renderings of anatomic structures of interest were then generated. Cases were evaluated preoperatively and manipulated interactively with the computer-generated images by a team consisting of neuroradiologists, neurosurgeons, and craniofacial surgeons. The preparation of 3D reconstructions required only a few hours and was performed mostly by a research assistant. The preoperative analysis of the 3D reconstructions was found to be a valuable tool, providing information complementing the surgeon's understanding of a case as derived from conventional imaging. The interactive manipulation of data proved to be a powerful way to evaluate alternative surgical approaches

  7. Primary tumor resection in metastatic breast cancer: A propensity-matched analysis, 1988-2011 SEER data base.

    Science.gov (United States)

    Vohra, Nasreen A; Brinkley, Jason; Kachare, Swapnil; Muzaffar, Mahvish

    2018-03-02

    Primary tumor resection (PTR) in metastatic breast cancer is not a standard treatment modality, and its impact on survival is conflicting. The primary objective of this study was to analyze impact of PTR on survival in metastatic patients with breast cancer. A retrospective study of metastatic patients with breast cancer was conducted using the 1988-2011 Surveillance, Epidemiology, and End Results (SEER) data base. Cox proportional hazards regression models were used to evaluate the relationship between PTR and survival and to adjust for the heterogeneity between the groups, and a propensity score-matched analysis was also performed. A total of 29 916 patients with metastatic breast cancer were included in the study, and 15 129 (51%) of patients underwent primary tumor resection, and 14 787 (49%) patients did not undergo surgery. Overall, decreasing trend in PTR for metastatic breast cancer in last decades was noted. Primary tumor resection was associated with a longer median OS (34 vs 18 months). In a propensity score-matched analysis, prognosis was also more favorable in the resected group (P = .0017). Primary tumor resection in metastatic breast cancer was associated with survival improvement, and the improvement persisted in propensity-matched analysis. © 2018 Wiley Periodicals, Inc.

  8. Phosphotyrosine-based-phosphoproteomics scaled-down to biopsy level for analysis of individual tumor biology and treatment selection.

    Science.gov (United States)

    Labots, Mariette; van der Mijn, Johannes C; Beekhof, Robin; Piersma, Sander R; de Goeij-de Haas, Richard R; Pham, Thang V; Knol, Jaco C; Dekker, Henk; van Grieken, Nicole C T; Verheul, Henk M W; Jiménez, Connie R

    2017-06-06

    Mass spectrometry-based phosphoproteomics of cancer cell and tissue lysates provides insight in aberrantly activated signaling pathways and potential drug targets. For improved understanding of individual patient's tumor biology and to allow selection of tyrosine kinase inhibitors in individual patients, phosphoproteomics of small clinical samples should be feasible and reproducible. We aimed to scale down a pTyr-phosphopeptide enrichment protocol to biopsy-level protein input and assess reproducibility and applicability to tumor needle biopsies. To this end, phosphopeptide immunoprecipitation using anti-phosphotyrosine beads was performed using 10, 5 and 1mg protein input from lysates of colorectal cancer (CRC) cell line HCT116. Multiple needle biopsies from 7 human CRC resection specimens were analyzed at the 1mg-level. The total number of phosphopeptides captured and detected by LC-MS/MS ranged from 681 at 10mg input to 471 at 1mg HCT116 protein. ID-reproducibility ranged from 60.5% at 10mg to 43.9% at 1mg. Per 1mg-level biopsy sample, >200 phosphopeptides were identified with 57% ID-reproducibility between paired tumor biopsies. Unsupervised analysis clustered biopsies from individual patients together and revealed known and potential therapeutic targets. This study demonstrates the feasibility of label-free pTyr-phosphoproteomics at the tumor biopsy level based on reproducible analyses using 1mg of protein input. The considerable number of identified phosphopeptides at this level is attributed to an effective down-scaled immuno-affinity protocol as well as to the application of ID propagation in the data processing and analysis steps. Unsupervised cluster analysis reveals patient-specific profiles. Together, these findings pave the way for clinical trials in which pTyr-phosphoproteomics will be performed on pre- and on-treatment biopsies. Such studies will improve our understanding of individual tumor biology and may enable future pTyr-phosphoproteomics-based

  9. Texture-Based Analysis of 100 MR Examinations of Head and Neck Tumors - Is It Possible to Discriminate Between Benign and Malignant Masses in a Multicenter Trial?

    Science.gov (United States)

    Fruehwald-Pallamar, J; Hesselink, J R; Mafee, M F; Holzer-Fruehwald, L; Czerny, C; Mayerhoefer, M E

    2016-02-01

    To evaluate whether texture-based analysis of standard MRI sequences can help in the discrimination between benign and malignant head and neck tumors. The MR images of 100 patients with a histologically clarified head or neck mass, from two different institutions, were analyzed. Texture-based analysis was performed using texture analysis software, with region of interest measurements for 2 D and 3 D evaluation independently for all axial sequences. COC, RUN, GRA, ARM, and WAV features were calculated for all ROIs. 10 texture feature subsets were used for a linear discriminant analysis, in combination with k-nearest-neighbor classification. Benign and malignant tumors were compared with regard to texture-based values. There were differences in the images from different field-strength scanners, as well as from different vendors. For the differentiation of benign and malignant tumors, we found differences on STIR and T2-weighted images for 2 D, and on contrast-enhanced T1-TSE with fat saturation for 3 D evaluation. In a separate analysis of the subgroups 1.5 and 3 Tesla, more discriminating features were found. Texture-based analysis is a useful tool in the discrimination of benign and malignant tumors when performed on one scanner with the same protocol. We cannot recommend this technique for the use of multicenter studies with clinical data. 2 D/3 D texture-based analysis can be performed in head and neck tumors. Texture-based analysis can differentiate between benign and malignant masses. Analyzed MR images should originate from one scanner with an identical protocol. © Georg Thieme Verlag KG Stuttgart · New York.

  10. Subtype differentiation of renal tumors using voxel-based histogram analysis of intravoxel incoherent motion parameters.

    Science.gov (United States)

    Gaing, Byron; Sigmund, Eric E; Huang, William C; Babb, James S; Parikh, Nainesh S; Stoffel, David; Chandarana, Hersh

    2015-03-01

    The aim of this study was to determine if voxel-based histogram analysis of intravoxel incoherent motion imaging (IVIM) parameters can differentiate various subtypes of renal tumors, including benign and malignant lesions. A total of 44 patients with renal tumors who underwent surgery and had histopathology available were included in this Health Insurance Portability and Accountability Act-compliant, institutional review board-approved, single-institution prospective study. In addition to routine renal magnetic resonance imaging examination performed on a 1.5-T system, all patients were imaged with axial diffusion-weighted imaging using 8 b values (range, 0-800 s/mm). A biexponential model was fitted to the diffusion signal data using a segmented algorithm to extract the IVIM parameters perfusion fraction (fp), tissue diffusivity (Dt), and pseudodiffusivity (Dp) for each voxel. Mean and histogram measures of heterogeneity (standard deviation, skewness, and kurtosis) of IVIM parameters were correlated with pathology results of tumor subtype using unequal variance t tests to compare subtypes in terms of each measure. Correction for multiple comparisons was accomplished using the Tukey honestly significant difference procedure. A total of 44 renal tumors including 23 clear cell (ccRCC), 4 papillary (pRCC), 5 chromophobe, and 5 cystic renal cell carcinomas, as well as benign lesions, 4 oncocytomas (Onc) and 3 angiomyolipomas (AMLs), were included in our analysis. Mean IVIM parameters fp and Dt differentiated 8 of 15 pairs of renal tumors. Histogram analysis of IVIM parameters differentiated 9 of 15 subtype pairs. One subtype pair (ccRCC vs pRCC) was differentiated by mean analysis but not by histogram analysis. However, 2 other subtype pairs (AML vs Onc and ccRCC vs Onc) were differentiated by histogram distribution parameters exclusively. The standard deviation of Dt [σ(Dt)] differentiated ccRCC (0.362 ± 0.136 × 10 mm/s) from AML (0.199 ± 0.043 × 10 mm/s) (P = 0

  11. Central nervous system tumors: a hospital based analysis

    International Nuclear Information System (INIS)

    Ayaz, B.; Lodhi, F.; Hasan, M.

    2011-01-01

    Objective: To assess the spectrum of CNS tumors and provide benchmark data for future studies assessing data in continuum. Patients and Methods: One hundred cases fulfilling the inclusion criteria were included between the ages of 1-85 years belonging to both genders. Results: Majority of the cases were seen in the year 2008 with the most commonly encountered lesion being the glial tumors followed by the meningiothelial neoplasms. Our findings were similar to previous similar studies in our setup with little change in trends. Conclusion: Glial tumors appear to be more common in our setup whereas the popularly believed Meningiothelial tumors though common came next. Our study can form the benchmark data upon which future studies can be conducted. (author)

  12. Paired Expression Analysis of Tumor Cell Surface Antigens

    Directory of Open Access Journals (Sweden)

    Rimas J. Orentas

    2017-08-01

    Full Text Available Adoptive immunotherapy with antibody-based therapy or with T cells transduced to express chimeric antigen receptors (CARs is useful to the extent that the cell surface membrane protein being targeted is not expressed on normal tissues. The most successful CAR-based (anti-CD19 or antibody-based therapy (anti-CD20 in hematologic malignancies has the side effect of eliminating the normal B cell compartment. Targeting solid tumors may not provide a similar expendable marker. Beyond antibody to Her2/NEU and EGFR, very few antibody-based and no CAR-based therapies have seen broad clinical application for solid tumors. To expand the way in which the surfaceome of solid tumors can be analyzed, we created an algorithm that defines the pairwise relative overexpression of surface antigens. This enables the development of specific immunotherapies that require the expression of two discrete antigens on the surface of the tumor target. This dyad analysis was facilitated by employing the Hotelling’s T-squared test (Hotelling–Lawley multivariate analysis of variance for two independent variables in comparison to a third constant entity (i.e., gene expression levels in normal tissues. We also present a unique consensus scoring mechanism for identifying transcripts that encode cell surface proteins. The unique application of our bioinformatics processing pipeline and statistical tools allowed us to compare the expression of two membrane protein targets as a pair, and to propose a new strategy based on implementing immunotherapies that require both antigens to be expressed on the tumor cell surface to trigger therapeutic effector mechanisms. Specifically, we found that, for MYCN amplified neuroblastoma, pairwise expression of ACVR2B or anaplastic lymphoma kinase (ALK with GFRA3, GFRA2, Cadherin 24, or with one another provided the strongest hits. For MYCN, non-amplified stage 4 neuroblastoma, neurotrophic tyrosine kinase 1, or ALK paired with GFRA2, GFRA3, SSK

  13. Texture-based classification of different gastric tumors at contrast-enhanced CT

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    Ba-Ssalamah, Ahmed, E-mail: ahmed.ba-ssalamah@meduniwien.ac.at [Department of Radiology, Medical University of Vienna (Austria); Muin, Dina; Schernthaner, Ruediger; Kulinna-Cosentini, Christiana; Bastati, Nina [Department of Radiology, Medical University of Vienna (Austria); Stift, Judith [Department of Pathology, Medical University of Vienna (Austria); Gore, Richard [Department of Radiology, University of Chicago Pritzker School of Medicine, Chicago, IL (United States); Mayerhoefer, Marius E. [Department of Radiology, Medical University of Vienna (Austria)

    2013-10-01

    Purpose: To determine the feasibility of texture analysis for the classification of gastric adenocarcinoma, lymphoma, and gastrointestinal stromal tumors on contrast-enhanced hydrodynamic-MDCT images. Materials and methods: The arterial phase scans of 47 patients with adenocarcinoma (AC) and a histologic tumor grade of [AC-G1, n = 4, G1, n = 4; AC-G2, n = 7; AC-G3, n = 16]; GIST, n = 15; and lymphoma, n = 5, and the venous phase scans of 48 patients with AC-G1, n = 3; AC-G2, n = 6; AC-G3, n = 14; GIST, n = 17; lymphoma, n = 8, were retrospectively reviewed. Based on regions of interest, texture analysis was performed, and features derived from the gray-level histogram, run-length and co-occurrence matrix, absolute gradient, autoregressive model, and wavelet transform were calculated. Fisher coefficients, probability of classification error, average correlation coefficients, and mutual information coefficients were used to create combinations of texture features that were optimized for tumor differentiation. Linear discriminant analysis in combination with a k-nearest neighbor classifier was used for tumor classification. Results: On arterial-phase scans, texture-based lesion classification was highly successful in differentiating between AC and lymphoma, and GIST and lymphoma, with misclassification rates of 3.1% and 0%, respectively. On venous-phase scans, texture-based classification was slightly less successful for AC vs. lymphoma (9.7% misclassification) and GIST vs. lymphoma (8% misclassification), but enabled the differentiation between AC and GIST (10% misclassification), and between the different grades of AC (4.4% misclassification). No texture feature combination was able to adequately distinguish between all three tumor types. Conclusion: Classification of different gastric tumors based on textural information may aid radiologists in establishing the correct diagnosis, at least in cases where the differential diagnosis can be narrowed down to two

  14. Texture-based classification of different gastric tumors at contrast-enhanced CT

    International Nuclear Information System (INIS)

    Ba-Ssalamah, Ahmed; Muin, Dina; Schernthaner, Ruediger; Kulinna-Cosentini, Christiana; Bastati, Nina; Stift, Judith; Gore, Richard; Mayerhoefer, Marius E.

    2013-01-01

    Purpose: To determine the feasibility of texture analysis for the classification of gastric adenocarcinoma, lymphoma, and gastrointestinal stromal tumors on contrast-enhanced hydrodynamic-MDCT images. Materials and methods: The arterial phase scans of 47 patients with adenocarcinoma (AC) and a histologic tumor grade of [AC-G1, n = 4, G1, n = 4; AC-G2, n = 7; AC-G3, n = 16]; GIST, n = 15; and lymphoma, n = 5, and the venous phase scans of 48 patients with AC-G1, n = 3; AC-G2, n = 6; AC-G3, n = 14; GIST, n = 17; lymphoma, n = 8, were retrospectively reviewed. Based on regions of interest, texture analysis was performed, and features derived from the gray-level histogram, run-length and co-occurrence matrix, absolute gradient, autoregressive model, and wavelet transform were calculated. Fisher coefficients, probability of classification error, average correlation coefficients, and mutual information coefficients were used to create combinations of texture features that were optimized for tumor differentiation. Linear discriminant analysis in combination with a k-nearest neighbor classifier was used for tumor classification. Results: On arterial-phase scans, texture-based lesion classification was highly successful in differentiating between AC and lymphoma, and GIST and lymphoma, with misclassification rates of 3.1% and 0%, respectively. On venous-phase scans, texture-based classification was slightly less successful for AC vs. lymphoma (9.7% misclassification) and GIST vs. lymphoma (8% misclassification), but enabled the differentiation between AC and GIST (10% misclassification), and between the different grades of AC (4.4% misclassification). No texture feature combination was able to adequately distinguish between all three tumor types. Conclusion: Classification of different gastric tumors based on textural information may aid radiologists in establishing the correct diagnosis, at least in cases where the differential diagnosis can be narrowed down to two

  15. Texture-based analysis of 100 MR examinations of head and neck tumors. Is it possible to discriminate between benign and malignant masses in a multicenter trial?

    International Nuclear Information System (INIS)

    Fruehwald-Pallamar, J.; Czerny, C.; Hesselink, J.R.; Mafee, M.F.; Holzer-Fruehwald, L.; Mayerhoefer, M.E.

    2016-01-01

    To evaluate whether texture-based analysis of standard MRI sequences can help in the discrimination between benign and malignant head and neck tumors. The MR images of 100 patients with a histologically clarified head or neck mass, from two different institutions, were analyzed. Texture-based analysis was performed using texture analysis software, with region of interest measurements for 2D and 3D evaluation independently for all axial sequences. COC, RUN, GRA, ARM, and WAV features were calculated for all ROIs. 10 texture feature subsets were used for a linear discriminant analysis, in combination with k-nearest-neighbor classification. Benign and malignant tumors were compared with regard to texture-based values. There were differences in the images from different field-strength scanners, as well as from different vendors. For the differentiation of benign and malignant tumors, we found differences on STIR and T2-weighted images for 2D, and on contrast-enhanced T1-TSE with fat saturation for 3D evaluation. In a separate analysis of the subgroups 1.5 and 3 Tesla, more discriminating features were found. Texture-based analysis is a useful tool in the discrimination of benign and malignant tumors when performed on one scanner with the same protocol. We cannot recommend this technique for the use of multicenter studies with clinical data.

  16. Texture-based analysis of 100 MR examinations of head and neck tumors. Is it possible to discriminate between benign and malignant masses in a multicenter trial?

    Energy Technology Data Exchange (ETDEWEB)

    Fruehwald-Pallamar, J.; Czerny, C. [Medical University of Vienna (Austria). Subdiv. of Neuroradiology and Musculoskeletal Radiology; Hesselink, J.R.; Mafee, M.F. [UCSD Medical Center, San Diego, CA (United States). Dept. of Radiology; Holzer-Fruehwald, L.; Mayerhoefer, M.E. [Medical University of Vienna (Austria). Dept. of Biomedical Imaging and Image-Guided Therapy

    2016-02-15

    To evaluate whether texture-based analysis of standard MRI sequences can help in the discrimination between benign and malignant head and neck tumors. The MR images of 100 patients with a histologically clarified head or neck mass, from two different institutions, were analyzed. Texture-based analysis was performed using texture analysis software, with region of interest measurements for 2D and 3D evaluation independently for all axial sequences. COC, RUN, GRA, ARM, and WAV features were calculated for all ROIs. 10 texture feature subsets were used for a linear discriminant analysis, in combination with k-nearest-neighbor classification. Benign and malignant tumors were compared with regard to texture-based values. There were differences in the images from different field-strength scanners, as well as from different vendors. For the differentiation of benign and malignant tumors, we found differences on STIR and T2-weighted images for 2D, and on contrast-enhanced T1-TSE with fat saturation for 3D evaluation. In a separate analysis of the subgroups 1.5 and 3 Tesla, more discriminating features were found. Texture-based analysis is a useful tool in the discrimination of benign and malignant tumors when performed on one scanner with the same protocol. We cannot recommend this technique for the use of multicenter studies with clinical data.

  17. Combined Scintigraphy and Tumor Marker Analysis Predicts Unfavorable Histopathology of Neuroblastic Tumors with High Accuracy.

    Directory of Open Access Journals (Sweden)

    Wolfgang Peter Fendler

    Full Text Available Our aim was to improve the prediction of unfavorable histopathology (UH in neuroblastic tumors through combined imaging and biochemical parameters.123I-MIBG SPECT and MRI was performed before surgical resection or biopsy in 47 consecutive pediatric patients with neuroblastic tumor. Semi-quantitative tumor-to-liver count-rate ratio (TLCRR, MRI tumor size and margins, urine catecholamine and NSE blood levels of neuron specific enolase (NSE were recorded. Accuracy of single and combined variables for prediction of UH was tested by ROC analysis with Bonferroni correction.34 of 47 patients had UH based on the International Neuroblastoma Pathology Classification (INPC. TLCRR and serum NSE both predicted UH with moderate accuracy. Optimal cut-off for TLCRR was 2.0, resulting in 68% sensitivity and 100% specificity (AUC-ROC 0.86, p < 0.001. Optimal cut-off for NSE was 25.8 ng/ml, resulting in 74% sensitivity and 85% specificity (AUC-ROC 0.81, p = 0.001. Combination of TLCRR/NSE criteria reduced false negative findings from 11/9 to only five, with improved sensitivity and specificity of 85% (AUC-ROC 0.85, p < 0.001.Strong 123I-MIBG uptake and high serum level of NSE were each predictive of UH. Combined analysis of both parameters improved the prediction of UH in patients with neuroblastic tumor. MRI parameters and urine catecholamine levels did not predict UH.

  18. Proton and carbon ion radiotherapy for primary brain tumors and tumors of the skull base

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    Combs, Stephanie E.; Kessel, Kerstin; Habermehl, Daniel; Debus, Jurgen [Univ. Hospital of Heidelberg, Dept. of Radiation Oncology, Heidelberg (Germany)], e-mail: Stephanie.Combs@med.uni-heidelberg.de; Haberer, Thomas [Heidelberger Ionenstrahl Therapiezentrum (HIT), Heidelberg (Germany); Jaekel, Oliver [Univ. Hospital of Heidelberg, Dept. of Radiation Oncology, Heidelberg (Germany); Heidelberger Ionenstrahl Therapiezentrum (HIT), Heidelberg (Germany)

    2013-10-15

    To analyze clinical concepts, toxicity and treatment outcome in patients with brain and skull base tumors treated with photons and particle therapy. Material and methods: In total 260 patients with brain tumors and tumors of the skull base were treated at the Heidelberg Ion Therapy Center (HIT). Patients enrolled in and randomized within prospective clinical trials as well as bony or soft tissue tumors are not included in this analysis. Treatment was delivered as protons, carbon ions, or combinations of photons and a carbon ion boost. All patients are included in a tight follow-up program. The median follow-up time is 12 months (range 2-39 months). Results: Main histologies included meningioma (n = 107) for skull base lesions, pituitary adenomas (n = 14), low-grade gliomas (n = 51) as well as high-grade gliomas (n = 55) for brain tumors. In all patients treatment could be completed without any unexpected severe toxicities. No side effects > CTC Grade III were observed. To date, no severe late toxicities were observed, however, for endpoints such as secondary malignancies or neuro cognitive side effects follow-up time still remains too short. Local recurrences were mainly seen in the group of high-grade gliomas or atypical meningiomas; for benign skull base meningiomas, to date, no recurrences were observed during follow-up. Conclusion: The specific benefit of particle therapy will potentially reduce the risk of secondary malignancies as well as improve neuro cognitive outcome and quality of life (QOL); thus, longer follow-up will be necessary to confirm these endpoints. Indication-specific trials on meningiomas and gliomas are underway to elucidate the role of protons and carbon ions in these indications.

  19. Proton and carbon ion radiotherapy for primary brain tumors and tumors of the skull base

    International Nuclear Information System (INIS)

    Combs, Stephanie E.; Kessel, Kerstin; Habermehl, Daniel; Debus, Jurgen; Haberer, Thomas; Jaekel, Oliver

    2013-01-01

    To analyze clinical concepts, toxicity and treatment outcome in patients with brain and skull base tumors treated with photons and particle therapy. Material and methods: In total 260 patients with brain tumors and tumors of the skull base were treated at the Heidelberg Ion Therapy Center (HIT). Patients enrolled in and randomized within prospective clinical trials as well as bony or soft tissue tumors are not included in this analysis. Treatment was delivered as protons, carbon ions, or combinations of photons and a carbon ion boost. All patients are included in a tight follow-up program. The median follow-up time is 12 months (range 2-39 months). Results: Main histologies included meningioma (n = 107) for skull base lesions, pituitary adenomas (n = 14), low-grade gliomas (n = 51) as well as high-grade gliomas (n = 55) for brain tumors. In all patients treatment could be completed without any unexpected severe toxicities. No side effects > CTC Grade III were observed. To date, no severe late toxicities were observed, however, for endpoints such as secondary malignancies or neuro cognitive side effects follow-up time still remains too short. Local recurrences were mainly seen in the group of high-grade gliomas or atypical meningiomas; for benign skull base meningiomas, to date, no recurrences were observed during follow-up. Conclusion: The specific benefit of particle therapy will potentially reduce the risk of secondary malignancies as well as improve neuro cognitive outcome and quality of life (QOL); thus, longer follow-up will be necessary to confirm these endpoints. Indication-specific trials on meningiomas and gliomas are underway to elucidate the role of protons and carbon ions in these indications

  20. Dielectrophoretic capture and genetic analysis of single neuroblastoma tumor cells

    Directory of Open Access Journals (Sweden)

    Erica L Carpenter

    2014-07-01

    Full Text Available Our understanding of the diversity of cells that escape the primary tumor and seed micrometastases remains rudimentary, and approaches for studying circulating and disseminated tumor cells have been limited by low throughput and sensitivity, reliance on single parameter sorting, and a focus on enumeration rather than phenotypic and genetic characterization. Here we utilize a highly sensitive microfluidic and dielectrophoretic approach for the isolation and genetic analysis of individual tumor cells. We employed fluorescence labeling to isolate 208 single cells from spiking experiments conducted with 11 cell lines, including 8 neuroblastoma cell lines, and achieved a capture sensitivity of 1 tumor cell per 106 white blood cells. Sample fixation or freezing had no detectable effect on cell capture. Point mutations were accurately detected in the whole genome amplification product of captured single tumor cells but not in negative control white blood cells. We applied this approach to capture 144 single tumor cells from 10 bone marrow samples from patients suffering from neuroblastoma. In this pediatric malignancy, high-risk patients often exhibit wide-spread hematogenous metastasis, but access to primary tumor can be difficult or impossible. Here we used flow-based sorting to pre-enrich samples with tumor involvement below 0.02%. For all patients for whom a mutation in the Anaplastic Lymphoma Kinase gene had already been detected in their primary tumor, the same mutation was detected in single cells from their marrow. These findings demonstrate a novel, non-invasive, and adaptable method for the capture and genetic analysis of single tumor cells from cancer patients.

  1. Analysis of the relationship between tumor dose inhomogeneity and local control in patients with skull base chordoma

    International Nuclear Information System (INIS)

    Terahara, Atsuro; Niemierko, Andrzej; Goitein, Michael; Finkelstein, Dianne; Hug, Eugen; Liebsch, Norbert; O'Farrell, Desmond; Lyons, Sue; Munzenrider, John

    1999-01-01

    Purpose: When irradiating a tumor that abuts or displaces any normal structures, the dose constraints to those structures (if lower than the prescribed dose) may cause dose inhomogeneity in the tumor volume at the tumor-critical structure interface. The low-dose region in the tumor volume may be one of the reasons for local failure. The aim of this study is to quantitate the effect of tumor dose inhomogeneity on local control and recurrence-free survival in patients with skull base chordoma. Methods and Materials: 132 patients with skull base chordoma were treated with combined photon and proton irradiation between 1978 and 1993. This study reviews 115 patients whose dose-volume data and follow-up data are available. The prescribed doses ranged from 66.6 Cobalt-Gray-Equivalent (CGE) to 79.2 CGE (median of 68.9 CGE). The dose to the optic structures (optic nerves and chiasma), the brain stem surface, and the brain stem center was limited to 60, 64, and 53 CGE, respectively. We used the dose-volume histogram data derived with the three-dimensional treatment planning system to evaluate several dose-volume parameters including the Equivalent Uniform Dose (EUD). We also analyzed several other patient and treatment factors in relation to local control and recurrence-free survival. Results: Local failure developed in 42 of 115 patients, with the actuarial local control rates at 5 and 10 years being 59% and 44%. Gender was a significant predictor for local control with the prognosis in males being significantly better than that in females (P 0.004, hazard ratio = 2.3). In a Cox univariate analysis, with stratification by gender, the significant predictors for local control (at the probability level of 0.05) were EUD, the target volume, the minimum dose, and the D 5cc dose. The prescribed dose, histology, age, the maximum dose, the mean dose, the median dose, the D 90% dose, and the overall treatment time were not significant factors. In a Cox multivariate analysis, the

  2. Automated Voxel-Based Analysis of Volumetric Dynamic Contrast-Enhanced CT Data Improves Measurement of Serial Changes in Tumor Vascular Biomarkers

    Energy Technology Data Exchange (ETDEWEB)

    Coolens, Catherine, E-mail: catherine.coolens@rmp.uhn.on.ca [Radiation Medicine Program, Princess Margaret Cancer Center and University Health Network, Toronto, Ontario (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario (Canada); Driscoll, Brandon [Radiation Medicine Program, Princess Margaret Cancer Center and University Health Network, Toronto, Ontario (Canada); Chung, Caroline [Radiation Medicine Program, Princess Margaret Cancer Center and University Health Network, Toronto, Ontario (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); Shek, Tina; Gorjizadeh, Alborz [Radiation Medicine Program, Princess Margaret Cancer Center and University Health Network, Toronto, Ontario (Canada); Ménard, Cynthia [Radiation Medicine Program, Princess Margaret Cancer Center and University Health Network, Toronto, Ontario (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); Jaffray, David [Radiation Medicine Program, Princess Margaret Cancer Center and University Health Network, Toronto, Ontario (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario (Canada)

    2015-01-01

    Objectives: Development of perfusion imaging as a biomarker requires more robust methodologies for quantification of tumor physiology that allow assessment of volumetric tumor heterogeneity over time. This study proposes a parametric method for automatically analyzing perfused tissue from volumetric dynamic contrast-enhanced (DCE) computed tomography (CT) scans and assesses whether this 4-dimensional (4D) DCE approach is more robust and accurate than conventional, region-of-interest (ROI)-based CT methods in quantifying tumor perfusion with preliminary evaluation in metastatic brain cancer. Methods and Materials: Functional parameter reproducibility and analysis of sensitivity to imaging resolution and arterial input function were evaluated in image sets acquired from a 320-slice CT with a controlled flow phantom and patients with brain metastases, whose treatments were planned for stereotactic radiation surgery and who consented to a research ethics board-approved prospective imaging biomarker study. A voxel-based temporal dynamic analysis (TDA) methodology was used at baseline, at day 7, and at day 20 after treatment. The ability to detect changes in kinetic parameter maps in clinical data sets was investigated for both 4D TDA and conventional 2D ROI-based analysis methods. Results: A total of 7 brain metastases in 3 patients were evaluated over the 3 time points. The 4D TDA method showed improved spatial efficacy and accuracy of perfusion parameters compared to ROI-based DCE analysis (P<.005), with a reproducibility error of less than 2% when tested with DCE phantom data. Clinically, changes in transfer constant from the blood plasma into the extracellular extravascular space (K{sub trans}) were seen when using TDA, with substantially smaller errors than the 2D method on both day 7 post radiation surgery (±13%; P<.05) and by day 20 (±12%; P<.04). Standard methods showed a decrease in K{sub trans} but with large uncertainty (111.6 ± 150.5) %. Conclusions

  3. Automated Voxel-Based Analysis of Volumetric Dynamic Contrast-Enhanced CT Data Improves Measurement of Serial Changes in Tumor Vascular Biomarkers

    International Nuclear Information System (INIS)

    Coolens, Catherine; Driscoll, Brandon; Chung, Caroline; Shek, Tina; Gorjizadeh, Alborz; Ménard, Cynthia; Jaffray, David

    2015-01-01

    Objectives: Development of perfusion imaging as a biomarker requires more robust methodologies for quantification of tumor physiology that allow assessment of volumetric tumor heterogeneity over time. This study proposes a parametric method for automatically analyzing perfused tissue from volumetric dynamic contrast-enhanced (DCE) computed tomography (CT) scans and assesses whether this 4-dimensional (4D) DCE approach is more robust and accurate than conventional, region-of-interest (ROI)-based CT methods in quantifying tumor perfusion with preliminary evaluation in metastatic brain cancer. Methods and Materials: Functional parameter reproducibility and analysis of sensitivity to imaging resolution and arterial input function were evaluated in image sets acquired from a 320-slice CT with a controlled flow phantom and patients with brain metastases, whose treatments were planned for stereotactic radiation surgery and who consented to a research ethics board-approved prospective imaging biomarker study. A voxel-based temporal dynamic analysis (TDA) methodology was used at baseline, at day 7, and at day 20 after treatment. The ability to detect changes in kinetic parameter maps in clinical data sets was investigated for both 4D TDA and conventional 2D ROI-based analysis methods. Results: A total of 7 brain metastases in 3 patients were evaluated over the 3 time points. The 4D TDA method showed improved spatial efficacy and accuracy of perfusion parameters compared to ROI-based DCE analysis (P<.005), with a reproducibility error of less than 2% when tested with DCE phantom data. Clinically, changes in transfer constant from the blood plasma into the extracellular extravascular space (K trans ) were seen when using TDA, with substantially smaller errors than the 2D method on both day 7 post radiation surgery (±13%; P<.05) and by day 20 (±12%; P<.04). Standard methods showed a decrease in K trans but with large uncertainty (111.6 ± 150.5) %. Conclusions: Parametric

  4. mRNA-based vaccines synergize with radiation therapy to eradicate established tumors

    International Nuclear Information System (INIS)

    Fotin-Mleczek, Mariola; Zanzinger, Kai; Heidenreich, Regina; Lorenz, Christina; Kowalczyk, Aleksandra; Kallen, Karl-Josef; Huber, Stephan M

    2014-01-01

    The eradication of large, established tumors by active immunotherapy is a major challenge because of the numerous cancer evasion mechanisms that exist. This study aimed to establish a novel combination therapy consisting of messenger RNA (mRNA)-based cancer vaccines and radiation, which would facilitate the effective treatment of established tumors with aggressive growth kinetics. The combination of a tumor-specific mRNA-based vaccination with radiation was tested in two syngeneic tumor models, a highly immunogenic E.G7-OVA and a low immunogenic Lewis lung cancer (LLC). The molecular mechanism induced by the combination therapy was evaluated via gene expression arrays as well as flow cytometry analyses of tumor infiltrating cells. In both tumor models we demonstrated that a combination of mRNA-based immunotherapy with radiation results in a strong synergistic anti-tumor effect. This was manifested as either complete tumor eradication or delay in tumor growth. Gene expression analysis of mouse tumors revealed a variety of substantial changes at the tumor site following radiation. Genes associated with antigen presentation, infiltration of immune cells, adhesion, and activation of the innate immune system were upregulated. A combination of radiation and immunotherapy induced significant downregulation of tumor associated factors and upregulation of tumor suppressors. Moreover, combination therapy significantly increased CD4 + , CD8 + and NKT cell infiltration of mouse tumors. Our data provide a scientific rationale for combining immunotherapy with radiation and provide a basis for the development of more potent anti-cancer therapies. The online version of this article (doi:10.1186/1748-717X-9-180) contains supplementary material, which is available to authorized users

  5. TU-D-207B-05: Intra-Tumor Partitioning and Texture Analysis of DCE-MRI Identifies Relevant Tumor Subregions to Predict Early Pathological Response of Breast Cancer to Neoadjuvant Chemotherapy

    International Nuclear Information System (INIS)

    Wu, J; Gong, G; Cui, Y; Li, R

    2016-01-01

    Purpose: To predict early pathological response of breast cancer to neoadjuvant chemotherapy (NAC) based on quantitative, multi-region analysis of dynamic contrast enhancement magnetic resonance imaging (DCE-MRI). Methods: In this institution review board-approved study, 35 patients diagnosed with stage II/III breast cancer were retrospectively investigated using DCE-MR images acquired before and after the first cycle of NAC. First, principal component analysis (PCA) was used to reduce the dimensionality of the DCE-MRI data with a high-temporal resolution. We then partitioned the whole tumor into multiple subregions using k-means clustering based on the PCA-defined eigenmaps. Within each tumor subregion, we extracted four quantitative Haralick texture features based on the gray-level co-occurrence matrix (GLCM). The change in texture features in each tumor subregion between pre- and during-NAC was used to predict pathological complete response after NAC. Results: Three tumor subregions were identified through clustering, each with distinct enhancement characteristics. In univariate analysis, all imaging predictors except one extracted from the tumor subregion associated with fast wash-out were statistically significant (p< 0.05) after correcting for multiple testing, with area under the ROC curve or AUCs between 0.75 and 0.80. In multivariate analysis, the proposed imaging predictors achieved an AUC of 0.79 (p = 0.002) in leave-one-out cross validation. This improved upon conventional imaging predictors such as tumor volume (AUC=0.53) and texture features based on whole-tumor analysis (AUC=0.65). Conclusion: The heterogeneity of the tumor subregion associated with fast wash-out on DCE-MRI predicted early pathological response to neoadjuvant chemotherapy in breast cancer.

  6. TU-D-207B-05: Intra-Tumor Partitioning and Texture Analysis of DCE-MRI Identifies Relevant Tumor Subregions to Predict Early Pathological Response of Breast Cancer to Neoadjuvant Chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Wu, J; Gong, G; Cui, Y; Li, R [Stanford University, Palo Alto, CA (United States)

    2016-06-15

    Purpose: To predict early pathological response of breast cancer to neoadjuvant chemotherapy (NAC) based on quantitative, multi-region analysis of dynamic contrast enhancement magnetic resonance imaging (DCE-MRI). Methods: In this institution review board-approved study, 35 patients diagnosed with stage II/III breast cancer were retrospectively investigated using DCE-MR images acquired before and after the first cycle of NAC. First, principal component analysis (PCA) was used to reduce the dimensionality of the DCE-MRI data with a high-temporal resolution. We then partitioned the whole tumor into multiple subregions using k-means clustering based on the PCA-defined eigenmaps. Within each tumor subregion, we extracted four quantitative Haralick texture features based on the gray-level co-occurrence matrix (GLCM). The change in texture features in each tumor subregion between pre- and during-NAC was used to predict pathological complete response after NAC. Results: Three tumor subregions were identified through clustering, each with distinct enhancement characteristics. In univariate analysis, all imaging predictors except one extracted from the tumor subregion associated with fast wash-out were statistically significant (p< 0.05) after correcting for multiple testing, with area under the ROC curve or AUCs between 0.75 and 0.80. In multivariate analysis, the proposed imaging predictors achieved an AUC of 0.79 (p = 0.002) in leave-one-out cross validation. This improved upon conventional imaging predictors such as tumor volume (AUC=0.53) and texture features based on whole-tumor analysis (AUC=0.65). Conclusion: The heterogeneity of the tumor subregion associated with fast wash-out on DCE-MRI predicted early pathological response to neoadjuvant chemotherapy in breast cancer.

  7. Nondestructive Analysis of Tumor-Associated Membrane Protein Integrating Imaging and Amplified Detection in situ Based on Dual-Labeled DNAzyme.

    Science.gov (United States)

    Chen, Xiaoxia; Zhao, Jing; Chen, Tianshu; Gao, Tao; Zhu, Xiaoli; Li, Genxi

    2018-01-01

    Comprehensive analysis of the expression level and location of tumor-associated membrane proteins (TMPs) is of vital importance for the profiling of tumor cells. Currently, two kinds of independent techniques, i.e. ex situ detection and in situ imaging, are usually required for the quantification and localization of TMPs respectively, resulting in some inevitable problems. Methods: Herein, based on a well-designed and fluorophore-labeled DNAzyme, we develop an integrated and facile method, in which imaging and quantification of TMPs in situ are achieved simultaneously in a single system. The labeled DNAzyme not only produces localized fluorescence for the visualization of TMPs but also catalyzes the cleavage of a substrate to produce quantitative fluorescent signals that can be collected from solution for the sensitive detection of TMPs. Results: Results from the DNAzyme-based in situ imaging and quantification of TMPs match well with traditional immunofluorescence and western blotting. In addition to the advantage of two-in-one, the DNAzyme-based method is highly sensitivity, allowing the detection of TMPs in only 100 cells. Moreover, the method is nondestructive. Cells after analysis could retain their physiological activity and could be cultured for other applications. Conclusion: The integrated system provides solid results for both imaging and quantification of TMPs, making it a competitive method over some traditional techniques for the analysis of TMPs, which offers potential application as a toolbox in the future.

  8. Quantitative CT analysis for the preoperative prediction of pathologic grade in pancreatic neuroendocrine tumors

    Science.gov (United States)

    Chakraborty, Jayasree; Pulvirenti, Alessandra; Yamashita, Rikiya; Midya, Abhishek; Gönen, Mithat; Klimstra, David S.; Reidy, Diane L.; Allen, Peter J.; Do, Richard K. G.; Simpson, Amber L.

    2018-02-01

    Pancreatic neuroendocrine tumors (PanNETs) account for approximately 5% of all pancreatic tumors, affecting one individual per million each year.1 PanNETs are difficult to treat due to biological variability from benign to highly malignant, indolent to very aggressive. The World Health Organization classifies PanNETs into three categories based on cell proliferative rate, usually detected using the Ki67 index and cell morphology: low-grade (G1), intermediate-grade (G2) and high-grade (G3) tumors. Knowledge of grade prior to treatment would select patients for optimal therapy: G1/G2 tumors respond well to somatostatin analogs and targeted or cytotoxic drugs whereas G3 tumors would be targeted with platinum or alkylating agents.2, 3 Grade assessment is based on the pathologic examination of the surgical specimen, biopsy or ne-needle aspiration; however, heterogeneity in the proliferative index can lead to sampling errors.4 Based on studies relating qualitatively assessed shape and enhancement characteristics on CT imaging to tumor grade in PanNET,5 we propose objective classification of PanNET grade with quantitative analysis of CT images. Fifty-five patients were included in our retrospective analysis. A pathologist graded the tumors. Texture and shape-based features were extracted from CT. Random forest and naive Bayes classifiers were compared for the classification of G1/G2 and G3 PanNETs. The best area under the receiver operating characteristic curve (AUC) of 0:74 and accuracy of 71:64% was achieved with texture features. The shape-based features achieved an AUC of 0:70 and accuracy of 78:73%.

  9. A simple method for detecting tumor in T2-weighted MRI brain images. An image-based analysis

    International Nuclear Information System (INIS)

    Lau, Phooi-Yee; Ozawa, Shinji

    2006-01-01

    The objective of this paper is to present a decision support system which uses a computer-based procedure to detect tumor blocks or lesions in digitized medical images. The authors developed a simple method with a low computation effort to detect tumors on T2-weighted Magnetic Resonance Imaging (MRI) brain images, focusing on the connection between the spatial pixel value and tumor properties from four different perspectives: cases having minuscule differences between two images using a fixed block-based method, tumor shape and size using the edge and binary images, tumor properties based on texture values using spatial pixel intensity distribution controlled by a global discriminate value, and the occurrence of content-specific tumor pixel for threshold images. Measurements of the following medical datasets were performed: different time interval images, and different brain disease images on single and multiple slice images. Experimental results have revealed that our proposed technique incurred an overall error smaller than those in other proposed methods. In particular, the proposed method allowed decrements of false alarm and missed alarm errors, which demonstrate the effectiveness of our proposed technique. In this paper, we also present a prototype system, known as PCB, to evaluate the performance of the proposed methods by actual experiments, comparing the detection accuracy and system performance. (author)

  10. Association between tumor-stroma ratio and prognosis in solid tumor patients: a systematic review and meta-analysis.

    Science.gov (United States)

    Wu, Jiayuan; Liang, Caixia; Chen, Manyu; Su, Wenmei

    2016-10-18

    Tumor-related stroma plays an active role in tumor invasion and metastasis. The tumor-stroma ratio (TSR) in the pathologic specimen has drawn increasing attention from the field of predicting tumor prognosis. However, the prognostic value of TSR in solid tumors necessitates further elucidation. We conducted a meta-analysis on 14 studies with 4238 patients through a comprehensive electronic search on databases updated on May 2016 to explore the relationship between TSR and prognosis of solid tumors. The overall hazard ratio showed that rich stroma in tumor tissue was associated with poor overall survival (OS) (14 studies, 4238 patients) and disease-free survival (DFS) (9 studies, 2235 patients) of patients with solid tumors. The effect of low TSR on poor OS was observed among various cancer types, but not in the early stage of cervical caner. A significant relationship between low TSR and poor OS was also observed in the subgroup analyses based on study region, blinding status, and Newcastle-Ottawa Scale (NOS) score. Subgroup analyses indicated that cancer type, clinical stage, study region, blinding status, and NOS score did not affect the prognostic value of TSR for DFS. Moreover, low TSR was significantly correlated with the serious clinical stage, advanced depth of invasion, and positive lymph node metastasis. These findings indicate that a high proportion of stroma in cancer tissue is associated with poor clinical outcomes in cancer patients, and TSR may serve as an independent prognostic factor for solid tumors.

  11. CHONDROID SKULL BASE TUMORS (A REVIEW OF LITERATURE

    Directory of Open Access Journals (Sweden)

    T. G. Gasparyan

    2012-01-01

    Full Text Available Chondroid skull base tumors are a rare and little studied pathology; many problems of their classification, diagnosis and treatment remain to be solved. This group of neoplasms is referred to as bone tumors arising from the cartilaginous tissue of the skull base bones, particularly from the bones formed during chondral osteogenesis. The paper details the clinical picture, X-ray and morphological diagnosis of chondroid tumors. Particular attention is given to surgery and radiotherapy for this category of tumors.

  12. Quantitative image analysis of cellular heterogeneity in breast tumors complements genomic profiling.

    Science.gov (United States)

    Yuan, Yinyin; Failmezger, Henrik; Rueda, Oscar M; Ali, H Raza; Gräf, Stefan; Chin, Suet-Feung; Schwarz, Roland F; Curtis, Christina; Dunning, Mark J; Bardwell, Helen; Johnson, Nicola; Doyle, Sarah; Turashvili, Gulisa; Provenzano, Elena; Aparicio, Sam; Caldas, Carlos; Markowetz, Florian

    2012-10-24

    Solid tumors are heterogeneous tissues composed of a mixture of cancer and normal cells, which complicates the interpretation of their molecular profiles. Furthermore, tissue architecture is generally not reflected in molecular assays, rendering this rich information underused. To address these challenges, we developed a computational approach based on standard hematoxylin and eosin-stained tissue sections and demonstrated its power in a discovery and validation cohort of 323 and 241 breast tumors, respectively. To deconvolute cellular heterogeneity and detect subtle genomic aberrations, we introduced an algorithm based on tumor cellularity to increase the comparability of copy number profiles between samples. We next devised a predictor for survival in estrogen receptor-negative breast cancer that integrated both image-based and gene expression analyses and significantly outperformed classifiers that use single data types, such as microarray expression signatures. Image processing also allowed us to describe and validate an independent prognostic factor based on quantitative analysis of spatial patterns between stromal cells, which are not detectable by molecular assays. Our quantitative, image-based method could benefit any large-scale cancer study by refining and complementing molecular assays of tumor samples.

  13. Avoiding Pitfalls in the Statistical Analysis of Heterogeneous Tumors

    Directory of Open Access Journals (Sweden)

    Judith-Anne W. Chapman

    2009-01-01

    Full Text Available Information about tumors is usually obtained from a single assessment of a tumor sample, performed at some point in the course of the development and progression of the tumor, with patient characteristics being surrogates for natural history context. Differences between cells within individual tumors (intratumor heterogeneity and between tumors of different patients (intertumor heterogeneity may mean that a small sample is not representative of the tumor as a whole, particularly for solid tumors which are the focus of this paper. This issue is of increasing importance as high-throughput technologies generate large multi-feature data sets in the areas of genomics, proteomics, and image analysis. Three potential pitfalls in statistical analysis are discussed (sampling, cut-points, and validation and suggestions are made about how to avoid these pitfalls.

  14. Radiosurgery of Glomus Jugulare Tumors: A Meta-Analysis

    International Nuclear Information System (INIS)

    Guss, Zachary D.; Batra, Sachin; Limb, Charles J.; Li, Gordon; Sughrue, Michael E.; Redmond, Kristin; Rigamonti, Daniele; Parsa, Andrew T.; Chang, Steven; Kleinberg, Lawrence; Lim, Michael

    2011-01-01

    Purpose: During the past two decades, radiosurgery has arisen as a promising approach to the management of glomus jugulare. In the present study, we report on a systematic review and meta-analysis of the available published data on the radiosurgical management of glomus jugulare tumors. Methods and Materials: To identify eligible studies, systematic searches of all glomus jugulare tumors treated with radiosurgery were conducted in major scientific publication databases. The data search yielded 19 studies, which were included in the meta-analysis. The data from 335 glomus jugulare patients were extracted. The fixed effects pooled proportions were calculated from the data when Cochrane's statistic was statistically insignificant and the inconsistency among studies was 36 months. In these studies, 95% of patients achieved clinical control and 96% achieved tumor control. The gamma knife, linear accelerator, and CyberKnife technologies all exhibited high rates of tumor and clinical control. Conclusions: The present study reports the results of a meta-analysis for the radiosurgical management of glomus jugulare. Because of its high effectiveness, we suggest considering radiosurgery for the primary management of glomus jugulare tumors.

  15. Regression of uveal malignant melanomas following cobalt-60 plaque. Correlates between acoustic spectrum analysis and tumor regression

    International Nuclear Information System (INIS)

    Coleman, D.J.; Lizzi, F.L.; Silverman, R.H.; Ellsworth, R.M.; Haik, B.G.; Abramson, D.H.; Smith, M.E.; Rondeau, M.J.

    1985-01-01

    Parameters derived from computer analysis of digital radio-frequency (rf) ultrasound scan data of untreated uveal malignant melanomas were examined for correlations with tumor regression following cobalt-60 plaque. Parameters included tumor height, normalized power spectrum and acoustic tissue type (ATT). Acoustic tissue type was based upon discriminant analysis of tumor power spectra, with spectra of tumors of known pathology serving as a model. Results showed ATT to be correlated with tumor regression during the first 18 months following treatment. Tumors with ATT associated with spindle cell malignant melanoma showed over twice the percentage reduction in height as those with ATT associated with mixed/epithelioid melanomas. Pre-treatment height was only weakly correlated with regression. Additionally, significant spectral changes were observed following treatment. Ultrasonic spectrum analysis thus provides a noninvasive tool for classification, prediction and monitoring of tumor response to cobalt-60 plaque

  16. Therapeutic Implications from Sensitivity Analysis of Tumor Angiogenesis Models

    Science.gov (United States)

    Poleszczuk, Jan; Hahnfeldt, Philip; Enderling, Heiko

    2015-01-01

    Anti-angiogenic cancer treatments induce tumor starvation and regression by targeting the tumor vasculature that delivers oxygen and nutrients. Mathematical models prove valuable tools to study the proof-of-concept, efficacy and underlying mechanisms of such treatment approaches. The effects of parameter value uncertainties for two models of tumor development under angiogenic signaling and anti-angiogenic treatment are studied. Data fitting is performed to compare predictions of both models and to obtain nominal parameter values for sensitivity analysis. Sensitivity analysis reveals that the success of different cancer treatments depends on tumor size and tumor intrinsic parameters. In particular, we show that tumors with ample vascular support can be successfully targeted with conventional cytotoxic treatments. On the other hand, tumors with curtailed vascular support are not limited by their growth rate and therefore interruption of neovascularization emerges as the most promising treatment target. PMID:25785600

  17. Theranostic GO-based nanohybrid for tumor induced imaging and potential combinational tumor therapy.

    Science.gov (United States)

    Qin, Si-Yong; Feng, Jun; Rong, Lei; Jia, Hui-Zhen; Chen, Si; Liu, Xiang-Ji; Luo, Guo-Feng; Zhuo, Ren-Xi; Zhang, Xian-Zheng

    2014-02-12

    Graphene oxide (GO)-based theranostic nanohybrid is designed for tumor induced imaging and potential combinational tumor therapy. The anti-tumor drug, Doxorubicin (DOX) is chemically conjugated to the poly(ethylenimine)-co-poly(ethylene glycol) (PEI-PEG) grafted GO via a MMP2-cleavable PLGLAG peptide linkage. The therapeutic efficacy of DOX is chemically locked and its intrinsic fluorescence is quenched by GO under normal physiological condition. Once stimulated by the MMP2 enzyme over-expressed in tumor tissues, the resulting peptide cleavage permits the unloading of DOX for tumor therapy and concurrent fluorescence recovery of DOX for in situ tumor cell imaging. Attractively, this PEI-bearing nanohybrid can mediate efficient DNA transfection and shows great potential for combinational drug/gene therapy. This tumor induced imaging and potential combinational therapy will open a window for tumor treatment by offering a unique theranostic approach through merging the diagnostic capability and pathology-responsive therapeutic function. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. DCE-MRI texture analysis with tumor subregion partitioning for predicting Ki-67 status of estrogen receptor-positive breast cancers

    KAUST Repository

    Fan, Ming

    2017-12-08

    Breast tumor heterogeneity is related to risk factors that lead to worse prognosis, yet such heterogeneity has not been well studied.To predict the Ki-67 status of estrogen receptor (ER)-positive breast cancer patients via analysis of tumor heterogeneity with subgroup identification based on patterns of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).Retrospective study.Seventy-seven breast cancer patients with ER-positive breast cancer were investigated, of whom 51 had low Ki-67 expression.T1 -weighted 3.0T DCE-MR images.Each tumor was partitioned into multiple subregions using three methods based on patterns of dynamic enhancement: 1) time to peak (TTP), 2) peak enhancement rate (PER), and 3) kinetic pattern clustering (KPC). In each tumor subregion, 18 texture features were computed.Univariate and multivariate logistic regression analyses were performed using a leave-one-out-based cross-validation (LOOCV) method. The partitioning results were compared with the same feature extraction methods across the whole tumor.In the univariate analysis, the best-performing feature was the texture statistic of sum variance in the tumor subregion with early TTP for differentiating between patients with high and low Ki-67 expression (area under the receiver operating characteristic curves, AUC = 0.748). Multivariate analysis showed that features from the tumor subregion associated with early TTP yielded the highest performance (AUC = 0.807) among the subregions for predicting the Ki-67 status. Among all regions, the tumor area with high PER at a precontrast MR image achieved the highest performance (AUC = 0.722), while the subregion that exhibited the highest overall enhancement rate based on KPC had an AUC of 0.731. These three models based on intratumoral texture analysis significantly (P < 0.01) outperformed the model using features from the whole tumor (AUC = 0.59).Texture analysis of intratumoral heterogeneity has the potential to serve as a valuable

  19. Tumor type resulting in upgrade: An analysis based on 333 low grade soft tissue sarcoma

    Directory of Open Access Journals (Sweden)

    Langer, Stefan

    2014-11-01

    Full Text Available [english] Introduction: Soft tissue sarcomas (STS are rare tumors. Based on histopathological criteria, three grades are distinguished from low (G1 to intermediate (G2 and high grade (G3. After complete initial surgical resection, some G1 STS recur as lesions with an upgrade of a previous G1 STS to a recurrent G2 STS. This upgrade indicates higher malignancy of the STS. Our aim was to find possible risk factors for these upgrades including age, localization of tumor and tumor type. Methods: This retrospective case-control study evaluated 333 patients. Of these 333, 54.7% were male and 45.3% female. All patients underwent R0 resections and among these, 10% subsequently upgraded. The processed data include age, gender, tumor type, tumor localization, local recurrence and upgrade. Results: Patients with upgrades have a higher mean age of 5.5 years than our reference collective. The tumor type has a significant effect on upgrades. Patients with fibrosarcomas are at a threefold risk of an upgrade compared to patients with other G1 STS.Conclusion: Our results indicate that age and tumor type play a key role in upgrades in G1 STS. Patients, age 60 and above and diagnosed with G1 fibrosarcomas, are three times as likely to upgrade compared to patients younger than 60 with other G1 STS. We discuss the significance of these risk factors and whether aside from complete tumor resection, additional therapies (e.g. irradiation may be applied to improve therapeutic outcome.

  20. Correcting for catchment area nonresidency in studies based on tumor-registry data

    International Nuclear Information System (INIS)

    Sposto, R.; Preston, D.L.

    1993-05-01

    We discuss the effect of catchment area nonresidency on estimates of cancer incidence from a tumor-registry-based cohort study and demonstrate that a relatively simple correction is possible in the context of Poisson regression analysis if individual residency histories or the probabilities of residency are known. A comparison of a complete data maximum likelihood analysis with several Poisson regression analyses demonstrates the adequacy of the simple correction in a large simulated data set. We compare analyses of stomach-cancer incidence from the Radiation Effects Research Foundation tumor registry with and without the correction. We also discuss some implications of including cases identified only on the basis of death certificates. (author)

  1. Mid-Ventilation Concept for Mobile Pulmonary Tumors: Internal Tumor Trajectory Versus Selective Reconstruction of Four-Dimensional Computed Tomography Frames Based on External Breathing Motion

    International Nuclear Information System (INIS)

    Guckenberger, Matthias; Wilbert, Juergen; Krieger, Thomas; Richter, Anne; Baier, Kurt; Flentje, Michael

    2009-01-01

    Purpose: To evaluate the accuracy of direct reconstruction of mid-ventilation and peak-phase four-dimensional (4D) computed tomography (CT) frames based on the external breathing signal. Methods and Materials: For 11 patients with 15 pulmonary targets, a respiration-correlated CT study (4D CT) was acquired for treatment planning. After retrospective time-based sorting of raw projection data and reconstruction of eight CT frames equally distributed over the breathing cycle, mean tumor position (P mean ), mid-ventilation frame, and breathing motion were evaluated based on the internal tumor trajectory. Analysis of the external breathing signal (pressure sensor around abdomen) with amplitude-based sorting of projections was performed for direct reconstruction of the mid-ventilation frame and frames at peak phases of the breathing cycle. Results: On the basis of the eight 4D CT frames equally spaced in time, tumor motion was largest in the craniocaudal direction, with 12 ± 7 mm on average. Tumor motion between the two frames reconstructed at peak phases was not different in the craniocaudal and anterior-posterior directions but was systematically smaller in the left-right direction by 1 mm on average. The 3-dimensional distance between P mean and the tumor position in the mid-ventilation frame based on the internal tumor trajectory was 1.2 ± 1 mm. Reconstruction of the mid-ventilation frame at the mean amplitude position of the external breathing signal resulted in tumor positions 2.0 ± 1.1 mm distant from P mean . Breathing-induced motion artifacts in mid-ventilation frames caused negligible changes in tumor volume and shape. Conclusions: Direct reconstruction of the mid-ventilation frame and frames at peak phases based on the external breathing signal was reliable. This makes the reconstruction of only three 4D CT frames sufficient for application of the mid-ventilation technique in clinical practice.

  2. Analysis of Factors Related to Hypopituitarism in Patients with Nonsellar Intracranial Tumor.

    Science.gov (United States)

    Lu, Song-Song; Gu, Jian-Jun; Luo, Xiao-Hong; Zhang, Jian-He; Wang, Shou-Sen

    2017-09-01

    Previous studies have suggested that postoperative hypopituitarism in patients with nonsellar intracranial tumors is caused by traumatic surgery. However, with development of minimally invasive and precise neurosurgical techniques, the degree of injury to brain tissue has been reduced significantly, especially for parenchymal tumors. Therefore, understanding preexisting hypopituitarism and related risk factors can improve perioperative management for patients with nonsellar intracranial tumors. Chart data were collected retrospectively from 83 patients with nonsellar intracranial tumors admitted to our hospital from May 2014 to April 2015. Pituitary function of each subject was determined based on results of preoperative serum pituitary hormone analysis. Univariate and multivariate logistic regression methods were used to analyze relationships between preoperative hypopituitarism and factors including age, sex, history of hypertension and secondary epilepsy, course of disease, tumor mass effect, site of tumor, intracranial pressure (ICP), cerebrospinal fluid content, and pituitary morphology. A total of 30 patients (36.14%) presented with preoperative hypopituitarism in either 1 axis or multiple axes; 23 (27.71%) were affected in 1 axis, and 7 (8.43%) were affected in multiple axes. Univariate analysis showed that risk factors for preoperative hypopituitarism in patients with a nonsellar intracranial tumor include an acute or subacute course (≤3 months), intracranial hypertension (ICP >200 mm H 2 O), and mass effect (P hypopituitarism in patients with nonsellar intracranial tumors (P hypopituitarism is high in patients with nonsellar intracranial tumors. The occurrence of hypopituitarism is correlated with factors including an acute or subacute course (≤3 months), intracranial hypertension (ICP >200 mm H 2 O), and mass effect (P hypopituitarism. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Pathway Relevance Ranking for Tumor Samples through Network-Based Data Integration.

    Directory of Open Access Journals (Sweden)

    Lieven P C Verbeke

    Full Text Available The study of cancer, a highly heterogeneous disease with different causes and clinical outcomes, requires a multi-angle approach and the collection of large multi-omics datasets that, ideally, should be analyzed simultaneously. We present a new pathway relevance ranking method that is able to prioritize pathways according to the information contained in any combination of tumor related omics datasets. Key to the method is the conversion of all available data into a single comprehensive network representation containing not only genes but also individual patient samples. Additionally, all data are linked through a network of previously identified molecular interactions. We demonstrate the performance of the new method by applying it to breast and ovarian cancer datasets from The Cancer Genome Atlas. By integrating gene expression, copy number, mutation and methylation data, the method's potential to identify key pathways involved in breast cancer development shared by different molecular subtypes is illustrated. Interestingly, certain pathways were ranked equally important for different subtypes, even when the underlying (epi-genetic disturbances were diverse. Next to prioritizing universally high-scoring pathways, the pathway ranking method was able to identify subtype-specific pathways. Often the score of a pathway could not be motivated by a single mutation, copy number or methylation alteration, but rather by a combination of genetic and epi-genetic disturbances, stressing the need for a network-based data integration approach. The analysis of ovarian tumors, as a function of survival-based subtypes, demonstrated the method's ability to correctly identify key pathways, irrespective of tumor subtype. A differential analysis of survival-based subtypes revealed several pathways with higher importance for the bad-outcome patient group than for the good-outcome patient group. Many of the pathways exhibiting higher importance for the bad

  4. Clinicopathological Analysis of Factors Related to Colorectal Tumor Perforation

    OpenAIRE

    Medina-Arana, Vicente; Martínez-Riera, Antonio; Delgado-Plasencia, Luciano; Rodríguez-González, Diana; Bravo-Gutiérrez, Alberto; Álvarez-Argüelles, Hugo; Alarcó-Hernández, Antonio; Salido-Ruiz, Eduardo; Fernández-Peralta, Antonia M.; González-Aguilera, Juan J.

    2015-01-01

    Abstract Colorectal tumor perforation is a life-threatening complication of this disease. However, little is known about the anatomopathological factors or pathophysiologic mechanisms involved. Pathological and immunohistochemical analysis of factors related with tumoral neo-angiogenesis, which could influence tumor perforation are assessed in this study. A retrospective study of patients with perforated colon tumors (Group P) and T4a nonperforated (controls) was conducted between 2001 and 20...

  5. Proton therapy for tumors of the skull base

    Energy Technology Data Exchange (ETDEWEB)

    Munzenrider, J.E.; Liebsch, N.J. [Dept. of Radiation Oncology, Harvard Univ. Medical School, Boston, MA (United States)

    1999-06-01

    Charged particle beams are ideal for treating skull base and cervical spine tumors: dose can be focused in the target, while achieving significant sparing of the brain, brain stem, cervical cord, and optic nerves and chiasm. For skull base tumors, 10-year local control rates with combined proton-photon therapy are highest for chondrosarcomas, intermediate for male chordomas, and lowest for female chordomas (94%, 65%, and 42%, respectively). For cervical spine tumors, 10-year local control rates are not significantly different for chordomas and chondrosarcomas (54% and 48%, respectively), nor is there any difference in local control between males and females. Observed treatment-related morbidity has been judged acceptable, in view of the major morbidity and mortality which accompany uncontrolled tumor growth. (orig.)

  6. Proton therapy for tumors of the skull base

    International Nuclear Information System (INIS)

    Munzenrider, J.E.; Liebsch, N.J.

    1999-01-01

    Charged particle beams are ideal for treating skull base and cervical spine tumors: dose can be focused in the target, while achieving significant sparing of the brain, brain stem, cervical cord, and optic nerves and chiasm. For skull base tumors, 10-year local control rates with combined proton-photon therapy are highest for chondrosarcomas, intermediate for male chordomas, and lowest for female chordomas (94%, 65%, and 42%, respectively). For cervical spine tumors, 10-year local control rates are not significantly different for chordomas and chondrosarcomas (54% and 48%, respectively), nor is there any difference in local control between males and females. Observed treatment-related morbidity has been judged acceptable, in view of the major morbidity and mortality which accompany uncontrolled tumor growth. (orig.)

  7. Real-time PCR analysis of genes encoding tumor antigens in esophageal tumors and a cancer vaccine

    DEFF Research Database (Denmark)

    Weinert, Brian T; Krishnadath, Kausilia K; Milano, Francesca

    2009-01-01

    Tumor antigens are the primary target of therapeutic cancer vaccines. We set out to define and compare the expression pattern of tumor antigen genes in esophagus carcinoma biopsies and in an allogeneic tumor lysate-based cancer vaccine, MelCancerVac. Cells used for vaccine production were treated...... in the production of the vaccine. Quantitative PCR was used to assay 74 tumor antigen genes in patients with squamous cell carcinoma of the esophagus. 81% (13/16) of tumors expressed more than five cancer/testis (CT) antigens. A total of 96 genes were assayed in the tumor cell clone (DDM1.7) used to make tumor cell...

  8. Quantitative image analysis of intra-tumoral bFGF level as a molecular marker of paclitaxel resistance

    Directory of Open Access Journals (Sweden)

    Wientjes M Guillaume

    2008-01-01

    Full Text Available Abstract Background The role of basic fibroblast growth factor (bFGF in chemoresistance is controversial; some studies showed a relationship between higher bFGF level and chemoresistance while other studies showed the opposite finding. The goal of the present study was to quantify bFGF levels in archived tumor tissues, and to determine its relationship with chemosensitivity. Methods We established an image analysis-based method to quantify and convert the immunostaining intensity of intra-tumor bFGF to concentrations; this was accomplished by generating standard curves using human xenograft tumors as the renewable tissue source for simultaneous image analysis and ELISA. The relationships between bFGF concentrations and tumor chemosensitivity of patient tumors (n = 87 to paclitaxel were evaluated using linear regression analysis. Results The image analysis results were compared to our previous results obtained using a conventional, semi-quantitative visual scoring method. While both analyses indicated an inverse relationship between bFGF level and tumor sensitivity to paclitaxel, the image analysis method, by providing bFGF levels in individual tumors and therefore more data points (87 numerical values as opposed to four groups of staining intensities, further enabled the quantitative analysis of the relationship in subgroups of tumors with different pathobiological properties. The results show significant correlation between bFGF level and tumor sensitivity to the antiproliferation effect, but not the apoptotic effect, of paclitaxel. We further found stronger correlations of bFGF level and paclitaxel sensitivity in four tumor subgroups (high stage, positive p53 staining, negative aFGF staining, containing higher-than-median bFGF level, compared to all other groups. These findings suggest that the relationship between intra-tumoral bFGF level and paclitaxel sensitivity was context-dependent, which may explain the previous contradictory findings

  9. Real-time PCR analysis of genes encoding tumor antigens in esophageal tumors and a cancer vaccine

    NARCIS (Netherlands)

    Weinert, Brian T.; Krishnadath, Kausilia K.; Milano, Francesca; Pedersen, Ayako W.; Claesson, Mogens H.; Zocca, Mai-Britt

    2009-01-01

    Tumor antigens are the primary target of therapeutic cancer vaccines. We set out to define and compare the expression pattern of tumor antigen genes in esophagus carcinoma biopsies and in an allogeneic tumor lysate-based cancer vaccine, MelCancerVac. Cells used for vaccine production were treated

  10. Photoacoustic imaging to assess pixel-based sO2 distributions in experimental prostate tumors

    Science.gov (United States)

    Bendinger, Alina L.; Glowa, Christin; Peter, Jörg; Karger, Christian P.

    2018-03-01

    A protocol for photoacoustic imaging (PAI) has been developed to assess pixel-based oxygen saturation (sO2) distributions of experimental tumor models. The protocol was applied to evaluate the dependence of PAI results on measurement settings, reproducibility of PAI, and for the characterization of the oxygenation status of experimental prostate tumor sublines (Dunning R3327-H, -HI, -AT1) implanted subcutaneously in male Copenhagen rats. The three-dimensional (3-D) PA data employing two wavelengths were used to estimate sO2 distributions. If the PA signal was sufficiently strong, the distributions were independent from signal gain, threshold, and positioning of animals. Reproducibility of sO2 distributions with respect to shape and median values was demonstrated over several days. The three tumor sublines were characterized by the shapes of their sO2 distributions and their temporal response after external changes of the oxygen supply (100% O2 or air breathing and clamping of tumor-supplying artery). The established protocol showed to be suitable for detecting temporal changes in tumor oxygenation as well as differences in oxygenation between tumor sublines. PA results were in accordance with histology for hypoxia, perfusion, and vasculature. The presented protocol for the assessment of pixel-based sO2 distributions provides more detailed information as compared to conventional region-of-interest-based analysis of PAI, especially with respect to the detection of temporal changes and tumor heterogeneity.

  11. Photoacoustic imaging to assess pixel-based sO2 distributions in experimental prostate tumors.

    Science.gov (United States)

    Bendinger, Alina L; Glowa, Christin; Peter, Jörg; Karger, Christian P

    2018-03-01

    A protocol for photoacoustic imaging (PAI) has been developed to assess pixel-based oxygen saturation (sO2) distributions of experimental tumor models. The protocol was applied to evaluate the dependence of PAI results on measurement settings, reproducibility of PAI, and for the characterization of the oxygenation status of experimental prostate tumor sublines (Dunning R3327-H, -HI, -AT1) implanted subcutaneously in male Copenhagen rats. The three-dimensional (3-D) PA data employing two wavelengths were used to estimate sO2 distributions. If the PA signal was sufficiently strong, the distributions were independent from signal gain, threshold, and positioning of animals. Reproducibility of sO2 distributions with respect to shape and median values was demonstrated over several days. The three tumor sublines were characterized by the shapes of their sO2 distributions and their temporal response after external changes of the oxygen supply (100% O2 or air breathing and clamping of tumor-supplying artery). The established protocol showed to be suitable for detecting temporal changes in tumor oxygenation as well as differences in oxygenation between tumor sublines. PA results were in accordance with histology for hypoxia, perfusion, and vasculature. The presented protocol for the assessment of pixel-based sO2 distributions provides more detailed information as compared to conventional region-of-interest-based analysis of PAI, especially with respect to the detection of temporal changes and tumor heterogeneity. (2018) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

  12. Ultrasound-based tumor movement compensation during navigated laparoscopic liver interventions.

    Science.gov (United States)

    Shahin, Osama; Beširević, Armin; Kleemann, Markus; Schlaefer, Alexander

    2014-05-01

    Image-guided navigation aims to provide better orientation and accuracy in laparoscopic interventions. However, the ability of the navigation system to reflect anatomical changes and maintain high accuracy during the procedure is crucial. This is particularly challenging in soft organs such as the liver, where surgical manipulation causes significant tumor movements. We propose a fast approach to obtain an accurate estimation of the tumor position throughout the procedure. Initially, a three-dimensional (3D) ultrasound image is reconstructed and the tumor is segmented. During surgery, the position of the tumor is updated based on newly acquired tracked ultrasound images. The initial segmentation of the tumor is used to automatically detect the tumor and update its position in the navigation system. Two experiments were conducted. First, a controlled phantom motion using a robot was performed to validate the tracking accuracy. Second, a needle navigation scenario based on pseudotumors injected into ex vivo porcine liver was studied. In the robot-based evaluation, the approach estimated the target location with an accuracy of 0.4 ± 0.3 mm. The mean navigation error in the needle experiment was 1.2 ± 0.6 mm, and the algorithm compensated for tumor shifts up to 38 mm in an average time of 1 s. We demonstrated a navigation approach based on tracked laparoscopic ultrasound (LUS), and focused on the neighborhood of the tumor. Our experimental results indicate that this approach can be used to quickly and accurately compensate for tumor movements caused by surgical manipulation during laparoscopic interventions. The proposed approach has the advantage of being based on the routinely used LUS; however, it upgrades its functionality to estimate the tumor position in 3D. Hence, the approach is repeatable throughout surgery, and enables high navigation accuracy to be maintained.

  13. Diagnostic Performance of Mammographic Texture Analysis in the Differential Diagnosis of Benign and Malignant Breast Tumors.

    Science.gov (United States)

    Li, Zhiming; Yu, Lan; Wang, Xin; Yu, Haiyang; Gao, Yuanxiang; Ren, Yande; Wang, Gang; Zhou, Xiaoming

    2017-11-09

    The purpose of this study was to investigate the diagnostic performance of mammographic texture analysis in the differential diagnosis of benign and malignant breast tumors. Digital mammography images were obtained from the Picture Archiving and Communication System at our institute. Texture features of mammographic images were calculated. Mann-Whitney U test was used to identify differences between the benign and malignant group. The receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic performance of texture features. Significant differences of texture features of histogram, gray-level co-occurrence matrix (GLCM) and run length matrix (RLM) were found between the benign and malignant breast group (P  .05). The AUROCs of imaging-based diagnosis, texture analysis, and imaging-based diagnosis combined with texture analysis were 0.873, 0.863, and 0.961, respectively. When imaging-based diagnosis was combined with texture analysis, the AUROC was higher than that of imaging-based diagnosis or texture analysis (P benign and malignant breast tumors. Furthermore, the combination of imaging-based diagnosis and texture analysis can significantly improve diagnostic performance. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Pancreatic tumor detection using hypericin-based fluorescence spectroscopy and cytology

    Science.gov (United States)

    Lavu, Harish; Geary, Kevin; Fetterman, Harold R.; Saxton, Romaine E.

    2005-04-01

    Hypericin is a novel, highly fluorescent photosensitizer that exhibits selective tumor cell uptake properties and is particularly resistant to photobleaching. In this study, we have characterized hypericin uptake in human pancreatic tumor cells with relation to incubation time, cell number, and drug concentration. Ex vivo hypericin based fluorescence spectroscopy was performed to detect the presence of MIA PaCa-2 pancreatic tumor cells in the peritoneal cavity of BALB/c nude mice, as well as to quantify gross tumor burden. Hypericin based cytology of peritoneal lavage samples, using both one and two photon laser confocal microscopy, demonstrated more than a two-fold increase in fluorescence emission of pancreatic tumor cells as compared to control samples. In vitro treatment of pancreatic cancer cells with hypericin based photodynamic therapy showed tumor cell cytotoxicity in a drug dose, incident laser power, and time dependent manner. For these experiments, a continuous wavelength solid-state laser source (532 nm) was operated at power levels in the range of 100-400 mW. Potential applications of hypericin in tumor diagnosis, staging, and therapy will be presented.

  15. Assessment of tumor heterogeneity by CT texture analysis: Can the largest cross-sectional area be used as an alternative to whole tumor analysis?

    International Nuclear Information System (INIS)

    Ng, Francesca; Kozarski, Robert; Ganeshan, Balaji; Goh, Vicky

    2013-01-01

    Objective: To determine if there is a difference between contrast enhanced CT texture features from the largest cross-sectional area versus the whole tumor, and its effect on clinical outcome prediction. Methods: Entropy (E) and uniformity (U) were derived for different filter values (1.0–2.5: fine to coarse textures) for the largest primary tumor cross-sectional area and the whole tumor of the staging contrast enhanced CT in 55 patients with primary colorectal cancer. Parameters were compared using non-parametric Wilcoxon test. Kaplan–Meier analysis was performed to determine the relationship between CT texture and 5-year overall survival. Results: E was higher and U lower for the whole tumor indicating greater heterogeneity at all filter levels (1.0–2.5): median (range) for E and U for whole tumor versus largest cross-sectional area of 7.89 (7.43–8.31) versus 7.62 (6.94–8.08) and 0.005 (0.004–0.01) versus 0.006 (0.005–0.01) for filter 1.0; 7.88 (7.22–8.48) versus 7.54 (6.86–8.1) and 0.005 (0.003–0.01) versus 0.007 (0.004–0.01) for filter 1.5; 7.88 (7.17–8.54) versus 7.48 (5.84–8.25) and 0.005 (0.003–0.01) versus 0.007 (0.004–0.02) for filter 2.0; and 7.83 (7.03–8.57) versus 7.42 (5.19–8.26) and 0.005 (0.003–0.01) versus 0.006 (0.004–0.03) for filter 2.5 respectively (p ≤ 0.001). Kaplan–Meier analysis demonstrated better separation of E and U for whole tumor analysis for 5-year overall survival. Conclusion: Whole tumor analysis appears more representative of tumor heterogeneity

  16. Automated lung tumor segmentation for whole body PET volume based on novel downhill region growing

    Science.gov (United States)

    Ballangan, Cherry; Wang, Xiuying; Eberl, Stefan; Fulham, Michael; Feng, Dagan

    2010-03-01

    We propose an automated lung tumor segmentation method for whole body PET images based on a novel downhill region growing (DRG) technique, which regards homogeneous tumor hotspots as 3D monotonically decreasing functions. The method has three major steps: thoracic slice extraction with K-means clustering of the slice features; hotspot segmentation with DRG; and decision tree analysis based hotspot classification. To overcome the common problem of leakage into adjacent hotspots in automated lung tumor segmentation, DRG employs the tumors' SUV monotonicity features. DRG also uses gradient magnitude of tumors' SUV to improve tumor boundary definition. We used 14 PET volumes from patients with primary NSCLC for validation. The thoracic region extraction step achieved good and consistent results for all patients despite marked differences in size and shape of the lungs and the presence of large tumors. The DRG technique was able to avoid the problem of leakage into adjacent hotspots and produced a volumetric overlap fraction of 0.61 +/- 0.13 which outperformed four other methods where the overlap fraction varied from 0.40 +/- 0.24 to 0.59 +/- 0.14. Of the 18 tumors in 14 NSCLC studies, 15 lesions were classified correctly, 2 were false negative and 15 were false positive.

  17. Frequency filtering based analysis on the cardiac induced lung tumor motion and its impact on the radiotherapy management

    International Nuclear Information System (INIS)

    Chen, Ting; Qin, Songbing; Xu, Xiaoting; Jabbour, Salma K.; Haffty, Bruce G.; Yue, Ning J.

    2014-01-01

    Purpose/objectives: Lung tumor motion may be impacted by heartbeat in addition to respiration. This study seeks to quantitatively analyze heart-motion-induced tumor motion and to evaluate its impact on lung cancer radiotherapy. Methods/materials: Fluoroscopy images were acquired for 30 lung cancer patients. Tumor, diaphragm, and heart were delineated on selected fluoroscopy frames, and their motion was tracked and converted into temporal signals based on deformable registration propagation. The clinical relevance of heart impact was evaluated using the dose volumetric histogram of the redefined target volumes. Results: Correlation was found between tumor and cardiac motion for 23 patients. The heart-induced motion amplitude ranged from 0.2 to 2.6 mm. The ratio between heart-induced tumor motion and the tumor motion was inversely proportional to the amplitude of overall tumor motion. When the heart motion impact was integrated, there was an average 9% increase in internal target volumes for 17 patients. Dose coverage decrease was observed on redefined planning target volume in simulated SBRT plans. Conclusions: The tumor motion of thoracic cancer patients is influenced by both heart and respiratory motion. The cardiac impact is relatively more significant for tumor with less motion, which may lead to clinically significant uncertainty in radiotherapy for some patients

  18. Computer-aided breast MR image feature analysis for prediction of tumor response to chemotherapy

    International Nuclear Information System (INIS)

    Aghaei, Faranak; Tan, Maxine; Liu, Hong; Zheng, Bin; Hollingsworth, Alan B.; Qian, Wei

    2015-01-01

    Purpose: To identify a new clinical marker based on quantitative kinetic image features analysis and assess its feasibility to predict tumor response to neoadjuvant chemotherapy. Methods: The authors assembled a dataset involving breast MR images acquired from 68 cancer patients before undergoing neoadjuvant chemotherapy. Among them, 25 patients had complete response (CR) and 43 had partial and nonresponse (NR) to chemotherapy based on the response evaluation criteria in solid tumors. The authors developed a computer-aided detection scheme to segment breast areas and tumors depicted on the breast MR images and computed a total of 39 kinetic image features from both tumor and background parenchymal enhancement regions. The authors then applied and tested two approaches to classify between CR and NR cases. The first one analyzed each individual feature and applied a simple feature fusion method that combines classification results from multiple features. The second approach tested an attribute selected classifier that integrates an artificial neural network (ANN) with a wrapper subset evaluator, which was optimized using a leave-one-case-out validation method. Results: In the pool of 39 features, 10 yielded relatively higher classification performance with the areas under receiver operating characteristic curves (AUCs) ranging from 0.61 to 0.78 to classify between CR and NR cases. Using a feature fusion method, the maximum AUC = 0.85 ± 0.05. Using the ANN-based classifier, AUC value significantly increased to 0.96 ± 0.03 (p < 0.01). Conclusions: This study demonstrated that quantitative analysis of kinetic image features computed from breast MR images acquired prechemotherapy has potential to generate a useful clinical marker in predicting tumor response to chemotherapy

  19. Computer-aided breast MR image feature analysis for prediction of tumor response to chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Aghaei, Faranak; Tan, Maxine; Liu, Hong; Zheng, Bin, E-mail: Bin.Zheng-1@ou.edu [School of Electrical and Computer Engineering, University of Oklahoma, Norman, Oklahoma 73019 (United States); Hollingsworth, Alan B. [Mercy Women’s Center, Mercy Health Center, Oklahoma City, Oklahoma 73120 (United States); Qian, Wei [Department of Electrical and Computer Engineering, University of Texas, El Paso, Texas 79968 (United States)

    2015-11-15

    Purpose: To identify a new clinical marker based on quantitative kinetic image features analysis and assess its feasibility to predict tumor response to neoadjuvant chemotherapy. Methods: The authors assembled a dataset involving breast MR images acquired from 68 cancer patients before undergoing neoadjuvant chemotherapy. Among them, 25 patients had complete response (CR) and 43 had partial and nonresponse (NR) to chemotherapy based on the response evaluation criteria in solid tumors. The authors developed a computer-aided detection scheme to segment breast areas and tumors depicted on the breast MR images and computed a total of 39 kinetic image features from both tumor and background parenchymal enhancement regions. The authors then applied and tested two approaches to classify between CR and NR cases. The first one analyzed each individual feature and applied a simple feature fusion method that combines classification results from multiple features. The second approach tested an attribute selected classifier that integrates an artificial neural network (ANN) with a wrapper subset evaluator, which was optimized using a leave-one-case-out validation method. Results: In the pool of 39 features, 10 yielded relatively higher classification performance with the areas under receiver operating characteristic curves (AUCs) ranging from 0.61 to 0.78 to classify between CR and NR cases. Using a feature fusion method, the maximum AUC = 0.85 ± 0.05. Using the ANN-based classifier, AUC value significantly increased to 0.96 ± 0.03 (p < 0.01). Conclusions: This study demonstrated that quantitative analysis of kinetic image features computed from breast MR images acquired prechemotherapy has potential to generate a useful clinical marker in predicting tumor response to chemotherapy.

  20. Treatment Analysis in a Cancer Stem Cell Context Using a Tumor Growth Model Based on Cellular Automata.

    Science.gov (United States)

    Monteagudo, Ángel; Santos, José

    2015-01-01

    Cancer can be viewed as an emergent behavior in terms of complex system theory and artificial life, Cellular Automata (CA) being the tool most used for studying and characterizing the emergent behavior. Different approaches with CA models were used to model cancer growth. The use of the abstract model of acquired cancer hallmarks permits the direct modeling at cellular level, where a cellular automaton defines the mitotic and apoptotic behavior of cells, and allows for an analysis of different dynamics of the cellular system depending on the presence of the different hallmarks. A CA model based on the presence of hallmarks in the cells, which includes a simulation of the behavior of Cancer Stem Cells (CSC) and their implications for the resultant growth behavior of the multicellular system, was employed. This modeling of cancer growth, in the avascular phase, was employed to analyze the effect of cancer treatments in a cancer stem cell context. The model clearly explains why, after treatment against non-stem cancer cells, the regrowth capability of CSCs generates a faster regrowth of tumor behavior, and also shows that a continuous low-intensity treatment does not favor CSC proliferation and differentiation, thereby allowing an unproblematic control of future tumor regrowth. The analysis performed indicates that, contrary to the current attempts at CSC control, trying to make CSC proliferation more difficult is an important point to consider, especially in the immediate period after a standard treatment for controlling non-stem cancer cell proliferation.

  1. Advances in establishment and analysis of three-dimensional tumor spheroid-based functional assays for target validation and drug evaluation

    Directory of Open Access Journals (Sweden)

    Vinci Maria

    2012-03-01

    Full Text Available Abstract Background There is overwhelming evidence that in vitro three-dimensional tumor cell cultures more accurately reflect the complex in vivo microenvironment than simple two-dimensional cell monolayers, not least with respect to gene expression profiles, signaling pathway activity and drug sensitivity. However, most currently available three-dimensional techniques are time consuming and/or lack reproducibility; thus standardized and rapid protocols are urgently needed. Results To address this requirement, we have developed a versatile toolkit of reproducible three-dimensional tumor spheroid models for dynamic, automated, quantitative imaging and analysis that are compatible with routine high-throughput preclinical studies. Not only do these microplate methods measure three-dimensional tumor growth, but they have also been significantly enhanced to facilitate a range of functional assays exemplifying additional key hallmarks of cancer, namely cell motility and matrix invasion. Moreover, mutual tissue invasion and angiogenesis is accommodated by coculturing tumor spheroids with murine embryoid bodies within which angiogenic differentiation occurs. Highly malignant human tumor cells were selected to exemplify therapeutic effects of three specific molecularly-targeted agents: PI-103 (phosphatidylinositol-3-kinase (PI3K-mammalian target of rapamycin (mTOR inhibitor, 17-N-allylamino-17-demethoxygeldanamycin (17-AAG (heat shock protein 90 (HSP90 inhibitor and CCT130234 (in-house phospholipase C (PLCγ inhibitor. Fully automated analysis using a Celigo cytometer was validated for tumor spheroid growth and invasion against standard image analysis techniques, with excellent reproducibility and significantly increased throughput. In addition, we discovered key differential sensitivities to targeted agents between two-dimensional and three-dimensional cultures, and also demonstrated enhanced potency of some agents against cell migration

  2. Solid KHT tumor dispersal for flow cytometric cell kinetic analysis

    International Nuclear Information System (INIS)

    Pallavicini, M.G.; Folstad, L.J.; Dunbar, C.

    1981-01-01

    A bacterial neutral protease was used to disperse KHT solid tumors into single cell suspensions suitable for routine cell kinetic analysis by flow cytometry and for clonogenic cell survival. Neutral protease disaggregation under conditions which would be suitable for routine tumor dispersal was compared with a trypsin/DNase procedure. Cell yield, clonogenic cell survival, DNA distributions of untreated and drug-perturbed tumors, rates of radioactive precursor incorporation during the cell cycle, and preferential cell cycle phase-specific cell loss were investigated. Tumors dispersed with neutral protease yielded approximately four times more cells than those dispersed with trypsin/DNase and approximately a 1.5-fold higher plating efficiency in a semisolid agar system. Quantitative analysis of DNA distributions obtained from untreated and cytosine-arabinoside-perturbed tumors produced similar results with both dispersal procedures. The rates of incorporation of tritiated thymidine during the cell cycle were also similar with neutral protease and trypsin/DNase dispersal. Preferential phase-specific cell loss was not obseved with either technique. We find that neutral protease provides good single cell suspensions of the KHT tumor for cell survival measurements and for cell kinetic analysis of drug-induced perturbations by flow cytometry. In addition, the high cell yields facilitate electronic cell sorting where large numbers of cells are often required

  3. Multi-Parametric MRI and Texture Analysis to Visualize Spatial Histologic Heterogeneity and Tumor Extent in Glioblastoma.

    Directory of Open Access Journals (Sweden)

    Leland S Hu

    Full Text Available Genetic profiling represents the future of neuro-oncology but suffers from inadequate biopsies in heterogeneous tumors like Glioblastoma (GBM. Contrast-enhanced MRI (CE-MRI targets enhancing core (ENH but yields adequate tumor in only ~60% of cases. Further, CE-MRI poorly localizes infiltrative tumor within surrounding non-enhancing parenchyma, or brain-around-tumor (BAT, despite the importance of characterizing this tumor segment, which universally recurs. In this study, we use multiple texture analysis and machine learning (ML algorithms to analyze multi-parametric MRI, and produce new images indicating tumor-rich targets in GBM.We recruited primary GBM patients undergoing image-guided biopsies and acquired pre-operative MRI: CE-MRI, Dynamic-Susceptibility-weighted-Contrast-enhanced-MRI, and Diffusion Tensor Imaging. Following image coregistration and region of interest placement at biopsy locations, we compared MRI metrics and regional texture with histologic diagnoses of high- vs low-tumor content (≥80% vs <80% tumor nuclei for corresponding samples. In a training set, we used three texture analysis algorithms and three ML methods to identify MRI-texture features that optimized model accuracy to distinguish tumor content. We confirmed model accuracy in a separate validation set.We collected 82 biopsies from 18 GBMs throughout ENH and BAT. The MRI-based model achieved 85% cross-validated accuracy to diagnose high- vs low-tumor in the training set (60 biopsies, 11 patients. The model achieved 81.8% accuracy in the validation set (22 biopsies, 7 patients.Multi-parametric MRI and texture analysis can help characterize and visualize GBM's spatial histologic heterogeneity to identify regional tumor-rich biopsy targets.

  4. Birth weight and risk of childhood solid tumors in Brazil: a record linkage between population-based data sets.

    Science.gov (United States)

    de Paula Silva, Neimar; de Souza Reis, Rejane; Cunha, Rafael Garcia; Oliveira, Julio Fernando; da Silva de Lima, Fernanda Cristina; Pombo-de-Oliveira, Maria Socorro; Santos, Marceli Oliveira; de Camargo, Beatriz

    2017-04-20

    To analyze the relationship between the development of childhood solid tumors and 1) birth weight and 2) fetal growth, using two Brazilian population-based data sets. A case-cohort study was performed using two population-based data sets, and linkage between the Live Birth Information System (Sistema de Informação sobre Nascidos Vivos, SINASC) and 14 population-based cancer registries (PBCRs) was established. Four controls per case were chosen randomly from the SINASC data set. Tumors were classified as central nervous system (CNS), non-CNS embryonal, and other tumors ("miscellaneous"). Adjustments were made for potential confounders (maternal age, mode of delivery, maternal education, birth order, gestational age, sex, and geographic region). Odds ratios (ORs) with 95% confidence intervals (CIs) were computed using unconditional logistic regression analysis. In a trend analysis, for every 500 g of additional birth weight, the crude OR was 1.12 (CI: 1.00-1.24) and the adjusted OR was 1.02 (CI: 0.90-1.16) for all tumors. For every 1 000 g of additional birth weight, the crude OR was 1.25 (CI: 1.00-1.55) and the adjusted OR was 1.04 (CI: 0.82-1.34) for all tumors. Among children diagnosed after reaching the age of 3 years, in the miscellaneous tumor category, the OR was significantly increased for every additional 500 g and 1 000 g of birth weight. The study data suggested that increased birth weight was associated with childhood solid tumor development, especially among children more than 3 years old with "miscellaneous" tumors.

  5. Performance Analysis of Unsupervised Clustering Methods for Brain Tumor Segmentation

    Directory of Open Access Journals (Sweden)

    Tushar H Jaware

    2013-10-01

    Full Text Available Medical image processing is the most challenging and emerging field of neuroscience. The ultimate goal of medical image analysis in brain MRI is to extract important clinical features that would improve methods of diagnosis & treatment of disease. This paper focuses on methods to detect & extract brain tumour from brain MR images. MATLAB is used to design, software tool for locating brain tumor, based on unsupervised clustering methods. K-Means clustering algorithm is implemented & tested on data base of 30 images. Performance evolution of unsupervised clusteringmethods is presented.

  6. Classification of brain tumors using texture based analysis of T1-post contrast MR scans in a preclinical model

    Science.gov (United States)

    Tang, Tien T.; Zawaski, Janice A.; Francis, Kathleen N.; Qutub, Amina A.; Gaber, M. Waleed

    2018-02-01

    Accurate diagnosis of tumor type is vital for effective treatment planning. Diagnosis relies heavily on tumor biopsies and other clinical factors. However, biopsies do not fully capture the tumor's heterogeneity due to sampling bias and are only performed if the tumor is accessible. An alternative approach is to use features derived from routine diagnostic imaging such as magnetic resonance (MR) imaging. In this study we aim to establish the use of quantitative image features to classify brain tumors and extend the use of MR images beyond tumor detection and localization. To control for interscanner, acquisition and reconstruction protocol variations, the established workflow was performed in a preclinical model. Using glioma (U87 and GL261) and medulloblastoma (Daoy) models, T1-weighted post contrast scans were acquired at different time points post-implant. The tumor regions at the center, middle, and peripheral were analyzed using in-house software to extract 32 different image features consisting of first and second order features. The extracted features were used to construct a decision tree, which could predict tumor type with 10-fold cross-validation. Results from the final classification model demonstrated that middle tumor region had the highest overall accuracy at 79%, while the AUC accuracy was over 90% for GL261 and U87 tumors. Our analysis further identified image features that were unique to certain tumor region, although GL261 tumors were more homogenous with no significant differences between the central and peripheral tumor regions. In conclusion our study shows that texture features derived from MR scans can be used to classify tumor type with high success rates. Furthermore, the algorithm we have developed can be implemented with any imaging datasets and may be applicable to multiple tumor types to determine diagnosis.

  7. Mitigating Errors in External Respiratory Surrogate-Based Models of Tumor Position

    Energy Technology Data Exchange (ETDEWEB)

    Malinowski, Kathleen T. [Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD (United States); Fischell Department of Bioengineering, University of Maryland, College Park, MD (United States); McAvoy, Thomas J. [Fischell Department of Bioengineering, University of Maryland, College Park, MD (United States); Department of Chemical and Biomolecular Engineering and Institute of Systems Research, University of Maryland, College Park, MD (United States); George, Rohini [Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD (United States); Dieterich, Sonja [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); D' Souza, Warren D., E-mail: wdsou001@umaryland.edu [Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD (United States); Fischell Department of Bioengineering, University of Maryland, College Park, MD (United States)

    2012-04-01

    Purpose: To investigate the effect of tumor site, measurement precision, tumor-surrogate correlation, training data selection, model design, and interpatient and interfraction variations on the accuracy of external marker-based models of tumor position. Methods and Materials: Cyberknife Synchrony system log files comprising synchronously acquired positions of external markers and the tumor from 167 treatment fractions were analyzed. The accuracy of Synchrony, ordinary-least-squares regression, and partial-least-squares regression models for predicting the tumor position from the external markers was evaluated. The quantity and timing of the data used to build the predictive model were varied. The effects of tumor-surrogate correlation and the precision in both the tumor and the external surrogate position measurements were explored by adding noise to the data. Results: The tumor position prediction errors increased during the duration of a fraction. Increasing the training data quantities did not always lead to more accurate models. Adding uncorrelated noise to the external marker-based inputs degraded the tumor-surrogate correlation models by 16% for partial-least-squares and 57% for ordinary-least-squares. External marker and tumor position measurement errors led to tumor position prediction changes 0.3-3.6 times the magnitude of the measurement errors, varying widely with model algorithm. The tumor position prediction errors were significantly associated with the patient index but not with the fraction index or tumor site. Partial-least-squares was as accurate as Synchrony and more accurate than ordinary-least-squares. Conclusions: The accuracy of surrogate-based inferential models of tumor position was affected by all the investigated factors, except for the tumor site and fraction index.

  8. A methodology for comprehensive breast cancer Ki67 labeling index with intra-tumor heterogeneity appraisal based on hexagonal tiling of digital image analysis data.

    Science.gov (United States)

    Plancoulaine, Benoit; Laurinaviciene, Aida; Herlin, Paulette; Besusparis, Justinas; Meskauskas, Raimundas; Baltrusaityte, Indra; Iqbal, Yasir; Laurinavicius, Arvydas

    2015-10-19

    Digital image analysis (DIA) enables higher accuracy, reproducibility, and capacity to enumerate cell populations by immunohistochemistry; however, the most unique benefits may be obtained by evaluating the spatial distribution and intra-tissue variance of markers. The proliferative activity of breast cancer tissue, estimated by the Ki67 labeling index (Ki67 LI), is a prognostic and predictive biomarker requiring robust measurement methodologies. We performed DIA on whole-slide images (WSI) of 302 surgically removed Ki67-stained breast cancer specimens; the tumour classifier algorithm was used to automatically detect tumour tissue but was not trained to distinguish between invasive and non-invasive carcinoma cells. The WSI DIA-generated data were subsampled by hexagonal tiling (HexT). Distribution and texture parameters were compared to conventional WSI DIA and pathology report data. Factor analysis of the data set, including total numbers of tumor cells, the Ki67 LI and Ki67 distribution, and texture indicators, extracted 4 factors, identified as entropy, proliferation, bimodality, and cellularity. The factor scores were further utilized in cluster analysis, outlining subcategories of heterogeneous tumors with predominant entropy, bimodality, or both at different levels of proliferative activity. The methodology also allowed the visualization of Ki67 LI heterogeneity in tumors and the automated detection and quantitative evaluation of Ki67 hotspots, based on the upper quintile of the HexT data, conceptualized as the "Pareto hotspot". We conclude that systematic subsampling of DIA-generated data into HexT enables comprehensive Ki67 LI analysis that reflects aspects of intra-tumor heterogeneity and may serve as a methodology to improve digital immunohistochemistry in general.

  9. Automatización de un registro hospitalario de tumores Automatization of a hospital-based tumor registry

    Directory of Open Access Journals (Sweden)

    Josepa Ribes

    2005-06-01

    Full Text Available Introducción: El Instituto Catalán de Oncología automatizó los procedimientos manuales de captación de la información de las bases de datos del alta hospitalaria (AH y anatomía patológica (APA mediante una aplicación informática (ASEDAT con el objetivo de aumentar la fiabilidad de los datos y reducir los costes del Registro Hospitalario de Tumores (RHT. Material y Método: ASEDAT detecta los tumores incidentes del centro a partir de las bases de datos de APA y de las AH mediante la selección de la información básica para cada uno de ellos. Se resolvió el RHT para el período 1999-2000 mediante el procedimiento manual y automatizado, y se compararon entre sí los resultados. Resultados: Se detectaron 10.498 pacientes oncológicos. La resolución manual detectó 8.309 tumores incidentes y 2.374 tumores prevalentes. ASEDAT resolvió automáticamente 8.901 pacientes (84,8%, en los cuales se detectaron 8.367 tumores incidentes, 58 tumores más que con el procedimiento manual. La validación de la concordancia se realizó en los tumores incidentes detectados por ambos métodos (7.063 tumores. En 6.185 tumores (87,6%, la información coincidió en todas las variables. De los tumores discordantes, 692 (9,8% fueron generados por el personal del RHT en la resolución manual y el resto (n = 186; 2,6% por la aplicación (resolución automática. Conclusiones: La automatización de un registro de cáncer es posible siempre y cuando el centro disponga de las bases de datos de APA y AH codificadas e informatizadas.Introduction: To increase data reliability and reduce the costs associated with the HTR, the Catalan Institute of Oncology programmed the manual procedures of data collection from databases by means of a computer application (ASEDAT. Material and method: ASEDAT detects the incident tumors of the registry from the databases of the pathology records (PR and discharge records (DR and selects the basic information from both databases. Data

  10. Proton radiotherapy in management of pediatric base of skull tumors

    International Nuclear Information System (INIS)

    Hug, Eugen B.; Sweeney, Reinhart A.; Nurre, Pamela M.; Holloway, Kitty C.; Slater, Jerry D.; Munzenrider, John E.

    2002-01-01

    Purpose: Primary skull base tumors of the developing child are rare and present a formidable challenge to both surgeons and radiation oncologists. Gross total resection with negative margins is rarely achieved, and the risks of functional, structural, and cosmetic deficits limit the radiation dose using conventional radiation techniques. Twenty-nine children and adolescents treated with conformal proton radiotherapy (proton RT) were analyzed to assess treatment efficacy and safety. Methods and Materials: Between July 1992 and April 1999, 29 patients with mesenchymal tumors underwent fractionated proton (13 patients) or fractionated combined proton and photon (16 patients) irradiation. The age at treatment ranged from 1 to 19 years (median 12); 14 patients were male and 15 female. Tumors were grouped as malignant or benign. Twenty patients had malignant histologic findings, including chordoma (n=10), chondrosarcoma (n=3), rhabdomyosarcoma (n=4), and other sarcomas (n=3). Target doses ranged between 50.4 and 78.6 Gy/cobalt Gray equivalent (CGE), delivered at doses of 1.8-2.0 Gy/CGE per fraction. The benign histologic findings included giant cell tumors (n=6), angiofibromas (n=2), and chondroblastoma (n=1). RT doses for this group ranged from 45.0 to 71.8 Gy/CGE. Despite maximal surgical resection, 28 (97%) of 29 patients had gross disease at the time of proton RT. Follow-up after proton RT ranged from 13 to 92 months (mean 40). Results: Of the 20 patients with malignant tumors, 5 (25%) had local failure; 1 patient had failure in the surgical access route and 3 patients developed distant metastases. Seven patients had died of progressive disease at the time of analysis. Local tumor control was maintained in 6 (60%) of 10 patients with chordoma, 3 (100%) of 3 with chondrosarcoma, 4 (100%) of 4 with rhabdomyosarcoma, and 2 (66%) of 3 with other sarcomas. The actuarial 5-year local control and overall survival rate was 72% and 56%, respectively, and the overall survival

  11. SU-E-I-83: Error Analysis of Multi-Modality Image-Based Volumes of Rodent Solid Tumors Using a Preclinical Multi-Modality QA Phantom

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Y [University of Kansas Hospital, Kansas City, KS (United States); Fullerton, G; Goins, B [University of Texas Health Science Center at San Antonio, San Antonio, TX (United States)

    2015-06-15

    Purpose: In our previous study a preclinical multi-modality quality assurance (QA) phantom that contains five tumor-simulating test objects with 2, 4, 7, 10 and 14 mm diameters was developed for accurate tumor size measurement by researchers during cancer drug development and testing. This study analyzed the errors during tumor volume measurement from preclinical magnetic resonance (MR), micro-computed tomography (micro- CT) and ultrasound (US) images acquired in a rodent tumor model using the preclinical multi-modality QA phantom. Methods: Using preclinical 7-Tesla MR, US and micro-CT scanners, images were acquired of subcutaneous SCC4 tumor xenografts in nude rats (3–4 rats per group; 5 groups) along with the QA phantom using the same imaging protocols. After tumors were excised, in-air micro-CT imaging was performed to determine reference tumor volume. Volumes measured for the rat tumors and phantom test objects were calculated using formula V = (π/6)*a*b*c where a, b and c are the maximum diameters in three perpendicular dimensions determined by the three imaging modalities. Then linear regression analysis was performed to compare image-based tumor volumes with the reference tumor volume and known test object volume for the rats and the phantom respectively. Results: The slopes of regression lines for in-vivo tumor volumes measured by three imaging modalities were 1.021, 1.101 and 0.862 for MRI, micro-CT and US respectively. For phantom, the slopes were 0.9485, 0.9971 and 0.9734 for MRI, micro-CT and US respectively. Conclusion: For both animal and phantom studies, random and systematic errors were observed. Random errors were observer-dependent and systematic errors were mainly due to selected imaging protocols and/or measurement method. In the animal study, there were additional systematic errors attributed to ellipsoidal assumption for tumor shape. The systematic errors measured using the QA phantom need to be taken into account to reduce measurement

  12. Study of Aided Diagnosis of Hepatic Carcinoma Based on Artificial Neural Network Combined with Tumor Marker Group

    Science.gov (United States)

    Tan, Shanjuan; Feng, Feifei; Wu, Yongjun; Wu, Yiming

    To develop a computer-aided diagnostic scheme by using an artificial neural network (ANN) combined with tumor markers for diagnosis of hepatic carcinoma (HCC) as a clinical assistant method. 140 serum samples (50 malignant, 40 benign and 50 normal) were analyzed for α-fetoprotein (AFP), carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA), sialic acid (SA) and calcium (Ca). The five tumor marker values were then used as ANN inputs data. The result of ANN was compared with that of discriminant analysis by receiver operating characteristic (ROC) curve (AUC) analysis. The diagnostic accuracy of ANN and discriminant analysis among all samples of the test group was 95.5% and 79.3%, respectively. Analysis of multiple tumor markers based on ANN may be a better choice than the traditional statistical methods for differentiating HCC from benign or normal.

  13. Birth weight and risk of childhood solid tumors in Brazil: a record linkage between population-based data sets

    Directory of Open Access Journals (Sweden)

    Neimar de Paula Silva

    2017-04-01

    Full Text Available ABSTRACT Objective To analyze the relationship between the development of childhood solid tumors and 1 birth weight and 2 fetal growth, using two Brazilian population-based data sets. Methods A case–cohort study was performed using two population-based data sets, and linkage between the Live Birth Information System (Sistema de Informação sobre Nascidos Vivos, SINASC and 14 population-based cancer registries (PBCRs was established. Four controls per case were chosen randomly from the SINASC data set. Tumors were classified as central nervous system (CNS, non-CNS embryonal, and other tumors (“miscellaneous”. Adjustments were made for potential confounders (maternal age, mode of delivery, maternal education, birth order, gestational age, sex, and geographic region. Odds ratios (ORs with 95% confidence intervals (CIs were computed using unconditional logistic regression analysis. Results In a trend analysis, for every 500 g of additional birth weight, the crude OR was 1.12 (CI: 1.00–1.24 and the adjusted OR was 1.02 (CI: 0.90–1.16 for all tumors. For every 1 000 g of additional birth weight, the crude OR was 1.25 (CI: 1.00–1.55 and the adjusted OR was 1.04 (CI: 0.82–1.34 for all tumors. Among children diagnosed after reaching the age of 3 years, in the miscellaneous tumor category, the OR was significantly increased for every additional 500 g and 1 000 g of birth weight. Conclusions The study data suggested that increased birth weight was associated with childhood solid tumor development, especially among children more than 3 years old with “miscellaneous” tumors.

  14. Logistic regression analysis of risk factors for postoperative recurrence of spinal tumors and analysis of prognostic factors.

    Science.gov (United States)

    Zhang, Shanyong; Yang, Lili; Peng, Chuangang; Wu, Minfei

    2018-02-01

    The aim of the present study was to investigate the risk factors for postoperative recurrence of spinal tumors by logistic regression analysis and analysis of prognostic factors. In total, 77 male and 48 female patients with spinal tumor were selected in our hospital from January, 2010 to December, 2015 and divided into the benign (n=76) and malignant groups (n=49). All the patients underwent microsurgical resection of spinal tumors and were reviewed regularly 3 months after operation. The McCormick grading system was used to evaluate the postoperative spinal cord function. Data were subjected to statistical analysis. Of the 125 cases, 63 cases showed improvement after operation, 50 cases were stable, and deterioration was found in 12 cases. The improvement rate of patients with cervical spine tumor, which reached 56.3%, was the highest. Fifty-two cases of sensory disturbance, 34 cases of pain, 30 cases of inability to exercise, 26 cases of ataxia, and 12 cases of sphincter disorders were found after operation. Seventy-two cases (57.6%) underwent total resection, 18 cases (14.4%) received subtotal resection, 23 cases (18.4%) received partial resection, and 12 cases (9.6%) were only treated with biopsy/decompression. Postoperative recurrence was found in 57 cases (45.6%). The mean recurrence time of patients in the malignant group was 27.49±6.09 months, and the mean recurrence time of patients in the benign group was 40.62±4.34. The results were significantly different (Pregression analysis of total resection-related factors showed that total resection should be the preferred treatment for patients with benign tumors, thoracic and lumbosacral tumors, and lower McCormick grade, as well as patients without syringomyelia and intramedullary tumors. Logistic regression analysis of recurrence-related factors revealed that the recurrence rate was relatively higher in patients with malignant, cervical, thoracic and lumbosacral, intramedullary tumors, and higher Mc

  15. DWI-associated entire-tumor histogram analysis for the differentiation of low-grade prostate cancer from intermediate-high-grade prostate cancer.

    Science.gov (United States)

    Wu, Chen-Jiang; Wang, Qing; Li, Hai; Wang, Xiao-Ning; Liu, Xi-Sheng; Shi, Hai-Bin; Zhang, Yu-Dong

    2015-10-01

    To investigate diagnostic efficiency of DWI using entire-tumor histogram analysis in differentiating the low-grade (LG) prostate cancer (PCa) from intermediate-high-grade (HG) PCa in comparison with conventional ROI-based measurement. DW images (b of 0-1400 s/mm(2)) from 126 pathology-confirmed PCa (diameter >0.5 cm) in 110 patients were retrospectively collected and processed by mono-exponential model. The measurement of tumor apparent diffusion coefficients (ADCs) was performed with using histogram-based and ROI-based approach, respectively. The diagnostic ability of ADCs from two methods for differentiating LG-PCa (Gleason score, GS ≤ 6) from HG-PCa (GS > 6) was determined by ROC regression, and compared by McNemar's test. There were 49 LG-tumor and 77 HG-tumor at pathologic findings. Histogram-based ADCs (mean, median, 10th and 90th) and ROI-based ADCs (mean) showed dominant relationships with ordinal GS of Pca (ρ = -0.225 to -0.406, p Histogram 10th ADCs had dominantly high Az (0.738), Youden index (0.415), and positive likelihood ratio (LR+, 2.45) in stratifying tumor GS against mean, median and 90th ADCs, and ROI-based ADCs. Histogram mean, median, and 10th ADCs showed higher specificity (65.3%-74.1% vs. 44.9%, p histogram analysis had higher specificity, Az, Youden index, and LR+ for differentiation of PCa Gleason grade than ROI-based approach.

  16. Mapping In Vivo Tumor Oxygenation within Viable Tumor by 19F-MRI and Multispectral Analysis

    Directory of Open Access Journals (Sweden)

    Yunzhou Shi

    2013-11-01

    Full Text Available Quantifying oxygenation in viable tumor remains a major obstacle toward a better understanding of the tumor microenvironment and improving treatment strategies. Current techniques are often complicated by tumor heterogeneity. Herein, a novel in vivo approach that combines 19F magnetic resonance imaging (19F-MRIR1 mapping with diffusionbased multispectral (MS analysis is introduced. This approach restricts the partial pressure of oxygen (pO2 measurements to viable tumor, the tissue of therapeutic interest. The technique exhibited sufficient sensitivity to detect a breathing gas challenge in a xenograft tumor model, and the hypoxic region measured by MS 19F-MRI was strongly correlated with histologic estimates of hypoxia. This approach was then applied to address the effects of antivascular agents on tumor oxygenation, which is a research question that is still under debate. The technique was used to monitor longitudinal pO2 changes in response to an antibody to vascular endothelial growth factor (B20.4.1.1 and a selective dual phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor (GDC-0980. GDC-0980 reduced viable tumor pO2 during a 3-day treatment period, and a significant reduction was also produced by B20.4.1.1. Overall, this method provides an unprecedented view of viable tumor pO2 and contributes to a greater understanding of the effects of antivascular therapies on the tumor's microenvironment.

  17. Treatment Analysis in a Cancer Stem Cell Context Using a Tumor Growth Model Based on Cellular Automata.

    Directory of Open Access Journals (Sweden)

    Ángel Monteagudo

    Full Text Available Cancer can be viewed as an emergent behavior in terms of complex system theory and artificial life, Cellular Automata (CA being the tool most used for studying and characterizing the emergent behavior. Different approaches with CA models were used to model cancer growth. The use of the abstract model of acquired cancer hallmarks permits the direct modeling at cellular level, where a cellular automaton defines the mitotic and apoptotic behavior of cells, and allows for an analysis of different dynamics of the cellular system depending on the presence of the different hallmarks. A CA model based on the presence of hallmarks in the cells, which includes a simulation of the behavior of Cancer Stem Cells (CSC and their implications for the resultant growth behavior of the multicellular system, was employed. This modeling of cancer growth, in the avascular phase, was employed to analyze the effect of cancer treatments in a cancer stem cell context. The model clearly explains why, after treatment against non-stem cancer cells, the regrowth capability of CSCs generates a faster regrowth of tumor behavior, and also shows that a continuous low-intensity treatment does not favor CSC proliferation and differentiation, thereby allowing an unproblematic control of future tumor regrowth. The analysis performed indicates that, contrary to the current attempts at CSC control, trying to make CSC proliferation more difficult is an important point to consider, especially in the immediate period after a standard treatment for controlling non-stem cancer cell proliferation.

  18. Skull base tumor model.

    Science.gov (United States)

    Gragnaniello, Cristian; Nader, Remi; van Doormaal, Tristan; Kamel, Mahmoud; Voormolen, Eduard H J; Lasio, Giovanni; Aboud, Emad; Regli, Luca; Tulleken, Cornelius A F; Al-Mefty, Ossama

    2010-11-01

    Resident duty-hours restrictions have now been instituted in many countries worldwide. Shortened training times and increased public scrutiny of surgical competency have led to a move away from the traditional apprenticeship model of training. The development of educational models for brain anatomy is a fascinating innovation allowing neurosurgeons to train without the need to practice on real patients and it may be a solution to achieve competency within a shortened training period. The authors describe the use of Stratathane resin ST-504 polymer (SRSP), which is inserted at different intracranial locations to closely mimic meningiomas and other pathological entities of the skull base, in a cadaveric model, for use in neurosurgical training. Silicone-injected and pressurized cadaveric heads were used for studying the SRSP model. The SRSP presents unique intrinsic metamorphic characteristics: liquid at first, it expands and foams when injected into the desired area of the brain, forming a solid tumorlike structure. The authors injected SRSP via different passages that did not influence routes used for the surgical approach for resection of the simulated lesion. For example, SRSP injection routes included endonasal transsphenoidal or transoral approaches if lesions were to be removed through standard skull base approach, or, alternatively, SRSP was injected via a cranial approach if the removal was planned to be via the transsphenoidal or transoral route. The model was set in place in 3 countries (US, Italy, and The Netherlands), and a pool of 13 physicians from 4 different institutions (all surgeons and surgeons in training) participated in evaluating it and provided feedback. All 13 evaluating physicians had overall positive impressions of the model. The overall score on 9 components evaluated--including comparison between the tumor model and real tumor cases, perioperative requirements, general impression, and applicability--was 88% (100% being the best possible

  19. Computer-assisted stereology and automated image analysis for quantification of tumor infiltrating lymphocytes in colon cancer.

    Science.gov (United States)

    Eriksen, Ann C; Andersen, Johnnie B; Kristensson, Martin; dePont Christensen, René; Hansen, Torben F; Kjær-Frifeldt, Sanne; Sørensen, Flemming B

    2017-08-29

    Precise prognostic and predictive variables allowing improved post-operative treatment stratification are missing in patients treated for stage II colon cancer (CC). Investigation of tumor infiltrating lymphocytes (TILs) may be rewarding, but the lack of a standardized analytic technique is a major concern. Manual stereological counting is considered the gold standard, but digital pathology with image analysis is preferred due to time efficiency. The purpose of this study was to compare manual stereological estimates of TILs with automatic counts obtained by image analysis, and at the same time investigate the heterogeneity of TILs. From 43 patients treated for stage II CC in 2002 three paraffin embedded, tumor containing tissue blocks were selected one of them representing the deepest invasive tumor front. Serial sections from each of the 129 blocks were immunohistochemically stained for CD3 and CD8, and the slides were scanned. Stereological estimates of the numerical density and area fraction of TILs were obtained using the computer-assisted newCAST stereology system. For the image analysis approach an app-based algorithm was developed using Visiopharm Integrator System software. For both methods the tumor areas of interest (invasive front and central area) were manually delineated by the observer. Based on all sections, the Spearman's correlation coefficients for density estimates varied from 0.9457 to 0.9638 (p heterogeneity, intra-class correlation coefficients (ICC) for CD3+ TILs varied from 0.615 to 0.746 in the central area, and from 0.686 to 0.746 in the invasive area. ICC for CD8+ TILs varied from 0.724 to 0.775 in the central area, and from 0.746 to 0.765 in the invasive area. Exact objective and time efficient estimates of numerical densities and area fractions of CD3+ and CD8+ TILs in stage II colon cancer can be obtained by image analysis and are highly correlated to the corresponding estimates obtained by the gold standard based on stereology

  20. Mitigating Errors in External Respiratory Surrogate-Based Models of Tumor Position

    International Nuclear Information System (INIS)

    Malinowski, Kathleen T.; McAvoy, Thomas J.; George, Rohini; Dieterich, Sonja; D'Souza, Warren D.

    2012-01-01

    Purpose: To investigate the effect of tumor site, measurement precision, tumor–surrogate correlation, training data selection, model design, and interpatient and interfraction variations on the accuracy of external marker-based models of tumor position. Methods and Materials: Cyberknife Synchrony system log files comprising synchronously acquired positions of external markers and the tumor from 167 treatment fractions were analyzed. The accuracy of Synchrony, ordinary-least-squares regression, and partial-least-squares regression models for predicting the tumor position from the external markers was evaluated. The quantity and timing of the data used to build the predictive model were varied. The effects of tumor–surrogate correlation and the precision in both the tumor and the external surrogate position measurements were explored by adding noise to the data. Results: The tumor position prediction errors increased during the duration of a fraction. Increasing the training data quantities did not always lead to more accurate models. Adding uncorrelated noise to the external marker-based inputs degraded the tumor–surrogate correlation models by 16% for partial-least-squares and 57% for ordinary-least-squares. External marker and tumor position measurement errors led to tumor position prediction changes 0.3–3.6 times the magnitude of the measurement errors, varying widely with model algorithm. The tumor position prediction errors were significantly associated with the patient index but not with the fraction index or tumor site. Partial-least-squares was as accurate as Synchrony and more accurate than ordinary-least-squares. Conclusions: The accuracy of surrogate-based inferential models of tumor position was affected by all the investigated factors, except for the tumor site and fraction index.

  1. CDNA Microarray Based Comparative Gene Expression Analysis of Primary Breast Tumors Versus In Vitro Transformed Neoplastic Breast Epithelium

    National Research Council Canada - National Science Library

    Szallasi, Zoltan

    2001-01-01

    .... The first group of clones is being sorted by their ability to form tumors. We are currently performing cDNA microarray analysis quantifying the expression level of about 15,000 genes in these cell lines...

  2. The results of gamma knife radiosurgery for malignant skull base tumors

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Takayuki; Kobayashi, Tatsuya; Kida, Yoshihisa; Oyama, Hirofumi; Niwa, Masahiro [Komaki City Hospital, Aichi (Japan)

    1996-03-01

    The results of gamma knife radiosurgery for malignant skull base tumors were analyzed using repeated magnetic resonance imagings and neurological examinations. Nineteen malignant skull base tumors were treated and followed up for 22.3 months (5-40 months) using MR imagings. The mean age was 54.4 years old (ranging from 16-85). Ten were male and 9 were female. Prior to the radiosurgery, removal of the tumors in 17 cases, conventional radiation therapy in 7, and chemotherapy in 4 etc. were performed. The pathological diagnoses were chordoma in 6 patients, metastatic tumors in 5, epipharyngeal carcinoma in 2, adenoid cystic carcinoma in 2, and others in 4. The locations of tumors were clivus in 8, parasellar region in 5, epipharynx in 2, paranasal sinus in 2, C-P angle in 1, and intraorbital region in 1 (14 intracranial and 5 extracranial). The mean diameter of the tumor was 33.5 mm. The mean maximum dose was 26.8 Gy and the mean marginal dose was 12.9 Gy during treatment. Repeated MR imagings revealed decrease of tumor size in 12 cases, showing no change in 1, and increase of tumor size in 5 (unknown in 1). Follow-up neurological examinations showed improvement in 3 patients, no change in 9, and deterioration in 7. There were 11 deaths during a mean follow-up period of 17.8 months (5-32 months) and another 8 cases are alive for a mean follow-up of 30.5 months (20-40 months) after the radiosurgery. Although the tumor size was large at the time of treatment, the results of gamma knife radiosurgery were promising. Considering the quality of life of patients with malignant skull base tumors, it is emphasized that gamma knife treatment is the method of choice compared with radical removal of the tumors. (author).

  3. Improving the accuracy of brain tumor surgery via Raman-based technology.

    Science.gov (United States)

    Hollon, Todd; Lewis, Spencer; Freudiger, Christian W; Sunney Xie, X; Orringer, Daniel A

    2016-03-01

    Despite advances in the surgical management of brain tumors, achieving optimal surgical results and identification of tumor remains a challenge. Raman spectroscopy, a laser-based technique that can be used to nondestructively differentiate molecules based on the inelastic scattering of light, is being applied toward improving the accuracy of brain tumor surgery. Here, the authors systematically review the application of Raman spectroscopy for guidance during brain tumor surgery. Raman spectroscopy can differentiate normal brain from necrotic and vital glioma tissue in human specimens based on chemical differences, and has recently been shown to differentiate tumor-infiltrated tissues from noninfiltrated tissues during surgery. Raman spectroscopy also forms the basis for coherent Raman scattering (CRS) microscopy, a technique that amplifies spontaneous Raman signals by 10,000-fold, enabling real-time histological imaging without the need for tissue processing, sectioning, or staining. The authors review the relevant basic and translational studies on CRS microscopy as a means of providing real-time intraoperative guidance. Recent studies have demonstrated how CRS can be used to differentiate tumor-infiltrated tissues from noninfiltrated tissues and that it has excellent agreement with traditional histology. Under simulated operative conditions, CRS has been shown to identify tumor margins that would be undetectable using standard bright-field microscopy. In addition, CRS microscopy has been shown to detect tumor in human surgical specimens with near-perfect agreement to standard H & E microscopy. The authors suggest that as the intraoperative application and instrumentation for Raman spectroscopy and imaging matures, it will become an essential component in the neurosurgical armamentarium for identifying residual tumor and improving the surgical management of brain tumors.

  4. Lateral skull base approaches in the management of benign parapharyngeal space tumors.

    Science.gov (United States)

    Prasad, Sampath Chandra; Piccirillo, Enrico; Chovanec, Martin; La Melia, Claudio; De Donato, Giuseppe; Sanna, Mario

    2015-06-01

    To evaluate the role of lateral skull base approaches in the management of benign parapharyngeal space tumors and to propose an algorithm for their surgical approach. Retrospective study of patients with benign parapharyngeal space tumors. The clinical features, radiology and preoperative management of skull base neurovasculature, the surgical approaches and overall results were recorded. 46 patients presented with 48 tumors. 12 were prestyloid and 36 poststyloid. 19 (39.6%) tumors were paragangliomas, 15 (31.25%) were schwannomas and 11 (23%) were pleomorphic adenomas. Preoperative embolization was performed in 19, stenting of the internal carotid artery in 4 and permanent balloon occlusion in 2 patients. 19 tumors were approached by the transcervical, 13 by transcervical-transparotid, 5 by transcervical-transmastoid, 6, 1 and 2 tumors by the infratemporal fossa approach types A, B and D, respectively. Total radical tumor removal was achieved in 46 (96%) of the cases. Lateral skull base approaches have an advantage over other approaches in the management of benign tumors of the parapharyngeal space due to the fact that they provide excellent exposure with less morbidity. The use of microscope combined with bipolar cautery reduces morbidity. Stenting of internal carotid artery gives a chance for complete tumor removal with arterial preservation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  5. Deep Learning and Texture-Based Semantic Label Fusion for Brain Tumor Segmentation.

    Science.gov (United States)

    Vidyaratne, L; Alam, M; Shboul, Z; Iftekharuddin, K M

    2018-01-01

    Brain tumor segmentation is a fundamental step in surgical treatment and therapy. Many hand-crafted and learning based methods have been proposed for automatic brain tumor segmentation from MRI. Studies have shown that these approaches have their inherent advantages and limitations. This work proposes a semantic label fusion algorithm by combining two representative state-of-the-art segmentation algorithms: texture based hand-crafted, and deep learning based methods to obtain robust tumor segmentation. We evaluate the proposed method using publicly available BRATS 2017 brain tumor segmentation challenge dataset. The results show that the proposed method offers improved segmentation by alleviating inherent weaknesses: extensive false positives in texture based method, and the false tumor tissue classification problem in deep learning method, respectively. Furthermore, we investigate the effect of patient's gender on the segmentation performance using a subset of validation dataset. Note the substantial improvement in brain tumor segmentation performance proposed in this work has recently enabled us to secure the first place by our group in overall patient survival prediction task at the BRATS 2017 challenge.

  6. Deep learning and texture-based semantic label fusion for brain tumor segmentation

    Science.gov (United States)

    Vidyaratne, L.; Alam, M.; Shboul, Z.; Iftekharuddin, K. M.

    2018-02-01

    Brain tumor segmentation is a fundamental step in surgical treatment and therapy. Many hand-crafted and learning based methods have been proposed for automatic brain tumor segmentation from MRI. Studies have shown that these approaches have their inherent advantages and limitations. This work proposes a semantic label fusion algorithm by combining two representative state-of-the-art segmentation algorithms: texture based hand-crafted, and deep learning based methods to obtain robust tumor segmentation. We evaluate the proposed method using publicly available BRATS 2017 brain tumor segmentation challenge dataset. The results show that the proposed method offers improved segmentation by alleviating inherent weaknesses: extensive false positives in texture based method, and the false tumor tissue classification problem in deep learning method, respectively. Furthermore, we investigate the effect of patient's gender on the segmentation performance using a subset of validation dataset. Note the substantial improvement in brain tumor segmentation performance proposed in this work has recently enabled us to secure the first place by our group in overall patient survival prediction task at the BRATS 2017 challenge.

  7. Correlation Between Minimum Apparent Diffusion Coefficient (ADCmin) and Tumor Cellularity: A Meta-analysis.

    Science.gov (United States)

    Surov, Alexey; Meyer, Hans Jonas; Wienke, Andreas

    2017-07-01

    Diffusion-weighted imaging (DWI) is a magnetic resonance imaging (MRI) technique based on measure of water diffusion that can provide information about tissue microstructure, especially about cell count. Increase of cell density induces restriction of water diffusion and decreases apparent diffusion coefficient (ADC). ADC can be divided into three sub-parameters: ADC minimum or ADC min , mean ADC or ADC mean and ADC maximum or ADC max Some studies have suggested that ADC min shows stronger correlations with cell count in comparison to other ADC fractions and may be used as a parameter for estimation of tumor cellularity. The aim of the present meta-analysis was to summarize correlation coefficients between ADC min and cellularity in different tumors based on large patient data. For this analysis, MEDLINE database was screened for associations between ADC and cell count in different tumors up to September 2016. For this work, only data regarding ADC min were included. Overall, 12 publications with 317 patients were identified. Spearman's correlation coefficient was used to analyze associations between ADC min and cellularity. The reported Pearson correlation coefficients in some publications were converted into Spearman correlation coefficients. The pooled correlation coefficient for all included studies was ρ=-0.59 (95% confidence interval (CI)=-0.72 to -0.45), heterogeneity Tau 2 =0.04 (pcorrelated moderately with tumor cellularity. The calculated correlation coefficient is not stronger in comparison to the reported coefficient for ADC mean and, therefore, ADC min does not represent a better means to reflect cellularity. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  8. DEMARCATE: Density-based magnetic resonance image clustering for assessing tumor heterogeneity in cancer.

    Science.gov (United States)

    Saha, Abhijoy; Banerjee, Sayantan; Kurtek, Sebastian; Narang, Shivali; Lee, Joonsang; Rao, Ganesh; Martinez, Juan; Bharath, Karthik; Rao, Arvind U K; Baladandayuthapani, Veerabhadran

    2016-01-01

    Tumor heterogeneity is a crucial area of cancer research wherein inter- and intra-tumor differences are investigated to assess and monitor disease development and progression, especially in cancer. The proliferation of imaging and linked genomic data has enabled us to evaluate tumor heterogeneity on multiple levels. In this work, we examine magnetic resonance imaging (MRI) in patients with brain cancer to assess image-based tumor heterogeneity. Standard approaches to this problem use scalar summary measures (e.g., intensity-based histogram statistics) that do not adequately capture the complete and finer scale information in the voxel-level data. In this paper, we introduce a novel technique, DEMARCATE (DEnsity-based MAgnetic Resonance image Clustering for Assessing Tumor hEterogeneity) to explore the entire tumor heterogeneity density profiles (THDPs) obtained from the full tumor voxel space. THDPs are smoothed representations of the probability density function of the tumor images. We develop tools for analyzing such objects under the Fisher-Rao Riemannian framework that allows us to construct metrics for THDP comparisons across patients, which can be used in conjunction with standard clustering approaches. Our analyses of The Cancer Genome Atlas (TCGA) based Glioblastoma dataset reveal two significant clusters of patients with marked differences in tumor morphology, genomic characteristics and prognostic clinical outcomes. In addition, we see enrichment of image-based clusters with known molecular subtypes of glioblastoma multiforme, which further validates our representation of tumor heterogeneity and subsequent clustering techniques.

  9. Molecular analysis of radiation-induced experimental tumors in mice

    International Nuclear Information System (INIS)

    Niwa, O.; Muto, M.; Suzuki, F.

    1992-01-01

    Molecular analysis was made on mouse tumors induced by radiation and chemicals. Expression of oncogenes was studied in 12 types of 178 mouse tumors. Southern blotting was done on tumors in which overexpression of oncogenes was noted. Amplification of the myc oncogene was found in chemically induced sarcomas, but not those induced by radiations. Radiogenic thymomas were studied in detail. These thymomas were induced in two different ways. The first was thymomas induced by direct irradiation of F1 mice between C57BL/6NxC3H/He. Southern analysis of DNA revealed deletion of specific minisatellite bands in these tumors. DNA from directly induced thymomas induced focus formation when transfected into normal Golden hamster cells. The mouse K-ras oncogene was detected in these transformants. The second type of thymomas was induced by X-irradiation of thymectomized B10.thy1.2 mice in which normal thymus from congenic B10,thy1.1. mice was grafted. Thymomas of the donor origin was analysed by transfection and the transformants by DNA from those indirectly induced thymomas did not contain activated ras oncogenes. (author)

  10. Intratumor partitioning and texture analysis of dynamic contrast-enhanced (DCE)-MRI identifies relevant tumor subregions to predict pathological response of breast cancer to neoadjuvant chemotherapy.

    Science.gov (United States)

    Wu, Jia; Gong, Guanghua; Cui, Yi; Li, Ruijiang

    2016-11-01

    To predict pathological response of breast cancer to neoadjuvant chemotherapy (NAC) based on quantitative, multiregion analysis of dynamic contrast enhancement magnetic resonance imaging (DCE-MRI). In this Institutional Review Board-approved study, 35 patients diagnosed with stage II/III breast cancer were retrospectively investigated using 3T DCE-MR images acquired before and after the first cycle of NAC. First, principal component analysis (PCA) was used to reduce the dimensionality of the DCE-MRI data with high temporal resolution. We then partitioned the whole tumor into multiple subregions using k-means clustering based on the PCA-defined eigenmaps. Within each tumor subregion, we extracted four quantitative Haralick texture features based on the gray-level co-occurrence matrix (GLCM). The change in texture features in each tumor subregion between pre- and during-NAC was used to predict pathological complete response after NAC. Three tumor subregions were identified through clustering, each with distinct enhancement characteristics. In univariate analysis, all imaging predictors except one extracted from the tumor subregion associated with fast washout were statistically significant (P < 0.05) after correcting for multiple testing, with area under the receiver operating characteristic (ROC) curve (AUC) or AUCs between 0.75 and 0.80. In multivariate analysis, the proposed imaging predictors achieved an AUC of 0.79 (P = 0.002) in leave-one-out cross-validation. This improved upon conventional imaging predictors such as tumor volume (AUC = 0.53) and texture features based on whole-tumor analysis (AUC = 0.65). The heterogeneity of the tumor subregion associated with fast washout on DCE-MRI predicted pathological response to NAC in breast cancer. J. Magn. Reson. Imaging 2016;44:1107-1115. © 2016 International Society for Magnetic Resonance in Medicine.

  11. Lung tumor tracking in fluoroscopic video based on optical flow

    International Nuclear Information System (INIS)

    Xu Qianyi; Hamilton, Russell J.; Schowengerdt, Robert A.; Alexander, Brian; Jiang, Steve B.

    2008-01-01

    Respiratory gating and tumor tracking for dynamic multileaf collimator delivery require accurate and real-time localization of the lung tumor position during treatment. Deriving tumor position from external surrogates such as abdominal surface motion may have large uncertainties due to the intra- and interfraction variations of the correlation between the external surrogates and internal tumor motion. Implanted fiducial markers can be used to track tumors fluoroscopically in real time with sufficient accuracy. However, it may not be a practical procedure when implanting fiducials bronchoscopically. In this work, a method is presented to track the lung tumor mass or relevant anatomic features projected in fluoroscopic images without implanted fiducial markers based on an optical flow algorithm. The algorithm generates the centroid position of the tracked target and ignores shape changes of the tumor mass shadow. The tracking starts with a segmented tumor projection in an initial image frame. Then, the optical flow between this and all incoming frames acquired during treatment delivery is computed as initial estimations of tumor centroid displacements. The tumor contour in the initial frame is transferred to the incoming frames based on the average of the motion vectors, and its positions in the incoming frames are determined by fine-tuning the contour positions using a template matching algorithm with a small search range. The tracking results were validated by comparing with clinician determined contours on each frame. The position difference in 95% of the frames was found to be less than 1.4 pixels (∼0.7 mm) in the best case and 2.8 pixels (∼1.4 mm) in the worst case for the five patients studied.

  12. MRI features of soft tissue tumors. Analysis of the contribution to the aetiological diagnosis based on a series of 32 cases

    International Nuclear Information System (INIS)

    Rose-Pittet, L.; Lebas, J.F.; Camuset, J.P.; Baudain, P.; Coulomb, M.

    1989-01-01

    This study concerns the investigation of 32 soft-tissue tumors by MRI, subsequently verified by biopsies or surgery (n = 28) or other investigations (n = 4). MRI can suggest the diagnosis in some cases: lipomas cysts, hematomas, neuromas, desmoid tumors, hemangiomas, by contrast analysis and morphologic aspects; sometimes, malignant lesions are suspected on particular anatomic criteria. MRI is excellent in the evaluation of local extension. MRI can therefore be performed when the staging of soft tissue tumor is incompletely provided by other investigations (CT or US) [fr

  13. In vitro quantitative analysis of Salmonella typhimurium preference for amino acids secreted by human breast tumor

    Science.gov (United States)

    Choi, Eunpyo; Maeng, Bohee; Lee, Jae-hun; Chang, Hyung-kwan; Park, Jungyul

    2016-12-01

    Bacterial therapies have been paid significant attentions by their ability to penetrate deep into the solid tumor tissue and its propensity to naturally accumulate in tumors of living animals. Understanding the actual mechanism for bacteria to target the tumor is therapeutically crucial but is poorly understood. We hypothesized that amino acids released from the specific tumors induced bacteria to those tumors and the experiments for chemotactic response of bacteria toward the cancer secreting amino acids was then performed by using the diffusion based multiple chemical gradient generator constructed by in situ self-assembly of microspheres. The quantitative analysis was carried out by comparison of intensity using green fluorescent protein (GFP) tagged Salmonella typhimurium ( S. typhimurium) in the gradient generator, which showed the clear preference to the released amino acids, especially from breast cancer patients. The understanding chemotaxis toward the cancer secreting amino acids is essential for controlling S. typhimurium targeting in tumors and will allow for the development of bacterial therapies.

  14. Automatic T1 bladder tumor detection by using wavelet analysis in cystoscopy images

    Science.gov (United States)

    Freitas, Nuno R.; Vieira, Pedro M.; Lima, Estevão; Lima, Carlos S.

    2018-02-01

    Correct classification of cystoscopy images depends on the interpreter’s experience. Bladder cancer is a common lesion that can only be confirmed by biopsying the tissue, therefore, the automatic identification of tumors plays a significant role in early stage diagnosis and its accuracy. To our best knowledge, the use of white light cystoscopy images for bladder tumor diagnosis has not been reported so far. In this paper, a texture analysis based approach is proposed for bladder tumor diagnosis presuming that tumors change in tissue texture. As is well accepted by the scientific community, texture information is more present in the medium to high frequency range which can be selected by using a discrete wavelet transform (DWT). Tumor enhancement can be improved by using automatic segmentation, since a mixing with normal tissue is avoided under ideal conditions. The segmentation module proposed in this paper takes advantage of the wavelet decomposition tree to discard poor texture information in such a way that both steps of the proposed algorithm segmentation and classification share the same focus on texture. Multilayer perceptron and a support vector machine with a stratified ten-fold cross-validation procedure were used for classification purposes by using the hue-saturation-value (HSV), red-green-blue, and CIELab color spaces. Performances of 91% in sensitivity and 92.9% in specificity were obtained regarding HSV color by using both preprocessing and classification steps based on the DWT. The proposed method can achieve good performance on identifying bladder tumor frames. These promising results open the path towards a deeper study regarding the applicability of this algorithm in computer aided diagnosis.

  15. MUC2 Expression Is Correlated with Tumor Differentiation and Inhibits Tumor Invasion in Gastric Carcinomas: A Systematic Review and Meta-analysis

    Directory of Open Access Journals (Sweden)

    Jung-Soo Pyo

    2015-05-01

    Full Text Available Background: While MUC2 is expressed in intestinal metaplasia and malignant lesions, the clinicopathological significance of MUC2 expression is not fully elucidated in gastric carcinoma (GC. Methods: The present study investigated the correlation between MUC2 expression and clinicopathological parameters in 167 human GCs. In addition, to confirm the clinicopathological significance of MUC2 expression, we performed a systematic review and meta-analysis in 1,832 GCs. Results: MUC2 expression was found in 58 of 167 GCs (34.7%. MUC2-expressing GC showed lower primary tumor (T, regional lymph node (N, and tumor node metastasis (TNM stages compared with GCs without MUC2 expression (p=.001, p=.001, and p=.011, respectively. However, MUC2 expression was not correlated with Lauren’s classification and tumor differentiation. In meta-analysis, MUC2 expression was significantly correlated with differentiation and lower tumor stage (odds ratio [OR], 1.303; 95% confidence interval [CI], 1.020 to 1.664; p = .034 and OR, 1.352; 95% CI, 1.055 to 1.734; p = .017, respectively but not with Lauren’s classification, pN stage, or pTNM stage. Conclusions: MUC2 expression was correlated with a lower tumor depth and lower lymph node metastasis in our study; the meta-analysis showed a correlation of MUC2 expression with tumor differentiation and lower tumor depth.

  16. In Silico Analysis of Microarray-Based Gene Expression Profiles Predicts Tumor Cell Response to Withanolides

    Directory of Open Access Journals (Sweden)

    Thomas Efferth

    2012-05-01

    Full Text Available Withania somnifera (L. Dunal (Indian ginseng, winter cherry, Solanaceae is widely used in traditional medicine. Roots are either chewed or used to prepare beverages (aqueous decocts. The major secondary metabolites of Withania somnifera are the withanolides, which are C-28-steroidal lactone triterpenoids. Withania somnifera extracts exert chemopreventive and anticancer activities in vitro and in vivo. The aims of the present in silico study were, firstly, to investigate whether tumor cells develop cross-resistance between standard anticancer drugs and withanolides and, secondly, to elucidate the molecular determinants of sensitivity and resistance of tumor cells towards withanolides. Using IC50 concentrations of eight different withanolides (withaferin A, withaferin A diacetate, 3-azerininylwithaferin A, withafastuosin D diacetate, 4-B-hydroxy-withanolide E, isowithanololide E, withafastuosin E, and withaperuvin and 19 established anticancer drugs, we analyzed the cross-resistance profile of 60 tumor cell lines. The cell lines revealed cross-resistance between the eight withanolides. Consistent cross-resistance between withanolides and nitrosoureas (carmustin, lomustin, and semimustin was also observed. Then, we performed transcriptomic microarray-based COMPARE and hierarchical cluster analyses of mRNA expression to identify mRNA expression profiles predicting sensitivity or resistance towards withanolides. Genes from diverse functional groups were significantly associated with response of tumor cells to withaferin A diacetate, e.g. genes functioning in DNA damage and repair, stress response, cell growth regulation, extracellular matrix components, cell adhesion and cell migration, constituents of the ribosome, cytoskeletal organization and regulation, signal transduction, transcription factors, and others.

  17. A system for tumor heterogeneity evaluation and diagnosis based on tumor markers measured routinely in the laboratory.

    Science.gov (United States)

    Hui, Liu; Rixv, Liu; Xiuying, Zhou

    2015-12-01

    To develop an efficient and reliable approach to estimate tumor heterogeneity and improve tumor diagnosis using multiple tumor markers measured routinely in the clinical laboratory. A total of 161 patients with different cancers were recruited as the cancer group, and 91 patients with non-oncological conditions were required as the non-oncological disease group. The control group comprised 90 randomly selected healthy subjects. AFP, CEA, CYFRA, CA125, CA153, CA199, CA724, and NSE levels were measured in all these subjects with a chemiluminescent microparticle immunoassay. The tumor marker with the maximum S/CO value (sample test value:cutoff value for discriminating individuals with and without tumors) was considered as a specific tumor marker (STM) for an individual. Tumor heterogeneity index (THI)=N/P (N: number of STMs; P: percentage of individuals with STMs in a certain tumor population) was used to quantify tumor heterogeneity: high THI indicated high tumor heterogeneity. The tumor marker index (TMI), TMI = STM×(number of positive tumor markers+1), was used for diagnosis. The THIs of lung, gastric, and liver cancers were 8.33, 9.63, and 5.2, respectively, while the ROC-areas under the curve for TMI were 0.862, 0.809, and 0.966. In this study, we developed a novel index for tumor heterogeneity based on the expression of various routinely evaluated serum tumor markers. Development of an evaluation system for tumor heterogeneity on the basis of this index could provide an effective diagnostic tool for some cancers. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  18. A novel approach for the detection and genetic analysis of live melanoma circulating tumor cells.

    Directory of Open Access Journals (Sweden)

    Melody J Xu

    Full Text Available Circulating tumor cell (CTC detection and genetic analysis may complement currently available disease assessments in patients with melanoma to improve risk stratification and monitoring. We therefore sought to establish the feasibility of a telomerase-based assay for detecting and isolating live melanoma CTCs.The telomerase-based CTC assay utilizes an adenoviral vector that, in the presence of elevated human telomerase activity, drives the amplification of green fluorescent protein. Tumor cells are then identified via an image processing system. The protocol was tested on melanoma cells in culture or spiked into control blood, and on samples from patients with metastatic melanoma. Genetic analysis of the isolated melanoma CTCs was then performed for BRAF mutation status.The adenoviral vector was effective for all melanoma cell lines tested with sensitivity of 88.7% (95%CI 85.6-90.4% and specificity of 99.9% (95%CI 99.8-99.9%. In a pilot trial of patients with metastatic disease, CTCs were identified in 9 of 10 patients, with a mean of 6.0 CTCs/mL. At a cutoff of 1.1 CTCs/mL, the telomerase-based assay exhibits test performance of 90.0% sensitivity and 91.7% specificity. BRAF mutation analysis of melanoma cells isolated from culture or spiked control blood, or from pilot patient samples was found to match the known BRAF mutation status of the cell lines and primary tumors.To our knowledge, this is the first report of a telomerase-based assay effective for detecting and isolating live melanoma CTCs. These promising findings support further studies, including towards integrating into the management of patients with melanoma receiving multimodality therapy.

  19. Building a high-resolution T2-weighted MR-based probabilistic model of tumor occurrence in the prostate.

    Science.gov (United States)

    Nagarajan, Mahesh B; Raman, Steven S; Lo, Pechin; Lin, Wei-Chan; Khoshnoodi, Pooria; Sayre, James W; Ramakrishna, Bharath; Ahuja, Preeti; Huang, Jiaoti; Margolis, Daniel J A; Lu, David S K; Reiter, Robert E; Goldin, Jonathan G; Brown, Matthew S; Enzmann, Dieter R

    2018-02-19

    We present a method for generating a T2 MR-based probabilistic model of tumor occurrence in the prostate to guide the selection of anatomical sites for targeted biopsies and serve as a diagnostic tool to aid radiological evaluation of prostate cancer. In our study, the prostate and any radiological findings within were segmented retrospectively on 3D T2-weighted MR images of 266 subjects who underwent radical prostatectomy. Subsequent histopathological analysis determined both the ground truth and the Gleason grade of the tumors. A randomly chosen subset of 19 subjects was used to generate a multi-subject-derived prostate template. Subsequently, a cascading registration algorithm involving both affine and non-rigid B-spline transforms was used to register the prostate of every subject to the template. Corresponding transformation of radiological findings yielded a population-based probabilistic model of tumor occurrence. The quality of our probabilistic model building approach was statistically evaluated by measuring the proportion of correct placements of tumors in the prostate template, i.e., the number of tumors that maintained their anatomical location within the prostate after their transformation into the prostate template space. Probabilistic model built with tumors deemed clinically significant demonstrated a heterogeneous distribution of tumors, with higher likelihood of tumor occurrence at the mid-gland anterior transition zone and the base-to-mid-gland posterior peripheral zones. Of 250 MR lesions analyzed, 248 maintained their original anatomical location with respect to the prostate zones after transformation to the prostate. We present a robust method for generating a probabilistic model of tumor occurrence in the prostate that could aid clinical decision making, such as selection of anatomical sites for MR-guided prostate biopsies.

  20. Anatomical specificity of vascular endothelial growth factor expression in glioblastomas: a voxel-based mapping analysis

    Energy Technology Data Exchange (ETDEWEB)

    Fan, Xing [Capital Medical University, Department of Neurosurgery, Beijing Tiantan Hospital, Beijing (China); Wang, Yinyan [Capital Medical University, Department of Neurosurgery, Beijing Tiantan Hospital, Beijing (China); Capital Medical University, Department of Neuropathology, Beijing Neurosurgical Institute, Beijing (China); Wang, Kai; Ma, Jun; Li, Shaowu [Capital Medical University, Department of Neuroradiology, Beijing Tiantan Hospital, Beijing (China); Liu, Shuai [Chinese Academy of Medical Sciences and Peking Union Medical College, Departments of Neurosurgery, Peking Union Medical College Hospital, Beijing (China); Liu, Yong [Chinese Academy of Sciences, Brainnetome Center, Institute of Automation, Beijing (China); Jiang, Tao [Capital Medical University, Department of Neurosurgery, Beijing Tiantan Hospital, Beijing (China); Beijing Academy of Critical Illness in Brain, Department of Clinical Oncology, Beijing (China)

    2016-01-15

    The expression of vascular endothelial growth factor (VEGF) is a common genetic alteration in malignant gliomas and contributes to the angiogenesis of tumors. This study aimed to investigate the anatomical specificity of VEGF expression levels in glioblastomas using voxel-based neuroimaging analysis. Clinical information, MR scans, and immunohistochemistry stains of 209 patients with glioblastomas were reviewed. All tumor lesions were segmented manually and subsequently registered to standard brain space. Voxel-based regression analysis was performed to correlate the brain regions of tumor involvement with the level of VEGF expression. Brain regions identified as significantly associated with high or low VEGF expression were preserved following permutation correction. High VEGF expression was detected in 123 (58.9 %) of the 209 patients. Voxel-based statistical analysis demonstrated that high VEGF expression was more likely in tumors located in the left frontal lobe and the right caudate and low VEGF expression was more likely in tumors that occurred in the posterior region of the right lateral ventricle. Voxel-based neuroimaging analysis revealed the anatomic specificity of VEGF expression in glioblastoma, which may further our understanding of genetic heterogeneity during tumor origination. This finding provides primary theoretical support for potential future application of customized antiangiogenic therapy. (orig.)

  1. Anatomical specificity of vascular endothelial growth factor expression in glioblastomas: a voxel-based mapping analysis

    International Nuclear Information System (INIS)

    Fan, Xing; Wang, Yinyan; Wang, Kai; Ma, Jun; Li, Shaowu; Liu, Shuai; Liu, Yong; Jiang, Tao

    2016-01-01

    The expression of vascular endothelial growth factor (VEGF) is a common genetic alteration in malignant gliomas and contributes to the angiogenesis of tumors. This study aimed to investigate the anatomical specificity of VEGF expression levels in glioblastomas using voxel-based neuroimaging analysis. Clinical information, MR scans, and immunohistochemistry stains of 209 patients with glioblastomas were reviewed. All tumor lesions were segmented manually and subsequently registered to standard brain space. Voxel-based regression analysis was performed to correlate the brain regions of tumor involvement with the level of VEGF expression. Brain regions identified as significantly associated with high or low VEGF expression were preserved following permutation correction. High VEGF expression was detected in 123 (58.9 %) of the 209 patients. Voxel-based statistical analysis demonstrated that high VEGF expression was more likely in tumors located in the left frontal lobe and the right caudate and low VEGF expression was more likely in tumors that occurred in the posterior region of the right lateral ventricle. Voxel-based neuroimaging analysis revealed the anatomic specificity of VEGF expression in glioblastoma, which may further our understanding of genetic heterogeneity during tumor origination. This finding provides primary theoretical support for potential future application of customized antiangiogenic therapy. (orig.)

  2. Circulating tumor DNA functions as an alternative for tissue to overcome tumor heterogeneity in advanced gastric cancer.

    Science.gov (United States)

    Gao, Jing; Wang, Haixing; Zang, Wanchun; Li, Beifang; Rao, Guanhua; Li, Lei; Yu, Yang; Li, Zhongwu; Dong, Bin; Lu, Zhihao; Jiang, Zhi; Shen, Lin

    2017-09-01

    Overcoming tumor heterogeneity is a major challenge for personalized treatment of gastric cancer, especially for human epidermal growth factor receptor-2 targeted therapy. Analysis of circulating tumor DNA allows a more comprehensive analysis of tumor heterogeneity than traditional biopsies in lung cancer and breast cancer, but little is known in gastric cancer. We assessed mutation profiles of ctDNA and primary tumors from 30 patients with advanced gastric cancer, then performed a comprehensive analysis of tumor mutations by multiple biopsies from five patients, and finally analyzed the concordance of HER2 amplification in ctDNA and paired tumor tissues in 70 patients. By comparing with a single tumor sample, ctDNA displayed a low concordance of mutation profile, only approximately 50% (138/275) somatic mutations were found in paired tissue samples, however, when compared with multiple biopsies, most DNA mutations in ctDNA were also shown in paired tumor tissues. ctDNA had a high concordance (91.4%, Kappa index = 0.784, P < 0.001) of HER2 amplification with tumor tissues, suggesting it might be an alternative for tissue. It implied that ctDNA-based assessment could partially overcome the tumor heterogeneity, and might serve as a potential surrogate for HER2 analysis in gastric cancer. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  3. Cluster analysis of quantitative parametric maps from DCE-MRI: application in evaluating heterogeneity of tumor response to antiangiogenic treatment.

    Science.gov (United States)

    Longo, Dario Livio; Dastrù, Walter; Consolino, Lorena; Espak, Miklos; Arigoni, Maddalena; Cavallo, Federica; Aime, Silvio

    2015-07-01

    The objective of this study was to compare a clustering approach to conventional analysis methods for assessing changes in pharmacokinetic parameters obtained from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) during antiangiogenic treatment in a breast cancer model. BALB/c mice bearing established transplantable her2+ tumors were treated with a DNA-based antiangiogenic vaccine or with an empty plasmid (untreated group). DCE-MRI was carried out by administering a dose of 0.05 mmol/kg of Gadocoletic acid trisodium salt, a Gd-based blood pool contrast agent (CA) at 1T. Changes in pharmacokinetic estimates (K(trans) and vp) in a nine-day interval were compared between treated and untreated groups on a voxel-by-voxel analysis. The tumor response to therapy was assessed by a clustering approach and compared with conventional summary statistics, with sub-regions analysis and with histogram analysis. Both the K(trans) and vp estimates, following blood-pool CA injection, showed marked and spatial heterogeneous changes with antiangiogenic treatment. Averaged values for the whole tumor region, as well as from the rim/core sub-regions analysis were unable to assess the antiangiogenic response. Histogram analysis resulted in significant changes only in the vp estimates (pclustering approach depicted marked changes in both the K(trans) and vp estimates, with significant spatial heterogeneity in vp maps in response to treatment (pclustered in three or four sub-regions. This study demonstrated the value of cluster analysis applied to pharmacokinetic DCE-MRI parametric maps for assessing tumor response to antiangiogenic therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Analysis on CT features of tumor-like gastric schwannomas

    International Nuclear Information System (INIS)

    Zhang Yu; Chen Jie

    2011-01-01

    Objective: To analyze CT imaging features of tumor-like gastric schwannomas. Methods: Ten patients with gastric schwannomas were retrospectively analyzed. All were scanned with pre-and pro-enhanced CT. Analysis of the CT findings included evaluation of the volume, number, location, contour, growth pattern, border, enhancement pattern, and enhancement grade as well as the presence of surface dimpling, integrity of overlying mucosa. All cases were confirmed by pathology. Results: In every case, simple tumor was present. The largest was about 5.7 cm in the diameter, the smallest was 2.3 cm. All tumors were round or oval, and one tumor was slightly lobulated. Endoluminal growth pattern was defined in two cases, exoluminal growth pattern was defined in one case, and a mixed growth pattern was noted in the rest. The borders of tumors were clear. In arterial phase, no visible enhancement was present in eight cases and mild enhancement in two cases. All cases were constantly enhanced in portal phase. Superficial ulcers were present in four cases. Conclusion: CT findings of tumor-like gastric schwannomas are distinctive to a certain degree. It can be used to guide clinical therapy. (authors)

  5. Development of a Prognostic Marker for Lung Cancer Using Analysis of Tumor Evolution

    Science.gov (United States)

    2017-08-01

    AWARD NUMBER: W81XWH-15-1-0243 TITLE: Development of a Prognostic Marker for Lung Cancer Using Analysis of Tumor Evolution PRINCIPAL...SUBTITLE 5a. CONTRACT NUMBER Development of a Prognostic Marker for Lung Cancer Using Analysis of Tumor Evolution 5b. GRANT NUMBER 5c. PROGRAM...derive a prognostic classifier. 15. SUBJECT TERMS NSCLC; tumor evolution ; whole exome sequencing 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF

  6. Mesenchymal stem cell 1 (MSC1-based therapy attenuates tumor growth whereas MSC2-treatment promotes tumor growth and metastasis.

    Directory of Open Access Journals (Sweden)

    Ruth S Waterman

    Full Text Available Currently, there are many promising clinical trials using mesenchymal stem cells (MSCs in cell-based therapies of numerous diseases. Increasingly, however, there is a concern over the use of MSCs because they home to tumors and can support tumor growth and metastasis. For instance, we established that MSCs in the ovarian tumor microenvironment promoted tumor growth and favored angiogenesis. In parallel studies, we also developed a new approach to induce the conventional mixed pool of MSCs into two uniform but distinct phenotypes we termed MSC1 and MSC2.Here we tested the in vitro and in vivo stability of MSC1 and MSC2 phenotypes as well as their effects on tumor growth and spread. In vitro co-culture of MSC1 with various cancer cells diminished growth in colony forming units and tumor spheroid assays, while conventional MSCs or MSC2 co-culture had the opposite effect in these assays. Co-culture of MSC1 and cancer cells also distinctly affected their migration and invasion potential when compared to MSCs or MSC2 treated samples. The expression of bioactive molecules also differed dramatically among these samples. MSC1-based treatment of established tumors in an immune competent model attenuated tumor growth and metastasis in contrast to MSCs- and MSC2-treated animals in which tumor growth and spread was increased. Also, in contrast to these groups, MSC1-therapy led to less ascites accumulation, increased CD45+leukocytes, decreased collagen deposition, and mast cell degranulation.These observations indicate that the MSC1 and MSC2 phenotypes may be convenient tools for the discovery of critical components of the tumor stroma. The continued investigation of these cells may help ensure that cell based-therapy is used safely and effectively in human disease.

  7. A new ODE tumor growth modeling based on tumor population dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Oroji, Amin; Omar, Mohd bin [Institute of Mathematical Sciences, Faculty of Science University of Malaya, 50603 Kuala Lumpur, Malaysia amin.oroji@siswa.um.edu.my, mohd@um.edu.my (Malaysia); Yarahmadian, Shantia [Mathematics Department Mississippi State University, USA Syarahmadian@math.msstate.edu (United States)

    2015-10-22

    In this paper a new mathematical model for the population of tumor growth treated by radiation is proposed. The cells dynamics population in each state and the dynamics of whole tumor population are studied. Furthermore, a new definition of tumor lifespan is presented. Finally, the effects of two main parameters, treatment parameter (q), and repair mechanism parameter (r) on tumor lifespan are probed, and it is showed that the change in treatment parameter (q) highly affects the tumor lifespan.

  8. A new ODE tumor growth modeling based on tumor population dynamics

    International Nuclear Information System (INIS)

    Oroji, Amin; Omar, Mohd bin; Yarahmadian, Shantia

    2015-01-01

    In this paper a new mathematical model for the population of tumor growth treated by radiation is proposed. The cells dynamics population in each state and the dynamics of whole tumor population are studied. Furthermore, a new definition of tumor lifespan is presented. Finally, the effects of two main parameters, treatment parameter (q), and repair mechanism parameter (r) on tumor lifespan are probed, and it is showed that the change in treatment parameter (q) highly affects the tumor lifespan

  9. Skull base tumors: a comprehensive review of transfacial swing osteotomy approaches.

    Science.gov (United States)

    Moreira-Gonzalez, Andrea; Pieper, Daniel R; Cambra, Jorge Balaguer; Simman, Richard; Jackson, Ian T

    2005-03-01

    Numerous techniques have been proposed for the resection of skull base tumors, each one unique with regard to the region exposed and degree of technical complexity. This study describes the use of transfacial swing osteotomies in accessing lesions located at various levels of the cranial base. Eight patients who underwent transfacial swings for exposure and resection of cranial base lesions between 1996 and 2002 were studied. The mandible was the choice when wide exposure of nasopharyngeal and midline skull base tumors was necessary, especially when they involved the infratemporal fossa. The midfacial swing osteotomy was an option when access to the entire clivus was necessary. An orbital swing approach was used to access large orbital tumors lying inferior to the optic nerve and posterior to the globe, a region that is often difficult to visualize. Gross total tumor excision was possible in all patients. Six patients achieved disease control and two had recurrences. The complications of cerebrospinal fluid leak, infection, hematoma, or cranial nerve damage did not occur. After surgery, some patients experienced temporary symptoms caused by local swelling. The aesthetic result was considered good. Transfacial swing osteotomies provide a wide exposure to tumors that occur in the central skull base area. Excellent knowledge of the detailed anatomy of this region is paramount to the success of this surgery. The team concept is essential; it is built around the craniofacial surgeon and an experienced skull base neurosurgeon.

  10. SU-E-J-275: Review - Computerized PET/CT Image Analysis in the Evaluation of Tumor Response to Therapy

    International Nuclear Information System (INIS)

    Lu, W; Wang, J; Zhang, H

    2015-01-01

    Purpose: To review the literature in using computerized PET/CT image analysis for the evaluation of tumor response to therapy. Methods: We reviewed and summarized more than 100 papers that used computerized image analysis techniques for the evaluation of tumor response with PET/CT. This review mainly covered four aspects: image registration, tumor segmentation, image feature extraction, and response evaluation. Results: Although rigid image registration is straightforward, it has been shown to achieve good alignment between baseline and evaluation scans. Deformable image registration has been shown to improve the alignment when complex deformable distortions occur due to tumor shrinkage, weight loss or gain, and motion. Many semi-automatic tumor segmentation methods have been developed on PET. A comparative study revealed benefits of high levels of user interaction with simultaneous visualization of CT images and PET gradients. On CT, semi-automatic methods have been developed for only tumors that show marked difference in CT attenuation between the tumor and the surrounding normal tissues. Quite a few multi-modality segmentation methods have been shown to improve accuracy compared to single-modality algorithms. Advanced PET image features considering spatial information, such as tumor volume, tumor shape, total glycolytic volume, histogram distance, and texture features have been found more informative than the traditional SUVmax for the prediction of tumor response. Advanced CT features, including volumetric, attenuation, morphologic, structure, and texture descriptors, have also been found advantage over the traditional RECIST and WHO criteria in certain tumor types. Predictive models based on machine learning technique have been constructed for correlating selected image features to response. These models showed improved performance compared to current methods using cutoff value of a single measurement for tumor response. Conclusion: This review showed that

  11. SU-E-J-275: Review - Computerized PET/CT Image Analysis in the Evaluation of Tumor Response to Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Lu, W; Wang, J; Zhang, H [University of Maryland School of Medicine, Baltimore, MD (United States)

    2015-06-15

    Purpose: To review the literature in using computerized PET/CT image analysis for the evaluation of tumor response to therapy. Methods: We reviewed and summarized more than 100 papers that used computerized image analysis techniques for the evaluation of tumor response with PET/CT. This review mainly covered four aspects: image registration, tumor segmentation, image feature extraction, and response evaluation. Results: Although rigid image registration is straightforward, it has been shown to achieve good alignment between baseline and evaluation scans. Deformable image registration has been shown to improve the alignment when complex deformable distortions occur due to tumor shrinkage, weight loss or gain, and motion. Many semi-automatic tumor segmentation methods have been developed on PET. A comparative study revealed benefits of high levels of user interaction with simultaneous visualization of CT images and PET gradients. On CT, semi-automatic methods have been developed for only tumors that show marked difference in CT attenuation between the tumor and the surrounding normal tissues. Quite a few multi-modality segmentation methods have been shown to improve accuracy compared to single-modality algorithms. Advanced PET image features considering spatial information, such as tumor volume, tumor shape, total glycolytic volume, histogram distance, and texture features have been found more informative than the traditional SUVmax for the prediction of tumor response. Advanced CT features, including volumetric, attenuation, morphologic, structure, and texture descriptors, have also been found advantage over the traditional RECIST and WHO criteria in certain tumor types. Predictive models based on machine learning technique have been constructed for correlating selected image features to response. These models showed improved performance compared to current methods using cutoff value of a single measurement for tumor response. Conclusion: This review showed that

  12. Analysis of image heterogeneity using 2D Minkowski functionals detects tumor responses to treatment.

    Science.gov (United States)

    Larkin, Timothy J; Canuto, Holly C; Kettunen, Mikko I; Booth, Thomas C; Hu, De-En; Krishnan, Anant S; Bohndiek, Sarah E; Neves, André A; McLachlan, Charles; Hobson, Michael P; Brindle, Kevin M

    2014-01-01

    The acquisition of ever increasing volumes of high resolution magnetic resonance imaging (MRI) data has created an urgent need to develop automated and objective image analysis algorithms that can assist in determining tumor margins, diagnosing tumor stage, and detecting treatment response. We have shown previously that Minkowski functionals, which are precise morphological and structural descriptors of image heterogeneity, can be used to enhance the detection, in T1 -weighted images, of a targeted Gd(3+) -chelate-based contrast agent for detecting tumor cell death. We have used Minkowski functionals here to characterize heterogeneity in T2 -weighted images acquired before and after drug treatment, and obtained without contrast agent administration. We show that Minkowski functionals can be used to characterize the changes in image heterogeneity that accompany treatment of tumors with a vascular disrupting agent, combretastatin A4-phosphate, and with a cytotoxic drug, etoposide. Parameterizing changes in the heterogeneity of T2 -weighted images can be used to detect early responses of tumors to drug treatment, even when there is no change in tumor size. The approach provides a quantitative and therefore objective assessment of treatment response that could be used with other types of MR image and also with other imaging modalities. Copyright © 2013 Wiley Periodicals, Inc.

  13. A statistical method for lung tumor segmentation uncertainty in PET images based on user inference.

    Science.gov (United States)

    Zheng, Chaojie; Wang, Xiuying; Feng, Dagan

    2015-01-01

    PET has been widely accepted as an effective imaging modality for lung tumor diagnosis and treatment. However, standard criteria for delineating tumor boundary from PET are yet to develop largely due to relatively low quality of PET images, uncertain tumor boundary definition, and variety of tumor characteristics. In this paper, we propose a statistical solution to segmentation uncertainty on the basis of user inference. We firstly define the uncertainty segmentation band on the basis of segmentation probability map constructed from Random Walks (RW) algorithm; and then based on the extracted features of the user inference, we use Principle Component Analysis (PCA) to formulate the statistical model for labeling the uncertainty band. We validated our method on 10 lung PET-CT phantom studies from the public RIDER collections [1] and 16 clinical PET studies where tumors were manually delineated by two experienced radiologists. The methods were validated using Dice similarity coefficient (DSC) to measure the spatial volume overlap. Our method achieved an average DSC of 0.878 ± 0.078 on phantom studies and 0.835 ± 0.039 on clinical studies.

  14. Detection of T790M, the acquired resistance EGFR mutation, by tumor biopsy versus noninvasive blood-based analyses

    Science.gov (United States)

    Sundaresan, Tilak K.; Sequist, Lecia V.; Heymach, John V.; Riely, Gregory J.; Jänne, Pasi A.; Koch, Walter H.; Sullivan, James P.; Fox, Douglas B.; Maher, Robert; Muzikansky, Alona; Webb, Andrew; Tran, Hai T.; Giri, Uma; Fleisher, Martin; Yu, Helena A.; Wei, Wen; Johnson, Bruce E.; Barber, Thomas A.; Walsh, John R.; Engelman, Jeffrey A.; Stott, Shannon L.; Kapur, Ravi; Maheswaran, Shyamala; Toner, Mehmet

    2015-01-01

    Purpose The T790M gatekeeper mutation in the Epidermal Growth Factor Receptor (EGFR) is acquired by some EGFR-mutant non-small cell lung cancers (NSCLC) as they become resistant to selective tyrosine kinase inhibitors (TKIs). As third generation EGFR TKIs that overcome T790M-associated resistance become available, noninvasive approaches to T790M detection will become critical to guide management. Experimental Design As part of a multi-institutional Stand-Up-To-Cancer collaboration, we performed an exploratory analysis of 40 patients with EGFR-mutant tumors progressing on EGFR TKI therapy. We compared the T790M genotype from tumor biopsies with analysis of simultaneously collected circulating tumor cells (CTC) and circulating tumor DNA (ctDNA). Results T790M genotypes were successfully obtained in 30 (75%) tumor biopsies, 28 (70%) CTC samples and 32 (80%) ctDNA samples. The resistance-associated mutation was detected in 47–50% of patients using each of the genotyping assays, with concordance among them ranging from 57–74%. While CTC- and ctDNA-based genotyping were each unsuccessful in 20–30% of cases, the two assays together enabled genotyping in all patients with an available blood sample, and they identified the T790M mutation in 14 (35%) patients in whom the concurrent biopsy was negative or indeterminate. Conclusion Discordant genotypes between tumor biopsy and blood-based analyses may result from technological differences, as well as sampling different tumor cell populations. The use of complementary approaches may provide the most complete assessment of each patient’s cancer, which should be validated in predicting response to T790M-targeted inhibitors. PMID:26446944

  15. Transcriptome Analysis of Individual Stromal Cell Populations Identifies Stroma-Tumor Crosstalk in Mouse Lung Cancer Model

    Directory of Open Access Journals (Sweden)

    Hyejin Choi

    2015-02-01

    Full Text Available Emerging studies have begun to demonstrate that reprogrammed stromal cells play pivotal roles in tumor growth, metastasis, and resistance to therapy. However, the contribution of stromal cells to non-small-cell lung cancer (NSCLC has remained underexplored. We used an orthotopic model of Kras-driven NSCLC to systematically dissect the contribution of specific hematopoietic stromal cells in lung cancer. RNA deep-sequencing analysis of individually sorted myeloid lineage and tumor epithelial cells revealed cell-type-specific differentially regulated genes, indicative of activated stroma. We developed a computational model for crosstalk signaling discovery based on ligand-receptor interactions and downstream signaling networks and identified known and novel tumor-stroma paracrine and tumor autocrine crosstalk-signaling pathways in NSCLC. We provide cellular and molecular insights into components of the lung cancer microenvironment that contribute to carcinogenesis. This study has the potential for development of therapeutic strategies that target tumor-stroma interactions and may complement conventional anti-cancer treatments.

  16. Nanobody-based cancer therapy of solid tumors

    NARCIS (Netherlands)

    Kijanka, Marta|info:eu-repo/dai/nl/328212792; Dorresteijn, Bram|info:eu-repo/dai/nl/31401635X; Oliveira, Sabrina; van Bergen en Henegouwen, Paul M P|info:eu-repo/dai/nl/071919481

    The development of tumor-targeted therapies using monoclonal antibodies has been successful during the last 30 years. Nevertheless, the efficacy of antibody-based therapy is still limited and further improvements are eagerly awaited. One of the promising novel developments that may overcome the

  17. SU-F-207-06: CT-Based Assessment of Tumor Volume in Malignant Pleural Mesothelioma

    International Nuclear Information System (INIS)

    Qayyum, F; Armato, S; Straus, C; Husain, A; Vigneswaran, W; Kindler, H

    2015-01-01

    Purpose: To determine the potential utility of computed tomography (CT) scans in the assessment of physical tumor bulk in malignant pleural mesothelioma patients. Methods: Twenty-eight patients with malignant pleural mesothelioma were used for this study. A CT scan was acquired for each patient prior to surgical resection of the tumor (median time between scan and surgery: 27 days). After surgery, the ex-vivo tumor volume was measured by a pathologist using a water displacement method. Separately, a radiologist identified and outlined the tumor boundary on each CT section that demonstrated tumor. These outlines then were analyzed to determine the total volume of disease present, the number of sections with outlines, and the mean volume of disease per outlined section. Subsets of the initial patient cohort were defined based on these parameters, i.e. cases with at least 30 sections of disease with a mean disease volume of at least 3mL per section. For each subset, the R- squared correlation between CT-based tumor volume and physical ex-vivo tumor volume was calculated. Results: The full cohort of 28 patients yielded a modest correlation between CT-based tumor volume and the ex-vivo tumor volume with an R-squared value of 0.66. In general, as the mean tumor volume per section increased, the correlation of CT-based volume with the physical tumor volume improved substantially. For example, when cases with at least 40 CT sections presenting a mean of at least 2mL of disease per section were evaluated (n=20) the R-squared correlation increased to 0.79. Conclusion: While image-based volumetry for mesothelioma may not generally capture physical tumor volume as accurately as one might expect, there exists a set of conditions in which CT-based volume is highly correlated with the physical tumor volume. SGA receives royalties and licensing fees through the University of Chicago for computer-aided diagnosis technology

  18. SU-F-207-06: CT-Based Assessment of Tumor Volume in Malignant Pleural Mesothelioma

    Energy Technology Data Exchange (ETDEWEB)

    Qayyum, F; Armato, S; Straus, C; Husain, A; Vigneswaran, W; Kindler, H [The University of Chicago, Chicago, IL (United States)

    2015-06-15

    Purpose: To determine the potential utility of computed tomography (CT) scans in the assessment of physical tumor bulk in malignant pleural mesothelioma patients. Methods: Twenty-eight patients with malignant pleural mesothelioma were used for this study. A CT scan was acquired for each patient prior to surgical resection of the tumor (median time between scan and surgery: 27 days). After surgery, the ex-vivo tumor volume was measured by a pathologist using a water displacement method. Separately, a radiologist identified and outlined the tumor boundary on each CT section that demonstrated tumor. These outlines then were analyzed to determine the total volume of disease present, the number of sections with outlines, and the mean volume of disease per outlined section. Subsets of the initial patient cohort were defined based on these parameters, i.e. cases with at least 30 sections of disease with a mean disease volume of at least 3mL per section. For each subset, the R- squared correlation between CT-based tumor volume and physical ex-vivo tumor volume was calculated. Results: The full cohort of 28 patients yielded a modest correlation between CT-based tumor volume and the ex-vivo tumor volume with an R-squared value of 0.66. In general, as the mean tumor volume per section increased, the correlation of CT-based volume with the physical tumor volume improved substantially. For example, when cases with at least 40 CT sections presenting a mean of at least 2mL of disease per section were evaluated (n=20) the R-squared correlation increased to 0.79. Conclusion: While image-based volumetry for mesothelioma may not generally capture physical tumor volume as accurately as one might expect, there exists a set of conditions in which CT-based volume is highly correlated with the physical tumor volume. SGA receives royalties and licensing fees through the University of Chicago for computer-aided diagnosis technology.

  19. Comparative expression pathway analysis of human and canine mammary tumors

    Directory of Open Access Journals (Sweden)

    Marconato Laura

    2009-03-01

    Full Text Available Abstract Background Spontaneous tumors in dog have been demonstrated to share many features with their human counterparts, including relevant molecular targets, histological appearance, genetics, biological behavior and response to conventional treatments. Mammary tumors in dog therefore provide an attractive alternative to more classical mouse models, such as transgenics or xenografts, where the tumour is artificially induced. To assess the extent to which dog tumors represent clinically significant human phenotypes, we performed the first genome-wide comparative analysis of transcriptional changes occurring in mammary tumors of the two species, with particular focus on the molecular pathways involved. Results We analyzed human and dog gene expression data derived from both tumor and normal mammary samples. By analyzing the expression levels of about ten thousand dog/human orthologous genes we observed a significant overlap of genes deregulated in the mammary tumor samples, as compared to their normal counterparts. Pathway analysis of gene expression data revealed a great degree of similarity in the perturbation of many cancer-related pathways, including the 'PI3K/AKT', 'KRAS', 'PTEN', 'WNT-beta catenin' and 'MAPK cascade'. Moreover, we show that the transcriptional relationships between different gene signatures observed in human breast cancer are largely maintained in the canine model, suggesting a close interspecies similarity in the network of cancer signalling circuitries. Conclusion Our data confirm and further strengthen the value of the canine mammary cancer model and open up new perspectives for the evaluation of novel cancer therapeutics and the development of prognostic and diagnostic biomarkers to be used in clinical studies.

  20. Analysis of Vision Loss Caused by Radiation-Induced Optic Neuropathy After Particle Therapy for Head-and-Neck and Skull-Base Tumors Adjacent to Optic Nerves

    International Nuclear Information System (INIS)

    Demizu, Yusuke; Murakami, Masao; Miyawaki, Daisuke; Niwa, Yasue; Akagi, Takashi; Sasaki, Ryohei; Terashima, Kazuki; Suga, Daisaku; Kamae, Isao; Hishikawa, Yoshio

    2009-01-01

    Purpose: To assess the incident rates of vision loss (VL; based on counting fingers or more severe) caused by radiation-induced optic neuropathy (RION) after particle therapy for tumors adjacent to optic nerves (ONs), and to evaluate factors that may contribute to VL. Methods and Materials: From August 2001 to August 2006, 104 patients with head-and-neck or skull-base tumors adjacent to ONs were treated with carbon ion or proton radiotherapy. Among them, 145 ONs of 75 patients were irradiated and followed for greater than 12 months. The incident rate of VL and the prognostic factors for occurrence of VL were evaluated. The late effects of carbon ion and proton beams were compared on the basis of a biologically effective dose at α/β = 3 gray equivalent (GyE 3 ). Results: Eight patients (11%) experienced VL resulting from RION. The onset of VL ranged from 17 to 58 months. The median follow-up was 25 months. No significant difference was observed between the carbon ion and proton beam treatment groups. On univariate analysis, age (>60 years), diabetes mellitus, and maximum dose to the ON (>110 GyE 3 ) were significant, whereas on multivariate analysis only diabetes mellitus was found to be significant for VL. Conclusions: The time to the onset of VL was highly variable. There was no statistically significant difference between carbon ion and proton beam treatments over the follow-up period. Based on multivariate analysis, diabetes mellitus correlated with the occurrence of VL. A larger study with longer follow-up is warranted.

  1. Protein expression based multimarker analysis of breast cancer samples

    International Nuclear Information System (INIS)

    Presson, Angela P; Horvath, Steve; Yoon, Nam K; Bagryanova, Lora; Mah, Vei; Alavi, Mohammad; Maresh, Erin L; Rajasekaran, Ayyappan K; Goodglick, Lee; Chia, David

    2011-01-01

    Tissue microarray (TMA) data are commonly used to validate the prognostic accuracy of tumor markers. For example, breast cancer TMA data have led to the identification of several promising prognostic markers of survival time. Several studies have shown that TMA data can also be used to cluster patients into clinically distinct groups. Here we use breast cancer TMA data to cluster patients into distinct prognostic groups. We apply weighted correlation network analysis (WGCNA) to TMA data consisting of 26 putative tumor biomarkers measured on 82 breast cancer patients. Based on this analysis we identify three groups of patients with low (5.4%), moderate (22%) and high (50%) mortality rates, respectively. We then develop a simple threshold rule using a subset of three markers (p53, Na-KATPase-β1, and TGF β receptor II) that can approximately define these mortality groups. We compare the results of this correlation network analysis with results from a standard Cox regression analysis. We find that the rule-based grouping variable (referred to as WGCNA*) is an independent predictor of survival time. While WGCNA* is based on protein measurements (TMA data), it validated in two independent Affymetrix microarray gene expression data (which measure mRNA abundance). We find that the WGCNA patient groups differed by 35% from mortality groups defined by a more conventional stepwise Cox regression analysis approach. We show that correlation network methods, which are primarily used to analyze the relationships between gene products, are also useful for analyzing the relationships between patients and for defining distinct patient groups based on TMA data. We identify a rule based on three tumor markers for predicting breast cancer survival outcomes

  2. Systematic Analysis of Time-Series Gene Expression Data on Tumor Cell-Selective Apoptotic Responses to HDAC Inhibitors

    Directory of Open Access Journals (Sweden)

    Yun-feng Qi

    2014-01-01

    Full Text Available SAHA (suberoylanilide hydroxamic acid or vorinostat is the first nonselective histone deacetylase (HDAC inhibitor approved by the US Food and Drug Administration (FDA. SAHA affects histone acetylation in chromatin and a variety of nonhistone substrates, thus influencing many cellular processes. In particularly, SAHA induces selective apoptosis of tumor cells, although the mechanism is not well understood. A series of microarray experiments was recently conducted to investigate tumor cell-selective proapoptotic transcriptional responses induced by SAHA. Based on that gene expression time series, we propose a novel framework for detailed analysis of the mechanism of tumor cell apoptosis selectively induced by SAHA. Our analyses indicated that SAHA selectively disrupted the DNA damage response, cell cycle, p53 expression, and mitochondrial integrity of tumor samples to induce selective tumor cell apoptosis. Our results suggest a possible regulation network. Our research extends the existing research.

  3. Whole-tumor histogram analysis of the cerebral blood volume map: tumor volume defined by 11C-methionine positron emission tomography image improves the diagnostic accuracy of cerebral glioma grading.

    Science.gov (United States)

    Wu, Rongli; Watanabe, Yoshiyuki; Arisawa, Atsuko; Takahashi, Hiroto; Tanaka, Hisashi; Fujimoto, Yasunori; Watabe, Tadashi; Isohashi, Kayako; Hatazawa, Jun; Tomiyama, Noriyuki

    2017-10-01

    This study aimed to compare the tumor volume definition using conventional magnetic resonance (MR) and 11C-methionine positron emission tomography (MET/PET) images in the differentiation of the pre-operative glioma grade by using whole-tumor histogram analysis of normalized cerebral blood volume (nCBV) maps. Thirty-four patients with histopathologically proven primary brain low-grade gliomas (n = 15) and high-grade gliomas (n = 19) underwent pre-operative or pre-biopsy MET/PET, fluid-attenuated inversion recovery, dynamic susceptibility contrast perfusion-weighted magnetic resonance imaging, and contrast-enhanced T1-weighted at 3.0 T. The histogram distribution derived from the nCBV maps was obtained by co-registering the whole tumor volume delineated on conventional MR or MET/PET images, and eight histogram parameters were assessed. The mean nCBV value had the highest AUC value (0.906) based on MET/PET images. Diagnostic accuracy significantly improved when the tumor volume was measured from MET/PET images compared with conventional MR images for the parameters of mean, 50th, and 75th percentile nCBV value (p = 0.0246, 0.0223, and 0.0150, respectively). Whole-tumor histogram analysis of CBV map provides more valuable histogram parameters and increases diagnostic accuracy in the differentiation of pre-operative cerebral gliomas when the tumor volume is derived from MET/PET images.

  4. Iterative volume morphing and learning for mobile tumor based on 4DCT.

    Science.gov (United States)

    Mao, Songan; Wu, Huanmei; Sandison, George; Fang, Shiaofen

    2017-02-21

    During image-guided cancer radiation treatment, three-dimensional (3D) tumor volumetric information is important for treatment success. However, it is typically not feasible to image a patient's 3D tumor continuously in real time during treatment due to concern over excessive patient radiation dose. We present a new iterative morphing algorithm to predict the real-time 3D tumor volume based on time-resolved computed tomography (4DCT) acquired before treatment. An offline iterative learning process has been designed to derive a target volumetric deformation function from one breathing phase to another. Real-time volumetric prediction is performed to derive the target 3D volume during treatment delivery. The proposed iterative deformable approach for tumor volume morphing and prediction based on 4DCT is innovative because it makes three major contributions: (1) a novel approach to landmark selection on 3D tumor surfaces using a minimum bounding box; (2) an iterative morphing algorithm to generate the 3D tumor volume using mapped landmarks; and (3) an online tumor volume prediction strategy based on previously trained deformation functions utilizing 4DCT. The experimental performance showed that the maximum morphing deviations are 0.27% and 1.25% for original patient data and artificially generated data, which is promising. This newly developed algorithm and implementation will have important applications for treatment planning, dose calculation and treatment validation in cancer radiation treatment.

  5. Molecular analysis of childhood primitive neuroectodermal tumors defines markers associated with poor outcome

    DEFF Research Database (Denmark)

    Scheurlen, W G; Schwabe, G C; Joos, S

    1998-01-01

    PURPOSE: The diagnostic and prognostic significance of well-defined molecular markers was investigated in childhood primitive neuroectodermal tumors (PNET). MATERIALS AND METHODS: Using microsatellite analysis, Southern blot analysis, and fluorescence in situ hybridization (FISH), 30 primary tumors......: In our study, amplification of c-myc was a poor-prognosis marker in PNET. LOH of chromosome 17p was associated with metastatic disease. Molecular analysis of primary tumors using these markers may be useful for stratification of children with PNET in future prospective studies. The other aberrations...... investigated were not of significant prognostic value, but may provide an entry point for future large-scale molecular studies....

  6. Maternal and Birth Characteristics and Childhood Embryonal Solid Tumors: A Population-Based Report from Brazil.

    Directory of Open Access Journals (Sweden)

    Neimar de Paula Silva

    Full Text Available Several maternal and birth characteristics have been reported to be associated with an increased risk of many childhood cancers. Our goal was to evaluate the risk of childhood embryonal solid tumors in relation to pre- and perinatal characteristics.A case-cohort study was performed using two population-based datasets, which were linked through R software. Tumors were classified as central nervous system (CNS or non-CNS-embryonal (retinoblastoma, neuroblastoma, renal tumors, germ cell tumors, hepatoblastoma and soft tissue sarcoma. Children aged <6 years were selected. Adjustments were made for potential confounders. Odds ratios (OR with 95% confidence intervals (CI were computed by unconditional logistic regression analysis using SPSS.Males, high maternal education level, and birth anomalies were independent risk factors. Among children diagnosed older than 24 months of age, cesarean section (CS was a significant risk factor. Five-minute Apgar ≤8 was an independent risk factor for renal tumors. A decreasing risk with increasing birth order was observed for all tumor types except for retinoblastoma. Among children with neuroblastoma, the risk decreased with increasing birth order (OR = 0.82 (95% CI 0.67-1.01. Children delivered by CS had a marginally significantly increased OR for all tumors except retinoblastoma. High maternal education level showed a significant increase in the odds for all tumors together, CNS tumors, and neuroblastoma.This evidence suggests that male gender, high maternal education level, and birth anomalies are risk factors for childhood tumors irrespective of the age at diagnosis. Cesarean section, birth order, and 5-minute Apgar score were risk factors for some tumor subtypes.

  7. Microarray Gene Expression Analysis of Murine Tumor Heterogeneity Defined by Dynamic Contrast-Enhanced MRI

    Directory of Open Access Journals (Sweden)

    Nick G. Costouros

    2002-07-01

    Full Text Available Current methods of studying angiogenesis are limited in their ability to serially evaluate in vivo function throughout a target tissue. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI and pharmacokinetic modeling provide a useful method for evaluating tissue vasculature based on contrast accumulation and washout. While it is often assumed that areas of high contrast enhancement and washout comprise areas of increased angiogenesis and tumor activity, the actual molecular pathways that are active in such areas are poorly understood. Using DCE-MRI in a murine subcutaneous tumor model, we were able to perform pharmacokinetic functional analysis of a tumor, coregistration of MRI images with histological cross-sections, immunohistochemistry, laser capture microdissection, and genetic profiling of tumor heterogeneity based on pharmacokinetic parameters. Using imaging as a template for biologic investigation, we have not found evidence of increased expression of proangiogenic modulators at the transcriptional level in either distinct pharmacokinetic region. Furthermore, these regions show no difference on histology and CD31 immunohistochemistry. However, the expression of ribosomal proteins was greatly increased in high enhancement and washout regions, implying increased protein translation and consequent increased cellular activity. Together, these findings point to the potential importance of posttranscriptional regulation in angiogenesis and the need for the development of angiogenesis-specific contrast agents to evaluate in vivo angiogenesis at a molecular level.

  8. A voxel-based multiscale model to simulate the radiation response of hypoxic tumors.

    Science.gov (United States)

    Espinoza, I; Peschke, P; Karger, C P

    2015-01-01

    In radiotherapy, it is important to predict the response of tumors to irradiation prior to the treatment. This is especially important for hypoxic tumors, which are known to be highly radioresistant. Mathematical modeling based on the dose distribution, biological parameters, and medical images may help to improve this prediction and to optimize the treatment plan. A voxel-based multiscale tumor response model for simulating the radiation response of hypoxic tumors was developed. It considers viable and dead tumor cells, capillary and normal cells, as well as the most relevant biological processes such as (i) proliferation of tumor cells, (ii) hypoxia-induced angiogenesis, (iii) spatial exchange of cells leading to tumor growth, (iv) oxygen-dependent cell survival after irradiation, (v) resorption of dead cells, and (vi) spatial exchange of cells leading to tumor shrinkage. Oxygenation is described on a microscopic scale using a previously published tumor oxygenation model, which calculates the oxygen distribution for each voxel using the vascular fraction as the most important input parameter. To demonstrate the capabilities of the model, the dependence of the oxygen distribution on tumor growth and radiation-induced shrinkage is investigated. In addition, the impact of three different reoxygenation processes is compared and tumor control probability (TCP) curves for a squamous cells carcinoma of the head and neck (HNSSC) are simulated under normoxic and hypoxic conditions. The model describes the spatiotemporal behavior of the tumor on three different scales: (i) on the macroscopic scale, it describes tumor growth and shrinkage during radiation treatment, (ii) on a mesoscopic scale, it provides the cell density and vascular fraction for each voxel, and (iii) on the microscopic scale, the oxygen distribution may be obtained in terms of oxygen histograms. With increasing tumor size, the simulated tumors develop a hypoxic core. Within the model, tumor shrinkage was

  9. A voxel-based multiscale model to simulate the radiation response of hypoxic tumors

    International Nuclear Information System (INIS)

    Espinoza, I.; Peschke, P.; Karger, C. P.

    2015-01-01

    Purpose: In radiotherapy, it is important to predict the response of tumors to irradiation prior to the treatment. This is especially important for hypoxic tumors, which are known to be highly radioresistant. Mathematical modeling based on the dose distribution, biological parameters, and medical images may help to improve this prediction and to optimize the treatment plan. Methods: A voxel-based multiscale tumor response model for simulating the radiation response of hypoxic tumors was developed. It considers viable and dead tumor cells, capillary and normal cells, as well as the most relevant biological processes such as (i) proliferation of tumor cells, (ii) hypoxia-induced angiogenesis, (iii) spatial exchange of cells leading to tumor growth, (iv) oxygen-dependent cell survival after irradiation, (v) resorption of dead cells, and (vi) spatial exchange of cells leading to tumor shrinkage. Oxygenation is described on a microscopic scale using a previously published tumor oxygenation model, which calculates the oxygen distribution for each voxel using the vascular fraction as the most important input parameter. To demonstrate the capabilities of the model, the dependence of the oxygen distribution on tumor growth and radiation-induced shrinkage is investigated. In addition, the impact of three different reoxygenation processes is compared and tumor control probability (TCP) curves for a squamous cells carcinoma of the head and neck (HNSSC) are simulated under normoxic and hypoxic conditions. Results: The model describes the spatiotemporal behavior of the tumor on three different scales: (i) on the macroscopic scale, it describes tumor growth and shrinkage during radiation treatment, (ii) on a mesoscopic scale, it provides the cell density and vascular fraction for each voxel, and (iii) on the microscopic scale, the oxygen distribution may be obtained in terms of oxygen histograms. With increasing tumor size, the simulated tumors develop a hypoxic core. Within the

  10. Temporalis Myofascial Flap for Primary Cranial Base Reconstruction after Tumor Resection

    OpenAIRE

    Eldaly, Ahmed; Magdy, Emad A.; Nour, Yasser A.; Gaafar, Alaa H.

    2008-01-01

    Objective: To evaluate the use of the temporalis myofascial flap in primary cranial base reconstruction following surgical tumor ablation and to explain technical issues, potential complications, and donor site consequences along with their management. Design: Retrospective case series. Setting: Tertiary referral center. Participants: Forty-one consecutive patients receiving primary temporalis myofascial flap reconstructions following cranial base tumor resections in a 4-year period. Main Out...

  11. Qualitative and Computational Analysis of a Mathematical Model for Tumor-Immune Interactions

    Directory of Open Access Journals (Sweden)

    F. A. Rihan

    2012-01-01

    Full Text Available We provide a family of ordinary and delay differential equations to model the dynamics of tumor-growth and immunotherapy interactions. We explore the effects of adoptive cellular immunotherapy on the model and describe under what circumstances the tumor can be eliminated. The possibility of clearing the tumor, with a strategy, is based on two parameters in the model: the rate of influx of the effector cells and the rate of influx of IL-2. The critical tumor-growth rate, below which endemic tumor does not exist, has been found. One can use the model to make predictions about tumor dormancy.

  12. Comparison of continuous versus categorical tumor measurement-based metrics to predict overall survival in cancer treatment trials

    Science.gov (United States)

    An, Ming-Wen; Mandrekar, Sumithra J.; Branda, Megan E.; Hillman, Shauna L.; Adjei, Alex A.; Pitot, Henry; Goldberg, Richard M.; Sargent, Daniel J.

    2011-01-01

    Purpose The categorical definition of response assessed via the Response Evaluation Criteria in Solid Tumors has documented limitations. We sought to identify alternative metrics for tumor response that improve prediction of overall survival. Experimental Design Individual patient data from three North Central Cancer Treatment Group trials (N0026, n=117; N9741, n=1109; N9841, n=332) were used. Continuous metrics of tumor size based on longitudinal tumor measurements were considered in addition to a trichotomized response (TriTR: Response vs. Stable vs. Progression). Cox proportional hazards models, adjusted for treatment arm and baseline tumor burden, were used to assess the impact of the metrics on subsequent overall survival, using a landmark analysis approach at 12-, 16- and 24-weeks post baseline. Model discrimination was evaluated using the concordance (c) index. Results The overall best response rates for the three trials were 26%, 45%, and 25% respectively. While nearly all metrics were statistically significantly associated with overall survival at the different landmark time points, the c-indices for the traditional response metrics ranged from 0.59-0.65; for the continuous metrics from 0.60-0.66 and for the TriTR metrics from 0.64-0.69. The c-indices for TriTR at 12-weeks were comparable to those at 16- and 24-weeks. Conclusions Continuous tumor-measurement-based metrics provided no predictive improvement over traditional response based metrics or TriTR; TriTR had better predictive ability than best TriTR or confirmed response. If confirmed, TriTR represents a promising endpoint for future Phase II trials. PMID:21880789

  13. Multitriggered Tumor-Responsive Drug Delivery Vehicles Based on Protein and Polypeptide Coassembly for Enhanced Photodynamic Tumor Ablation.

    Science.gov (United States)

    Zhang, Ning; Zhao, Fenfang; Zou, Qianli; Li, Yongxin; Ma, Guanghui; Yan, Xuehai

    2016-11-01

    Tumor-responsive nanocarriers are highly valuable and demanded for smart drug delivery particularly in the field of photodynamic therapy (PDT), where a quick release of photosensitizers in tumors is preferred. Herein, it is demonstrated that protein-based nanospheres, prepared by the electrostatic assembly of proteins and polypeptides with intermolecular disulfide cross-linking and surface polyethylene glycol coupling, can be used as versatile tumor-responsive drug delivery vehicles for effective PDT. These nanospheres are capable of encapsulation of various photosensitizers including Chlorin e6 (Ce6), protoporphyrin IX, and verteporfin. The Chlorin e6-encapsulated nanospheres (Ce6-Ns) are responsive to changes in pH, redox potential, and proteinase concentration, resulting in multitriggered rapid release of Ce6 in an environment mimicking tumor tissues. In vivo fluorescence imaging results indicate that Ce6-Ns selectively accumulate near tumors and the quick release of Ce6 from Ce6-Ns can be triggered by tumors. In tumors the fluorescence of released Ce6 from Ce6-Ns is observed at 0.5 h postinjection, while in normal tissues the fluorescence appeared at 12 h postinjection. Tumor ablation is demonstrated by in vivo PDT using Ce6-Ns and the biocompatibility of Ce6-Ns is evident from the histopathology imaging, confirming the enhanced in vivo PDT efficacy and the biocompatibility of the assembled drug delivery vehicles. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Analysis of hyperspectral fluorescence images for poultry skin tumor inspection

    Science.gov (United States)

    Kong, Seong G.; Chen, Yud-Ren; Kim, Intaek; Kim, Moon S.

    2004-02-01

    We present a hyperspectral fluorescence imaging system with a fuzzy inference scheme for detecting skin tumors on poultry carcasses. Hyperspectral images reveal spatial and spectral information useful for finding pathological lesions or contaminants on agricultural products. Skin tumors are not obvious because the visual signature appears as a shape distortion rather than a discoloration. Fluorescence imaging allows the visualization of poultry skin tumors more easily than reflectance. The hyperspectral image samples obtained for this poultry tumor inspection contain 65 spectral bands of fluorescence in the visible region of the spectrum at wavelengths ranging from 425 to 711 nm. The large amount of hyperspectral image data is compressed by use of a discrete wavelet transform in the spatial domain. Principal-component analysis provides an effective compressed representation of the spectral signal of each pixel in the spectral domain. A small number of significant features are extracted from two major spectral peaks of relative fluorescence intensity that have been identified as meaningful spectral bands for detecting tumors. A fuzzy inference scheme that uses a small number of fuzzy rules and Gaussian membership functions successfully detects skin tumors on poultry carcasses. Spatial-filtering techniques are used to significantly reduce false positives.

  15. Whole-tumor apparent diffusion coefficient (ADC) histogram analysis to differentiate benign peripheral neurogenic tumors from soft tissue sarcomas.

    Science.gov (United States)

    Nakajo, Masanori; Fukukura, Yoshihiko; Hakamada, Hiroto; Yoneyama, Tomohide; Kamimura, Kiyohisa; Nagano, Satoshi; Nakajo, Masayuki; Yoshiura, Takashi

    2018-02-22

    Apparent diffusion coefficient (ADC) histogram analyses have been used to differentiate tumor grades and predict therapeutic responses in various anatomic sites with moderate success. To determine the ability of diffusion-weighted imaging (DWI) with a whole-tumor ADC histogram analysis to differentiate benign peripheral neurogenic tumors (BPNTs) from soft tissue sarcomas (STSs). Retrospective study, single institution. In all, 25 BPNTs and 31 STSs. Two-b value DWI (b-values = 0, 1000s/mm 2 ) was at 3.0T. The histogram parameters of whole-tumor for ADC were calculated by two radiologists and compared between BPNTs and STSs. Nonparametric tests were performed for comparisons between BPNTs and STSs. P histogram parameters except kurtosis and entropy differed significantly between BPNTs and STSs. 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018. © 2018 International Society for Magnetic Resonance in Medicine.

  16. Histogram analysis of T2*-based pharmacokinetic imaging in cerebral glioma grading.

    Science.gov (United States)

    Liu, Hua-Shan; Chiang, Shih-Wei; Chung, Hsiao-Wen; Tsai, Ping-Huei; Hsu, Fei-Ting; Cho, Nai-Yu; Wang, Chao-Ying; Chou, Ming-Chung; Chen, Cheng-Yu

    2018-03-01

    To investigate the feasibility of histogram analysis of the T2*-based permeability parameter volume transfer constant (K trans ) for glioma grading and to explore the diagnostic performance of the histogram analysis of K trans and blood plasma volume (v p ). We recruited 31 and 11 patients with high- and low-grade gliomas, respectively. The histogram parameters of K trans and v p , derived from the first-pass pharmacokinetic modeling based on the T2* dynamic susceptibility-weighted contrast-enhanced perfusion-weighted magnetic resonance imaging (T2* DSC-PW-MRI) from the entire tumor volume, were evaluated for differentiating glioma grades. Histogram parameters of K trans and v p showed significant differences between high- and low-grade gliomas and exhibited significant correlations with tumor grades. The mean K trans derived from the T2* DSC-PW-MRI had the highest sensitivity and specificity for differentiating high-grade gliomas from low-grade gliomas compared with other histogram parameters of K trans and v p . Histogram analysis of T2*-based pharmacokinetic imaging is useful for cerebral glioma grading. The histogram parameters of the entire tumor K trans measurement can provide increased accuracy with additional information regarding microvascular permeability changes for identifying high-grade brain tumors. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Multimodal navigated skull base tumor resection using image-based vascular and cranial nerve segmentation: A prospective pilot study.

    Science.gov (United States)

    Dolati, Parviz; Gokoglu, Abdulkerim; Eichberg, Daniel; Zamani, Amir; Golby, Alexandra; Al-Mefty, Ossama

    2015-01-01

    Skull base tumors frequently encase or invade adjacent normal neurovascular structures. For this reason, optimal tumor resection with incomplete knowledge of patient anatomy remains a challenge. To determine the accuracy and utility of image-based preoperative segmentation in skull base tumor resections, we performed a prospective study. Ten patients with skull base tumors underwent preoperative 3T magnetic resonance imaging, which included thin section three-dimensional (3D) space T2, 3D time of flight, and magnetization-prepared rapid acquisition gradient echo sequences. Imaging sequences were loaded in the neuronavigation system for segmentation and preoperative planning. Five different neurovascular landmarks were identified in each case and measured for accuracy using the neuronavigation system. Each segmented neurovascular element was validated by manual placement of the navigation probe, and errors of localization were measured. Strong correspondence between image-based segmentation and microscopic view was found at the surface of the tumor and tumor-normal brain interfaces in all cases. The accuracy of the measurements was 0.45 ± 0.21 mm (mean ± standard deviation). This information reassured the surgeon and prevented vascular injury intraoperatively. Preoperative segmentation of the related cranial nerves was possible in 80% of cases and helped the surgeon localize involved cranial nerves in all cases. Image-based preoperative vascular and neural element segmentation with 3D reconstruction is highly informative preoperatively and could increase the vigilance of neurosurgeons for preventing neurovascular injury during skull base surgeries. Additionally, the accuracy found in this study is superior to previously reported measurements. This novel preliminary study is encouraging for future validation with larger numbers of patients.

  18. Valine-based biphenylsulphonamide matrix metalloproteinase inhibitors as tumor imaging agents

    Energy Technology Data Exchange (ETDEWEB)

    Oltenfreiter, Ruth [Faculty of Pharmaceutical Sciences, Department of Radiopharmacy, Ghent University, Harelbekestraat 72, 9000 Ghent (Belgium)]. E-mail: ruth.oltenfreiter@ugent.be; Staelens, Ludovicus [Faculty of Pharmaceutical Sciences, Department of Radiopharmacy, Ghent University, Harelbekestraat 72, 9000 Ghent (Belgium); Kersemans, Veerle [Faculty of Pharmaceutical Sciences, Department of Radiopharmacy, Ghent University, Harelbekestraat 72, 9000 Ghent (Belgium); Cornelissen, Bart [Faculty of Pharmaceutical Sciences, Department of Radiopharmacy, Ghent University, Harelbekestraat 72, 9000 Ghent (Belgium); Frankenne, Francis [Laboratory of Tumor and Developmental Biology, University of Liege, Sart-Tilman, Liege (Belgium); Foidart, Jean-Michel [Laboratory of Tumor and Developmental Biology, University of Liege, Sart-Tilman, Liege (Belgium); Wiele, Christophe van de [Division of Nuclear Medicine, Gent University Hospital, De Pintelaan 185, 9000 Gent (Belgium); Slegers, Guido [Faculty of Pharmaceutical Sciences, Department of Radiopharmacy, Ghent University, Harelbekestraat 72, 9000 Ghent (Belgium)

    2006-06-15

    Among matrix metalloproteinases (MMPs), the subfamily of gelatinases (MMP-2, MMP-9) is of particular interest due to their ability to degrade type IV collagen and other non-fibrillar collagen domains and proteins such as fibronectin and laminin. Whilst malignant cells often over-express various MMPs, the gelatinases have been most consistently detected in malignant tissues and associated with tumor growth, metastatic potential and angiogenesis. Radiosynthesis of carboxylic (1') and hydroxamic (2') MMPIs resulted in radiochemical yields of 70+/-5% (n=6) and 60+/-5% (n=4), respectively. Evaluation in A549-inoculated athymic mice showed a tumor uptake of 2.0+/-0.7%ID/g (3h p.i.), a tumor/blood ratio of 0.5 and a tumor/muscle ratio of 4.6 at 48hp.i. for 1'. For compound 2' a tumor uptake of 0.7+/-0.2%ID/g (3hp.i.), a tumor/blood ratio of 1.2 and a tumor/muscle ratio of 1.8 at 24hp.i. were observed. HPLC analysis of the blood (plasma) showed no dehalogenation or other metabolites of 1' 2hp.i. For compound 2', 65.4% of intact compound was found in the blood (plasma) and one polar metabolite (31%) was detected whereas in the tumor 91.8% of the accumulated activity was caused by intact compound and only 8.1% by the metabolite. Planar imaging, using a Toshiba GCA-9300A/hg SPECT camera, showed that tumor tissue could be visualized and that image quality improved by decreasing specific activity resulting in lower liver uptake, indicating some degree of saturable binding in the liver. In vivo evaluation of these radioiodinated carboxylic and hydroxamic MMP inhibitor tracers revealed that MMP inhibitors could have potential as tumor imaging agents, but that further research is necessary.

  19. Valine-based biphenylsulphonamide matrix metalloproteinase inhibitors as tumor imaging agents

    International Nuclear Information System (INIS)

    Oltenfreiter, Ruth; Staelens, Ludovicus; Kersemans, Veerle; Cornelissen, Bart; Frankenne, Francis; Foidart, Jean-Michel; Wiele, Christophe van de; Slegers, Guido

    2006-01-01

    Among matrix metalloproteinases (MMPs), the subfamily of gelatinases (MMP-2, MMP-9) is of particular interest due to their ability to degrade type IV collagen and other non-fibrillar collagen domains and proteins such as fibronectin and laminin. Whilst malignant cells often over-express various MMPs, the gelatinases have been most consistently detected in malignant tissues and associated with tumor growth, metastatic potential and angiogenesis. Radiosynthesis of carboxylic (1') and hydroxamic (2') MMPIs resulted in radiochemical yields of 70+/-5% (n=6) and 60+/-5% (n=4), respectively. Evaluation in A549-inoculated athymic mice showed a tumor uptake of 2.0+/-0.7%ID/g (3h p.i.), a tumor/blood ratio of 0.5 and a tumor/muscle ratio of 4.6 at 48hp.i. for 1'. For compound 2' a tumor uptake of 0.7+/-0.2%ID/g (3hp.i.), a tumor/blood ratio of 1.2 and a tumor/muscle ratio of 1.8 at 24hp.i. were observed. HPLC analysis of the blood (plasma) showed no dehalogenation or other metabolites of 1' 2hp.i. For compound 2', 65.4% of intact compound was found in the blood (plasma) and one polar metabolite (31%) was detected whereas in the tumor 91.8% of the accumulated activity was caused by intact compound and only 8.1% by the metabolite. Planar imaging, using a Toshiba GCA-9300A/hg SPECT camera, showed that tumor tissue could be visualized and that image quality improved by decreasing specific activity resulting in lower liver uptake, indicating some degree of saturable binding in the liver. In vivo evaluation of these radioiodinated carboxylic and hydroxamic MMP inhibitor tracers revealed that MMP inhibitors could have potential as tumor imaging agents, but that further research is necessary

  20. Targeted Tumor Therapy Based on Nanodiamonds Decorated with Doxorubicin and Folic Acid.

    Science.gov (United States)

    Ryu, Tae-Kyung; Baek, Seung Woon; Lee, Gyoung-Ja; Rhee, Chang-Kyu; Choi, Sung-Wook

    2017-02-01

    The fabrication of nanodiamond (ND)-based drug carriers for tumor-targeted drug delivery is described. The ND clusters with an average size of 52.84 nm are fabricated using a simple fluidic device combined with a precipitation method and then conjugated with folic acid (FA) and doxorubicin (Dox) via carbodiimide chemistry to obtain FA/Dox-modified ND (FA/Dox-ND) clusters. Cell culture experiments revealed that KB (folate receptor-positive) cells are preferentially ablated by FA/Dox-ND clusters compared to A549 (folate receptor-negative) cells. In vivo results revealed that FA/Dox-ND clusters are specifically accumulated in tumor tissues after intravenous injection into tumor-bearing mice, effectively reducing the volume of tumor. Based on these results, this study suggests that FA/Dox-ND clusters can be a good candidate as tumor-targeted nanovehicles for delivery of antitumor drug. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Treatment Algorithms Based on Tumor Molecular Profiling: The Essence of Precision Medicine Trials.

    Science.gov (United States)

    Le Tourneau, Christophe; Kamal, Maud; Tsimberidou, Apostolia-Maria; Bedard, Philippe; Pierron, Gaëlle; Callens, Céline; Rouleau, Etienne; Vincent-Salomon, Anne; Servant, Nicolas; Alt, Marie; Rouzier, Roman; Paoletti, Xavier; Delattre, Olivier; Bièche, Ivan

    2016-04-01

    With the advent of high-throughput molecular technologies, several precision medicine (PM) studies are currently ongoing that include molecular screening programs and PM clinical trials. Molecular profiling programs establish the molecular profile of patients' tumors with the aim to guide therapy based on identified molecular alterations. The aim of prospective PM clinical trials is to assess the clinical utility of tumor molecular profiling and to determine whether treatment selection based on molecular alterations produces superior outcomes compared with unselected treatment. These trials use treatment algorithms to assign patients to specific targeted therapies based on tumor molecular alterations. These algorithms should be governed by fixed rules to ensure standardization and reproducibility. Here, we summarize key molecular, biological, and technical criteria that, in our view, should be addressed when establishing treatment algorithms based on tumor molecular profiling for PM trials. © The Author 2015. Published by Oxford University Press.

  2. Image-based modeling of tumor shrinkage in head and neck radiation therapy

    International Nuclear Information System (INIS)

    Chao Ming; Xie Yaoqin; Moros, Eduardo G.; Le, Quynh-Thu; Xing Lei

    2010-01-01

    Purpose: Understanding the kinetics of tumor growth/shrinkage represents a critical step in quantitative assessment of therapeutics and realization of adaptive radiation therapy. This article presents a novel framework for image-based modeling of tumor change and demonstrates its performance with synthetic images and clinical cases. Methods: Due to significant tumor tissue content changes, similarity-based models are not suitable for describing the process of tumor volume changes. Under the hypothesis that tissue features in a tumor volume or at the boundary region are partially preserved, the kinetic change was modeled in two steps: (1) Autodetection of homologous tissue features shared by two input images using the scale invariance feature transformation (SIFT) method; and (2) establishment of a voxel-to-voxel correspondence between the images for the remaining spatial points by interpolation. The correctness of the tissue feature correspondence was assured by a bidirectional association procedure, where SIFT features were mapped from template to target images and reversely. A series of digital phantom experiments and five head and neck clinical cases were used to assess the performance of the proposed technique. Results: The proposed technique can faithfully identify the known changes introduced when constructing the digital phantoms. The subsequent feature-guided thin plate spline calculation reproduced the ''ground truth'' with accuracy better than 1.5 mm. For the clinical cases, the new algorithm worked reliably for a volume change as large as 30%. Conclusions: An image-based tumor kinetic algorithm was developed to model the tumor response to radiation therapy. The technique provides a practical framework for future application in adaptive radiation therapy.

  3. Filter Paper-based Nucleic Acid Storage in High-throughput Solid Tumor Genotyping.

    Science.gov (United States)

    Stachler, Matthew; Jia, Yonghui; Sharaf, Nematullah; Wade, Jacqueline; Longtine, Janina; Garcia, Elizabeth; Sholl, Lynette M

    2015-01-01

    Molecular testing of tumors from formalin-fixed paraffin-embedded (FFPE) tissue blocks is central to clinical practice; however, it requires histology support and increases test turnaround time. Prospective fresh frozen tissue collection requires special handling, additional storage space, and may not be feasible for small specimens. Filter paper-based collection of tumor DNA reduces the need for histology support, requires little storage space, and preserves high-quality nucleic acid. We investigated the performance of tumor smears on filter paper in solid tumor genotyping, as compared with paired FFPE samples. Whatman FTA Micro Card (FTA preps) smears were prepared from 21 fresh tumor samples. A corresponding cytology smear was used to assess tumor cellularity and necrosis. DNA was isolated from FTA preps and FFPE core samples using automated methods and quantified using SYBR green dsDNA detection. Samples were genotyped for 471 mutations on a mass spectrophotometry-based platform (Sequenom). DNA concentrations from FTA preps and FFPE correlated for untreated carcinomas but not for mesenchymal tumors (Spearman σ=0.39 and σ=-0.1, respectively). Average DNA concentrations were lower from FTA preps as compared with FFPE, but DNA quality was higher with less fragmentation. Seventy-six percent of FTA preps and 86% of FFPE samples generated adequate DNA for genotyping. FTA preps tended to perform poorly for collection of DNA from pretreated carcinomas and mesenchymal neoplasms. Of the 16 paired DNA samples that were genotyped, 15 (94%) gave entirely concordant results. Filter paper-based sample preservation is a feasible alternative to FFPE for use in automated, high-throughput genotyping of carcinomas.

  4. MiR-139 in digestive system tumor diagnosis and detection: Bioinformatics and meta-analysis.

    Science.gov (United States)

    Wang, Yu-Hui; Ji, Jia; Weng, Hong; Wang, Bi-Cheng; Wang, Fu-Bing

    2018-06-05

    Accumulating evidence has indicated that microRNAs play important roles in the initiation and progression of digestive system tumors. However, previous studies suggest that the accuracy of miRNA detection in digestive system tumors was inconsistent. The candidate miRNAs were obtained from The Cancer Genome Atlas (TCGA). Meta-analysis was performed to evaluate the diagnostic value of these miRNAs in digestive system tumors. Furthermore, the potential target genes of the miRNAs were predicted and assessed with functional analysis. According to TCGA data, miR-139 was a common biomarker of digestive system tumors. It was markedly reduced in tumor tissues as compared with non-cancerous tissues in digestive system tumors. In the meta-analysis, the pooled diagnostic odds ratio (DOR) and AUC was 57.51 (95% CI: 14.25-232.04) and 0.96 (95% CI: 0.94-0.97), respectively. Furthermore, the overall sensitivity and specificity was 0.89 (95% CI: 0.73-0.96) and 0.91 (95% CI: 0.75-0.97), respectively. The diagnostic value of tissue miR-139 was higher than the diagnostic value of blood miR-139. In particular, miR-139 was a superior marker for distinguishing colorectal cancer. miR-139 could be a potential biomarker for diagnosis of digestive system tumors especially colorectal cancer. Copyright © 2017. Published by Elsevier B.V.

  5. Integrated genomic classification of melanocytic tumors of the central nervous system using mutation analysis, copy number alterations and DNA methylation profiling.

    Science.gov (United States)

    Griewank, Klaus; Koelsche, Christian; van de Nes, Johannes A P; Schrimpf, Daniel; Gessi, Marco; Möller, Inga; Sucker, Antje; Scolyer, Richard A; Buckland, Michael E; Murali, Rajmohan; Pietsch, Torsten; von Deimling, Andreas; Schadendorf, Dirk

    2018-06-11

    In the central nervous system, distinguishing primary leptomeningeal melanocytic tumors from melanoma metastases and predicting their biological behavior solely using histopathologic criteria can be challenging. We aimed to assess the diagnostic and prognostic value of integrated molecular analysis. Targeted next-generation-sequencing, array-based genome-wide methylation analysis and BAP1 immunohistochemistry was performed on the largest cohort of central nervous system melanocytic tumors analyzed to date, incl. 47 primary tumors of the central nervous system, 16 uveal melanomas. 13 cutaneous melanoma metastasis and 2 blue nevus-like melanomas. Gene mutation, DNA-methylation and copy-number profiles were correlated with clinicopathological features. Combining mutation, copy-number and DNA-methylation profiles clearly distinguished cutaneous melanoma metastases from other melanocytic tumors. Primary leptomeningeal melanocytic tumors, uveal melanomas and blue nevus-like melanoma showed common DNA-methylation, copy-number alteration and gene mutation signatures. Notably, tumors demonstrating chromosome 3 monosomy and BAP1 alterations formed a homogeneous subset within this group. Integrated molecular profiling aids in distinguishing primary from metastatic melanocytic tumors of the central nervous system. Primary leptomeningeal melanocytic tumors, uveal melanoma and blue nevus-like melanoma share molecular similarity with chromosome 3 and BAP1 alterations markers of poor prognosis. Copyright ©2018, American Association for Cancer Research.

  6. A sequence-based survey of the complex structural organization of tumor genomes

    Energy Technology Data Exchange (ETDEWEB)

    Collins, Colin; Raphael, Benjamin J.; Volik, Stanislav; Yu, Peng; Wu, Chunxiao; Huang, Guiqing; Linardopoulou, Elena V.; Trask, Barbara J.; Waldman, Frederic; Costello, Joseph; Pienta, Kenneth J.; Mills, Gordon B.; Bajsarowicz, Krystyna; Kobayashi, Yasuko; Sridharan, Shivaranjani; Paris, Pamela; Tao, Quanzhou; Aerni, Sarah J.; Brown, Raymond P.; Bashir, Ali; Gray, Joe W.; Cheng, Jan-Fang; de Jong, Pieter; Nefedov, Mikhail; Ried, Thomas; Padilla-Nash, Hesed M.; Collins, Colin C.

    2008-04-03

    The genomes of many epithelial tumors exhibit extensive chromosomal rearrangements. All classes of genome rearrangements can be identified using End Sequencing Profiling (ESP), which relies on paired-end sequencing of cloned tumor genomes. In this study, brain, breast, ovary and prostate tumors along with three breast cancer cell lines were surveyed with ESP yielding the largest available collection of sequence-ready tumor genome breakpoints and providing evidence that some rearrangements may be recurrent. Sequencing and fluorescence in situ hybridization (FISH) confirmed translocations and complex tumor genome structures that include coamplification and packaging of disparate genomic loci with associated molecular heterogeneity. Comparison of the tumor genomes suggests recurrent rearrangements. Some are likely to be novel structural polymorphisms, whereas others may be bona fide somatic rearrangements. A recurrent fusion transcript in breast tumors and a constitutional fusion transcript resulting from a segmental duplication were identified. Analysis of end sequences for single nucleotide polymorphisms (SNPs) revealed candidate somatic mutations and an elevated rate of novel SNPs in an ovarian tumor. These results suggest that the genomes of many epithelial tumors may be far more dynamic and complex than previously appreciated and that genomic fusions including fusion transcripts and proteins may be common, possibly yielding tumor-specific biomarkers and therapeutic targets.

  7. Cone-Beam CT Angiography for Determination of Tumor-Feeding Vessels During Chemoembolization of Liver Tumors: Comparison of Conventional and Dedicated-Software Analysis.

    Science.gov (United States)

    Ronot, Maxime; Abdel-Rehim, Mohamed; Hakimé, Antoine; Kuoch, Viseth; Roux, Marion; Chiaradia, Mélanie; Vilgrain, Valérie; de Baere, Thierry; Deschamps, Frédéric

    2016-01-01

    To compare the ability of dedicated software and conventional cone-beam computed tomography (CT) analysis to identify tumor-feeding vessels in hypervascular liver tumors treated with chemoembolization. Between January 2012 and January 2013, 45 patients (32 men, mean age of 61 y; range, 27-85 y) were enrolled, and 66 tumors were treated (mean, 32 mm ± 18; range, 10-81 mm) with conventional chemoembolization with arterial cone-beam CT. Data were independently analyzed by six interventional radiologists with standard postprocessing software, a computer-aided analysis with FlightPlan for liver (FPFL; ie, "raw FPFL"), and a review of this computer-aided FPFL analysis ("reviewed FPFL"). Analyses were compared with a reference reading established by two study supervisors in consensus who had access to all imaging data. Sensitivities, positive predictive values (PPVs), and false-positive (FP) ratios were compared by McNemar, χ(2), and Fisher exact tests. Analysis durations were compared by Mann-Whitney test, and interreader agreement was assessed. Reference reading identified 179 feeder vessels. The sensitivity of raw FPFL was significantly higher than those of reviewed FPFL and conventional analyses (90.9% vs 83.2% and 82.1%; P software enabled a fast, accurate, and sensitive detection of tumor feeder vessels. Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.

  8. A clinicopathological analysis of papillary endolymphatic sac tumor in inner ear

    Directory of Open Access Journals (Sweden)

    LIN Yu-jing

    2013-05-01

    Full Text Available Background Endolymphatic sac tumor (ELST is a rare tumor originating fromendolymphatic epithelium of inner ear. This tumor exhibits low-grade malignancy with benign histopathological appearance and clinically destructive behavior which occurs in the skull base and frequently invades the posterior petrous bone, the mastoid, semicircular canal, cerebellopontine angle structures and cranial nerve. The presence of intracranial ELST always makes the diagnosis challenge for clinicians and pathologists. Herein we describe a case of ELST in skull base. The clinicopathology of this tumor and its differential diagnosis are discussed. Methods The clinical manifestation of a patient with primary ELST occurring in right cerebellopontine angle was presented retrospectively. Resected mass was routinely paraffin-embedded and stained with hematoxylin and eosin. Dako EnVision immunohistochemical staining system was used to detect the tumor antigen expressions, including cytokeratin (CK, vimentin (Vim, epithelial membrane antigen (EMA, carcinoembryonic antigen (CEA, synaptophysin (Syn, chromogranin A (CgA, S-100 protein (S-100, glial fibrillary acidic protein (GFAP, thyroglobulin (TG, thyroid transcription factor-1 (TTF-1 and Ki-67. Results A 32-year-old male patient presented with 20-year history of progressive hearing loss. MRI scan revealed an expansile lytic lesion of the mastoid process of the right petrous bone, measuring 4.20 cm × 3.30 cm × 2.00 cm, occupied the right cerebellopontine angle with infiltration of surrounding dura mater. But the lesion did not break the dura mater and invade the brain parenchyma. Craniotomy was performed and the tumor was removed totally. Histological examination revealed a papillary, cystic or glandular architecture in mass. The papillary and glandular structures were lined by a single layer of flattened cuboidal-to-columnar cells. The stroma of the papillary fronds was richly vascularized and chronically inflamed. There

  9. Reconstruction of the cranial base in surgery for jugular foramen tumors.

    Science.gov (United States)

    Ramina, Ricardo; Maniglia, Joao J; Paschoal, Jorge R; Fernandes, Yvens B; Neto, Mauricio Coelho; Honorato, Donizeti C

    2005-04-01

    The surgical removal of a jugular foramen (JF) tumor presents the neurosurgeon with a complex management problem that requires an understanding of the natural history, diagnosis, surgical approaches, and postoperative complications. Cerebrospinal fluid (CSF) leakage is one of the most common complications of this surgery. Different surgical approaches and management concepts to avoid this complication have been described, mainly in the ear, nose, and throat literature. The purpose of this study was to review the results of CSF leakage prevention in a series of 66 patients with JF tumors operated on by a multidisciplinary cranial base team using a new technique for cranial base reconstruction. We retrospectively studied 66 patients who had JF tumors with intracranial extension and who underwent surgical treatment in our institutions from January 1987 to December 2001. Paragangliomas were the most frequent lesions, followed by schwannomas and meningiomas. All patients were operated on using the same multidisciplinary surgical approach (neurosurgeons and ear, nose, and throat surgeons). A surgical strategy for reconstruction of the cranial base using vascularized flaps was carried out. The closure of the surgical wound was performed in three layers. A specially developed myofascial flap (temporalis fascia, cervical fascia, and sternocleidomastoid muscle) associated to the inferior rotation of the posterior portion of the temporalis muscle was used to reconstruct the cranial base with vascularized flaps. In this series of 66 patients, postoperative CSF leakage developed in three cases. These patients presented with very large or recurrent tumors, and the postoperative CSF fistulae were surgically closed. The cosmetic result obtained with this reconstruction was classified as excellent or good in all patients. Our results compare favorably with those reported in the literature. The surgical strategy used for cranial base reconstruction presented in this article has

  10. Analytical validation of the PAM50-based Prosigna Breast Cancer Prognostic Gene Signature Assay and nCounter Analysis System using formalin-fixed paraffin-embedded breast tumor specimens

    International Nuclear Information System (INIS)

    Nielsen, Torsten; Storhoff, James; Wallden, Brett; Schaper, Carl; Ferree, Sean; Liu, Shuzhen; Gao, Dongxia; Barry, Garrett; Dowidar, Naeem; Maysuria, Malini

    2014-01-01

    NanoString’s Prosigna™ Breast Cancer Prognostic Gene Signature Assay is based on the PAM50 gene expression signature. The test outputs a risk of recurrence (ROR) score, risk category, and intrinsic subtype (Luminal A/B, HER2-enriched, Basal-like). The studies described here were designed to validate the analytical performance of the test on the nCounter Analysis System across multiple laboratories. Analytical precision was measured by testing five breast tumor RNA samples across 3 sites. Reproducibility was measured by testing replicate tissue sections from 43 FFPE breast tumor blocks across 3 sites following independent pathology review at each site. The RNA input range was validated by comparing assay results at the extremes of the specified range to the nominal RNA input level. Interference was evaluated by including non-tumor tissue into the test. The measured standard deviation (SD) was less than 1 ROR unit within the analytical precision study and the measured total SD was 2.9 ROR units within the reproducibility study. The ROR scores for RNA inputs at the extremes of the range were the same as those at the nominal input level. Assay results were stable in the presence of moderate amounts of surrounding non-tumor tissue (<70% by area). The analytical performance of NanoString’s Prosigna assay has been validated using FFPE breast tumor specimens across multiple clinical testing laboratories

  11. Computer-based image studies on tumor nests mathematical features of breast cancer and their clinical prognostic value.

    Science.gov (United States)

    Wang, Lin-Wei; Qu, Ai-Ping; Yuan, Jing-Ping; Chen, Chuang; Sun, Sheng-Rong; Hu, Ming-Bai; Liu, Juan; Li, Yan

    2013-01-01

    The expending and invasive features of tumor nests could reflect the malignant biological behaviors of breast invasive ductal carcinoma. Useful information on cancer invasiveness hidden within tumor nests could be extracted and analyzed by computer image processing and big data analysis. Tissue microarrays from invasive ductal carcinoma (n = 202) were first stained with cytokeratin by immunohistochemical method to clearly demarcate the tumor nests. Then an expert-aided computer analysis system was developed to study the mathematical and geometrical features of the tumor nests. Computer recognition system and imaging analysis software extracted tumor nests information, and mathematical features of tumor nests were calculated. The relationship between tumor nests mathematical parameters and patients' 5-year disease free survival was studied. There were 8 mathematical parameters extracted by expert-aided computer analysis system. Three mathematical parameters (number, circularity and total perimeter) with area under curve >0.5 and 4 mathematical parameters (average area, average perimeter, total area/total perimeter, average (area/perimeter)) with area under curve nests could be a useful parameter to predict the prognosis of early stage breast invasive ductal carcinoma.

  12. Intra-tumor genetic heterogeneity and mortality in head and neck cancer: analysis of data from the Cancer Genome Atlas.

    Science.gov (United States)

    Mroz, Edmund A; Tward, Aaron D; Tward, Aaron M; Hammon, Rebecca J; Ren, Yin; Rocco, James W

    2015-02-01

    Although the involvement of intra-tumor genetic heterogeneity in tumor progression, treatment resistance, and metastasis is established, genetic heterogeneity is seldom examined in clinical trials or practice. Many studies of heterogeneity have had prespecified markers for tumor subpopulations, limiting their generalizability, or have involved massive efforts such as separate analysis of hundreds of individual cells, limiting their clinical use. We recently developed a general measure of intra-tumor genetic heterogeneity based on whole-exome sequencing (WES) of bulk tumor DNA, called mutant-allele tumor heterogeneity (MATH). Here, we examine data collected as part of a large, multi-institutional study to validate this measure and determine whether intra-tumor heterogeneity is itself related to mortality. Clinical and WES data were obtained from The Cancer Genome Atlas in October 2013 for 305 patients with head and neck squamous cell carcinoma (HNSCC), from 14 institutions. Initial pathologic diagnoses were between 1992 and 2011 (median, 2008). Median time to death for 131 deceased patients was 14 mo; median follow-up of living patients was 22 mo. Tumor MATH values were calculated from WES results. Despite the multiple head and neck tumor subsites and the variety of treatments, we found in this retrospective analysis a substantial relation of high MATH values to decreased overall survival (Cox proportional hazards analysis: hazard ratio for high/low heterogeneity, 2.2; 95% CI 1.4 to 3.3). This relation of intra-tumor heterogeneity to survival was not due to intra-tumor heterogeneity's associations with other clinical or molecular characteristics, including age, human papillomavirus status, tumor grade and TP53 mutation, and N classification. MATH improved prognostication over that provided by traditional clinical and molecular characteristics, maintained a significant relation to survival in multivariate analyses, and distinguished outcomes among patients having

  13. Biodistribution of ultra small gadolinium-based nanoparticles as theranostic agent: application to brain tumors.

    Science.gov (United States)

    Miladi, Imen; Duc, Géraldine Le; Kryza, David; Berniard, Aurélie; Mowat, Pierre; Roux, Stéphane; Taleb, Jacqueline; Bonazza, Pauline; Perriat, Pascal; Lux, François; Tillement, Olivier; Billotey, Claire; Janier, Marc

    2013-09-01

    Gadolinium-based nanoparticles are novel objects with interesting physical properties, allowing their use for diagnostic and therapeutic applications. Gadolinium-based nanoparticles were imaged following intravenous injection in healthy rats and rats grafted with 9L gliosarcoma tumors using magnetic resonance imaging and scintigraphic imaging. Quantitative biodistribution using gamma-counting of each sampled organ confirmed that these nanoparticles were rapidly cleared essentially by renal excretion. Accumulation of these nanoparticles in 9L gliosarcoma tumors implanted in the rat brain was quantitated. This passive and long-duration accumulation of gadolinium-based nanoparticles in tumor, which is related to disruption of the blood-brain barrier, is in good agreement with the use of these nanoparticles as radiosensitizers for brain tumors.

  14. Correlation of a hypoxia based tumor control model with observed local control rates in nasopharyngeal carcinoma treated with chemoradiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Avanzo, Michele; Stancanello, Joseph; Franchin, Giovanni; Sartor, Giovanna; Jena, Rajesh; Drigo, Annalisa; Dassie, Andrea; Gigante, Marco; Capra, Elvira [Department of Medical Physics, Centro di Riferimento Oncologico, Aviano 33081 (Italy); Research and Clinical Collaborations, Siemens Healthcare, Erlangen 91052 (Germany); Department of Radiation Oncology, Centro di Riferimento Oncologico, Aviano 33081 (Italy); Department of Medical Physics, Centro di Riferimento Oncologico, Aviano 33081 (Italy); Oncology Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ (United Kingdom); Department of Medical Physics, Centro di Riferimento Oncologico, Aviano 33081 (Italy); Department of Radiation Oncology, Centro di Riferimento Oncologico, Aviano 33081 (Italy); Department of Medical Physics, Centro di Riferimento Oncologico, Aviano 33081 (Italy)

    2010-04-15

    Purpose: To extend the application of current radiation therapy (RT) based tumor control probability (TCP) models of nasopharyngeal carcinoma (NPC) to include the effects of hypoxia and chemoradiotherapy (CRT). Methods: A TCP model is described based on the linear-quadratic model modified to account for repopulation, chemotherapy, heterogeneity of dose to the tumor, and hypoxia. Sensitivity analysis was performed to determine which parameters exert the greatest influence on the uncertainty of modeled TCP. On the basis of the sensitivity analysis, the values of specific radiobiological parameters were set to nominal values reported in the literature for NPC or head and neck tumors. The remaining radiobiological parameters were determined by fitting TCP to clinical local control data from published randomized studies using both RT and CRT. Validation of the model was performed by comparison of estimated TCP and average overall local control rate (LCR) for 45 patients treated at the institution with conventional linear-accelerator-based or helical tomotherapy based intensity-modulated RT and neoadjuvant chemotherapy. Results: Sensitivity analysis demonstrates that the model is most sensitive to the radiosensitivity term {alpha} and the dose per fraction. The estimated values of {alpha} and OER from data fitting were 0.396 Gy{sup -1} and 1.417. The model estimate of TCP (average 90.9%, range 26.9%-99.2%) showed good correlation with the LCR (86.7%). Conclusions: The model implemented in this work provides clinicians with a useful tool to predict the success rate of treatment, optimize treatment plans, and compare the effects of multimodality therapy.

  15. Correlation of a hypoxia based tumor control model with observed local control rates in nasopharyngeal carcinoma treated with chemoradiotherapy

    International Nuclear Information System (INIS)

    Avanzo, Michele; Stancanello, Joseph; Franchin, Giovanni; Sartor, Giovanna; Jena, Rajesh; Drigo, Annalisa; Dassie, Andrea; Gigante, Marco; Capra, Elvira

    2010-01-01

    Purpose: To extend the application of current radiation therapy (RT) based tumor control probability (TCP) models of nasopharyngeal carcinoma (NPC) to include the effects of hypoxia and chemoradiotherapy (CRT). Methods: A TCP model is described based on the linear-quadratic model modified to account for repopulation, chemotherapy, heterogeneity of dose to the tumor, and hypoxia. Sensitivity analysis was performed to determine which parameters exert the greatest influence on the uncertainty of modeled TCP. On the basis of the sensitivity analysis, the values of specific radiobiological parameters were set to nominal values reported in the literature for NPC or head and neck tumors. The remaining radiobiological parameters were determined by fitting TCP to clinical local control data from published randomized studies using both RT and CRT. Validation of the model was performed by comparison of estimated TCP and average overall local control rate (LCR) for 45 patients treated at the institution with conventional linear-accelerator-based or helical tomotherapy based intensity-modulated RT and neoadjuvant chemotherapy. Results: Sensitivity analysis demonstrates that the model is most sensitive to the radiosensitivity term α and the dose per fraction. The estimated values of α and OER from data fitting were 0.396 Gy -1 and 1.417. The model estimate of TCP (average 90.9%, range 26.9%-99.2%) showed good correlation with the LCR (86.7%). Conclusions: The model implemented in this work provides clinicians with a useful tool to predict the success rate of treatment, optimize treatment plans, and compare the effects of multimodality therapy.

  16. Modeling protective anti-tumor immunity via preventative cancer vaccines using a hybrid agent-based and delay differential equation approach.

    Science.gov (United States)

    Kim, Peter S; Lee, Peter P

    2012-01-01

    A next generation approach to cancer envisions developing preventative vaccinations to stimulate a person's immune cells, particularly cytotoxic T lymphocytes (CTLs), to eliminate incipient tumors before clinical detection. The purpose of our study is to quantitatively assess whether such an approach would be feasible, and if so, how many anti-cancer CTLs would have to be primed against tumor antigen to provide significant protection. To understand the relevant dynamics, we develop a two-compartment model of tumor-immune interactions at the tumor site and the draining lymph node. We model interactions at the tumor site using an agent-based model (ABM) and dynamics in the lymph node using a system of delay differential equations (DDEs). We combine the models into a hybrid ABM-DDE system and investigate dynamics over a wide range of parameters, including cell proliferation rates, tumor antigenicity, CTL recruitment times, and initial memory CTL populations. Our results indicate that an anti-cancer memory CTL pool of 3% or less can successfully eradicate a tumor population over a wide range of model parameters, implying that a vaccination approach is feasible. In addition, sensitivity analysis of our model reveals conditions that will result in rapid tumor destruction, oscillation, and polynomial rather than exponential decline in the tumor population due to tumor geometry.

  17. Image-based modeling of tumor shrinkage in head and neck radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Chao Ming; Xie Yaoqin; Moros, Eduardo G.; Le, Quynh-Thu; Xing Lei [Department of Radiation Oncology, Stanford University School of Medicine, 875 Blake Wilbur Drive, Stanford, California 94305-5847 and Department of Radiation Oncology, University of Arkansas for Medical Sciences, 4301 W. Markham Street, Little Rock, Arkansas 72205-1799 (United States); Department of Radiation Oncology, Stanford University School of Medicine, 875 Blake Wilbur Drive, Stanford, California 94305-5847 (United States); Department of Radiation Oncology, University of Arkansas for Medical Sciences, 4301 W. Markham Street, Little Rock, Arkansas 72205-1799 (United States); Department of Radiation Oncology, Stanford University School of Medicine, 875 Blake Wilbur Drive, Stanford, California 94305-5847 (United States)

    2010-05-15

    Purpose: Understanding the kinetics of tumor growth/shrinkage represents a critical step in quantitative assessment of therapeutics and realization of adaptive radiation therapy. This article presents a novel framework for image-based modeling of tumor change and demonstrates its performance with synthetic images and clinical cases. Methods: Due to significant tumor tissue content changes, similarity-based models are not suitable for describing the process of tumor volume changes. Under the hypothesis that tissue features in a tumor volume or at the boundary region are partially preserved, the kinetic change was modeled in two steps: (1) Autodetection of homologous tissue features shared by two input images using the scale invariance feature transformation (SIFT) method; and (2) establishment of a voxel-to-voxel correspondence between the images for the remaining spatial points by interpolation. The correctness of the tissue feature correspondence was assured by a bidirectional association procedure, where SIFT features were mapped from template to target images and reversely. A series of digital phantom experiments and five head and neck clinical cases were used to assess the performance of the proposed technique. Results: The proposed technique can faithfully identify the known changes introduced when constructing the digital phantoms. The subsequent feature-guided thin plate spline calculation reproduced the ''ground truth'' with accuracy better than 1.5 mm. For the clinical cases, the new algorithm worked reliably for a volume change as large as 30%. Conclusions: An image-based tumor kinetic algorithm was developed to model the tumor response to radiation therapy. The technique provides a practical framework for future application in adaptive radiation therapy.

  18. Birth characteristics and Wilms tumors in children in the Nordic countries: a register-based case-control study.

    Science.gov (United States)

    Schüz, Joachim; Schmidt, Lisbeth Samsø; Kogner, Per; Lähteenmäki, Päivi M; Pal, Niklas; Stokland, Tore; Schmiegelow, Kjeld

    2011-05-01

    Little is known about causes of Wilms tumor. Because of the young age at diagnosis, several studies have looked at various birth characteristics. We conducted a registry-based case-control study involving 690 cases of Wilms tumor aged 0-14 years, occurring in Denmark, Finland, Norway or Sweden during 1985-2006, individually matched to five controls drawn randomly from the Nordic childhood population. Information on birth characteristics was obtained from the population-based medical birth registries. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression analysis. We observed a distinct association between Wilms tumor and high birth weight (≥4 kg) for girls (OR 1.97, CI 1.50-2.59) but not for boys (1.04, 0.78-1.38); overall, the OR was 1.43 (1.17-1.74). Among girls, risk increased by 28% (15-42%) per 500 g increase in birth weight. Large-for-gestational age girls also had a higher risk (2.48, 1.51-4.05), whereas no effect was seen for boys (1.12, 0.60-2.07). An association was seen with Apgar score at 5 min birth order. In our large-scale, registry-based study, we confirmed earlier observations of an association between high birth weight and risk of Wilms tumor, but we found an effect only in girls. The higher risk of infants with low Apgar score might reflect hypoxia causing cell damage, adverse side effects of neonatal treatment or reverse causation as low Apgar score might indicate the presence of a tumor. Copyright © 2010 UICC.

  19. Poor prognosis of hexokinase 2 overexpression in solid tumors of digestive system: a meta-analysis.

    Science.gov (United States)

    Wu, Jiayuan; Hu, Liren; Wu, Fenping; Zou, Lei; He, Taiping

    2017-05-09

    Several previous studies have reported the prognostic value of hexokinase 2 (HK2) in digestive system tumors. However, these studies were limited by the small sample sizes and the results were inconsistent among them. Therefore, we conducted a meta-analysis based on 15 studies with 1932 patients to assess the relationship between HK2 overexpression and overall survival (OS) of digestive system malignancies. The relationship of HK2 and clinicopathological features was also evaluated. Hazard ratio (HR) or odds ratio (OR) with its 95% confidence intervals (CI) were calculated to estimate the effect size. Positive HK2 expression showed poor OS in all tumor types (HR = 1.75 [1.41-2.18], P digestive system cancers.

  20. [Extensive tumor of the skull base: sphenoid sinus adenocarcinoma].

    Science.gov (United States)

    Kallel, Souha; Sellami, Moncef

    2017-01-01

    We report a rare case of adenocarcinoma of the sphenoid sinus manifesting as extended skull base tumor. The patient included in the study was a 42-year old woman presenting with unilateral right symptomatology consisting of nasal obstruction, diplopia and hemifacial neuralgias. Clinical examination showed paralysis of the cranial nerve pairs V and VI. Brain scanner showed voluminous heterogeneous sphenoid and clival mass reaching the right cavernous sinus, with a peripheral tissue component at the level of the sphenoid sinus. Biopsy was performed under general anesthesia, through endonasal sphenoidotomy approach. Histological examination showed non-intestinal adenocarcinoma. The patient died due to impaired general condition occurred during examinations. Skull base adenocarcinomas mainly occur in the ethmoid bone. Sphenoid origin is exceptional. Radiological appearance is not specific and suggests malignancy. Diagnosis should be suspected in patients with aggressive tumor, even when it occurs in the midline skull base.

  1. Treatment results and prognostic indicators in thymic epithelial tumors: a clinicopathological analysis of 45 patients.

    Science.gov (United States)

    Ansari, Mansour; Dehsara, Farzin; Mohammadianpanah, Mohammad; Mosalaei, Ahmad; Omidvari, Shapour; Ahmadloo, Niloofar

    2014-07-01

    Thymomas are rare epithelial tumors arising from thymus gland. This study aims at investigating the clinical presentation, prognostic factors and treatment outcome of forty five patients with thymoma and thymic carcinoma. Forty-five patients being histologically diagnosed with thymoma or thymic carcinoma that were treated and followed-up at a tertiary academic hospital during January 1987 and December 2008 were selected for the present study. Twelve patients were solely treated with surgery, 14 with surgery followed by adjuvant radiotherapy, 12 with sequential combined treatment of surgery, radiotherapy and/or chemotherapy and 7 with non-surgical approach including radiotherapy and/or chemotherapy.  Tumors were classified based on the new World Health Organization (WHO) histological classification. There were 18 women and 27 men with a median age of 43 years. Twelve patients (26.7%) had stage I, 7 (17.8%) had stage II, 23 (51%) had stage III and 2 (4.5%) had stage IV disease. Tumors types were categorized as type A (n=4), type AB (n=10), type B1 (n=9), type B2 (n=10), type B3 (n=5) and type C (n=7). In univariate analysis for overall survival, disease stage (P=0.001), tumor size (P=0.017) and the extent of surgical resection (P<0.001) were prognostic factors. Regarding the multivariate analysis, only the extent of the surgical resection (P<0.001) was the independent prognostic factor and non-surgical treatment had a negative influence on the survival. The 5-year and 10-year overall survival rates were 70.8% and 62.9%, respectively. Complete surgical resection is the most important prognostic factor in patients with thymic epithelial tumors.

  2. Healthcare resource use, comorbidity, treatment and clinical outcomes for patients with primary intracranial tumors: a Swedish population-based register study.

    Science.gov (United States)

    Bergqvist, Jenny; Iderberg, Hanna; Mesterton, Johan; Bengtsson, Nils; Wettermark, Björn; Henriksson, Roger

    2017-03-01

    Primary intracranial tumors are relatively uncommon and heterogeneous, which make them challenging to study. We coupled data from unique Swedish population-based registries in order to deeper analyze the most common intracranical tumor types. Patient characteristics (e.g. comorbidities), care process measures like adherence to national guidelines, healthcare resource use and clinical outcome was evaluated. A register-based study including several population-based registries for all patients living in Stockholm-Gotland, diagnosed with primary intracranial tumor between 2001 and 2013 was performed. Patient characteristics were captured and investigated in relation to survival, healthcare resource use (inpatient-, outpatient- and primary care) and treatment process. High-grade glioma and meningioma were the most common tumor types and most patients (76%) were above the age of 40 in the patient population (n = 3664). Older age, comorbidity (Elixhauser comorbidity index) and type of tumor (high-grade glioma) were associated with lower survival rate and increased use of healthcare resources, analyzed for patients living in Stockholm (n = 3031). The analyses of healthcare use and survival showed no differences between males and females, when stratifying by tumor types. Healthcare processes were not always consistent with existing national treatment recommendations for patients with high-grade gliomas (n = 474) with regard to specified lead times, analyzed in the Swedish Brain Tumor Registry, as also observed at the national level. Age, comorbidity and high-grade gliomas, but not sex, were associated with decreased survival and increased use of healthcare resources. Fewer patients than aimed for in national guidelines received care according to specified lead times. The analysis of comprehensive population-based register data can be used to improve future care processes and outcomes.

  3. Tumor Heterogeneity: Mechanisms and Bases for a Reliable Application of Molecular Marker Design

    Science.gov (United States)

    Diaz-Cano, Salvador J.

    2012-01-01

    Tumor heterogeneity is a confusing finding in the assessment of neoplasms, potentially resulting in inaccurate diagnostic, prognostic and predictive tests. This tumor heterogeneity is not always a random and unpredictable phenomenon, whose knowledge helps designing better tests. The biologic reasons for this intratumoral heterogeneity would then be important to understand both the natural history of neoplasms and the selection of test samples for reliable analysis. The main factors contributing to intratumoral heterogeneity inducing gene abnormalities or modifying its expression include: the gradient ischemic level within neoplasms, the action of tumor microenvironment (bidirectional interaction between tumor cells and stroma), mechanisms of intercellular transference of genetic information (exosomes), and differential mechanisms of sequence-independent modifications of genetic material and proteins. The intratumoral heterogeneity is at the origin of tumor progression and it is also the byproduct of the selection process during progression. Any analysis of heterogeneity mechanisms must be integrated within the process of segregation of genetic changes in tumor cells during the clonal expansion and progression of neoplasms. The evaluation of these mechanisms must also consider the redundancy and pleiotropism of molecular pathways, for which appropriate surrogate markers would support the presence or not of heterogeneous genetics and the main mechanisms responsible. This knowledge would constitute a solid scientific background for future therapeutic planning. PMID:22408433

  4. Preoperative surgical planning and simulation of complex cranial base tumors in virtual reality

    Institute of Scientific and Technical Information of China (English)

    YI Zhi-qiang; LI Liang; MO Da-peng; ZHANG Jia-yong; ZHANG Yang; BAO Sheng-de

    2008-01-01

    @@ The extremely complex anatomic relationships among bone,tumor,blood vessels and cranial nerves remains a big challenge for cranial base tumor surgery.Therefore.a good understanding of the patient specific anatomy and a preoperative planning are helpful and crocial for the neurosurgeons.Three dimensional (3-D) visualization of various imaging techniques have been widely explored to enhance the comprehension of volumetric data for surgical planning.1 We used the Destroscope Virtual Reality (VR) System (Singapore,Volume Interaction Pte Ltd,software:RadioDexterTM 1.0) to optimize preoperative plan in the complex cranial base tumors.This system uses patient-specific,coregistered,fused radiology data sets that may be viewed stereoscopically and can be manipulated in a virtual reality environment.This article describes our experience with the Destroscope VR system in preoperative surgical planning and simulation for 5 patients with complex cranial base tumors and evaluates the clinical usefulness of this system.

  5. Microfluidic bead-based multienzyme-nanoparticle amplification for detection of circulating tumor cells in the blood using quantum dots labels

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, He, E-mail: mzhang_he@126.com; Fu, Xin; Hu, Jiayi; Zhu, Zhenjun

    2013-05-24

    Graphical abstract: A microfluidic beads-based nucleic acid sensor for sensitive detection of circulating tumor cells (CTCs) in the blood using multienzyme-nanoparticle amplification and quantum dots labels was developed. The chip-based CTCs analysis could detect reverse transcription-polymerase chain reaction (RT-PCR) products of tumor cell as low as 1 tumor cell (e.g. CEA expressing cell) in 1 mL blood sample. This microfluidic beads-based nucleic acid sensor is a promising platform for disease-related nucleic acid molecules at the lowest level at their earliest incidence. -- Highlights: •Combination of microfluidic bead-based platform and enzyme–probe–AuNPs is proposed. •The developed nucleic acid sensor could respond to 5 fM of tumor associated DNA. •Microfluidic platform and multienzyme-labeled AuNPs greatly enhanced sensitivity. •The developed nucleic acid sensor could respond to RT-PCR products of tumor cell as low as 1 tumor cell in 1 mL blood sample. •We report a sensitive nucleic acid sensor for detection of circulating tumor cells. -- Abstract: This study reports the development of a microfluidic bead-based nucleic acid sensor for sensitive detection of circulating tumor cells in blood samples using multienzyme-nanoparticle amplification and quantum dot labels. In this method, the microbeads functionalized with the capture probes and modified electron rich proteins were arrayed within a microfluidic channel as sensing elements, and the gold nanoparticles (AuNPs) functionalized with the horseradish peroxidases (HRP) and DNA probes were used as labels. Hence, two signal amplification approaches are integrated for enhancing the detection sensitivity of circulating tumor cells. First, the large surface area of Au nanoparticle carrier allows several binding events of HRP on each nanosphere. Second, enhanced mass transport capability inherent from microfluidics leads to higher capture efficiency of targets because continuous flow within micro

  6. meta-analysis of Serum Tumor Markers in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Xianfeng LU

    2010-12-01

    Full Text Available Background and objective The detection of serum tumor markers is of great value for early diagnosis of lung cancer. The aim of this study is to summarize the clinic significance characteristics of serum markers contributing to the detection of lung cancer. Methods References about serum markers of lung cancer were estimated using meta-analysis method. 712 references which included more than 20 cases, 20 controls, the serum markers of 52 832 patients with malignancies and 32 037 patients as controls were evaluated. Results Overall the detection of 13 markers play a significant part in lung cancer diagnosis. The sensitivity of CEA, CA125, CYFRA21-1, TPA, SCCAg, DKK1, NSE, ProGRP in the patients’ serum with lung cancer were 47.50%, 50.11%, 57.00%, 50.93%, 49.00%, 69.50%, 39.73%, 51.48% and the specificity were 92.34%, 80.19%, 90.16%, 88.41%, 91.07%, 92.20%, 89.11%, 94.89%. In the combined analysis of tumor markers: the sensitivity, specificity of NSE+ProGRP were 88.90% and 72.82% in diagnosis of small cell lung cancer, respectively. In diagnosis of squamous corcinoma, the sensitivity and specificity of TSGF+SCCAg+CYFRA21-1 were 95.30% and 74.20%. The the sensitivity and specificity of CA153+Ferrtin+CEA were 91.90% and 44.00% in diagnosis of lung cancer. Conclusion Although the assay of tumor markers in serum is useful for diagnosis of early lung cancer, the sensitivity and specificity are low. Combined detection of these tumor markers could increase sensitivity and specificity.

  7. Histogram Analysis of CT Perfusion of Hepatocellular Carcinoma for Predicting Response to Transarterial Radioembolization: Value of Tumor Heterogeneity Assessment.

    Science.gov (United States)

    Reiner, Caecilia S; Gordic, Sonja; Puippe, Gilbert; Morsbach, Fabian; Wurnig, Moritz; Schaefer, Niklaus; Veit-Haibach, Patrick; Pfammatter, Thomas; Alkadhi, Hatem

    2016-03-01

    To evaluate in patients with hepatocellular carcinoma (HCC), whether assessment of tumor heterogeneity by histogram analysis of computed tomography (CT) perfusion helps predicting response to transarterial radioembolization (TARE). Sixteen patients (15 male; mean age 65 years; age range 47-80 years) with HCC underwent CT liver perfusion for treatment planning prior to TARE with Yttrium-90 microspheres. Arterial perfusion (AP) derived from CT perfusion was measured in the entire tumor volume, and heterogeneity was analyzed voxel-wise by histogram analysis. Response to TARE was evaluated on follow-up imaging (median follow-up, 129 days) based on modified Response Evaluation Criteria in Solid Tumors (mRECIST). Results of histogram analysis and mean AP values of the tumor were compared between responders and non-responders. Receiver operating characteristics were calculated to determine the parameters' ability to discriminate responders from non-responders. According to mRECIST, 8 patients (50%) were responders and 8 (50%) non-responders. Comparing responders and non-responders, the 50th and 75th percentile of AP derived from histogram analysis was significantly different [AP 43.8/54.3 vs. 27.6/34.3 mL min(-1) 100 mL(-1)); p 0.05) was not. Further heterogeneity parameters from histogram analysis (skewness, coefficient of variation, and 25th percentile) did not differ between responders and non-responders (p > 0.05). If the cut-off for the 75th percentile was set to an AP of 37.5 mL min(-1) 100 mL(-1), therapy response could be predicted with a sensitivity of 88% (7/8) and specificity of 75% (6/8). Voxel-wise histogram analysis of pretreatment CT perfusion indicating tumor heterogeneity of HCC improves the pretreatment prediction of response to TARE.

  8. Curettage of benign bone tumors and tumor like lesions: A retrospective analysis

    Directory of Open Access Journals (Sweden)

    Zile Singh Kundu

    2013-01-01

    Full Text Available Background: Curettage is one of the most common treatment options for benign lytic bone tumors and tumor like lesions. The resultant defect is usually filled. We report our outcome curettage of benign bone tumors and tumor like lesions without filling the cavity. Materials and Methods: We retrospectively studied 42 patients (28 males and 14 females with benign bone tumors who had undergone curettage without grafting or filling of the defect by any other bone graft substitute. The age of the patients ranged from 14 to 66 years. The most common histological diagnosis was that of giant cell tumor followed by simple bone cyst, aneurysamal bone cyst, enchondroma, fibrous dysplasia, chondromyxoid fibroma, and chondroblastoma and giant cell reparative granuloma. Of the 15 giant cell tumors, 4 were radiographic grade 1 lesions, 8 were grade 2 and 3 grade 3. The mean maximum diameter of the cysts was 5.1 (range 1.1-9 cm cm and the mean volume of the lesions was 34.89 cm 3 (range 0.94-194.52 cm 3 . The plain radiographs of the part before and after curettage were reviewed to establish the size of the initial defect and the rate of reconstitution, filling and remodeling of the bone defect. Patients were reviewed every 3 monthly for a minimum period of 2 years. Results: Most of the bone defects completely reconstituted to a normal appearance while the rest filled partially. Two patients had preoperative and three had postoperative fractures. All the fractures healed uneventfully. Local recurrence occurred in three patients with giant cell tumor who were then reoperated. All other patients had unrestricted activities of daily living after surgery. The rate of bone reconstitution, risk of subsequent fracture or the incidence of complications was related to the size of the cyst/tumor at diagnosis. The benign cystic bone lesions with volume greater than approximately 70 cm 3 were found to have higher incidence of complications. Conclusion: This study

  9. Frame-based and frameless stereotactic radiosurgery for intracranial and extracranial tumors

    International Nuclear Information System (INIS)

    Petrovich, Z.; Cheng Yu

    2003-01-01

    During the past 10 years stereotactic frame-based radiosurgery (SRS) emerged as an important treatment modality in the management of selected intracranial lesions. More recently, frameless SRS has extended the potential of ibis treatment to include lesions virtually in any site of the body. Many thousands of patients are being treated annually with frame-based SRS limited to the cranial cavity. A total of 180,222 patients were treated to December 2001 with gamma knife (GK) and, very likely, a similar number was treated with various linear accelerator based SRS systems. Frameless SRS has been performed uncommonly until cyber knife (CK) became available. Over 3,000 patients were treated with CK in the US and Japan. This included patients treated for extracranial lesions. Treatment results in patients treated with GK at University of Southern California (USC) will be presented. From 1994 to 2002, a total of 1,126 patients received GK at USC for various indications. Since metastatic tumor constituted the largest (42.4%) diagnostic category treated, the outcome in this group is specifically discussed. The overall median survival was 9.2 months. The median survival was 8.3, 9.0, 17 and 12 months, for melanoma, lung cancer, breast cancer and renal cell carcinoma, respectively. In multivariate analysis Karnofsky's performance status (70 vs. >70), status of systemic disease (inactive vs. active), tumor histology and total intracranial tumor volume were the only important factors predictive of survival, p=0.0001. Cause of death was found to be due to CNS problems in about 25% of patients with a diagnosis other than melanoma, while it was 42% in those with melanoma. GK SRS was given on an outpatient basis and was very well tolerated by the patients. Symptomatic focal radionecrosis requiring craniotomy for its removal was noted in <5% of patients. An excellent palliative benefit was obtained in nearly all patients. The treatment was compatible with a good quality of life

  10. A GPU-based framework for modeling real-time 3D lung tumor conformal dosimetry with subject-specific lung tumor motion

    International Nuclear Information System (INIS)

    Min Yugang; Santhanam, Anand; Ruddy, Bari H; Neelakkantan, Harini; Meeks, Sanford L; Kupelian, Patrick A

    2010-01-01

    In this paper, we present a graphics processing unit (GPU)-based simulation framework to calculate the delivered dose to a 3D moving lung tumor and its surrounding normal tissues, which are undergoing subject-specific lung deformations. The GPU-based simulation framework models the motion of the 3D volumetric lung tumor and its surrounding tissues, simulates the dose delivery using the dose extracted from a treatment plan using Pinnacle Treatment Planning System, Phillips, for one of the 3DCTs of the 4DCT and predicts the amount and location of radiation doses deposited inside the lung. The 4DCT lung datasets were registered with each other using a modified optical flow algorithm. The motion of the tumor and the motion of the surrounding tissues were simulated by measuring the changes in lung volume during the radiotherapy treatment using spirometry. The real-time dose delivered to the tumor for each beam is generated by summing the dose delivered to the target volume at each increase in lung volume during the beam delivery time period. The simulation results showed the real-time capability of the framework at 20 discrete tumor motion steps per breath, which is higher than the number of 4DCT steps (approximately 12) reconstructed during multiple breathing cycles.

  11. A GPU-based framework for modeling real-time 3D lung tumor conformal dosimetry with subject-specific lung tumor motion

    Energy Technology Data Exchange (ETDEWEB)

    Min Yugang; Santhanam, Anand; Ruddy, Bari H [University of Central Florida, FL (United States); Neelakkantan, Harini; Meeks, Sanford L [M D Anderson Cancer Center Orlando, FL (United States); Kupelian, Patrick A, E-mail: anand.santhanam@orlandohealth.co [Department of Radiation Oncology, University of California, Los Angeles, CA (United States)

    2010-09-07

    In this paper, we present a graphics processing unit (GPU)-based simulation framework to calculate the delivered dose to a 3D moving lung tumor and its surrounding normal tissues, which are undergoing subject-specific lung deformations. The GPU-based simulation framework models the motion of the 3D volumetric lung tumor and its surrounding tissues, simulates the dose delivery using the dose extracted from a treatment plan using Pinnacle Treatment Planning System, Phillips, for one of the 3DCTs of the 4DCT and predicts the amount and location of radiation doses deposited inside the lung. The 4DCT lung datasets were registered with each other using a modified optical flow algorithm. The motion of the tumor and the motion of the surrounding tissues were simulated by measuring the changes in lung volume during the radiotherapy treatment using spirometry. The real-time dose delivered to the tumor for each beam is generated by summing the dose delivered to the target volume at each increase in lung volume during the beam delivery time period. The simulation results showed the real-time capability of the framework at 20 discrete tumor motion steps per breath, which is higher than the number of 4DCT steps (approximately 12) reconstructed during multiple breathing cycles.

  12. A GPU-based framework for modeling real-time 3D lung tumor conformal dosimetry with subject-specific lung tumor motion.

    Science.gov (United States)

    Min, Yugang; Santhanam, Anand; Neelakkantan, Harini; Ruddy, Bari H; Meeks, Sanford L; Kupelian, Patrick A

    2010-09-07

    In this paper, we present a graphics processing unit (GPU)-based simulation framework to calculate the delivered dose to a 3D moving lung tumor and its surrounding normal tissues, which are undergoing subject-specific lung deformations. The GPU-based simulation framework models the motion of the 3D volumetric lung tumor and its surrounding tissues, simulates the dose delivery using the dose extracted from a treatment plan using Pinnacle Treatment Planning System, Phillips, for one of the 3DCTs of the 4DCT and predicts the amount and location of radiation doses deposited inside the lung. The 4DCT lung datasets were registered with each other using a modified optical flow algorithm. The motion of the tumor and the motion of the surrounding tissues were simulated by measuring the changes in lung volume during the radiotherapy treatment using spirometry. The real-time dose delivered to the tumor for each beam is generated by summing the dose delivered to the target volume at each increase in lung volume during the beam delivery time period. The simulation results showed the real-time capability of the framework at 20 discrete tumor motion steps per breath, which is higher than the number of 4DCT steps (approximately 12) reconstructed during multiple breathing cycles.

  13. Histogram Analysis of Diffusion Tensor Imaging Parameters in Pediatric Cerebellar Tumors.

    Science.gov (United States)

    Wagner, Matthias W; Narayan, Anand K; Bosemani, Thangamadhan; Huisman, Thierry A G M; Poretti, Andrea

    2016-05-01

    Apparent diffusion coefficient (ADC) values have been shown to assist in differentiating cerebellar pilocytic astrocytomas and medulloblastomas. Previous studies have applied only ADC measurements and calculated the mean/median values. Here we investigated the value of diffusion tensor imaging (DTI) histogram characteristics of the entire tumor for differentiation of cerebellar pilocytic astrocytomas and medulloblastomas. Presurgical DTI data were analyzed with a region of interest (ROI) approach to include the entire tumor. For each tumor, histogram-derived metrics including the 25th percentile, 75th percentile, and skewness were calculated for fractional anisotropy (FA) and mean (MD), axial (AD), and radial (RD) diffusivity. The histogram metrics were used as primary predictors of interest in a logistic regression model. Statistical significance levels were set at p histogram skewness showed statistically significant differences for MD between low- and high-grade tumors (P = .008). The 25th percentile for MD yields the best results for the presurgical differentiation between pediatric cerebellar pilocytic astrocytomas and medulloblastomas. The analysis of other DTI metrics does not provide additional diagnostic value. Our study confirms the diagnostic value of the quantitative histogram analysis of DTI data in pediatric neuro-oncology. Copyright © 2015 by the American Society of Neuroimaging.

  14. Tumor control probability after a radiation of animal tumors

    International Nuclear Information System (INIS)

    Urano, Muneyasu; Ando, Koichi; Koike, Sachiko; Nesumi, Naofumi

    1975-01-01

    Tumor control and regrowth probability of animal tumors irradiated with a single x-ray dose were determined, using a spontaneous C3H mouse mammary carcinoma. Cellular radiation sensitivity of tumor cells and tumor control probability of the tumor were examined by the TD 50 and TCD 50 assays respectively. Tumor growth kinetics were measured by counting the percentage of labelled mitosis and by measuring the growth curve. A mathematical analysis of tumor control probability was made from these results. A formula proposed, accounted for cell population kinetics or division probability model, cell sensitivity to radiation and number of tumor cells. (auth.)

  15. Cross platform analysis of methylation, miRNA and stem cell gene expression data in germ cell tumors highlights characteristic differences by tumor histology

    International Nuclear Information System (INIS)

    Poynter, Jenny N.; Bestrashniy, Jessica R. B. M.; Silverstein, Kevin A. T.; Hooten, Anthony J.; Lees, Christopher; Ross, Julie A.; Tolar, Jakub

    2015-01-01

    Alterations in methylation patterns, miRNA expression, and stem cell protein expression occur in germ cell tumors (GCTs). Our goal is to integrate molecular data across platforms to identify molecular signatures in the three main histologic subtypes of Type I and Type II GCTs (yolk sac tumor (YST), germinoma, and teratoma). We included 39 GCTs and 7 paired adjacent tissue samples in the current analysis. Molecular data available for analysis include DNA methylation data (Illumina GoldenGate Cancer Methylation Panel I), miRNA expression (NanoString nCounter miRNA platform), and stem cell factor expression (SABiosciences Human Embryonic Stem Cell Array). We evaluated the cross platform correlations of the data features using the Maximum Information Coefficient (MIC). In analyses of individual datasets, differences were observed by tumor histology. Germinomas had higher expression of transcription factors maintaining stemness, while YSTs had higher expression of cytokines, endoderm and endothelial markers. We also observed differences in miRNA expression, with miR-371-5p, miR-122, miR-302a, miR-302d, and miR-373 showing elevated expression in one or more histologic subtypes. Using the MIC, we identified correlations across the data features, including six major hubs with higher expression in YST (LEFTY1, LEFTY2, miR302b, miR302a, miR 126, and miR 122) compared with other GCT. While prognosis for GCTs is overall favorable, many patients experience resistance to chemotherapy, relapse and/or long term adverse health effects following treatment. Targeted therapies, based on integrated analyses of molecular tumor data such as that presented here, may provide a way to secure high cure rates while reducing unintended health consequences

  16. [Computer aided diagnosis model for lung tumor based on ensemble convolutional neural network].

    Science.gov (United States)

    Wang, Yuanyuan; Zhou, Tao; Lu, Huiling; Wu, Cuiying; Yang, Pengfei

    2017-08-01

    The convolutional neural network (CNN) could be used on computer-aided diagnosis of lung tumor with positron emission tomography (PET)/computed tomography (CT), which can provide accurate quantitative analysis to compensate for visual inertia and defects in gray-scale sensitivity, and help doctors diagnose accurately. Firstly, parameter migration method is used to build three CNNs (CT-CNN, PET-CNN, and PET/CT-CNN) for lung tumor recognition in CT, PET, and PET/CT image, respectively. Then, we aimed at CT-CNN to obtain the appropriate model parameters for CNN training through analysis the influence of model parameters such as epochs, batchsize and image scale on recognition rate and training time. Finally, three single CNNs are used to construct ensemble CNN, and then lung tumor PET/CT recognition was completed through relative majority vote method and the performance between ensemble CNN and single CNN was compared. The experiment results show that the ensemble CNN is better than single CNN on computer-aided diagnosis of lung tumor.

  17. A 40 GHz fully integrated circuit with a vector network analyzer and a coplanar-line-based detection area for circulating tumor cell analysis using 65 nm CMOS technology

    Science.gov (United States)

    Nakanishi, Taiki; Matsunaga, Maya; Kobayashi, Atsuki; Nakazato, Kazuo; Niitsu, Kiichi

    2018-03-01

    A 40-GHz fully integrated CMOS-based circuit for circulating tumor cells (CTC) analysis, consisting of an on-chip vector network analyzer (VNA) and a highly sensitive coplanar-line-based detection area is presented in this paper. In this work, we introduce a fully integrated architecture that eliminates unwanted parasitic effects. The proposed analyzer was designed using 65 nm CMOS technology, and SPICE and MWS simulations were used to validate its operation. The simulation confirmed that the proposed circuit can measure S-parameter shifts resulting from the addition of various types of tumor cells to the detection area, the data of which are provided in a previous study: the |S 21| values for HepG2, A549, and HEC-1-A cells are -0.683, -0.580, and -0.623 dB, respectively. Additionally, the measurement demonstrated an S-parameters reduction of -25.7% when a silicone resin was put on the circuit. Hence, the proposed system is expected to contribute to cancer diagnosis.

  18. Lipid nanocarriers based on natural oils with high activity against oxygen free radicals and tumor cell proliferation

    International Nuclear Information System (INIS)

    Lacatusu, I.; Badea, N.; Badea, G.; Oprea, O.; Mihaila, M.A.; Kaya, D.A.; Stan, R.; Meghea, A.

    2015-01-01

    The development of nano-dosage forms of phytochemicals represents a significant progress of the scientific approach in the biomedical research. The aim of this study was to assess the effectiveness of lipid nanocarriers based on natural oils (grape seed oil, fish oil and laurel leaf oil) in counteracting free radicals and combating certain tumor cells. No drug was encapsulated in the nanocarriers. The cytotoxic effect exerted by bioactive nanocarriers against two tumor cells, MDA-MB 231 and HeLa cell lines, and two normal cells, L929 and B16 cell lines, was measured using the MTT assay, while oxidative damage was assessed by measuring the total antioxidant activity using chemiluminescence analysis. The best performance was obtained for nanocarriers based on an association of grape seed and laurel leaf oils, with a capacity to scavenge about 98% oxygen free radicals. A dose of nanocarriers of 5 mg·mL −1 has led to a drastic decrease in tumor cell proliferation even in the absence of an antitumor drug (e.g. about 50% viability for MDA-MB 231 cell line and 60% viability for HeLa cell line). A comparative survival profile of normal and tumor cells, which were exposed to an effective dose of 2.5 mg·mL −1 lipid nanocarriers, has revealed a death rate of 20% for normal B16 cells and of 40% death rate for MDA-MB 231 and HeLa tumor cells. The results in this study imply that lipid nanocarriers based on grape seed oil in association with laurel leaf oil could be a candidate to reduce the delivery system toxicity and may significantly improve the therapeutic efficacy of antitumor drugs in clinical applications. - Highlights: • Functional lipid nanocarriers with unique features and broad spectrum effectiveness • Lipid nanocarriers based on laureal leaf oil (LLO) and grape seed oil (GSO) • Antioxidant activity has reached 98% for nanocarriers containing 25% GSO and 2% LLO. • LLO exerts a significant cytotoxic effect against HeLa and MDA-MB 231 tumor cells. • 50

  19. Lipid nanocarriers based on natural oils with high activity against oxygen free radicals and tumor cell proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Lacatusu, I.; Badea, N.; Badea, G.; Oprea, O. [University Politehnica of Bucharest, Faculty of Applied Chemistry and Materials Science, Polizu Street No 1, 011061 Bucharest (Romania); Mihaila, M.A. [Institute of Virusology “Stefan S. Nicolau”, Center of Immunology, Bravu Road, No. 285, 030304 Bucharest (Romania); Kaya, D.A. [Department of Field Crops, Faculty of Agriculture, Mustafa Kemal University, 31030 Antakya, Hatay (Turkey); Stan, R., E-mail: rl_stan2000@yahoo.com [University Politehnica of Bucharest, Faculty of Applied Chemistry and Materials Science, Polizu Street No 1, 011061 Bucharest (Romania); Meghea, A. [University Politehnica of Bucharest, Faculty of Applied Chemistry and Materials Science, Polizu Street No 1, 011061 Bucharest (Romania)

    2015-11-01

    The development of nano-dosage forms of phytochemicals represents a significant progress of the scientific approach in the biomedical research. The aim of this study was to assess the effectiveness of lipid nanocarriers based on natural oils (grape seed oil, fish oil and laurel leaf oil) in counteracting free radicals and combating certain tumor cells. No drug was encapsulated in the nanocarriers. The cytotoxic effect exerted by bioactive nanocarriers against two tumor cells, MDA-MB 231 and HeLa cell lines, and two normal cells, L929 and B16 cell lines, was measured using the MTT assay, while oxidative damage was assessed by measuring the total antioxidant activity using chemiluminescence analysis. The best performance was obtained for nanocarriers based on an association of grape seed and laurel leaf oils, with a capacity to scavenge about 98% oxygen free radicals. A dose of nanocarriers of 5 mg·mL{sup −1} has led to a drastic decrease in tumor cell proliferation even in the absence of an antitumor drug (e.g. about 50% viability for MDA-MB 231 cell line and 60% viability for HeLa cell line). A comparative survival profile of normal and tumor cells, which were exposed to an effective dose of 2.5 mg·mL{sup −1} lipid nanocarriers, has revealed a death rate of 20% for normal B16 cells and of 40% death rate for MDA-MB 231 and HeLa tumor cells. The results in this study imply that lipid nanocarriers based on grape seed oil in association with laurel leaf oil could be a candidate to reduce the delivery system toxicity and may significantly improve the therapeutic efficacy of antitumor drugs in clinical applications. - Highlights: • Functional lipid nanocarriers with unique features and broad spectrum effectiveness • Lipid nanocarriers based on laureal leaf oil (LLO) and grape seed oil (GSO) • Antioxidant activity has reached 98% for nanocarriers containing 25% GSO and 2% LLO. • LLO exerts a significant cytotoxic effect against HeLa and MDA-MB 231 tumor

  20. Mutational analysis of circulating tumor cells from colorectal cancer patients and correlation with primary tumor tissue.

    Directory of Open Access Journals (Sweden)

    Anna Lyberopoulou

    Full Text Available Circulating tumor cells (CTCs provide a non-invasive accessible source of tumor material from patients with cancer. The cellular heterogeneity within CTC populations is of great clinical importance regarding the increasing number of adjuvant treatment options for patients with metastatic carcinomas, in order to eliminate residual disease. Moreover, the molecular profiling of these rare cells might lead to insight on disease progression and therapeutic strategies than simple CTCs counting. In the present study we investigated the feasibility to detect KRAS, BRAF, CD133 and Plastin3 (PLS3 mutations in an enriched CTCs cell suspension from patients with colorectal cancer, with the hypothesis that these genes` mutations are of great importance regarding the generation of CTCs subpopulations. Subsequently, we compared CTCs mutational status with that of the corresponding primary tumor, in order to access the possibility of tumor cells characterization without biopsy. CTCs were detected and isolated from blood drawn from 52 colorectal cancer (CRC patients using a quantum-dot-labelled magnetic immunoassay method. Mutations were detected by PCR-RFLP or allele-specific PCR and confirmed by direct sequencing. In 52 patients, discordance between primary tumor and CTCs was 5.77% for KRAS, 3.85% for BRAF, 11.54% for CD133 rs3130, 7.69% for CD133 rs2286455 and 11.54% for PLS3 rs6643869 mutations. Our results support that DNA mutational analysis of CTCs may enable non-invasive, specific biomarker diagnostics and expand the scope of personalized medicine for cancer patients.

  1. Precision cancer immunotherapy: optimizing dendritic cell-based strategies to induce tumor antigen-specific T-cell responses against individual patient tumors.

    Science.gov (United States)

    Osada, Takuya; Nagaoka, Koji; Takahara, Masashi; Yang, Xiao Yi; Liu, Cong-Xiao; Guo, Hongtao; Roy Choudhury, Kingshuk; Hobeika, Amy; Hartman, Zachary; Morse, Michael A; Lyerly, H Kim

    2015-05-01

    Most dendritic cell (DC)-based vaccines have loaded the DC with defined antigens, but loading with autologos tumor-derived antigens would generate DCs that activate personalized tumor-specific T-cell responses. We hypothesized that DC matured with an optimized combination of reagents and loaded with tumor-derived antigens using a clinically feasible electroporation strategy would induce potent antitumor immunity. We first studied the effects on DC maturation and antigen presentation of the addition of picibanil (OK432) to a combination of zoledronic acid, tumor necrosis factor-α, and prostaglandin E2. Using DC matured with the optimized combination, we tested 2 clinically feasible sources of autologous antigen for electroloading, total tumor mRNA or total tumor lysate, to determine which stimulated more potent antigen-specific T cells in vitro and activated more potent antitumor immunity in vivo. The combination of tumor necrosis factor-α/prostaglandin E2/zoledronic acid/OK432 generated DC with high expression of maturation markers and antigen-specific T-cell stimulatory function in vitro. Mature DC electroloaded with tumor-derived mRNA [mRNA electroporated dendritic cell (EPDC)] induced greater expansion of antigen-specific T cells in vitro than DC electroloaded with tumor lysate (lysate EPDC). In a therapeutic model of MC38-carcinoembryonic antigen colon cancer-bearing mice, vaccination with mRNA EPDC induced the most efficient anti-carcinoembryonic antigen cellular immune response, which significantly suppressed tumor growth. In conclusion, mature DC electroloaded with tumor-derived mRNA are a potent cancer vaccine, especially useful when specific tumor antigens for vaccination have not been identified, allowing autologous tumor, and if unavailable, allogeneic cell lines to be used as an unbiased source of antigen. Our data support clinical testing of this strategy.

  2. Imaging analysis of colonic villous tumors

    International Nuclear Information System (INIS)

    Lee, Choon Hyeong; Lim, Joo Won; Lee, Dong Ho; Ko, Yung Tae; Yang, Ik

    1996-01-01

    To evaluate the CT and US features of the colonic villous tumors. We retrospectively reviewed the CT findings of 11 cases with histologically proved colonic villous tumor. CT parameters evaluated were morphological appearances and enhancing pattern (size, shape, margin, presence or absence of fronds, bowel wall thickening). CT features of six cases with malignant change were compared with five tumors without malignant change. US features available in 10 patients were also analyzed. On CT, the tumors showed irregular margin(n=9), presence of fronds(n=6), lobulated shape(n=11), with pericolonic invasion(n=1). Six cases with malignant change were larger(mean, 6.8 cm in diameter) than those without malignant change(mean, 3.3cm). US features in 10 cases were intraluminal mass(n=5), colonic wall thickening(n=5), with variable echogenicity. Colonic villous tumor appeared as a nonspecific mass on CT and US with a difficulty in distinguishing from colon carcinoma

  3. The role of stereotactic radiosurgery in the treatment of malignant skull base tumors

    International Nuclear Information System (INIS)

    Miller, Robert C.; Foote, Robert L.; Coffey, Robert J.; Gorman, Deborah A.; Earle, John D.; Schomberg, Paula J.; Kline, Robert W.

    1997-01-01

    Purpose: To determine the efficacy and toxicity of stereotactic radiosurgery in the treatment of malignant skull base tumors. Methods and Materials: Thirty-two patients with 35 newly diagnosed or recurrent malignant skull base tumors ≤33.5 cm 3 were treated using the Leksell Gamma unit. Tumor histologies included: adenoid cystic carcinoma, basal cell carcinoma, chondrosarcoma, chordoma, nasopharyngeal carcinoma, osteogenic sarcoma, and squamous cell carcinoma. Results: After a median follow-up of 2.3 years, 83% ± 15% (±95% confidence interval) of patients experienced a symptomatic response to treatment. Local control at the skull base was 95 ± 9% at 2 years and 78 ± 23% at 3 years. Local-regional control above the clavicles was 75 ± 15% at 1 year and 51 ± 20% at 2 years. Overall and cause specific survival were identical, 82 ± 13% at 1 year, 76 ± 14% at 2 years, and 72 ± 16% at 3 years. One patient developed a radiation-induced optic neuropathy 12 months after radiosurgery. Conclusion: Stereotactic radiosurgery using the Leksell Gamma Unit can provide durable tumor control and symptomatic relief with acceptable toxicity in the majority of patients with malignant tumors 4 cm or less in size involving the skull base. Further evaluation of more patients with longer follow-up is warranted

  4. Preoperative Visualization of Cranial Nerves in Skull Base Tumor Surgery Using Diffusion Tensor Imaging Technology.

    Science.gov (United States)

    Ma, Jun; Su, Shaobo; Yue, Shuyuan; Zhao, Yan; Li, Yonggang; Chen, Xiaochen; Ma, Hui

    2016-01-01

    To visualize cranial nerves (CNs) using diffusion tensor imaging (DTI) with special parameters. This study also involved the evaluation of preoperative estimates and intraoperative confirmation of the relationship between nerves and tumor by verifying the accuracy of visualization. 3T magnetic resonance imaging scans including 3D-FSPGR, FIESTA, and DTI were used to collect information from 18 patients with skull base tumor. DTI data were integrated into the 3D slicer for fiber tracking and overlapped anatomic images to determine course of nerves. 3D reconstruction of tumors was achieved to perform neighboring, encasing, and invading relationship between lesion and nerves. Optic pathway including the optic chiasm could be traced in cases of tuberculum sellae meningioma and hypophysoma (pituitary tumor). The oculomotor nerve, from the interpeduncular fossa out of the brain stem to supraorbital fissure, was clearly visible in parasellar meningioma cases. Meanwhile, cisternal parts of trigeminal nerve and abducens nerve, facial nerve were also imaged well in vestibular schwannomas and petroclival meningioma cases. The 3D-spatial relationship between CNs and skull base tumor estimated preoperatively by tumor modeling and tractography corresponded to the results determined during surgery. Supported by DTI and 3D slicer, preoperative 3D reconstruction of most CNs related to skull base tumor is feasible in pathological circumstances. We consider DTI Technology to be a useful tool for predicting the course and location of most CNs, and syntopy between them and skull base tumor.

  5. Tumor Heterogeneity: Mechanisms and Bases for a Reliable Application of Molecular Marker Design

    Directory of Open Access Journals (Sweden)

    Salvador J. Diaz-Cano

    2012-02-01

    Full Text Available Tumor heterogeneity is a confusing finding in the assessment of neoplasms, potentially resulting in inaccurate diagnostic, prognostic and predictive tests. This tumor heterogeneity is not always a random and unpredictable phenomenon, whose knowledge helps designing better tests. The biologic reasons for this intratumoral heterogeneity would then be important to understand both the natural history of neoplasms and the selection of test samples for reliable analysis. The main factors contributing to intratumoral heterogeneity inducing gene abnormalities or modifying its expression include: the gradient ischemic level within neoplasms, the action of tumor microenvironment (bidirectional interaction between tumor cells and stroma, mechanisms of intercellular transference of genetic information (exosomes, and differential mechanisms of sequence-independent modifications of genetic material and proteins. The intratumoral heterogeneity is at the origin of tumor progression and it is also the byproduct of the selection process during progression. Any analysis of heterogeneity mechanisms must be integrated within the process of segregation of genetic changes in tumor cells during the clonal expansion and progression of neoplasms. The evaluation of these mechanisms must also consider the redundancy and pleiotropism of molecular pathways, for which appropriate surrogate markers would support the presence or not of heterogeneous genetics and the main mechanisms responsible. This knowledge would constitute a solid scientific background for future therapeutic planning.

  6. FDTD analysis of a noninvasive hyperthermia system for brain tumors.

    Science.gov (United States)

    Yacoob, Sulafa M; Hassan, Noha S

    2012-08-14

    Hyperthermia is considered one of the new therapeutic modalities for cancer treatment and is based on the difference in thermal sensitivity between healthy tissues and tumors. During hyperthermia treatment, the temperature of the tumor is raised to 40-45°C for a definite period resulting in the destruction of cancer cells. This paper investigates design, modeling and simulation of a new non-invasive hyperthermia applicator system capable of effectively heating deep seated as well as superficial brain tumors using inexpensive, simple, and easy to fabricate components without harming surrounding healthy brain tissues. The proposed hyperthermia applicator system is composed of an air filled partial half ellipsoidal chamber, a patch antenna, and a head model with an embedded tumor at an arbitrary location. The irradiating antenna is placed at one of the foci of the hyperthermia chamber while the center of the brain tumor is placed at the other focus. The finite difference time domain (FDTD) method is used to compute both the SAR patterns and the temperature distribution in three different head models due to two different patch antennas at a frequency of 915 MHz. The obtained results suggest that by using the proposed noninvasive hyperthermia system it is feasible to achieve sufficient and focused energy deposition and temperature rise to therapeutic values in deep seated as well as superficial brain tumors without harming surrounding healthy tissue. The proposed noninvasive hyperthermia system proved suitable for raising the temperature in tumors embedded in the brain to therapeutic values by carefully selecting the systems components. The operator of the system only needs to place the center of the brain tumor at a pre-specified location and excite the antenna at a single frequency of 915 MHz. Our study may provide a basis for a clinical applicator prototype capable of heating brain tumors.

  7. Needle-based polarization-sensitive OCT of breast tumor (Conference Presentation)

    Science.gov (United States)

    Villiger, Martin; Lorenser, Dirk; McLaughlin, Robert A.; Quirk, Bryden C.; Kirk, Rodney W.; Bouma, Brett E.; Sampson, David D.

    2016-03-01

    OCT imaging through miniature needle probes has extended the range of OCT and enabled structural imaging deep inside breast tissue, with the potential to assist in the intraoperative assessment of tumor margins. However, in many situations, scattering contrast alone is insufficient to clearly identify and delineate malignant areas. Here, we present a portable, depth-encoded polarization-sensitive OCT system, connected to a miniature needle probe. From the measured polarization states we constructed the tissue Mueller matrix at each sample location and improved the accuracy of the measured polarization states through incoherent averaging before retrieving the depth-resolved tissue birefringence. With the Mueller matrix at hand, additional polarization properties such as depolarization are readily available. We then imaged freshly excised breast tissue from a patient undergoing lumpectomy. The reconstructed local retardation highlighted regions of connective tissue, which exhibited birefringence due to the abundance of collagen fibers, and offered excellent contrast to areas of malignant tissue, which exhibited less birefringence due to their different tissue composition. Results were validated against co-located histology sections. The combination of needle-based imaging with the complementary contrast provided by polarization-sensitive analysis offers a powerful instrument for advanced tissue imaging and has potential to aid in the assessment of tumor margins during the resection of breast cancer.

  8. Treatment Results and Prognostic Indicators in Thymic Epithelial Tumors: A Clinicopathological Analysis of 45 Patients

    Directory of Open Access Journals (Sweden)

    Mansour Ansari

    2014-07-01

    Full Text Available Background: Thymomas are rare epithelial tumors arising from thymus gland. This study aims at investigating the clinical presentation, prognostic factors and treatment outcome of forty five patients with thymoma and thymic carcinoma. Methods: Forty-five patients being histologically diagnosed with thymoma or thymic carcinoma that were treated and followed-up at a tertiary academic hospital during January 1987 and December 2008 were selected for the present study. Twelve patients were solely treated with surgery, 14 with surgery followed by adjuvant radiotherapy, 12 with sequential combined treatment of surgery, radiotherapy and/or chemotherapy and 7 with non-surgical approach including radiotherapy and/or chemotherapy. Tumors were classified based on the new World Health Organization (WHO histological classification. Results: There were 18 women and 27 men with a median age of 43 years. Twelve patients (26.7% had stage I, 7 (17.8% had stage II, 23 (51% had stage III and 2 (4.5% had stage IV disease. Tumors types were categorized as type A (n=4, type AB (n=10, type B1 (n=9, type B2 (n=10, type B3 (n=5 and type C (n=7. In univariate analysis for overall survival, disease stage (P=0.001, tumor size (P=0.017 and the extent of surgical resection (P<0.001 were prognostic factors. Regarding the multivariate analysis, only the extent of the surgical resection (P<0.001 was the independent prognostic factor and non-surgical treatment had a negative influence on the survival. The 5-year and 10-year overall survival rates were 70.8% and 62.9%, respectively. Conclusion: Complete surgical resection is the most important prognostic factor in patients with thymic epithelial tumors.

  9. A magnetic micropore chip for rapid (<1 hour) unbiased circulating tumor cell isolation and in situ RNA analysis.

    Science.gov (United States)

    Ko, Jina; Bhagwat, Neha; Yee, Stephanie S; Black, Taylor; Redlinger, Colleen; Romeo, Janae; O'Hara, Mark; Raj, Arjun; Carpenter, Erica L; Stanger, Ben Z; Issadore, David

    2017-09-12

    The use of microtechnology for the highly selective isolation and sensitive detection of circulating tumor cells has shown enormous promise. One challenge for this technology is that the small feature sizes - which are the key to this technology's performance - can result in low sample throughput and susceptibility to clogging. Additionally, conventional molecular analysis of CTCs often requires cells to be taken off-chip for sample preparation and purification before analysis, leading to the loss of rare cells. To address these challenges, we have developed a microchip platform that combines fast, magnetic micropore based negative immunomagnetic selection (>10 mL h -1 ) with rapid on-chip in situ RNA profiling (>100× faster than conventional RNA labeling). This integrated chip can isolate both rare circulating cells and cell clusters directly from whole blood and allow individual cells to be profiled for multiple RNA cancer biomarkers, achieving sample-to-answer in less than 1 hour for 10 mL of whole blood. To demonstrate the power of this approach, we applied our device to the circulating tumor cell based diagnosis of pancreatic cancer. We used a genetically engineered lineage-labeled mouse model of pancreatic cancer (KPCY) to validate the performance of our chip. We show that in a cohort of patient samples (N = 25) that this device can detect and perform in situ RNA analysis on circulating tumor cells in patients with pancreatic cancer, even in those with extremely sparse CTCs (<1 CTC mL -1 of whole blood).

  10. Nanobody-Based Delivery Systems for Diagnosis and Targeted Tumor Therapy

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    Yaozhong Hu

    2017-11-01

    Full Text Available The development of innovative targeted therapeutic approaches are expected to surpass the efficacy of current forms of treatments and cause less damage to healthy cells surrounding the tumor site. Since the first development of targeting agents from hybridoma’s, monoclonal antibodies (mAbs have been employed to inhibit tumor growth and proliferation directly or to deliver effector molecules to tumor cells. However, the full potential of such a delivery strategy is hampered by the size of mAbs, which will obstruct the targeted delivery system to access the tumor tissue. By serendipity, a new kind of functional homodimeric antibody format was discovered in camelidae, known as heavy-chain antibodies (HCAbs. The cloning of the variable domain of HCAbs produces an attractive minimal-sized alternative for mAbs, referred to as VHH or nanobodies (Nbs. Apart from their dimensions in the single digit nanometer range, the unique characteristics of Nbs combine a high stability and solubility, low immunogenicity and excellent affinity and specificity against all possible targets including tumor markers. This stimulated the development of tumor-targeted therapeutic strategies. Some autonomous Nbs have been shown to act as antagonistic drugs, but more importantly, the targeting capacity of Nbs has been exploited to create drug delivery systems. Obviously, Nb-based targeted cancer therapy is mainly focused toward extracellular tumor markers, since the membrane barrier prevents antibodies to reach the most promising intracellular tumor markers. Potential strategies, such as lentiviral vectors and bacterial type 3 secretion system, are proposed to deliver target-specific Nbs into tumor cells and to block tumor markers intracellularly. Simultaneously, Nbs have also been employed for in vivo molecular imaging to diagnose diseased tissues and to monitor the treatment effects. Here, we review the state of the art and focus on recent developments with Nbs as

  11. US Intergroup Anal Carcinoma Trial: Tumor Diameter Predicts for Colostomy

    Science.gov (United States)

    Ajani, Jaffer A.; Winter, Kathryn A.; Gunderson, Leonard L.; Pedersen, John; Benson, Al B.; Thomas, Charles R.; Mayer, Robert J.; Haddock, Michael G.; Rich, Tyvin A.; Willett, Christopher G.

    2009-01-01

    Purpose The US Gastrointestinal Intergroup Radiation Therapy Oncology Group 98-11 anal carcinoma trial showed that cisplatin-based concurrent chemoradiotherapy resulted in a significantly higher rate of colostomy compared with mitomycin-based therapy. Established prognostic variables for patients with anal carcinoma include tumor diameter, clinical nodal status, and sex, but pretreatment variables that would predict the likelihood of colostomy are unknown. Methods A secondary analysis was performed by combining patients in the two treatment arms to evaluate whether new predictive and prognostic variables would emerge. Univariate and multivariate analyses were carried out to correlate overall survival (OS), disease-free survival, and time to colostomy (TTC) with pretreatment and treatment variables. Results Of 682 patients enrolled, 644 patients were assessable and analyzed. In the multivariate analysis, tumor-related prognosticators for poorer OS included node-positive cancer (P ≤ .0001), large (> 5 cm) tumor diameter (P = .01), and male sex (P = .016). In the treatment-related categories, cisplatin-based therapy was statistically significantly associated with a higher rate of colostomy (P = .03) than was mitomycin-based therapy. In the pretreatment variables category, only large tumor diameter independently predicted for TTC (P = .008). Similarly, the cumulative 5-year colostomy rate was statistically significantly higher for large tumor diameter than for small tumor diameter (Gray's test; P = .0074). Clinical nodal status and sex were not predictive of TTC. Conclusion The combined analysis of the two arms of RTOG 98-11, representing the largest prospective database, reveals that tumor diameter (irrespective of the nodal status) is the only independent pretreatment variable that predicts TTC and 5-year colostomy rate in patients with anal carcinoma. PMID:19139424

  12. SU-G-BRA-04: Simulation of Errors in Maximal Intensity Projection (MIP)-Based Lung Tumor Internal Target Volumes (ITV) Using Real-Time 2D MRI and Deformable Image Registration Based Lung Tumor Tracking

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    Thomas, D; Kishan, A; Santhanam, A; Min, Y; O’Connell, D; Lamb, J; Cao, M; Agazaryan, N; Yang, Y; Lee, P; Low, D [University of California, Los Angeles, Ca (United States)

    2016-06-15

    Purpose: To evaluate the effect of inter- and intra-fractional tumor motion on the error in four-dimensional computed tomography (4DCT) maximal intensity projection (MIP)–based lung tumor internal target volumes (ITV), using deformable image registration of real-time 2D-sagital cine-mode MRI acquired during lung SBRT treatments. Methods: Five lung tumor patients underwent free breathing SBRT treatment on the ViewRay, with dose prescribed to PTV (4DCT MIP-based ITV+3–6mm margin). Sagittal slice cine-MR images (3.5×3.5mm pixels) were acquired through the center of the tumor at 4 frames per second throughout the treatments (3–4 fractions of 21–32 minutes duration). Tumor GTVs were contoured on the first frame of the cine and tracked throughout the treatment using off-line optical-flow based deformable registration implemented on a GPU cluster. Pseudo-4DCT MIP-based ITVs were generated from MIPs of the deformed GTV contours limited to short segments of image data. All possible pseudo-4DCT MIP-based ITV volumes were generated with 1s resolution and compared to the ITV volume of the entire treatment course. Varying pseudo-4DCT durations from 10-50s were analyzed. Results: Tumors were covered in their entirety by PTV in the patients analysed here. However, pseudo-4DCT based ITV volumes were observed that were as small as 29% of the entire treatment-ITV, depending on breathing irregularity and the duration of pseudo-4DCT. With an increase in duration of pseudo-4DCT from 10–50s the minimum volume acquired from 95% of all pseudo-4DCTs increased from 62%–81% of the treatment ITV. Conclusion: A 4DCT MIP-based ITV offers a ‘snap-shot’ of breathing motion for the brief period of time the tumor is imaged on a specific day. Real time MRI over prolonged periods of time and over multiple treatment fractions shows that the accuracy of this snap-shot varies according to inter- and intra-fractional tumor motion. Further work is required to investigate the dosimetric

  13. SU-G-BRA-04: Simulation of Errors in Maximal Intensity Projection (MIP)-Based Lung Tumor Internal Target Volumes (ITV) Using Real-Time 2D MRI and Deformable Image Registration Based Lung Tumor Tracking

    International Nuclear Information System (INIS)

    Thomas, D; Kishan, A; Santhanam, A; Min, Y; O’Connell, D; Lamb, J; Cao, M; Agazaryan, N; Yang, Y; Lee, P; Low, D

    2016-01-01

    Purpose: To evaluate the effect of inter- and intra-fractional tumor motion on the error in four-dimensional computed tomography (4DCT) maximal intensity projection (MIP)–based lung tumor internal target volumes (ITV), using deformable image registration of real-time 2D-sagital cine-mode MRI acquired during lung SBRT treatments. Methods: Five lung tumor patients underwent free breathing SBRT treatment on the ViewRay, with dose prescribed to PTV (4DCT MIP-based ITV+3–6mm margin). Sagittal slice cine-MR images (3.5×3.5mm pixels) were acquired through the center of the tumor at 4 frames per second throughout the treatments (3–4 fractions of 21–32 minutes duration). Tumor GTVs were contoured on the first frame of the cine and tracked throughout the treatment using off-line optical-flow based deformable registration implemented on a GPU cluster. Pseudo-4DCT MIP-based ITVs were generated from MIPs of the deformed GTV contours limited to short segments of image data. All possible pseudo-4DCT MIP-based ITV volumes were generated with 1s resolution and compared to the ITV volume of the entire treatment course. Varying pseudo-4DCT durations from 10-50s were analyzed. Results: Tumors were covered in their entirety by PTV in the patients analysed here. However, pseudo-4DCT based ITV volumes were observed that were as small as 29% of the entire treatment-ITV, depending on breathing irregularity and the duration of pseudo-4DCT. With an increase in duration of pseudo-4DCT from 10–50s the minimum volume acquired from 95% of all pseudo-4DCTs increased from 62%–81% of the treatment ITV. Conclusion: A 4DCT MIP-based ITV offers a ‘snap-shot’ of breathing motion for the brief period of time the tumor is imaged on a specific day. Real time MRI over prolonged periods of time and over multiple treatment fractions shows that the accuracy of this snap-shot varies according to inter- and intra-fractional tumor motion. Further work is required to investigate the dosimetric

  14. Brain Tumor Database, a free relational database for collection and analysis of brain tumor patient information.

    Science.gov (United States)

    Bergamino, Maurizio; Hamilton, David J; Castelletti, Lara; Barletta, Laura; Castellan, Lucio

    2015-03-01

    In this study, we describe the development and utilization of a relational database designed to manage the clinical and radiological data of patients with brain tumors. The Brain Tumor Database was implemented using MySQL v.5.0, while the graphical user interface was created using PHP and HTML, thus making it easily accessible through a web browser. This web-based approach allows for multiple institutions to potentially access the database. The BT Database can record brain tumor patient information (e.g. clinical features, anatomical attributes, and radiological characteristics) and be used for clinical and research purposes. Analytic tools to automatically generate statistics and different plots are provided. The BT Database is a free and powerful user-friendly tool with a wide range of possible clinical and research applications in neurology and neurosurgery. The BT Database graphical user interface source code and manual are freely available at http://tumorsdatabase.altervista.org. © The Author(s) 2013.

  15. PCR Expression Analysis Of the Estrogeninducible Gene Bcei in Gastrointestinal and Other Human Tumors

    Directory of Open Access Journals (Sweden)

    Iris Wundrack

    1994-01-01

    Full Text Available A polymerase chain reaction (PCR assay was developed to test for tumor cell specific expression of the BCEI gene. This new marker gene, reported at first for human breast cancer, was found specifically active in various gastrointestinal carcinomas by previously applying immunohistochemistry and RNA (Northern blot analysis. Presently, by using reverse transcription -PCR analysis, a series of primary tumor tissues and established tumor cell lines were testcd for BCEI transcription. This approach was compared to immunostaining achieved by an antibody directed against the BCEI gene’s product. The result demonstrate the superior sensitivity of PCR by indicating the gene’ s expression in cases where immunohistochemical testing remained negative.

  16. An Improved Binary Differential Evolution Algorithm to Infer Tumor Phylogenetic Trees.

    Science.gov (United States)

    Liang, Ying; Liao, Bo; Zhu, Wen

    2017-01-01

    Tumourigenesis is a mutation accumulation process, which is likely to start with a mutated founder cell. The evolutionary nature of tumor development makes phylogenetic models suitable for inferring tumor evolution through genetic variation data. Copy number variation (CNV) is the major genetic marker of the genome with more genes, disease loci, and functional elements involved. Fluorescence in situ hybridization (FISH) accurately measures multiple gene copy number of hundreds of single cells. We propose an improved binary differential evolution algorithm, BDEP, to infer tumor phylogenetic tree based on FISH platform. The topology analysis of tumor progression tree shows that the pathway of tumor subcell expansion varies greatly during different stages of tumor formation. And the classification experiment shows that tree-based features are better than data-based features in distinguishing tumor. The constructed phylogenetic trees have great performance in characterizing tumor development process, which outperforms other similar algorithms.

  17. Characterization of adjacent breast tumors using oligonucleotide microarrays

    International Nuclear Information System (INIS)

    Unger, Meredith A; Rishi, Mazhar; Clemmer, Virginia B; Hartman, Jennifer L; Keiper, Elizabeth A; Greshock, Joel D; Chodosh, Lewis A; Liebman, Michael N; Weber, Barbara L

    2001-01-01

    Current methodology often cannot distinguish second primary breast cancers from multifocal disease, a potentially important distinction for clinical management. In the present study we evaluated the use of oligonucleotide-based microarray analysis in determining the clonality of tumors by comparing gene expression profiles. Total RNA was extracted from two tumors with no apparent physical connection that were located in the right breast of an 87-year-old woman diagnosed with invasive ductal carcinoma (IDC). The RNA was hybridized to the Affymetrix Human Genome U95A Gene Chip ® (12,500 known human genes) and analyzed using the Gene Chip Analysis Suite ® 3.3 (Affymetrix, Inc, Santa Clara, CA, USA) and JMPIN ® 3.2.6 (SAS Institute, Inc, Cary, NC, USA). Gene expression profiles of tumors from five additional patients were compared in order to evaluate the heterogeneity in gene expression between tumors with similar clinical characteristics. The adjacent breast tumors had a pairwise correlation coefficient of 0.987, and were essentially indistinguishable by microarray analysis. Analysis of gene expression profiles from different individuals, however, generated a pairwise correlation coefficient of 0.710. Transcriptional profiling may be a useful diagnostic tool for determining tumor clonality and heterogeneity, and may ultimately impact on therapeutic decision making

  18. Delivered dose uncertainty analysis at the tumor apex for ocular brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Morrison, Hali, E-mail: hamorris@ualberta.ca; Menon, Geetha; Larocque, Matthew P.; Jans, Hans-Sonke; Sloboda, Ron S. [Department of Medical Physics, Cross Cancer Institute, Edmonton, Alberta T6G 1Z2, Canada and Department of Oncology, University of Alberta, Edmonton, Alberta T6G 2R3 (Canada); Weis, Ezekiel [Department of Ophthalmology, University of Alberta, Edmonton, Alberta T6G 2R3 (Canada)

    2016-08-15

    depth, thus resulting in the changing uncertainties and margins with depth. Conclusions: The margins determined in this work can be used as a guide for determining an appropriate apex margin for a given treatment, which can be chosen based on the tumor height. The required margin may need to be increased for more complex scenarios (mushroom shaped tumors, tumors close to the optic nerve, oblique muscle related tilt, etc.) than the simple dome-shaped tumor examined and should be chosen on a case-by-case basis. The sources of uncertainty contributing most significantly to the total dosimetric uncertainty are seed placement within the plaques, treatment planning calculations, tumor height measurement, and plaque tilt. This work presents an uncertainty-based, rational approach to estimating an appropriate apex margin.

  19. Tumor immunology.

    Science.gov (United States)

    Mocellin, Simone; Lise, Mario; Nitti, Donato

    2007-01-01

    Advances in tumor immunology are supporting the clinical implementation of several immunological approaches to cancer in the clinical setting. However, the alternate success of current immunotherapeutic regimens underscores the fact that the molecular mechanisms underlying immune-mediated tumor rejection are still poorly understood. Given the complexity of the immune system network and the multidimensionality of tumor/host interactions, the comprehension of tumor immunology might greatly benefit from high-throughput microarray analysis, which can portrait the molecular kinetics of immune response on a genome-wide scale, thus accelerating the discovery pace and ultimately catalyzing the development of new hypotheses in cell biology. Although in its infancy, the implementation of microarray technology in tumor immunology studies has already provided investigators with novel data and intriguing new hypotheses on the molecular cascade leading to an effective immune response against cancer. Although the general principles of microarray-based gene profiling have rapidly spread in the scientific community, the need for mastering this technique to produce meaningful data and correctly interpret the enormous output of information generated by this technology is critical and represents a tremendous challenge for investigators, as outlined in the first section of this book. In the present Chapter, we report on some of the most significant results obtained with the application of DNA microarray in this oncology field.

  20. Image-based modeling of tumor shrinkage in head and neck radiation therapy1

    Science.gov (United States)

    Chao, Ming; Xie, Yaoqin; Moros, Eduardo G.; Le, Quynh-Thu; Xing, Lei

    2010-01-01

    Purpose: Understanding the kinetics of tumor growth∕shrinkage represents a critical step in quantitative assessment of therapeutics and realization of adaptive radiation therapy. This article presents a novel framework for image-based modeling of tumor change and demonstrates its performance with synthetic images and clinical cases. Methods: Due to significant tumor tissue content changes, similarity-based models are not suitable for describing the process of tumor volume changes. Under the hypothesis that tissue features in a tumor volume or at the boundary region are partially preserved, the kinetic change was modeled in two steps: (1) Autodetection of homologous tissue features shared by two input images using the scale invariance feature transformation (SIFT) method; and (2) establishment of a voxel-to-voxel correspondence between the images for the remaining spatial points by interpolation. The correctness of the tissue feature correspondence was assured by a bidirectional association procedure, where SIFT features were mapped from template to target images and reversely. A series of digital phantom experiments and five head and neck clinical cases were used to assess the performance of the proposed technique. Results: The proposed technique can faithfully identify the known changes introduced when constructing the digital phantoms. The subsequent feature-guided thin plate spline calculation reproduced the “ground truth” with accuracy better than 1.5 mm. For the clinical cases, the new algorithm worked reliably for a volume change as large as 30%. Conclusions: An image-based tumor kinetic algorithm was developed to model the tumor response to radiation therapy. The technique provides a practical framework for future application in adaptive radiation therapy. PMID:20527569

  1. Comprehensive Analysis of Genome Rearrangements in Eight Human Malignant Tumor Tissues.

    Directory of Open Access Journals (Sweden)

    Stefanie Marczok

    Full Text Available Carcinogenesis is a complex multifactorial, multistage process, but the precise mechanisms are not well understood. In this study, we performed a genome-wide analysis of the copy number variation (CNV, breakpoint region (BPR and fragile sites in 2,737 tumor samples from eight tumor entities and in 432 normal samples. CNV detection and BPR identification revealed that BPRs tended to accumulate in specific genomic regions in tumor samples whereas being dispersed genome-wide in the normal samples. Hotspots were observed, at which segments with similar alteration in copy number were overlapped along with BPRs adjacently clustered. Evaluation of BPR occurrence frequency showed that at least one was detected in about and more than 15% of samples for each tumor entity while BPRs were maximal in 12% of the normal samples. 127 of 2,716 tumor-relevant BPRs (termed 'common BPRs' exhibited also a noticeable occurrence frequency in the normal samples. Colocalization assessment identified 20,077 CNV-affecting genes and 169 of these being known tumor-related genes. The most noteworthy genes are KIAA0513 important for immunologic, synaptic and apoptotic signal pathways, intergenic non-coding RNA RP11-115C21.2 possibly acting as oncogene or tumor suppressor by changing the structure of chromatin, and ADAM32 likely importance in cancer cell proliferation and progression by ectodomain-shedding of diverse growth factors, and the well-known tumor suppressor gene p53. The BPR distributions indicate that CNV mutations are likely non-random in tumor genomes. The marked recurrence of BPRs at specific regions supports common progression mechanisms in tumors. The presence of hotspots together with common BPRs, despite its small group size, imply a relation between fragile sites and cancer-gene alteration. Our data further suggest that both protein-coding and non-coding genes possessing a range of biological functions might play a causative or functional role in tumor

  2. Anti-tumor effects of metformin in animal models of hepatocellular carcinoma: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Juan Li

    Full Text Available Several studies have reported that metformin can reduce the risk of hepatocellular carcinoma (HCC in diabetes patients. However, the direct anti-HCC effects of metformin have hardly been studied in patients, but have been extensively investigated in animal models of HCC. We therefore performed a systematic review and meta-analysis of animal studies evaluating the effects of metformin on HCC.We collected the relevant studies by searching EMBASE, Medline (OvidSP, Web of Science, Scopus, PubMed Publisher, and Google Scholar. Studies were included according to the following inclusion criteria: HCC, animal study, and metformin intervention. Study quality was assessed using SYRCLE's risk of bias tool. A meta-analysis was performed for the outcome measures: tumor growth (tumor volume, weight and size, tumor number and incidence.The search resulted in 573 references, of which 13 could be included in the review and 12 included in the meta-analysis. The study characteristics of the included studies varied considerably. Two studies used rats, while the others used mice. Only one study used female animals, nine used male, and three studies didn't mention the gender of animals in their experiments. The quality of the included studies was low to moderate based on the assessment of their risk of bias. The meta-analysis showed that metformin significantly inhibited the growth of HCC tumour (SMD -2.20[-2.96,-1.43]; n=16, but no significant effect on the number of tumors (SMD-1.05[-2.13,0.03]; n=5 or the incidence of HCC was observed (RR 0.62[0.33,1.16]; n=6. To investigate the potential sources of significant heterogeneities found in outcome of tumor growth (I2=81%, subgroup analyses of scales of growth measures and of types of animal models used were performed.Metformin appears to have a direct anti-HCC effect in animal models. Although the intrinsic limitations of animal studies, this systematic review could provide an important reference for future

  3. Optimizing 4-Dimensional Magnetic Resonance Imaging Data Sampling for Respiratory Motion Analysis of Pancreatic Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Stemkens, Bjorn, E-mail: b.stemkens@umcutrecht.nl [Department of Radiotherapy, University Medical Center Utrecht, Utrecht (Netherlands); Tijssen, Rob H.N. [Department of Radiotherapy, University Medical Center Utrecht, Utrecht (Netherlands); Senneville, Baudouin D. de [Imaging Division, University Medical Center Utrecht, Utrecht (Netherlands); L' Institut de Mathématiques de Bordeaux, Unité Mixte de Recherche 5251, Centre National de la Recherche Scientifique/University of Bordeaux, Bordeaux (France); Heerkens, Hanne D.; Vulpen, Marco van; Lagendijk, Jan J.W.; Berg, Cornelis A.T. van den [Department of Radiotherapy, University Medical Center Utrecht, Utrecht (Netherlands)

    2015-03-01

    Purpose: To determine the optimum sampling strategy for retrospective reconstruction of 4-dimensional (4D) MR data for nonrigid motion characterization of tumor and organs at risk for radiation therapy purposes. Methods and Materials: For optimization, we compared 2 surrogate signals (external respiratory bellows and internal MRI navigators) and 2 MR sampling strategies (Cartesian and radial) in terms of image quality and robustness. Using the optimized protocol, 6 pancreatic cancer patients were scanned to calculate the 4D motion. Region of interest analysis was performed to characterize the respiratory-induced motion of the tumor and organs at risk simultaneously. Results: The MRI navigator was found to be a more reliable surrogate for pancreatic motion than the respiratory bellows signal. Radial sampling is most benign for undersampling artifacts and intraview motion. Motion characterization revealed interorgan and interpatient variation, as well as heterogeneity within the tumor. Conclusions: A robust 4D-MRI method, based on clinically available protocols, is presented and successfully applied to characterize the abdominal motion in a small number of pancreatic cancer patients.

  4. Analysis of Lung Tumor Motion in a Large Sample: Patterns and Factors Influencing Precise Delineation of Internal Target Volume

    International Nuclear Information System (INIS)

    Knybel, Lukas; Cvek, Jakub; Molenda, Lukas; Stieberova, Natalie; Feltl, David

    2016-01-01

    Purpose/Objective: To evaluate lung tumor motion during respiration and to describe factors affecting the range and variability of motion in patients treated with stereotactic ablative radiation therapy. Methods and Materials: Log file analysis from online respiratory tumor tracking was performed in 145 patients. Geometric tumor location in the lungs, tumor volume and origin (primary or metastatic), sex, and tumor motion amplitudes in the superior-inferior (SI), latero-lateral (LL), and anterior-posterior (AP) directions were recorded. Tumor motion variability during treatment was described using intrafraction/interfraction amplitude variability and tumor motion baseline changes. Tumor movement dependent on the tumor volume, position and origin, and sex were evaluated using statistical regression and correlation analysis. Results: After analysis of >500 hours of data, the highest rates of motion amplitudes, intrafraction/interfraction variation, and tumor baseline changes were in the SI direction (6.0 ± 2.2 mm, 2.2 ± 1.8 mm, 1.1 ± 0.9 mm, and −0.1 ± 2.6 mm). The mean motion amplitudes in the lower/upper geometric halves of the lungs were significantly different (P 15 mm were observed only in the lower geometric quarter of the lungs. Higher tumor motion amplitudes generated higher intrafraction variations (R=.86, P 3 mm indicated tumors contacting mediastinal structures or parietal pleura. On univariate analysis, neither sex nor tumor origin (primary vs metastatic) was an independent predictive factor of different movement patterns. Metastatic lesions in women, but not men, showed significantly higher mean amplitudes (P=.03) and variability (primary, 2.7 mm; metastatic, 4.9 mm; P=.002) than primary tumors. Conclusion: Online tracking showed significant irregularities in lung tumor movement during respiration. Motion amplitude was significantly lower in upper lobe tumors; higher interfraction amplitude variability indicated tumors in contact

  5. Histogram Analysis of CT Perfusion of Hepatocellular Carcinoma for Predicting Response to Transarterial Radioembolization: Value of Tumor Heterogeneity Assessment

    International Nuclear Information System (INIS)

    Reiner, Caecilia S.; Gordic, Sonja; Puippe, Gilbert; Morsbach, Fabian; Wurnig, Moritz; Schaefer, Niklaus; Veit-Haibach, Patrick; Pfammatter, Thomas; Alkadhi, Hatem

    2016-01-01

    PurposeTo evaluate in patients with hepatocellular carcinoma (HCC), whether assessment of tumor heterogeneity by histogram analysis of computed tomography (CT) perfusion helps predicting response to transarterial radioembolization (TARE).Materials and MethodsSixteen patients (15 male; mean age 65 years; age range 47–80 years) with HCC underwent CT liver perfusion for treatment planning prior to TARE with Yttrium-90 microspheres. Arterial perfusion (AP) derived from CT perfusion was measured in the entire tumor volume, and heterogeneity was analyzed voxel-wise by histogram analysis. Response to TARE was evaluated on follow-up imaging (median follow-up, 129 days) based on modified Response Evaluation Criteria in Solid Tumors (mRECIST). Results of histogram analysis and mean AP values of the tumor were compared between responders and non-responders. Receiver operating characteristics were calculated to determine the parameters’ ability to discriminate responders from non-responders.ResultsAccording to mRECIST, 8 patients (50 %) were responders and 8 (50 %) non-responders. Comparing responders and non-responders, the 50th and 75th percentile of AP derived from histogram analysis was significantly different [AP 43.8/54.3 vs. 27.6/34.3 mL min −1  100 mL −1 ); p < 0.05], while the mean AP of HCCs (43.5 vs. 27.9 mL min −1  100 mL −1 ; p > 0.05) was not. Further heterogeneity parameters from histogram analysis (skewness, coefficient of variation, and 25th percentile) did not differ between responders and non-responders (p > 0.05). If the cut-off for the 75th percentile was set to an AP of 37.5 mL min −1  100 mL −1 , therapy response could be predicted with a sensitivity of 88 % (7/8) and specificity of 75 % (6/8).ConclusionVoxel-wise histogram analysis of pretreatment CT perfusion indicating tumor heterogeneity of HCC improves the pretreatment prediction of response to TARE

  6. Analysis of DCE-MRI features in tumor and the surrounding stroma for prediction of Ki-67 proliferation status in breast cancer

    Science.gov (United States)

    Li, Hui; Fan, Ming; Zhang, Peng; Li, Yuanzhe; Cheng, Hu; Zhang, Juan; Shao, Guoliang; Li, Lihua

    2018-03-01

    Breast cancer, with its high heterogeneity, is the most common malignancies in women. In addition to the entire tumor itself, tumor microenvironment could also play a fundamental role on the occurrence and development of tumors. The aim of this study is to investigate the role of heterogeneity within a tumor and the surrounding stromal tissue in predicting the Ki-67 proliferation status of oestrogen receptor (ER)-positive breast cancer patients. To this end, we collected 62 patients imaged with preoperative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for analysis. The tumor and the peritumoral stromal tissue were segmented into 8 shells with 5 mm width outside of tumor. The mean enhancement rate in the stromal shells showed a decreasing order if their distances to the tumor increase. Statistical and texture features were extracted from the tumor and the surrounding stromal bands, and multivariate logistic regression classifiers were trained and tested based on these features. An area under the receiver operating characteristic curve (AUC) were calculated to evaluate performance of the classifiers. Furthermore, the statistical model using features extracted from boundary shell next to the tumor produced AUC of 0.796+/-0.076, which is better than that using features from the other subregions. Furthermore, the prediction model using 7 features from the entire tumor produced an AUC value of 0.855+/-0.065. The classifier based on 9 selected features extracted from peritumoral stromal region showed an AUC value of 0.870+/-0.050. Finally, after fusion of the predictive model obtained from entire tumor and the peritumoral stromal regions, the classifier performance was significantly improved with AUC of 0.920. The results indicated that heterogeneity in tumor boundary and peritumoral stromal region could be valuable in predicting the indicator associated with prognosis.

  7. Enrichment of tumor cells for cell kinetic analysis in human tumor biopsies using cytokeratin gating

    International Nuclear Information System (INIS)

    Haustermans, K.; Hofland, I.; Ramaekers, M.; Ivanyi, D.; Balm, A.J.M.; Geboes, K.; Lerut, T.; Schueren, E. van der; Begg, A.C.

    1996-01-01

    Purpose: To determine the feasibility of using cytokeratin antibodies to distinguish normal and malignant cells in human tumors using flow cytometry. The goal was ultimately to increase the accuracy of cell kinetic measurements on human tumor biopsies. Material and methods: A panel of four antibodies was screened on a series of 48 tumors from two centres; 22 head and neck tumors (Amsterdam) and 26 esophagus carcinomas (Leuven). First, screening was carried out by immunohistochemistry on frozen sections to test intensity of staining and the fraction of cytokeratin-positive tumor cells. The antibody showing the most positive staining was then used for flow cytometry on the same tumor. Results: The two broadest spectrum antibodies (AE1/AE3, E3/C4) showed overall the best results with immunohistochemical staining, being positive in over 95% of tumors. Good cell suspensions for DNA flow cytometry could be made from frozen material by a mechanical method, whereas enzymatic methods with trypsin or collagenase were judged failures in almost all cases. >From fresh material, both collagenase and trypsin produced good suspensions for flow cytometry, although the fraction of tumor cells, judged by proportion aneuploid cells, was markedly higher for trypsin. Using the best cytokeratin antibody for each tumor, two parameter flow cytometry was done (cytokeratin versus DNA content). Enrichment of tumor cells was then tested by measuring the fraction of aneuploid cells (the presumed malignant population) of cytokeratin-positive cells versus all cells. An enrichment factor ranging between 0 (no enrichment) and 1 (perfect enrichment, tumor cells only) was then calculated. The average enrichment was 0.60 for head and neck tumors and 0.59 for esophagus tumors. Conclusions: We conclude that this method can substantially enrich the proportion of tumor cells in biopsies from carcinomas. Application of this method could significantly enhance accuracy of tumor cell kinetic measurements

  8. Tumor Suppressor Gene-Based Nanotherapy: From Test Tube to the Clinic

    Directory of Open Access Journals (Sweden)

    Manish Shanker

    2011-01-01

    Full Text Available Cancer is a major health problem in the world. Advances made in cancer therapy have improved the survival of patients in certain types of cancer. However, the overall five-year survival has not significantly improved in the majority of cancer types. Major challenges encountered in having effective cancer therapy are development of drug resistance by the tumor cells, nonspecific cytotoxicity, and inability to affect metastatic tumors by the chemodrugs. Overcoming these challenges requires development and testing of novel therapies. One attractive cancer therapeutic approach is cancer gene therapy. Several laboratories including the authors' laboratory have been investigating nonviral formulations for delivering therapeutic genes as a mode for effective cancer therapy. In this paper the authors will summarize their experience in the development and testing of a cationic lipid-based nanocarrier formulation and the results from their preclinical studies leading to a Phase I clinical trial for nonsmall cell lung cancer. Their nanocarrier formulation containing therapeutic genes such as tumor suppressor genes when administered intravenously effectively controls metastatic tumor growth. Additional Phase I clinical trials based on the results of their nanocarrier formulation have been initiated or proposed for treatment of cancer of the breast, ovary, pancreas, and metastatic melanoma, and will be discussed.

  9. Tumor suppressor gene-based nanotherapy: from test tube to the clinic.

    Science.gov (United States)

    Shanker, Manish; Jin, Jiankang; Branch, Cynthia D; Miyamoto, Shinya; Grimm, Elizabeth A; Roth, Jack A; Ramesh, Rajagopal

    2011-01-01

    Cancer is a major health problem in the world. Advances made in cancer therapy have improved the survival of patients in certain types of cancer. However, the overall five-year survival has not significantly improved in the majority of cancer types. Major challenges encountered in having effective cancer therapy are development of drug resistance by the tumor cells, nonspecific cytotoxicity, and inability to affect metastatic tumors by the chemodrugs. Overcoming these challenges requires development and testing of novel therapies. One attractive cancer therapeutic approach is cancer gene therapy. Several laboratories including the authors' laboratory have been investigating nonviral formulations for delivering therapeutic genes as a mode for effective cancer therapy. In this paper the authors will summarize their experience in the development and testing of a cationic lipid-based nanocarrier formulation and the results from their preclinical studies leading to a Phase I clinical trial for nonsmall cell lung cancer. Their nanocarrier formulation containing therapeutic genes such as tumor suppressor genes when administered intravenously effectively controls metastatic tumor growth. Additional Phase I clinical trials based on the results of their nanocarrier formulation have been initiated or proposed for treatment of cancer of the breast, ovary, pancreas, and metastatic melanoma, and will be discussed.

  10. A bispecific peptide based near-infrared probe for in vivo tumor diagnosis

    Science.gov (United States)

    Ding, Li; Chen, Wei R.; Gu, Yueqing

    2013-02-01

    The epidermal growth factor receptor EGFR and HER2 are members of recepeter tyrosine kinase family. Overexpression of EGFR and HER2 has been observed in a variety of human tumors, making these receptors promising targets for tumor diagnosis. An affibody targeting HER2 and a nanobody targeting EGFR were reported before. In this Manuscript, we described an bispecific peptide combined with an affibody and a nanonbody through a linker―(G4S)3 . And the bispecific peptide was labeled with near-infrared (NIR) fluorochrome ICG-Der-02 for in vivo tumor EGFR and HER2 targeting. Afterwards, the EGFR and HER2 specificity of the fluorescent probe was tested in vitro for receptor binding assay and fluorescence microscopy and in vivo for subcutaneous MDA-MB-231 tumor targeting. The results indicated that the bispecific peptide had a high affinity to EGFR and HER2. Besides, in vitro and in vivo tumor targeting experiment indicated that the ICG-Der-02-( bispecific peptide) showed excellent tumor activity accumulation. Noninvasive NIR fluorescence imaging is able to detect tumor EGFR and HER2 expression based upon the highly potent bispecific peptide probe.

  11. FDTD analysis of a noninvasive hyperthermia system for brain tumors

    Directory of Open Access Journals (Sweden)

    Yacoob Sulafa M

    2012-08-01

    Full Text Available Abstract Background Hyperthermia is considered one of the new therapeutic modalities for cancer treatment and is based on the difference in thermal sensitivity between healthy tissues and tumors. During hyperthermia treatment, the temperature of the tumor is raised to 40–45°C for a definite period resulting in the destruction of cancer cells. This paper investigates design, modeling and simulation of a new non-invasive hyperthermia applicator system capable of effectively heating deep seated as well as superficial brain tumors using inexpensive, simple, and easy to fabricate components without harming surrounding healthy brain tissues. Methods The proposed hyperthermia applicator system is composed of an air filled partial half ellipsoidal chamber, a patch antenna, and a head model with an embedded tumor at an arbitrary location. The irradiating antenna is placed at one of the foci of the hyperthermia chamber while the center of the brain tumor is placed at the other focus. The finite difference time domain (FDTD method is used to compute both the SAR patterns and the temperature distribution in three different head models due to two different patch antennas at a frequency of 915 MHz. Results The obtained results suggest that by using the proposed noninvasive hyperthermia system it is feasible to achieve sufficient and focused energy deposition and temperature rise to therapeutic values in deep seated as well as superficial brain tumors without harming surrounding healthy tissue. Conclusions The proposed noninvasive hyperthermia system proved suitable for raising the temperature in tumors embedded in the brain to therapeutic values by carefully selecting the systems components. The operator of the system only needs to place the center of the brain tumor at a pre-specified location and excite the antenna at a single frequency of 915 MHz. Our study may provide a basis for a clinical applicator prototype capable of heating brain tumors.

  12. Textural analysis of pre-therapeutic [18F]-FET-PET and its correlation with tumor grade and patient survival in high-grade gliomas

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    Pyka, Thomas; Hiob, Daniela; Wester, Hans-Juergen [Klinikum Rechts der Isar der TU Muenchen, Department of Nuclear Medicine, Munich (Germany); Gempt, Jens; Ringel, Florian; Meyer, Bernhard [Klinikum Rechts der Isar der TU Muenchen, Neurosurgic Department, Munich (Germany); Schlegel, Juergen [Klinikum Rechts der Isar der TU Muenchen, Institute of Pathology and Neuropathology, Munich (Germany); Bette, Stefanie [Klinikum Rechts der Isar der TU Muenchen, Neuroradiologic department, Munich (Germany); Foerster, Stefan [Klinikum Rechts der Isar der TU Muenchen, Department of Nuclear Medicine, Munich (Germany); Klinikum Rechts der Isar der TU Muenchen, TUM Neuroimaging Center (TUM-NIC), Munich (Germany)

    2016-01-15

    Amino acid positron emission tomography (PET) with [18F]-fluoroethyl-L-tyrosine (FET) is well established in the diagnostic work-up of malignant brain tumors. Analysis of FET-PET data using tumor-to-background ratios (TBR) has been shown to be highly valuable for the detection of viable hypermetabolic brain tumor tissue; however, it has not proven equally useful for tumor grading. Recently, textural features in 18-fluorodeoxyglucose-PET have been proposed as a method to quantify the heterogeneity of glucose metabolism in a variety of tumor entities. Herein we evaluate whether textural FET-PET features are of utility for grading and prognostication in patients with high-grade gliomas. One hundred thirteen patients (70 men, 43 women) with histologically proven high-grade gliomas were included in this retrospective study. All patients received static FET-PET scans prior to first-line therapy. TBR (max and mean), volumetric parameters and textural parameters based on gray-level neighborhood difference matrices were derived from static FET-PET images. Receiver operating characteristic (ROC) and discriminant function analyses were used to assess the value for tumor grading. Kaplan-Meier curves and univariate and multivariate Cox regression were employed for analysis of progression-free and overall survival. All FET-PET textural parameters showed the ability to differentiate between World Health Organization (WHO) grade III and IV tumors (p < 0.001; AUC 0.775). Further improvement in discriminatory power was possible through a combination of texture and metabolic tumor volume, classifying 85 % of tumors correctly (AUC 0.830). TBR and volumetric parameters alone were correlated with tumor grade, but showed lower AUC values (0.644 and 0.710, respectively). Furthermore, a correlation of FET-PET texture but not TBR was shown with patient PFS and OS, proving significant in multivariate analysis as well. Volumetric parameters were predictive for OS, but this correlation did not

  13. Content-based retrieval of brain tumor in contrast-enhanced MRI images using tumor margin information and learned distance metric.

    Science.gov (United States)

    Yang, Wei; Feng, Qianjin; Yu, Mei; Lu, Zhentai; Gao, Yang; Xu, Yikai; Chen, Wufan

    2012-11-01

    A content-based image retrieval (CBIR) method for T1-weighted contrast-enhanced MRI (CE-MRI) images of brain tumors is presented for diagnosis aid. The method is thoroughly evaluated on a large image dataset. Using the tumor region as a query, the authors' CBIR system attempts to retrieve tumors of the same pathological category. Aside from commonly used features such as intensity, texture, and shape features, the authors use a margin information descriptor (MID), which is capable of describing the characteristics of tissue surrounding a tumor, for representing image contents. In addition, the authors designed a distance metric learning algorithm called Maximum mean average Precision Projection (MPP) to maximize the smooth approximated mean average precision (mAP) to optimize retrieval performance. The effectiveness of MID and MPP algorithms was evaluated using a brain CE-MRI dataset consisting of 3108 2D scans acquired from 235 patients with three categories of brain tumors (meningioma, glioma, and pituitary tumor). By combining MID and other features, the mAP of retrieval increased by more than 6% with the learned distance metrics. The distance metric learned by MPP significantly outperformed the other two existing distance metric learning methods in terms of mAP. The CBIR system using the proposed strategies achieved a mAP of 87.3% and a precision of 89.3% when top 10 images were returned by the system. Compared with scale-invariant feature transform, the MID, which uses the intensity profile as descriptor, achieves better retrieval performance. Incorporating tumor margin information represented by MID with the distance metric learned by the MPP algorithm can substantially improve the retrieval performance for brain tumors in CE-MRI.

  14. A D-D/D-T fusion reaction based neutron generator system for liver tumor BNCT

    International Nuclear Information System (INIS)

    Koivunoro, H.; Lou, T.P.; Leung, K. N.; Reijonen, J.

    2003-01-01

    Boron-neutron capture therapy (BNCT) is an experimental radiation treatment modality used for highly malignant tumor treatments. Prior to irradiation with low energetic neutrons, a 10B compound is located selectively in the tumor cells. The effect of the treatment is based on the high LET radiation released in the 10 B(n,α) 7 Li reaction with thermal neutrons. BNCT has been used experimentally for brain tumor and melanoma treatments. Lately applications of other severe tumor type treatments have been introduced. Results have shown that liver tumors can also be treated by BNCT. At Lawrence Berkeley National Laboratory, various compact neutron generators based on D-D or D-T fusion reactions are being developed. The earlier theoretical studies of the D-D or D-T fusion reaction based neutron generators have shown that the optimal moderator and reflector configuration for brain tumor BNCT can be created. In this work, the applicability of 2.5 MeV neutrons for liver tumor BNCT application was studied. The optimal neutron energy for external liver treatments is not known. Neutron beams of different energies (1eV < E < 100 keV) were simulated and the dose distribution in the liver was calculated with the MCNP simulation code. In order to obtain the optimal neutron energy spectrum with the D-D neutrons, various moderator designs were performed using MCNP simulations. In this article the neutron spectrum and the optimized beam shaping assembly for liver tumor treatments is presented

  15. Quantitative Analysis of Signaling Networks across Differentially Embedded Tumors Highlights Interpatient Heterogeneity in Human Glioblastoma

    Science.gov (United States)

    2015-01-01

    Glioblastoma multiforme (GBM) is the most aggressive malignant primary brain tumor, with a dismal mean survival even with the current standard of care. Although in vitro cell systems can provide mechanistic insight into the regulatory networks governing GBM cell proliferation and migration, clinical samples provide a more physiologically relevant view of oncogenic signaling networks. However, clinical samples are not widely available and may be embedded for histopathologic analysis. With the goal of accurately identifying activated signaling networks in GBM tumor samples, we investigated the impact of embedding in optimal cutting temperature (OCT) compound followed by flash freezing in LN2 vs immediate flash freezing (iFF) in LN2 on protein expression and phosphorylation-mediated signaling networks. Quantitative proteomic and phosphoproteomic analysis of 8 pairs of tumor specimens revealed minimal impact of the different sample processing strategies and highlighted the large interpatient heterogeneity present in these tumors. Correlation analyses of the differentially processed tumor sections identified activated signaling networks present in selected tumors and revealed the differential expression of transcription, translation, and degradation associated proteins. This study demonstrates the capability of quantitative mass spectrometry for identification of in vivo oncogenic signaling networks from human tumor specimens that were either OCT-embedded or immediately flash-frozen. PMID:24927040

  16. Evaluation of B1 inhomogeneity effect on DCE-MRI data analysis of brain tumor patients at 3T.

    Science.gov (United States)

    Sengupta, Anirban; Gupta, Rakesh Kumar; Singh, Anup

    2017-12-02

    Dynamic-contrast-enhanced (DCE) MRI data acquired using gradient echo based sequences is affected by errors in flip angle (FA) due to transmit B 1 inhomogeneity (B 1 inh). The purpose of the study was to evaluate the effect of B 1 inh on quantitative analysis of DCE-MRI data of human brain tumor patients and to evaluate the clinical significance of B 1 inh correction of perfusion parameters (PPs) on tumor grading. An MRI study was conducted on 35 glioma patients at 3T. The patients had histologically confirmed glioma with 23 high-grade (HG) and 12 low-grade (LG). Data for B 1 -mapping, T 1 -mapping and DCE-MRI were acquired. Relative B 1 maps (B 1rel ) were generated using the saturated-double-angle method. T 1 -maps were computed using the variable flip-angle method. Post-processing was performed for conversion of signal-intensity time (S(t)) curve to concentration-time (C(t)) curve followed by tracer kinetic analysis (K trans , Ve, Vp, Kep) and first pass analysis (CBV, CBF) using the general tracer-kinetic model. DCE-MRI data was analyzed without and with B 1 inh correction and errors in PPs were computed. Receiver-operating-characteristic (ROC) analysis was performed on HG and LG patients. Simulations were carried out to understand the effect of B 1 inhomogeneity on DCE-MRI data analysis in a systematic way. S(t) curves mimicking those in tumor tissue, were generated and FA errors were introduced followed by error analysis of PPs. Dependence of FA-based errors on the concentration of contrast agent and on the duration of DCE-MRI data was also studied. Simulations were also done to obtain K trans of glioma patients at different B 1rel values and see whether grading is affected or not. Current study shows that B 1rel value higher than nominal results in an overestimation of C(t) curves as well as derived PPs and vice versa. Moreover, at same B 1rel values, errors were large for larger values of C(t). Simulation results showed that grade of patients can change

  17. Kinetic Analysis of 2-[11C]Thymidine PET Imaging Studies of Malignant Brain Tumors: Compartmental Model Investigation and Mathematical Analysis

    Directory of Open Access Journals (Sweden)

    Joanne M. Wells

    2002-07-01

    Full Text Available 2-[11C]Thymidine (TdR, a PET tracer for cellular proliferation, may be advantageous for monitoring brain tumor progression and response to therapy. We previously described and validated a five-compartment model for thymidine incorporation into DNA in somatic tissues, but the effect of the blood–brain barrier on the transport of TdR and its metabolites necessitated further validation before it could be applied to brain tumors. Methods: We investigated the behavior of the model under conditions experienced in the normal brain and brain tumors, performed sensitivity and identifiability analysis to determine the ability of the model to estimate the model parameters, and conducted simulations to determine whether it can distinguish between thymidine transport and retention. Results: Sensitivity and identifiability analysis suggested that the non-CO2 metabolite parameters could be fixed without significantly affecting thymidine parameter estimation. Simulations showed that K1t and KTdR could be estimated accurately (r = .97 and .98 for estimated vs. true parameters with standard errors < 15%. The model was able to separate increased transport from increased retention associated with tumor proliferation. Conclusion: Our model adequately describes normal brain and brain tumor kinetics for thymidine and its metabolites, and it can provide an estimate of the rate of cellular proliferation in brain tumors.

  18. The correlation between apparent diffusion coefficient and tumor cellularity in patients: a meta-analysis.

    Science.gov (United States)

    Chen, Lihua; Liu, Min; Bao, Jing; Xia, Yunbao; Zhang, Jiuquan; Zhang, Lin; Huang, Xuequan; Wang, Jian

    2013-01-01

    To perform a meta-analysis exploring the correlation between the apparent diffusion coefficient (ADC) and tumor cellularity in patients. We searched medical and scientific literature databases for studies discussing the correlation between the ADC and tumor cellularity in patients. Only studies that were published in English or Chinese prior to November 2012 were considered for inclusion. Summary correlation coefficient (r) values were extracted from each study, and 95% confidence intervals (CIs) were calculated. Sensitivity and subgroup analyses were performed to investigate potential heterogeneity. Of 189 studies, 28 were included in the meta-analysis, comprising 729 patients. The pooled r for all studies was -0.57 (95% CI: -0.62, -0.52), indicating notable heterogeneity (Pcorrelation between the ADC and cellularity for brain tumors. There was no notable evidence of publication bias. There is a strong negative correlation between the ADC and tumor cellularity in patients, particularly in the brain. However, larger, prospective studies are warranted to validate these findings in other cancer types.

  19. Circulating Tumor Cells: From Theory to Nanotechnology-Based Detection

    Science.gov (United States)

    Ming, Yue; Li, Yuanyuan; Xing, Haiyan; Luo, Minghe; Li, Ziwei; Chen, Jianhong; Mo, Jingxin; Shi, Sanjun

    2017-01-01

    Cancer stem cells with stem-cell properties are regarded as tumor initiating cells. Sharing stem-cell properties, circulating tumor cells (CTCs) are responsible for the development of metastasis, which significant affects CTC analysis in clinical practice. Due to their extremely low occurrence in blood, however, it is challenging to enumerate and analyze CTCs. Nanotechnology is able to address the problems of insufficient capture efficiency and low purity of CTCs owing to the unique structural and functional properties of nanomaterials, showing strong promise for CTC isolation and detection. In this review, we discuss the role of stem-like CTCs in metastases, provide insight into recent progress in CTC isolation and detection approaches using various nanoplatforms, and highlight the role of nanotechnology in the advancement of CTC research. PMID:28203204

  20. Polyomavirus-Negative Merkel Cell Carcinoma: A More Aggressive Subtype Based on Analysis of 282 Cases Using Multimodal Tumor Virus Detection.

    Science.gov (United States)

    Moshiri, Ata S; Doumani, Ryan; Yelistratova, Lola; Blom, Astrid; Lachance, Kristina; Shinohara, Michi M; Delaney, Martha; Chang, Oliver; McArdle, Susan; Thomas, Hannah; Asgari, Maryam M; Huang, Meei-Li; Schwartz, Stephen M; Nghiem, Paul

    2017-04-01

    Previous studies have reached conflicting conclusions regarding the proportion of Merkel cell carcinomas (MCCs) that contain the Merkel cell polyomavirus (MCPyV) and the clinical significance of tumor viral status. To address these controversies, we detected MCPyV large T antigen using immunohistochemistry with two distinct antibodies and MCPyV DNA using quantitative PCR. Tumors were called MCPyV-positive if two or more of these three assays indicated presence of this virus. A total of 53 of 282 (19%) MCC tumors in this cohort were virus-negative using this multimodal system. Immunohistochemistry with the CM2B4 antibody had the best overall performance (sensitivity = 0.882, specificity = 0.943) compared with the multimodal classification. Multivariate analysis including age, sex, and immunosuppression showed that, relative to MCC patients with virus-positive tumors, virus-negative MCC patients had significantly increased risk of disease progression (hazard ratio = 1.77, 95% confidence interval = 1.20-2.62) and death from MCC (hazard ratio = 1.85, 95% confidence interval = 1.19-2.89). We confirm that approximately 20% of MCCs are not driven by MCPyV and that such virus-negative MCCs, which can be quite reliably identified by immunohistochemistry using the CM2B4 antibody alone, represent a more aggressive subtype that warrants closer clinical follow-up. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Automatic computer aided analysis algorithms and system for adrenal tumors on CT images.

    Science.gov (United States)

    Chai, Hanchao; Guo, Yi; Wang, Yuanyuan; Zhou, Guohui

    2017-12-04

    The adrenal tumor will disturb the secreting function of adrenocortical cells, leading to many diseases. Different kinds of adrenal tumors require different therapeutic schedules. In the practical diagnosis, it highly relies on the doctor's experience to judge the tumor type by reading the hundreds of CT images. This paper proposed an automatic computer aided analysis method for adrenal tumors detection and classification. It consisted of the automatic segmentation algorithms, the feature extraction and the classification algorithms. These algorithms were then integrated into a system and conducted on the graphic interface by using MATLAB Graphic user interface (GUI). The accuracy of the automatic computer aided segmentation and classification reached 90% on 436 CT images. The experiments proved the stability and reliability of this automatic computer aided analytic system.

  2. Mitigation of motion artifacts in CBCT of lung tumors based on tracked tumor motion during CBCT acquisition

    International Nuclear Information System (INIS)

    Lewis, John H; Li Ruijiang; Jia Xun; Watkins, W Tyler; Song, William Y; Jiang, Steve B; Lou, Yifei

    2011-01-01

    An algorithm capable of mitigating respiratory motion blurring artifacts in cone-beam computed tomography (CBCT) lung tumor images based on the motion of the tumor during the CBCT scan is developed. The tumor motion trajectory and probability density function (PDF) are reconstructed from the acquired CBCT projection images using a recently developed algorithm Lewis et al (2010 Phys. Med. Biol. 55 2505-22). Assuming that the effects of motion blurring can be represented by convolution of the static lung (or tumor) anatomy with the motion PDF, a cost function is defined, consisting of a data fidelity term and a total variation regularization term. Deconvolution is performed through iterative minimization of this cost function. The algorithm was tested on digital respiratory phantom, physical respiratory phantom and patient data. A clear qualitative improvement is evident in the deblurred images as compared to the motion-blurred images for all cases. Line profiles show that the tumor boundaries are more accurately and clearly represented in the deblurred images. The normalized root-mean-squared error between the images used as ground truth and the motion-blurred images are 0.29, 0.12 and 0.30 in the digital phantom, physical phantom and patient data, respectively. Deblurring reduces the corresponding values to 0.13, 0.07 and 0.19. Application of a -700 HU threshold to the digital phantom results in tumor dimension measurements along the superior-inferior axis of 2.8, 1.8 and 1.9 cm in the motion-blurred, ground truth and deblurred images, respectively. Corresponding values for the physical phantom are 3.4, 2.7 and 2.7 cm. A threshold of -500 HU applied to the patient case gives measurements of 3.1, 1.6 and 1.7 cm along the SI axis in the CBCT, 4DCT and deblurred images, respectively. This technique could provide more accurate information about a lung tumor's size and shape on the day of treatment.

  3. Anti-Tumor Effects of Ketogenic Diets in Mice: A Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Rainer J Klement

    Full Text Available Currently ketogenic diets (KDs are hyped as an anti-tumor intervention aimed at exploiting the metabolic abnormalities of cancer cells. However, while data in humans is sparse, translation of murine tumor models to the clinic is further hampered by small sample sizes, heterogeneous settings and mixed results concerning tumor growth retardation. The aim was therefore to synthesize the evidence for a growth inhibiting effect of KDs when used as a monotherapy in mice.We conducted a Bayesian random effects meta-analysis on all studies assessing the survival (defined as the time to reach a pre-defined endpoint such as tumor volume of mice on an unrestricted KD compared to a high carbohydrate standard diet (SD. For 12 studies meeting the inclusion criteria either a mean survival time ratio (MR or hazard ratio (HR between the KD and SD groups could be obtained. The posterior estimates for the MR and HR averaged over four priors on the between-study heterogeneity τ2 were MR = 0.85 (95% highest posterior density interval (HPDI = [0.73, 0.97] and HR = 0.55 (95% HPDI = [0.26, 0.87], indicating a significant overall benefit of the KD in terms of prolonged mean survival times and reduced hazard rate. All studies that used a brain tumor model also chose a late starting point for the KD (at least one day after tumor initiation which accounted for 26% of the heterogeneity. In this subgroup the KD was less effective (MR = 0.89, 95% HPDI = [0.76, 1.04].There was an overall tumor growth delaying effect of unrestricted KDs in mice. Future experiments should aim at differentiating the effects of KD timing versus tumor location, since external evidence is currently consistent with an influence of both of these factors.

  4. Analysis of Lung Tumor Motion in a Large Sample: Patterns and Factors Influencing Precise Delineation of Internal Target Volume

    Energy Technology Data Exchange (ETDEWEB)

    Knybel, Lukas [Department of Oncology, University Hospital Ostrava, Ostrava (Czech Republic); VŠB-Technical University of Ostrava, Ostrava (Czech Republic); Cvek, Jakub, E-mail: Jakub.cvek@fno.cz [Department of Oncology, University Hospital Ostrava, Ostrava (Czech Republic); Molenda, Lukas; Stieberova, Natalie; Feltl, David [Department of Oncology, University Hospital Ostrava, Ostrava (Czech Republic)

    2016-11-15

    Purpose/Objective: To evaluate lung tumor motion during respiration and to describe factors affecting the range and variability of motion in patients treated with stereotactic ablative radiation therapy. Methods and Materials: Log file analysis from online respiratory tumor tracking was performed in 145 patients. Geometric tumor location in the lungs, tumor volume and origin (primary or metastatic), sex, and tumor motion amplitudes in the superior-inferior (SI), latero-lateral (LL), and anterior-posterior (AP) directions were recorded. Tumor motion variability during treatment was described using intrafraction/interfraction amplitude variability and tumor motion baseline changes. Tumor movement dependent on the tumor volume, position and origin, and sex were evaluated using statistical regression and correlation analysis. Results: After analysis of >500 hours of data, the highest rates of motion amplitudes, intrafraction/interfraction variation, and tumor baseline changes were in the SI direction (6.0 ± 2.2 mm, 2.2 ± 1.8 mm, 1.1 ± 0.9 mm, and −0.1 ± 2.6 mm). The mean motion amplitudes in the lower/upper geometric halves of the lungs were significantly different (P<.001). Motion amplitudes >15 mm were observed only in the lower geometric quarter of the lungs. Higher tumor motion amplitudes generated higher intrafraction variations (R=.86, P<.001). Interfraction variations and baseline changes >3 mm indicated tumors contacting mediastinal structures or parietal pleura. On univariate analysis, neither sex nor tumor origin (primary vs metastatic) was an independent predictive factor of different movement patterns. Metastatic lesions in women, but not men, showed significantly higher mean amplitudes (P=.03) and variability (primary, 2.7 mm; metastatic, 4.9 mm; P=.002) than primary tumors. Conclusion: Online tracking showed significant irregularities in lung tumor movement during respiration. Motion amplitude was significantly lower in upper lobe

  5. Characterization of sonographically indeterminate ovarian tumors with MR imaging. A logistic regression analysis

    International Nuclear Information System (INIS)

    Yamashita, Y.; Hatanaka, Y.; Torashima, M.; Takahashi, M.; Miyazaki, K.; Okamura, H.

    1997-01-01

    Purpose: The goal of this study was to maximize the discrimination between benign and malignant masses in patients with sonographically indeterminate ovarian lesions by means of unenhanced and contrast-enhanced MR imaging, and to develop a computer-assisted diagnosis system. Material and Methods: Findings in precontrast and Gd-DTPA contrast-enhanced MR images of 104 patients with 115 sonographically indeterminate ovarian masses were analyzed, and the results were correlated with histopathological findings. Of 115 lesions, 65 were benign (23 cystadenomas, 13 complex cysts, 11 teratomas, 6 fibrothecomas, 12 others) and 50 were malignant (32 ovarian carcinomas, 7 metastatic tumors of the ovary, 4 carcinomas of the fallopian tubes, 7 others). A logistic regression analysis was performed to discriminate between benign and malignant lesions, and a model of a computer-assisted diagnosis was developed. This model was prospectively tested in 75 cases of ovarian tumors found at other institutions. Results: From the univariate analysis, the following parameters were selected as significant for predicting malignancy (p≤0.05): A solid or cystic mass with a large solid component or wall thickness greater than 3 mm; complex internal architecture; ascites; and bilaterality. Based on these parameters, a model of a computer-assisted diagnosis system was developed with the logistic regression analysis. To distinguish benign from malignant lesions, the maximum cut-off point was obtained between 0.47 and 0.51. In a prospective application of this model, 87% of the lesions were accurately identified as benign or malignant. (orig.)

  6. Systemic Administration of Interleukin 2 Enhances the Therapeutic Efficacy of Dendritic Cell-Based Tumor Vaccines

    Science.gov (United States)

    Shimizu, K.; Fields, R. C.; Giedlin, M.; Mule, J. J.

    1999-03-01

    We have reported previously that murine bone marrow-derived dendritic cells (DC) pulsed with whole tumor lysates can mediate potent antitumor immune responses both in vitro and in vivo. Because successful therapy was dependent on host immune T cells, we have now evaluated whether the systemic administration of the T cell stimulatory/growth promoting cytokine interleukin-2 (IL-2) could enhance tumor lysate-pulsed DC-based immunizations to further promote protective immunity toward, and therapeutic rejection of, syngeneic murine tumors. In three separate approaches using a weakly immunogenic sarcoma (MCA-207), the systemic administration of non-toxic doses of recombinant IL-2 (20,000 and 40,000 IU/dose) was capable of mediating significant increases in the potency of DC-based immunizations. IL-2 could augment the efficacy of tumor lysate-pulsed DC to induce protective immunity to lethal tumor challenge as well as enhance splenic cytotoxic T lymphocyte activity and interferon-γ production in these treated mice. Moreover, treatment with the combination of tumor lysate-pulsed DC and IL-2 could also mediate regressions of established pulmonary 3-day micrometastases and 7-day macrometastases as well as established 14- and 28-day s.c. tumors, leading to either significant cure rates or prolongation in overall survival. Collectively, these findings show that nontoxic doses of recombinant IL-2 can potentiate the antitumor effects of tumor lysate-pulsed DC in vivo and provide preclinical rationale for the use of IL-2 in DC-based vaccine strategies in patients with advanced cancer.

  7. Breast tumor segmentation in high resolution x-ray phase contrast analyzer based computed tomography.

    Science.gov (United States)

    Brun, E; Grandl, S; Sztrókay-Gaul, A; Barbone, G; Mittone, A; Gasilov, S; Bravin, A; Coan, P

    2014-11-01

    Phase contrast computed tomography has emerged as an imaging method, which is able to outperform present day clinical mammography in breast tumor visualization while maintaining an equivalent average dose. To this day, no segmentation technique takes into account the specificity of the phase contrast signal. In this study, the authors propose a new mathematical framework for human-guided breast tumor segmentation. This method has been applied to high-resolution images of excised human organs, each of several gigabytes. The authors present a segmentation procedure based on the viscous watershed transform and demonstrate the efficacy of this method on analyzer based phase contrast images. The segmentation of tumors inside two full human breasts is then shown as an example of this procedure's possible applications. A correct and precise identification of the tumor boundaries was obtained and confirmed by manual contouring performed independently by four experienced radiologists. The authors demonstrate that applying the watershed viscous transform allows them to perform the segmentation of tumors in high-resolution x-ray analyzer based phase contrast breast computed tomography images. Combining the additional information provided by the segmentation procedure with the already high definition of morphological details and tissue boundaries offered by phase contrast imaging techniques, will represent a valuable multistep procedure to be used in future medical diagnostic applications.

  8. Analysis of limb function after various reconstruction methods according to tumor location following resection of pediatric malignant bone tumors

    Directory of Open Access Journals (Sweden)

    Tokuhashi Yasuaki

    2010-05-01

    Full Text Available Abstract Background In the reconstruction of the affected limb in pediatric malignant bone tumors, since the loss of joint function affects limb-length discrepancy expected in the future, reconstruction methods that not only maximally preserve the joint function but also maintain good limb function are necessary. We analysis limb function of reconstruction methods by tumor location following resection of pediatric malignant bone tumors. Patients and methods We classified the tumors according to their location into 3 types by preoperative MRI, and evaluated reconstruction methods after wide resection, paying attention to whether the joint function could be preserved. The mean age of the patients was 10.6 years, Osteosarcoma was observed in 26 patients, Ewing's sarcoma in 3, and PNET(primitive neuroectodermal tumor and chondrosarcoma (grade 1 in 1 each. Results Type I were those located in the diaphysis, and reconstruction was performed using a vascularized fibular graft(vascularized fibular graft. Type 2 were those located in contact with the epiphyseal line or within 1 cm from this line, and VFG was performed in 1, and distraction osteogenesis in 1. Type III were those extending from the diaphysis to the epiphysis beyond the epiphyseal line, and a Growing Kotz was mainly used in 10 patients. The mean functional assessment score was the highest for Type I (96%: n = 4 according to the type and for VFG (99% according to the reconstruction method. Conclusion The final functional results were the most satisfactory for Types I and II according to tumor location. Biological reconstruction such as VFG and distraction osteogenesis without a prosthesis are so high score in the MSTS rating system. Therefore, considering the function of the affected limb, a limb reconstruction method allowing the maximal preservation of joint function should be selected after careful evaluation of the effects of chemotherapy and the location of the tumor.

  9. Prognostic factors in breast phyllodes tumors: a nomogram based on a retrospective cohort study of 404 patients.

    Science.gov (United States)

    Zhou, Zhi-Rui; Wang, Chen-Chen; Sun, Xiang-Jie; Yang, Zhao-Zhi; Chen, Xing-Xing; Shao, Zhi-Ming; Yu, Xiao-Li; Guo, Xiao-Mao

    2018-04-01

    The aim of this study was to explore the independent prognostic factors related to postoperative recurrence-free survival (RFS) in patients with breast phyllodes tumors (PTBs). A retrospective analysis was conducted in Fudan University Shanghai Cancer Center. According to histological type, patients with benign PTBs were classified as a low-risk group, while borderline and malignant PTBs were classified as a high-risk group. The Cox regression model was adopted to identify factors affecting postoperative RFS in the two groups, and a nomogram was generated to predict recurrence-free survival at 1, 3, and 5 years. Among the 404 patients, 168 (41.6%) patients had benign PTB, 184 (45.5%) had borderline PTB, and 52 (12.9%) had malignant PTB. Fifty-five patients experienced postoperative local recurrence, including six benign cases, 26 borderline cases, and 22 malignant cases; the three histological types of PTB had local recurrence rates of 3.6%, 14.1%, and 42.3%, respectively. Stromal cell atypia was an independent prognostic factor for RFS in the low-risk group, while the surgical approach and tumor border were independent prognostic factors for RFS in the high-risk group, and patients receiving simple excision with an infiltrative tumor border had a higher recurrence rate. A nomogram developed based on clinicopathologic features and surgical approaches could predict recurrence-free survival at 1, 3, and 5 years. For high-risk patients, this predictive nomogram based on tumor border, tumor residue, mitotic activity, degree of stromal cell hyperplasia, and atypia can be applied for patient counseling and clinical management. The efficacy of adjuvant radiotherapy remains uncertain. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  10. Hurdles of CAR-T cell-based cancer immunotherapy directed against solid tumors.

    Science.gov (United States)

    Zhang, Bing-Lan; Qin, Di-Yuan; Mo, Ze-Ming; Li, Yi; Wei, Wei; Wang, Yong-Sheng; Wang, Wei; Wei, Yu-Quan

    2016-04-01

    Recent reports on the impressive efficacy of chimeric antigen receptor (CAR)-modified T cells against hematologic malignancies have inspired oncologists to extend these efforts for the treatment of solid tumors. Clinical trials of CAR-T-based cancer immunotherapy for solid tumors showed that the efficacies are not as remarkable as in the case of hematologic malignancies. There are several challenges that researchers must face when treating solid cancers with CAR-T cells, these include choosing an ideal target, promoting efficient trafficking and infiltration, overcoming the immunosuppressive microenvironment, and avoiding associated toxicity. In this review, we discuss the obstacles imposed by solid tumors on CAR-T cell-based immunotherapy and strategies adopted to improve the therapeutic potential of this approach. Continued investigations are necessary to improve therapeutic outcomes and decrease the adverse effects of CAR-T cell therapy in patients with solid malignancies in the future.

  11. Diagnosis and treatment of ampullary tumors

    Directory of Open Access Journals (Sweden)

    YIN Tao

    2017-02-01

    Full Text Available Ampullary tumors mainly manifest as obstructive jaundice and ampullary mass in clinical practice and are difficult to be identified in early stage due to a complex structure of the anatomical site, a deep location, and hidden symptoms. Sometimes a qualitative diagnosis cannot be made. Based on the experience in the treatment of ampullary tumors for many years in our center, this article summarizes the features of ampullary tumors from the aspects of clinical manifestations, diagnosis, treatment, and prognosis, especially the issues regarding imaging evaluation of ampullary tumors, selection of surgical procedure, and prognosis. An early diagnosis is the key to the treatment of ampullary tumors, and early identification and treatment of lesions have great impacts on patients′ prognosis. Accurate preoperative imaging evaluation, a professional diagnosis and treatment team, accurate preoperative and intraoperative pathological analysis, and implementation of reasonable therapeutic strategy are the key to patients′ recovery.

  12. A proposed grading system for standardizing tumor consistency of intracranial meningiomas.

    Science.gov (United States)

    Zada, Gabriel; Yashar, Parham; Robison, Aaron; Winer, Jesse; Khalessi, Alexander; Mack, William J; Giannotta, Steven L

    2013-12-01

    Tumor consistency plays an important and underrecognized role in the surgeon's ability to resect meningiomas, especially with evolving trends toward minimally invasive and keyhole surgical approaches. Aside from descriptors such as "hard" or "soft," no objective criteria exist for grading, studying, and conveying the consistency of meningiomas. The authors designed a practical 5-point scale for intraoperative grading of meningiomas based on the surgeon's ability to internally debulk the tumor and on the subsequent resistance to folding of the tumor capsule. Tumor consistency grades and features are as follows: 1) extremely soft tumor, internal debulking with suction only; 2) soft tumor, internal debulking mostly with suction, and remaining fibrous strands resected with easily folded capsule; 3) average consistency, tumor cannot be freely suctioned and requires mechanical debulking, and the capsule then folds with relative ease; 4) firm tumor, high degree of mechanical debulking required, and capsule remains difficult to fold; and 5) extremely firm, calcified tumor, approaches density of bone, and capsule does not fold. Additional grading categories included tumor heterogeneity (with minimum and maximum consistency scores) and a 3-point vascularity score. This grading system was prospectively assessed in 50 consecutive patients undergoing craniotomy for meningioma resection by 2 surgeons in an independent fashion. Grading scores were subjected to a linear weighted kappa analysis for interuser reliability. Fifty patients (100 scores) were included in the analysis. The mean maximal tumor diameter was 4.3 cm. The distribution of overall tumor consistency scores was as follows: Grade 1, 4%; Grade 2, 9%; Grade 3, 43%; Grade 4, 44%; and Grade 5, 0%. Regions of Grade 5 consistency were reported only focally in 14% of heterogeneous tumors. Tumors were designated as homogeneous in 68% and heterogeneous in 32% of grades. The kappa analysis score for overall tumor consistency

  13. A two-stage multi-view learning framework based computer-aided diagnosis of liver tumors with contrast enhanced ultrasound images.

    Science.gov (United States)

    Guo, Le-Hang; Wang, Dan; Qian, Yi-Yi; Zheng, Xiao; Zhao, Chong-Ke; Li, Xiao-Long; Bo, Xiao-Wan; Yue, Wen-Wen; Zhang, Qi; Shi, Jun; Xu, Hui-Xiong

    2018-04-04

    With the fast development of artificial intelligence techniques, we proposed a novel two-stage multi-view learning framework for the contrast-enhanced ultrasound (CEUS) based computer-aided diagnosis for liver tumors, which adopted only three typical CEUS images selected from the arterial phase, portal venous phase and late phase. In the first stage, the deep canonical correlation analysis (DCCA) was performed on three image pairs between the arterial and portal venous phases, arterial and delayed phases, and portal venous and delayed phases respectively, which then generated total six-view features. While in the second stage, these multi-view features were then fed to a multiple kernel learning (MKL) based classifier to further promote the diagnosis result. Two MKL classification algorithms were evaluated in this MKL-based classification framework. We evaluated proposed DCCA-MKL framework on 93 lesions (47 malignant cancers vs. 46 benign tumors). The proposed DCCA-MKL framework achieved the mean classification accuracy, sensitivity, specificity, Youden index, false positive rate, and false negative rate of 90.41 ± 5.80%, 93.56 ± 5.90%, 86.89 ± 9.38%, 79.44 ± 11.83%, 13.11 ± 9.38% and 6.44 ± 5.90%, respectively, by soft margin MKL classifier. The experimental results indicate that the proposed DCCA-MKL framework achieves best performance for discriminating benign liver tumors from malignant liver cancers. Moreover, it is also proved that the three-phase CEUS image based CAD is feasible for liver tumors with the proposed DCCA-MKL framework.

  14. Assessment of Canine Mast Cell Tumor Mortality Risk Based on Clinical, Histologic, Immunohistochemical, and Molecular Features.

    Science.gov (United States)

    Horta, Rodrigo S; Lavalle, Gleidice E; Monteiro, Lidianne N; Souza, Mayara C C; Cassali, Geovanni D; Araújo, Roberto B

    2018-03-01

    Mast cell tumor (MCT) is a frequent cutaneous neoplasm in dogs that is heterogeneous in clinical presentation and biological behavior, with a variable potential for recurrence and metastasis. Accurate prediction of clinical outcomes has been challenging. The study objective was to develop a system for classification of canine MCT according to the mortality risk based on individual assessment of clinical, histologic, immunohistochemical, and molecular features. The study included 149 dogs with a histologic diagnosis of cutaneous or subcutaneous MCT. By univariate analysis, MCT metastasis and related death was significantly associated with clinical stage ( P < .0001, r P = -0.610), history of tumor recurrence ( P < .0001, r P = -0.550), Patnaik ( P < .0001, r P = -0.380) and Kiupel grades ( P < .0001, r P = -0.500), predominant organization of neoplastic cells ( P < .0001, r P = -0.452), mitotic count ( P < .0001, r P = -0.325), Ki-67 labeling index ( P < .0001, r P = -0.414), KITr pattern ( P = .02, r P = 0.207), and c-KIT mutational status ( P < .0001, r P = -0.356). By multivariate analysis with Cox proportional hazard model, only 2 features were independent predictors of overall survival: an amendment of the World Health Organization clinical staging system (hazard ratio [95% CI]: 1.824 [1.210-4.481]; P = .01) and a history of tumor recurrence (hazard ratio [95% CI]: 9.250 [2.158-23.268]; P < .001]. From these results, we propose an amendment of the WHO staging system, a method of risk analysis, and a suggested approach to clinical and laboratory evaluation of dogs with cutaneous MCT.

  15. Electroporation-based treatment planning for deep-seated tumors based on automatic liver segmentation of MRI images.

    Science.gov (United States)

    Pavliha, Denis; Mušič, Maja M; Serša, Gregor; Miklavčič, Damijan

    2013-01-01

    Electroporation is the phenomenon that occurs when a cell is exposed to a high electric field, which causes transient cell membrane permeabilization. A paramount electroporation-based application is electrochemotherapy, which is performed by delivering high-voltage electric pulses that enable the chemotherapeutic drug to more effectively destroy the tumor cells. Electrochemotherapy can be used for treating deep-seated metastases (e.g. in the liver, bone, brain, soft tissue) using variable-geometry long-needle electrodes. To treat deep-seated tumors, patient-specific treatment planning of the electroporation-based treatment is required. Treatment planning is based on generating a 3D model of the organ and target tissue subject to electroporation (i.e. tumor nodules). The generation of the 3D model is done by segmentation algorithms. We implemented and evaluated three automatic liver segmentation algorithms: region growing, adaptive threshold, and active contours (snakes). The algorithms were optimized using a seven-case dataset manually segmented by the radiologist as a training set, and finally validated using an additional four-case dataset that was previously not included in the optimization dataset. The presented results demonstrate that patient's medical images that were not included in the training set can be successfully segmented using our three algorithms. Besides electroporation-based treatments, these algorithms can be used in applications where automatic liver segmentation is required.

  16. Tumor Classification Using High-Order Gene Expression Profiles Based on Multilinear ICA

    Directory of Open Access Journals (Sweden)

    Ming-gang Du

    2009-01-01

    Full Text Available Motivation. Independent Components Analysis (ICA maximizes the statistical independence of the representational components of a training gene expression profiles (GEP ensemble, but it cannot distinguish relations between the different factors, or different modes, and it is not available to high-order GEP Data Mining. In order to generalize ICA, we introduce Multilinear-ICA and apply it to tumor classification using high order GEP. Firstly, we introduce the basis conceptions and operations of tensor and recommend Support Vector Machine (SVM classifier and Multilinear-ICA. Secondly, the higher score genes of original high order GEP are selected by using t-statistics and tabulate tensors. Thirdly, the tensors are performed by Multilinear-ICA. Finally, the SVM is used to classify the tumor subtypes. Results. To show the validity of the proposed method, we apply it to tumor classification using high order GEP. Though we only use three datasets, the experimental results show that the method is effective and feasible. Through this survey, we hope to gain some insight into the problem of high order GEP tumor classification, in aid of further developing more effective tumor classification algorithms.

  17. Identification of novel biomarkers in pediatric primitive neuroectodermal tumors and ependymomas by proteome-wide analysis

    NARCIS (Netherlands)

    de Bont, Judith M.; den Boer, Monique L.; Kros, Johan M.; Passier, Monique M. C. J.; Reddinglus, Roel E.; Smitt, Peter A. E. Sillevis; Luider, Theo M.; Pieters, Rob

    The aim of this study was to identify aberrantly expressed proteins in pediatric primitive neuroectodermal tumors (PNETs) and ependymornas. Tumor tissue of 29 PNET and 12 ependymoma patients was subjected to 2-dimensional difference gel electrophoresis. Gel analysis resulted in 79 protein spots

  18. Exosome-Based Cell-Cell Communication in the Tumor Microenvironment

    Directory of Open Access Journals (Sweden)

    Joana Maia

    2018-02-01

    Full Text Available Tumors are not isolated entities, but complex systemic networks involving cell-cell communication between transformed and non-transformed cells. The milieu created by tumor-associated cells may either support or halt tumor progression. In addition to cell-cell contact, cells communicate through secreted factors via a highly complex system involving characteristics such as ligand concentration, receptor expression and integration of diverse signaling pathways. Of these, extracellular vesicles, such as exosomes, are emerging as novel cell-cell communication mediators in physiological and pathological scenarios. Exosomes, membrane vesicles of endocytic origin released by all cells (both healthy and diseased, ranging in size from 30 to 150 nm, transport all the main biomolecules, including lipids, proteins, DNAs, messenger RNAs and microRNA, and perform intercellular transfer of components, locally and systemically. By acting not only in tumor cells, but also in tumor-associated cells such as fibroblasts, endothelium, leukocytes and progenitor cells, tumor- and non-tumor cells-derived exosomes have emerged as new players in tumor growth and invasion, tumor-associated angiogenesis, tissue inflammation and immunologic remodeling. In addition, due to their property of carrying molecules from their cell of origin to the peripheral circulation, exosomes have been increasingly studied as sources of tumor biomarkers in liquid biopsies. Here we review the current literature on the participation of exosomes in the communication between tumor and tumor-associated cells, highlighting the role of this process in the setup of tumor microenvironments that modulate tumor initiation and metastasis.

  19. Tumor-selective replication herpes simplex virus-based technology significantly improves clinical detection and prognostication of viable circulating tumor cells

    DEFF Research Database (Denmark)

    Zhang, Wen; Bao, Li; Yang, Shaoxing

    2016-01-01

    Detection of circulating tumor cells remains a significant challenge due to their vast physical and biological heterogeneity. We developed a cell-surface-marker-independent technology based on telomerase-specific, replication-selective oncolytic herpes-simplex-virus-1 that targets telomerase......-reverse-transcriptase-positive cancer cells and expresses green-fluorescent-protein that identifies viable CTCs from a broad spectrum of malignancies. Our method recovered 75.5-87.2% of tumor cells spiked into healthy donor blood, as validated by different methods, including single cell sequencing. CTCs were detected in 59-100% of 326...

  20. Cone-Beam Computed Tomography (CBCT) Hepatic Arteriography in Chemoembolization for Hepatocellular Carcinoma: Performance Depicting Tumors and Tumor Feeders

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    Lee, In Joon [National Cancer Center, Department of Radiology (Korea, Republic of); Chung, Jin Wook, E-mail: chungjw@snu.ac.kr; Yin, Yong Hu; Kim, Hyo-Cheol; Kim, Young Il; Jae, Hwan Jun; Park, Jae Hyung [Seoul National University College of Medicine, Seoul National University Hospital, Department of Radiology (Korea, Republic of)

    2015-10-15

    PurposeThis study was designed to analyze retrospectively the performance of cone-beam computed tomography (CBCT) hepatic arteriography in depicting tumors and their feeders and to investigate the related determining factors in chemoembolization for hepatocellular carcinoma (HCC).MethodsEighty-six patients with 142 tumors satisfying the imaging diagnosis criteria of HCC were included in this study. The performance of CBCT hepatic arteriography for chemoembolization per tumor and per patient was evaluated using maximum intensity projection images alone (MIP analysis) or MIP combined with multiplanar reformation images (MIP + MPR analysis) regarding the following three aspects: tumor depiction, confidence of tumor feeder detection, and trackability of tumor feeders. Tumor size, tumor enhancement, tumor location, number of feeders, diaphragmatic motion, portal vein enhancement, and hepatic artery to parenchyma enhancement ratio were regarded as potential determining factors.ResultsTumors were depicted in 125 (88.0 %) and 142 tumors (100 %) on MIP and MIP + MPR analysis, respectively. Imaging performances on MIP and MIP + MPR analysis were good enough to perform subsegmental chemoembolization without additional angiographic investigation in 88 (62.0 %) and 128 tumors (90.1 %) on per-tumor basis and in 43 (50 %) and 73 (84.9 %) on per-patient basis, respectively. Significant determining factors for performance in MIP + MPR analysis on per tumor basis were tumor size (p = 0.030), tumor enhancement (0.005), tumor location (p = 0.001), and diaphragmatic motion (p < 0.001).ConclusionsCBCT hepatic arteriography provided sufficient information for subsegmental chemoembolization by depicting tumors and their feeders in the vast majority of patients. Combined analysis of MIP and MPR images was essential to enhance the performance of CBCT hepatic arteriography.

  1. Intra-tumor heterogeneity in breast cancer has limited impact on transcriptomic-based molecular profiling.

    Science.gov (United States)

    Karthik, Govindasamy-Muralidharan; Rantalainen, Mattias; Stålhammar, Gustav; Lövrot, John; Ullah, Ikram; Alkodsi, Amjad; Ma, Ran; Wedlund, Lena; Lindberg, Johan; Frisell, Jan; Bergh, Jonas; Hartman, Johan

    2017-11-29

    Transcriptomic profiling of breast tumors provides opportunity for subtyping and molecular-based patient stratification. In diagnostic applications the specimen profiled should be representative of the expression profile of the whole tumor and ideally capture properties of the most aggressive part of the tumor. However, breast cancers commonly exhibit intra-tumor heterogeneity at molecular, genomic and in phenotypic level, which can arise during tumor evolution. Currently it is not established to what extent a random sampling approach may influence molecular breast cancer diagnostics. In this study we applied RNA-sequencing to quantify gene expression in 43 pieces (2-5 pieces per tumor) from 12 breast tumors (Cohort 1). We determined molecular subtype and transcriptomic grade for all tumor pieces and analysed to what extent pieces originating from the same tumors are concordant or discordant with each other. Additionally, we validated our finding in an independent cohort consisting of 19 pieces (2-6 pieces per tumor) from 6 breast tumors (Cohort 2) profiled using microarray technique. Exome sequencing was also performed on this cohort, to investigate the extent of intra-tumor genomic heterogeneity versus the intra-tumor molecular subtype classifications. Molecular subtyping was consistent in 11 out of 12 tumors and transcriptomic grade assignments were consistent in 11 out of 12 tumors as well. Molecular subtype predictions revealed consistent subtypes in four out of six patients in this cohort 2. Interestingly, we observed extensive intra-tumor genomic heterogeneity in these tumor pieces but not in their molecular subtype classifications. Our results suggest that macroscopic intra-tumoral transcriptomic heterogeneity is limited and unlikely to have an impact on molecular diagnostics for most patients.

  2. Analysis of factors affecting local tumor progression of colorectal cancer liver metastasis after radiofrequency ablation

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    Jeon, Seong Hee; Cho, Yun Ku; Choi, Seung A; Kim, Mi Young; Lee, Ho Suk [Veterans Health Service Medical Center, Seoul (Korea, Republic of)

    2017-03-15

    The purpose of this study was to evaluate the independent predictive factors for local tumor progression (LTP) of colorectal liver metastasis (CRLM) after radiofrequency ablation (RFA). Patients with CRLM were included in the analysis if nodules were up to five in number, each nodule was ≤ 5 cm, and RFA was performed in our center from January 2006 to December 2015. Univariate and multivariate analyses to identify the predictors of LTP were performed by using a Cox proportional hazard model. Overall, 58 tumors from 38 patients were included in this study. LTP occurred in 14 tumors from 9 patients. The overall 1- and 3-year LTP rates were 23.5% and 29.4%, respectively. Multivariate analysis showed that tumor size > 2 cm and insufficient ablative margin were two independently significant adverse prognostic factors for LTP (p = 0.045 and 0.022, respectively). The 3-year LTP rates for 33 and 25 tumors with and without sufficient ablative margin were 4.5% and 61.2%, respectively. The difference was statistically significant (p < 0.001). The difference in the 3-year LTP rates according to the tumor size was not statistically significant (p = 0.791). Insufficient ablative margin seems to be the most potent predictor of LTP after RFA of CRLM.

  3. Lung tumor segmentation in PET images using graph cuts.

    Science.gov (United States)

    Ballangan, Cherry; Wang, Xiuying; Fulham, Michael; Eberl, Stefan; Feng, David Dagan

    2013-03-01

    The aim of segmentation of tumor regions in positron emission tomography (PET) is to provide more accurate measurements of tumor size and extension into adjacent structures, than is possible with visual assessment alone and hence improve patient management decisions. We propose a segmentation energy function for the graph cuts technique to improve lung tumor segmentation with PET. Our segmentation energy is based on an analysis of the tumor voxels in PET images combined with a standardized uptake value (SUV) cost function and a monotonic downhill SUV feature. The monotonic downhill feature avoids segmentation leakage into surrounding tissues with similar or higher PET tracer uptake than the tumor and the SUV cost function improves the boundary definition and also addresses situations where the lung tumor is heterogeneous. We evaluated the method in 42 clinical PET volumes from patients with non-small cell lung cancer (NSCLC). Our method improves segmentation and performs better than region growing approaches, the watershed technique, fuzzy-c-means, region-based active contour and tumor customized downhill. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  4. High Birth Weight Increases the Risk for Bone Tumor: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Songfeng Chen

    2015-09-01

    Full Text Available There have been several epidemiologic studies on the relationship between high birth weight and the risk for bone tumor in the past decades. However, due to the rarity of bone tumors, the sample size of individual studies was generally too small for reliable conclusions. Therefore, we have performed a meta-analysis to pool all published data on electronic databases with the purpose to clarify the potential relationship. According to the inclusion and exclusion criteria, 18 independent studies with more than 2796 cases were included. As a result, high birth weight was found to increase the risk for bone tumor with an Odds Ratio (OR of 1.13, with the 95% confidence interval (95% CI ranging from 1.01 to 1.27. The OR of bone tumor for an increase of 500 gram of birth weight was 1.01 (95% CI 1.00–1.02; p = 0.048 for linear trend. Interestingly, individuals with high birth weight had a greater risk for osteosarcoma (OR = 1.22, 95% CI 1.06–1.40, p = 0.006 than those with normal birth weight. In addition, in the subgroup analysis by geographical region, elevated risk was detected among Europeans (OR = 1.14, 95% CI 1.00–1.29, p = 0.049. The present meta-analysis supported a positive association between high birth weight and bone tumor risk.

  5. Residual tumor size and IGCCCG risk classification predict additional vascular procedures in patients with germ cell tumors and residual tumor resection: a multicenter analysis of the German Testicular Cancer Study Group.

    Science.gov (United States)

    Winter, Christian; Pfister, David; Busch, Jonas; Bingöl, Cigdem; Ranft, Ulrich; Schrader, Mark; Dieckmann, Klaus-Peter; Heidenreich, Axel; Albers, Peter

    2012-02-01

    Residual tumor resection (RTR) after chemotherapy in patients with advanced germ cell tumors (GCT) is an important part of the multimodal treatment. To provide a complete resection of residual tumor, additional surgical procedures are sometimes necessary. In particular, additional vascular interventions are high-risk procedures that require multidisciplinary planning and adequate resources to optimize outcome. The aim was to identify parameters that predict additional vascular procedures during RTR in GCT patients. A retrospective analysis was performed in 402 GCT patients who underwent 414 RTRs in 9 German Testicular Cancer Study Group (GTCSG) centers. Overall, 339 of 414 RTRs were evaluable with complete perioperative data sets. The RTR database was queried for additional vascular procedures (inferior vena cava [IVC] interventions, aortic prosthesis) and correlated to International Germ Cell Cancer Collaborative Group (IGCCCG) classification and residual tumor volume. In 40 RTRs, major vascular procedures (23 IVC resections with or without prosthesis, 11 partial IVC resections, and 6 aortic prostheses) were performed. In univariate analysis, the necessity of IVC intervention was significantly correlated with IGCCCG (14.1% intermediate/poor vs 4.8% good; p=0.0047) and residual tumor size (3.7% size risk features must initially be identified as high-risk patients for vascular procedures and therefore should be referred to specialized surgical centers with the ad hoc possibility of vascular interventions. Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  6. Performance of next-generation sequencing on small tumor specimens and/or low tumor content samples using a commercially available platform.

    Directory of Open Access Journals (Sweden)

    Scott Morris

    Full Text Available Next generation sequencing tests (NGS are usually performed on relatively small core biopsy or fine needle aspiration (FNA samples. Data is limited on what amount of tumor by volume or minimum number of FNA passes are needed to yield sufficient material for running NGS. We sought to identify the amount of tumor for running the PCDx NGS platform.2,723 consecutive tumor tissues of all cancer types were queried and reviewed for inclusion. Information on tumor volume, success of performing NGS, and results of NGS were compiled. Assessment of sequence analysis, mutation calling and sensitivity, quality control, drug associations, and data aggregation and analysis were performed.6.4% of samples were rejected from all testing due to insufficient tumor quantity. The number of genes with insufficient sensitivity make definitive mutation calls increased as the percentage of tumor decreased, reaching statistical significance below 5% tumor content. The number of drug associations also decreased with a lower percentage of tumor, but this difference only became significant between 1-3%. The number of drug associations did decrease with smaller tissue size as expected. Neither specimen size or percentage of tumor affected the ability to pass mRNA quality control. A tumor area of 10 mm2 provides a good margin of error for specimens to yield adequate drug association results.Specimen suitability remains a major obstacle to clinical NGS testing. We determined that PCR-based library creation methods allow the use of smaller specimens, and those with a lower percentage of tumor cells to be run on the PCDx NGS platform.

  7. SVM-based glioma grading. Optimization by feature reduction analysis

    International Nuclear Information System (INIS)

    Zoellner, Frank G.; Schad, Lothar R.; Emblem, Kyrre E.; Harvard Medical School, Boston, MA; Oslo Univ. Hospital

    2012-01-01

    We investigated the predictive power of feature reduction analysis approaches in support vector machine (SVM)-based classification of glioma grade. In 101 untreated glioma patients, three analytic approaches were evaluated to derive an optimal reduction in features; (i) Pearson's correlation coefficients (PCC), (ii) principal component analysis (PCA) and (iii) independent component analysis (ICA). Tumor grading was performed using a previously reported SVM approach including whole-tumor cerebral blood volume (CBV) histograms and patient age. Best classification accuracy was found using PCA at 85% (sensitivity = 89%, specificity = 84%) when reducing the feature vector from 101 (100-bins rCBV histogram + age) to 3 principal components. In comparison, classification accuracy by PCC was 82% (89%, 77%, 2 dimensions) and 79% by ICA (87%, 75%, 9 dimensions). For improved speed (up to 30%) and simplicity, feature reduction by all three methods provided similar classification accuracy to literature values (∝87%) while reducing the number of features by up to 98%. (orig.)

  8. SVM-based glioma grading. Optimization by feature reduction analysis

    Energy Technology Data Exchange (ETDEWEB)

    Zoellner, Frank G.; Schad, Lothar R. [University Medical Center Mannheim, Heidelberg Univ., Mannheim (Germany). Computer Assisted Clinical Medicine; Emblem, Kyrre E. [Massachusetts General Hospital, Charlestown, A.A. Martinos Center for Biomedical Imaging, Boston MA (United States). Dept. of Radiology; Harvard Medical School, Boston, MA (United States); Oslo Univ. Hospital (Norway). The Intervention Center

    2012-11-01

    We investigated the predictive power of feature reduction analysis approaches in support vector machine (SVM)-based classification of glioma grade. In 101 untreated glioma patients, three analytic approaches were evaluated to derive an optimal reduction in features; (i) Pearson's correlation coefficients (PCC), (ii) principal component analysis (PCA) and (iii) independent component analysis (ICA). Tumor grading was performed using a previously reported SVM approach including whole-tumor cerebral blood volume (CBV) histograms and patient age. Best classification accuracy was found using PCA at 85% (sensitivity = 89%, specificity = 84%) when reducing the feature vector from 101 (100-bins rCBV histogram + age) to 3 principal components. In comparison, classification accuracy by PCC was 82% (89%, 77%, 2 dimensions) and 79% by ICA (87%, 75%, 9 dimensions). For improved speed (up to 30%) and simplicity, feature reduction by all three methods provided similar classification accuracy to literature values ({proportional_to}87%) while reducing the number of features by up to 98%. (orig.)

  9. Clinicopathologic and prognostic significance of C-reactive protein/albumin ratio in patients with solid tumors: an updated systemic review and meta-analysis.

    Science.gov (United States)

    Wu, Jiayuan; Tan, Wenkai; Chen, Lin; Huang, Zhe; Mai, Shao

    2018-03-02

    C-reactive protein/albumin ratio (CAR) was originally used as a novel inflammation-based prognostic score in predicting outcomes in septic patients. Recently, more and more studies have reported the prognostic value of pretreatment CAR in solid tumors. However, the results remain controversial rather than conclusive. We conducted a meta-analysis based on 24 studies with 10203 patients to explore the relationship between CAR and survival outcomes in patients with solid tumors. The correlation between CAR and clinicopathological parameters was also assessed. Hazard ratio (HR) or odds ratio (OR) with its 95% confidence interval (CI) was applied to be the effect size estimate. The overall results showed that elevated CAR was associated with shorter overall survival (OS) (including 23 studies and 10067 patients) and poorer disease-free survival (DFS) (including 6 studies and 2904 patients). Significant associations between high CAR level and poor OS were also found in the subgroup analyses of study region, cancer type, primary treatment, clinical stage, cut-off selection, sample size, and cut-off value. Moreover, subgroup analyses demonstrated that study region, primary treatment, clinical stage, sample size, and cut-off value did not alter the prognostic value of CAR for DFS. Furthermore, elevated CAR was correlated with certain phenotypes of tumor aggressiveness, such as poor histological grade, serious clinical stage, advanced tumor depth, positive lymph node metastasis, and positive distant metastasis. Together, our meta-analysis suggests that elevated level of serum CAR predicts worse survival and unfavorable clinical characteristics in cancer patients, and CAR may serve as an effective prognostic factor for solid tumors.

  10. Real-time tumor motion estimation using respiratory surrogate via memory-based learning

    International Nuclear Information System (INIS)

    Li Ruijiang; Xing Lei; Lewis, John H; Berbeco, Ross I

    2012-01-01

    Respiratory tumor motion is a major challenge in radiation therapy for thoracic and abdominal cancers. Effective motion management requires an accurate knowledge of the real-time tumor motion. External respiration monitoring devices (optical, etc) provide a noninvasive, non-ionizing, low-cost and practical approach to obtain the respiratory signal. Due to the highly complex and nonlinear relations between tumor and surrogate motion, its ultimate success hinges on the ability to accurately infer the tumor motion from respiratory surrogates. Given their widespread use in the clinic, such a method is critically needed. We propose to use a powerful memory-based learning method to find the complex relations between tumor motion and respiratory surrogates. The method first stores the training data in memory and then finds relevant data to answer a particular query. Nearby data points are assigned high relevance (or weights) and conversely distant data are assigned low relevance. By fitting relatively simple models to local patches instead of fitting one single global model, it is able to capture highly nonlinear and complex relations between the internal tumor motion and external surrogates accurately. Due to the local nature of weighting functions, the method is inherently robust to outliers in the training data. Moreover, both training and adapting to new data are performed almost instantaneously with memory-based learning, making it suitable for dynamically following variable internal/external relations. We evaluated the method using respiratory motion data from 11 patients. The data set consists of simultaneous measurement of 3D tumor motion and 1D abdominal surface (used as the surrogate signal in this study). There are a total of 171 respiratory traces, with an average peak-to-peak amplitude of ∼15 mm and average duration of ∼115 s per trace. Given only 5 s (roughly one breath) pretreatment training data, the method achieved an average 3D error of 1.5 mm and 95

  11. Real-time tumor motion estimation using respiratory surrogate via memory-based learning

    Science.gov (United States)

    Li, Ruijiang; Lewis, John H.; Berbeco, Ross I.; Xing, Lei

    2012-08-01

    Respiratory tumor motion is a major challenge in radiation therapy for thoracic and abdominal cancers. Effective motion management requires an accurate knowledge of the real-time tumor motion. External respiration monitoring devices (optical, etc) provide a noninvasive, non-ionizing, low-cost and practical approach to obtain the respiratory signal. Due to the highly complex and nonlinear relations between tumor and surrogate motion, its ultimate success hinges on the ability to accurately infer the tumor motion from respiratory surrogates. Given their widespread use in the clinic, such a method is critically needed. We propose to use a powerful memory-based learning method to find the complex relations between tumor motion and respiratory surrogates. The method first stores the training data in memory and then finds relevant data to answer a particular query. Nearby data points are assigned high relevance (or weights) and conversely distant data are assigned low relevance. By fitting relatively simple models to local patches instead of fitting one single global model, it is able to capture highly nonlinear and complex relations between the internal tumor motion and external surrogates accurately. Due to the local nature of weighting functions, the method is inherently robust to outliers in the training data. Moreover, both training and adapting to new data are performed almost instantaneously with memory-based learning, making it suitable for dynamically following variable internal/external relations. We evaluated the method using respiratory motion data from 11 patients. The data set consists of simultaneous measurement of 3D tumor motion and 1D abdominal surface (used as the surrogate signal in this study). There are a total of 171 respiratory traces, with an average peak-to-peak amplitude of ∼15 mm and average duration of ∼115 s per trace. Given only 5 s (roughly one breath) pretreatment training data, the method achieved an average 3D error of 1.5 mm and 95

  12. Histogram Analysis of CT Perfusion of Hepatocellular Carcinoma for Predicting Response to Transarterial Radioembolization: Value of Tumor Heterogeneity Assessment

    Energy Technology Data Exchange (ETDEWEB)

    Reiner, Caecilia S., E-mail: caecilia.reiner@usz.ch; Gordic, Sonja; Puippe, Gilbert; Morsbach, Fabian; Wurnig, Moritz [University Hospital Zurich, Institute of Diagnostic and Interventional Radiology (Switzerland); Schaefer, Niklaus; Veit-Haibach, Patrick [University Hospital Zurich, Division of Nuclear Medicine (Switzerland); Pfammatter, Thomas; Alkadhi, Hatem [University Hospital Zurich, Institute of Diagnostic and Interventional Radiology (Switzerland)

    2016-03-15

    PurposeTo evaluate in patients with hepatocellular carcinoma (HCC), whether assessment of tumor heterogeneity by histogram analysis of computed tomography (CT) perfusion helps predicting response to transarterial radioembolization (TARE).Materials and MethodsSixteen patients (15 male; mean age 65 years; age range 47–80 years) with HCC underwent CT liver perfusion for treatment planning prior to TARE with Yttrium-90 microspheres. Arterial perfusion (AP) derived from CT perfusion was measured in the entire tumor volume, and heterogeneity was analyzed voxel-wise by histogram analysis. Response to TARE was evaluated on follow-up imaging (median follow-up, 129 days) based on modified Response Evaluation Criteria in Solid Tumors (mRECIST). Results of histogram analysis and mean AP values of the tumor were compared between responders and non-responders. Receiver operating characteristics were calculated to determine the parameters’ ability to discriminate responders from non-responders.ResultsAccording to mRECIST, 8 patients (50 %) were responders and 8 (50 %) non-responders. Comparing responders and non-responders, the 50th and 75th percentile of AP derived from histogram analysis was significantly different [AP 43.8/54.3 vs. 27.6/34.3 mL min{sup −1} 100 mL{sup −1}); p < 0.05], while the mean AP of HCCs (43.5 vs. 27.9 mL min{sup −1} 100 mL{sup −1}; p > 0.05) was not. Further heterogeneity parameters from histogram analysis (skewness, coefficient of variation, and 25th percentile) did not differ between responders and non-responders (p > 0.05). If the cut-off for the 75th percentile was set to an AP of 37.5 mL min{sup −1} 100 mL{sup −1}, therapy response could be predicted with a sensitivity of 88 % (7/8) and specificity of 75 % (6/8).ConclusionVoxel-wise histogram analysis of pretreatment CT perfusion indicating tumor heterogeneity of HCC improves the pretreatment prediction of response to TARE.

  13. Anti-tumor effects of nitrosylcobalamin against spontaneous tumors in dogs.

    Science.gov (United States)

    Bauer, Joseph A; Frye, Gerald; Bahr, Anne; Gieg, Jennifer; Brofman, Peter

    2010-10-01

    Given the limited options available to treat canine cancers, the use of companion animals for evaluating new drugs may identify better therapies for veterinary and human oncology. The anti-tumor effects of nitrosylcobalamin (NO-Cbl), an apoptosis-inducing, vitamin B12-based carrier of nitric oxide (NO), was evaluated in four dogs with spontaneous cancer. (1) A 13 year-old female spayed Giant Schnauzer with inoperable thyroid carcinoma and hypercalcemia. (2) A 6 year-old male neutered Golden Retriever with a malignant peripheral nerve sheath tumor (MPNST). (3) A ten yr-old neutered male Bichon Frise with apocrine gland anal sac adenocarcinoma (AGACA). (4) A 7 year-old female spayed Labrador mix with spinal meningioma following partial surgical resection. Tumor regression was measured by physical exam and verified using ultrasound (case 1) and MRI (case 2-4). Serum chemistries and hematologic parameters were monitored throughout the studies. (1) The Giant Schnauzer demonstrated a 77% reduction in tumor volume after ten weeks of daily NO-Cbl treatment. (2) The Golden Retriever demonstrated a 53% reduction in tumor volume after 15 months of daily NO-Cbl therapy. (3) The Bichon Frise demonstrated a 43% regression of the primary tumor and a 90% regression of an iliac lymph node measured by MRI after 15 months of treatment. After 61 months, the dog currently has stable disease, normal liver enzymes, CBC analysis, and no evidence of toxicity. (4) The Labrador demonstrated complete regression of the residual tumor after 6 months of treatment. We have shown previously that NO-Cbl is endocytosed by malignant cells, resulting in intra-tumoral NO release. In this study, we have shown that daily long-term use of NO-Cbl induced responses in all dogs without any signs of toxicity. The use of NO-Cbl capitalizes on the tumor-specific properties of the vitamin B12 receptor and represents a promising anti-cancer therapy.

  14. Clinical and pathological analysis of benign brain tumors resected after Gamma Knife surgery.

    Science.gov (United States)

    Liu, Ali; Wang, Jun-Mei; Li, Gui-Lin; Sun, Yi-Lin; Sun, Shi-Bin; Luo, Bin; Wang, Mei-Hua

    2014-12-01

    The goal of this study was to assess the clinical and pathological features of benign brain tumors that had been treated with Gamma Knife surgery (GKS) followed by resection. In this retrospective chart review, the authors identified 61 patients with intracranial benign tumors who had undergone neurosurgical intervention after GKS. Of these 61 patients, 27 were male and 34 were female; mean age was 49.1 years (range 19-73 years). There were 24 meningiomas, 18 schwannomas, 14 pituitary adenomas, 3 hemangioblastomas, and 2 craniopharyngiomas. The interval between GKS and craniotomy was 2-168 months, with a median of 24 months; for 7 patients, the interval was 10 years or longer. For 21 patients, a craniotomy was performed before and after GKS; in 9 patients, pathological specimens were obtained before and after GKS. A total of 29 patients underwent GKS at the Beijing Tiantan Hospital. All specimens obtained by surgical intervention underwent histopathological examination. Most patients underwent craniotomy because of tumor recurrence and/or exacerbation of clinical signs and symptoms. Neuroimaging analyses indicated tumor growth in 42 patients, hydrocephalus in 10 patients with vestibular schwannoma, cystic formation with mass effect in 7 patients, and tumor hemorrhage in 13 patients, of whom 10 had pituitary adenoma. Pathological examination demonstrated that, regardless of the type of tumor, GKS mainly induced coagulative necrosis of tumor parenchyma and stroma with some apoptosis and, ultimately, scar formation. In addition, irradiation induced vasculature stenosis and occlusion and tumor degeneration as a result of reduced blood supply. GKS-induced vasculature reaction was rarely observed in patients with pituitary adenoma. Pathological analysis of tumor specimens obtained before and after GKS did not indicate increased tumor proliferation after GKS. Radiosurgery is effective for intracranial benign tumors of small size and deep location and for tumor recurrence

  15. The relationship between mobile phone use and risk of brain tumor: a systematic review and meta-analysis of trails in the last decade

    Institute of Scientific and Technical Information of China (English)

    Lige Leng

    2017-01-01

    The aim of the present meta-analysis was to identify whether there was a relationship between mobile phone use and risk of brain tumor.A comprehensive search strategy was developed,and studies were eliminated in a stepwise manner,based on the inclusion criteria.The current meta-analysis collected data from the 24 eligible studies to investigate the relationship between mobile phone use and risk of brain tumor,while a detailed analysis of different classification was also conducted in order to identify the risk of mobile phone use.From the results,the relationship between cell phone use and brain tumor incidence had no significant difference between men and women.Cell phone use can increase the RF energy absorbed in the brain and apoptosis genes expression level,but glioma cell line cells were not significantly affected.Most calculations of laterality show a trend of increasing risk for time since first use,cumulative duration of subscriptions,cumulative duration of calls,and cumulative number of calls.In Asian people's,cell phone use and glioma had certain relations,while has verylittle relationship with meningioma incidence.This result seems to be no racial difference.In children and teenagers,cell phone use is associated with the incidence of brain tumors.We need longer time observation to supervise longer time (>20 years) mobile phone use whether has severe effects on incidence of brain tumor.

  16. Breast tumor segmentation in high resolution x-ray phase contrast analyzer based computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Brun, E., E-mail: emmanuel.brun@esrf.fr [European Synchrotron Radiation Facility (ESRF), Grenoble 380000, France and Department of Physics, Ludwig-Maximilians University, Garching 85748 (Germany); Grandl, S.; Sztrókay-Gaul, A.; Gasilov, S. [Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital Munich, 81377 Munich (Germany); Barbone, G. [Department of Physics, Harvard University, Cambridge, Massachusetts 02138 (United States); Mittone, A.; Coan, P. [Department of Physics, Ludwig-Maximilians University, Garching 85748, Germany and Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital Munich, 81377 Munich (Germany); Bravin, A. [European Synchrotron Radiation Facility (ESRF), Grenoble 380000 (France)

    2014-11-01

    Purpose: Phase contrast computed tomography has emerged as an imaging method, which is able to outperform present day clinical mammography in breast tumor visualization while maintaining an equivalent average dose. To this day, no segmentation technique takes into account the specificity of the phase contrast signal. In this study, the authors propose a new mathematical framework for human-guided breast tumor segmentation. This method has been applied to high-resolution images of excised human organs, each of several gigabytes. Methods: The authors present a segmentation procedure based on the viscous watershed transform and demonstrate the efficacy of this method on analyzer based phase contrast images. The segmentation of tumors inside two full human breasts is then shown as an example of this procedure’s possible applications. Results: A correct and precise identification of the tumor boundaries was obtained and confirmed by manual contouring performed independently by four experienced radiologists. Conclusions: The authors demonstrate that applying the watershed viscous transform allows them to perform the segmentation of tumors in high-resolution x-ray analyzer based phase contrast breast computed tomography images. Combining the additional information provided by the segmentation procedure with the already high definition of morphological details and tissue boundaries offered by phase contrast imaging techniques, will represent a valuable multistep procedure to be used in future medical diagnostic applications.

  17. Exploring the rising incidence of neuroendocrine tumors: a population-based analysis of epidemiology, metastatic presentation, and outcomes.

    Science.gov (United States)

    Hallet, Julie; Law, Calvin How Lim; Cukier, Moises; Saskin, Refik; Liu, Ning; Singh, Simron

    2015-02-15

    An increased incidence of neuroendocrine tumors (NETs) has been reported worldwide, but the reasons underlying this rise have not been identified. By assessing patterns of metastatic presentation, this study sought to examine the epidemiologic characteristics of NETs and the contribution of early-stage detection to the rising incidence. A population-based retrospective cohort study was conducted with prospectively maintained databases linked at the Institute for Clinical Evaluative Sciences. Adult patients with a NET diagnosis from 1994 to 2009 in Ontario, Canada were included. The main outcomes included the overall and site-specific incidence, proportion of metastatic disease, overall survival (OS), and recurrence-free survival (RFS). Five thousand six hundred nineteen NET cases were identified. The incidence of NETs increased from 2.48 to 5.86 per 100,000 per year. Metastases were found in 20.8% at presentation and in another 38% after the initial diagnosis. The proportion of metastases at presentation decreased from 1994 to 2009 (from 29% to 13%). Therefore, although the incidence of all NETs increased, the overall incidence of metastases did not change (0.63-0.69 per 100,000 per year). The 10-year OS rate was 46.5%, and the RFS rate was 64.6%. In addition to the primary tumor site, independent predictors of worse OS included an advanced age (P incidence of NETs has markedly increased over the course of 15 years. This is the first study to provide evidence suggesting that the increase in the incidence of NETs may be due to increased detection. In addition to tumor characteristics, low income and rural residency portend worse survival for patients with NETs. © 2014 American Cancer Society.

  18. Skull base tumors: a kaleidoscope of challenge.

    Science.gov (United States)

    Khanna, J N; Natrajan, Srivalli; Galinde, Jyotsna

    2014-08-01

    Resection of skull base lesions has always been riddled with problems like inadequate access, proximity to major vessels, dural tears, cranial nerve damage, and infection. Understanding the modular concept of the facial skeleton has led to the development of transfacial swing osteotomies that facilitates resection in a difficult area with minimal morbidity and excellent cosmetic results. In spite of the current trend toward endonasal endoscopic management of skull base tumors, our series presents nine cases of diverse extensive skull base lesions, 33% of which were recurrent. These cases were approached through different transfacial swing osteotomies through the mandible, a midfacial swing, or a zygomaticotemporal osteotomy as dictated by the three-dimensional spatial location of the lesion, and its extent and proximity to vital structures. Access osteotomies ensured complete removal and good results through the most direct and safe route and good vascular control. This reiterated the fact that transfacial approaches still hold a special place in the management of extensive skull base lesions.

  19. SU-C-207B-03: A Geometrical Constrained Chan-Vese Based Tumor Segmentation Scheme for PET

    International Nuclear Information System (INIS)

    Chen, L; Zhou, Z; Wang, J

    2016-01-01

    Purpose: Accurate segmentation of tumor in PET is challenging when part of tumor is connected with normal organs/tissues with no difference in intensity. Conventional segmentation methods, such as thresholding or region growing, cannot generate satisfactory results in this case. We proposed a geometrical constrained Chan-Vese based scheme to segment tumor in PET for this special case by considering the similarity between two adjacent slices. Methods: The proposed scheme performs segmentation in a slice-by-slice fashion where an accurate segmentation of one slice is used as the guidance for segmentation of rest slices. For a slice that the tumor is not directly connected to organs/tissues with similar intensity values, a conventional clustering-based segmentation method under user’s guidance is used to obtain an exact tumor contour. This is set as the initial contour and the Chan-Vese algorithm is applied for segmenting the tumor in the next adjacent slice by adding constraints of tumor size, position and shape information. This procedure is repeated until the last slice of PET containing tumor. The proposed geometrical constrained Chan-Vese based algorithm was implemented in Matlab and its performance was tested on several cervical cancer patients where cervix and bladder are connected with similar activity values. The positive predictive values (PPV) are calculated to characterize the segmentation accuracy of the proposed scheme. Results: Tumors were accurately segmented by the proposed method even when they are connected with bladder in the image with no difference in intensity. The average PPVs were 0.9571±0.0355 and 0.9894±0.0271 for 17 slices and 11 slices of PET from two patients, respectively. Conclusion: We have developed a new scheme to segment tumor in PET images for the special case that the tumor is quite similar to or connected to normal organs/tissues in the image. The proposed scheme can provide a reliable way for segmenting tumors.

  20. SU-C-207B-03: A Geometrical Constrained Chan-Vese Based Tumor Segmentation Scheme for PET

    Energy Technology Data Exchange (ETDEWEB)

    Chen, L; Zhou, Z; Wang, J [UT Southwestern Medical Center, Dallas, TX (United States)

    2016-06-15

    Purpose: Accurate segmentation of tumor in PET is challenging when part of tumor is connected with normal organs/tissues with no difference in intensity. Conventional segmentation methods, such as thresholding or region growing, cannot generate satisfactory results in this case. We proposed a geometrical constrained Chan-Vese based scheme to segment tumor in PET for this special case by considering the similarity between two adjacent slices. Methods: The proposed scheme performs segmentation in a slice-by-slice fashion where an accurate segmentation of one slice is used as the guidance for segmentation of rest slices. For a slice that the tumor is not directly connected to organs/tissues with similar intensity values, a conventional clustering-based segmentation method under user’s guidance is used to obtain an exact tumor contour. This is set as the initial contour and the Chan-Vese algorithm is applied for segmenting the tumor in the next adjacent slice by adding constraints of tumor size, position and shape information. This procedure is repeated until the last slice of PET containing tumor. The proposed geometrical constrained Chan-Vese based algorithm was implemented in Matlab and its performance was tested on several cervical cancer patients where cervix and bladder are connected with similar activity values. The positive predictive values (PPV) are calculated to characterize the segmentation accuracy of the proposed scheme. Results: Tumors were accurately segmented by the proposed method even when they are connected with bladder in the image with no difference in intensity. The average PPVs were 0.9571±0.0355 and 0.9894±0.0271 for 17 slices and 11 slices of PET from two patients, respectively. Conclusion: We have developed a new scheme to segment tumor in PET images for the special case that the tumor is quite similar to or connected to normal organs/tissues in the image. The proposed scheme can provide a reliable way for segmenting tumors.

  1. Impact of muscular uptake and statistical noise on tumor quantification based on simulated FDG-PET studies

    International Nuclear Information System (INIS)

    Silva-Rodríguez, Jesús; Domínguez-Prado, Inés; Pardo-Montero, Juan; Ruibal, Álvaro

    2017-01-01

    Purpose: The aim of this work is to study the effect of physiological muscular uptake variations and statistical noise on tumor quantification in FDG-PET studies. Methods: We designed a realistic framework based on simulated FDG-PET acquisitions from an anthropomorphic phantom that included different muscular uptake levels and three spherical lung lesions with diameters of 31, 21 and 9 mm. A distribution of muscular uptake levels was obtained from 136 patients remitted to our center for whole-body FDG-PET. Simulated FDG-PET acquisitions were obtained by using the Simulation System for Emission Tomography package (SimSET) Monte Carlo package. Simulated data was reconstructed by using an iterative Ordered Subset Expectation Maximization (OSEM) algorithm implemented in the Software for Tomographic Image Reconstruction (STIR) library. Tumor quantification was carried out by using estimations of SUV max , SUV 50 and SUV mean from different noise realizations, lung lesions and multiple muscular uptakes. Results: Our analysis provided quantification variability values of 17–22% (SUV max ), 11–19% (SUV 50 ) and 8–10% (SUV mean ) when muscular uptake variations and statistical noise were included. Meanwhile, quantification variability due only to statistical noise was 7–8% (SUV max ), 3–7% (SUV 50 ) and 1–2% (SUV mean ) for large tumors (>20 mm) and 13% (SUV max ), 16% (SUV 50 ) and 8% (SUV mean ) for small tumors (<10 mm), thus showing that the variability in tumor quantification is mainly affected by muscular uptake variations when large enough tumors are considered. In addition, our results showed that quantification variability is strongly dominated by statistical noise when the injected dose decreases below 222 MBq. Conclusions: Our study revealed that muscular uptake variations between patients who are totally relaxed should be considered as an uncertainty source of tumor quantification values. - Highlights: • Distribution of muscular uptake from 136 PET

  2. Genetic and modifying factors that determine the risk of brain tumors

    DEFF Research Database (Denmark)

    Montelli, Terezinha de Cresci Braga; Peraçoli, Maria Terezinha Serrão; Rogatto, Silvia Regina

    2011-01-01

    of tumor escape, CNS tumor immunology, immune defects that impair anti-tumor systemic immunity in brain tumor patients and local immuno-suppressive factors within CNS are also reviewed. New hope to treatment perspectives, as dendritic-cell-based vaccines is summarized too. Concluding, it seems well...... responses can alert immune system. However, it is necessary to clarify if individuals with both constitutional defects in immune functions and genetic instability have higher risk of developing brain tumors. Cytogenetic prospective studies and gene copy number variations analysis also must be performed...

  3. Image-Based Monitoring of Magnetic Resonance-Guided Thermoablative Therapies for Liver Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Rempp, Hansjoerg, E-mail: hansjoerg.rempp@med.uni-tuebingen.de; Clasen, Stephan [Eberhard Karls University of Tuebingen, Department of Diagnostic and Interventional Radiology (Germany); Pereira, Philippe L. [SLK-Kliniken, Clinic for Radiology, Nuclear Medicine, and Minimal Invasive Therapies (Germany)

    2012-12-15

    Minimally invasive treatment options for liver tumor therapy have been increasingly used during the last decade because their benefit has been proven for primary and inoperable secondary liver tumors. Among these, radiofrequency ablation has gained widespread consideration. Optimal image-guidance offers precise anatomical information, helps to position interventional devices, and allows for differentiation between already-treated and remaining tumor tissue. Patient safety and complete ablation of the entire tumor are the overriding objectives of tumor ablation. These may be achieved most elegantly with magnetic resonance (MR)-guided therapy, where monitoring can be performed based on precise soft-tissue imaging and additional components, such as diffusion-weighted imaging and temperature mapping. New MR scanner types and newly developed sequence techniques have enabled MR-guided intervention to move beyond the experimental phase. This article reviews the current role of MR imaging in guiding radiofrequency ablation. Signal characteristics of primary and secondary liver tumors are identified, and signal alteration during therapy is described. Diffusion-weighted imaging (DWI) and temperature mapping as special components of MR therapy monitoring are introduced. Practical information concerning coils, sequence selection, and parameters, as well as sequence gating, is given. In addition, sources of artifacts are identified and techniques to decrease them are introduced, and the characteristic signs of residual tumor in T1-, T2-, and DWI are described. We hope to enable the reader to choose MR sequences that allow optimal therapy monitoring depending on the initial signal characteristics of the tumor as well as its size and location in the liver.

  4. Image-Based Monitoring of Magnetic Resonance-Guided Thermoablative Therapies for Liver Tumors

    International Nuclear Information System (INIS)

    Rempp, Hansjörg; Clasen, Stephan; Pereira, Philippe L.

    2012-01-01

    Minimally invasive treatment options for liver tumor therapy have been increasingly used during the last decade because their benefit has been proven for primary and inoperable secondary liver tumors. Among these, radiofrequency ablation has gained widespread consideration. Optimal image-guidance offers precise anatomical information, helps to position interventional devices, and allows for differentiation between already-treated and remaining tumor tissue. Patient safety and complete ablation of the entire tumor are the overriding objectives of tumor ablation. These may be achieved most elegantly with magnetic resonance (MR)-guided therapy, where monitoring can be performed based on precise soft-tissue imaging and additional components, such as diffusion-weighted imaging and temperature mapping. New MR scanner types and newly developed sequence techniques have enabled MR-guided intervention to move beyond the experimental phase. This article reviews the current role of MR imaging in guiding radiofrequency ablation. Signal characteristics of primary and secondary liver tumors are identified, and signal alteration during therapy is described. Diffusion-weighted imaging (DWI) and temperature mapping as special components of MR therapy monitoring are introduced. Practical information concerning coils, sequence selection, and parameters, as well as sequence gating, is given. In addition, sources of artifacts are identified and techniques to decrease them are introduced, and the characteristic signs of residual tumor in T1-, T2-, and DWI are described. We hope to enable the reader to choose MR sequences that allow optimal therapy monitoring depending on the initial signal characteristics of the tumor as well as its size and location in the liver.

  5. Circulating Tumor DNA Analysis for Liver Cancers and Its Usefulness as a Liquid BiopsySummary

    Directory of Open Access Journals (Sweden)

    Atsushi Ono

    2015-09-01

    Full Text Available Background & Aims: Circulating tumor DNA (ctDNA carrying tumor-specific sequence alterations has been found in the cell-free fraction of blood. Liver cancer tumor specimens are difficult to obtain, and noninvasive methods are required to assess cancer progression and characterize underlying genomic features. Methods: We analyzed 46 patients with hepatocellular carcinoma who underwent hepatectomy or liver transplantation and for whom whole-genome sequencing data was available. We designed personalized assays targeting somatic rearrangements of each tumor to quantify serum ctDNA. Exome sequencing was performed using cell-free DNA paired primary tumor tissue DNA from a patient with recurrent liver cancer after transcatheter arterial chemoembolization (TACE. Results: We successfully detected ctDNA from 100 μL of serum samples in 7 of the 46 patients before surgery, increasing with disease progression. The cumulative incidence of recurrence and extrahepatic metastasis in the ctDNA-positive group were statistically significantly worse than in the ctDNA-negative group (P = .0102 and .0386, respectively. Multivariate analysis identified ctDNA (OR 6.10; 95% CI, 1.11–33.33, P = .038 as an independent predictor of microscopic vascular invasion of the portal vein (VP. We identified 45 nonsynonymous somatic mutations in cell-free DNA after TACE and 71 nonsynonymous somatic mutations in primary tumor tissue by exome sequencing. We identified 25 common mutations in both samples, and 83% of mutations identified in the primary tumor could be detected in the cell-free DNA. Conclusions: The presence of ctDNA reflects tumor progression, and detection of ctDNA can predict VP and recurrence, especially extrahepatic metastasis within 2 years. Our study demonstrated the usefulness of ctDNA detection and sequencing analysis of cell-free DNA for personalized treatment of liver cancer. Keywords: Circulating Tumor DNA, Exome Sequencing, Hepatocellular

  6. Cystic pancreatic neuroendocrine tumors (cPNETs: a systematic review and meta-analysis of case series

    Directory of Open Access Journals (Sweden)

    Luis Hurtado-Pardo

    Full Text Available Cystic pancreatic neuroendocrine tumors represent 13% of all neuroendocrine tumors. The aim of this study is to analyze the phenotype and biologic behavior of resected cystic neuroendocrine tumors. A systematic review and meta-analysis were conducted until September 2016 using a search in Medline, Scopus, and EMBASE with the terms "cystic pancreatic endocrine neoplasm", "cystic islets tumors" and "cystic islets neoplasms". From the 795 citations recovered 80 studies reporting on 431 patients were selected. 87.1% (n = 387 were sporadic tumors and 10.3% (n = 40 corresponded to multiple endocrine neoplasia type 1. Were diagnosed incidentally 44.6% (n = 135. Cytology was found to have a sensitivity of 78.5%. Were non-functional tumors 85% (n = 338, and among the functional tumors, insulinoma was the most frequent. According to the European Neuroendocrine Tumor Society staging, 87.8% were limited to the pancreas (I-IIb, and 12.2% were advanced (III-IV. Disease-free survival at 5 years in stages (I-IIIa and (IIIb-IV was 91.5% and 54.2%, respectively; and was significantly lower (p = 0.0001 in functional tumors. In patients with multiple endocrine neoplasia there was a higher incidence of functional (62.5% and multifocal (28.1% tumors. Disease-free survival at 5 and 10 years was 60%. Cystic pancreatic neuroendocrine tumors exhibit phenotypical characteristics which are different to those of solid neuroendocrine tumors.

  7. Nasopharyngeal carcinomas: analysis of patient, tumor and treatment characteristics determining outcome

    International Nuclear Information System (INIS)

    Erkal, Haldun S.; Serin, Meltem; Cakmak, Ahmet

    2001-01-01

    Purpose: The present study reviews the experience in treatment of 447 patients with nasopharyngeal carcinomas, analyzing patient, tumor and treatment characteristics determining outcome. Materials and methods: There were 322 males and 125 females, their ages ranging from 7 to 85 years (median, 45 years). Two-hundred and seventy-two patients had World Health Organization (WHO) type 3 carcinomas, 123 patients had T4 tumors and 320 patients had metastatic cervical lymph nodes. Three-hundred and eight patients were treated with radiation therapy alone and 139 patients with chemotherapy in combination with radiation therapy. Cumulative radiation dose to primary tumor ranged from 50 to 76 Gy (median, 70 Gy) and radiation dose to metastatic cervical lymph nodes ranged from 46 to 74 Gy (median, 66 Gy). Results: Follow-up ranged from 0.1 to 19.5 years (mean, 7.6 years). Local complete response was achieved in 357 patients. In multivariate analysis, T-classification, cumulative radiation dose to primary tumor and treatment with chemotherapy in combination with radiation therapy predicted local response. Nodal complete response was achieved in 272 patients. In multivariate analysis, N-classification and radiation dose to metastatic cervical lymph nodes predicted nodal response. Local failure was observed in 70 patients, nodal failure in 35 patients and systemic failure in 114 patients. Overall survival, disease-free survival and disease-specific survival were 33, 32 and 37%, respectively, at 10 years. In multivariate analysis, age, T-classification, N-classification, radiation dose and treatment with chemotherapy in combination with radiation therapy predicted overall survival whereas T-classification, N-classification, radiation dose and treatment with chemotherapy in combination with radiation therapy predicted both disease-free survival and disease-specific survival. Conclusions: Radiation therapy alone appears to be an adequate and viable treatment for patients with early

  8. Immunohistochemical analysis and prognostic significance of PD-L1, PD-1, and CD8+ tumor-infiltrating lymphocytes in Ewing's sarcoma family of tumors (ESFT).

    Science.gov (United States)

    Machado, Isidro; López-Guerrero, Jose Antonio; Scotlandi, Katia; Picci, Piero; Llombart-Bosch, Antonio

    2018-05-01

    Ewing's sarcoma family of tumors (ESFT) are aggressive neoplasms with scant tumor-infiltrating lymphocytes. We analyzed the immunohistochemical (IHC) expression of PD-L1 and PD-1 and their prognostic significance in clinically localized neoplasms in a cohort of 370 ESFT. Slides prepared from tissue microarrays were stained for PD-L1, PD-1, and CD8. Membranous/cytoplasmic staining over 5% of tumor cells was regarded as positive for PD-L1 and PD-1. Prognostic analysis was done considering only clinically localized tumors (n = 217). PD-L1 expression was present in 19% of ESFT, while PD-1 was expressed in 26%. Forty-eight percent of tumors were negative and 12% were positive for both PD-L1 and PD-1. Metastatic tumors displayed higher expression of PD-L1 (p < 0.0001). Histological subtypes were not correlated with PD-L1 or PD-1 positivity. ESFT with elevated proliferation index (Ki-67) were associated with higher PD-L1 expression (p = 0.049). Regarding prognosis, no significant association was found between PD-L1 expression and progression-free survival (PFS) or overall survival (OS), whereas lack of PD-1 expression in tumor cells was correlated with both poor PFS (p = 0.02) and poor OS (p = 0.004). Tumor-infiltrating CD8(+) T lymphocytes were observed in 15.4% of ESFT with informative results (347 tumors). No correlation was found between tumor-infiltrating CD8(+) T lymphocytes and ESFT histological subtypes, tumor location, or PD-1 and PD-L1 expression, nor with PFS (p = 0.473) or OS (p = 0.087). PD-L1 expression was not significantly related to prognosis. PD-1 was expressed in 26% of ESFT tumor cells and may have prognostic and therapeutic implications. CD8 expression in tumor-infiltrating lymphocytes was not related to prognosis.

  9. Cell membrane-based nanoparticles: a new biomimetic platform for tumor diagnosis and treatment

    Directory of Open Access Journals (Sweden)

    Ruixiang Li

    2018-01-01

    Full Text Available Taking inspiration from nature, the biomimetic concept has been integrated into drug delivery systems in cancer therapy. Disguised with cell membranes, the nanoparticles can acquire various functions of natural cells. The cell membrane-coating technology has pushed the limits of common nano-systems (fast elimination in circulation to more effectively navigate within the body. Moreover, because of the various functional molecules on the surface, cell membrane-based nanoparticles (CMBNPs are capable of interacting with the complex biological microenvironment of the tumor. Various sources of cell membranes have been explored to camouflage CMBNPs and different tumor-targeting strategies have been developed to enhance the anti-tumor drug delivery therapy. In this review article we highlight the most recent advances in CMBNP-based cancer targeting systems and address the challenges and opportunities in this field.

  10. Selected anti-tumor vaccines merit a place in multimodal tumor therapies

    Energy Technology Data Exchange (ETDEWEB)

    Weiss, Eva-Maria; Wunderlich, Roland [Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (Germany); Ebel, Nina [Department of Process Technology and Machinery, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (Germany); Rubner, Yvonne [Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (Germany); Schlücker, Eberhard [Department of Process Technology and Machinery, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (Germany); Meyer-Pittroff, Roland [Competence Pool Weihenstephan, Technische Universität München, Freising (Germany); Ott, Oliver J.; Fietkau, Rainer; Gaipl, Udo S.; Frey, Benjamin, E-mail: benjamin.frey@uk-erlangen.de [Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (Germany)

    2012-10-09

    Multimodal approaches are nowadays successfully applied in cancer therapy. Primary locally acting therapies such as radiotherapy (RT) and surgery are combined with systemic administration of chemotherapeutics. Nevertheless, the therapy of cancer is still a big challenge in medicine. The treatments often fail to induce long-lasting anti-tumor responses. Tumor recurrences and metastases result. Immunotherapies are therefore ideal adjuncts to standard tumor therapies since they aim to activate the patient's immune system against malignant cells even outside the primary treatment areas (abscopal effects). Especially cancer vaccines may have the potential both to train the immune system against cancer cells and to generate an immunological memory, resulting in long-lasting anti-tumor effects. However, despite promising results in phase I and II studies, most of the concepts finally failed. There are some critical aspects in development and application of cancer vaccines that may decide on their efficiency. The time point and frequency of medication, usage of an adequate immune adjuvant, the vaccine's immunogenic potential, and the tumor burden of the patient are crucial. Whole tumor cell vaccines have advantages compared to peptide-based ones since a variety of tumor antigens (TAs) are present. The master requirements of cell-based, therapeutic tumor vaccines are the complete inactivation of the tumor cells and the increase of their immunogenicity. Since the latter is highly connected with the cell death modality, the inactivation procedure of the tumor cell material may significantly influence the vaccine's efficiency. We therefore also introduce high hydrostatic pressure (HHP) as an innovative inactivation technology for tumor cell-based vaccines and outline that HHP efficiently inactivates tumor cells by enhancing their immunogenicity. Finally studies are presented proving that anti-tumor immune responses can be triggered by combining RT with selected

  11. Surgical management of spinal intramedullary tumors: radical and safe strategy for benign tumors.

    Science.gov (United States)

    Takami, Toshihiro; Naito, Kentaro; Yamagata, Toru; Ohata, Kenji

    2015-01-01

    Surgery for spinal intramedullary tumors remains one of the major challenges for neurosurgeons, due to their relative infrequency, unknown natural history, and surgical difficulty. We are sure that safe and precise resection of spinal intramedullary tumors, particularly encapsulated benign tumors, can result in acceptable or satisfactory postoperative outcomes. General surgical concepts and strategies, technical consideration, and functional outcomes after surgery are discussed with illustrative cases of spinal intramedullary benign tumors such as ependymoma, cavernous malformation, and hemangioblastoma. Selection of a posterior median sulcus, posterolateral sulcus, or direct transpial approach was determined based on the preoperative imaging diagnosis and careful inspection of the spinal cord surface. Tumor-cord interface was meticulously delineated in cases of benign encapsulated tumors. Our retrospective functional analysis of 24 consecutive cases of spinal intramedullary ependymoma followed for at least 6 months postoperatively demonstrated a mean grade on the modified McCormick functional schema of 1.8 before surgery, deteriorating significantly to 2.6 early after surgery ( 6 months after surgery). The risk of functional deterioration after surgery should be taken into serious consideration. Functional deterioration after surgery, including neuropathic pain even long after surgery, significantly affects patient quality of life. Better balance between tumor control and functional preservation can be achieved not only by the surgical technique or expertise, but also by intraoperative neurophysiological monitoring, vascular image guidance, and postoperative supportive care. Quality of life after surgery should inarguably be given top priority.

  12. Assessment of tumor blood flow and its correlation with histopathologic features in skull base meningiomas and schwannomas by using pseudo-continuous arterial spin labeling images

    International Nuclear Information System (INIS)

    Yamamoto, Tatsuya; Takeuchi, Hiroaki; Kinoshita, Kazuyuki; Kosaka, Nobuyuki; Kimura, Hirohiko

    2014-01-01

    Objective: We aimed to investigate whether pseudo-continuous arterial spin labeling (pcASL)-MRI can adequately evaluate tumor perfusion even if the tumors are located in the skull base region and evaluate the correlation between tumor blood flow (TBF) and the histopathologic features of skull base meningiomas and schwannomas. Materials and methods: We enrolled 31 patients with skull base meningioma (n = 14) and schwannoma (n = 17) who underwent surgical resection. TBF was calculated from pcASL. Tissue sections were stained with CD34 to evaluate microvessel area (MVA). TBF and MVA ratio were compared between meningiomas and schwannomas using Mann–Whitney U-test. The correlations between MVA ratio and TBF were evaluated in each tumor by using single linear regression analysis and Spearman's rank correlation coefficients (r s ). Results: MVA ratio and TBF were significantly higher in meningioma than in schwannoma (both p < 0.01). Correlation analyses revealed significant positive correlations between MVA ratio and both mean and max TBF for meningiomas (r s = 0.89, 0.81, both p < 0.01). There was a weak positive correlation between MVA ratio and mean TBF for schwannomas (r s = 0.43, p = 0.04). However, no significant correlation was found between MVA ratio and max TBF for schwannoma. Conclusions: pcASL-MRI is useful for evaluating tumor perfusion even if the tumors are located in the skull base region. Moreover, pcASL-TBF was significantly higher in most meningiomas compared to schwannomas, which can help in the differential diagnosis of the 2 tumor types even without the use of contrast material

  13. Bioinformatics Analysis Reveals Genes Involved in the Pathogenesis of Ameloblastoma and Keratocystic Odontogenic Tumor.

    Science.gov (United States)

    Santos, Eliane Macedo Sobrinho; Santos, Hércules Otacílio; Dos Santos Dias, Ivoneth; Santos, Sérgio Henrique; Batista de Paula, Alfredo Maurício; Feltenberger, John David; Sena Guimarães, André Luiz; Farias, Lucyana Conceição

    2016-01-01

    Pathogenesis of odontogenic tumors is not well known. It is important to identify genetic deregulations and molecular alterations. This study aimed to investigate, through bioinformatic analysis, the possible genes involved in the pathogenesis of ameloblastoma (AM) and keratocystic odontogenic tumor (KCOT). Genes involved in the pathogenesis of AM and KCOT were identified in GeneCards. Gene list was expanded, and the gene interactions network was mapped using the STRING software. "Weighted number of links" (WNL) was calculated to identify "leader genes" (highest WNL). Genes were ranked by K-means method and Kruskal-Wallis test was used (Preview data was used to corroborate the bioinformatics data. CDK1 was identified as leader gene for AM. In KCOT group, results show PCNA and TP53 . Both tumors exhibit a power law behavior. Our topological analysis suggested leader genes possibly important in the pathogenesis of AM and KCOT, by clustering coefficient calculated for both odontogenic tumors (0.028 for AM, zero for KCOT). The results obtained in the scatter diagram suggest an important relationship of these genes with the molecular processes involved in AM and KCOT. Ontological analysis for both AM and KCOT demonstrated different mechanisms. Bioinformatics analyzes were confirmed through literature review. These results may suggest the involvement of promising genes for a better understanding of the pathogenesis of AM and KCOT.

  14. Flow Cytometric DNA Analysis Using Cytokeratin Labeling for Identification of Tumor Cells in Carcinomas of the Breast and the Female Genital Tract

    Directory of Open Access Journals (Sweden)

    Rainer Kimmig

    2001-01-01

    Full Text Available Flow cytometric assessment of DNA‐ploidy and S‐phase fraction in malignant tumors is compromised by the heterogeneity of cell subpopulations derived from the malignant and surrounding connective tissue, e.g., tumor, stromal and inflammatory cells. To evaluate the effect on quality of DNA cell cycle analysis and determination of DNA ploidy, cytokeratin labeling of epithelial cells was used for tumor cell enrichment in breast, ovarian, cervical and endometrial cancer prior to DNA analysis. In a prospective study, tumor cell subpopulations of 620 malignant tumors were labeled by a FITC‐conjugated cytokeratin antibody (CK 5, 6, CK18 and CK 5, 6, 8 and CK 17, respectively prior to flow cytometric cell cycle analysis. Compared to total cell analysis, detection rate of DNA‐aneuploid tumors following cytokeratin labeling was increased from 62% to 76.5% in breast cancer, from 68% to 77% in ovarian cancer, from 60% to 80% in cervical cancer and from 30% to 53% in endometrial cancer. Predominantly in DNA‐diploid tumors, a significantly improved detection of S‐phase fraction of the tumor cells was shown due to the elimination of contaminating nonproliferating “normal cells”. S‐phase fraction following tumor cell enrichment was increased by 10% (mean following cytokeratin staining in ovarian and endometrial cancer, by 30% in breast cancer and even by 70% in cervical cancer compared to total cell analysis. Thus, diagnostic accuracy of DNA‐analysis was enhanced by cytokeratin labeling of tumor cells for all tumor entities investigated.

  15. Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

    Directory of Open Access Journals (Sweden)

    Hua-Sheng Chiu

    2018-04-01

    Full Text Available Summary: Long noncoding RNAs (lncRNAs are commonly dysregulated in tumors, but only a handful are known to play pathophysiological roles in cancer. We inferred lncRNAs that dysregulate cancer pathways, oncogenes, and tumor suppressors (cancer genes by modeling their effects on the activity of transcription factors, RNA-binding proteins, and microRNAs in 5,185 TCGA tumors and 1,019 ENCODE assays. Our predictions included hundreds of candidate onco- and tumor-suppressor lncRNAs (cancer lncRNAs whose somatic alterations account for the dysregulation of dozens of cancer genes and pathways in each of 14 tumor contexts. To demonstrate proof of concept, we showed that perturbations targeting OIP5-AS1 (an inferred tumor suppressor and TUG1 and WT1-AS (inferred onco-lncRNAs dysregulated cancer genes and altered proliferation of breast and gynecologic cancer cells. Our analysis indicates that, although most lncRNAs are dysregulated in a tumor-specific manner, some, including OIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergistically dysregulate cancer pathways in multiple tumor contexts. : Chiu et al. present a pan-cancer analysis of lncRNA regulatory interactions. They suggest that the dysregulation of hundreds of lncRNAs target and alter the expression of cancer genes and pathways in each tumor context. This implies that hundreds of lncRNAs can alter tumor phenotypes in each tumor context. Keywords: lncRNA, regulation, modulation, cancer gene, pan-cancer, noncoding RNA, microRNA, RNA-binding proteins, interactome

  16. Endocrine tumors other than thyroid tumors

    International Nuclear Information System (INIS)

    Takeichi, Norio; Dohi, Kiyohiko

    1992-01-01

    This paper discusses the tendency for the occurrence of tumors in the endocrine glands, other than the thyroid gland, in A-bomb survivors using both autopsy and clinical data. ABCC-RERF sample data using 4136 autopsy cases (1961-1977) revealed parathyroid tumors in 13 A-bomb survivors, including 3 with the associated hyperparathyroidism, with the suggestion of dose-dependent increase in the occurrence of tumors. Based on clinical data from Hiroshima University, 7 (46.7%) of 15 parathyroid tumors cases were A-bomb survivors. Data (1974-1987) from the Tumor Registry Committee (TRC) in Hiroshima Prefecture revealed that a relative risk of parathyroid tumors was 5.6 times higher in the entire group of A-bomb survivors and 16.2 times higher in the group of heavily exposed A-bomb survivors, suggesting the dose-dependent increase in their occurrence. Adrenal tumors were detected in 47 of 123 cases from the TRC data, and 15 (31.5%) of these 47 were A-bomb survivors. Particularly, 11 cases of adrenal tumors associated with Cushing syndrome included 6 A-bomb survivors (54.5%). The incidence of multiple endocrine gonadial tumors (MEGT) tended to be higher with increasing exposure doses; and the 1-9 rad group, the 10-99 rad group, and the 100 or more rad group had a risk of developing MEGT of 4.1, 5.7, and 7.1, respectively, relative to both the not-in the city group and the 0 rad group. These findings suggested that there is a correlation between A-bomb radiation and the occurrence of parathyroid tumors (including hyperparathyroidism), adrenal tumors associated with Cushing syndrome and MEGT (especially, the combined thyroid and ovarian tumors and the combined thyroid and parathyroid tumors). (N.K.)

  17. WE-E-17A-01: Characterization of An Imaging-Based Model of Tumor Angiogenesis

    International Nuclear Information System (INIS)

    Adhikarla, V; Jeraj, R

    2014-01-01

    Purpose: Understanding the transient dynamics of tumor oxygenation is important when evaluating tumor-vasculature response to anti-angiogenic therapies. An imaging-based tumor-vasculature model was used to elucidate factors that affect these dynamics. Methods: Tumor growth depends on its doubling time (Td). Hypoxia increases pro-angiogenic factor (VEGF) concentration which is modeled to reduce vessel perfusion, attributing to its effect of increasing vascular permeability. Perfused vessel recruitment depends on the existing perfused vasculature, VEGF concentration and maximum VEGF concentration (VEGFmax) for vessel dysfunction. A convolution-based algorithm couples the tumor to the normal tissue vessel density (VD-nt). The parameters are benchmarked to published pre-clinical data and a sensitivity study evaluating the changes in the peak and time to peak tumor oxygenation characterizes them. The model is used to simulate changes in hypoxia and proliferation PET imaging data obtained using [Cu- 61]Cu-ATSM and [F-18]FLT respectively. Results: Td and VD-nt were found to be the most influential on peak tumor pO2 while VEGFmax was marginally influential. A +20 % change in Td, VD-nt and VEGFmax resulted in +50%, +25% and +5% increase in peak pO2. In contrast, Td was the most influential on the time to peak oxygenation with VD-nt and VEGFmax playing marginal roles. A +20% change in Td, VD-nt and VEGFmax increased the time to peak pO2 by +50%, +5% and +0%. A −20% change in the above parameters resulted in comparable decreases in the peak and time to peak pO2. Model application to the PET data was able to demonstrate the voxel-specific changes in hypoxia of the imaged tumor. Conclusion: Tumor-specific doubling time and vessel density are important parameters to be considered when evaluating hypoxia transients. While the current model simulates the oxygen dynamics of an untreated tumor, incorporation of therapeutic effects can make the model a potent tool for analyzing

  18. Effect of intravenous drug administration mode on drug distribution in a tumor slab: a finite Fourier transform analysis.

    Science.gov (United States)

    Subramaniam, B; Claudius, J S

    1990-03-08

    for optimum scheduling of subsequent bolus injections in a multiple bolus dosing regimen. There are no reported applications of the FFT method to solve repeated input functions in either the chemical engineering or pharmaceutical science literature. Thus, the application of FFT method to solve multiple bolus injections is a unique one. Use of this FFT based analysis as a predictor tool can limit the number of costly experiments which are being done now to achieve this purpose. Even though the model in its present form is simplified, the analysis thereof has nevertheless led to a better understanding of the various factors that must be taken into account for rational design of drug therapy.

  19. Neurophysiological Identification of Cranial Nerves During Endoscopic Endonasal Surgery of Skull Base Tumors: Pilot Study Technical Report.

    Science.gov (United States)

    Shkarubo, Alexey Nikolaevich; Chernov, Ilia Valerievich; Ogurtsova, Anna Anatolievna; Moshchev, Dmitry Aleksandrovich; Lubnin, Andrew Jurievich; Andreev, Dmitry Nicolaevich; Koval, Konstantin Vladimirovich

    2017-02-01

    Intraoperative identification of cranial nerves is crucial for safe surgery of skull base tumors. Currently, only a small number of published papers describe the technique of trigger electromyography (t-EMG) in endoscopic endonasal removal of such tumors. To assess the effectiveness of t-EMG in preventing intraoperative cranial nerve damage in endoscopic endonasal surgery of skull base tumors. Nine patients were operated on using the endoscopic endonasal approach within a 1-year period. The tumors included large skull base chordomas and trigeminal neurinomas localized in the cavernous sinus. During the surgical process, cranial nerve identification was carried out using monopolar and bipolar t-EMG methods. Assessment of cranial nerve functional activity was conducted both before and after tumor removal. We mapped 17 nerves in 9 patients. Third, fifth, and sixth cranial nerves were identified intraoperatively. There were no cases of postoperative functional impairment of the mapped cranial nerves. In one case we were unable to get an intraoperative response from the fourth cranial nerve and observed its postoperative transient plegia (the function was normal before surgery). t-EMG allows surgeons to control the safety of cranial nerves both during and after skull base tumor removal. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Quantitative analysis of topoisomerase IIα to rapidly evaluate cell proliferation in brain tumors

    International Nuclear Information System (INIS)

    Oda, Masashi; Arakawa, Yoshiki; Kano, Hideyuki; Kawabata, Yasuhiro; Katsuki, Takahisa; Shirahata, Mitsuaki; Ono, Makoto; Yamana, Norikazu; Hashimoto, Nobuo; Takahashi, Jun A.

    2005-01-01

    Immunohistochemical cell proliferation analyses have come into wide use for evaluation of tumor malignancy. Topoisomerase IIα (topo IIα), an essential nuclear enzyme, has been known to have cell cycle coupled expression. We here show the usefulness of quantitative analysis of topo IIα mRNA to rapidly evaluate cell proliferation in brain tumors. A protocol to quantify topo IIα mRNA was developed with a real-time RT-PCR. It took only 3 h to quantify from a specimen. A total of 28 brain tumors were analyzed, and the level of topo IIα mRNA was significantly correlated with its immuno-staining index (p < 0.0001, r = 0.9077). Furthermore, it sharply detected that topo IIα mRNA decreased in growth-inhibited glioma cell. These results support that topo IIα mRNA may be a good and rapid indicator to evaluate cell proliferate potential in brain tumors

  1. Flow mode analysis by Imatron C100 of 44 focal liver tumors

    International Nuclear Information System (INIS)

    Simon-Karneff, J.; Hernigou, A.; Grataloup, C.; Charpentier, A.; Bouillot, J.L.; Plainfosse, M.C.

    1994-01-01

    We studied 44 patients with focal benign (n = 13) or malignant (n = 31) liver tumors proved by histology or follow-up. The flow mode was acquired by electron beam CT (EBCT) after injection (35 cc at 6 ml/sec): 20 slices with a 400 ms exposure time. We looked for abnormal vessels and density curves inside the tumor, liver and aorta. We describe arterial vascularization in most cases (type 1) and particularly in all the hepatocarcinomas (n = 15) associated with abnormal vessels, and also in rare tumors (n = 4). For benign lesions like angiomas (n = 9) we showed surrounding the mass arterial vascularization in add to the typical aspect (type 3); for nodular hyperplasia (n = 3) arterial blush was associated with the last part of the tumoral curve at the same level as liver. Most often metastasis (n = 13) had no central vascularization and a slight peripheral density increased (type 2). Flow mode by EBCT allows a good density curves analysis particularly at arterial time. (authors). 20 refs., 12 figs

  2. Ewing's Sarcoma: An Analysis of miRNA Expression Profiles and Target Genes in Paraffin-Embedded Primary Tumor Tissue.

    Science.gov (United States)

    Parafioriti, Antonina; Bason, Caterina; Armiraglio, Elisabetta; Calciano, Lucia; Daolio, Primo Andrea; Berardocco, Martina; Di Bernardo, Andrea; Colosimo, Alessia; Luksch, Roberto; Berardi, Anna C

    2016-04-30

    The molecular mechanism responsible for Ewing's Sarcoma (ES) remains largely unknown. MicroRNAs (miRNAs), a class of small non-coding RNAs able to regulate gene expression, are deregulated in tumors and may serve as a tool for diagnosis and prediction. However, the status of miRNAs in ES has not yet been thoroughly investigated. This study compared global miRNAs expression in paraffin-embedded tumor tissue samples from 20 ES patients, affected by primary untreated tumors, with miRNAs expressed in normal human mesenchymal stromal cells (MSCs) by microarray analysis. A miRTarBase database was used to identify the predicted target genes for differentially expressed miRNAs. The miRNAs microarray analysis revealed distinct patterns of miRNAs expression between ES samples and normal MSCs. 58 of the 954 analyzed miRNAs were significantly differentially expressed in ES samples compared to MSCs. Moreover, the qRT-PCR analysis carried out on three selected miRNAs showed that miR-181b, miR-1915 and miR-1275 were significantly aberrantly regulated, confirming the microarray results. Bio-database analysis identified BCL-2 as a bona fide target gene of the miR-21, miR-181a, miR-181b, miR-29a, miR-29b, miR-497, miR-195, miR-let-7a, miR-34a and miR-1915. Using paraffin-embedded tissues from ES patients, this study has identified several potential target miRNAs and one gene that might be considered a novel critical biomarker for ES pathogenesis.

  3. Molecular Understanding of Growth Inhibitory Effect from Irradiated to Bystander Tumor Cells in Mouse Fibrosarcoma Tumor Model

    Science.gov (United States)

    Desai, Sejal; Srambikkal, Nishad; Yadav, Hansa D.; Shetake, Neena; Balla, Murali M. S.; Kumar, Amit; Ray, Pritha; Ghosh, Anu

    2016-01-01

    Even though bystander effects pertaining to radiation risk assessment has been extensively studied, the molecular players of radiation induced bystander effect (RIBE) in the context of cancer radiotherapy are poorly known. In this regard, the present study is aimed to investigate the effect of irradiated tumor cells on the bystander counterparts in mouse fibrosarcoma (WEHI 164 cells) tumor model. Mice co-implanted with WEHI 164 cells γ-irradiated with a lethal dose of 15 Gy and unirradiated (bystander) WEHI 164 cells showed inhibited tumor growth, which was measured in terms of tumor volume and Luc+WEHI 164 cells based bioluminescence in vivo imaging. Histopathological analysis and other assays revealed decreased mitotic index, increased apoptosis and senescence in these tumor tissues. In addition, poor angiogenesis was observed in these tumor tissues, which was further confirmed by fluorescence imaging of tumor vascularisation and CD31 expression by immuno-histochemistry. Interestingly, the growth inhibitory bystander effect was exerted more prominently by soluble factors obtained from the irradiated tumor cells than the cellular fraction. Cytokine profiling of the supernatants obtained from the irradiated tumor cells showed increased levels of VEGF, Rantes, PDGF, GMCSF and IL-2 and decreased levels of IL-6 and SCF. Comparative proteomic analysis of the supernatants from the irradiated tumor cells showed differential expression of total 24 protein spots (21 up- and 3 down-regulated) when compared with the supernatant from the unirradiated control cells. The proteins which showed substantially higher level in the supernatant from the irradiated cells included diphosphate kinase B, heat shock cognate, annexin A1, angiopoietin-2, actin (cytoplasmic 1/2) and stress induced phosphoprotein 1. However, the levels of proteins like annexin A2, protein S100 A4 and cofilin was found to be lower in this supernatant. In conclusion, our results provided deeper insight about

  4. Molecular Understanding of Growth Inhibitory Effect from Irradiated to Bystander Tumor Cells in Mouse Fibrosarcoma Tumor Model.

    Directory of Open Access Journals (Sweden)

    Sejal Desai

    Full Text Available Even though bystander effects pertaining to radiation risk assessment has been extensively studied, the molecular players of radiation induced bystander effect (RIBE in the context of cancer radiotherapy are poorly known. In this regard, the present study is aimed to investigate the effect of irradiated tumor cells on the bystander counterparts in mouse fibrosarcoma (WEHI 164 cells tumor model. Mice co-implanted with WEHI 164 cells γ-irradiated with a lethal dose of 15 Gy and unirradiated (bystander WEHI 164 cells showed inhibited tumor growth, which was measured in terms of tumor volume and Luc+WEHI 164 cells based bioluminescence in vivo imaging. Histopathological analysis and other assays revealed decreased mitotic index, increased apoptosis and senescence in these tumor tissues. In addition, poor angiogenesis was observed in these tumor tissues, which was further confirmed by fluorescence imaging of tumor vascularisation and CD31 expression by immuno-histochemistry. Interestingly, the growth inhibitory bystander effect was exerted more prominently by soluble factors obtained from the irradiated tumor cells than the cellular fraction. Cytokine profiling of the supernatants obtained from the irradiated tumor cells showed increased levels of VEGF, Rantes, PDGF, GMCSF and IL-2 and decreased levels of IL-6 and SCF. Comparative proteomic analysis of the supernatants from the irradiated tumor cells showed differential expression of total 24 protein spots (21 up- and 3 down-regulated when compared with the supernatant from the unirradiated control cells. The proteins which showed substantially higher level in the supernatant from the irradiated cells included diphosphate kinase B, heat shock cognate, annexin A1, angiopoietin-2, actin (cytoplasmic 1/2 and stress induced phosphoprotein 1. However, the levels of proteins like annexin A2, protein S100 A4 and cofilin was found to be lower in this supernatant. In conclusion, our results provided deeper

  5. Radiological indeterminate vestibular schwannoma and meningioma in cerebellopontine angle area: differentiating using whole-tumor histogram analysis of apparent diffusion coefficient.

    Science.gov (United States)

    Xu, Xiao-Quan; Li, Yan; Hong, Xun-Ning; Wu, Fei-Yun; Shi, Hai-Bin

    2017-02-01

    To assess the role of whole-tumor histogram analysis of apparent diffusion coefficient (ADC) maps in differentiating radiological indeterminate vestibular schwannoma (VS) from meningioma in cerebellopontine angle (CPA). Diffusion-weighted (DW) images (b = 0 and 1000 s/mm 2 ) of pathologically confirmed and radiological indeterminate CPA meningioma (CPAM) (n = 27) and VS (n = 12) were retrospectively collected and processed with mono-exponential model. Whole-tumor regions of interest were drawn on all slices of the ADC maps to obtain histogram parameters, including the mean ADC (ADC mean ), median ADC (ADC median ), 10th/25th/75th/90th percentile ADC (ADC 10 , ADC 25 , ADC 75 and ADC 90 ), skewness and kurtosis. The differences of ADC histogram parameters between CPAM and VS were compared using unpaired t-test. Multiple receiver operating characteristic (ROC) curves analysis was used to determine and compare the diagnostic value of each significant parameter. Significant differences were found on the ADC mean , ADC median , ADC 10 , ADC 25 , ADC 75 and ADC 90 between CPAM and VS (all p values Histogram analysis of ADC maps based on whole tumor can be a useful tool for differentiating radiological indeterminate CPAM from VS. The ADC 90 value was the most promising parameter for differentiating these two entities.

  6. Multi-Parametric MRI and Texture Analysis to Visualize Spatial Histologic Heterogeneity and Tumor Extent in Glioblastoma.

    Science.gov (United States)

    Hu, Leland S; Ning, Shuluo; Eschbacher, Jennifer M; Gaw, Nathan; Dueck, Amylou C; Smith, Kris A; Nakaji, Peter; Plasencia, Jonathan; Ranjbar, Sara; Price, Stephen J; Tran, Nhan; Loftus, Joseph; Jenkins, Robert; O'Neill, Brian P; Elmquist, William; Baxter, Leslie C; Gao, Fei; Frakes, David; Karis, John P; Zwart, Christine; Swanson, Kristin R; Sarkaria, Jann; Wu, Teresa; Mitchell, J Ross; Li, Jing

    2015-01-01

    Genetic profiling represents the future of neuro-oncology but suffers from inadequate biopsies in heterogeneous tumors like Glioblastoma (GBM). Contrast-enhanced MRI (CE-MRI) targets enhancing core (ENH) but yields adequate tumor in only ~60% of cases. Further, CE-MRI poorly localizes infiltrative tumor within surrounding non-enhancing parenchyma, or brain-around-tumor (BAT), despite the importance of characterizing this tumor segment, which universally recurs. In this study, we use multiple texture analysis and machine learning (ML) algorithms to analyze multi-parametric MRI, and produce new images indicating tumor-rich targets in GBM. We recruited primary GBM patients undergoing image-guided biopsies and acquired pre-operative MRI: CE-MRI, Dynamic-Susceptibility-weighted-Contrast-enhanced-MRI, and Diffusion Tensor Imaging. Following image coregistration and region of interest placement at biopsy locations, we compared MRI metrics and regional texture with histologic diagnoses of high- vs low-tumor content (≥80% vs heterogeneity to identify regional tumor-rich biopsy targets.

  7. Use of Tumor Markers in Gastrointestinal Cancers: Surgeon Perceptions and Cost-Benefit Trade-Off Analysis.

    Science.gov (United States)

    Acharya, Amish; Markar, Sheraz R; Matar, Michael; Ni, Melody; Hanna, George B

    2017-05-01

    Gastrointestinal cancers constitute the third most common cancers worldwide. Tumor markers have long since been used in the postoperative surveillance of these malignancies; however, the true value in clinical practice remains undetermined. This study aimed to evaluate the clinical utility of three tumor markers in colorectal and esophagogastric cancer. A systematic review of the literature was undertaken to elicit the sensitivity, specificity, statistical heterogeneity and ability to predict recurrence and metastases for carcinoembryonic antigen (CEA), cancer antigen (CA) 19-9 and CA125. European surgeons were surveyed to assess their current practice and the characteristics of tumor markers they most valued. Data from the included studies and survey were combined in a cost-benefit trade-off analysis to assess which tumor markers are of most use in clinical practice. Diagnostic sensitivity and specificity were ranked the most desirable characteristics of a tumor marker by those surveyed. Overall, 156 studies were included to inform the cost-benefit trade-off. The cost-benefit trade-off showed that CEA outperformed both CA19-9 and CA125, with lower financial cost and a higher sensitivity, and diagnostic accuracy for metastases at presentation (area under the curve [AUC] 0.70 vs. 0.61 vs. 0.46), as well as similar diagnostic accuracy for recurrence (AUC 0.46 vs. 0.48). Cost-benefit trade-off analysis identified CEA to be the best performing tumor marker. Further studies should seek to evaluate new tumor markers, with investigation tailored to factors that meet the requirements of practicing clinicians.

  8. Correlation between apparent diffusion coefficient (ADC) and cellularity is different in several tumors: a meta-analysis.

    Science.gov (United States)

    Surov, Alexey; Meyer, Hans Jonas; Wienke, Andreas

    2017-08-29

    The purpose of this meta-analysis was to provide clinical evidence regarding relationship between ADC and cellularity in different tumors based on large patient data. Medline library was screened for associations between ADC and cell count in different tumors up to September 2016. Only publications in English were extracted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA) was used for the research. Overall, 39 publications with 1530 patients were included into the analysis. The following data were extracted from the literature: authors, year of publication, number of patients, tumor type, and correlation coefficients. The pooled correlation coefficient for all studies was ρ = -0.56 (95 % CI = [-0.62; -0.50]),. Correlation coefficients ranged from ρ =-0.25 (95 % CI = [-0.63; 0.12]) in lymphoma to ρ=-0.66 (95 % CI = [-0.85; -0.47]) in glioma. Other coefficients were as follows: ovarian cancer, ρ = -0.64 (95% CI = [-0.76; -0.52]); lung cancer, ρ = -0.63 (95 % CI = [-0.78; -0.48]); uterine cervical cancer, ρ = -0.57 (95 % CI = [-0.80; -0.34]); prostatic cancer, ρ = -0.56 (95 % CI = [-0.69; -0.42]); renal cell carcinoma, ρ = -0.53 (95 % CI = [-0.93; -0.13]); head and neck squamous cell carcinoma, ρ = -0.53 (95 % CI = [-0.74; -0.32]); breast cancer, ρ = -0.48 (95 % CI = [-0.74; -0.23]); and meningioma, ρ = -0.45 (95 % CI = [-0.73; -0.17]).

  9. Oxygen distribution in tumors: A qualitative analysis and modeling study providing a novel Monte Carlo approach

    International Nuclear Information System (INIS)

    Lagerlöf, Jakob H.; Kindblom, Jon; Bernhardt, Peter

    2014-01-01

    Purpose: To construct a Monte Carlo (MC)-based simulation model for analyzing the dependence of tumor oxygen distribution on different variables related to tumor vasculature [blood velocity, vessel-to-vessel proximity (vessel proximity), and inflowing oxygen partial pressure (pO 2 )]. Methods: A voxel-based tissue model containing parallel capillaries with square cross-sections (sides of 10 μm) was constructed. Green's function was used for diffusion calculations and Michaelis-Menten's kinetics to manage oxygen consumption. The model was tuned to approximately reproduce the oxygenational status of a renal carcinoma; the depth oxygenation curves (DOC) were fitted with an analytical expression to facilitate rapid MC simulations of tumor oxygen distribution. DOCs were simulated with three variables at three settings each (blood velocity, vessel proximity, and inflowing pO 2 ), which resulted in 27 combinations of conditions. To create a model that simulated variable oxygen distributions, the oxygen tension at a specific point was randomly sampled with trilinear interpolation in the dataset from the first simulation. Six correlations between blood velocity, vessel proximity, and inflowing pO 2 were hypothesized. Variable models with correlated parameters were compared to each other and to a nonvariable, DOC-based model to evaluate the differences in simulated oxygen distributions and tumor radiosensitivities for different tumor sizes. Results: For tumors with radii ranging from 5 to 30 mm, the nonvariable DOC model tended to generate normal or log-normal oxygen distributions, with a cut-off at zero. The pO 2 distributions simulated with the six-variable DOC models were quite different from the distributions generated with the nonvariable DOC model; in the former case the variable models simulated oxygen distributions that were more similar to in vivo results found in the literature. For larger tumors, the oxygen distributions became truncated in the lower

  10. IDH Mutation Analysis in Ewing Sarcoma Family Tumors

    Directory of Open Access Journals (Sweden)

    Ki Yong Na

    2015-05-01

    Full Text Available Background: Isocitrate dehydrogenase (IDH catalyzes the oxidative decarboxylation of isocitrate to yield α-ketoglutarate (α-KG with production of reduced nicotinamide adenine dinucleotide (NADH. Dysfunctional IDH leads to reduced production of α-KG and NADH and increased production of 2-hydroxyglutarate, an oncometabolite. This results in increased oxidative damage and stabilization of hypoxia-inducible factor α, causing cells to be prone to tumorigenesis. Methods: This study investigated IDH mutations in 61 Ewing sarcoma family tumors (ESFTs, using a pentose nucleic acid clamping method and direct sequencing. Results: We identified four cases of ESFTs harboring IDH mutations. The number of IDH1 and IDH2 mutations was equal and the subtype of IDH mutations was variable. Clinicopathologic analysis according to IDH mutation status did not reveal significant results. Conclusions: This study is the first to report IDH mutations in ESFTs. The results indicate that ESFTs can harbor IDH mutations in previously known hot-spot regions, although their incidence is rare. Further validation with a larger case-based study would establish more reliable and significant data on prevalence rate and the biological significance of IDH mutations in ESFTs.

  11. Immune response to uv-induced tumors: transplantation immunity and lymphocyte populations exhibiting anti-tumor activity

    International Nuclear Information System (INIS)

    Streeter, P.R.

    1985-01-01

    Ultraviolet light-induced murine skin tumors were analyzed for their ability to induce tumor-specific and cross-protective transplantation immunity in immunocompetent syngeneic mice. These studies revealed that progressor UV-tumors, like regressor UV-tumors, possess tumor-specific transplantation antigens. Cross-protective transplantation immunity to UV-tumors, however, was associated with sensitization to the serum used to culture the tumor lines rather than to cross-reactive or common determinants on UV-tumors. An analysis of the cytolytic activity of lymphocytes from the spleens of mice immunized with either regressor or progressor UV-tumors revealed a striking difference between the two immune splenocyte populations. From regressor tumor-immune animals, cytolytic T (Tc) lymphocytes with specificity for the immunizing tumor were found. However, the analysis of splenic lymphocytes from progressor tumor immune animals revealed no such effector cells. To more effectively examine those lymphocytes exhibiting cytolytic activity in vitro, T lymphocyte cloning technology was used as a means of isolating homogeneous lymphocyte populations with the effector activities described above. The mechanisms where NK cells and other nonspecific effector cells could be induced in tumor-immune animals are discussed in the context of class II restricted immune responses

  12. Research Progress on the Relationship Between Oral Microbial Community and Tumor

    Directory of Open Access Journals (Sweden)

    Ma Shujun

    2016-03-01

    Full Text Available Significant progress was observed in studies of the relationship between oral Helicobacter pylori and gastric cancer and tumors. Based on three distinct and close relationships, namely, the relationship between oral H. pylori and gastric cancer, between oral microbial communities and oral squamous cell carcinoma, and between oral microbial communities of human immunodeficiency virus-infected patients and tumors, this work reviews the relationship between oral microbial communities and tumors. This research also provides reference for further analysis of the relationship between oral microorganisms and tumors to realize early diagnosis of tumor patients through detecting oral microorganisms under adjuvant therapy.

  13. Dose painting based on tumor uptake of Cu-ATSM and FDG: a comparative study

    International Nuclear Information System (INIS)

    Clausen, Malene Martini; Hansen, Anders Elias; Lundemann, Michael; Hollensen, Christian; Pommer, Tobias; Munck af Rosenschöld, Per; Kristensen, Annemarie Thuri; Kjær, Andreas; McEvoy, Fintan J; Engelholm, Svend Aage

    2014-01-01

    Hypoxia and increased glycolytic activity of tumors are associated with poor prognosis. The purpose of this study was to investigate differences in radiotherapy (RT) dose painting based on the uptake of 2-deoxy-2-[ 18 F]-fluorodeoxyglucose (FDG) and the proposed hypoxia tracer, copper(II)diacetyl-bis(N 4 )-methylsemithiocarbazone (Cu-ATSM) using spontaneous clinical canine tumor models. Positron emission tomography/computed tomography scans of five spontaneous canine sarcomas and carcinomas were obtained; FDG on day 1 and 64 Cu-ATSM on day 2 and 3 (approx. 3 and 24 hours pi.). Sub-volumes for dose escalation were defined by a threshold-based method for both tracers and five dose escalation levels were formed in each sub-volume. Volumetric modulated arc therapy plans were optimized based on the dose escalation regions for each scan for a total of three dose plans for each dog. The prescription dose for the GTV was 45 Gy (100%) and it was linearly escalated to a maximum of 150%. The correlations between dose painting plans were analyzed with construction of dose distribution density maps and quality volume histograms (QVH). Correlation between high-dose regions was investigated with Dice correlation coefficients. Comparison of dose plans revealed varying degree of correlation between cases. Some cases displayed a separation of high-dose regions in the comparison of FDG vs. 64 Cu-ATSM dose plans at both time points. Among the Dice correlation coefficients, the high dose regions showed the lowest degree of agreement, indicating potential benefit of using multiple tracers for dose painting. QVH analysis revealed that FDG-based dose painting plans adequately covered approximately 50% of the hypoxic regions. Radiotherapy plans optimized with the current approach for cut-off values and dose region definitions based on FDG, 64 Cu-ATSM 3 h and 24 h uptake in canine tumors had different localization of the regional dose escalation levels. This indicates that 64 Cu-ATSM at two

  14. Inference of Tumor Evolution during Chemotherapy by Computational Modeling and In Situ Analysis of Genetic and Phenotypic Cellular Diversity

    Directory of Open Access Journals (Sweden)

    Vanessa Almendro

    2014-02-01

    Full Text Available Cancer therapy exerts a strong selection pressure that shapes tumor evolution, yet our knowledge of how tumors change during treatment is limited. Here, we report the analysis of cellular heterogeneity for genetic and phenotypic features and their spatial distribution in breast tumors pre- and post-neoadjuvant chemotherapy. We found that intratumor genetic diversity was tumor-subtype specific, and it did not change during treatment in tumors with partial or no response. However, lower pretreatment genetic diversity was significantly associated with pathologic complete response. In contrast, phenotypic diversity was different between pre- and posttreatment samples. We also observed significant changes in the spatial distribution of cells with distinct genetic and phenotypic features. We used these experimental data to develop a stochastic computational model to infer tumor growth patterns and evolutionary dynamics. Our results highlight the importance of integrated analysis of genotypes and phenotypes of single cells in intact tissues to predict tumor evolution.

  15. Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity

    International Nuclear Information System (INIS)

    Almendro, Vanessa; Cheng, Yu-Kang; Randles, Amanda; Itzkovitz, Shalev; Marusyk, Andriy; Ametller, Elisabet; Gonzalez-Farre, Xavier; Muñoz, Montse; Russnes, Hege G.; Helland, Åslaug; Rye, Inga H.; Borresen-Dale, Anne-Lise; Maruyama, Reo; Van Oudenaarden, Alexander; Dowsett, Mitchell; Jones, Robin L.; Reis-Filho, Jorge; Gascon, Pere; Gönen, Mithat; Michor, Franziska; Polyak, Kornelia

    2014-01-01

    Cancer therapy exerts a strong selection pressure that shapes tumor evolution, yet our knowledge of how tumors change during treatment is limited. Here, we report the analysis of cellular heterogeneity for genetic and phenotypic features and their spatial distribution in breast tumors pre- and post-neoadjuvant chemotherapy. We found that intratumor genetic diversity was tumor-subtype specific, and it did not change during treatment in tumors with partial or no response. However, lower pretreatment genetic diversity was significantly associated with pathologic complete response. In contrast, phenotypic diversity was different between pre- and post-treatment samples. We also observed significant changes in the spatial distribution of cells with distinct genetic and phenotypic features. We used these experimental data to develop a stochastic computational model to infer tumor growth patterns and evolutionary dynamics. Our results highlight the importance of integrated analysis of genotypes and phenotypes of single cells in intact tissues to predict tumor evolution

  16. Infiltration of M2 Tumor-Associated Macrophages in Oral Squamous Cell Carcinoma Correlates with Tumor Malignancy

    International Nuclear Information System (INIS)

    Mori, Kazumasa; Hiroi, Miki; Shimada, Jun; Ohmori, Yoshihiro

    2011-01-01

    Tumor-associated macrophages (TAMs) are a major cellular component in the tumor microenvironment of many solid tumors. The functional competence of TAMs varies depending on the type of tumors and their respective microenvironments. The classically activated M1 macrophages exhibit antitumor functions, whereas the alternatively activated M2 macrophages exhibit protumor functions that contribute to tumor development and progression. Although TAMs have been detected in oral squamous cell carcinoma (OSCC), little is known about their phenotype. In the present study, we performed an immunohistochemical analysis to identify TAMs in surgically resected specimens from 50 patients with OSCC and evaluated the relationship between infiltrated TAMs and the pathological grade of OSCC. Positive staining for CD163, which has been used as a marker for M2 macrophages, was observed in OSCC specimens, and the percentages of CD163 + cells were significantly increased based on the pathological grade. CD163 + cells were detected in the tumor stroma in grade I tumors, whereas an increase in the CD163 + cells in the tumor nest was observed in higher grades of tumors. Although infiltrated CD4 + and CD8 + T cells were detected in all pathological grades of OSCC, no correlation between the infiltrated T cells and the CD163 + TAMs was observed. These results indicate that the infiltrated TAMs in OSCC have an M2 phenotype and that the M2 macrophages may participate in the development of OSCC

  17. Infiltration of M2 Tumor-Associated Macrophages in Oral Squamous Cell Carcinoma Correlates with Tumor Malignancy

    Energy Technology Data Exchange (ETDEWEB)

    Mori, Kazumasa [Division of Oral and Maxillofacial Surgery, Department of Diagnosis and Therapeutics, Meikai University of School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283 (Japan); Hiroi, Miki [Division of Microbiology and Immunology, Department of Oral Biology and Tissue Engineering, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283 (Japan); Shimada, Jun [Division of Oral and Maxillofacial Surgery, Department of Diagnosis and Therapeutics, Meikai University of School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283 (Japan); Ohmori, Yoshihiro, E-mail: ohmori@dent.meikai.ac.jp [Division of Microbiology and Immunology, Department of Oral Biology and Tissue Engineering, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283 (Japan)

    2011-09-28

    Tumor-associated macrophages (TAMs) are a major cellular component in the tumor microenvironment of many solid tumors. The functional competence of TAMs varies depending on the type of tumors and their respective microenvironments. The classically activated M1 macrophages exhibit antitumor functions, whereas the alternatively activated M2 macrophages exhibit protumor functions that contribute to tumor development and progression. Although TAMs have been detected in oral squamous cell carcinoma (OSCC), little is known about their phenotype. In the present study, we performed an immunohistochemical analysis to identify TAMs in surgically resected specimens from 50 patients with OSCC and evaluated the relationship between infiltrated TAMs and the pathological grade of OSCC. Positive staining for CD163, which has been used as a marker for M2 macrophages, was observed in OSCC specimens, and the percentages of CD163{sup +} cells were significantly increased based on the pathological grade. CD163{sup +} cells were detected in the tumor stroma in grade I tumors, whereas an increase in the CD163{sup +} cells in the tumor nest was observed in higher grades of tumors. Although infiltrated CD4{sup +} and CD8{sup +} T cells were detected in all pathological grades of OSCC, no correlation between the infiltrated T cells and the CD163{sup +} TAMs was observed. These results indicate that the infiltrated TAMs in OSCC have an M2 phenotype and that the M2 macrophages may participate in the development of OSCC.

  18. SU-E-J-249: Characterization of Gynecological Tumor Heterogeneity Using Texture Analysis in the Context of An 18F-FDG PET Adaptive Protocol

    Energy Technology Data Exchange (ETDEWEB)

    Nawrocki, J [Duke University Medical Physics Graduate Program, Durham, NC (United States); Chino, J; Craciunescu, O [Duke University Medical Center Department of Radiation Oncology, Durham, NC (United States); Das, S [University of North Carolina School of Medicine, Chapel Hill, NC (United States)

    2015-06-15

    Purpose: We propose a method to examine gynecological tumor heterogeneity using texture analysis in the context of an adaptive PET protocol in order to establish if texture metrics from baseline PET-CT predict tumor response better than SUV metrics alone as well as determine texture features correlating with tumor response during radiation therapy. Methods: This IRB approved protocol included 29 women with node positive gynecological cancers visible on FDG-PET treated with EBRT to the PET positive nodes. A baseline and intra-treatment PET-CT was obtained. Tumor outcome was determined based on RECIST on posttreatment PET-CT. Primary GTVs were segmented using 40% threshold and a semi-automatic gradient-based contouring tool, PET Edge (MIM Software Inc., Cleveland, OH). SUV histogram features, Metabolic Volume (MV), and Total Lesion Glycolysis (TLG) were calculated. Four 3D texture matrices describing local and regional relationships between voxel intensities in the GTV were generated: co-occurrence, run length, size zone, and neighborhood difference. From these, 39 texture features were calculated. Prognostic power of baseline features derived from gradientbased and threshold GTVs were determined using the Wilcoxon rank-sum test. Receiver Operating Characteristics and logistic regression was performed using JMP (SAS Institute Inc., Cary, NC) to find probabilities of predicting response. Changes in features during treatment were determined using the Wilcoxon signed-rank test. Results: Of the 29 patients, there were 16 complete responders, 7 partial responders, and 6 non-responders. Comparing CR/PR vs. NR for gradient-based GTVs, 7 texture values, TLG, and SUV kurtosis had a p < 0.05. Threshold GTVs yielded 4 texture features and TLG with p < 0.05. From baseline to intra-treatment, 14 texture features, SUVmean, SUVmax, MV, and TLG changed with p < 0.05. Conclusion: Texture analysis of PET imaged gynecological tumors is an effective method for early prognosis and should

  19. SU-E-J-249: Characterization of Gynecological Tumor Heterogeneity Using Texture Analysis in the Context of An 18F-FDG PET Adaptive Protocol

    International Nuclear Information System (INIS)

    Nawrocki, J; Chino, J; Craciunescu, O; Das, S

    2015-01-01

    Purpose: We propose a method to examine gynecological tumor heterogeneity using texture analysis in the context of an adaptive PET protocol in order to establish if texture metrics from baseline PET-CT predict tumor response better than SUV metrics alone as well as determine texture features correlating with tumor response during radiation therapy. Methods: This IRB approved protocol included 29 women with node positive gynecological cancers visible on FDG-PET treated with EBRT to the PET positive nodes. A baseline and intra-treatment PET-CT was obtained. Tumor outcome was determined based on RECIST on posttreatment PET-CT. Primary GTVs were segmented using 40% threshold and a semi-automatic gradient-based contouring tool, PET Edge (MIM Software Inc., Cleveland, OH). SUV histogram features, Metabolic Volume (MV), and Total Lesion Glycolysis (TLG) were calculated. Four 3D texture matrices describing local and regional relationships between voxel intensities in the GTV were generated: co-occurrence, run length, size zone, and neighborhood difference. From these, 39 texture features were calculated. Prognostic power of baseline features derived from gradientbased and threshold GTVs were determined using the Wilcoxon rank-sum test. Receiver Operating Characteristics and logistic regression was performed using JMP (SAS Institute Inc., Cary, NC) to find probabilities of predicting response. Changes in features during treatment were determined using the Wilcoxon signed-rank test. Results: Of the 29 patients, there were 16 complete responders, 7 partial responders, and 6 non-responders. Comparing CR/PR vs. NR for gradient-based GTVs, 7 texture values, TLG, and SUV kurtosis had a p < 0.05. Threshold GTVs yielded 4 texture features and TLG with p < 0.05. From baseline to intra-treatment, 14 texture features, SUVmean, SUVmax, MV, and TLG changed with p < 0.05. Conclusion: Texture analysis of PET imaged gynecological tumors is an effective method for early prognosis and should

  20. Analysis of mice tumor models using dynamic MRI data and a dedicated software platform

    Energy Technology Data Exchange (ETDEWEB)

    Alfke, H.; Maurer, E.; Klose, K.J. [Philipps Univ. Marburg (Germany). Dept. of Radiology; Kohle, S.; Rascher-Friesenhausen, R.; Behrens, S.; Peitgen, H.O. [MeVis - Center for Medical Diagnostic Systems and Visualization, Bremen (Germany); Celik, I. [Philipps Univ. Marburg (Germany). Inst. for Theoretical Surgery; Heverhagen, J.T. [Philipps Univ. Marburg (Germany). Dept. of Radiology; Ohio State Univ., Columbus (United States). Dept. of Radiology

    2004-09-01

    Purpose: To implement a software platform (DynaVision) dedicated to analyze data from functional imaging of tumors with different mathematical approaches, and to test the software platform in pancreatic carcinoma xenografts in mice with severe combined immunodeficiency disease (SCID). Materials and Methods: A software program was developed for extraction and visualization of tissue perfusion parameters from dynamic contrast-enhanced images. This includes regional parameter calculation from enhancement curves, parametric images (e.g., blood flow), animation, 3D visualization, two-compartment modeling a mode for comparing different datasets (e.g., therapy monitoring), and motion correction. We analyzed xenograft tumors from two pancreatic carcinoma cell lines (B x PC3 and ASPC1) implanted in 14 SCID mice after injection of Gd-DTPA into the tail vein. These data were correlated with histopathological findings. Results: Image analysis was completed in approximately 15 minutes per data set. The possibility of drawing and editing ROIs within the whole data set makes it easy to obtain quantitative data from the intensity-time curves. In one animal, motion artifacts reduced the image quality to a greater extent but data analysis was still possible after motion correction. Dynamic MRI of mice tumor models revealed a highly heterogeneous distribution of the contrast-enhancement curves and derived parameters, which correlated with differences in histopathology. ASPc1 tumors showed a more hypervascular type of curves with faster and higher signal enhancement rate (wash-in) and a faster signal decrease (wash-out). BXPC3 tumors showed a more hypovascular type with slower wash-in and wash-out. This correlated with the biological properties of the tumors. (orig.)

  1. Analysis of mice tumor models using dynamic MRI data and a dedicated software platform

    International Nuclear Information System (INIS)

    Alfke, H.; Maurer, E.; Klose, K.J.; Celik, I.; Heverhagen, J.T.; Ohio State Univ., Columbus

    2004-01-01

    Purpose: To implement a software platform (DynaVision) dedicated to analyze data from functional imaging of tumors with different mathematical approaches, and to test the software platform in pancreatic carcinoma xenografts in mice with severe combined immunodeficiency disease (SCID). Materials and Methods: A software program was developed for extraction and visualization of tissue perfusion parameters from dynamic contrast-enhanced images. This includes regional parameter calculation from enhancement curves, parametric images (e.g., blood flow), animation, 3D visualization, two-compartment modeling a mode for comparing different datasets (e.g., therapy monitoring), and motion correction. We analyzed xenograft tumors from two pancreatic carcinoma cell lines (B x PC3 and ASPC1) implanted in 14 SCID mice after injection of Gd-DTPA into the tail vein. These data were correlated with histopathological findings. Results: Image analysis was completed in approximately 15 minutes per data set. The possibility of drawing and editing ROIs within the whole data set makes it easy to obtain quantitative data from the intensity-time curves. In one animal, motion artifacts reduced the image quality to a greater extent but data analysis was still possible after motion correction. Dynamic MRI of mice tumor models revealed a highly heterogeneous distribution of the contrast-enhancement curves and derived parameters, which correlated with differences in histopathology. ASPc1 tumors showed a more hypervascular type of curves with faster and higher signal enhancement rate (wash-in) and a faster signal decrease (wash-out). BXPC3 tumors showed a more hypovascular type with slower wash-in and wash-out. This correlated with the biological properties of the tumors. (orig.)

  2. A state-based probabilistic model for tumor respiratory motion prediction

    International Nuclear Information System (INIS)

    Kalet, Alan; Sandison, George; Schmitz, Ruth; Wu Huanmei

    2010-01-01

    This work proposes a new probabilistic mathematical model for predicting tumor motion and position based on a finite state representation using the natural breathing states of exhale, inhale and end of exhale. Tumor motion was broken down into linear breathing states and sequences of states. Breathing state sequences and the observables representing those sequences were analyzed using a hidden Markov model (HMM) to predict the future sequences and new observables. Velocities and other parameters were clustered using a k-means clustering algorithm to associate each state with a set of observables such that a prediction of state also enables a prediction of tumor velocity. A time average model with predictions based on average past state lengths was also computed. State sequences which are known a priori to fit the data were fed into the HMM algorithm to set a theoretical limit of the predictive power of the model. The effectiveness of the presented probabilistic model has been evaluated for gated radiation therapy based on previously tracked tumor motion in four lung cancer patients. Positional prediction accuracy is compared with actual position in terms of the overall RMS errors. Various system delays, ranging from 33 to 1000 ms, were tested. Previous studies have shown duty cycles for latencies of 33 and 200 ms at around 90% and 80%, respectively, for linear, no prediction, Kalman filter and ANN methods as averaged over multiple patients. At 1000 ms, the previously reported duty cycles range from approximately 62% (ANN) down to 34% (no prediction). Average duty cycle for the HMM method was found to be 100% and 91 ± 3% for 33 and 200 ms latency and around 40% for 1000 ms latency in three out of four breathing motion traces. RMS errors were found to be lower than linear and no prediction methods at latencies of 1000 ms. The results show that for system latencies longer than 400 ms, the time average HMM prediction outperforms linear, no prediction, and the more

  3. Comparative Analysis of Immune Checkpoint Molecules and Their Potential Role in the Transmissible Tasmanian Devil Facial Tumor Disease

    Directory of Open Access Journals (Sweden)

    Andrew S. Flies

    2017-05-01

    Full Text Available Immune checkpoint molecules function as a system of checks and balances that enhance or inhibit immune responses to infectious agents, foreign tissues, and cancerous cells. Immunotherapies that target immune checkpoint molecules, particularly the inhibitory molecules programmed cell death 1 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4, have revolutionized human oncology in recent years, yet little is known about these key immune signaling molecules in species other than primates and rodents. The Tasmanian devil facial tumor disease is caused by transmissible cancers that have resulted in a massive decline in the wild Tasmanian devil population. We have recently demonstrated that the inhibitory checkpoint molecule PD-L1 is upregulated on Tasmanian devil (Sarcophilus harrisii facial tumor cells in response to the interferon-gamma cytokine. As this could play a role in immune evasion by tumor cells, we performed a thorough comparative analysis of checkpoint molecule protein sequences among Tasmanian devils and eight other species. We report that many of the key signaling motifs and ligand-binding sites in the checkpoint molecules are highly conserved across the estimated 162 million years of evolution since the last common ancestor of placental and non-placental mammals. Specifically, we discovered that the CTLA-4 (MYPPPY ligand-binding motif and the CTLA-4 (GVYVKM inhibitory domain are completely conserved across all nine species used in our comparative analysis, suggesting that the function of CTLA-4 is likely conserved in these species. We also found that cysteine residues for intra- and intermolecular disulfide bonds were also highly conserved. For instance, all 20 cysteine residues involved in disulfide bonds in the human 4-1BB molecule were also present in devil 4-1BB. Although many key sequences were conserved, we have also identified immunoreceptor tyrosine-based inhibitory motifs (ITIMs and immunoreceptor tyrosine-based switch

  4. Diagnostic markers of urothelial cancer based on DNA methylation analysis

    International Nuclear Information System (INIS)

    Chihara, Yoshitomo; Hirao, Yoshihiko; Kanai, Yae; Fujimoto, Hiroyuki; Sugano, Kokichi; Kawashima, Kiyotaka; Liang, Gangning; Jones, Peter A; Fujimoto, Kiyohide; Kuniyasu, Hiroki

    2013-01-01

    Early detection and risk assessment are crucial for treating urothelial cancer (UC), which is characterized by a high recurrence rate, and necessitates frequent and invasive monitoring. We aimed to establish diagnostic markers for UC based on DNA methylation. In this multi-center study, three independent sample sets were prepared. First, DNA methylation levels at CpG loci were measured in the training sets (tumor samples from 91 UC patients, corresponding normal-appearing tissue from these patients, and 12 normal tissues from age-matched bladder cancer-free patients) using the Illumina Golden Gate methylation assay to identify differentially methylated loci. Next, these methylated loci were validated by quantitative DNA methylation by pyrosequencing, using another cohort of tissue samples (Tissue validation set). Lastly, methylation of these markers was analyzed in the independent urine samples (Urine validation set). ROC analysis was performed to evaluate the diagnostic accuracy of these 12 selected markers. Of the 1303 CpG sites, 158 were hyper ethylated and 356 were hypo ethylated in tumor tissues compared to normal tissues. In the panel analysis, 12 loci showed remarkable alterations between tumor and normal samples, with 94.3% sensitivity and 97.8% specificity. Similarly, corresponding normal tissue could be distinguished from normal tissues with 76.0% sensitivity and 100% specificity. Furthermore, the diagnostic accuracy for UC of these markers determined in urine samples was high, with 100% sensitivity and 100% specificity. Based on these preliminary findings, diagnostic markers based on differential DNA methylation at specific loci can be useful for non-invasive and reliable detection of UC and epigenetic field defect

  5. Pharmacokinetic Analysis of 64Cu-ATSM Dynamic PET in Human Xenograft Tumors in Mice

    DEFF Research Database (Denmark)

    Li, Fan; Jørgensen, Jesper Tranekjær; Madsen, Jacob

    2015-01-01

    The aim of this study was to evaluate the feasibility to perform voxel-wise kinetic modeling on datasets obtained from tumor-bearing mice that underwent dynamic PET scans with 64Cu-ATSM and extract useful physiological parameters.METHODS: Tumor-bearing mice underwent 90-min dynamic PET scans...... relevant parameters from voxel-wise pharmacokinetic analysis to be used for preclinical validation of 64Cu-ATSM as a hypoxia-specific PET tracer....

  6. The correlation analysis of tumor necrosis factor-alpha-308G/A polymorphism and venous thromboembolism risk: A meta-analysis.

    Science.gov (United States)

    Gao, Quangen; Zhang, Peijin; Wang, Wei; Ma, He; Tong, Yue; Zhang, Jing; Lu, Zhaojun

    2016-10-01

    Venous thromboembolism is a common complex disorder, being the resultant of gene-gene and gene-environment interactions. Tumor necrosis factor-alpha is a proinflammatory cytokine which has been implicated in venous thromboembolism risk. A promoter 308G/A polymorphism in the tumor necrosis factor-alpha gene has been suggested to modulate the risk for venous thromboembolism. However, the published findings remain inconsistent. In this study, we conducted a meta-analysis of all available data regarding this issue. Eligible studies were identified through search of Pubmed, EBSCO Medline, Web of Science, and China National Knowledge Infrastructure (CNKI, Chinese) databases up to June 2014. Pooled Odd ratios (ORs) with 95% confidence intervals were applied to estimating the strength of the genetic association in the random-effects model or fixed-effects model. A total of 10 studies involving 1999 venous thromboembolism cases and 2166 controls were included in this meta-analysis to evaluate the association between tumor necrosis factor-alpha-308G/A polymorphism and venous thromboembolism risk. Overall, no significantly increased risk venous thromboembolism was observed in all comparison models when all studies were pooled into the meta-analysis. However, in stratified analyses by ethnicity, there was a pronounced association with venous thromboembolism risk among West Asians in three genetic models (A vs. G: OR = 1.82, 95%CI = 1.13-2.94; GA vs. GG: OR = 1.82, 95%CI = 1.08-3.06; AA/GA vs. GG: OR = 1.88, 95%CI = 1.12-3.16). When stratifying by source of controls, no significant result was detected in all genetic models. This meta-analysis demonstrates that tumor necrosis factor-alpha 308G/A polymorphism may contribute to susceptibility to venous thromboembolism among West Asians. Studies are needed to ascertain these findings in larger samples and different racial groups. © The Author(s) 2015.

  7. Hemodynamic analysis of bladder tumors using T1-dynamic contrast-enhanced fast spin-echo MRI

    International Nuclear Information System (INIS)

    Kanazawa, Yuki; Miyati, Tosiaki; Sato, Osamu

    2012-01-01

    Objectives: To evaluate the hemodynamics of bladder tumors, we developed a method to calculate change in R 1 value (ΔR 1 ) from T 1 -dynamic contrast-enhanced fast spin-echo magnetic resonance imaging (T 1 DCE-FSE-MRI). Materials and methods: On a 1.5-T MR system, T 1 DCE-FSE-MRI was performed. This study was applied to 12 patients with urinary bladder tumor, i.e. urothelial carcinoma. We compared ΔR 1 –time and ΔSI–time between a peak in the ΔR 1 –time and ΔSI–time curve occurred during the first pass within 60 s. Next, we assessed the slope of increase for 180 s after CA injection (Slope 0–180 ). Results: The mean slope of the first pass was significantly higher for bladder tumors on both the ΔR 1 –time and the ΔSI–time curve compared with normal bladder walls. Moreover, a significant difference was apparent between bladder tumors and normal bladder walls on the mean Slope 0–180 in the ΔR 1 -time curve. However, no significant difference in the mean Slope 0–180 was observed on the ΔSI-time curve between bladder tumors and normal bladder walls. Conclusion: T 1 DCE-FSE-MRI offers three advantages: quantitative analysis; high-quality (i.e., artifact-free) images; and high temporal resolution even for SE images. Use of ΔR 1 analysis with T 1 DCE-FSE-MRI allows more detailed information on the hemodynamics of bladder tumors to be obtained and assists in differentiation between bladder tumors and the normal bladder wall.

  8. Endoscopic transnasal approach for removing pituitary tumors

    Directory of Open Access Journals (Sweden)

    Mirian Cabral Moreira de Castro

    2014-05-01

    Full Text Available To describe a series of 129 consecutive patients submitted to the resection of pituitary tumors using the endoscopic transsphenoidal approach in a public medical center. Method: Retrospective analysis based on the records of patients submitted to the resection of a pituitary tumor through the endoscopic transsphenoidal approach between 2004 and 2009. Results: One hundred and twenty-nine records were analyzed. The tumor was non-secreting in 96 (74.42% and secreting in 33 patients (22.58%. Out of the secretory tumors, the most prevalent was the growth hormone producer (7.65%, followed by the prolactinoma, (6.98%. Eleven patients developed cerebral spinal fluid (CSF fistulas, and four of them developed meningitis. One patient died due to intracerebral hemorrhage in the postoperative period. Conclusion: The endoscopic transsphenoidal approach to sellar tumors proved to be safe when the majority of the tumors were non-secreting. The most frequent complication was CSF. This technique can be done even in a public hospital with financial limits, since the health professionals are integrated.

  9. Maternal and Birth Characteristics and Childhood Embryonal Solid Tumors: A Population-Based Report from Brazil.

    Science.gov (United States)

    de Paula Silva, Neimar; de Souza Reis, Rejane; Garcia Cunha, Rafael; Pinto Oliveira, Júlio Fernando; Santos, Marceli de Oliveira; Pombo-de-Oliveira, Maria S; de Camargo, Beatriz

    2016-01-01

    Several maternal and birth characteristics have been reported to be associated with an increased risk of many childhood cancers. Our goal was to evaluate the risk of childhood embryonal solid tumors in relation to pre- and perinatal characteristics. A case-cohort study was performed using two population-based datasets, which were linked through R software. Tumors were classified as central nervous system (CNS) or non-CNS-embryonal (retinoblastoma, neuroblastoma, renal tumors, germ cell tumors, hepatoblastoma and soft tissue sarcoma). Children aged birth anomalies were independent risk factors. Among children diagnosed older than 24 months of age, cesarean section (CS) was a significant risk factor. Five-minute Apgar ≤8 was an independent risk factor for renal tumors. A decreasing risk with increasing birth order was observed for all tumor types except for retinoblastoma. Among children with neuroblastoma, the risk decreased with increasing birth order (OR = 0.82 (95% CI 0.67-1.01)). Children delivered by CS had a marginally significantly increased OR for all tumors except retinoblastoma. High maternal education level showed a significant increase in the odds for all tumors together, CNS tumors, and neuroblastoma. This evidence suggests that male gender, high maternal education level, and birth anomalies are risk factors for childhood tumors irrespective of the age at diagnosis. Cesarean section, birth order, and 5-minute Apgar score were risk factors for some tumor subtypes.

  10. Primary Squamous Cell Carcinoma of the Thyroid: A Population-Based Analysis.

    Science.gov (United States)

    Au, Joshua K; Alonso, Jose; Kuan, Edward C; Arshi, Armin; St John, Maie A

    2017-07-01

    Objectives To analyze the epidemiology and describe the prognostic indicators of patients with primary squamous cell carcinoma of the thyroid. Study Design and Setting Retrospective cohort study based on a national database. Methods The US National Cancer Institute's SEER registry (Surveillance, Epidemiology, and End Results) was reviewed for patients with primary squamous cell carcinoma of the thyroid from 1973 to 2012. Study variables included age, sex, race, tumor size, tumor grade, regional and distant metastases, and treatment modality. Survival measures included overall survival (OS) and disease-specific survival (DSS). Results A total of 199 cases of primary squamous cell carcinoma of the thyroid were identified. Mean age at diagnosis was 68.1 years; 58.3% were female; and 79.4% were white. Following diagnosis, 46.3% of patients underwent surgery; 55.7%, radiation therapy; and 45.8%, surgery with radiation therapy. Kaplan-Meier analysis demonstrated OS and DSS of 16% and 21% at 5 years, respectively. Median survival after diagnosis was 9.1 months. Multivariate Cox regression analysis showed that predictors of OS and DSS included age ( P Squamous cell carcinoma of the thyroid is a rare malignancy with a very poor prognosis. Surgical resection confers an overall survival benefit. Age, tumor grade, and tumor size are predictors of OS and DSS.

  11. Optic neuropathy following combined proton and photon radiotherapy for base of skull tumors

    International Nuclear Information System (INIS)

    Kim, June; Munzenrider, John; Maas, Alicea; Finkelstein, Dianne; Liebsch, Norbert; Hug, Eugen; Suit, Herman; Smith, Al; Goitein, Michael

    1997-01-01

    of impairment ranged from 7 to 40 months following the completion of therapies, with a median duration of 12 months. The maximum dose to the optic apparatus ranged from 50.21 to 69.60 CGE, with a median value of 59.43 CGE. By Student t-test analysis, patch distance was the only variable significantly related to radiation-induced optic neuropathy. While the proportion of patients with patches was not different in the two groups, the patch distances were significantly smaller (p = 0.0284) in the cases than in the controls. Conclusion: Twelve of 274 patients (4.4%) who received high dose external beam proton and photon radiotherapy for skull base tumors developed radiation-induced optic neuropathy in 7 to 40 months from the completion of therapies. Patch distance was a significant risk factor for developing optic neuropathy (p = 0.0284)

  12. Acute Metabolic Alkalosis Enhances Response of C3H Mouse Mammary Tumors to the Weak Base Mitoxantrone

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    Natarajan Raghunand

    2001-01-01

    Full Text Available Uptake of weak acid and weak base chemotherapeutic drugs by tumors is greatly influenced by the tumor extracellular/interstitial pH (pHe, the intracellular pH (pHi maintained by the tumor cells, and by the ionization properties of the drug itself. The acid-outside plasmalemmal pH gradient in tumors acts to exclude weak base drugs like the anthracyclines, anthraquinones, and vinca alkaloids from the cells, leading to a substantial degree of “physiological drug resistance” in tumors. We have induced acute metabolic alkalosis in C3H tumor-bearing C3H/hen mice, by gavage and by intraperitoneal (i.p. administration of NaHCO3. 31P magnetic resonance spectroscopic measurements of 3-aminopropylphosphonate show increases of up to 0.6 pH units in tumor pHe, and 0.2 to 0.3 pH units in hind leg tissue pHe, within 2 hours of i.p. administration of NaHCO3. Theoretical calculations of mitoxantrone uptake into tumor and normal (hind leg tissue at the measured pH, and pHI values indicate that a gain in therapeutic index of up to 3.3-fold is possible with NaHCO3 pretreatment. Treatment of C3H tumor-bearing mice with 12 mg/kg mitoxantrone resulted in a tumor growth delay of 9 days, whereas combined NaHCO3mitoxantrone therapy resulted in an enhancement of the TGD to 16 days.

  13. CT findings of parotid gland tumors: benign versus malignant tumors

    International Nuclear Information System (INIS)

    Lee, Moon Ok; Han, Chun Hwan; Kim, Mie Young; Yi, Jeong Geun; Park, Kyung Joo; Lee, Joo Hyuk; Bae, Sang Hoon; Kim, Jeung Sook

    1994-01-01

    The purpose of this study is to evaluate the characteristics of parotid gland tumors to help in the differentiation between benign and malignant lesions. The CT findings of 22 patients with surgically proven parotid gland tumors were reviewed. Analysis was focused on the density and margin characteristics of the tumors, and the relationship between the tumor and surrounding structures. Those tumors were pleomorphic adenoma (n = 8), Warthin's tumor (n = 5), basal cell adenoma (n = 1), lipoma (n = 1), dermoid cyst (n = 1), adenoid cystic carcinoma (n = 2), mucoepidermoid carcinoma (n 1), epidermoid carcinoma (n = 1), and carcinoma in pleomorphic adenoma (n 1). Most of benign and malignant tumors were heterogeneous in density on contrast enhanced CT scans. In 5 of 6 malignant cases, the tumors had irregular or ill-defined margin and a tendancy to involve or cross the superficial layer of deep cervical fascia with obliteration of subcutaneous fat. Two malignant tumors invaded surrounding structures. Although the heterogeneous density of tumor is not a specific finding for malignancy at CT, following findings, such as, irregular or blurred margin of the lesion, the involvement of fascial plane, and the infiltration of surrounding structures may suggest the possibility of malignant parotid tumor

  14. Brain Tumor Segmentation Based on Random Forest

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    László Lefkovits

    2016-09-01

    Full Text Available In this article we present a discriminative model for tumor detection from multimodal MR images. The main part of the model is built around the random forest (RF classifier. We created an optimization algorithm able to select the important features for reducing the dimensionality of data. This method is also used to find out the training parameters used in the learning phase. The algorithm is based on random feature properties for evaluating the importance of the variable, the evolution of learning errors and the proximities between instances. The detection performances obtained have been compared with the most recent systems, offering similar results.

  15. Modulating the Tumor Microenvironment to Enhance Tumor Nanomedicine Delivery

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    Bo Zhang

    2017-12-01

    Full Text Available Nanomedicines including liposomes, micelles, and nanoparticles based on the enhanced permeability and retention (EPR effect have become the mainstream for tumor treatment owing to their superiority over conventional anticancer agents. Advanced design of nanomedicine including active targeting nanomedicine, tumor-responsive nanomedicine, and optimization of physicochemical properties to enable highly effective delivery of nanomedicine to tumors has further improved their therapeutic benefits. However, these strategies still could not conquer the delivery barriers of a tumor microenvironment such as heterogeneous blood flow, dense extracellular matrix, abundant stroma cells, and high interstitial fluid pressure, which severely impaired vascular transport of nanomedicines, hindered their effective extravasation, and impeded their interstitial transport to realize uniform distribution inside tumors. Therefore, modulation of tumor microenvironment has now emerged as an important strategy to improve nanomedicine delivery to tumors. Here, we review the existing strategies and approaches for tumor microenvironment modulation to improve tumor perfusion for helping more nanomedicines to reach the tumor site, to facilitate nanomedicine extravasation for enhancing transvascular transport, and to improve interstitial transport for optimizing the distribution of nanomedicines. These strategies may provide an avenue for the development of new combination chemotherapeutic regimens and reassessment of previously suboptimal agents.

  16. Modulating the Tumor Microenvironment to Enhance Tumor Nanomedicine Delivery

    Science.gov (United States)

    Zhang, Bo; Hu, Yu; Pang, Zhiqing

    2017-01-01

    Nanomedicines including liposomes, micelles, and nanoparticles based on the enhanced permeability and retention (EPR) effect have become the mainstream for tumor treatment owing to their superiority over conventional anticancer agents. Advanced design of nanomedicine including active targeting nanomedicine, tumor-responsive nanomedicine, and optimization of physicochemical properties to enable highly effective delivery of nanomedicine to tumors has further improved their therapeutic benefits. However, these strategies still could not conquer the delivery barriers of a tumor microenvironment such as heterogeneous blood flow, dense extracellular matrix, abundant stroma cells, and high interstitial fluid pressure, which severely impaired vascular transport of nanomedicines, hindered their effective extravasation, and impeded their interstitial transport to realize uniform distribution inside tumors. Therefore, modulation of tumor microenvironment has now emerged as an important strategy to improve nanomedicine delivery to tumors. Here, we review the existing strategies and approaches for tumor microenvironment modulation to improve tumor perfusion for helping more nanomedicines to reach the tumor site, to facilitate nanomedicine extravasation for enhancing transvascular transport, and to improve interstitial transport for optimizing the distribution of nanomedicines. These strategies may provide an avenue for the development of new combination chemotherapeutic regimens and reassessment of previously suboptimal agents. PMID:29311946

  17. Tumor response to ionizing radiation and combined 2-deoxy-D-glucose application in EATC tumor bearing mice: monitoring of tumor size and microscopic observations

    International Nuclear Information System (INIS)

    Latz, D.; Thonke, A.; Jueling-Pohlit, L.; Pohlit, W.

    1993-01-01

    The present study deals with the changes induced by two fractionation schedules (5x9 Gy and 10x4.5 Gy; 30 MeV-electrons) of ionizing radiations and 2-Deoxy-D-Glucose (2-DG) application on EATC tumor bearing swiss albino mice. The monitoring of tumor response was carried out by means of calliper measurement on the macroscopic level and by histopathological examination of tumor preparations stained with hematoxiline and eosine on the microscopic level. The tumor material was assessed at suitable intervals after treatment by killing the animals. The tumor response was analysed in the histological preparations and the thickness of the tumor band was determined quantitatively by an ocularmicrometric technique. Tumor damage was most extensive in the combined treated animals (5x9 Gy + 2-DG). Only in this group local tumor control was achievable. The histological analysis of tumor preparations revealed additional data about treatment-induced changes in the tumor compared to the measurement of the tumor volume with mechanical callipers. We also found that the treatment outcome could be predicted from the histopathological analysis. It is concluded that studies involving histopathological examinations may give some insight into the way cancer is controlled by radiotherapy and may be of value in prognosis and selection of treatment in patients. (orig.) [de

  18. A cytogenetic analysis of 2 cases of phosphaturic mesenchymal tumor of mixed connective tissue type.

    Science.gov (United States)

    Graham, Rondell P; Hodge, Jennelle C; Folpe, Andrew L; Oliveira, Andre M; Meyer, Kevin J; Jenkins, Robert B; Sim, Franklin H; Sukov, William R

    2012-08-01

    Phosphaturic mesenchymal tumor of mixed connective tissue type is a rare, histologically distinctive mesenchymal neoplasm associated with tumor-induced osteomalacia resulting from production of the phosphaturic hormone fibroblast growth factor 23. Because of its rarity, specific genetic alterations that contribute to the pathogenesis of these tumors have yet to be elucidated. Herein, we report the abnormal karyotypes from 2 cases of confirmed phosphaturic mesenchymal tumor of mixed connective tissue type. G-banded analysis demonstrated the first tumor to have a karyotype of 46,Y,t(X;3;14)(q13;p25;q21)[15]/46XY[5], and the second tumor to have a karyotype of 46, XY,add(2)(q31),add(4)(q31.1)[2]/92,slx2[3]/46,sl,der(2)t(2;4)(q14.2;p14),der(4)t(2;4)(q14.2;p14),add(4)(q31.1)[10]/46,sdl,add(13)(q34)[4]/92,sdl2x2[1]. These represent what is, to our knowledge, the first examples of abnormal karyotypes obtained from phosphaturic mesenchymal tumor of mixed connective tissue type. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Differentiation between benign and malignant palatal tumors using conventional MRI: a retrospective analysis of 130 cases.

    Science.gov (United States)

    Zheng, Yingyan; Xiao, Zebin; Zhang, Hua; She, Dejun; Lin, Xuehua; Lin, Yu; Cao, Dairong

    2018-04-01

    To evaluate the discriminative value of conventional magnetic resonance imaging between benign and malignant palatal tumors. Conventional magnetic resonance imaging features of 130 patients with palatal tumors confirmed by histopathologic examination were retrospectively reviewed. Clinical data and imaging findings were assessed between benign and malignant tumors and between benign and low-grade malignant salivary gland tumors. The variables that were significant in differentiating benign from malignant lesions were further identified using logistic regression analysis. Moreover, imaging features of each common palatal histologic entity were statistically analyzed with the rest of the tumors to define their typical imaging features. Older age, partially defined and ill-defined margins, and absence of a capsule were highly suggestive of malignant palatal tumors, especially ill-defined margins (β = 6.400). The precision in determining malignant palatal tumors achieved a sensitivity of 92.8% and a specificity of 85.6%. In addition, irregular shape, ill-defined margins, lack of a capsule, perineural spread, and invasion of surrounding structures were more often associated with low-grade malignant salivary gland tumors. Conventional magnetic resonance imaging is useful for differentiating benign from malignant palatal tumors as well as benign salivary gland tumors from low-grade salivary gland malignancies. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Reproducibility of tumor uptake heterogeneity characterization through textural feature analysis in 18F-FDG PET.

    Science.gov (United States)

    Tixier, Florent; Hatt, Mathieu; Le Rest, Catherine Cheze; Le Pogam, Adrien; Corcos, Laurent; Visvikis, Dimitris

    2012-05-01

    (18)F-FDG PET measurement of standardized uptake value (SUV) is increasingly used for monitoring therapy response and predicting outcome. Alternative parameters computed through textural analysis were recently proposed to quantify the heterogeneity of tracer uptake by tumors as a significant predictor of response. The primary objective of this study was to evaluate the reproducibility of these heterogeneity measurements. Double baseline (18)F-FDG PET scans were acquired within 4 d of each other for 16 patients before any treatment was considered. A Bland-Altman analysis was performed on 8 parameters based on histogram measurements and 17 parameters based on textural heterogeneity features after discretization with values between 8 and 128. The reproducibility of maximum and mean SUV was similar to that in previously reported studies, with a mean percentage difference of 4.7% ± 19.5% and 5.5% ± 21.2%, respectively. By comparison, better reproducibility was measured for some textural features describing local heterogeneity of tracer uptake, such as entropy and homogeneity, with a mean percentage difference of -2% ± 5.4% and 1.8% ± 11.5%, respectively. Several regional heterogeneity parameters such as variability in the intensity and size of regions of homogeneous activity distribution had reproducibility similar to that of SUV measurements, with 95% confidence intervals of -22.5% to 3.1% and -1.1% to 23.5%, respectively. These parameters were largely insensitive to the discretization range. Several parameters derived from textural analysis describing heterogeneity of tracer uptake by tumors on local and regional scales had reproducibility similar to or better than that of simple SUV measurements. These reproducibility results suggest that these (18)F-FDG PET-derived parameters, which have already been shown to have predictive and prognostic value in certain cancer models, may be used to monitor therapy response and predict patient outcome.

  1. Temporalis myofascial flap for primary cranial base reconstruction after tumor resection.

    Science.gov (United States)

    Eldaly, Ahmed; Magdy, Emad A; Nour, Yasser A; Gaafar, Alaa H

    2008-07-01

    To evaluate the use of the temporalis myofascial flap in primary cranial base reconstruction following surgical tumor ablation and to explain technical issues, potential complications, and donor site consequences along with their management. Retrospective case series. Tertiary referral center. Forty-one consecutive patients receiving primary temporalis myofascial flap reconstructions following cranial base tumor resections in a 4-year period. Flap survival, postoperative complications, and donor site morbidity. Patients included 37 males and 4 females ranging in age from 10 to 65 years. Two patients received preoperative and 18 postoperative radiation therapy. Patient follow-up ranged from 4 to 39 months. The whole temporalis muscle was used in 26 patients (63.4%) and only part of a coronally split muscle was used in 15 patients (36.6%). Nine patients had primary donor site reconstruction using a Medpor((R)) (Porex Surgical, Inc., Newnan, GA) temporal fossa implant; these had excellent aesthetic results. There were no cases of complete flap loss. Partial flap dehiscence was seen in six patients (14.6%); only two required surgical débridement. None of the patients developed cerebrospinal leaks or meningitis. One patient was left with complete paralysis of the temporal branch of the facial nerve. Three patients (all had received postoperative irradiation) developed permanent trismus. The temporalis myofascial flap was found to be an excellent reconstructive alternative for a wide variety of skull base defects following tumor ablation. It is a very reliable, versatile flap that is usually available in the operative field with relatively low donor site aesthetic and functional morbidity.

  2. Comparison of the efficacy and feasibility of en bloc transurethral resection of bladder tumor versus conventional transurethral resection of bladder tumor: A meta-analysis.

    Science.gov (United States)

    Wu, Yu-Peng; Lin, Ting-Ting; Chen, Shao-Hao; Xu, Ning; Wei, Yong; Huang, Jin-Bei; Sun, Xiong-Lin; Zheng, Qing-Shui; Xue, Xue-Yi; Li, Xiao-Dong

    2016-11-01

    The aim of this meta-analysis was to compare the feasibility of en bloc transurethral resection of bladder tumor (ETURBT) versus conventional transurethral resection of bladder tumor (CTURBT). Relevant trials were identified in a literature search of MEDLINE, EMBASE, Cochrane Library, Web of Science, and Google Scholar using appropriate search terms. All comparative studies reporting participant demographics, tumor characteristics, study characteristics, and outcome data were included. Seven trials with 886 participants were included, 438 underwent ETURBT and 448 underwent CTURBT. There was no significant difference in operation time between 2 groups (P = 0.38). The hospitalization time (HT) and catheterization time (CT) were shorter in ETURBT group (mean difference[MD] -1.22, 95% confidence interval [CI] -1.63 to -0.80, P analysis, and 24-month RR in CTURBT is higher than that in ETURBT in mitomycin intravesical irrigation group (P = 0.02). The first meta-analysis indicates that ETURBT might prove to be preferable alternative to CTURBT management of nonmuscle invasive bladder carcinoma. ETURBT is associated with shorter HT and CT, less complication rate, and lower recurrence-free rate. Moreover, it can provide high-qualified specimen for the pathologic diagnosis. Well designed randomized controlled trials are needed to make results comparable.

  3. A polymer-based magnetic resonance tracer for visualization of solid tumors by 13C spectroscopic imaging.

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    Yoshikazu Suzuki

    Full Text Available Morphological imaging precedes lesion-specific visualization in magnetic resonance imaging (MRI because of the superior ability of this technique to depict tissue morphology with excellent spatial and temporal resolutions. To achieve lesion-specific visualization of tumors by MRI, we investigated the availability of a novel polymer-based tracer. Although the 13C nucleus is a candidate for a detection nucleus because of its low background signal in the body, the low magnetic resonance sensitivity of the nucleus needs to be resolved before developing a 13C-based tracer. In order to overcome this problem, we enriched polyethylene glycol (PEG, a biocompatible polymer, with 13C atoms. 13C-PEG40,000 (13C-PEG with an average molecular weight of 40 kDa emitted a single 13C signal with a high signal-to-noise ratio due to its ability to maintain signal sharpness, as was confirmed by in vivo investigation, and displayed a chemical shift sufficiently distinct from that of endogenous fat. 13C-PEG40,000 intravenously injected into mice showed long retention in circulation, leading to its effective accumulation in tumors reflecting the well-known phenomenon that macromolecules accumulate in tumors because of leaky tumor capillaries. These properties of 13C-PEG40,000 allowed visualization of tumors in mice by 13C spectroscopic imaging. These findings suggest that a technique based on 13C-PEG is a promising strategy for tumor detection.

  4. Central nervous system tumors: Radiologic pathologic correlation and diagnostic approach

    Directory of Open Access Journals (Sweden)

    Ishita Pant

    2015-01-01

    Full Text Available Objective: This study was conducted to formulate location-wise radiologic diagnostic algorithms and assess their concordance with the final histopathological diagnosis so as to evaluate their utility in a rural setting where only basic facilities are available. Materials and Methods: A retrospective analysis to assess the concordance of radiology (primarily MRI with final histopathology report was done. Based on the most common incidence of tumor location and basic radiology findings, diagnostic algorithms were prepared. Results: For supratentorial intraaxial parenchymal location concordance was seen in all high-grade astrocytomas, low- and high-grade oligodendrogliomas, metastatic tumors, primitive neuroectodermal tumors, high-grade ependymomas, neuronal and mixed neuro-glial tumors and tumors of hematopoietic system. Lowest concordance was seen in low-grade astrocytomas. In the supratentorial intraaxial ventricular location, agreement was observed in choroid plexus tumors, ependymomas, low-grade astrocytomas and meningiomas; in the supratentorial extraaxial location, except for the lack of concordance in the only case of metastatic tumor, concordance was observed in meningeal tumors, tumors of the sellar region, tumors of cranial and paraspinal nerves; the infratentorial intraaxial parenchymal location showed agreement in low- as well as high-grade astrocytomas, metastatic tumors, high-grade ependymoma, embryonal tumors and hematopoietic tumors; in the infratentorial intraaxial ventricular location, except for the lack of concordance in one case of low-grade astrocytoma and two cases of medulloblastomas, agreement was observed in low- and high-grade ependymoma; infratentorial extraaxial tumors showed complete agreement in all tumors of cranial and paraspinal nerves, meningiomas, and hematopoietic tumors. Conclusion: A location-based approach to central nervous system (CNS tumors is helpful in establishing an appropriate differential diagnosis.

  5. Radiotherapy planning for glioblastoma based on a tumor growth model: improving target volume delineation

    Science.gov (United States)

    Unkelbach, Jan; Menze, Bjoern H.; Konukoglu, Ender; Dittmann, Florian; Le, Matthieu; Ayache, Nicholas; Shih, Helen A.

    2014-02-01

    Glioblastoma differ from many other tumors in the sense that they grow infiltratively into the brain tissue instead of forming a solid tumor mass with a defined boundary. Only the part of the tumor with high tumor cell density can be localized through imaging directly. In contrast, brain tissue infiltrated by tumor cells at low density appears normal on current imaging modalities. In current clinical practice, a uniform margin, typically two centimeters, is applied to account for microscopic spread of disease that is not directly assessable through imaging. The current treatment planning procedure can potentially be improved by accounting for the anisotropy of tumor growth, which arises from different factors: anatomical barriers such as the falx cerebri represent boundaries for migrating tumor cells. In addition, tumor cells primarily spread in white matter and infiltrate gray matter at lower rate. We investigate the use of a phenomenological tumor growth model for treatment planning. The model is based on the Fisher-Kolmogorov equation, which formalizes these growth characteristics and estimates the spatial distribution of tumor cells in normal appearing regions of the brain. The target volume for radiotherapy planning can be defined as an isoline of the simulated tumor cell density. This paper analyzes the model with respect to implications for target volume definition and identifies its most critical components. A retrospective study involving ten glioblastoma patients treated at our institution has been performed. To illustrate the main findings of the study, a detailed case study is presented for a glioblastoma located close to the falx. In this situation, the falx represents a boundary for migrating tumor cells, whereas the corpus callosum provides a route for the tumor to spread to the contralateral hemisphere. We further discuss the sensitivity of the model with respect to the input parameters. Correct segmentation of the brain appears to be the most

  6. Radiotherapy planning for glioblastoma based on a tumor growth model: improving target volume delineation

    International Nuclear Information System (INIS)

    Unkelbach, Jan; Dittmann, Florian; Le, Matthieu; Shih, Helen A; Menze, Bjoern H; Ayache, Nicholas; Konukoglu, Ender

    2014-01-01

    Glioblastoma differ from many other tumors in the sense that they grow infiltratively into the brain tissue instead of forming a solid tumor mass with a defined boundary. Only the part of the tumor with high tumor cell density can be localized through imaging directly. In contrast, brain tissue infiltrated by tumor cells at low density appears normal on current imaging modalities. In current clinical practice, a uniform margin, typically two centimeters, is applied to account for microscopic spread of disease that is not directly assessable through imaging. The current treatment planning procedure can potentially be improved by accounting for the anisotropy of tumor growth, which arises from different factors: anatomical barriers such as the falx cerebri represent boundaries for migrating tumor cells. In addition, tumor cells primarily spread in white matter and infiltrate gray matter at lower rate. We investigate the use of a phenomenological tumor growth model for treatment planning. The model is based on the Fisher–Kolmogorov equation, which formalizes these growth characteristics and estimates the spatial distribution of tumor cells in normal appearing regions of the brain. The target volume for radiotherapy planning can be defined as an isoline of the simulated tumor cell density. This paper analyzes the model with respect to implications for target volume definition and identifies its most critical components. A retrospective study involving ten glioblastoma patients treated at our institution has been performed. To illustrate the main findings of the study, a detailed case study is presented for a glioblastoma located close to the falx. In this situation, the falx represents a boundary for migrating tumor cells, whereas the corpus callosum provides a route for the tumor to spread to the contralateral hemisphere. We further discuss the sensitivity of the model with respect to the input parameters. Correct segmentation of the brain appears to be the most

  7. Tumor stem cells: A new approach for tumor therapy (Review)

    Science.gov (United States)

    MENG, MIN; ZHAO, XIN-HAN; NING, QIAN; HOU, LEI; XIN, GUO-HONG; LIU, LI-FENG

    2012-01-01

    Recent studies have demonstrated the existence of a minority of tumor cells possessing the stem cell properties of self-renewal and differentiation in leukemia and several solid tumors. However, these cells do not possess the normal regulatory mechanisms of stem cells. Following transplantation, they are capable of initiating tumorigenesis and are therefore known as ‘tumor stem cells’. Cellular origin analysis of tumor stem cells has resulted in three hypotheses: Embryonal rest hypothesis, anaplasia and maturation arrest. Several signaling pathways which are involved in carcinogenesis, including Wnt/β-catenin, Notch and Oct-4 signaling pathways are crucial in normal stem cell self-renewal decisions, suggesting that breakdown in the regulation of self-renewal may be a key event in the development of tumors. Thus, tumors can be regarded as an abnormal organ in which stem cells have escaped from the normal constraints on self-renewal, thus, leading to abnormally differentiated tumor cells that lose the ability to form tumors. This new model for maligancies has significance for clinical research and treatment. PMID:22844351

  8. Local control of extra-abdominal desmoid tumors: systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Michelle A. Ghert

    2013-02-01

    Full Text Available The local control of desmoid tumors constitutes a continuing treatment dilemma due to its high recurrence rates. The purpose of this systematic review was to critically examine the current treatment of these rare tumors and to specifically evaluate the local failure and response rates of surgery, radiation and systemic therapy. We comprehensively searched the literature for relevant studies across Cinahl, Embase, Medline and the Cochrane databases. Articles were categorized as surgery, radiation, surgery + radiation and systemic therapy (including cytotoxic and non cytotoxic. Methodological quality of included studies was assessed using the Newcastle-Ottawa Scale. Pooled odd ratios (OR for comparative studies and weighted proportions with 95% confidence intervals (CI are reported. Thirty-five articles were included in the final analysis. Weighted mean local failure rates were 22% [95% CI (16-28%], 35% [95% CI (26-44%] and 28% [95% CI (18-39%] for radiation alone, surgery alone and surgery + radiation respectively. In the analysis of comparative studies, surgery and radiation in combination had lower local failure rates than radiation alone [OR 0.7 (0.4, 1.2] and surgery alone [OR 0.7 (0.4, 1.0]. Weighted mean stable disease rates were 91% [95% CI (85-96%] and 52% [95% CI (38-65%] for non cytotoxic and cytotoxic chemotherapy respectively. The current evidence suggests that surgery alone has a consistently high rate of local recurrence in managing extra-abdominal desmoid tumors. Radiation therapy in combination with surgery improves local control rates. However, the limited data on systemic therapy for this rare tumor suggests the benefit of using both cytotoxic and non cytotoxic chemotherapy to achieve stable disease.

  9. Mobile phone use and risk of intracranial tumors: a consistency analysis.

    Science.gov (United States)

    Lagorio, Susanna; Röösli, Martin

    2014-02-01

    A meta-analysis of studies on intracranial tumors and mobile phone use published by the end of 2012 was performed to evaluate the overall consistency of findings, assess the sensitivity of results to changes in the dataset, and try to detect the sources of between-study heterogeneity. Twenty-nine papers met our inclusion criteria. These papers reported on 47 eligible studies (17 on glioma, 15 on meningioma, 15 on acoustic neuroma), consisting of either primary investigations or pooled analyses. Five combinations of non-overlapping studies per outcome were identified. The combined relative risks (cRRs) in long-term mobile phone users (≥10 years) ranged between 0.98 (0.75-1.28) and 1.11 (0.86-1.44) for meningioma, with little heterogeneity across studies. High heterogeneity was detected across estimates of glioma and acoustic neuroma risk in long term users, with cRRs ranging between 1.19 (95% CI 0.86-1.64) and 1.40 (0.96-2.04), and from 1.14 (0.65-1.99) to 1.33 (0.65-2.73), respectively. A meta-regression of primary studies showed that the methodological differences embedded in the variable "study-group" explained most of the overall heterogeneity in results. Summary risk estimates based on heterogeneous findings should not be over-interpreted. Overall, the results of our study detract from the hypothesis that mobile phone use affects the occurrence of intracranial tumors. However, reproducibility (or lack of) is just one clue in the critical appraisal of epidemiological evidence. Based on other considerations, such as the limited knowledge currently available on risk beyond 15 years from first exposure, or following mobile phone use started in childhood, the pursuance of epidemiological surveillance is warranted. © 2013 Wiley Periodicals, Inc.

  10. Single-cell analysis of targeted transcriptome predicts drug sensitivity of single cells within human myeloma tumors.

    Science.gov (United States)

    Mitra, A K; Mukherjee, U K; Harding, T; Jang, J S; Stessman, H; Li, Y; Abyzov, A; Jen, J; Kumar, S; Rajkumar, V; Van Ness, B

    2016-05-01

    Multiple myeloma (MM) is characterized by significant genetic diversity at subclonal levels that have a defining role in the heterogeneity of tumor progression, clinical aggressiveness and drug sensitivity. Although genome profiling studies have demonstrated heterogeneity in subclonal architecture that may ultimately lead to relapse, a gene expression-based prediction program that can identify, distinguish and quantify drug response in sub-populations within a bulk population of myeloma cells is lacking. In this study, we performed targeted transcriptome analysis on 528 pre-treatment single cells from 11 myeloma cell lines and 418 single cells from 8 drug-naïve MM patients, followed by intensive bioinformatics and statistical analysis for prediction of proteasome inhibitor sensitivity in individual cells. Using our previously reported drug response gene expression profile signature at the single-cell level, we developed an R Statistical analysis package available at https://github.com/bvnlabSCATTome, SCATTome (single-cell analysis of targeted transcriptome), that restructures the data obtained from Fluidigm single-cell quantitative real-time-PCR analysis run, filters missing data, performs scaling of filtered data, builds classification models and predicts drug response of individual cells based on targeted transcriptome using an assortment of machine learning methods. Application of SCATT should contribute to clinically relevant analysis of intratumor heterogeneity, and better inform drug choices based on subclonal cellular responses.

  11. A curcumin-based TPA four-branched copper(II) complex probe for in vivo early tumor detection

    Energy Technology Data Exchange (ETDEWEB)

    Pi, Zongxin [Department of Chemical and Chemical Engineering, Hefei Normal University, Hefei 230001 (China); Wang, Jiafeng; Jiang, Bo [Department of Pharmacy, Anhui University of Chinese Medicine, Hefei 230038 (China); Cheng, Gang [Department of Chemical and Chemical Engineering, Hefei Normal University, Hefei 230001 (China); Zhou, Shuangsheng, E-mail: zshuangsheng@126.com [Department of Pharmacy, Anhui University of Chinese Medicine, Hefei 230038 (China); Center of Modern Experimental Technology, Anhui University, Hefei 230038 (China)

    2015-01-01

    A multibranched Cu(II) complex CuL{sub 2} curcumin-based was synthesized and characterized by single-crystal X-ray diffraction analysis. The photophysical properties of the complex have been investigated both experimentally and theoretically. The results show that the target complex exhibits higher quantum yield and larger two-photon absorption (TPA) cross-section in the near infrared (NIR) region compared with its free ligand. The cell imaging studies in vitro and in vivo reveal that the complex shows good photostability and excellent tumor targeting capability to tested cancerous cells, which can be potentially used for early tumor detection. - Graphical abstract: A multibranched Cu(II) complex was prepared from curcumin. The photophysical properties of the obtained complex have been investigated. The results exhibit that the complex has high capability to test cancerous cells and can distinguish between the cancerous and noncancerous cells, which should be potentially used for early tumor detection. - Highlights: • A novel multi-branched copper complex was synthesized. • The obtained compounds exhibited obvious TPA in high polar solvents. • The complex is a low toxicity at low-micromolar concentrations. • The complex exhibits larger TPA cross-section and brighter TPF imaging. • The complex has excellent targeting capability to tested cancerous cells.

  12. The force pyramid: a spatial analysis of force application during virtual reality brain tumor resection.

    Science.gov (United States)

    Azarnoush, Hamed; Siar, Samaneh; Sawaya, Robin; Zhrani, Gmaan Al; Winkler-Schwartz, Alexander; Alotaibi, Fahad Eid; Bugdadi, Abdulgadir; Bajunaid, Khalid; Marwa, Ibrahim; Sabbagh, Abdulrahman Jafar; Del Maestro, Rolando F

    2017-07-01

    OBJECTIVE Virtual reality simulators allow development of novel methods to analyze neurosurgical performance. The concept of a force pyramid is introduced as a Tier 3 metric with the ability to provide visual and spatial analysis of 3D force application by any instrument used during simulated tumor resection. This study was designed to answer 3 questions: 1) Do study groups have distinct force pyramids? 2) Do handedness and ergonomics influence force pyramid structure? 3) Are force pyramids dependent on the visual and haptic characteristics of simulated tumors? METHODS Using a virtual reality simulator, NeuroVR (formerly NeuroTouch), ultrasonic aspirator force application was continually assessed during resection of simulated brain tumors by neurosurgeons, residents, and medical students. The participants performed simulated resections of 18 simulated brain tumors with different visual and haptic characteristics. The raw data, namely, coordinates of the instrument tip as well as contact force values, were collected by the simulator. To provide a visual and qualitative spatial analysis of forces, the authors created a graph, called a force pyramid, representing force sum along the z-coordinate for different xy coordinates of the tool tip. RESULTS Sixteen neurosurgeons, 15 residents, and 84 medical students participated in the study. Neurosurgeon, resident and medical student groups displayed easily distinguishable 3D "force pyramid fingerprints." Neurosurgeons had the lowest force pyramids, indicating application of the lowest forces, followed by resident and medical student groups. Handedness, ergonomics, and visual and haptic tumor characteristics resulted in distinct well-defined 3D force pyramid patterns. CONCLUSIONS Force pyramid fingerprints provide 3D spatial assessment displays of instrument force application during simulated tumor resection. Neurosurgeon force utilization and ergonomic data form a basis for understanding and modulating resident force

  13. [Maxillary swing approach in the management of tumors in the central and lateral cranial base].

    Science.gov (United States)

    Liao, Hua; Hua, Qing-quan; Wu, Zhan-yuan

    2006-04-01

    A retrospective review of seventeen patients who were operated through the maxillary swing approach was carried out to assess the efficacy of this approach in the management of tumors of the central and lateral cranial base. From May 2000 to January 2005, 17 patients with primary or recurrent neoplasms involving the central cranial or lateral base underwent surgical resection via maxillary swing approach. Ten patients were male, and other seven patients were female, and age range was 7 to 58 years, with a mean age of 42. 6 years. Eight patients had tumors originally involving lateral cranial base, and nine patients had tumors originated from central cranial base. The pathology spectrum was very wide. Among them, five suffered from chordoma, two had rhabdomyosarcoma, two had squamous cell carcinoma, one had malignant fibrous histiocytoma, one had malignant melanoma, one had esthesioneuroblastoma, one had invaded hypophysoma, two had schwannoma, one had pleomorphic adenoma, and one had angiofibroma. Three patients had received previous surgery, two patients had previous radiation therapy and nine patients received postoperative radiotherapy. Sixteen of all seventeen patients had oncologically complete resection, one had near-total resection. This group patients was followed up from 10 to 60 months, with a median follow-up time of 28 months. Two patients died 14 and 26 months after surgery respectively, as a result of local recurrence and metastasis. One patient defaulted follow-up at 12 months after operation, and the other 14 patients were alive at the time of analysis. Of the 12 malignant tumors, the 1-and 2-year survival rate were 91.67% and 72.92%, respectively. The facial wounds of all patients healed primarily, and there were no necrosis of the maxilla, damage of the temporal branch of the facial nerve, lower-lid ectropion, and facial deformity. Epiphora and facial hypoesthesia were detected in all patients. Four patients (23.5%) developed palatal fistula, ten

  14. Prediction of Metastasis and Recurrence in Colorectal Cancer Based on Gene Expression Analysis: Ready for the Clinic?

    Energy Technology Data Exchange (ETDEWEB)

    Shibayama, Masaki [Sysmex Corporation, Central Research Laboratories, Kobe 651-2271 (Japan); Maak, Matthias; Nitsche, Ulrich [Chirurgische Klinik, Klinikum Rechts der Isar der TUM, München 81657 (Germany); Gotoh, Kengo [Sysmex Corporation, Central Research Laboratories, Kobe 651-2271 (Japan); Rosenberg, Robert; Janssen, Klaus-Peter, E-mail: klaus-peter.janssen@lrz.tum.de [Chirurgische Klinik, Klinikum Rechts der Isar der TUM, München 81657 (Germany)

    2011-07-07

    Cancers of the colon and rectum, which rank among the most frequent human tumors, are currently treated by surgical resection in locally restricted tumor stages. However, disease recurrence and formation of local and distant metastasis frequently occur even in cases with successful curative resection of the primary tumor (R0). Recent technological advances in molecular diagnostic analysis have led to a wealth of knowledge about the changes in gene transcription in all stages of colorectal tumors. Differential gene expression, or transcriptome analysis, has been proposed by many groups to predict disease recurrence, clinical outcome, and also response to therapy, in addition to the well-established clinico-pathological factors. However, the clinical usability of gene expression profiling as a reliable and robust prognostic tool that allows evidence-based clinical decisions is currently under debate. In this review, we will discuss the most recent data on the prognostic significance and potential clinical application of genome wide expression analysis in colorectal cancer.

  15. Prediction of Metastasis and Recurrence in Colorectal Cancer Based on Gene Expression Analysis: Ready for the Clinic?

    International Nuclear Information System (INIS)

    Shibayama, Masaki; Maak, Matthias; Nitsche, Ulrich; Gotoh, Kengo; Rosenberg, Robert; Janssen, Klaus-Peter

    2011-01-01

    Cancers of the colon and rectum, which rank among the most frequent human tumors, are currently treated by surgical resection in locally restricted tumor stages. However, disease recurrence and formation of local and distant metastasis frequently occur even in cases with successful curative resection of the primary tumor (R0). Recent technological advances in molecular diagnostic analysis have led to a wealth of knowledge about the changes in gene transcription in all stages of colorectal tumors. Differential gene expression, or transcriptome analysis, has been proposed by many groups to predict disease recurrence, clinical outcome, and also response to therapy, in addition to the well-established clinico-pathological factors. However, the clinical usability of gene expression profiling as a reliable and robust prognostic tool that allows evidence-based clinical decisions is currently under debate. In this review, we will discuss the most recent data on the prognostic significance and potential clinical application of genome wide expression analysis in colorectal cancer

  16. Comparative analysis of tumor spheroid generation techniques for differential in vitro drug toxicity

    Science.gov (United States)

    Raghavan, Shreya; Rowley, Katelyn R.; Mehta, Geeta

    2016-01-01

    Multicellular tumor spheroids are powerful in vitro models to perform preclinical chemosensitivity assays. We compare different methodologies to generate tumor spheroids in terms of resultant spheroid morphology, cellular arrangement and chemosensitivity. We used two cancer cell lines (MCF7 and OVCAR8) to generate spheroids using i) hanging drop array plates; ii) liquid overlay on ultra-low attachment plates; iii) liquid overlay on ultra-low attachment plates with rotating mixing (nutator plates). Analysis of spheroid morphometry indicated that cellular compaction was increased in spheroids generated on nutator and hanging drop array plates. Collagen staining also indicated higher compaction and remodeling in tumor spheroids on nutator and hanging drop arrays compared to conventional liquid overlay. Consequently, spheroids generated on nutator or hanging drop plates had increased chemoresistance to cisplatin treatment (20-60% viability) compared to spheroids on ultra low attachment plates (10-20% viability). Lastly, we used a mathematical model to demonstrate minimal changes in oxygen and cisplatin diffusion within experimentally generated spheroids. Our results demonstrate that in vitro methods of tumor spheroid generation result in varied cellular arrangement and chemosensitivity. PMID:26918944

  17. Assessment of basal-like breast cancer by circulating tumor DNA analysis.

    Science.gov (United States)

    Wei, Wei; Zhang, Xianyu; Sun, Shanshan; Xia, Bingshu; Liang, Xiaoshuan; Cui, Yan; Gao, Song; Pang, Da

    2018-05-01

    Standardized methods for the detection and assessment of circulating tumor DNA (ctDNA) in breast cancer are not sufficient. In the present study, the method and the potential application of ctDNA in the diagnosis of breast cancer were explored. DNA was extracted from the tumor tissues, plasma and peripheral blood cells of 11 patients with early-stage invasive breast cancer. Primers were designed against the exons of phosphatidylinositol-4,5-biphosphate 3-kinase catalytic subunit α, p53, epidermal growth factor receptor, Akt and phosphatase and tensin homolog. The amplicon-based method for whole-exon sequencing was performed. The associations between the ctDNA mutant frequency with the tumor DNA mutant frequency, and the ctDNA concentration with clinical data were analyzed. A linear association was identified between the concentration of ctDNA and the tumor volume for the 3 patients with basal-like breast cancer, and not in other subtypes. The mutation frequency differed the least between ctDNA and tissue DNA in basal-like breast cancer. ctDNA retained the constituent ratio of gene mutations identified in the corresponding tumor tissue. The ctDNA detection rate depended to a certain extent on the mutation frequency in tumor tissue; for example, a mutant locus with a mutation frequency of >30% in tissues presented a detection rate of >40% in plasma samples, whereas a locus with a mutation frequency of <10% in tissue was associated with a detection rate of ≤1% in the plasma. Therefore, ctDNA may reflect the mutations observed in cancer. Compared with other subtypes, ctDNA may be a more sensitive biomarker for the assessment of mutation and cancer burden in basal-like breast cancer relative to other subtypes.

  18. Development of a new rapid isolation device for circulating tumor cells (CTCs using 3D palladium filter and its application for genetic analysis.

    Directory of Open Access Journals (Sweden)

    Akiko Yusa

    Full Text Available Circulating tumor cells (CTCs in the blood of patients with epithelial malignancies provide a promising and minimally invasive source for early detection of metastasis, monitoring of therapeutic effects and basic research addressing the mechanism of metastasis. In this study, we developed a new filtration-based, sensitive CTC isolation device. This device consists of a 3-dimensional (3D palladium (Pd filter with an 8 µm-sized pore in the lower layer and a 30 µm-sized pocket in the upper layer to trap CTCs on a filter micro-fabricated by precise lithography plus electroforming process. This is a simple pump-less device driven by gravity flow and can enrich CTCs from whole blood within 20 min. After on-device staining of CTCs for 30 min, the filter cassette was removed from the device, fixed in a cassette holder and set up on the upright fluorescence microscope. Enumeration and isolation of CTCs for subsequent genetic analysis from the beginning were completed within 1.5 hr and 2 hr, respectively. Cell spike experiments demonstrated that the recovery rate of tumor cells from blood by this Pd filter device was more than 85%. Single living tumor cells were efficiently isolated from these spiked tumor cells by a micromanipulator, and KRAS mutation, HER2 gene amplification and overexpression, for example, were successfully detected from such isolated single tumor cells. Sequential analysis of blood from mice bearing metastasis revealed that CTC increased with progression of metastasis. Furthermore, a significant increase in the number of CTCs from the blood of patients with metastatic breast cancer was observed compared with patients without metastasis and healthy volunteers. These results suggest that this new 3D Pd filter-based device would be a useful tool for the rapid, cost effective and sensitive detection, enumeration, isolation and genetic analysis of CTCs from peripheral blood in both preclinical and clinical settings.

  19. Tumor spatial heterogeneity in myxoid-containing soft tissue using texture analysis of diffusion-weighted MRI.

    Directory of Open Access Journals (Sweden)

    Hyun Su Kim

    Full Text Available The objective of this study was to examine the tumor spatial heterogeneity in myxoid-containing soft-tissue tumors (STTs using texture analysis of diffusion-weighted imaging (DWI. A total of 40 patients with myxoid-containing STTs (23 benign and 17 malignant were included in this study. The region of interest (ROI was manually drawn on the apparent diffusion coefficient (ADC map. For texture analysis, the global (mean, standard deviation, skewness, and kurtosis, regional (intensity variability and size-zone variability, and local features (energy, entropy, correlation, contrast, homogeneity, variance, and maximum probability were extracted from the ADC map. Student's t-test was used to test the difference between group means. Analysis of covariance (ANCOVA was performed with adjustments for age, sex, and tumor volume. The receiver operating characteristic (ROC analysis was performed to compare diagnostic performances. Malignant myxoid-containing STTs had significantly higher kurtosis (P = 0.040, energy (P = 0.034, correlation (P<0.001, and homogeneity (P = 0.003, but significantly lower contrast (P<0.001 and variance (P = 0.001 compared with benign myxoid-containing STTs. Contrast showed the highest area under the curve (AUC = 0.923, P<0.001, sensitivity (94.12%, and specificity (86.96%. Our results reveal the potential utility of texture analysis of ADC maps for differentiating benign and malignant myxoid-containing STTs.

  20. Dose painting based on tumor uptake of Cu-ATSM and FDG

    DEFF Research Database (Denmark)

    Clausen, Malene Martini; Hansen, Anders Elias; Lundemann, Michael

    2014-01-01

    Background: Hypoxia and increased glycolytic activity of tumors are associated with poor prognosis. The of this study was to investigate differences in radiotherapy (RT) dose painting based on the uptake of 2-deoxy-2-[18 F]- fluorodeoxyglucose (FDG) and the proposed hypoxia tracer, copper(II)diacetyl-bis...

  1. A resampling-based meta-analysis for detection of differential gene expression in breast cancer

    International Nuclear Information System (INIS)

    Gur-Dedeoglu, Bala; Konu, Ozlen; Kir, Serkan; Ozturk, Ahmet Rasit; Bozkurt, Betul; Ergul, Gulusan; Yulug, Isik G

    2008-01-01

    Accuracy in the diagnosis of breast cancer and classification of cancer subtypes has improved over the years with the development of well-established immunohistopathological criteria. More recently, diagnostic gene-sets at the mRNA expression level have been tested as better predictors of disease state. However, breast cancer is heterogeneous in nature; thus extraction of differentially expressed gene-sets that stably distinguish normal tissue from various pathologies poses challenges. Meta-analysis of high-throughput expression data using a collection of statistical methodologies leads to the identification of robust tumor gene expression signatures. A resampling-based meta-analysis strategy, which involves the use of resampling and application of distribution statistics in combination to assess the degree of significance in differential expression between sample classes, was developed. Two independent microarray datasets that contain normal breast, invasive ductal carcinoma (IDC), and invasive lobular carcinoma (ILC) samples were used for the meta-analysis. Expression of the genes, selected from the gene list for classification of normal breast samples and breast tumors encompassing both the ILC and IDC subtypes were tested on 10 independent primary IDC samples and matched non-tumor controls by real-time qRT-PCR. Other existing breast cancer microarray datasets were used in support of the resampling-based meta-analysis. The two independent microarray studies were found to be comparable, although differing in their experimental methodologies (Pearson correlation coefficient, R = 0.9389 and R = 0.8465 for ductal and lobular samples, respectively). The resampling-based meta-analysis has led to the identification of a highly stable set of genes for classification of normal breast samples and breast tumors encompassing both the ILC and IDC subtypes. The expression results of the selected genes obtained through real-time qRT-PCR supported the meta-analysis results. The

  2. A resampling-based meta-analysis for detection of differential gene expression in breast cancer

    Directory of Open Access Journals (Sweden)

    Ergul Gulusan

    2008-12-01

    Full Text Available Abstract Background Accuracy in the diagnosis of breast cancer and classification of cancer subtypes has improved over the years with the development of well-established immunohistopathological criteria. More recently, diagnostic gene-sets at the mRNA expression level have been tested as better predictors of disease state. However, breast cancer is heterogeneous in nature; thus extraction of differentially expressed gene-sets that stably distinguish normal tissue from various pathologies poses challenges. Meta-analysis of high-throughput expression data using a collection of statistical methodologies leads to the identification of robust tumor gene expression signatures. Methods A resampling-based meta-analysis strategy, which involves the use of resampling and application of distribution statistics in combination to assess the degree of significance in differential expression between sample classes, was developed. Two independent microarray datasets that contain normal breast, invasive ductal carcinoma (IDC, and invasive lobular carcinoma (ILC samples were used for the meta-analysis. Expression of the genes, selected from the gene list for classification of normal breast samples and breast tumors encompassing both the ILC and IDC subtypes were tested on 10 independent primary IDC samples and matched non-tumor controls by real-time qRT-PCR. Other existing breast cancer microarray datasets were used in support of the resampling-based meta-analysis. Results The two independent microarray studies were found to be comparable, although differing in their experimental methodologies (Pearson correlation coefficient, R = 0.9389 and R = 0.8465 for ductal and lobular samples, respectively. The resampling-based meta-analysis has led to the identification of a highly stable set of genes for classification of normal breast samples and breast tumors encompassing both the ILC and IDC subtypes. The expression results of the selected genes obtained through real

  3. Application of Image Processing Algorithms for Brain Tumor Analysis in 2D and 3D Leading to Tumor’s Positioning in Skull: Overview

    Directory of Open Access Journals (Sweden)

    AYESHA AMIR SIDDIQI

    2017-01-01

    Full Text Available Segmentation of brain tumors has been found challenging throughout in the field of image processing. Different algorithms have been applied to the segmentation of solid or cystic tumors individually but little work has been done for solid cum cystic tumor. The papers reviewed in this article only deal with the case study of patients suffering from solid cum cystic brain tumor as this type of tumor is rarely found for the purpose of research. The research work conducted so far on this topic has been reviewed. The study begins with 2D (Two Dimensional segmentation of tumor using MATLAB. It is then extended to study of slices of tumor and its volume calculation using open source software named 3D Slicer which represents the tumor in 3D. This software can intake the 2D slices and process them to give a combined 3D view. Various techniques are available in the software. According to the particular requirement an appropriate algorithm can be chosen. This paper gives a promising hierarchy for volume calculation of tumor and the three dimensional view. Further we can also find the position of tumor in the skull using the same software. This piece of work is a valuable guideline for the researchers interested in segmentation and three dimensional representations of different areas of human body. The models extracted out using the given algorithms can also be treated for matching and comparison of any future research. This will also aid surgeons and physicians in efficient analysis and reporting techniques.

  4. SU-F-R-13: Decoding 18F-FDG Uptake Heterogeneity for Primary and Lymphoma Tumors by Using Texture Analysis in PET Images

    Energy Technology Data Exchange (ETDEWEB)

    Ma, C; Yin, Y [Shandong Cancer Hospital and Institute, Jinan, Shandong (China)

    2016-06-15

    Purpose: To explore 18F-FDG uptake heterogeneity of primary tumor and lymphoma tumor by texture features of PET image and quantify the heterogeneity difference between primary tumor and lymphoma tumor. Methods: 18 patients with primary tumor and lymphoma tumor in lung cancer were enrolled. All patients underwent whole-body 18F-FDG PET/CT scans before treatment. Texture features, based on Gray-level Co-occurrence Matrix, second and high order matrices are extracted from code using MATLAB software to quantify 18F-FDG uptake heterogeneity. The relationships of volume between energy, entropy, correlation, homogeneity and contrast were analyzed. Results: For different cases, tumor heterogeneity was not the same. Texture parameters (contrast, entropy, and correlation) of lymphoma were lower than primary tumor. On the contrast, the texture parameters (energy, homogeneity and inverse different moment) of lymphoma were higher than primary tumor. Significantly, correlations were observed between volume and energy (primary, r=−0.194, p=0.441; lymphoma, r=−0.339, p=0.582), homogeneity (primary, r=−0.146, p=0.382; lymphoma, r=−0.193, p=0.44), inverse difference moment (primary, r=−0.14, p=0.374; lymphoma, r=−0.172, p=0.414) and a positive correlation between volume and entropy (primary, r=0.233, p=0.483; lymphoma, r=0.462, p=0.680), contrast (primary, r=0.159, p=0.399; lymphoma, r=0.341, p=0.584), correlation (primary, r=0.027, p=0.165; lymphoma, r=0.046, p=0.215). For the same patient, energy for primary and lymphoma tumor is equal. The volume of lymphoma is smaller than primary tumor, but the homogeneity were higher than primary tumor. Conclusion: This study showed that there were effective heterogeneity differences between primary and lymphoma tumor by FDG-PET image texture analysis.

  5. SU-F-R-13: Decoding 18F-FDG Uptake Heterogeneity for Primary and Lymphoma Tumors by Using Texture Analysis in PET Images

    International Nuclear Information System (INIS)

    Ma, C; Yin, Y

    2016-01-01

    Purpose: To explore 18F-FDG uptake heterogeneity of primary tumor and lymphoma tumor by texture features of PET image and quantify the heterogeneity difference between primary tumor and lymphoma tumor. Methods: 18 patients with primary tumor and lymphoma tumor in lung cancer were enrolled. All patients underwent whole-body 18F-FDG PET/CT scans before treatment. Texture features, based on Gray-level Co-occurrence Matrix, second and high order matrices are extracted from code using MATLAB software to quantify 18F-FDG uptake heterogeneity. The relationships of volume between energy, entropy, correlation, homogeneity and contrast were analyzed. Results: For different cases, tumor heterogeneity was not the same. Texture parameters (contrast, entropy, and correlation) of lymphoma were lower than primary tumor. On the contrast, the texture parameters (energy, homogeneity and inverse different moment) of lymphoma were higher than primary tumor. Significantly, correlations were observed between volume and energy (primary, r=−0.194, p=0.441; lymphoma, r=−0.339, p=0.582), homogeneity (primary, r=−0.146, p=0.382; lymphoma, r=−0.193, p=0.44), inverse difference moment (primary, r=−0.14, p=0.374; lymphoma, r=−0.172, p=0.414) and a positive correlation between volume and entropy (primary, r=0.233, p=0.483; lymphoma, r=0.462, p=0.680), contrast (primary, r=0.159, p=0.399; lymphoma, r=0.341, p=0.584), correlation (primary, r=0.027, p=0.165; lymphoma, r=0.046, p=0.215). For the same patient, energy for primary and lymphoma tumor is equal. The volume of lymphoma is smaller than primary tumor, but the homogeneity were higher than primary tumor. Conclusion: This study showed that there were effective heterogeneity differences between primary and lymphoma tumor by FDG-PET image texture analysis.

  6. Exploiting tumor shrinkage through temporal optimization of radiotherapy

    International Nuclear Information System (INIS)

    Unkelbach, Jan; Craft, David; Hong, Theodore; Papp, Dávid; Wolfgang, John; Bortfeld, Thomas; Ramakrishnan, Jagdish; Salari, Ehsan

    2014-01-01

    In multi-stage radiotherapy, a patient is treated in several stages separated by weeks or months. This regimen has been motivated mostly by radiobiological considerations, but also provides an approach to reduce normal tissue dose by exploiting tumor shrinkage. The paper considers the optimal design of multi-stage treatments, motivated by the clinical management of large liver tumors for which normal liver dose constraints prohibit the administration of an ablative radiation dose in a single treatment. We introduce a dynamic tumor model that incorporates three factors: radiation induced cell kill, tumor shrinkage, and tumor cell repopulation. The design of multi-stage radiotherapy is formulated as a mathematical optimization problem in which the total dose to the normal tissue is minimized, subject to delivering the prescribed dose to the tumor. Based on the model, we gain insight into the optimal administration of radiation over time, i.e. the optimal treatment gaps and dose levels. We analyze treatments consisting of two stages in detail. The analysis confirms the intuition that the second stage should be delivered just before the tumor size reaches a minimum and repopulation overcompensates shrinking. Furthermore, it was found that, for a large range of model parameters, approximately one-third of the dose should be delivered in the first stage. The projected benefit of multi-stage treatments in terms of normal tissue sparing depends on model assumptions. However, the model predicts large dose reductions by more than a factor of 2 for plausible model parameters. The analysis of the tumor model suggests that substantial reduction in normal tissue dose can be achieved by exploiting tumor shrinkage via an optimal design of multi-stage treatments. This suggests taking a fresh look at multi-stage radiotherapy for selected disease sites where substantial tumor regression translates into reduced target volumes. (paper)

  7. Quantification of tumor extension in prostate biopsies: importance in the identification of confined tumors

    Directory of Open Access Journals (Sweden)

    Leite Kátia R.M.

    2003-01-01

    Full Text Available OBJECTIVE: To assess the importance of quantifying the adenocarcinoma in prostate biopsies when determining the tumor's final stage in patients who undergo radical prostatectomy. To identify the best methodology for obtaining such data. PATIENTS AND METHODS: Prostate biopsies from 132 patients were examined, with determination of Gleason histological grade and tumor volume in number of involved fragments, tumor extent of the fragment mostly affected by the tumor and the total percentage of tumor in the specimen. Theses parameters were statistically correlated with the neoplasia's final stage following the evaluation of radical prostatectomy specimens. RESULTS: An average of 12 and a median of 14 biopsy fragments were evaluated per patient. In the univariate analysis the Gleason histological grade, the largest tumor extent in one fragment and the total percentage of tumor in the specimen were correlated with tumor stage of the surgical specimen. In the multivariate analysis, the Gleason histological grade and the total percentage of tumor were strongly correlated with the neoplasia's final stage. The risk of the tumor not being confined was 3 for Gleason 7 tumors and 10.6 for Gleason 8 tumors or above. In cases where the tumor involved more than 60% of the specimen, the risk of non-confined disease was 4.4 times. Among 19 patients with unfavorable histological parameters, Gleason > 7 and extension greater than 60% the tumor final stage was pT3 in 95%. CONCLUSION: When associated to the Gleason histological grade, tumor quantification in prostate biopsies is an important factor for determining organ-confined disease, and among the methods, total percentage of tumor is the most informative one. Such data should be included in the pathological report and must be incorporated in future nomograms.

  8. Perspective on Cancer Therapeutics Utilizing Analysis of Circulating Tumor Cells

    Directory of Open Access Journals (Sweden)

    Keun-Yeong Jeong

    2018-04-01

    Full Text Available Various methods are available for cancer screening, and the methods are performed depending on the origin site of cancer. Among these methods, biopsy followed by medical imaging is the most common. After cancer progression is determined, an optimal treatment—such as surgery, chemotherapy, and/or radiation therapy—is selected. A new assay has been developed that detects circulating tumor cells (CTCs. Tracking changes in CTCs may reveal important tumoral sensitivity information or resistance patterns to specific regimens and prompt changes in therapy on a personalized basis. Characterization of CTCs at the DNA, RNA, and protein levels is important for gaining insight for clinical applications. A small number of CTCs can be analyzed to obtain genome information such as the progression of cancer including metastasis, even in a single cluster. Although many clinical studies, particularly CTC enumeration and detection of specific oncogene expression, have increased the success rate of diagnosis and predicting prognosis, there is no consensus regarding the technical approaches and various aspects of the methodology, making it difficult to standardize optimal methods for CTC analysis. However, ongoing technological advances are currently being achieved and large-scale clinical studies are being conducted. Applying CTC analysis in the clinic would be very useful for advancing diagnosis, prognosis prediction, and therapeutics.

  9. A Whole-Tumor Histogram Analysis of Apparent Diffusion Coefficient Maps for Differentiating Thymic Carcinoma from Lymphoma.

    Science.gov (United States)

    Zhang, Wei; Zhou, Yue; Xu, Xiao-Quan; Kong, Ling-Yan; Xu, Hai; Yu, Tong-Fu; Shi, Hai-Bin; Feng, Qing

    2018-01-01

    To assess the performance of a whole-tumor histogram analysis of apparent diffusion coefficient (ADC) maps in differentiating thymic carcinoma from lymphoma, and compare it with that of a commonly used hot-spot region-of-interest (ROI)-based ADC measurement. Diffusion weighted imaging data of 15 patients with thymic carcinoma and 13 patients with lymphoma were retrospectively collected and processed with a mono-exponential model. ADC measurements were performed by using a histogram-based and hot-spot-ROI-based approach. In the histogram-based approach, the following parameters were generated: mean ADC (ADC mean ), median ADC (ADC median ), 10th and 90th percentile of ADC (ADC 10 and ADC 90 ), kurtosis, and skewness. The difference in ADCs between thymic carcinoma and lymphoma was compared using a t test. Receiver operating characteristic analyses were conducted to determine and compare the differentiating performance of ADCs. Lymphoma demonstrated significantly lower ADC mean , ADC median , ADC 10 , ADC 90 , and hot-spot-ROI-based mean ADC than those found in thymic carcinoma (all p values histogram analysis of ADC maps can improve the differentiating performance between thymic carcinoma and lymphoma.

  10. Odontogenic tumors: analysis of 127 cases Tumores odontogênicos: análise de 127 casos

    Directory of Open Access Journals (Sweden)

    Jean Nunes SANTOS

    2001-12-01

    Full Text Available One hundred and twenty-seven cases of histologically confirmed odontogenic tumors were retrieved from a total of 5,289 oral and maxillary lesions diagnosed at the Division of Oral Pathology, Federal University of Rio Grande do Norte, during a period of 30 years (l970-l999. The most common histological diagnosis was odontoma (50.40%, followed by ameloblastoma (30.70%. The prevalence of odontogenic tumors was greater in females and the peak incidence occurred in the second and third decades of life. The main anatomical location was the mandible, and no malignant tumors were found.De uma série de 5.289 casos de lesões orais e dos maxilares diagnosticadas no Laboratório de Patologia Oral da Faculdade de Odontologia da Universidade Federal do Rio Grande do Norte no período de 30 anos (1970-1999, foram analisados 127 casos de tumores odontogênicos confirmados histologicamente. A lesão mais freqüente foi o odontoma (50,40% seguida pelo ameloblastoma (30,70%. A prevalência de tumores odontogênicos foi maior nas mulheres e o pico de incidência ocorreu na segunda e terceira décadas de vida. A localização anatômica mais comum foi a mandíbula e não foram encontrados casos de tumores malignos.

  11. Magnetic resonance imaging textural evaluation of posterior cranial fossa tumors in childhood; Avaliacao textural por ressonancia magnetica dos tumores da fossa posterior em criancas

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Joelson Alves dos; Costa, Maria Olivia Rodrigues da; Otaduy, Maria Concepcion Garcia; Lacerda, Maria Teresa Carvalho de; Leite, Claudia da Costa [Sao Paulo Univ., SP (Brazil). Faculdade de Medicina. Dept. de Radiologia]. E-mail: joelson_alves@ig.com.br; Matsushita, Hamilton [Sao Paulo Univ., SP (Brazil). Faculdade de Medicina. Dept. de Neurologia

    2004-08-01

    Objective: To distinguish healthy from pathological tissues in pediatric patients with posterior cranial fossa tumors using calculated textural parameters from magnetic resonance images. Materials And Methods: We evaluated 14 pediatric patients with posterior cranial fossa tumors using the software MaZda to define the texture parameters in selected regions of interest representing healthy and pathological tissues based on T2-weighted magnetic resonance images. Results: There was a statistically significant difference between normal and tumoral tissues as well as between supposedly normal tissues adjacent and distant from the tumoral lesion. Conclusion: Magnetic resonance textural evaluation is an useful tool for determining differences among various tissues, including tissues that appear apparently normal on visual analysis. (author)

  12. Multiparametric classification links tumor microenvironments with tumor cell phenotype.

    Directory of Open Access Journals (Sweden)

    Bojana Gligorijevic

    2014-11-01

    occurred in spatially distinct microenvironments of primary tumors. We show how machine-learning analysis can classify heterogeneous microenvironments in vivo to enable prediction of motility phenotypes and tumor cell fate. The ability to predict the locations of tumor cell behavior leading to metastasis in breast cancer models may lead towards understanding the heterogeneity of response to treatment.

  13. Growth analysis of pulmonary metastases from salivary gland tumors.

    Science.gov (United States)

    Twardzik, F G; Sklaroff, D M

    1976-03-01

    Three cases of primary salivary gland tumors with lung metastasis are presented with extremely long survival (six, ten, and twelve years). The tumor doubling time was calculated and the growth rate of the pulmonary metastasis was found to be slow and erratic. A simplified table was devised, which permits rapid calculation of the tumor doubling time without the use of graphs. The presence of lung metastasis from some primary malignant salivary tumor is not necessarily an ominous sign: a long survival without symtoms is possible.

  14. Interrogation of metabolic and oxygen states of tumors with fiber-based luminescence lifetime spectroscopy.

    Science.gov (United States)

    Lukina, Maria; Orlova, Anna; Shirmanova, Marina; Shirokov, Daniil; Pavlikov, Anton; Neubauer, Antje; Studier, Hauke; Becker, Wolfgang; Zagaynova, Elena; Yoshihara, Toshitada; Tobita, Seiji; Shcheslavskiy, Vladislav

    2017-02-15

    The study of metabolic and oxygen states of cells in a tumor in vivo is crucial for understanding of the mechanisms responsible for tumor development and provides background for the relevant tumor's treatment. Here, we show that a specially designed implantable fiber-optic probe provides a promising tool for optical interrogation of metabolic and oxygen states of a tumor in vivo. In our experiments, the excitation light from a ps diode laser source is delivered to the sample through an exchangeable tip via a multimode fiber, and the emission light is transferred to the detector by another multimode fiber. Fluorescence lifetime of a nicotinamid adenine dinucleotide (NAD(P)H) and phosphorescence lifetime of an oxygen sensor based on an iridium (III) complex of enzothienylpyridine (BTPDM1) are explored both in model experiment in solutions and in living mice.

  15. A 3-D model of tumor progression based on complex automata driven by particle dynamics.

    Science.gov (United States)

    Wcisło, Rafał; Dzwinel, Witold; Yuen, David A; Dudek, Arkadiusz Z

    2009-12-01

    The dynamics of a growing tumor involving mechanical remodeling of healthy tissue and vasculature is neglected in most of the existing tumor models. This is due to the lack of efficient computational framework allowing for simulation of mechanical interactions. Meanwhile, just these interactions trigger critical changes in tumor growth dynamics and are responsible for its volumetric and directional progression. We describe here a novel 3-D model of tumor growth, which combines particle dynamics with cellular automata concept. The particles represent both tissue cells and fragments of the vascular network. They interact with their closest neighbors via semi-harmonic central forces simulating mechanical resistance of the cell walls. The particle dynamics is governed by both the Newtonian laws of motion and the cellular automata rules. These rules can represent cell life-cycle and other biological interactions involving smaller spatio-temporal scales. We show that our complex automata, particle based model can reproduce realistic 3-D dynamics of the entire system consisting of the tumor, normal tissue cells, blood vessels and blood flow. It can explain phenomena such as the inward cell motion in avascular tumor, stabilization of tumor growth by the external pressure, tumor vascularization due to the process of angiogenesis, trapping of healthy cells by invading tumor, and influence of external (boundary) conditions on the direction of tumor progression. We conclude that the particle model can serve as a general framework for designing advanced multiscale models of tumor dynamics and it is very competitive to the modeling approaches presented before.

  16. A Novel Markerless Technique to Evaluate Daily Lung Tumor Motion Based on Conventional Cone-Beam CT Projection Data

    International Nuclear Information System (INIS)

    Yang Yin; Zhong Zichun; Guo Xiaohu; Wang Jing; Anderson, John; Solberg, Timothy; Mao Weihua

    2012-01-01

    Purpose: In this study, we present a novel markerless technique, based on cone beam computed tomography (CBCT) raw projection data, to evaluate lung tumor daily motion. Method and Materials: The markerless technique, which uses raw CBCT projection data and locates tumors directly on every projection, consists of three steps. First, the tumor contour on the planning CT is used to create digitally reconstructed radiographs (DRRs) at every projection angle. Two sets of DRRs are created: one showing only the tumor, and another with the complete anatomy without the tumor. Second, a rigid two-dimensional image registration is performed to register the DRR set without the tumor to the CBCT projections. After the registration, the projections are subtracted from the DRRs, resulting in a projection dataset containing primarily tumor. Finally, a second registration is performed between the subtracted projection and tumor-only DRR. The methodology was evaluated using a chest phantom containing a moving tumor, and retrospectively in 4 lung cancer patients treated by stereotactic body radiation therapy. Tumors detected on projection images were compared with those from three-dimensional (3D) and four-dimensional (4D) CBCT reconstruction results. Results: Results in both static and moving phantoms demonstrate that the accuracy is within 1 mm. The subsequent application to 22 sets of CBCT scan raw projection data of 4 lung cancer patients includes about 11,000 projections, with the detected tumor locations consistent with 3D and 4D CBCT reconstruction results. This technique reveals detailed lung tumor motion and provides additional information than conventional 4D images. Conclusion: This technique is capable of accurately characterizing lung tumor motion on a daily basis based on a conventional CBCT scan. It provides daily verification of the tumor motion to ensure that these motions are within prior estimation and covered by the treatment planning volume.

  17. Perivascular epithelioid cell tumor (PEComa of the uterine cervix associated with intraabdominal "PEComatosis": A clinicopathological study with comparative genomic hybridization analysis

    Directory of Open Access Journals (Sweden)

    Ma Linglei

    2004-10-01

    Full Text Available Abstract Background The World Health Organization recently recognized a family of neoplasms showing at least partial morphological or immunohistochemical evidence of a putative perivascular epithelioid cell (PEC differentiation. These tumors include angiomyolipoma (AML, clear cell "sugar" tumors of the lung (CCST, lymphangioleiomyomatosis (LAM, clear cell myomelanocytic tumors of the falciform ligament and distinctive clear cell tumors at various other anatomic sites. Case presentation & methods A 41-year old gravida-1 para-1 with tuberous sclerosis presented with an incidentally identified 2.2 cm mass. The morphology and immunohistochemical profile was consistent with PEComa. Distinct aggregates of HMB-45 epithelioid cells were present in an occasionally distinctive perivascular distribution in the myometrium, small bowel lamina propria and ovarian hila. These distinctive aggregates, for which we propose the designation "PEComatosis" based on their intraabdominal distribution, did not display cytological atypia, mitotic activity or necrosis. CGH and DNA ploidy analysis showed a balanced chromosomal profile and diploid nuclei, respectively. There was no recurrence or metastases at 35 months' follow-up. Fifty-one previously reported cases of non-AML, LAM and CCST PEComas [perivascular epithelioid cell tumors- not otherwise specified (PEComa-NOS] are reviewed. Conclusions The lesions may be a reflection of tumor multicentricity, in which each may be a potential nidus for the development of future more well-developed tumors. Alternatively, they may be a manifestation of a poorly understood "field effect", in which there is an increased propensity to develop tumors of this type throughout the abdomen. Finally, and least likely in our opinion, they may represent tumor spread from its primary site.

  18. Estimation of lung tumor position from multiple anatomical features on 4D-CT using multiple regression analysis.

    Science.gov (United States)

    Ono, Tomohiro; Nakamura, Mitsuhiro; Hirose, Yoshinori; Kitsuda, Kenji; Ono, Yuka; Ishigaki, Takashi; Hiraoka, Masahiro

    2017-09-01

    To estimate the lung tumor position from multiple anatomical features on four-dimensional computed tomography (4D-CT) data sets using single regression analysis (SRA) and multiple regression analysis (MRA) approach and evaluate an impact of the approach on internal target volume (ITV) for stereotactic body radiotherapy (SBRT) of the lung. Eleven consecutive lung cancer patients (12 cases) underwent 4D-CT scanning. The three-dimensional (3D) lung tumor motion exceeded 5 mm. The 3D tumor position and anatomical features, including lung volume, diaphragm, abdominal wall, and chest wall positions, were measured on 4D-CT images. The tumor position was estimated by SRA using each anatomical feature and MRA using all anatomical features. The difference between the actual and estimated tumor positions was defined as the root-mean-square error (RMSE). A standard partial regression coefficient for the MRA was evaluated. The 3D lung tumor position showed a high correlation with the lung volume (R = 0.92 ± 0.10). Additionally, ITVs derived from SRA and MRA approaches were compared with ITV derived from contouring gross tumor volumes on all 10 phases of the 4D-CT (conventional ITV). The RMSE of the SRA was within 3.7 mm in all directions. Also, the RMSE of the MRA was within 1.6 mm in all directions. The standard partial regression coefficient for the lung volume was the largest and had the most influence on the estimated tumor position. Compared with conventional ITV, average percentage decrease of ITV were 31.9% and 38.3% using SRA and MRA approaches, respectively. The estimation accuracy of lung tumor position was improved by the MRA approach, which provided smaller ITV than conventional ITV. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

  19. Tumor-Associated Macrophages as Major Players in the Tumor Microenvironment

    International Nuclear Information System (INIS)

    Chanmee, Theerawut; Ontong, Pawared; Konno, Kenjiro; Itano, Naoki

    2014-01-01

    During tumor progression, circulating monocytes and macrophages are actively recruited into tumors where they alter the tumor microenvironment to accelerate tumor progression. Macrophages shift their functional phenotypes in response to various microenvironmental signals generated from tumor and stromal cells. Based on their function, macrophages are divided broadly into two categories: classical M1 and alternative M2 macrophages. The M1 macrophage is involved in the inflammatory response, pathogen clearance, and antitumor immunity. In contrast, the M2 macrophage influences an anti-inflammatory response, wound healing, and pro-tumorigenic properties. Tumor-associated macrophages (TAMs) closely resemble the M2-polarized macrophages and are critical modulators of the tumor microenvironment. Clinicopathological studies have suggested that TAM accumulation in tumors correlates with a poor clinical outcome. Consistent with that evidence, experimental and animal studies have supported the notion that TAMs can provide a favorable microenvironment to promote tumor development and progression. In this review article, we present an overview of mechanisms responsible for TAM recruitment and highlight the roles of TAMs in the regulation of tumor angiogenesis, invasion, metastasis, immunosuppression, and chemotherapeutic resistance. Finally, we discuss TAM-targeting therapy as a promising novel strategy for an indirect cancer therapy

  20. Tumor-Associated Macrophages as Major Players in the Tumor Microenvironment

    Energy Technology Data Exchange (ETDEWEB)

    Chanmee, Theerawut [Institute of Advanced Technology, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555 (Japan); Ontong, Pawared [Division of Engineering (Biotechnology), Graduate School of Engineering, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555 (Japan); Konno, Kenjiro [Department of Animal Medical Sciences, Faculty of Life Sciences, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555 (Japan); Itano, Naoki, E-mail: itanon@cc.kyoto-su.ac.jp [Institute of Advanced Technology, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555 (Japan); Division of Engineering (Biotechnology), Graduate School of Engineering, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555 (Japan); Department of Molecular Biosciences, Faculty of Life Sciences, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555 (Japan)

    2014-08-13

    During tumor progression, circulating monocytes and macrophages are actively recruited into tumors where they alter the tumor microenvironment to accelerate tumor progression. Macrophages shift their functional phenotypes in response to various microenvironmental signals generated from tumor and stromal cells. Based on their function, macrophages are divided broadly into two categories: classical M1 and alternative M2 macrophages. The M1 macrophage is involved in the inflammatory response, pathogen clearance, and antitumor immunity. In contrast, the M2 macrophage influences an anti-inflammatory response, wound healing, and pro-tumorigenic properties. Tumor-associated macrophages (TAMs) closely resemble the M2-polarized macrophages and are critical modulators of the tumor microenvironment. Clinicopathological studies have suggested that TAM accumulation in tumors correlates with a poor clinical outcome. Consistent with that evidence, experimental and animal studies have supported the notion that TAMs can provide a favorable microenvironment to promote tumor development and progression. In this review article, we present an overview of mechanisms responsible for TAM recruitment and highlight the roles of TAMs in the regulation of tumor angiogenesis, invasion, metastasis, immunosuppression, and chemotherapeutic resistance. Finally, we discuss TAM-targeting therapy as a promising novel strategy for an indirect cancer therapy.

  1. Ewing’s Sarcoma: An Analysis of miRNA Expression Profiles and Target Genes in Paraffin-Embedded Primary Tumor Tissue

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    Antonina Parafioriti

    2016-04-01

    Full Text Available The molecular mechanism responsible for Ewing’s Sarcoma (ES remains largely unknown. MicroRNAs (miRNAs, a class of small non-coding RNAs able to regulate gene expression, are deregulated in tumors and may serve as a tool for diagnosis and prediction. However, the status of miRNAs in ES has not yet been thoroughly investigated. This study compared global miRNAs expression in paraffin-embedded tumor tissue samples from 20 ES patients, affected by primary untreated tumors, with miRNAs expressed in normal human mesenchymal stromal cells (MSCs by microarray analysis. A miRTarBase database was used to identify the predicted target genes for differentially expressed miRNAs. The miRNAs microarray analysis revealed distinct patterns of miRNAs expression between ES samples and normal MSCs. 58 of the 954 analyzed miRNAs were significantly differentially expressed in ES samples compared to MSCs. Moreover, the qRT-PCR analysis carried out on three selected miRNAs showed that miR-181b, miR-1915 and miR-1275 were significantly aberrantly regulated, confirming the microarray results. Bio-database analysis identified BCL-2 as a bona fide target gene of the miR-21, miR-181a, miR-181b, miR-29a, miR-29b, miR-497, miR-195, miR-let-7a, miR-34a and miR-1915. Using paraffin-embedded tissues from ES patients, this study has identified several potential target miRNAs and one gene that might be considered a novel critical biomarker for ES pathogenesis.

  2. Pattern of malignant tumors in children: a hospital based study

    International Nuclear Information System (INIS)

    Khan, S.M.; Nasreen, S.; Zai, S.

    2001-01-01

    From 1990 to 1999 data from 32743 cancer patients (males 18502, females 14241) were analyzed to know the frequency of the most common cancers in local and well as well as afghan refugees. There were 3760 children with biopsy proven cancers 2910 belonged to the north-west frontier province (NWFP), while the remaining 850 were Afghan refugees. Among children of NWFP male were 1945 (67%) and 965(33%) females. In Afghan children, males were 570(67%) and females were 280(33%). The most common tumors in children of NWFP were lymphoid leukemia, lymphoma, tumors of the central nervous system (CNS), myeloid leukemia, soft tissue sarcoma wilms, tumours, retinoblastoma, bone tumor neuroblastoma, and ovarian tumors. Whereas Afghan children had Lymphoid leukemia, lymphoma, myeloid leukemia, wilms, tumor, retinoblastoma, tumors of soft tissue bones CNS, neuroblastoma and ovarian tumors. (author)

  3. Mesenchymal Stem Cell-Based Tumor-Targeted Gene Therapy in Gastrointestinal Cancer

    OpenAIRE

    Bao, Qi; Zhao, Yue; Niess, Hanno; Conrad, Claudius; Schwarz, Bettina; Jauch, Karl-Walter; Huss, Ralf; Nelson, Peter J.; Bruns, Christiane J.

    2012-01-01

    Mesenchymal stem (or stromal) cells (MSCs) are nonhematopoietic progenitor cells that can be obtained from bone marrow aspirates or adipose tissue, expanded and genetically modified in vitro, and then used for cancer therapeutic strategies in vivo. Here, we review available data regarding the application of MSC-based tumor-targeted therapy in gastrointestinal cancer, provide an overview of the general history of MSC-based gene therapy in cancer research, and discuss potential problems associa...

  4. Defining Survivorship Trajectories Across Patients With Solid Tumors: An Evidence-Based Approach.

    Science.gov (United States)

    Dood, Robert L; Zhao, Yang; Armbruster, Shannon D; Coleman, Robert L; Tworoger, Shelley; Sood, Anil K; Baggerly, Keith A

    2018-06-02

    Survivorship involves a multidisciplinary approach to surveillance and management of comorbidities and secondary cancers, overseen by oncologists, surgeons, and primary care physicians. Optimal timing and coordination of care, however, is unclear and often based on arbitrary 5-year cutoffs. To determine high- and low-risk periods for all tumor types that could define when survivorship care might best be overseen by oncologists and when to transition to primary care physicians. In this pan-cancer, longitudinal, observational study, excess mortality hazard, calculated as an annualized mortality risk above a baseline population, was plotted over time. The time this hazard took to stabilize defined a high-risk period. The percent morality elevation above age- and sex-matched controls in the latter low-risk period was reported as a mortality gap. The US population-based Surveillance, Epidemiology, and End Results database defined the cancer population, and the US Census life tables defined controls. Incident cases of patients with cancer were separated into tumor types based on International Classification of Diseases for Oncology definitions. Population-level data on incident cancer cases was compared with the general US population. Overall mortality and cause of death were reported on observed cancer cases. A total of 2 317 185 patients (median age, 63 years; 49.8% female) with 66 primary tumor types were evaluated. High-risk surveillance period durations ranged from less than 1 year (breast, prostate, lip, ocular, and parathyroid cancers) up to 19 years (unspecified gastrointestinal cancers). The annualized mortality gap, representing the excess mortality in the stable period, ranged from a median 0.26% to 9.33% excess annual mortality (thyroid and hypopharyngeal cancer populations, respectively). Cluster analysis produced 6 risk cluster groups: group 1, with median survival of 16.2 (5th to 95th percentile range [PR], 10.7-40.2) years and median high-risk period

  5. Analysis of reproducibility of respiration-triggered gated radiotherapy for lung tumors

    International Nuclear Information System (INIS)

    Spoelstra, Femke O.B.; Soernsen de Koste, John R. van; Cuijpers, Johan P.; Lagerwaard, Frank J.; Slotman, Ben J.; Senan, Suresh

    2008-01-01

    Purpose: Respiration-gated radiotherapy (RGRT) can decrease the toxicity of chemo-radiotherapy (CT-RT) by allowing use of smaller treatment fields. RGRT requires a predictable relationship between tumor position and external surrogate, which must be verified during treatment. Time-integrated electronic portal imaging (TI-EPI) identifies mean intra-fractional positions of moving structures, and was used to study reproducibility of anatomy during RGRT for lung tumors. Materials and methods: TI-EPIs were acquired using an amorphous silicon-based electronic portal imaging system (EPID, aS500) in continuous image acquisition mode in 11 patients treated with audio-coached RGRT at end-inspiration. The Varian Real-time Position Management (RPM) system was used for 4DCT imaging and RGRT delivery. All TI-EPI portals were co-registered to corresponding digitally reconstructed radiographs (DRR) of the planning 4DCT using the spinal column. Displacements in tumor position or that of an adjacent bronchus during RGRT was measured relative to the reference structure on the DRR. Results: Vertebra-matched portals revealed systematic (Σ) and random (σ) errors of 1.8 and 1.3 mm in medial-lateral direction and 1.7 and 1.7 mm in cranial-caudal direction, indicating a reproducible tumor/bronchus position during the RPM-triggered gates. Conclusions: RGRT delivery at end-inspiration can achieve reproducible internal anatomy in 'gated' fields delivered with audio-coaching

  6. Management of Renal Tumors by Image-Guided Radiofrequency Ablation: Experience in 105 Tumors

    International Nuclear Information System (INIS)

    Breen, David J.; Rutherford, Elizabeth E.; Stedman, Brian; Roy-Choudhury, Shuvro H.; Cast, James E. I.; Hayes, Matthew C.; Smart, Christopher J.

    2007-01-01

    Aims. In this article we present our experience with radiofrequency ablation (RFA) in the treatment of 105 renal tumors. Materials and Methods. RFA was performed on 105 renal tumors in 97 patients, with a mean tumor size of 32 mm (11-68 mm). The mean patient age was 71.7 years (range, 36-89 years). The ablations were carried out under ultrasound (n = 43) or CT (n = 62) guidance. Imaging follow-up was by contrast-enhanced CT within 10 days and then at 6-monthly intervals. Multivariate analysis was performed to determine variables associated with procedural outcome. Results. Eighty-three tumors were completely treated at a single sitting (79%). Twelve of the remaining tumors were successfully re-treated and a clinical decision was made not to re-treat seven patients. A patient with a small residual crescent of tumor is under follow-up and may require further treatment. In another patient, re-treatment was abandoned due to complicating pneumothorax and difficult access. One patient is awaiting further re-treatment. The overall technical success rate was 90.5%. Multivariate analysis revealed tumor size to be the only significant variable affecting procedural outcome. (p = 0.007, Pearson χ 2 ) Five patients had complications. There have been no local recurrences. Conclusion. Our experience to date suggests that RFA is a safe and effective, minimally invasive treatment for small renal tumors

  7. Breast-conserving surgery in locally advanced breast cancer submitted to neoadjuvant chemotherapy. Safety and effectiveness based on ipsilateral breast tumor recurrence and long-term follow-up

    Directory of Open Access Journals (Sweden)

    Guilherme Freire Angotti Carrara

    Full Text Available OBJECTIVE: To evaluate ipsilateral breast tumor recurrence after breast-conserving surgery for locally advanced breast cancer. METHODS: A retrospective observational cohort study was performed in patients with locally advanced breast cancer submitted to breast-conserving surgery after neoadjuvant chemotherapy based on an adriamycin-cyclophosphamide-paclitaxel regimen. We evaluated the clinical, pathologic, immunohistochemistry, and surgical factors that contribute to ipsilateral breast tumor recurrence and locoregional recurrence. A Kaplan-Meier analysis and Cox model were used to evaluate the main factors related to disease-free survival. RESULTS: Of the 449 patients who received neoadjuvant chemotherapy, 98 underwent breast-conserving surgery. The average diameter of the tumors was 5.3 cm, and 87.2% reached a size of up to 3 cm. Moreover, 86.7% were classified as clinical stage III, 74.5% had T3-T4 tumors, 80.5% had N1-N2 axilla, and 89.8% had invasive ductal carcinoma. A pathologic complete response was observed in 27.6% of the tumors, and 100.0% of samples had free margins. The 5-year actuarial overall survival rate was 81.2%, and the mean follow-up was 72.8 months. The rates of ipsilateral breast tumor recurrence and locoregional recurrence were 11.2% and 15.3%, respectively. Multifocal morphology response was the only factor related to ipsilateral breast tumor recurrence disease-free survival (p=0.04. A multivariate analysis showed that the pathologic response evaluation criteria in solid tumors (RECIST-breast cutoff was the only factor related to locoregional recurrence disease-free survival (p=0.01. CONCLUSIONS: Breast-conserving surgery is a safe and effective therapy for selected locally advanced breast tumors.

  8. Characterization of Tumor Heterogeneity by Texture Analysis in 18F-FDG PET images: A Pilot Study

    Energy Technology Data Exchange (ETDEWEB)

    Manso, M.; Martino, M.E.; Rodriguez, E.A.; Landaeta, L.C.; Carreras, J.L.; Calvo, F.A.; Desco, M.; Pascau, J.; Muñoz-Barrutia, M.

    2016-07-01

    2-Deoxy-2-[18F]-fluoro-D-glucose (FDG) positron emission tomography (PET) is often used in clinic for cancer diagnosis, staging, therapy planning and monitoring. Alternative features to the classical semi-quantitative variables have been recently proposed to study the heterogeneity of tumors. The method to extract such characteristics is texture analysis, which quantifies variations of uptake distribution within the lesions. Methods: Fifty-three head and neck and twelve rectal cancer patients were included in the analysis. A workflow in an open-source software, 3D slicer, was designed and expert clinicians were trained on its use, sixty six features were calculated including metabolic and texture parameters. Statistical analysis and dimensionality reduction techniques were performed on the data. Results: After observing a high correlation between variables, dimensions were reduced to five and three independent components for head and neck and rectal cancer cohort, respectively. Conclusion: Tumor heterogeneity parameters could be expressing important information about tumor and cancer disease, information that could be used to assess disease staging, patients’ prognosis, therapy plan and survival. (Author)

  9. Is it beneficial to selectively boost high-risk tumor subvolumes? A comparison of selectively boosting high-risk tumor subvolumes versus homogeneous dose escalation of the entire tumor based on equivalent EUD plans

    International Nuclear Information System (INIS)

    Kim, Yusung; To me, Wolfgang A.

    2008-01-01

    Purpose. To quantify and compare expected local tumor control and expected normal tissue toxicities between selective boosting IMRT and homogeneous dose escalation IMRT for the case of prostate cancer. Methods. Four different selective boosting scenarios and three different high-risk tumor subvolume geometries were designed to compare selective boosting and homogeneous dose escalation IMRT plans delivering the same equivalent uniform dose (EUD) to the entire PTV. For each scenario, differences in tumor control probability between both boosting strategies were calculated for the high-risk tumor subvolume and remaining low-risk PTV, and were visualized using voxel based iso-TCP maps. Differences in expected rectal and bladder complications were quantified using radiobiological indices (generalized EUD (gEUD) and normal tissue complication probability (NTCP)) as well as %-volumes. Results. For all investigated scenarios and high-risk tumor subvolume geometries, selective boosting IMRT improves expected TCP compared to homogeneous dose escalation IMRT, especially when lack of control of the high-risk tumor subvolume could be the cause for tumor recurrence. Employing, selective boosting IMRT significant increases in expected TCP can be achieved for the high-risk tumor subvolumes. The three conventional selective boosting IMRT strategies, employing physical dose objectives, did not show significant improvement in rectal and bladder sparing as compared to their counterpart homogeneous dose escalation plans. However, risk-adaptive optimization, utilizing radiobiological objective functions, resulted in reduction in NTCP for the rectum when compared to its corresponding homogeneous dose escalation plan. Conclusions. Selective boosting is a more effective method than homogeneous dose escalation for achieving optimal treatment outcomes. Furthermore, risk-adaptive optimization increases the therapeutic ratio as compared to conventional selective boosting IMRT

  10. Analysis of p53- immunoreactivity in astrocytic brain tumors

    Directory of Open Access Journals (Sweden)

    Shinkarenko T.V.

    2016-12-01

    Full Text Available P53 is an antioncogene with the frequently occured mutations in human tumor cells, leading to corresponding protein overexpression which can be detected by immunohistochemistry. Researches dedicated to the investigation of possibilities of using this technique gave controversial results. The authors investigated features of p53 protein expression in astrocytic brain tumors with different degrees of malignancy. Analyzed the relationship of the expression level of p53 by tumor cells with clinical parameters and Ki-67 proliferation index (PI as well. Tissues were collected from 52 cases with diagnosed astrocytic brain tumors. The sections were immunohistochemically stained with p53 and Ki-67. For each marker, 1000 tumor cells were counted and the ratio of positive tumor cells was calculated using software package ImageJ 1,47v. In normal brain tissue p53- expression was not identified. p53-immunoreactive tumor cells were detected in 25% (1/4 pilocytic astrocytomas, 33.3% (2/6 of diffuse astrocytomas, 53.8% (7/13 anaplastic astrocytomas, 58.6% (17/29 glioblastomas. A high proportion of p53-immunoreactive cells (> 30% was observed only in glioblastomas. The level of p53-imunoreactivity was not related to the age, gender and Grade WHO (p> 0,05. Spearman correlation coefficient between the relative quantity of ki-67- and p53-immunoreactive nuclei showed weak direct correlation (0.023, but the one was not statistically significant (p> 0,05. The level of p53-imunoreactivity is not dependent from age and sex of patients, Grade (WHO and proliferative activity (p>0,05 but the high level of p53-immunoreactive cells (>30% is found in glioblastoma specimens only, that may be due to the accumulation of mutations in DNA of tumor cells. There is insignificant weak relationship between relative quantities of ki-67- and p53-immunoreactive tumor cells (p>0,05.

  11. Human CD34+ cells engineered to express membrane-bound tumor necrosis factor-related apoptosis-inducing ligand target both tumor cells and tumor vasculature.

    Science.gov (United States)

    Lavazza, Cristiana; Carlo-Stella, Carmelo; Giacomini, Arianna; Cleris, Loredana; Righi, Marco; Sia, Daniela; Di Nicola, Massimo; Magni, Michele; Longoni, Paolo; Milanesi, Marco; Francolini, Maura; Gloghini, Annunziata; Carbone, Antonino; Formelli, Franca; Gianni, Alessandro M

    2010-03-18

    Adenovirus-transduced CD34+ cells expressing membrane-bound tumor necrosis factor-related apoptosis-inducing ligand (CD34-TRAIL+ cells) exert potent antitumor activity. To further investigate the mechanism(s) of action of CD34-TRAIL+ cells, we analyzed their homing properties as well as antitumor and antivascular effects using a subcutaneous myeloma model in immunodeficient mice. After intravenous injection, transduced cells homed in the tumor peaking at 48 hours when 188 plus or minus 25 CD45+ cells per 10(5) tumor cells were detected. Inhibition experiments showed that tumor homing of CD34-TRAIL+ cells was largely mediated by vascular cell adhesion molecule-1 and stromal cell-derived factor-1. Both CD34-TRAIL+ cells and soluble (s)TRAIL significantly reduced tumor volume by 40% and 29%, respectively. Computer-aided analysis of TdT-mediated dUTP nick end-labeling-stained tumor sections demonstrated significantly greater effectiveness for CD34-TRAIL+ cells in increasing tumor cell apoptosis and necrosis over sTRAIL. Proteome array analysis indicated that CD34-TRAIL+ cells and sTRAIL activate similar apoptotic machinery. In vivo staining of tumor vasculature with sulfosuccinimidyl-6-(biotinamido) hexanoate-biotin revealed that CD34-TRAIL+ cells but not sTRAIL significantly damaged tumor vasculature, as shown by TdT-mediated dUTP nick end-labeling+ endothelial cells, appearance of hemorrhagic areas, and marked reduction of endothelial area. These results demonstrate that tumor homing of CD34-TRAIL+ cells induces early vascular disruption, resulting in hemorrhagic necrosis and tumor destruction.

  12. Imitation-tumor targeting based on continuous-wave near-infrared tomography.

    Science.gov (United States)

    Liu, Dan; Liu, Xin; Zhang, Yan; Wang, Qisong; Lu, Jingyang; Sun, Jinwei

    2017-12-01

    Continuous-wave Near-Infrared (NIR) optical spectroscopy has shown great diagnostic capability in the early tumor detection with advantages of low-cost, portable, non-invasive, and non-radiative. In this paper, Modified Lambert-Beer Theory is deployed to address the low-resolution issues of the NIR technique and to design the tumor detecting and imaging system. Considering that tumor tissues have features such as high blood flow and hypoxia, the proposed technique can detect the location, size, and other information of the tumor tissues by comparing the absorbance between pathological and normal tissues. Finally, the tumor tissues can be imaged through tomographic method. The simulation experiments prove that the proposed technique and designed system can efficiently detect the tumor tissues, achieving imaging precision within 1 mm. The work of the paper has shown great potential in the diagnosis of tumor close to body surface.

  13. Three-dimensional reconstruction of colorectal tumors from serial tissue sections by computer graphics: a preliminary study.

    Science.gov (United States)

    Kikuchi, S; Matsuzaki, H; Kondo, K; Ohtani, Y; Ihara, A; Hiki, Y; Kakita, A; Kuwao, S

    2000-01-01

    We present herein the three-dimensional reconstruction of colorectal tumors, with particular reference to growth pattern into each layer of the colorectal wall, and measurement of tumor volume and surface area. Conventional tissue section images of colorectal tumors were analyzed using a computer graphics analysis program. The two-dimensional extent of invasion by each tumor into each layer of intestinal wall were determined from the images of each section. Based on data from multiple sections, tumor and surrounding normal tissue layers were reconstructed three-dimensionally, and volume and surface area of the tumors were determined. Using this technique, three-dimensional morphology of tumor and tumor progression into colorectal wall could be determined. Volume and surface area of the colon tumor were 4871 mm3 and 1741 mm2, respectively. Volume and surface area of the rectal tumor were 1090 mm3 and 877 mm2, respectively. This technique may provide a new approach for pathological analysis of colorectal carcinoma.

  14. Brainstem tolerance to conformal radiotherapy of skull base tumors

    International Nuclear Information System (INIS)

    Debus, J.; Hug, E.B.; Munzenrider, J.E.; Liebsch, N.J.; O'Farrell, D.; Efird, J.; Daly, W.; Suit, H.D.

    1996-01-01

    Purpose/Objective: Brainstem tolerance to inhomogenous radiation doses applied by modern conformal radiotherapy has not yet been examined. The aim of this study was to analyse the incidence of brainstem toxicity in patients treated for skull base tumors with high dose conformal radiotherapy. Materials and Methods: Between 1974 and 1995, 367 patients with chordomas (n=195) and chondrosarcomas (n=172) of the base of skull have been treated with combined megavoltage photon and 160 MeV proton radiotherapy. All patients had previously undergone biopsy, subtotal or total tumor removal. 104 patients had two or more surgical procedures before radiotherapy. Following 3D treatment planning with delineation of target volumes and critical non-target structures, dose distributions and dose volume histograms were calculated [at the time of treatment delivery]. Radiotherapy was given once a day, 1.8 Gy or CGE (Cobalt Gy Equivalent: Proton Gy X 1.1) per fraction, 5 fractions per week, with prescribed target doses ranging from 63 CGE to 79.2 CGE (mean = 67.8 CGE). Doses to the brainstem surface were limited to ≤64 CGE and to the brainstem center to ≤53 CGE. Dose distributions were developed to limit dose to brainstem surface and center; current plans limit dose to surface and center to ≤64 CGE and ≤53 CGE, respectively. Brainstem toxicity was scored according to the RTOG grading system. Results: Follow-up ranged from 6 months to 21.4 years (mean = 42.5 months). Brainstem symptoms, attributable to the treatment, developed in 17 of 282 patients with local tumor control (6.0%), resulting in death of three patients. The mean time to onset of symptoms was 17 months (range: 4.5 to 177 months). These symptoms appeared in 89.5% within 3 years. Grading of the brainstem toxicity is listed in table 1. Actuarial rates of 5 and 10 year toxicity free survival were 87% and 82% respectively. Increased risk of brainstem toxicity was significantly associated with maximum brainstem dose

  15. Gliomas: Application of Cumulative Histogram Analysis of Normalized Cerebral Blood Volume on 3 T MRI to Tumor Grading

    Science.gov (United States)

    Kim, Hyungjin; Choi, Seung Hong; Kim, Ji-Hoon; Ryoo, Inseon; Kim, Soo Chin; Yeom, Jeong A.; Shin, Hwaseon; Jung, Seung Chai; Lee, A. Leum; Yun, Tae Jin; Park, Chul-Kee; Sohn, Chul-Ho; Park, Sung-Hye

    2013-01-01

    Background Glioma grading assumes significant importance in that low- and high-grade gliomas display different prognoses and are treated with dissimilar therapeutic strategies. The objective of our study was to retrospectively assess the usefulness of a cumulative normalized cerebral blood volume (nCBV) histogram for glioma grading based on 3 T MRI. Methods From February 2010 to April 2012, 63 patients with astrocytic tumors underwent 3 T MRI with dynamic susceptibility contrast perfusion-weighted imaging. Regions of interest containing the entire tumor volume were drawn on every section of the co-registered relative CBV (rCBV) maps and T2-weighted images. The percentile values from the cumulative nCBV histograms and the other histogram parameters were correlated with tumor grades. Cochran’s Q test and the McNemar test were used to compare the diagnostic accuracies of the histogram parameters after the receiver operating characteristic curve analysis. Using the parameter offering the highest diagnostic accuracy, a validation process was performed with an independent test set of nine patients. Results The 99th percentile of the cumulative nCBV histogram (nCBV C99), mean and peak height differed significantly between low- and high-grade gliomas (P = histogram analysis of nCBV using 3 T MRI can be a useful method for preoperative glioma grading. The nCBV C99 value is helpful in distinguishing high- from low-grade gliomas and grade IV from III gliomas. PMID:23704910

  16. Tumor cell proliferation kinetics and tumor growth rate

    Energy Technology Data Exchange (ETDEWEB)

    Tubiana, M

    1989-01-01

    The present knowledge on the growth rate and the proliferation kinetics of human tumor is based on the measurement of the tumor doubling times (DT) in several hundred patients and on the determination of the proportion of proliferating cells with radioactive thymidine or by flow cytometry in large numbers of patients. The results show that the DT of human tumor varies widely, from less than one week to over one year with a median value of approximately 2 months. The DTs are significantly correlated with the histological type. They depend upon (1) the duration of the cell cycle whose mean duration is 2 days with small variations from tumor to tumor, (2) the proportion of proliferating cells and consequently the cell birth rate which varies widely among tumors and which is significantly correlated to the DT, (3) the cell loss factors which also vary widely and which are the greatest when proliferation is most intensive. These studies have several clinical implications: (a) they have further increased our understanding of the natural history of human tumor, (b) they have therapeutic implications since tumor responsiveness and curability by radiation and drugs are strongly influenced by the cell kinetic parameters of the tumor, (c) the proportion of proliferating cells is of great prognostic value in several types of human cancers. The investigation of the molecular defects, which are correlated with the perturbation of control of cell proliferation, should lead to significant fundamental and therapeutic advances. (orig.).

  17. Improving abdomen tumor low-dose CT images using a fast dictionary learning based processing

    International Nuclear Information System (INIS)

    Chen Yang; Shi Luyao; Shu Huazhong; Luo Limin; Coatrieux, Jean-Louis; Yin Xindao; Toumoulin, Christine

    2013-01-01

    In abdomen computed tomography (CT), repeated radiation exposures are often inevitable for cancer patients who receive surgery or radiotherapy guided by CT images. Low-dose scans should thus be considered in order to avoid the harm of accumulative x-ray radiation. This work is aimed at improving abdomen tumor CT images from low-dose scans by using a fast dictionary learning (DL) based processing. Stemming from sparse representation theory, the proposed patch-based DL approach allows effective suppression of both mottled noise and streak artifacts. The experiments carried out on clinical data show that the proposed method brings encouraging improvements in abdomen low-dose CT images with tumors. (paper)

  18. Testicular germinal tumors

    International Nuclear Information System (INIS)

    Fresco, R.

    2010-01-01

    This work is about diagnosis, treatment and monitoring of testicular germinal tumors. The presumed diagnosis is based in the anamnesis, clinical examination, testicular ultrasound and tumor markers. The definitive diagnosis is obtained through the inguinal radical orchidectomy

  19. Mesenchymal Stem Cell-Based Tumor-Targeted Gene Therapy in Gastrointestinal Cancer

    Science.gov (United States)

    Bao, Qi; Zhao, Yue; Niess, Hanno; Conrad, Claudius; Schwarz, Bettina; Jauch, Karl-Walter; Huss, Ralf; Nelson, Peter J.

    2012-01-01

    Mesenchymal stem (or stromal) cells (MSCs) are nonhematopoietic progenitor cells that can be obtained from bone marrow aspirates or adipose tissue, expanded and genetically modified in vitro, and then used for cancer therapeutic strategies in vivo. Here, we review available data regarding the application of MSC-based tumor-targeted therapy in gastrointestinal cancer, provide an overview of the general history of MSC-based gene therapy in cancer research, and discuss potential problems associated with the utility of MSC-based therapy such as biosafety, immunoprivilege, transfection methods, and distribution in the host. PMID:22530882

  20. Quantitation of Murine Stroma and Selective Purification of the Human Tumor Component of Patient-Derived Xenografts for Genomic Analysis.

    Directory of Open Access Journals (Sweden)

    Valentina E Schneeberger

    Full Text Available Patient-derived xenograft (PDX mouse models are increasingly used for preclinical therapeutic testing of human cancer. A limitation in molecular and genetic characterization of PDX tumors is the presence of integral murine stroma. This is particularly problematic for genomic sequencing of PDX models. Rapid and dependable approaches for quantitating stromal content and purifying the malignant human component of these tumors are needed. We used a recently developed technique exploiting species-specific polymerase chain reaction (PCR amplicon length (ssPAL differences to define the fractional composition of murine and human DNA, which was proportional to the fractional composition of cells in a series of lung cancer PDX lines. We compared four methods of human cancer cell isolation: fluorescence-activated cell sorting (FACS, an immunomagnetic mouse cell depletion (MCD approach, and two distinct EpCAM-based immunomagnetic positive selection methods. We further analyzed DNA extracted from the resulting enriched human cancer cells by targeted sequencing using a clinically validated multi-gene panel. Stromal content varied widely among tumors of similar histology, but appeared stable over multiple serial tumor passages of an individual model. FACS and MCD were superior to either positive selection approach, especially in cases of high stromal content, and consistently allowed high quality human-specific genomic profiling. ssPAL is a dependable approach to quantitation of murine stromal content, and MCD is a simple, efficient, and high yield approach to human cancer cell isolation for genomic analysis of PDX tumors.

  1. Occurrence of mammary tumors in beagls given radium-226

    International Nuclear Information System (INIS)

    Bruenger, F.W.; Lloyd, R.D.; Miller, S.C.; Taylor, G.N.; Angus, W.; Huth, D.A.

    1994-01-01

    A total of 128 primary mammary tumors (66 of them malignant) occurred in 35 female beagles injected with 226 Ra at eight dose levels ranging from 0.2 to 440 kBq/kg body mass as young adults, while a total of 156 mammary tumors (57 of them malignant) were seen in 46 female control beagles not given any radioactivity. Sixty-three of 65 control dogs and 59 of 61 dogs given 226 Ra survived the minimum age for diagnosis of mammary tumors of 3.75 years. Based on the observed age-dependent tumor incidence rates in the controls and on the corresponding number of dog-years at risk, the total number of observed malignant tumors in the radium group was statistically greater than the number of expected malignant tumors (66 observed vs 34 expected, P < 0.005). There was no such difference for the benign tumors. Cox regression analysis indicated no increased risk for the first tumor occurrence in irradiated dogs. Cox regression analysis of the multivariate risk sets showed no significantly increased risk for the occurrence of benign tumors but a statistically higher risk of 1.66 with a confidence interval of 1.15-2.40 for the occurrence of malignant tumors. The increased risk was dependent on dose, but a dependence on the frequency of previous occurrence of mammary tumors could not be confirmed. Censoring ovariectomized dogs at time of surgery decreased the relative risks slightly but did not alter the significance. Exposure to diagnostic X rays with cumulative exposures below 0.2 Gy had no effect on tumor formation. It is unknown whether the increased risk for malignant mammary tumors was due to some initial deposition of radium in sensitive tissue, a possible irradiation of fatty mammary tissue from transient radon → polonium deposition, or a general effect of the overall radium deposition on the immune system of the dogs that lowered their resistance to formation of mammary tumors. 27 refs., 5 figs., 4 tabs

  2. Multicolor microRNA FISH effectively differentiates tumor types

    Science.gov (United States)

    Renwick, Neil; Cekan, Pavol; Masry, Paul A.; McGeary, Sean E.; Miller, Jason B.; Hafner, Markus; Li, Zhen; Mihailovic, Aleksandra; Morozov, Pavel; Brown, Miguel; Gogakos, Tasos; Mobin, Mehrpouya B.; Snorrason, Einar L.; Feilotter, Harriet E.; Zhang, Xiao; Perlis, Clifford S.; Wu, Hong; Suárez-Fariñas, Mayte; Feng, Huichen; Shuda, Masahiro; Moore, Patrick S.; Tron, Victor A.; Chang, Yuan; Tuschl, Thomas

    2013-01-01

    MicroRNAs (miRNAs) are excellent tumor biomarkers because of their cell-type specificity and abundance. However, many miRNA detection methods, such as real-time PCR, obliterate valuable visuospatial information in tissue samples. To enable miRNA visualization in formalin-fixed paraffin-embedded (FFPE) tissues, we developed multicolor miRNA FISH. As a proof of concept, we used this method to differentiate two skin tumors, basal cell carcinoma (BCC) and Merkel cell carcinoma (MCC), with overlapping histologic features but distinct cellular origins. Using sequencing-based miRNA profiling and discriminant analysis, we identified the tumor-specific miRNAs miR-205 and miR-375 in BCC and MCC, respectively. We addressed three major shortcomings in miRNA FISH, identifying optimal conditions for miRNA fixation and ribosomal RNA (rRNA) retention using model compounds and high-pressure liquid chromatography (HPLC) analyses, enhancing signal amplification and detection by increasing probe-hapten linker lengths, and improving probe specificity using shortened probes with minimal rRNA sequence complementarity. We validated our method on 4 BCC and 12 MCC tumors. Amplified miR-205 and miR-375 signals were normalized against directly detectable reference rRNA signals. Tumors were classified using predefined cutoff values, and all were correctly identified in blinded analysis. Our study establishes a reliable miRNA FISH technique for parallel visualization of differentially expressed miRNAs in FFPE tumor tissues. PMID:23728175

  3. Comparison of lung tumor motion measured using a model-based 4DCT technique and a commercial protocol.

    Science.gov (United States)

    O'Connell, Dylan; Shaverdian, Narek; Kishan, Amar U; Thomas, David H; Dou, Tai H; Lewis, John H; Lamb, James M; Cao, Minsong; Tenn, Stephen; Percy, Lee P; Low, Daniel A

    2017-11-11

    To compare lung tumor motion measured with a model-based technique to commercial 4-dimensional computed tomography (4DCT) scans and describe a workflow for using model-based 4DCT as a clinical simulation protocol. Twenty patients were imaged using a model-based technique and commercial 4DCT. Tumor motion was measured on each commercial 4DCT dataset and was calculated on model-based datasets for 3 breathing amplitude percentile intervals: 5th to 85th, 5th to 95th, and 0th to 100th. Internal target volumes (ITVs) were defined on the 4DCT and 5th to 85th interval datasets and compared using Dice similarity. Images were evaluated for noise and rated by 2 radiation oncologists for artifacts. Mean differences in tumor motion magnitude between commercial and model-based images were 0.47 ± 3.0, 1.63 ± 3.17, and 5.16 ± 4.90 mm for the 5th to 85th, 5th to 95th, and 0th to 100th amplitude intervals, respectively. Dice coefficients between ITVs defined on commercial and 5th to 85th model-based images had a mean value of 0.77 ± 0.09. Single standard deviation image noise was 11.6 ± 9.6 HU in the liver and 6.8 ± 4.7 HU in the aorta for the model-based images compared with 57.7 ± 30 and 33.7 ± 15.4 for commercial 4DCT. Mean model error within the ITV regions was 1.71 ± 0.81 mm. Model-based images exhibited reduced presence of artifacts at the tumor compared with commercial images. Tumor motion measured with the model-based technique using the 5th to 85th percentile breathing amplitude interval corresponded more closely to commercial 4DCT than the 5th to 95th or 0th to 100th intervals, which showed greater motion on average. The model-based technique tended to display increased tumor motion when breathing amplitude intervals wider than 5th to 85th were used because of the influence of unusually deep inhalations. These results suggest that care must be taken in selecting the appropriate interval during image generation when using model-based 4DCT methods. Copyright © 2017

  4. Identification of Genetic Susceptibility Loci for Colorectal Tumors in a Genome-Wide Meta-analysis.

    Science.gov (United States)

    Peters, Ulrike; Jiao, Shuo; Schumacher, Fredrick R; Hutter, Carolyn M; Aragaki, Aaron K; Baron, John A; Berndt, Sonja I; Bézieau, Stéphane; Brenner, Hermann; Butterbach, Katja; Caan, Bette J; Campbell, Peter T; Carlson, Christopher S; Casey, Graham; Chan, Andrew T; Chang-Claude, Jenny; Chanock, Stephen J; Chen, Lin S; Coetzee, Gerhard A; Coetzee, Simon G; Conti, David V; Curtis, Keith R; Duggan, David; Edwards, Todd; Fuchs, Charles S; Gallinger, Steven; Giovannucci, Edward L; Gogarten, Stephanie M; Gruber, Stephen B; Haile, Robert W; Harrison, Tabitha A; Hayes, Richard B; Henderson, Brian E; Hoffmeister, Michael; Hopper, John L; Hudson, Thomas J; Hunter, David J; Jackson, Rebecca D; Jee, Sun Ha; Jenkins, Mark A; Jia, Wei-Hua; Kolonel, Laurence N; Kooperberg, Charles; Küry, Sébastien; Lacroix, Andrea Z; Laurie, Cathy C; Laurie, Cecelia A; Le Marchand, Loic; Lemire, Mathieu; Levine, David; Lindor, Noralane M; Liu, Yan; Ma, Jing; Makar, Karen W; Matsuo, Keitaro; Newcomb, Polly A; Potter, John D; Prentice, Ross L; Qu, Conghui; Rohan, Thomas; Rosse, Stephanie A; Schoen, Robert E; Seminara, Daniela; Shrubsole, Martha; Shu, Xiao-Ou; Slattery, Martha L; Taverna, Darin; Thibodeau, Stephen N; Ulrich, Cornelia M; White, Emily; Xiang, Yongbing; Zanke, Brent W; Zeng, Yi-Xin; Zhang, Ben; Zheng, Wei; Hsu, Li

    2013-04-01

    Heritable factors contribute to the development of colorectal cancer. Identifying the genetic loci associated with colorectal tumor formation could elucidate the mechanisms of pathogenesis. We conducted a genome-wide association study that included 14 studies, 12,696 cases of colorectal tumors (11,870 cancer, 826 adenoma), and 15,113 controls of European descent. The 10 most statistically significant, previously unreported findings were followed up in 6 studies; these included 3056 colorectal tumor cases (2098 cancer, 958 adenoma) and 6658 controls of European and Asian descent. Based on the combined analysis, we identified a locus that reached the conventional genome-wide significance level at less than 5.0 × 10(-8): an intergenic region on chromosome 2q32.3, close to nucleic acid binding protein 1 (most significant single nucleotide polymorphism: rs11903757; odds ratio [OR], 1.15 per risk allele; P = 3.7 × 10(-8)). We also found evidence for 3 additional loci with P values less than 5.0 × 10(-7): a locus within the laminin gamma 1 gene on chromosome 1q25.3 (rs10911251; OR, 1.10 per risk allele; P = 9.5 × 10(-8)), a locus within the cyclin D2 gene on chromosome 12p13.32 (rs3217810 per risk allele; OR, 0.84; P = 5.9 × 10(-8)), and a locus in the T-box 3 gene on chromosome 12q24.21 (rs59336; OR, 0.91 per risk allele; P = 3.7 × 10(-7)). In a large genome-wide association study, we associated polymorphisms close to nucleic acid binding protein 1 (which encodes a DNA-binding protein involved in DNA repair) with colorectal tumor risk. We also provided evidence for an association between colorectal tumor risk and polymorphisms in laminin gamma 1 (this is the second gene in the laminin family to be associated with colorectal cancers), cyclin D2 (which encodes for cyclin D2), and T-box 3 (which encodes a T-box transcription factor and is a target of Wnt signaling to β-catenin). The roles of these genes and their products in cancer pathogenesis warrant further

  5. RNA-Seq of Tumor-Educated Platelets Enables Blood-Based Pan-Cancer, Multiclass, and Molecular Pathway Cancer Diagnostics.

    Science.gov (United States)

    Best, Myron G; Sol, Nik; Kooi, Irsan; Tannous, Jihane; Westerman, Bart A; Rustenburg, François; Schellen, Pepijn; Verschueren, Heleen; Post, Edward; Koster, Jan; Ylstra, Bauke; Ameziane, Najim; Dorsman, Josephine; Smit, Egbert F; Verheul, Henk M; Noske, David P; Reijneveld, Jaap C; Nilsson, R Jonas A; Tannous, Bakhos A; Wesseling, Pieter; Wurdinger, Thomas

    2015-11-09

    Tumor-educated blood platelets (TEPs) are implicated as central players in the systemic and local responses to tumor growth, thereby altering their RNA profile. We determined the diagnostic potential of TEPs by mRNA sequencing of 283 platelet samples. We distinguished 228 patients with localized and metastasized tumors from 55 healthy individuals with 96% accuracy. Across six different tumor types, the location of the primary tumor was correctly identified with 71% accuracy. Also, MET or HER2-positive, and mutant KRAS, EGFR, or PIK3CA tumors were accurately distinguished using surrogate TEP mRNA profiles. Our results indicate that blood platelets provide a valuable platform for pan-cancer, multiclass cancer, and companion diagnostics, possibly enabling clinical advances in blood-based "liquid biopsies". Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  6. The potential diagnostic power of circulating tumor cell analysis for non-small-cell lung cancer.

    Science.gov (United States)

    Ross, Kirsty; Pailler, Emma; Faugeroux, Vincent; Taylor, Melissa; Oulhen, Marianne; Auger, Nathalie; Planchard, David; Soria, Jean-Charles; Lindsay, Colin R; Besse, Benjamin; Vielh, Philippe; Farace, Françoise

    2015-01-01

    In non-small-cell lung cancer (NSCLC), genotyping tumor biopsies for targetable somatic alterations has become routine practice. However, serial biopsies have limitations: they may be technically difficult or impossible and could incur serious risks to patients. Circulating tumor cells (CTCs) offer an alternative source for tumor analysis that is easily accessible and presents the potential to identify predictive biomarkers to tailor therapies on a personalized basis. Examined here is our current knowledge of CTC detection and characterization in NSCLC and their potential role in EGFR-mutant, ALK-rearranged and ROS1-rearranged patients. This is followed by discussion of the ongoing issues such as the question of CTC partnership as diagnostic tools in NSCLC.

  7. [Tumor and tumor-like benign mesenchymal lesions of the breast].

    Science.gov (United States)

    Bisceglia, M; Nirchio, V; Carosi, I; Cappucci, U; Decata, A; Paragone, T; Di Mattia, A L

    1995-02-01

    All the spectrum is encompassed of those miscellaneous pathologic entities occurring in the mammary stroma which are on record up to date other than "mixed fibroepithelial" tumors (fibroadenomas and phyllodes tumors) and tumors both "pure" and "mixed" originating from myoepithelium (adenomyoepitheliomas and pleomorphic adenomas). Also they were excluded those dysreactive-autoimmune diseases (sarcoidosis, sclerosing lymphocytic lobulitis, lobular granulomatous mastitis) and those inflammatory-infectious conditions (tuberculosis, actinomycosis, foreign body reactions, Mondor's disease) which can mimick breast tumors clinically or on image analysis, but on the contrary not evoking the idea of a tumor on histology. Specifically, inflammatory pseudotumor, myofibroblastoma, leiomyoma, neurinoma/neurofibroma, benign fibrous histiocytoma, hemangiopericytoma, fibromatosis, nodular fascitis, variants of lipoma, mesenchymoma, amartoma and its variants, hemangiomas, pseudoangiomatous hyperplasia of stroma, amyloid tumor, granular cell tumor, are consecutively described and discussed, with a large list of references enclosed to each rubric. Most of the pictures are taken from personally observed lesions of the breast. Only few pictures referred to are from their analogue lesions which occurred in soft parts of other locations, with specific mention of that when it was the case. Of note after reviewing the literature the fact that no glomus tumor, nor Kaposi's sarcoma either sporadic or in the context of any immunodeficiency, nor myelolipoma has been recorded yet.

  8. Dose painting based on tumor uptake of Cu-ATSM and FDG

    DEFF Research Database (Denmark)

    Clausen, Malene Martini; Hansen, Anders Elias; Lundemann, Michael

    2014-01-01

    definitions based on FDG, 64Cu-ATSM 3 h and 24 h uptake in canine tumors had different localization of the regional dose escalation levels. This indicates that 64Cu-ATSM at two different time-points and FDG provide different biological information that has to be taken into account when using the dose painting...

  9. Geometric accuracy of a novel gimbals based radiation therapy tumor tracking system.

    Science.gov (United States)

    Depuydt, Tom; Verellen, Dirk; Haas, Olivier; Gevaert, Thierry; Linthout, Nadine; Duchateau, Michael; Tournel, Koen; Reynders, Truus; Leysen, Katrien; Hoogeman, Mischa; Storme, Guy; De Ridder, Mark

    2011-03-01

    VERO is a novel platform for image guided stereotactic body radiotherapy. Orthogonal gimbals hold the linac-MLC assembly allowing real-time moving tumor tracking. This study determines the geometric accuracy of the tracking. To determine the tracking error, an 1D moving phantom produced sinusoidal motion with frequencies up to 30 breaths per minute (bpm). Tumor trajectories of patients were reproduced using a 2D robot and pursued with the gimbals tracking system prototype. Using the moving beam light field and a digital-camera-based detection unit tracking errors, system lag and equivalence of pan/tilt performance were measured. The system lag was 47.7 ms for panning and 47.6 ms for tilting. Applying system lag compensation, sinusoidal motion tracking was accurate, with a tracking error 90% percentile E(90%)tracking errors were below 0.14 mm. The 2D tumor trajectories were tracked with an average E(90%) of 0.54 mm, and tracking error standard deviations of 0.20 mm for pan and 0.22 mm for tilt. In terms of dynamic behavior, the gimbaled linac of the VERO system showed to be an excellent approach for providing accurate real-time tumor tracking in radiation therapy. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  10. Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context.

    Science.gov (United States)

    Chiu, Hua-Sheng; Somvanshi, Sonal; Patel, Ektaben; Chen, Ting-Wen; Singh, Vivek P; Zorman, Barry; Patil, Sagar L; Pan, Yinghong; Chatterjee, Sujash S; Sood, Anil K; Gunaratne, Preethi H; Sumazin, Pavel

    2018-04-03

    Long noncoding RNAs (lncRNAs) are commonly dysregulated in tumors, but only a handful are known to play pathophysiological roles in cancer. We inferred lncRNAs that dysregulate cancer pathways, oncogenes, and tumor suppressors (cancer genes) by modeling their effects on the activity of transcription factors, RNA-binding proteins, and microRNAs in 5,185 TCGA tumors and 1,019 ENCODE assays. Our predictions included hundreds of candidate onco- and tumor-suppressor lncRNAs (cancer lncRNAs) whose somatic alterations account for the dysregulation of dozens of cancer genes and pathways in each of 14 tumor contexts. To demonstrate proof of concept, we showed that perturbations targeting OIP5-AS1 (an inferred tumor suppressor) and TUG1 and WT1-AS (inferred onco-lncRNAs) dysregulated cancer genes and altered proliferation of breast and gynecologic cancer cells. Our analysis indicates that, although most lncRNAs are dysregulated in a tumor-specific manner, some, including OIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergistically dysregulate cancer pathways in multiple tumor contexts. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  11. [Neurophysiological identification of the cranial nerves in endoscopic endonasal surgery of skull base tumors].

    Science.gov (United States)

    Shkarubo, A N; Ogurtsova, A A; Moshchev, D A; Lubnin, A Yu; Andreev, D N; Koval', K V; Chernov, I V

    2016-01-01

    Intraoperative identification of the cranial nerves is a useful technique in removal of skull base tumors through the endoscopic endonasal approach. Searching through the scientific literature found one pilot study on the use of triggered electromyography (t-EMG) for identification of the VIth nerve in endonasal endoscopic surgery of skull base tumors (D. San-Juan, et al, 2014). The study objective was to prevent iatrogenic injuries to the cranial nerves without reducing the completeness of tumor tissue resection. In 2014, 5 patients were operated on using the endoscopic endonasal approach. Surgeries were performed for large skull base chordomas (2 cases) and trigeminal nerve neurinomas located in the cavernous sinus (3). Intraoperatively, identification of the cranial nerves was performed by triggered electromyography using a bipolar electrode (except 1 case of chordoma where a monopolar electrode was used). Evaluation of the functional activity of the cranial nerves was carried out both preoperatively and postoperatively. Tumor resection was total in 4 out of 5 cases and subtotal (chordoma) in 1 case. Intraoperatively, the IIIrd (2 patients), Vth (2), and VIth (4) cranial nerves were identified. No deterioration in the function of the intraoperatively identified nerves was observed in the postoperative period. In one case, no responses from the VIth nerve on the right (in the cavernous sinus region) were intraoperatively obtained, and deep paresis (up to plegia) of the nerve-innervated muscles developed in the postoperative period. The nerve function was not impaired before surgery. The t-EMG technique is promising and requires further research.

  12. Tumor-altered dendritic cell function: implications for anti-tumor immunity

    Directory of Open Access Journals (Sweden)

    Kristian Michael Hargadon

    2013-07-01

    Full Text Available Dendritic cells are key regulators of both innate and adaptive immunity, and the array of immunoregulatory functions exhibited by these cells is dictated by their differentiation, maturation, and activation status. Although a major role for these cells in the induction of immunity to pathogens has long been appreciated, data accumulated over the last several years has demonstrated that DC are also critical regulators of anti-tumor immune responses. However, despite the potential for stimulation of robust anti-tumor immunity by DC, tumor-altered DC function has been observed in many cancer patients and tumor-bearing animals and is often associated with tumor immune escape. Such dysfunction has significant implications for both the induction of natural anti-tumor immune responses as well as the efficacy of immunotherapeutic strategies that target endogenous DC in situ or that employ exogenous DC as part of anti-cancer immunization maneuvers. In this review, the major types of tumor-altered DC function will be described, with emphasis on recent insights into the mechanistic bases for the inhibition of DC differentiation from hematopoietic precursors, the altered programming of DC precursors to differentiate into myeloid-derived suppressor cells or tumor-associated macrophages, the suppression of DC maturation and activation, and the induction of immunoregulatory DC by tumors, tumor-derived factors, and tumor-associated cells within the milieu of the tumor microenvironment. The impact of these tumor-altered cells on the quality of the overall anti-tumor immune response will also be discussed. Finally, this review will also highlight questions concerning tumor-altered DC function that remain unanswered, and it will address factors that have limited advances in the study of this phenomenon in order to focus future research efforts in the field on identifying strategies for interfering with tumor-associated DC dysfunction and improving DC-mediated anti-tumor

  13. Age-stratified analysis of tumor markers and tumor characteristics in adolescents and young women with mature cystic teratoma

    Directory of Open Access Journals (Sweden)

    Huseyin Yesilyurt

    2018-06-01

    Full Text Available Background: Serum tumor markers are widely used for the preoperative evaluation of an adnexal mass. Elevations of cancer antigen (CA 125 and CA 19-9 have been reported in patients with mature cystic teratoma (MCT. The aim of the study is to investigate the relation of serum tumor markers with tumor characteristics in young women with MCT. Methods: We conducted a retrospective review of 157 patients under the age of 35 who underwent laparoscopic surgery for ovarian MCT. Patients were divided into two age groups: Group I (n = 80: adolescents/young adults (aged 13–25 years and Group II (n = 77: women aged 26–35 years. Data were analyzed for serum tumor markers, tumor size, and bilaterality. Results: The rates of elevated CA 125 and CA 19-9 were 10.7% and 31.5%, respectively, for Group I, and 13.9% and 26.5%, respectively, for Group II. The bilaterality rate was higher in Group II compared to Group I (19.5% vs. 8.8%, respectively, p = 0.04. Serum CA 125 and CA 19-9 elevations were not related to tumor size in Group I. In Group II, elevated levels of CA 125 were also unrelated to tumor size. However, significant elevation in CA 19-9 levels was observed when tumor size was larger than 4 cm in this age group (p = 0.004. Elevated CA 125 and CA 19-9 levels were not significantly associated with the presence of bilateral MCT in either group. Conclusion: The results of our study indicate that elevations of CA 19-9 are associated with larger tumor size in women aged 26–35 years, but not in adolescents/young adults. However, elevated serum CA 125 levels are not related to tumor size in either age group. Keywords: Adolescents, Mature cystic teratoma, Tumor marker, Tumor size, Young women

  14. Tumor Hypoxia is Independent of Hemoglobin and Prognostic for Loco-regional Tumor Control after Primary Radiotherapy in Advanced Head and Neck Cancer

    International Nuclear Information System (INIS)

    Nordsmark, Marianne; Overgaard, Jens

    2004-01-01

    There is evidence that tumor hypoxia adversely affects loco-regional tumor control and survival in head and neck cancer. The aim of the current study was to compare pretreatment tumor oxygenation measured by Eppendorf pO2 electrodes with known prognostic factors in advanced head and neck tumors after definitive radiotherapy, and to evaluate the prognostic significance of these parameters on loco-regional tumor control. Sixty-seven patients, median age 56 years (22-82), all with primary stage III-IV squamous cell carcinoma were available for survival analysis. Tumor oxygenation was described as the fraction of pO2 values=2.5 mmHg (HP2.5) and the median tumor pO2. By regression analysis HP2.5 was independent of known prognostic factors including stage, pretreatment hemoglobin (Hb) and the largest tumor diameter at the site of pO2 measurement. By Kaplan-Meier analysis loco-regional tumor control at 5 years was in favor of less hypoxic tumors using either HP2.5 or median tumor pO2 as descriptors and stratifying by the median values. Also, Hb was prognostic of loco-regional tumor control at 5 years using the median value as cut off. HP2.5 as continuous parameter was highly significant for loco-regional tumor control in a multivariate analysis. In conclusion both HP2.5 and total Hb were prognostic for loco-regional tumor control, but HP2.5 as continuous variable was independently the strongest prognostic indicator for loco-regional tumor control after definitive primary radiotherapy in advanced head and neck tumors

  15. Accounting for measurement error in biomarker data and misclassification of subtypes in the analysis of tumor data.

    Science.gov (United States)

    Nevo, Daniel; Zucker, David M; Tamimi, Rulla M; Wang, Molin

    2016-12-30

    A common paradigm in dealing with heterogeneity across tumors in cancer analysis is to cluster the tumors into subtypes using marker data on the tumor, and then to analyze each of the clusters separately. A more specific target is to investigate the association between risk factors and specific subtypes and to use the results for personalized preventive treatment. This task is usually carried out in two steps-clustering and risk factor assessment. However, two sources of measurement error arise in these problems. The first is the measurement error in the biomarker values. The second is the misclassification error when assigning observations to clusters. We consider the case with a specified set of relevant markers and propose a unified single-likelihood approach for normally distributed biomarkers. As an alternative, we consider a two-step procedure with the tumor type misclassification error taken into account in the second-step risk factor analysis. We describe our method for binary data and also for survival analysis data using a modified version of the Cox model. We present asymptotic theory for the proposed estimators. Simulation results indicate that our methods significantly lower the bias with a small price being paid in terms of variance. We present an analysis of breast cancer data from the Nurses' Health Study to demonstrate the utility of our method. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  16. Does cell phone use increase the chances of parotid gland tumor development? A systematic review and meta-analysis.

    Science.gov (United States)

    de Siqueira, Elisa Carvalho; de Souza, Fabrício Tinoco Alvim; Gomez, Ricardo Santiago; Gomes, Carolina Cavalieri; de Souza, Renan Pedra

    2017-08-01

    Prior epidemiological studies had examined the association between cell phone use and the development of tumors in the parotid glands. However, there is no consensus about the question of whether cell phone use is associated with increased risk of tumors in the parotid glands. We performed a meta-analysis to evaluate the existing literature about the mean question and to determine their statistical significance. Primary association studies. Papers that associated cell phone use and parotid gland tumors development were included, with no restrictions regarding publication date, language, and place of publication. Systematic literature search using PubMed, SciELO and Embase followed by meta-analysis. Initial screening included 37 articles, and three were included in meta-analysis. Using three independent samples including 5087 subjects from retrospective case-control studies, cell phone use seems to be associated with greater odds (1.28, 95%- confidence interval: 1.09-1.51) to develop salivary gland tumor. Results should be read with caution due to the limited number of studies available and their retrospective design. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Tumor-stroma ratio(TSR) as a potential novel predictor of prognosis in digestive system cancers: A meta-analysis.

    Science.gov (United States)

    Zhang, Runjin; Song, Wei; Wang, Kai; Zou, Shubing

    2017-09-01

    The tumor-stroma ratio (TSR) has been reported as a prognosis predictor in multiple cancers. The aim of this meta-analysis was to investigate the potential value of TSR as a prognostic predictor of cancer in the digestive system. We searched PubMed, Embase, Elsevier and Web of Science. All studies exploring the association of TSR with overall survival (OS) or disease-free survival (DFS), and lymph node metastasis (LNM) were identified. In total, eight studies were eligible for analysis, and they included 1959 patients. Meta-analysis showed that the low TSR in the tumor could predict poor overall survival (OS) in multiple cancers (pooled Hazard Ratio [HR]: 2.15, 95%CI: 1.80-2.57, P<0.00001, fixed effects). For disease-free survival (DFS), low TSR was also a significant predictor (pooled Hazard Ratio [HR]: 2.31, 95%CI: 1.88-2.83, P<0.00001, fixed effects). In addition, low TSR was correlated with tumor stage. The tumor-stroma ratio (TSR) may potentially serve as a poor prognostic predictor for the metastasis and prognosis of cancer. Copyright © 2017. Published by Elsevier B.V.

  18. Improved tumor-targeting MRI contrast agents: Gd(DOTA) conjugates of a cycloalkane-based RGD peptide

    International Nuclear Information System (INIS)

    Park, Ji-Ae; Lee, Yong Jin; Ko, In Ok; Kim, Tae-Jeong; Chang, Yongmin; Lim, Sang Moo; Kim, Kyeong Min; Kim, Jung Young

    2014-01-01

    Highlights: • Development of improved tumor-targeting MRI contrast agents. • To increase the targeting ability of RGD, we developed cycloalkane-based RGD peptides. • Gd(DOTA) conjugates of cycloalkane-based RGD peptide show improved tumor signal enhancement in vivo MR images. - Abstract: Two new MRI contrast agents, Gd-DOTA-c(RGD-ACP-K) (1) and Gd-DOTA-c(RGD-ACH-K) (2), which were designed by incorporating aminocyclopentane (ACP)- or aminocyclohexane (ACH)-carboxylic acid into Gd-DOTA (gadolinium-tetraazacyclo dodecanetetraacetic acid) and cyclic RGDK peptides, were synthesized and evaluated for tumor-targeting ability in vitro and in vivo. Binding affinity studies showed that both 1 and 2 exhibited higher affinity for integrin receptors than cyclic RGDyK peptides, which were used as a reference. These complexes showed high relaxivity and good stability in human serum and have the potential to improve target-specific signal enhancement in vivo MR images

  19. Improved tumor-targeting MRI contrast agents: Gd(DOTA) conjugates of a cycloalkane-based RGD peptide

    Energy Technology Data Exchange (ETDEWEB)

    Park, Ji-Ae, E-mail: jpark@kirams.re.kr [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Lee, Yong Jin; Ko, In Ok [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kim, Tae-Jeong; Chang, Yongmin [Institute of Biomedical Engineering, Kyungpook National University, Daegu (Korea, Republic of); Lim, Sang Moo [Department of Nuclear Medicine, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kim, Kyeong Min [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kim, Jung Young, E-mail: jykim@kirams.re.kr [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2014-12-12

    Highlights: • Development of improved tumor-targeting MRI contrast agents. • To increase the targeting ability of RGD, we developed cycloalkane-based RGD peptides. • Gd(DOTA) conjugates of cycloalkane-based RGD peptide show improved tumor signal enhancement in vivo MR images. - Abstract: Two new MRI contrast agents, Gd-DOTA-c(RGD-ACP-K) (1) and Gd-DOTA-c(RGD-ACH-K) (2), which were designed by incorporating aminocyclopentane (ACP)- or aminocyclohexane (ACH)-carboxylic acid into Gd-DOTA (gadolinium-tetraazacyclo dodecanetetraacetic acid) and cyclic RGDK peptides, were synthesized and evaluated for tumor-targeting ability in vitro and in vivo. Binding affinity studies showed that both 1 and 2 exhibited higher affinity for integrin receptors than cyclic RGDyK peptides, which were used as a reference. These complexes showed high relaxivity and good stability in human serum and have the potential to improve target-specific signal enhancement in vivo MR images.

  20. Mutation Detection in Patients With Advanced Cancer by Universal Sequencing of Cancer-Related Genes in Tumor and Normal DNA vs Guideline-Based Germline Testing.

    Science.gov (United States)

    Mandelker, Diana; Zhang, Liying; Kemel, Yelena; Stadler, Zsofia K; Joseph, Vijai; Zehir, Ahmet; Pradhan, Nisha; Arnold, Angela; Walsh, Michael F; Li, Yirong; Balakrishnan, Anoop R; Syed, Aijazuddin; Prasad, Meera; Nafa, Khedoudja; Carlo, Maria I; Cadoo, Karen A; Sheehan, Meg; Fleischut, Megan H; Salo-Mullen, Erin; Trottier, Magan; Lipkin, Steven M; Lincoln, Anne; Mukherjee, Semanti; Ravichandran, Vignesh; Cambria, Roy; Galle, Jesse; Abida, Wassim; Arcila, Marcia E; Benayed, Ryma; Shah, Ronak; Yu, Kenneth; Bajorin, Dean F; Coleman, Jonathan A; Leach, Steven D; Lowery, Maeve A; Garcia-Aguilar, Julio; Kantoff, Philip W; Sawyers, Charles L; Dickler, Maura N; Saltz, Leonard; Motzer, Robert J; O'Reilly, Eileen M; Scher, Howard I; Baselga, Jose; Klimstra, David S; Solit, David B; Hyman, David M; Berger, Michael F; Ladanyi, Marc; Robson, Mark E; Offit, Kenneth

    2017-09-05

    Guidelines for cancer genetic testing based on family history may miss clinically actionable genetic changes with established implications for cancer screening or prevention. To determine the proportion and potential clinical implications of inherited variants detected using simultaneous sequencing of the tumor and normal tissue ("tumor-normal sequencing") compared with genetic test results based on current guidelines. From January 2014 until May 2016 at Memorial Sloan Kettering Cancer Center, 10 336 patients consented to tumor DNA sequencing. Since May 2015, 1040 of these patients with advanced cancer were referred by their oncologists for germline analysis of 76 cancer predisposition genes. Patients with clinically actionable inherited mutations whose genetic test results would not have been predicted by published decision rules were identified. Follow-up for potential clinical implications of mutation detection was through May 2017. Tumor and germline sequencing compared with the predicted yield of targeted germline sequencing based on clinical guidelines. Proportion of clinically actionable germline mutations detected by universal tumor-normal sequencing that would not have been detected by guideline-directed testing. Of 1040 patients, the median age was 58 years (interquartile range, 50.5-66 years), 65.3% were male, and 81.3% had stage IV disease at the time of genomic analysis, with prostate, renal, pancreatic, breast, and colon cancer as the most common diagnoses. Of the 1040 patients, 182 (17.5%; 95% CI, 15.3%-19.9%) had clinically actionable mutations conferring cancer susceptibility, including 149 with moderate- to high-penetrance mutations; 101 patients tested (9.7%; 95% CI, 8.1%-11.7%) would not have had these mutations detected using clinical guidelines, including 65 with moderate- to high-penetrance mutations. Frequency of inherited mutations was related to case mix, stage, and founder mutations. Germline findings led to discussion or initiation of

  1. Recommendations for reporting tumor budding in colorectal cancer based on the International Tumor Budding Consensus Conference (ITBCC) 2016

    DEFF Research Database (Denmark)

    Lugli, Alessandro; Kirsch, Richard; Ajioka, Yoichi

    2017-01-01

    to determine the strength of recommendations and quality of evidence. The following 10 statements achieved consensus: Tumor budding is defined as a single tumor cell or a cell cluster consisting of four tumor cells or less (22/22, 100%). Tumor budding is an independent predictor of lymph node metastases in pT1......%). Intratumoral budding exists in colorectal cancer and has been shown to be related to lymph node metastasis (22/22, 100%). Tumor budding is assessed in one hotspot (in a field measuring 0.785 mm 2) at the invasive front (22/22, 100%). A three-tier system should be used along with the budding count in order...

  2. Chemotherapy-Induced Macrophage Infiltration into Tumors Enhances Nanographene-Based Photodynamic Therapy.

    Science.gov (United States)

    Zhao, Yang; Zhang, Chenran; Gao, Liquan; Yu, Xinhe; Lai, Jianhao; Lu, Dehua; Bao, Rui; Wang, Yanpu; Jia, Bing; Wang, Fan; Liu, Zhaofei

    2017-11-01

    Increased recruitment of tumor-associated macrophages (TAM) to tumors following chemotherapy promotes tumor resistance and recurrence and correlates with poor prognosis. TAM depletion suppresses tumor growth, but is not highly effective due to the effects of tumorigenic mediators from other stromal sources. Here, we report that adoptive macrophage transfer led to a dramatically enhanced photodynamic therapy (PDT) effect of 2-(1-hexyloxyethyl)-2-devinyl pyropheophor-bide-alpha (HPPH)-coated polyethylene glycosylated nanographene oxide [GO(HPPH)-PEG] by increasing its tumor accumulation. Moreover, tumor treatment with commonly used chemotherapeutic drugs induced an increase in macrophage infiltration into tumors, which also enhanced tumor uptake and the PDT effects of GO(HPPH)-PEG, resulting in tumor eradication. Macrophage recruitment to tumors after chemotherapy was visualized noninvasively by near-infrared fluorescence and single-photon emission CT imaging using F4/80-specific imaging probes. Our results demonstrate that chemotherapy combined with GO(HPPH)-PEG PDT is a promising strategy for the treatment of tumors, especially those resistant to chemotherapy. Furthermore, TAM-targeted molecular imaging could potentially be used to predict the efficacy of combination therapy and select patients who would most benefit from this treatment approach. Cancer Res; 77(21); 6021-32. ©2017 AACR . ©2017 American Association for Cancer Research.

  3. DNA methylation analysis reveals distinct methylation signatures in pediatric germ cell tumors

    International Nuclear Information System (INIS)

    Amatruda, James F; Frazier, A Lindsay; Poynter, Jenny N; Ross, Julie A; Christensen, Brock; Fustino, Nicholas J; Chen, Kenneth S; Hooten, Anthony J; Nelson, Heather; Kuriger, Jacquelyn K; Rakheja, Dinesh

    2013-01-01

    Aberrant DNA methylation is a prominent feature of many cancers, and may be especially relevant in germ cell tumors (GCTs) due to the extensive epigenetic reprogramming that occurs in the germ line during normal development. We used the Illumina GoldenGate Cancer Methylation Panel to compare DNA methylation in the three main histologic subtypes of pediatric GCTs (germinoma, teratoma and yolk sac tumor (YST); N = 51) and used recursively partitioned mixture models (RPMM) to test associations between methylation pattern and tumor and demographic characteristics. We identified genes and pathways that were differentially methylated using generalized linear models and Ingenuity Pathway Analysis. We also measured global DNA methylation at LINE1 elements and evaluated methylation at selected imprinted loci using pyrosequencing. Methylation patterns differed by tumor histology, with 18/19 YSTs forming a distinct methylation class. Four pathways showed significant enrichment for YSTs, including a human embryonic stem cell pluripotency pathway. We identified 190 CpG loci with significant methylation differences in mature and immature teratomas (q < 0.05), including a number of CpGs in stem cell and pluripotency-related pathways. Both YST and germinoma showed significantly lower methylation at LINE1 elements compared with normal adjacent tissue while there was no difference between teratoma (mature and immature) and normal tissue. DNA methylation at imprinted loci differed significantly by tumor histology and location. Understanding methylation patterns may identify the developmental stage at which the GCT arose and the at-risk period when environmental exposures could be most harmful. Further, identification of relevant genetic pathways could lead to the development of new targets for therapy

  4. TumorBoost: Normalization of allele-specific tumor copy numbers from a single pair of tumor-normal genotyping microarrays

    Directory of Open Access Journals (Sweden)

    Neuvial Pierre

    2010-05-01

    Full Text Available Abstract Background High-throughput genotyping microarrays assess both total DNA copy number and allelic composition, which makes them a tool of choice for copy number studies in cancer, including total copy number and loss of heterozygosity (LOH analyses. Even after state of the art preprocessing methods, allelic signal estimates from genotyping arrays still suffer from systematic effects that make them difficult to use effectively for such downstream analyses. Results We propose a method, TumorBoost, for normalizing allelic estimates of one tumor sample based on estimates from a single matched normal. The method applies to any paired tumor-normal estimates from any microarray-based technology, combined with any preprocessing method. We demonstrate that it increases the signal-to-noise ratio of allelic signals, making it significantly easier to detect allelic imbalances. Conclusions TumorBoost increases the power to detect somatic copy-number events (including copy-neutral LOH in the tumor from allelic signals of Affymetrix or Illumina origin. We also conclude that high-precision allelic estimates can be obtained from a single pair of tumor-normal hybridizations, if TumorBoost is combined with single-array preprocessing methods such as (allele-specific CRMA v2 for Affymetrix or BeadStudio's (proprietary XY-normalization method for Illumina. A bounded-memory implementation is available in the open-source and cross-platform R package aroma.cn, which is part of the Aroma Project (http://www.aroma-project.org/.

  5. SNPase-ARMS qPCR: Ultrasensitive Mutation-Based Detection of Cell-Free Tumor DNA in Melanoma Patients.

    Directory of Open Access Journals (Sweden)

    Julia Stadler

    Full Text Available Cell-free circulating tumor DNA in the plasma of cancer patients has become a common point of interest as indicator of therapy options and treatment response in clinical cancer research. Especially patient- and tumor-specific single nucleotide variants that accurately distinguish tumor DNA from wild type DNA are promising targets. The reliable detection and quantification of these single-base DNA variants is technically challenging. Currently, a variety of techniques is applied, with no apparent "gold standard". Here we present a novel qPCR protocol that meets the conditions of extreme sensitivity and specificity that are required for detection and quantification of tumor DNA. By consecutive application of two polymerases, one of them designed for extreme base-specificity, the method reaches unprecedented sensitivity and specificity. Three qPCR assays were tested with spike-in experiments, specific for point mutations BRAF V600E, PTEN T167A and NRAS Q61L of melanoma cell lines. It was possible to detect down to one copy of tumor DNA per reaction (Poisson distribution, at a background of up to 200 000 wild type DNAs. To prove its clinical applicability, the method was successfully tested on a small cohort of BRAF V600E positive melanoma patients.

  6. Wilms tumor in adults. About 3 cases

    International Nuclear Information System (INIS)

    Castillo, C.; Krygier, G.; Decia, R.; Castillo, L.

    2004-01-01

    Wilms tumor has an incidence of 5% in pediatric tumors .s u Prognosis in this population has improved with the introduction and refinement of therapeutic schemes based radiotherapy and chemotherapy, with a rate of Current 90% cure. In the adult, the Nephroblastoma is outstanding and there are currently no guidelines for terapéutico.Si handling well in the literature, there are a few hundred cases of Wilms tumor, not all of them have been duly confirmed, as a result pathological variety of nomenclatures used in the past. in compared to the pediatric population, Wilms tumor in adults diagnosed with more advanced disease and have a worse prognosis. We present a series of 3 adult patients with Wilms tumor. While two of the patients had histological elements of poor prognosis, the third of these patients had a favorable histology, although the diagnosis was made at an advanced stage. These 3 clinical cases and treatment recommendations for these are described tumors arising from the analysis of the scant literature, and that evolution of these patients seems to corroborate. There is no consensus on how monitoring should be performed curatively operated patients of colon cancer (C C). It is often it is comprehensive

  7. Molecular genetic studies of glial tumors in children

    Directory of Open Access Journals (Sweden)

    P. S. Soltan

    2016-01-01

    Full Text Available Glioblastomas are the most frequent malignant neoplasm among primary brain tumors of childhood. Despite the advances in a multimodality treatment approach including neurosurgery, radiotherapy and chemotherapy, the overall survival of such patients remains poor and doesn’t exceed 14 months. The using of targeted agents such as gefitinib in unselected patient populations showed insufficient efficacy. Nowadays, the most perspective approach is a selection of patient populations potentially sensitive to targeted therapy based on predictive markers of response. We performed a comprehensive analysis of the mutational patterns in 30 glioblastomas of children. Data Analysis was based on the new method of mass spectrometry (OncoCarta v1.0, Sequenom that enabled us to estimate 298 mutations in 19 genes and to identify 10 mutations in 9 tumors (30 %. Mutations were found in BRAF, CDK, HRAS, EGFR, FGFR, MET and PI3K. The most mutated pathway was EGFR – in 20 % of the samples (6/30. The obtained results seem to be very promising in terms of possibilities of using new targeted agents including BRAF inhibitors for treatment of children with glial brain tumors.

  8. Genetic alterations of hepatocellular carcinoma by random amplified polymorphic DNA analysis and cloning sequencing of tumor differential DNA fragment

    Science.gov (United States)

    Xian, Zhi-Hong; Cong, Wen-Ming; Zhang, Shu-Hui; Wu, Meng-Chao

    2005-01-01

    AIM: To study the genetic alterations and their association with clinicopathological characteristics of hepatocellular carcinoma (HCC), and to find the tumor related DNA fragments. METHODS: DNA isolated from tumors and corresponding noncancerous liver tissues of 56 HCC patients was amplified by random amplified polymorphic DNA (RAPD) with 10 random 10-mer arbitrary primers. The RAPD bands showing obvious differences in tumor tissue DNA corresponding to that of normal tissue were separated, purified, cloned and sequenced. DNA sequences were analyzed and compared with GenBank data. RESULTS: A total of 56 cases of HCC were demonstrated to have genetic alterations, which were detected by at least one primer. The detestability of genetic alterations ranged from 20% to 70% in each case, and 17.9% to 50% in each primer. Serum HBV infection, tumor size, histological grade, tumor capsule, as well as tumor intrahepatic metastasis, might be correlated with genetic alterations on certain primers. A band with a higher intensity of 480 bp or so amplified fragments in tumor DNA relative to normal DNA could be seen in 27 of 56 tumor samples using primer 4. Sequence analysis of these fragments showed 91% homology with Homo sapiens double homeobox protein DUX10 gene. CONCLUSION: Genetic alterations are a frequent event in HCC, and tumor related DNA fragments have been found in this study, which may be associated with hepatocarcin-ogenesis. RAPD is an effective method for the identification and analysis of genetic alterations in HCC, and may provide new information for further evaluating the molecular mechanism of hepatocarcinogenesis. PMID:15996039

  9. Residual motion of lung tumors in end-of-inhale respiratory gated radiotherapy based on external surrogates

    International Nuclear Information System (INIS)

    Berbeco, Ross I.; Nishioka, Seiko; Shirato, Hiroki; Jiang, Steve B.

    2006-01-01

    It has been noted that some lung tumors exhibit large periodic motion due to respiration. To limit the amount of dose to healthy lung tissues, many clinics have begun gating radiotherapy treatment using externally placed surrogates. It has been observed by several institutions that the end-of-exhale (EOE) tumor position is more reproducible than other phases of the breathing cycle, so the gating window is often set there. From a treatment planning perspective, end-of-inhale (EOI) phase might be preferred for gating because the expanded lungs will further decrease the healthy tissue within the treatment field. We simulate gated treatment at the EOI phase, using a set of recently measured internal/external anatomy patient data. This paper attempts to answer three questions: (1) How much is the tumor residual motion when we use an external surrogate gating window at EOI? (2) How could we reduce the residual motion in the EOI gating window? (3) Is there a preference for amplitude- versus phase-based gating at EOI? We found that under free breathing conditions the residual motion of the tumors is much larger for EOI phase than for EOE phase. The mean values of residual motion at EOI were found to be 2.2 and 2.7 mm for amplitude- and phase-based gating, respectively, and, at EOE, 1.0 and 1.2 mm for amplitude- and phase-based gating, respectively. However, we note that the residual motion in the EOI gating window is correlated well with the reproducibility of the external surface position in the EOI phase. Using the results of a published breath-coaching study, we deduce that the residual motion of a lung tumor at EOI would approach that at EOE, with the same duty cycle (30%), under breath-coaching conditions. Additionally, we found that under these same conditions, phase-based gating approaches the same residual motion as amplitude-based gating, going from a 28% difference to 11%, for the patient with the largest difference between the two gating modalities. We conclude

  10. Prognostic Impact of Primary Tumor Location on Clinical Outcomes of Metastatic Colorectal Cancer Treated With Cetuximab Plus Oxaliplatin-Based Chemotherapy: A Subgroup Analysis of the JACCRO CC-05/06 Trials.

    Science.gov (United States)

    Sunakawa, Yu; Ichikawa, Wataru; Tsuji, Akihito; Denda, Tadamichi; Segawa, Yoshihiko; Negoro, Yuji; Shimada, Ken; Kochi, Mitsugu; Nakamura, Masato; Kotaka, Masahito; Tanioka, Hiroaki; Takagane, Akinori; Tani, Satoshi; Yamaguchi, Tatsuro; Watanabe, Takanori; Takeuchi, Masahiro; Fujii, Masashi; Nakajima, Toshifusa

    2017-09-01

    Primary tumor location is a critical prognostic factor in metastatic colorectal cancer (mCRC); however, it remains unclear whether tumor location is a predictor of the response to cetuximab treatment. It is also uncertain if BRAF mutation contributes to the impact of tumor location on survival. We assessed the prognostic impact of tumor location on clinical outcomes in mCRC patients treated with first-line cetuximab chemotherapy. The associations of tumor location with overall survival and progression-free survival were evaluated in mCRC patients with KRAS exon 2 wild-type tumors who were enrolled onto 2 clinical trials: JACCRO CC-05 of cetuximab plus FOLFOX (n = 57, UMIN000004197) and CC-06 of cetuximab plus SOX (n = 61, UMIN000007022). Tumors proximal or from splenic flexure to rectum were defined as right-sided or left-sided, respectively. In addition, exploratory RAS and BRAF mutation analyses were performed. A total of 110 patients were assessable for tumor location; 90 had left-sided tumors. Left-sided tumors were significantly associated with longer overall survival (36.2 vs. 12.6 months, hazard ratio = 0.28, P location was an independent prognostic factor irrespective of BRAF status in RAS wild-type patients. Primary tumor location might be a predictor of survival independent of BRAF status in mCRC patients who receive first-line cetuximab combined with oxaliplatin-based chemotherapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. End-to-end workflow for finite element analysis of tumor treating fields in glioblastomas

    Science.gov (United States)

    Timmons, Joshua J.; Lok, Edwin; San, Pyay; Bui, Kevin; Wong, Eric T.

    2017-11-01

    Tumor Treating Fields (TTFields) therapy is an approved modality of treatment for glioblastoma. Patient anatomy-based finite element analysis (FEA) has the potential to reveal not only how these fields affect tumor control but also how to improve efficacy. While the automated tools for segmentation speed up the generation of FEA models, multi-step manual corrections are required, including removal of disconnected voxels, incorporation of unsegmented structures and the addition of 36 electrodes plus gel layers matching the TTFields transducers. Existing approaches are also not scalable for the high throughput analysis of large patient volumes. A semi-automated workflow was developed to prepare FEA models for TTFields mapping in the human brain. Magnetic resonance imaging (MRI) pre-processing, segmentation, electrode and gel placement, and post-processing were all automated. The material properties of each tissue were applied to their corresponding mask in silico using COMSOL Multiphysics (COMSOL, Burlington, MA, USA). The fidelity of the segmentations with and without post-processing was compared against the full semi-automated segmentation workflow approach using Dice coefficient analysis. The average relative differences for the electric fields generated by COMSOL were calculated in addition to observed differences in electric field-volume histograms. Furthermore, the mesh file formats in MPHTXT and NASTRAN were also compared using the differences in the electric field-volume histogram. The Dice coefficient was less for auto-segmentation without versus auto-segmentation with post-processing, indicating convergence on a manually corrected model. An existent but marginal relative difference of electric field maps from models with manual correction versus those without was identified, and a clear advantage of using the NASTRAN mesh file format was found. The software and workflow outlined in this article may be used to accelerate the investigation of TTFields in

  12. End-to-end workflow for finite element analysis of tumor treating fields in glioblastomas.

    Science.gov (United States)

    Timmons, Joshua J; Lok, Edwin; San, Pyay; Bui, Kevin; Wong, Eric T

    2017-10-12

    Tumor Treating Fields (TTFields) therapy is an approved modality of treatment for glioblastoma. Patient anatomy-based finite element analysis (FEA) has the potential to reveal not only how these fields affect tumor control but also how to improve efficacy. While the automated tools for segmentation speed up the generation of FEA models, multi-step manual corrections are required, including removal of disconnected voxels, incorporation of unsegmented structures and the addition of 36 electrodes plus gel layers matching the TTFields transducers. Existing approaches are also not scalable for the high throughput analysis of large patient volumes. A semi-automated workflow was developed to prepare FEA models for TTFields mapping in the human brain. Magnetic resonance imaging (MRI) pre-processing, segmentation, electrode and gel placement, and post-processing were all automated. The material properties of each tissue were applied to their corresponding mask in silico using COMSOL Multiphysics (COMSOL, Burlington, MA, USA). The fidelity of the segmentations with and without post-processing was compared against the full semi-automated segmentation workflow approach using Dice coefficient analysis. The average relative differences for the electric fields generated by COMSOL were calculated in addition to observed differences in electric field-volume histograms. Furthermore, the mesh file formats in MPHTXT and NASTRAN were also compared using the differences in the electric field-volume histogram. The Dice coefficient was less for auto-segmentation without versus auto-segmentation with post-processing, indicating convergence on a manually corrected model. An existent but marginal relative difference of electric field maps from models with manual correction versus those without was identified, and a clear advantage of using the NASTRAN mesh file format was found. The software and workflow outlined in this article may be used to accelerate the investigation of TTFields in

  13. Development of amphiphilic gamma-PGA-nanoparticle based tumor vaccine: potential of the nanoparticulate cytosolic protein delivery carrier.

    Science.gov (United States)

    Yoshikawa, Tomoaki; Okada, Naoki; Oda, Atsushi; Matsuo, Kazuhiko; Matsuo, Keisuke; Mukai, Yohei; Yoshioka, Yasuo; Akagi, Takami; Akashi, Mitsuru; Nakagawa, Shinsaku

    2008-02-08

    Nanoscopic therapeutic systems that incorporate biomacromolecules, such as protein and peptides, are emerging as the next generation of nanomedicine aimed at improving the therapeutic efficacy of biomacromolecular drugs. In this study, we report that poly(gamma-glutamic acid)-based nanoparticles (gamma-PGA NPs) are excellent protein delivery carriers for tumor vaccines that delivered antigenic proteins to antigen-presenting cells and elicited potent immune responses. Importantly, gamma-PGA NPs efficiently delivered entrapped antigenic proteins through cytosolic translocation from the endosomes, which is a key process of gamma-PGA NP-mediated anti-tumor immune responses. Our findings suggest that the gamma-PGA NP system is suitable for the intracellular delivery of protein-based drugs as well as tumor vaccines.

  14. Gastrointestinal stromal tumors: retrospective analysis of the computer-tomographic aspects.

    Science.gov (United States)

    Lupescu, Ioana G; Grasu, Mugur; Boros, Mirela; Gheorghe, Cristian; Ionescu, Mihnea; Popescu, Irinel; Herlea, Vlad; Georgescu, Serban A

    2007-06-01

    To describe the computer-tomographic (CT) aspects of gastrointestinal stromal tumors (GISTs) in correlation to their histology. The medical records of all patients at our hospital with a histologic diagnosis of GIST between January 2002 and June 2006, and investigated before surgery by CT, were reviewed. Two radiologists with knowledge of the diagnosis reviewed the CT findings. Amongst 15 cases of GISTs, 9 cases involved the stomach and 4 cases the small intestine. Location of the primary tumor could not be determined for 2 of 15 tumors, because of the presence of extensive peritoneal metastases. Most primary tumors were predominantly extraluminal (13 cases) while two were clearly endoluminal. The mean diameter of the primary tumor was 8 cm. The tumor margin was well defined in 12 patients and irregular in 3 cases. Central fluid attenuation was present in 11 tumors, while central gas was seen in two cases. Metastases were seen in 2 cases at presentation and in another 2 patients during follow-up. Spread was exclusive to the liver or peritoneum. Visceral obstruction was absent even in extensive peritoneal metastatic disease. Ascites was an unusual finding. CT plays an important role not only in the detection and the localization but also in the evaluation of the extension and follow-up of theses tumors. Using only CT aspects, we can only suspect the diagnosis to GISTs. Often other soft-tissue tumors with gastrointestinal involvement can mimic GISTs. In all cases histological diagnosis is essential.

  15. DCE-MRI texture analysis with tumor subregion partitioning for predicting Ki-67 status of estrogen receptor-positive breast cancers

    KAUST Repository

    Fan, Ming; Cheng, Hu; Zhang, Peng; Gao, Xin; Zhang, Juan; Shao, Guoliang; Li, Lihua

    2017-01-01

    Breast tumor heterogeneity is related to risk factors that lead to worse prognosis, yet such heterogeneity has not been well studied.To predict the Ki-67 status of estrogen receptor (ER)-positive breast cancer patients via analysis of tumor

  16. Hypermethylated APC in serous carcinoma based on a meta-analysis of ovarian cancer.

    Science.gov (United States)

    Shen, Chunyan; Sheng, Qifang; Zhang, Xiaojie; Fu, Yuling; Zhu, Kemiao

    2016-09-26

    The reduced expression of the Adenomatous polyposis coli (APC) gene, a tumor suppressor gene, through promoter hypermethylation has been reported to play a key role in the carcinogenesis. However, the correlation between APC promoter hypermethylation and ovarian cancer (OC) remains to be clarified. A comprehensive literature search was carried out in related research databases. The overall odds ratio (OR) and corresponding 95 % confidence interval (CI) were used to evaluate the effects of APC promoter hypermethylation on OC and clinicopathological characteristics. Ultimately, 12 eligible studies were used in our study, including 806 OC samples, 429 normal controls, 109 benign lesions and 75 LMP samples. The pooled OR showed that APC promoter hypermethylation was significantly higher in OC than in normal and benign controls (OR = 6.18 and OR = 3.26, respectively). No significant correlation was observed between OC and low malignant potential (LMP) tumors (P = 0.436). In the comparison of OC and normal controls, subgroup analysis based on race showed that the overall OR of APC promoter hypermethylation was significant and similar in Asians and Caucasians (OR = 8.34 and OR = 5.39, respectively). A subgroup analysis based on sample type found that the pooled OR was significantly higher in blood than in tissue (OR = 18.71 and OR = 5.74, respectively). A significant association was not observed between APC promoter hypermethylation and tumor grade or tumor stage. The pooled OR indicated that APC promoter hypermethylation was significantly lower in serous carcinoma than in non-serous carcinoma (OR = 0.56, P = 0.02). No obvious publication bias was detected by Egger's test (all P > 0.05). APC promoter hypermethylation may be linked to the increased risk of OC. It was associated with histological type, but not with tumor grade or tumor stage. Moreover, hypermethylated APC may be a noninvasive biomarker using blood samples. Future

  17. Spectral imaging based in vivo model system for characterization of tumor microvessel response to vascular targeting agents

    Science.gov (United States)

    Wankhede, Mamta

    Functional vasculature is vital for tumor growth, proliferation, and metastasis. Many tumor-specific vascular targeting agents (VTAs) aim to destroy this essential tumor vasculature to induce indirect tumor cell death via oxygen and nutrition deprivation. The tumor angiogenesis-inhibiting anti-angiogenics (AIs) and the established tumor vessel targeting vascular disrupting agents (VDAs) are the two major players in the vascular targeting field. Combination of VTAs with conventional therapies or with each other, have been shown to have additive or supra-additive effects on tumor control and treatment. Pathophysiological changes post-VTA treatment in terms of structural and vessel function changes are important parameters to characterize the treatment efficacy. Despite the abundance of information regarding these parameters acquired using various techniques, there remains a need for a quantitative, real-time, and direct observation of these phenomenon in live animals. Through this research we aspired to develop a spectral imaging based mouse tumor system for real-time in vivo microvessel structure and functional measurements for VTA characterization. A model tumor system for window chamber studies was identified, and then combinatorial effects of VDA and AI were characterized in model tumor system. (Full text of this dissertation may be available via the University of Florida Libraries web site. Please check http://www.uflib.ufl.edu/etd.html)

  18. A block matching-based registration algorithm for localization of locally advanced lung tumors

    Energy Technology Data Exchange (ETDEWEB)

    Robertson, Scott P.; Weiss, Elisabeth; Hugo, Geoffrey D., E-mail: gdhugo@vcu.edu [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia, 23298 (United States)

    2014-04-15

    Purpose: To implement and evaluate a block matching-based registration (BMR) algorithm for locally advanced lung tumor localization during image-guided radiotherapy. Methods: Small (1 cm{sup 3}), nonoverlapping image subvolumes (“blocks”) were automatically identified on the planning image to cover the tumor surface using a measure of the local intensity gradient. Blocks were independently and automatically registered to the on-treatment image using a rigid transform. To improve speed and robustness, registrations were performed iteratively from coarse to fine image resolution. At each resolution, all block displacements having a near-maximum similarity score were stored. From this list, a single displacement vector for each block was iteratively selected which maximized the consistency of displacement vectors across immediately neighboring blocks. These selected displacements were regularized using a median filter before proceeding to registrations at finer image resolutions. After evaluating all image resolutions, the global rigid transform of the on-treatment image was computed using a Procrustes analysis, providing the couch shift for patient setup correction. This algorithm was evaluated for 18 locally advanced lung cancer patients, each with 4–7 weekly on-treatment computed tomography scans having physician-delineated gross tumor volumes. Volume overlap (VO) and border displacement errors (BDE) were calculated relative to the nominal physician-identified targets to establish residual error after registration. Results: Implementation of multiresolution registration improved block matching accuracy by 39% compared to registration using only the full resolution images. By also considering multiple potential displacements per block, initial errors were reduced by 65%. Using the final implementation of the BMR algorithm, VO was significantly improved from 77% ± 21% (range: 0%–100%) in the initial bony alignment to 91% ± 8% (range: 56%–100%;p < 0

  19. A block matching-based registration algorithm for localization of locally advanced lung tumors

    International Nuclear Information System (INIS)

    Robertson, Scott P.; Weiss, Elisabeth; Hugo, Geoffrey D.

    2014-01-01

    Purpose: To implement and evaluate a block matching-based registration (BMR) algorithm for locally advanced lung tumor localization during image-guided radiotherapy. Methods: Small (1 cm 3 ), nonoverlapping image subvolumes (“blocks”) were automatically identified on the planning image to cover the tumor surface using a measure of the local intensity gradient. Blocks were independently and automatically registered to the on-treatment image using a rigid transform. To improve speed and robustness, registrations were performed iteratively from coarse to fine image resolution. At each resolution, all block displacements having a near-maximum similarity score were stored. From this list, a single displacement vector for each block was iteratively selected which maximized the consistency of displacement vectors across immediately neighboring blocks. These selected displacements were regularized using a median filter before proceeding to registrations at finer image resolutions. After evaluating all image resolutions, the global rigid transform of the on-treatment image was computed using a Procrustes analysis, providing the couch shift for patient setup correction. This algorithm was evaluated for 18 locally advanced lung cancer patients, each with 4–7 weekly on-treatment computed tomography scans having physician-delineated gross tumor volumes. Volume overlap (VO) and border displacement errors (BDE) were calculated relative to the nominal physician-identified targets to establish residual error after registration. Results: Implementation of multiresolution registration improved block matching accuracy by 39% compared to registration using only the full resolution images. By also considering multiple potential displacements per block, initial errors were reduced by 65%. Using the final implementation of the BMR algorithm, VO was significantly improved from 77% ± 21% (range: 0%–100%) in the initial bony alignment to 91% ± 8% (range: 56%–100%;p < 0.001). Left

  20. First experience with a novel luminescence-based optical sensor for measurement of oxygenation in tumors

    International Nuclear Information System (INIS)

    Jarm, T.; Miklavcic, D.; Lesnicar, H.; Sersa, G.

    2001-01-01

    Background. The purpose of this preliminary study was to evaluate a novel luminescence-based fiber-optic sensor (OxyLite system) for the measurement of partial pressure of oxygen (pO 2 ) in tumors and for the detection of changes in pO 2 as a function of time. The new method was used simultaneously with the laser Doppler flowmetry method for the measurement of relative tissue perfusion. Materials and methods. Blood perfusion and pO 2 were measured continuously via fiber-optic sensors inserted into SA-1 tumors in anesthetized A/J mice. The changes in blood flow and oxygenation of tumors were induced by transient changes of the parameters of anesthesia and by injection of a vasoactive drug hydralazine. Results. Both optical methods used in the study successfully detected the induced changes in blood flow and pO 2 . The measurements of pO 2 were well correlated with measurements of microcirculatory blood perfusion. In the majority of pO 2 measurements, we observed an unexpected behavior of the signal during the stabilization process immediately after the insertion of the probe into tumor. This behaviour of the pO 2 signal was most probably caused by local tissue damage induced by the insertion of the probe. Conclusion. The novel luminescence-based optical oximetry can reliably detect local pO 2 changes in tumors as a function of time but some aspects of prolonged pO 2 measurement by this method require further investigation. (author)

  1. Tumor Volume-Adapted Dosing in Stereotactic Ablative Radiotherapy of Lung Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Trakul, Nicholas; Chang, Christine N.; Harris, Jeremy [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); Chapman, Christopher [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); University of Michigan School of Medicine, Ann Arbor, MI (United States); Rao, Aarti [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); University of California, Davis, School of Medicine, Davis, CA (United States); Shen, John [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); University of California, Irvine, School of Medicine, Irvine, CA (United States); Quinlan-Davidson, Sean [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); Department of Radiation Oncology, McMaster University, Juravinski Cancer Centre, Hamilton, Ontario (Canada); Filion, Edith J. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); Departement de Medecine, Service de Radio-Oncologie, Centre Hospitalier de l' Universite de Montreal, Montreal, Quebec (Canada); Wakelee, Heather A.; Colevas, A. Dimitrios [Department of Medicine, Division of Oncology, Stanford University School of Medicine, Stanford, CA (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA (United States); Whyte, Richard I. [Department of Cardiothoracic Surgery, Division of General Thoracic Surgery, Stanford University School of Medicine, Stanford, CA (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA (United States); and others

    2012-09-01

    Purpose: Current stereotactic ablative radiotherapy (SABR) protocols for lung tumors prescribe a uniform dose regimen irrespective of tumor size. We report the outcomes of a lung tumor volume-adapted SABR dosing strategy. Methods and Materials: We retrospectively reviewed the outcomes in 111 patients with a total of 138 primary or metastatic lung tumors treated by SABR, including local control, regional control, distant metastasis, overall survival, and treatment toxicity. We also performed subset analysis on 83 patients with 97 tumors treated with a volume-adapted dosing strategy in which small tumors (gross tumor volume <12 mL) received single-fraction regimens with biologically effective doses (BED) <100 Gy (total dose, 18-25 Gy) (Group 1), and larger tumors (gross tumor volume {>=}12 mL) received multifraction regimens with BED {>=}100 Gy (total dose, 50-60 Gy in three to four fractions) (Group 2). Results: The median follow-up time was 13.5 months. Local control for Groups 1 and 2 was 91.4% and 92.5%, respectively (p = 0.24) at 12 months. For primary lung tumors only (excluding metastases), local control was 92.6% and 91.7%, respectively (p = 0.58). Regional control, freedom from distant metastasis, and overall survival did not differ significantly between Groups 1 and 2. Rates of radiation pneumonitis, chest wall toxicity, and esophagitis were low in both groups, but all Grade 3 toxicities developed in Group 2 (p = 0.02). Conclusion: A volume-adapted dosing approach for SABR of lung tumors seems to provide excellent local control for both small- and large-volume tumors and may reduce toxicity.

  2. Comprehensive allelotype and genetic anaysis of 466 human nervous system tumors

    DEFF Research Database (Denmark)

    von Deimling, A; Fimmers, R; Schmidt, M C

    2000-01-01

    Brain tumors pose a particular challenge to molecular oncology. Many different tumor entities develop in the nervous system and some of them appear to follow distinct pathogenic routes. Molecular genetic alterations have increasingly been reported in nervous system neoplasms. However......, a considerable number of affected genes remain to be identified. We present here a comprehensive allelotype analysis of 466 nervous system tumors based on loss of heterozygosity (LOH) studies with 129 microsatellite markers that span the genome. Specific alterations of the EGFR, CDK4, CDKN2A, TP53, DMBT1, NF2...... may provide a valuable framework for future studies to delineate molecular pathways in many types of human central nervous system tumors....

  3. Microenvironment alters epigenetic and gene expression profiles in Swarm rat chondrosarcoma tumors

    International Nuclear Information System (INIS)

    Hamm, Christopher A; Wang, Deli; Malchenko, Sergey; Fatima Bonaldo, Maria de; Casavant, Thomas L; Hendrix, Mary JC; Soares, Marcelo B; Stevens, Jeff W; Xie, Hehuang; Vanin, Elio F; Morcuende, Jose A; Abdulkawy, Hakeem; Seftor, Elisabeth A; Sredni, Simone T; Bischof, Jared M

    2010-01-01

    Chondrosarcomas are malignant cartilage tumors that do not respond to traditional chemotherapy or radiation. The 5-year survival rate of histologic grade III chondrosarcoma is less than 30%. An animal model of chondrosarcoma has been established - namely, the Swarm Rat Chondrosarcoma (SRC) - and shown to resemble the human disease. Previous studies with this model revealed that tumor microenvironment could significantly influence chondrosarcoma malignancy. To examine the effect of the microenvironment, SRC tumors were initiated at different transplantation sites. Pyrosequencing assays were utilized to assess the DNA methylation of the tumors, and SAGE libraries were constructed and sequenced to determine the gene expression profiles of the tumors. Based on the gene expression analysis, subsequent functional assays were designed to determine the relevancy of the specific genes in the development and progression of the SRC. The site of transplantation had a significant impact on the epigenetic and gene expression profiles of SRC tumors. Our analyses revealed that SRC tumors were hypomethylated compared to control tissue, and that tumors at each transplantation site had a unique expression profile. Subsequent functional analysis of differentially expressed genes, albeit preliminary, provided some insight into the role that thymosin-β4, c-fos, and CTGF may play in chondrosarcoma development and progression. This report describes the first global molecular characterization of the SRC model, and it demonstrates that the tumor microenvironment can induce epigenetic alterations and changes in gene expression in the SRC tumors. We documented changes in gene expression that accompany changes in tumor phenotype, and these gene expression changes provide insight into the pathways that may play a role in the development and progression of chondrosarcoma. Furthermore, specific functional analysis indicates that thymosin-β4 may have a role in chondrosarcoma metastasis

  4. Microenvironment alters epigenetic and gene expression profiles in Swarm rat chondrosarcoma tumors

    Directory of Open Access Journals (Sweden)

    Hamm Christopher A

    2010-09-01

    Full Text Available Abstract Background Chondrosarcomas are malignant cartilage tumors that do not respond to traditional chemotherapy or radiation. The 5-year survival rate of histologic grade III chondrosarcoma is less than 30%. An animal model of chondrosarcoma has been established - namely, the Swarm Rat Chondrosarcoma (SRC - and shown to resemble the human disease. Previous studies with this model revealed that tumor microenvironment could significantly influence chondrosarcoma malignancy. Methods To examine the effect of the microenvironment, SRC tumors were initiated at different transplantation sites. Pyrosequencing assays were utilized to assess the DNA methylation of the tumors, and SAGE libraries were constructed and sequenced to determine the gene expression profiles of the tumors. Based on the gene expression analysis, subsequent functional assays were designed to determine the relevancy of the specific genes in the development and progression of the SRC. Results The site of transplantation had a significant impact on the epigenetic and gene expression profiles of SRC tumors. Our analyses revealed that SRC tumors were hypomethylated compared to control tissue, and that tumors at each transplantation site had a unique expression profile. Subsequent functional analysis of differentially expressed genes, albeit preliminary, provided some insight into the role that thymosin-β4, c-fos, and CTGF may play in chondrosarcoma development and progression. Conclusion This report describes the first global molecular characterization of the SRC model, and it demonstrates that the tumor microenvironment can induce epigenetic alterations and changes in gene expression in the SRC tumors. We documented changes in gene expression that accompany changes in tumor phenotype, and these gene expression changes provide insight into the pathways that may play a role in the development and progression of chondrosarcoma. Furthermore, specific functional analysis indicates that

  5. Preclinical experiments for analysis of tumor regression due to negative pions

    International Nuclear Information System (INIS)

    Blattmann, H.; Cabeza, L.; Fritz-Niggli, H.

    To test the potential therapeutic value of negative pions in comparison with conventional x-rays, cobalt-60 γ rays, and high energy electrons and photons (Betatron), experimental analyses with induced tumors (transplant tumors) after irradiation are to be performed in vivo and in vitro (tumor cell suspensions, cell cultures, spontaneous tumors, carcinoma in ascites form); in addition to tumors primarily of mice, human cell tumors will be used; studies will also be made of cell kinetics with various cell types (normal cells, transformed (malignant) cells, beam-resistant, beam-sensitive types) using cell cultures from Chinese hamsters. An attempt will be made to compare slow- and fast-growing tumors. In a second phase, human tumors in conditioned animals will be tested in situ or as cell cultures. Skin, small intestine, regenerating liver and kidney, together with cell cultures, will serve as normal reaction systems

  6. The relationship between elevated interstitial fluid pressure and blood flow in tumors: a bioengineering analysis

    International Nuclear Information System (INIS)

    Milosevic, Michael F.; Fyles, Anthony W.; Hill, Richard P.

    1999-01-01

    Purpose: To examine the hypothesis that elevated interstitial fluid pressure (IFP) is a cause of reduced blood flow in tumors. Materials and Methods: A physiologic model of tumor blood flow was developed based on a semipermeable, compliant capillary in the center of a spherical tumor. The model incorporates the interaction between the tumor vasculature and the interstitium, as mediated by IFP. It also incorporates the dynamic behavior of the capillary wall in response to changes in transmural pressure, and the effect of viscosity on blood flow. Results: The model predicted elevated tumor IFP in the range of 0 to 56 mmHg. The capillary diameter in the setting of elevated IFP was greatest at the arterial end, and constricted to between 3.2 and 4.4 μm at the venous end. This corresponded to a 2.4- to 3.5-fold reduction in diameter along the length of the capillary. The IFP exceeded the intravascular pressure distally in the capillary, but vascular collapse did not occur. Capillary diameter constriction resulted in a 2.3- to 9.1-fold steady-state reduction in tumor blood flow relative to a state of near-zero IFP. Conclusion: The results suggest that steady-state vascular constriction occurs in the setting of elevated IFP, and leads to reduced tumor blood flow. This may in turn contribute to the development of hypoxia, which is an important cause of radiation treatment failure in many tumors

  7. PCA based clustering for brain tumor segmentation of T1w MRI images.

    Science.gov (United States)

    Kaya, Irem Ersöz; Pehlivanlı, Ayça Çakmak; Sekizkardeş, Emine Gezmez; Ibrikci, Turgay

    2017-03-01

    Medical images are huge collections of information that are difficult to store and process consuming extensive computing time. Therefore, the reduction techniques are commonly used as a data pre-processing step to make the image data less complex so that a high-dimensional data can be identified by an appropriate low-dimensional representation. PCA is one of the most popular multivariate methods for data reduction. This paper is focused on T1-weighted MRI images clustering for brain tumor segmentation with dimension reduction by different common Principle Component Analysis (PCA) algorithms. Our primary aim is to present a comparison between different variations of PCA algorithms on MRIs for two cluster methods. Five most common PCA algorithms; namely the conventional PCA, Probabilistic Principal Component Analysis (PPCA), Expectation Maximization Based Principal Component Analysis (EM-PCA), Generalize Hebbian Algorithm (GHA), and Adaptive Principal Component Extraction (APEX) were applied to reduce dimensionality in advance of two clustering algorithms, K-Means and Fuzzy C-Means. In the study, the T1-weighted MRI images of the human brain with brain tumor were used for clustering. In addition to the original size of 512 lines and 512 pixels per line, three more different sizes, 256 × 256, 128 × 128 and 64 × 64, were included in the study to examine their effect on the methods. The obtained results were compared in terms of both the reconstruction errors and the Euclidean distance errors among the clustered images containing the same number of principle components. According to the findings, the PPCA obtained the best results among all others. Furthermore, the EM-PCA and the PPCA assisted K-Means algorithm to accomplish the best clustering performance in the majority as well as achieving significant results with both clustering algorithms for all size of T1w MRI images. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Intra-Tumor Genetic Heterogeneity in Wilms Tumor: Clonal Evolution and Clinical Implications

    Directory of Open Access Journals (Sweden)

    George D. Cresswell

    2016-07-01

    Full Text Available The evolution of pediatric solid tumors is poorly understood. There is conflicting evidence of intra-tumor genetic homogeneity vs. heterogeneity (ITGH in a small number of studies in pediatric solid tumors. A number of copy number aberrations (CNA are proposed as prognostic biomarkers to stratify patients, for example 1q+ in Wilms tumor (WT; current clinical trials use only one sample per tumor to profile this genetic biomarker. We multisampled 20 WT cases and assessed genome-wide allele-specific CNA and loss of heterozygosity, and inferred tumor evolution, using Illumina CytoSNP12v2.1 arrays, a custom analysis pipeline, and the MEDICC algorithm. We found remarkable diversity of ITGH and evolutionary trajectories in WT. 1q+ is heterogeneous in the majority of tumors with this change, with variable evolutionary timing. We estimate that at least three samples per tumor are needed to detect >95% of cases with 1q+. In contrast, somatic 11p15 LOH is uniformly an early event in WT development. We find evidence of two separate tumor origins in unilateral disease with divergent histology, and in bilateral WT. We also show subclonal changes related to differential response to chemotherapy. Rational trial design to include biomarkers in risk stratification requires tumor multisampling and reliable delineation of ITGH and tumor evolution.

  9. Development of Antibody-Based Vaccines Targeting the Tumor Vasculature.

    Science.gov (United States)

    Zhuang, Xiaodong; Bicknell, Roy

    2016-01-01

    A functional vasculature is essential for tumor progression and malignant cell metastasis. Endothelial cells lining blood vessels in the tumor are exposed to a unique microenvironment, which in turn induces expression of specific proteins designated as tumor endothelial markers (TEMs). TEMs either localized at the plasma membrane or secreted into the extracellular matrix are accessible for antibody targeting, which can be either infused or generated de novo via vaccination. Recent studies have demonstrated vaccines against several TEMs can induce a strong antibody response accompanied by a potent antitumor effect in animal models. These findings present an exciting field for novel anticancer therapy development. As most of the TEMs are self-antigens, breaking tolerance is necessary for a successful vaccine. This chapter describes approaches to efficiently induce a robust antibody response against the tumor vasculature.

  10. Brain Tumor Image Segmentation in MRI Image

    Science.gov (United States)

    Peni Agustin Tjahyaningtijas, Hapsari

    2018-04-01

    Brain tumor segmentation plays an important role in medical image processing. Treatment of patients with brain tumors is highly dependent on early detection of these tumors. Early detection of brain tumors will improve the patient’s life chances. Diagnosis of brain tumors by experts usually use a manual segmentation that is difficult and time consuming because of the necessary automatic segmentation. Nowadays automatic segmentation is very populer and can be a solution to the problem of tumor brain segmentation with better performance. The purpose of this paper is to provide a review of MRI-based brain tumor segmentation methods. There are number of existing review papers, focusing on traditional methods for MRI-based brain tumor image segmentation. this paper, we focus on the recent trend of automatic segmentation in this field. First, an introduction to brain tumors and methods for brain tumor segmentation is given. Then, the state-of-the-art algorithms with a focus on recent trend of full automatic segmentaion are discussed. Finally, an assessment of the current state is presented and future developments to standardize MRI-based brain tumor segmentation methods into daily clinical routine are addressed.

  11. Encouraging Early Clinical Outcomes With Helical Tomotherapy–Based Image-Guided Intensity-Modulated Radiation Therapy for Residual, Recurrent, and/or Progressive Benign/Low-Grade Intracranial Tumors: A Comprehensive Evaluation

    International Nuclear Information System (INIS)

    Gupta, Tejpal; Wadasadawala, Tabassum; Master, Zubin; Phurailatpam, Reena; Pai-Shetty, Rajershi; Jalali, Rakesh

    2012-01-01

    Purpose: To report early clinical outcomes of helical tomotherapy (HT)-based image-guided intensity-modulated radiation therapy (IMRT) in brain tumors of varying shape, size, and location. Materials and Methods: Patients with residual, recurrent, and/or progressive low-grade intracranial and skull-base tumors were treated on a prospective protocol of HT-based IMRT and followed clinicoradiologically. Standardized metrics were used for plan evaluation and outcome analysis. Results: Twenty-seven patients with 30 lesions were treated to a median radiotherapy dose of 54 Gy in 30 fractions. All HT plans resulted in excellent target volume coverage with steep dose-gradients. The mean (standard deviation) dose homogeneity index and conformity index was 0.07 (0.05) and 0.71 (0.08) respectively. At first response assessment, 20 of 30 lesions were stable, whereas 9 showed partial regression. One patient with a recurrent clival chordoma though neurologically stable showed imaging-defined progression, whereas another patient with stable disease on serial imaging had sustained neurologic worsening. With a median follow-up of 19 months (interquartile range, 11–26 months), the 2-year clinicoradiological progression-free survival and overall survival was 93.3% and 100% respectively. Conclusions: Careful selection of radiotherapy technique is warranted for benign/low-grade brain tumors to achieve durable local control with minimum long-term morbidity. Large or complex-shaped tumors benefit most from IMRT. Our early clinical experience of HT-based IMRT for brain tumors has been encouraging.

  12. Encouraging Early Clinical Outcomes With Helical Tomotherapy-Based Image-Guided Intensity-Modulated Radiation Therapy for Residual, Recurrent, and/or Progressive Benign/Low-Grade Intracranial Tumors: A Comprehensive Evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, Tejpal [Department of Radiation Oncology, ACTREC/TMH, Tata Memorial Centre, Kharghar, Navi Mumbai (India); Wadasadawala, Tabassum; Master, Zubin; Phurailatpam, Reena; Pai-Shetty, Rajershi; Jalali, Rakesh [Department of Radiation Oncology, ACTREC/TMH, Tata Memorial Centre, Kharghar, Navi Mumbai (India)

    2012-02-01

    Purpose: To report early clinical outcomes of helical tomotherapy (HT)-based image-guided intensity-modulated radiation therapy (IMRT) in brain tumors of varying shape, size, and location. Materials and Methods: Patients with residual, recurrent, and/or progressive low-grade intracranial and skull-base tumors were treated on a prospective protocol of HT-based IMRT and followed clinicoradiologically. Standardized metrics were used for plan evaluation and outcome analysis. Results: Twenty-seven patients with 30 lesions were treated to a median radiotherapy dose of 54 Gy in 30 fractions. All HT plans resulted in excellent target volume coverage with steep dose-gradients. The mean (standard deviation) dose homogeneity index and conformity index was 0.07 (0.05) and 0.71 (0.08) respectively. At first response assessment, 20 of 30 lesions were stable, whereas 9 showed partial regression. One patient with a recurrent clival chordoma though neurologically stable showed imaging-defined progression, whereas another patient with stable disease on serial imaging had sustained neurologic worsening. With a median follow-up of 19 months (interquartile range, 11-26 months), the 2-year clinicoradiological progression-free survival and overall survival was 93.3% and 100% respectively. Conclusions: Careful selection of radiotherapy technique is warranted for benign/low-grade brain tumors to achieve durable local control with minimum long-term morbidity. Large or complex-shaped tumors benefit most from IMRT. Our early clinical experience of HT-based IMRT for brain tumors has been encouraging.

  13. Genome-wide gene copy number and expression analysis of primary gastric tumors and gastric cancer cell lines

    International Nuclear Information System (INIS)

    Junnila, Siina; Kokkola, Arto; Karjalainen-Lindsberg, Marja-Liisa; Puolakkainen, Pauli; Monni, Outi

    2010-01-01

    Gastric cancer is one of the most common malignancies worldwide and the second most common cause of cancer related death. Gene copy number alterations play an important role in the development of gastric cancer and a change in gene copy number is one of the main mechanisms for a cancer cell to control the expression of potential oncogenes and tumor suppressor genes. To highlight genes of potential biological and clinical relevance in gastric cancer, we carried out a systematic array-based survey of gene expression and copy number levels in primary gastric tumors and gastric cancer cell lines and validated the results using an affinity capture based transcript analysis (TRAC assay) and real-time qRT-PCR. Integrated microarray analysis revealed altogether 256 genes that were located in recurrent regions of gains or losses and had at least a 2-fold copy number- associated change in their gene expression. The expression levels of 13 of these genes, ALPK2, ASAP1, CEACAM5, CYP3A4, ENAH, ERBB2, HHIPL2, LTB4R, MMP9, PERLD1, PNMT, PTPRA, and OSMR, were validated in a total of 118 gastric samples using either the qRT-PCR or TRAC assay. All of these 13 genes were differentially expressed between cancerous samples and nonmalignant tissues (p < 0.05) and the association between copy number and gene expression changes was validated for nine (69.2%) of these genes (p < 0.05). In conclusion, integrated gene expression and copy number microarray analysis highlighted genes that may be critically important for gastric carcinogenesis. TRAC and qRT-PCR analyses validated the microarray results and therefore the role of these genes as potential biomarkers for gastric cancer

  14. Tumor penetrating peptides

    Directory of Open Access Journals (Sweden)

    Tambet eTeesalu

    2013-08-01

    Full Text Available Tumor-homing peptides can be used to deliver drugs into tumors. Phage library screening in live mice has recently identified homing peptides that specifically recognize the endothelium of tumor vessels, extravasate, and penetrate deep into the extravascular tumor tissue. The prototypic peptide of this class, iRGD (CRGDKGPDC, contains the integrin-binding RGD motif. RGD mediates tumor homing through binding to αv integrins, which are selectively expressed on various cells in tumors, including tumor endothelial cells. The tumor-penetrating properties of iRGD are mediated by a second sequence motif, R/KXXR/K. This C-end Rule (or CendR motif is active only when the second basic residue is exposed at the C-terminus of the peptide. Proteolytic processing of iRGD in tumors activates the cryptic CendR motif, which then binds to neuropilin-1 activating an endocytic bulk transport pathway through tumor tissue. Phage screening has also yielded tumor-penetrating peptides that function like iRGD in activating the CendR pathway, but bind to a different primary receptor. Moreover, novel tumor-homing peptides can be constructed from tumor-homing motifs, CendR elements and protease cleavage sites. Pathologies other than tumors can be targeted with tissue-penetrating peptides, and the primary receptor can also be a vascular zip code of a normal tissue. The CendR technology provides a solution to a major problem in tumor therapy, poor penetration of drugs into tumors. The tumor-penetrating peptides are capable of taking a payload deep into tumor tissue in mice, and they also penetrate into human tumors ex vivo. Targeting with these peptides specifically increases the accumulation in tumors of a variety of drugs and contrast agents, such as doxorubicin, antibodies and nanoparticle-based compounds. Remarkably the drug to be targeted does not have to be coupled to the peptide; the bulk transport system activated by the peptide sweeps along any compound that is

  15. Stochastic models for tumoral growth

    Science.gov (United States)

    Escudero, Carlos

    2006-02-01

    Strong experimental evidence has indicated that tumor growth belongs to the molecular beam epitaxy universality class. This type of growth is characterized by the constraint of cell proliferation to the tumor border and the surface diffusion of cells at the growing edge. Tumor growth is thus conceived as a competition for space between the tumor and the host, and cell diffusion at the tumor border is an optimal strategy adopted for minimizing the pressure and helping tumor development. Two stochastic partial differential equations are reported in this paper in order to correctly model the physical properties of tumoral growth in (1+1) and (2+1) dimensions. The advantage of these models is that they reproduce the correct geometry of the tumor and are defined in terms of polar variables. An analysis of these models allows us to quantitatively estimate the response of the tumor to an unfavorable perturbation during growth.

  16. Flow cytometric DNA ploidy analysis of ovarian granulosa cell tumors

    NARCIS (Netherlands)

    D. Chadha; C.J. Cornelisse; A. Schabert (A.)

    1990-01-01

    textabstractAbstract The nuclear DNA content of 50 ovarian tumors initially diagnosed as granulosa cell tumors was measured by flow cytometry using paraffin-embedded archival material. The follow-up period of the patients ranged from 4 months to 19 years. Thirty-eight tumors were diploid or

  17. Pathway-specific differences between tumor cell lines and normal and tumor tissue cells

    Directory of Open Access Journals (Sweden)

    Tozeren Aydin

    2006-11-01

    Full Text Available Abstract Background Cell lines are used in experimental investigation of cancer but their capacity to represent tumor cells has yet to be quantified. The aim of the study was to identify significant alterations in pathway usage in cell lines in comparison with normal and tumor tissue. Methods This study utilized a pathway-specific enrichment analysis of publicly accessible microarray data and quantified the gene expression differences between cell lines, tumor, and normal tissue cells for six different tissue types. KEGG pathways that are significantly different between cell lines and tumors, cell lines and normal tissues and tumor and normal tissue were identified through enrichment tests on gene lists obtained using Significance Analysis of Microarrays (SAM. Results Cellular pathways that were significantly upregulated in cell lines compared to tumor cells and normal cells of the same tissue type included ATP synthesis, cell communication, cell cycle, oxidative phosphorylation, purine, pyrimidine and pyruvate metabolism, and proteasome. Results on metabolic pathways suggested an increase in the velocity nucleotide metabolism and RNA production. Pathways that were downregulated in cell lines compared to tumor and normal tissue included cell communication, cell adhesion molecules (CAMs, and ECM-receptor interaction. Only a fraction of the significantly altered genes in tumor-to-normal comparison had similar expressions in cancer cell lines and tumor cells. These genes were tissue-specific and were distributed sparsely among multiple pathways. Conclusion Significantly altered genes in tumors compared to normal tissue were largely tissue specific. Among these genes downregulation was a major trend. In contrast, cell lines contained large sets of significantly upregulated genes that were common to multiple tissue types. Pathway upregulation in cell lines was most pronounced over metabolic pathways including cell nucleotide metabolism and oxidative

  18. Classification of brain tumor extracts by high resolution ¹H MRS using partial least squares discriminant analysis

    Directory of Open Access Journals (Sweden)

    A.V. Faria

    2011-02-01

    Full Text Available High resolution proton nuclear magnetic resonance spectroscopy (¹H MRS can be used to detect biochemical changes in vitro caused by distinct pathologies. It can reveal distinct metabolic profiles of brain tumors although the accurate analysis and classification of different spectra remains a challenge. In this study, the pattern recognition method partial least squares discriminant analysis (PLS-DA was used to classify 11.7 T ¹H MRS spectra of brain tissue extracts from patients with brain tumors into four classes (high-grade neuroglial, low-grade neuroglial, non-neuroglial, and metastasis and a group of control brain tissue. PLS-DA revealed 9 metabolites as the most important in group differentiation: γ-aminobutyric acid, acetoacetate, alanine, creatine, glutamate/glutamine, glycine, myo-inositol, N-acetylaspartate, and choline compounds. Leave-one-out cross-validation showed that PLS-DA was efficient in group characterization. The metabolic patterns detected can be explained on the basis of previous multimodal studies of tumor metabolism and are consistent with neoplastic cell abnormalities possibly related to high turnover, resistance to apoptosis, osmotic stress and tumor tendency to use alternative energetic pathways such as glycolysis and ketogenesis.

  19. Visual outcome after fractionated stereotactic radiation therapy of benign anterior skull base tumors

    DEFF Research Database (Denmark)

    Astradsson, Arnar; Wiencke, Anne Katrine; Munck af Rosenschold, Per

    2014-01-01

    To determine visual outcome including the occurrence of radiation induced optic neuropathy (RION) as well as tumor control after fractionated stereotactic radiation therapy (FSRT) of benign anterior skull base meningiomas or pituitary adenomas. Thirty-nine patients treated with FSRT for anterior...

  20. Tumor Volume-Adapted Dosing in Stereotactic Ablative Radiotherapy of Lung Tumors

    International Nuclear Information System (INIS)

    Trakul, Nicholas; Chang, Christine N.; Harris, Jeremy; Chapman, Christopher; Rao, Aarti; Shen, John; Quinlan-Davidson, Sean; Filion, Edith J.; Wakelee, Heather A.; Colevas, A. Dimitrios; Whyte, Richard I.

    2012-01-01

    Purpose: Current stereotactic ablative radiotherapy (SABR) protocols for lung tumors prescribe a uniform dose regimen irrespective of tumor size. We report the outcomes of a lung tumor volume-adapted SABR dosing strategy. Methods and Materials: We retrospectively reviewed the outcomes in 111 patients with a total of 138 primary or metastatic lung tumors treated by SABR, including local control, regional control, distant metastasis, overall survival, and treatment toxicity. We also performed subset analysis on 83 patients with 97 tumors treated with a volume-adapted dosing strategy in which small tumors (gross tumor volume <12 mL) received single-fraction regimens with biologically effective doses (BED) <100 Gy (total dose, 18–25 Gy) (Group 1), and larger tumors (gross tumor volume ≥12 mL) received multifraction regimens with BED ≥100 Gy (total dose, 50–60 Gy in three to four fractions) (Group 2). Results: The median follow-up time was 13.5 months. Local control for Groups 1 and 2 was 91.4% and 92.5%, respectively (p = 0.24) at 12 months. For primary lung tumors only (excluding metastases), local control was 92.6% and 91.7%, respectively (p = 0.58). Regional control, freedom from distant metastasis, and overall survival did not differ significantly between Groups 1 and 2. Rates of radiation pneumonitis, chest wall toxicity, and esophagitis were low in both groups, but all Grade 3 toxicities developed in Group 2 (p = 0.02). Conclusion: A volume-adapted dosing approach for SABR of lung tumors seems to provide excellent local control for both small- and large-volume tumors and may reduce toxicity.

  1. SU-G-JeP4-06: Evaluation of Interfractional and Intrafractional Tumor Motion in Stereotactic Liver Radiotherapy, Based On Four-Dimensional Cone-Beam Computed Tomography Using Fiducial Markers

    International Nuclear Information System (INIS)

    Shimohigashi, Y; Araki, F; Toya, R; Maruyama, M; Nakaguchi, Y

    2016-01-01

    Purpose: The purpose of this study was to evaluate the interfractional and intrafractional motion of liver tumors in stereotactic body radiation therapy (SBRT), based on four-dimensional cone-beam computed tomography using fiducial markers. (4D-CBCT). Methods: Seven patients with liver tumors were treated by SBRT with abdominal compression (AC) in five fractions with image guidance based on 4D-CBCT. The 4D-CBCT studies were performed to determine the individualized internal margin for the planning simulation. The interfractional and intrafractional changes of liver tumor motion for all patients was measured, based on the planning simulation 4D-CBCT, pre-SBRT 4D-CBCT, and post-SBRT 4D-CBCT. The interfractional motion change was calculated from the difference in liver tumor amplitude on pre-SBRT 4D-CBCT relative to that of the planning simulation 4D-CBCT for each fraction. The intrafractional motion change was calculated from the difference between the liver tumor amplitudes of the pre- and post-SBRT 4D-CBCT for each fraction. Significant interfractional and intrafractional changes in liver tumor motion were defined as a change ≥3 mm. Statistical analysis was performed using the Pearson correlation. Results: The values of the mean amplitude of liver tumor, as indicated by planning simulation 4D-CBCT, were 1.6 ± 0.8 mm, 1.6 ± 0.9 mm, and 4.9 ± 2.2 mm in the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions, respectively. Pearson correlation coefficients between the liver tumor amplitudes, based on planning simulation 4D-CBCT, and pre-SBRT 4D-CBCT during fraction treatment in the LR, AP, and SI directions were 0.6, 0.7, and 0.8, respectively. Interfractional and intrafractional motion changes of ≥3 mm occurred in 23% and 3% of treatment fractions, respectively. Conclusion: The interfractional and intrafractional changes of liver tumor motion were small in most patients who received liver SBRT with AC. In addition, planning

  2. SU-G-JeP4-06: Evaluation of Interfractional and Intrafractional Tumor Motion in Stereotactic Liver Radiotherapy, Based On Four-Dimensional Cone-Beam Computed Tomography Using Fiducial Markers

    Energy Technology Data Exchange (ETDEWEB)

    Shimohigashi, Y [Department of Radiological Technology, Kumamoto University Hospital, Department of Graduate School of Health Sciences, Kumamoto University (Japan); Araki, F [Department of Health Sciences, Kumamoto University (Japan); Toya, R [Department of Radiation Oncology, Kumamoto University Hospital (Japan); Department of Human Oncology, University of Wisconsin School of Medicine and Public Health (United States); Maruyama, M; Nakaguchi, Y [Department of Radiological Technology, Kumamoto University Hospital (Japan)

    2016-06-15

    Purpose: The purpose of this study was to evaluate the interfractional and intrafractional motion of liver tumors in stereotactic body radiation therapy (SBRT), based on four-dimensional cone-beam computed tomography using fiducial markers. (4D-CBCT). Methods: Seven patients with liver tumors were treated by SBRT with abdominal compression (AC) in five fractions with image guidance based on 4D-CBCT. The 4D-CBCT studies were performed to determine the individualized internal margin for the planning simulation. The interfractional and intrafractional changes of liver tumor motion for all patients was measured, based on the planning simulation 4D-CBCT, pre-SBRT 4D-CBCT, and post-SBRT 4D-CBCT. The interfractional motion change was calculated from the difference in liver tumor amplitude on pre-SBRT 4D-CBCT relative to that of the planning simulation 4D-CBCT for each fraction. The intrafractional motion change was calculated from the difference between the liver tumor amplitudes of the pre- and post-SBRT 4D-CBCT for each fraction. Significant interfractional and intrafractional changes in liver tumor motion were defined as a change ≥3 mm. Statistical analysis was performed using the Pearson correlation. Results: The values of the mean amplitude of liver tumor, as indicated by planning simulation 4D-CBCT, were 1.6 ± 0.8 mm, 1.6 ± 0.9 mm, and 4.9 ± 2.2 mm in the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions, respectively. Pearson correlation coefficients between the liver tumor amplitudes, based on planning simulation 4D-CBCT, and pre-SBRT 4D-CBCT during fraction treatment in the LR, AP, and SI directions were 0.6, 0.7, and 0.8, respectively. Interfractional and intrafractional motion changes of ≥3 mm occurred in 23% and 3% of treatment fractions, respectively. Conclusion: The interfractional and intrafractional changes of liver tumor motion were small in most patients who received liver SBRT with AC. In addition, planning

  3. Imaging-genomics reveals driving pathways of MRI derived volumetric tumor phenotype features in Glioblastoma

    International Nuclear Information System (INIS)

    Grossmann, Patrick; Gutman, David A.; Dunn, William D. Jr; Holder, Chad A.; Aerts, Hugo J. W. L.

    2016-01-01

    Glioblastoma (GBM) tumors exhibit strong phenotypic differences that can be quantified using magnetic resonance imaging (MRI), but the underlying biological drivers of these imaging phenotypes remain largely unknown. An Imaging-Genomics analysis was performed to reveal the mechanistic associations between MRI derived quantitative volumetric tumor phenotype features and molecular pathways. One hundred fourty one patients with presurgery MRI and survival data were included in our analysis. Volumetric features were defined, including the necrotic core (NE), contrast-enhancement (CE), abnormal tumor volume assessed by post-contrast T1w (tumor bulk or TB), tumor-associated edema based on T2-FLAIR (ED), and total tumor volume (TV), as well as ratios of these tumor components. Based on gene expression where available (n = 91), pathway associations were assessed using a preranked gene set enrichment analysis. These results were put into context of molecular subtypes in GBM and prognostication. Volumetric features were significantly associated with diverse sets of biological processes (FDR < 0.05). While NE and TB were enriched for immune response pathways and apoptosis, CE was associated with signal transduction and protein folding processes. ED was mainly enriched for homeostasis and cell cycling pathways. ED was also the strongest predictor of molecular GBM subtypes (AUC = 0.61). CE was the strongest predictor of overall survival (C-index = 0.6; Noether test, p = 4x10 −4 ). GBM volumetric features extracted from MRI are significantly enriched for information about the biological state of a tumor that impacts patient outcomes. Clinical decision-support systems could exploit this information to develop personalized treatment strategies on the basis of noninvasive imaging. The online version of this article (doi:10.1186/s12885-016-2659-5) contains supplementary material, which is available to authorized users

  4. Deep learning based classification of breast tumors with shear-wave elastography.

    Science.gov (United States)

    Zhang, Qi; Xiao, Yang; Dai, Wei; Suo, Jingfeng; Wang, Congzhi; Shi, Jun; Zheng, Hairong

    2016-12-01

    This study aims to build a deep learning (DL) architecture for automated extraction of learned-from-data image features from the shear-wave elastography (SWE), and to evaluate the DL architecture in differentiation between benign and malignant breast tumors. We construct a two-layer DL architecture for SWE feature extraction, comprised of the point-wise gated Boltzmann machine (PGBM) and the restricted Boltzmann machine (RBM). The PGBM contains task-relevant and task-irrelevant hidden units, and the task-relevant units are connected to the RBM. Experimental evaluation was performed with five-fold cross validation on a set of 227 SWE images, 135 of benign tumors and 92 of malignant tumors, from 121 patients. The features learned with our DL architecture were compared with the statistical features quantifying image intensity and texture. Results showed that the DL features achieved better classification performance with an accuracy of 93.4%, a sensitivity of 88.6%, a specificity of 97.1%, and an area under the receiver operating characteristic curve of 0.947. The DL-based method integrates feature learning with feature selection on SWE. It may be potentially used in clinical computer-aided diagnosis of breast cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. First Application of 7T Magnetic Resonance Imaging in Endoscopic Endonasal Surgery of Skull Base Tumors

    Science.gov (United States)

    Barrett, Thomas F; Dyvorne, Hadrien A; Padormo, Francesco; Pawha, Puneet S; Delman, Bradley N; Shrivastava, Raj K; Balchandani, Priti

    2018-01-01

    Background Successful endoscopic endonasal surgery for the resection of skull base tumors is reliant on preoperative imaging to delineate pathology from the surrounding anatomy. The increased signal-to-noise ratio afforded by 7T MRI can be used to increase spatial and contrast resolution, which may lend itself to improved imaging of skull base. In this study, we apply a 7T imaging protocol to patients with skull base tumors and compare the images to clinical standard of care. Methods Images were acquired at 7T on 11 patients with skull base lesions. Two neuroradiologists evaluated clinical 1.5T, 3T, and 7T scans for detection of intracavernous cranial nerves and ICA branches. Detection rates were compared. Images were utilized for surgical planning and uploaded to a neuronavigation platform and used to guide surgery. Results Image analysis yielded improved detection rates of cranial nerves and ICA branches at 7T. 7T images were successfully incorporated into preoperative planning and intraoperative neuronavigation. Conclusion Our study represents the first application of 7T MRI to the full neurosurgical workflow for endoscopic endonasal surgery. We detected higher rates of cranial nerves and ICA branches at 7T MRI compared to 3T and 1.5 T, and found that integration of 7T into surgical planning and guidance was feasible. These results suggest a potential for 7T MRI to reduce surgical complications. Future studies comparing standardized 7T, 3T, and 1.5 T MRI protocols in a larger number of patients are warranted to determine the relative benefit of 7T MRI for endonasal endoscopic surgical efficacy. PMID:28359922

  6. First Application of 7-T Magnetic Resonance Imaging in Endoscopic Endonasal Surgery of Skull Base Tumors.

    Science.gov (United States)

    Barrett, Thomas F; Dyvorne, Hadrien A; Padormo, Francesco; Pawha, Puneet S; Delman, Bradley N; Shrivastava, Raj K; Balchandani, Priti

    2017-07-01

    Successful endoscopic endonasal surgery for the resection of skull base tumors is reliant on preoperative imaging to delineate pathology from the surrounding anatomy. The increased signal-to-noise ratio afforded by 7-T MRI can be used to increase spatial and contrast resolution, which may lend itself to improved imaging of the skull base. In this study, we apply a 7-T imaging protocol to patients with skull base tumors and compare the images with clinical standard of care. Images were acquired at 7 T on 11 patients with skull base lesions. Two neuroradiologists evaluated clinical 1.5-, 3-, and 7-T scans for detection of intracavernous cranial nerves and internal carotid artery (ICA) branches. Detection rates were compared. Images were used for surgical planning and uploaded to a neuronavigation platform and used to guide surgery. Image analysis yielded improved detection rates of cranial nerves and ICA branches at 7 T. The 7-T images were successfully incorporated into preoperative planning and intraoperative neuronavigation. Our study represents the first application of 7-T MRI to the full neurosurgical workflow for endoscopic endonasal surgery. We detected higher rates of cranial nerves and ICA branches at 7-T MRI compared with 3- and 1.5-T MRI, and found that integration of 7 T into surgical planning and guidance was feasible. These results suggest a potential for 7-T MRI to reduce surgical complications. Future studies comparing standardized 7-, 3-, and 1.5-T MRI protocols in a larger number of patients are warranted to determine the relative benefit of 7-T MRI for endonasal endoscopic surgical efficacy. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Clinical Evaluation and Cost-Effectiveness Analysis of Serum Tumor Markers in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Rong Wang

    2013-01-01

    Full Text Available The detection of serum tumor markers is valuable for the early diagnosis of lung cancer. Tumor markers are frequently used for the management of cancer patients. However, single markers are less efficient but marker combinations increase the cost, which is troublesome for clinics. To find an optimal serum marker combination panel that benefits the patients and the medical management system as well, four routine lung cancer serum markers (SCCA, NSE, CEA, and CYFRA21-1 were evaluated individually and in combination. Meanwhile, the costs and effects of these markers in clinical practice in China were assessed by cost-effectiveness analysis. As expected, combinations of these tumor markers improved their sensitivity for lung cancer and different combination panels had their own usefulness. NSE + CEA + CYFRA21-1 was the optimal combination panel with highest Youden’s index (0.64, higher sensitivity (75.76%, and specificity (88.57%, which can aid the clinical diagnosis of lung cancer. Nevertheless, the most cost-effective combination was SCCA + CEA, which can be used to screen the high-risk group.

  8. MDM2 SNP309, gene-gene interaction, and tumor susceptibility: an updated meta-analysis

    Directory of Open Access Journals (Sweden)

    Wu Wei

    2011-05-01

    Full Text Available Abstract Background The tumor suppressor gene p53 is involved in multiple cellular pathways including apoptosis, transcriptional control, and cell cycle regulation. In the last decade it has been demonstrated that the single nucleotide polymorphism (SNP at codon 72 of the p53 gene is associated with the risk for development of various neoplasms. MDM2 SNP309 is a single nucleotide T to G polymorphism located in the MDM2 gene promoter. From the time that this well-characterized functional polymorphism was identified, a variety of case-control studies have been published that investigate the possible association between MDM2 SNP309 and cancer risk. However, the results of the published studies, as well as the subsequent meta-analyses, remain contradictory. Methods To investigate whether currently published epidemiological studies can clarify the potential interaction between MDM2 SNP309 and the functional genetic variant in p53 codon72 (Arg72Pro and p53 mutation status, we performed a meta-analysis of the risk estimate on 27,813 cases with various tumor types and 30,295 controls. Results The data we reviewed indicated that variant homozygote 309GG and heterozygote 309TG were associated with a significant increased risk of all tumor types (homozygote comparison: odds ratio (OR = 1.25, 95% confidence interval (CI = 1.13-1.37; heterozygote comparison: OR = 1.10, 95% CI = 1.03-1.17. We also found that the combination of GG and Pro/Pro, TG and Pro/Pro, GG and Arg/Arg significantly increased the risk of cancer (OR = 3.38, 95% CI = 1.77-6.47; OR = 1.88, 95% CI = 1.26-2.81; OR = 1.96, 95% CI = 1.01-3.78, respectively. In a stratified analysis by tumor location, we also found a significant increased risk in brain, liver, stomach and uterus cancer (OR = 1.47, 95% CI = 1.06-2.03; OR = 2.24, 95%CI = 1.57-3.18; OR = 1.54, 95%CI = 1.04-2.29; OR = 1.34, 95%CI = 1.07-1.29, respectively. However, no association was seen between MDM2 SNP309 and tumor susceptibility

  9. A new assessment model for tumor heterogeneity analysis with [18]F-FDG PET images.

    Science.gov (United States)

    Wang, Ping; Xu, Wengui; Sun, Jian; Yang, Chengwen; Wang, Gang; Sa, Yu; Hu, Xin-Hua; Feng, Yuanming

    2016-01-01

    It has been shown that the intratumor heterogeneity can be characterized with quantitative analysis of the [18]F-FDG PET image data. The existing models employ multiple parameters for feature extraction which makes it difficult to implement in clinical settings for the quantitative characterization. This article reports an easy-to-use and differential SUV based model for quantitative assessment of the intratumor heterogeneity from 3D [18]F-FDG PET image data. An H index is defined to assess tumor heterogeneity by summing voxel-wise distribution of differential SUV from the [18]F-FDG PET image data. The summation is weighted by the distance of SUV difference among neighboring voxels from the center of the tumor and can thus yield increased values for tumors with peripheral sub-regions of high SUV that often serves as an indicator of augmented malignancy. Furthermore, the sign of H index is used to differentiate the rate of change for volume averaged SUV from its center to periphery. The new model with the H index has been compared with a widely-used model of gray level co-occurrence matrix (GLCM) for image texture characterization with phantoms of different configurations and the [18]F-FDG PET image data of 6 lung cancer patients to evaluate its effectiveness and feasibility for clinical uses. The comparison of the H index and GLCM parameters with the phantoms demonstrate that the H index can characterize the SUV heterogeneity in all of 6 2D phantoms while only 1 GLCM parameter can do for 1 and fail to differentiate for other 2D phantoms. For the 8 3D phantoms, the H index can clearly differentiate all of them while the 4 GLCM parameters provide complicated patterns in the characterization. Feasibility study with the PET image data from 6 lung cancer patients show that the H index provides an effective single-parameter metric to characterize tumor heterogeneity in terms of the local SUV variation, and it has higher correlation with tumor volume change after

  10. Information dynamics in carcinogenesis and tumor growth.

    Science.gov (United States)

    Gatenby, Robert A; Frieden, B Roy

    2004-12-21

    The storage and transmission of information is vital to the function of normal and transformed cells. We use methods from information theory and Monte Carlo theory to analyze the role of information in carcinogenesis. Our analysis demonstrates that, during somatic evolution of the malignant phenotype, the accumulation of genomic mutations degrades intracellular information. However, the degradation is constrained by the Darwinian somatic ecology in which mutant clones proliferate only when the mutation confers a selective growth advantage. In that environment, genes that normally decrease cellular proliferation, such as tumor suppressor or differentiation genes, suffer maximum information degradation. Conversely, those that increase proliferation, such as oncogenes, are conserved or exhibit only gain of function mutations. These constraints shield most cellular populations from catastrophic mutator-induced loss of the transmembrane entropy gradient and, therefore, cell death. The dynamics of constrained information degradation during carcinogenesis cause the tumor genome to asymptotically approach a minimum information state that is manifested clinically as dedifferentiation and unconstrained proliferation. Extreme physical information (EPI) theory demonstrates that altered information flow from cancer cells to their environment will manifest in-vivo as power law tumor growth with an exponent of size 1.62. This prediction is based only on the assumption that tumor cells are at an absolute information minimum and are capable of "free field" growth that is, they are unconstrained by external biological parameters. The prediction agrees remarkably well with several studies demonstrating power law growth in small human breast cancers with an exponent of 1.72+/-0.24. This successful derivation of an analytic expression for cancer growth from EPI alone supports the conceptual model that carcinogenesis is a process of constrained information degradation and that malignant

  11. siRNA-based Analysis of the Abrogation of the Protective Function of Membrane-associated Catalase of Tumor Cells.

    Science.gov (United States)

    Bauer, Georg

    2017-02-01

    Tumor cells, in contrast to non-malignant cells, show sustained expression of membrane-associated NADPH oxidase-1 and therefore generate extracellular superoxide anions and their dismutation product H 2 O 2 In order to prevent intercellular reactive oxygen species/reactive nitrogen species (ROS/RNS)-dependent apoptosis-inducing signaling, tumor cells need to express membrane-associated catalase that interferes with HOCl and nitric oxide/peroxynitrite signaling. Catalase is attached to tumor cells through the activity of transglutaminase-2 and is prevented from superoxide anion-dependent inhibition through coexpression of membrane-associated superoxide dismutase. Therefore, specific inhibition of membrane-associated catalase should reactivate intercellular ROS/RNS-dependent apoptosis-inducing signaling. These processes are analyzed here through small interfering RNA-mediated knockdown of essential signaling compounds. This allows to establish a rather comprehensive picture of intercellular ROS/RNS signaling that may be instrumental for future therapeutic approaches. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  12. Macroscopy predicts tumor progression in gastric cancer: A retrospective patho-historical analysis based on Napoleon Bonaparte's autopsy report.

    Science.gov (United States)

    Dawson, Heather; Novotny, Alexander; Becker, Karen; Reim, Daniel; Langer, Rupert; Gullo, Irene; Svrcek, Magali; Niess, Jan H; Tutuian, Radu; Truninger, Kaspar; Diamantis, Ioannis; Blank, Annika; Zlobec, Inti; Riddell, Robert H; Carneiro, Fatima; Fléjou, Jean-François; Genta, Robert M; Lugli, Alessandro

    2016-11-01

    The cause of Napoleon Bonaparte's death remains controversial. Originally suggested to be gastric cancer, whether this was truly neoplastic or a benign lesion has been recently debated. To interpret findings of original autopsy reports in light of the current knowledge of gastric cancer and to highlight the significance of accurate macroscopy in modern-day medicine. Using original autopsy documents, endoscopic images and data from current literature, Napoleon's gastric situation was reconstructed. In a multicenter collection of 2071 gastric cancer specimens, the relationship between tumor size and features of tumor progression was assessed. Greater tumor size was associated with advanced pT, nodal metastases and Borrmann types 3-4 (pNapoleon's autopsy with present-day knowledge to support gastric cancer as his terminal illness and emphasizes the role of macroscopy, which may provide valuable information on gastric cancer progression and aid patient management. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  13. Feasibility of the evidence-based cognitive telerehabilitation program Remind for patients with primary brain tumors.

    Science.gov (United States)

    van der Linden, Sophie D; Sitskoorn, Margriet M; Rutten, Geert-Jan M; Gehring, Karin

    2018-05-01

    Many patients with primary brain tumors experience cognitive deficits. Cognitive rehabilitation programs focus on alleviating these deficits, but availability of such programs is limited. Our large randomized controlled trial (RCT) demonstrated positive effects of the cognitive rehabilitation program developed by our group. We converted the program into the iPad-based cognitive rehabilitation program ReMind, to increase its accessibility. The app incorporates psychoeducation, strategy training and retraining. This pilot study in patients with primary brain tumors evaluates the feasibility of the use of the ReMind-app in a clinical (research) setting in terms of accrual, attrition, adherence and patient satisfaction. The intervention commenced 3 months after resective surgery and patients were advised to spend 3 h per week on the program for 10 weeks. Of 28 eligible patients, 15 patients with presumed low-grade glioma or meningioma provided informed consent. Most important reason for decline was that patients (7) experienced no cognitive complaints. Participants completed on average 71% of the strategy training and 76% of the retraining. Some patients evaluated the retraining as too easy. Overall, 85% of the patients evaluated the intervention as "good" or "excellent". All patients indicated that they would recommend the program to other patients with brain tumors. The ReMind-app is the first evidence-based cognitive telerehabilitation program for adult patients with brain tumors and this pilot study suggests that postoperative cognitive rehabilitation via this app is feasible. Based on patients' feedback, we have expanded the retraining with more difficult exercises. We will evaluate the efficacy of ReMind in an RCT.

  14. Computer-aided analysis of CT images for the differentiation of cerebral tumors

    International Nuclear Information System (INIS)

    Michalik, M.; Michalik, S.; Bornholdt, F.

    1988-01-01

    For the integration of CT imaging into the differential diagnostics of intracranial space occupations, the selection and description of characteristics facilitating a good discrimination of serveral classes of tumors becomes a very important task. From images of 93 patients with the most frequent brain tumors the optimal set of characteristics was determined. The four most significant characteristics for the differentiation of brain tumors are 'uptake of contrast medium by the tumor', 'deliniation of the tumor contours', 'progression of the tumor' and the 'average tumor density after administration of contrast media'. Very good results were obtained for the differentiation of menigneomas with and without anaplasia and for the differentiation of meningeomas from all other tumors examined. The differentiation of the degree of malignancy for various gliomatous tumors was difficult. An accurate reclassification with the computer program was obtained for 83.4% of all tumors. (author)

  15. TH-E-17A-10: Markerless Lung Tumor Tracking Based On Beams Eye View EPID Images

    Energy Technology Data Exchange (ETDEWEB)

    Chiu, T; Kearney, V; Liu, H; Jiang, L; Foster, R; Mao, W [UT Southwestern Medical Center, Dallas, Texas (United States); Rozario, T; Bereg, S [University of Texas at Dallas, Richardson, Texas (United States); Klash, S [Premier Cancer Centers, Dallas, TX (United States)

    2014-06-15

    Purpose: Dynamic tumor tracking or motion compensation techniques have proposed to modify beam delivery following lung tumor motion on the flight. Conventional treatment plan QA could be performed in advance since every delivery may be different. Markerless lung tumor tracking using beams eye view EPID images provides a best treatment evaluation mechanism. The purpose of this study is to improve the accuracy of the online markerless lung tumor motion tracking method. Methods: The lung tumor could be located on every frame of MV images during radiation therapy treatment by comparing with corresponding digitally reconstructed radiograph (DRR). A kV-MV CT corresponding curve is applied on planning kV CT to generate MV CT images for patients in order to enhance the similarity between DRRs and MV treatment images. This kV-MV CT corresponding curve was obtained by scanning a same CT electron density phantom by a kV CT scanner and MV scanner (Tomotherapy) or MV CBCT. Two sets of MV DRRs were then generated for tumor and anatomy without tumor as the references to tracking the tumor on beams eye view EPID images. Results: Phantom studies were performed on a Varian TrueBeam linac. MV treatment images were acquired continuously during each treatment beam delivery at 12 gantry angles by iTools. Markerless tumor tracking was applied with DRRs generated from simulated MVCT. Tumors were tracked on every frame of images and compared with expected positions based on programed phantom motion. It was found that the average tracking error were 2.3 mm. Conclusion: This algorithm is capable of detecting lung tumors at complicated environment without implanting markers. It should be noted that the CT data has a slice thickness of 3 mm. This shows the statistical accuracy is better than the spatial accuracy. This project has been supported by a Varian Research Grant.

  16. Staging of gastroenteropancreatic neuroendocrine tumors: how we do it based on an evidence-based approach.

    LENUS (Irish Health Repository)

    McDermott, Shaunagh

    2013-01-01

    In contrast to other common types of malignant tumors, the vast majority of gastroenteropancreatic neuroendocrine tumors are well differentiated and slowly growing with only a minority showing aggressive behavior. It is important to accurately stage patients radiologically so the correct treatment can be implemented and to improve prognosis. In this article, we critically appraise the current literature in an effort to establish the current role of radiologic imaging in the staging of neuroendocrine tumors. We also discuss our protocol for staging neuroendocrine tumors.

  17. Surgical options in benign parotid tumors: a proposal for classification.

    Science.gov (United States)

    Quer, Miquel; Vander Poorten, Vincent; Takes, Robert P; Silver, Carl E; Boedeker, Carsten C; de Bree, Remco; Rinaldo, Alessandra; Sanabria, Alvaro; Shaha, Ashok R; Pujol, Albert; Zbären, Peter; Ferlito, Alfio

    2017-11-01

    Different surgical options are currently available for treating benign tumors of the parotid gland, and the discussion on optimal treatment continues despite several meta-analyses. These options include more limited resections (extracapsular dissection, partial lateral parotidectomy) versus more extensive and traditional options (lateral parotid lobectomy, total parotidectomy). Different schools favor one option or another based on their experience, skills and tradition. This review provides a critical analysis of the literature regarding these options. The main limitation of all the studies is the bias of selection for different surgical approaches. For this reason, we propose a staging system that could facilitate clinical decision making and the comparison of results. We propose four categories based on the size of the tumor and its location within the parotid gland. Category I includes tumors up to 3 cm, which are mobile, close to the outer surface and close to the parotid borders. Category II includes deeper tumors up to 3 cm. Category III comprises tumors greater than 3 cm involving two levels of the parotid gland, and category IV tumors are greater than 3 cm and involve more than 2 levels. For each category and for the various pathologic types, a guideline of surgical extent is proposed. The objective of this classification is to facilitate prospective multicentric studies on surgical techniques in the treatment of benign parotid tumors and to enable the comparison of results of different clinical studies.

  18. An off-on fluorescence probe targeting mitochondria based on oxidation-reduction response for tumor cell and tissue imaging

    Science.gov (United States)

    Yao, Hanchun; Cao, Li; Zhao, Weiwei; Zhang, Suge; Zeng, Man; Du, Bin

    2017-10-01

    In this study, a tumor-targeting poly( d, l-lactic-co-glycolic acid) (PLGA) loaded "off-on" fluorescent probe nanoparticle (PFN) delivery system was developed to evaluate the region of tumor by off-on fluorescence. The biodegradability of the nanosize PFN delivery system readily released the probe under tumor acidic conditions. The probe with good biocompatibility was used to monitor the intracellular glutathione (GSH) of cancer cells and selectively localize to mitochondria for tumor imaging. The incorporated tumor-targeting probe was based on the molecular photoinduced electron transfer (PET) mechanism preventing fluorescence ("off" state) and could be easily released under tumor acidic conditions. However, the released tumor-targeting fluorescence probe molecule was selective towards GSH with high selectivity and an ultra-sensitivity for the mitochondria of cancer cells and tissues significantly increasing the probe molecule fluorescence signal ("on" state). The tumor-targeting fluorescence probe showed sensitivity to GSH avoiding interference from cysteine and homocysteine. The PFNs could enable fluorescence-guided cancer imaging during cancer therapy. This work may expand the biological applications of PFNs as a diagnostic reagent, which will be beneficial for fundamental research in tumor imaging. [Figure not available: see fulltext.

  19. Metabolic Control Analysis aimed at the ribose synthesis pathways of tumor cells: a new strategy for antitumor drug development

    NARCIS (Netherlands)

    Boren, Joan; Montoya, Antonio Ramos; de Atauri, Pedro; Comin-Anduix, Begoña; Cortes, Antonio; Centelles, Josep J.; Frederiks, Wilma M.; van Noorden, Cornelis J. F.; Cascante, Marta

    2002-01-01

    Metabolic control analysis predicts that effects on tumor growth are likely to be obtained with lower concentrations of drug, if an enzyme with a high control coefficient on tumor growth is being inhibited. Here we measure glucose-6-phosphate dehydrogenase (G6PDH) control coefficient on in vivo

  20. Updated Outcome and Analysis of Tumor Response in Mobile Spine and Sacral Chordoma Treated With Definitive High-Dose Photon/Proton Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Kabolizadeh, Peyman, E-mail: peyman.kabolizadeh@beaumont.org [Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States); Chen, Yen-Lin; Liebsch, Norbert [Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States); Hornicek, Francis J.; Schwab, Joseph H. [Department of Orthopedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States); Choy, Edwin [Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States); Rosenthal, Daniel I. [Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States); Niemierko, Andrzej; DeLaney, Thomas F. [Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States)

    2017-02-01

    Purpose: Treatment of spine and sacral chordoma generally involves surgical resection, usually in conjunction with radiation therapy. In certain circumstances where resection may result in significant neurologic or organ dysfunction, patients can be treated definitively with radiation therapy alone. Herein, we report the outcome and the assessment of tumor response to definitive radiation therapy. Methods and Materials: A retrospective analysis was performed on 40 patients with unresected chordoma treated with photon/proton radiation therapy. Nineteen patients had complete sets of imaging scans. The soft tissue and bone compartments of the tumor were defined separately. Tumor response was evaluated by the modified Response Evaluation Criteria in Solid Tumors (RECIST) and volumetric analysis. Results: With a median follow-up time of 50.3 months, the rates of 5-year local control, overall survival, disease-specific survival, and distant failure were 85.4%, 81.9%, 89.4%, and 20.2%, respectively. Eighty-four computed tomographic and magnetic resonance imaging scans were reviewed. Among the 19 patients, only 4 local failures occurred, and the median tumor dose was 77.4 GyRBE. Analysis at a median follow-up time of 18 months showed significant volumetric reduction of the total target volume (TTV) and the soft tissue target volume (STTV) within the first 24 months after treatment initiation, followed by further gradual reduction throughout the rest of the follow-up period. The median maximum percentage volumetric regressions of TTV and STTV were 43.2% and 70.4%, respectively. There was only a small reduction in bone target volume over time. In comparison with the modified RECIST, volumetric analysis was more reliable, more reproducible, and could help in measuring minimal changes in the tumor volume. Conclusion: These results continue to support the use of high-dose definitive radiation therapy for selected patients with unresected spine and sacral chordomas

  1. Updated Outcome and Analysis of Tumor Response in Mobile Spine and Sacral Chordoma Treated With Definitive High-Dose Photon/Proton Radiation Therapy

    International Nuclear Information System (INIS)

    Kabolizadeh, Peyman; Chen, Yen-Lin; Liebsch, Norbert; Hornicek, Francis J.; Schwab, Joseph H.; Choy, Edwin; Rosenthal, Daniel I.; Niemierko, Andrzej; DeLaney, Thomas F.

    2017-01-01

    Purpose: Treatment of spine and sacral chordoma generally involves surgical resection, usually in conjunction with radiation therapy. In certain circumstances where resection may result in significant neurologic or organ dysfunction, patients can be treated definitively with radiation therapy alone. Herein, we report the outcome and the assessment of tumor response to definitive radiation therapy. Methods and Materials: A retrospective analysis was performed on 40 patients with unresected chordoma treated with photon/proton radiation therapy. Nineteen patients had complete sets of imaging scans. The soft tissue and bone compartments of the tumor were defined separately. Tumor response was evaluated by the modified Response Evaluation Criteria in Solid Tumors (RECIST) and volumetric analysis. Results: With a median follow-up time of 50.3 months, the rates of 5-year local control, overall survival, disease-specific survival, and distant failure were 85.4%, 81.9%, 89.4%, and 20.2%, respectively. Eighty-four computed tomographic and magnetic resonance imaging scans were reviewed. Among the 19 patients, only 4 local failures occurred, and the median tumor dose was 77.4 GyRBE. Analysis at a median follow-up time of 18 months showed significant volumetric reduction of the total target volume (TTV) and the soft tissue target volume (STTV) within the first 24 months after treatment initiation, followed by further gradual reduction throughout the rest of the follow-up period. The median maximum percentage volumetric regressions of TTV and STTV were 43.2% and 70.4%, respectively. There was only a small reduction in bone target volume over time. In comparison with the modified RECIST, volumetric analysis was more reliable, more reproducible, and could help in measuring minimal changes in the tumor volume. Conclusion: These results continue to support the use of high-dose definitive radiation therapy for selected patients with unresected spine and sacral chordomas

  2. A conceptual design of neutron tumor therapy reactor facility with a YAYOI based fast neutron source reactor

    International Nuclear Information System (INIS)

    Wakabayashi, Hiroaki; An, Shigehiro.

    1983-01-01

    Fast neutron is known as one of useful radiations for radiation therapy of tumors. Boron neutron capture therapy (BNCT) of tumors which makes use of 10 B(n, α) 7 Li reaction of 10 B compounds selectively attached to tumor cells with thermal and intermediate neutrons is another way of neutron based radiation therapy which is, above all, attractive enough to kill tumor cells selectively sparing normal tissue. In Japan, BNCT has already been applied and leaned to be effective. After more than a decade operational experiences and the specific experiments designed for therapeutical purposes, in this paper, a conceptual design of a special neutron therapy reactor facility based on YAYOI - fast neutron source reactor of Nuclear Engineering Research Laboratory, Faculty of Engineering, the University of Tokyo - modified to provide an upward beam of fast and intermediate neutrons is presented. Emphasis is placed on the in-house nature of facility and on the coordinating capability of biological and physical researches as well as maintenances of the facility. (author)

  3. Magnetic resonance imaging textural evaluation of posterior cranial fossa tumors in childhood

    International Nuclear Information System (INIS)

    Santos, Joelson Alves dos; Costa, Maria Olivia Rodrigues da; Otaduy, Maria Concepcion Garcia; Lacerda, Maria Teresa Carvalho de; Leite, Claudia da Costa; Matsushita, Hamilton

    2004-01-01

    Objective: To distinguish healthy from pathological tissues in pediatric patients with posterior cranial fossa tumors using calculated textural parameters from magnetic resonance images. Materials And Methods: We evaluated 14 pediatric patients with posterior cranial fossa tumors using the software MaZda to define the texture parameters in selected regions of interest representing healthy and pathological tissues based on T2-weighted magnetic resonance images. Results: There was a statistically significant difference between normal and tumoral tissues as well as between supposedly normal tissues adjacent and distant from the tumoral lesion. Conclusion: Magnetic resonance textural evaluation is an useful tool for determining differences among various tissues, including tissues that appear apparently normal on visual analysis. (author)

  4. Pitfalls in the assessment of radioresponse as determined by tumor regression. Consideration based on the location and histologic constitution of tumors

    Energy Technology Data Exchange (ETDEWEB)

    Ohara, Kiyoshi; Shimizu, Wakako; Itai, Yuji [Tsukuba Univ., Ibaraki (Japan). Inst. of Clinical Medicine

    2000-05-01

    To prove the following hypotheses regarding tumor shrinkage after radiotherapy. Tumors located on an outer tissue surface, e.g. esophageal tumors shrink faster than parenchymal tumors, e.g. lymph-node metastasis, because two clearance mechanisms, exfoliation and absorption, can operate in the former type of tumors whereas only absorption can function in the latter. Tumors which are being controlled do not necessarily respond completely, because tumors are constituted not only of tumor cells but also stromal tissues that are difficult to be absorbed. Long-term shrinkage patterns of a parenchymal tumor were determined by using 18 curatively irradiated hepatomas. Preoperatively irradiated thymomas (10) and lymph-node metastases (37) from head and neck cancers were examined histopathologically. Twenty-one esophageal cancers were used for intra-patient response comparison between the primary disease and the lymph-node metastases. Shrinkage patterns were generally biphasic: rapid exponential regression followed by a plateau phase. Histologically, thymomas generally consisted of predominant fibrous tissues and few remaining tumor cells. Radioresponse did not predict the presence of remaining cancer cells in the lymph nodes. Esophageal-cancer radiorespone was always higher for the primary disease than the lymph-node metastases. The location and histologic constitution of tumors must be taken into account in predicting radiocurability using radioresponse. (author)

  5. Prognostic significance of pretreatment plasma fibrinogen level in patients with digestive system tumors: a meta-analysis.

    Science.gov (United States)

    Ji, Rui; Ren, Qian; Bai, Suyang; Wang, Yuping; Zhou, Yongning

    2018-06-01

    High pretreatment levels of plasma fibrinogen have been widely reported to be a potential predictor of prognosis in digestive system tumors; however, the conclusions are not consistent. Therefore, we performed a meta-analysis to comprehensively assess the prognostic roles of high pretreatment plasma fibrinogen levels in digestive system tumors. We searched for eligible studies in the PubMed, Embase, and Web of Science electronic databases for publications from the database inception to 1 September 2017. The endpoints of interest included overall survival, disease-free survival, and recurrence-free survival. We investigated the relationship between fibrinogenemia and overall survival in colorectal cancer (10 studies), gastric cancer (6), pancreatic cancer (6), hepatocellular carcinoma (7), and esophageal squamous cell carcinoma (10); the pooled results indicated that fibrinogenemia was significantly related to a worse overall survival (hazard ratio (HR) 1.73; 95% confidence interval (CI) 1.52, 1.97; P digestive system tumors, indicating that it could be a useful prognostic marker in these types of tumors.

  6. Circulating Tumor Cells in Breast Cancer Patients Treated by Neoadjuvant Chemotherapy: A Meta-analysis.

    Science.gov (United States)

    Bidard, François-Clément; Michiels, Stefan; Riethdorf, Sabine; Mueller, Volkmar; Esserman, Laura J; Lucci, Anthony; Naume, Bjørn; Horiguchi, Jun; Gisbert-Criado, Rafael; Sleijfer, Stefan; Toi, Masakazu; Garcia-Saenz, Jose A; Hartkopf, Andreas; Generali, Daniele; Rothé, Françoise; Smerage, Jeffrey; Muinelo-Romay, Laura; Stebbing, Justin; Viens, Patrice; Magbanua, Mark Jesus M; Hall, Carolyn S; Engebraaten, Olav; Takata, Daisuke; Vidal-Martínez, José; Onstenk, Wendy; Fujisawa, Noriyoshi; Diaz-Rubio, Eduardo; Taran, Florin-Andrei; Cappelletti, Maria Rosa; Ignatiadis, Michail; Proudhon, Charlotte; Wolf, Denise M; Bauldry, Jessica B; Borgen, Elin; Nagaoka, Rin; Carañana, Vicente; Kraan, Jaco; Maestro, Marisa; Brucker, Sara Yvonne; Weber, Karsten; Reyal, Fabien; Amara, Dominic; Karhade, Mandar G; Mathiesen, Randi R; Tokiniwa, Hideaki; Llombart-Cussac, Antonio; Meddis, Alessandra; Blanche, Paul; d'Hollander, Koenraad; Cottu, Paul; Park, John W; Loibl, Sibylle; Latouche, Aurélien; Pierga, Jean-Yves; Pantel, Klaus

    2018-04-12

    We conducted a meta-analysis in nonmetastatic breast cancer patients treated by neoadjuvant chemotherapy (NCT) to assess the clinical validity of circulating tumor cell (CTC) detection as a prognostic marker. We collected individual patient data from 21 studies in which CTC detection by CellSearch was performed in early breast cancer patients treated with NCT. The primary end point was overall survival, analyzed according to CTC detection, using Cox regression models stratified by study. Secondary end points included distant disease-free survival, locoregional relapse-free interval, and pathological complete response. All statistical tests were two-sided. Data from patients were collected before NCT (n = 1574) and before surgery (n = 1200). CTC detection revealed one or more CTCs in 25.2% of patients before NCT; this was associated with tumor size (P < .001). The number of CTCs detected had a detrimental and decremental impact on overall survival (P < .001), distant disease-free survival (P < .001), and locoregional relapse-free interval (P < .001), but not on pathological complete response. Patients with one, two, three to four, and five or more CTCs before NCT displayed hazard ratios of death of 1.09 (95% confidence interval [CI] = 0.65 to 1.69), 2.63 (95% CI = 1.42 to 4.54), 3.83 (95% CI = 2.08 to 6.66), and 6.25 (95% CI = 4.34 to 9.09), respectively. In 861 patients with full data available, adding CTC detection before NCT increased the prognostic ability of multivariable prognostic models for overall survival (P < .001), distant disease-free survival (P < .001), and locoregional relapse-free interval (P = .008). CTC count is an independent and quantitative prognostic factor in early breast cancer patients treated by NCT. It complements current prognostic models based on tumor characteristics and response to therapy.

  7. Dosimetric impact of a frame-based strategy in stereotactic radiotherapy of lung tumors

    International Nuclear Information System (INIS)

    Waldeland, Einar; Ramberg, Christina; Arnesen, Marius Roethe; Helland, Aaslaug; Brustugun, Odd Terje; Malinen, Eirik

    2012-01-01

    Introduction. Technological innovations have taken stereotactic body radiotherapy (SBRT) from frame-based strategies to image-guided strategies. In this study, cone beam computed tomography (CBCT) images acquired prior to SBRT of patients with lung tumors was used to study the dosimetric impact of a pure frame-based strategy. Material and methods. Thirty patients with inoperable lung tumors were retrospectively analyzed. All patients had received CBCT-guided SBRT with 3 fractions of 15 Gy to the planning target volume (PTV) margin including immobilization in a stereotactic body frame (SBF). Using the set-up corrections from the co-registration of the CBCT with the planning CT, all individual dose plans were recalculated with an isocenter position equal to the initial set-up position. Dose Volume Histogram (DVH) parameters of the recalculated dose plans were then analyzed. Results. The simulated plans showed that 88% of all fractions resulted in minimum 14.5 Gy to the internal target volume (ITV). For the simulated summed treatment (3 fractions per patient), 83% of the patients would minimum receive the prescription dose (45 Gy) to 100% of the ITV and all except one would receive the prescription dose to more than 90% of the ITV. Conclusions. SBRT including SBF, but without image guidance, results in appropriate dose coverage in most cases, using the current margins. With image guidance, margins for SBRT of lung tumors could possibly be reduced

  8. Eningiomas: outcome, and analysis of prognostic factors of primarily resected tumors

    International Nuclear Information System (INIS)

    Stafford, S.L.; Perry, A.; Suman, V.; Meyer, B.; Scheithauer, B.W.; Shaw, E.G.; Earle, J.D.

    1996-01-01

    Purpose: 582 consecutive cases of primary intracranial meningioma undergoing resection at the Mayo Clinic, (Rochester, MN) were reviewed to determine overall survival (OS), progression free survival(PFS), prognostic factors predicting recurrence, and to determine the importance of radiation therapy in the management of this tumor. Materials and Methods: Between 1978-1988, 582 cases of primarily resected meningiomas were identified based on the tumor and operative registries where diagnosis was between 1978-1988 inclusive. PFS was identified by radiographic progression. Follow-up was accomplished by chart review, and a detailed questionnaire sent to patients and referring physicians. Estimation of OS and PFS distributions were done by the Kaplan-Meier method. The log rank test was used to assess which factors were associated with PFS. Proportional hazard modeling was performed to obtain a subset of independent predictors of PFS. Results: the median age was 57(5-93). 67% were female. CT identified the tumor in 91% of cases. There was associated edema in 21% and 2% were radiographically en plaque. There were 17 patients with multiple tumors, four of whom had a known diagnosis of neurofibromatosis. Gross total resection (GTR) was accomplished in 80%, radical subtotal or subtotal resection(STR) in 20%, and biopsy in 53) cellularity, and four or more mitoses per 10 HPF. Multivariate analysis indicated young age, male sex, en plaque at surgery, were significant for decreased PFS when only patient characteristics were considered. When treatment and pathologic factors were also considered, then young age, male sex, less than GTR, and tumor sheeting were predictors for decreased PFS. 10 patients had RT after initial resection, two of whom recurred. There were 107 first recurrences. 50 were observed(no intervention within 3 months), 35 treated by surgery alone, 11 had S+RT, and 11 were treated with RT alone. Considering those patients treated at recurrence (n=57), PFS was at

  9. SU-E-I-100: Heterogeneity Studying for Primary and Lymphoma Tumors by Using Multi-Scale Image Texture Analysis with PET-CT Images

    Energy Technology Data Exchange (ETDEWEB)

    Li, Dengwang [Shandong Normal University, Jinan, Shandong Province (China); Wang, Qinfen [Shandong Normal University, Jinan, Shandong (China); Li, H; Chen, J [Shandong Cancer Hospital and Institute, Jinan, Shandong (China)

    2014-06-01

    Purpose: The purpose of this research is studying tumor heterogeneity of the primary and lymphoma by using multi-scale texture analysis with PET-CT images, where the tumor heterogeneity is expressed by texture features. Methods: Datasets were collected from 12 lung cancer patients, and both of primary and lymphoma tumors were detected with all these patients. All patients underwent whole-body 18F-FDG PET/CT scan before treatment.The regions of interest (ROI) of primary and lymphoma tumor were contoured by experienced clinical doctors. Then the ROI of primary and lymphoma tumor is extracted automatically by using Matlab software. According to the geometry size of contour structure, the images of tumor are decomposed by multi-scale method.Wavelet transform was performed on ROI structures within images by L layers sampling, and then wavelet sub-bands which have the same size of the original image are obtained. The number of sub-bands is 3L+1.The gray level co-occurrence matrix (GLCM) is calculated within different sub-bands, thenenergy, inertia, correlation and gray in-homogeneity were extracted from GLCM.Finally, heterogeneity statistical analysis was studied for primary and lymphoma tumor using the texture features. Results: Energy, inertia, correlation and gray in-homogeneity are calculated with our experiments for heterogeneity statistical analysis.Energy for primary and lymphomatumor is equal with the same patient, while gray in-homogeneity and inertia of primaryare 2.59595±0.00855, 0.6439±0.0007 respectively. Gray in-homogeneity and inertia of lymphoma are 2.60115±0.00635, 0.64435±0.00055 respectively. The experiments showed that the volume of lymphoma is smaller than primary tumor, but thegray in-homogeneity and inertia were higher than primary tumor with the same patient, and the correlation with lymphoma tumors is zero, while the correlation with primary tumor isslightly strong. Conclusion: This studying showed that there were effective heterogeneity

  10. Self-scaling tumor growth

    DEFF Research Database (Denmark)

    Schmiegel, Jürgen

    We study the statistical properties of the star-shaped approximation of in vitro tumor profiles. The emphasis is on the two-point correlation structure of the radii of the tumor as a function of time and angle. In particular, we show that spatial two-point correlators follow a cosine law. Further......We study the statistical properties of the star-shaped approximation of in vitro tumor profiles. The emphasis is on the two-point correlation structure of the radii of the tumor as a function of time and angle. In particular, we show that spatial two-point correlators follow a cosine law....... Furthermore, we observe self-scaling behaviour of two-point correlators of different orders, i.e. correlators of a given order are a power law of the correlators of some other order. This power-law dependence is similar to what has been observed for the statistics of the energy-dissipation in a turbulent flow....... Based on this similarity, we provide a Lévy based model that captures the correlation structure of the radii of the star-shaped tumor profiles....

  11. Strategy to find molecular signatures in a small series of rare cancers: validation for radiation-induced breast and thyroid tumors.

    Directory of Open Access Journals (Sweden)

    Nicolas Ugolin

    Full Text Available Methods of classification using transcriptome analysis for case-by-case tumor diagnosis could be limited by tumor heterogeneity and masked information in the gene expression profiles, especially as the number of tumors is small. We propose a new strategy, EMts_2PCA, based on: 1 The identification of a gene expression signature with a great potential for discriminating subgroups of tumors (EMts stage, which includes: a a learning step, based on an expectation-maximization (EM algorithm, to select sets of candidate genes whose expressions discriminate two subgroups, b a training step to select from the sets of candidate genes those with the highest potential to classify training tumors, c the compilation of genes selected during the training step, and standardization of their levels of expression to finalize the signature. 2 The predictive classification of independent prospective tumors, according to the two subgroups of interest, by the definition of a validation space based on a two-step principal component analysis (2PCA. The present method was evaluated by classifying three series of tumors and its robustness, in terms of tumor clustering and prediction, was further compared with that of three classification methods (Gene expression bar code, Top-scoring pair(s and a PCA-based method. Results showed that EMts_2PCA was very efficient in tumor classification and prediction, with scores always better that those obtained by the most common methods of tumor clustering. Specifically, EMts_2PCA permitted identification of highly discriminating molecular signatures to differentiate post-Chernobyl thyroid or post-radiotherapy breast tumors from their sporadic counterparts that were previously unsuccessfully classified or classified with errors.

  12. Tumor Vessel Compression Hinders Perfusion of Ultrasonographic Contrast Agents

    Directory of Open Access Journals (Sweden)

    Mirco Galiè

    2005-05-01

    Full Text Available Contrast-enhanced ultrasound (CEUS is an advanced approach to in vivo assessment of tumor vascularity and is being increasingly adopted in clinical oncology. It is based on 1- to 10 μm-sized gas microbubbles, which can cross the capillary beds of the lungs and are effective echo enhancers. It is known that high cell density, high transendothelial fluid exchange, and poorly functioning lymphatic circulation all provoke solid stress, which compresses vessels and drastically reduces tumor blood flow. Given their size, we supposed that the perfusion of microbubbles is affected by anatomic features of tumor vessels more than are contrast agents traditionally used in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI. Here, we compared dynamic information obtained from CEUS and DCE-MRI on two experimental tumor models exhibiting notable differences in vessel anatomy. We found that tumors with small, flattened vessels show a much higher resistance to microbubble perfusion than to MRI contrast agents, and appear scarcely vascularized at CEUS examination, despite vessel volume adequate for normal function. Thus, whereas CEUS alone could induce incorrect diagnosis when tumors have small or collapsed vessels, integrated analysis using CEUS and DCE-MRI allows in vivo identification of tumors with a vascular profile frequently associated with malignant phenotypes.

  13. ASSESSMENT OF THE RESIDUAL TUMOR IN PATIENTS WITH MULTIPLE MYELOMA BASED ON THE ANALYSIS OF THE FREE LIGHT CHAINS OF IMMUNOGLOBULINS IN BLOOD SERUM

    Directory of Open Access Journals (Sweden)

    T. A. Мitina

    2013-01-01

    Full Text Available Efficiency of the multiple myeloma treatment with chemotherapy including bortezomib was assessed based on determination of the level of immunoglobulin free light chains in blood serum. The method enables estimation of changes in kinetic parameters of the residual tumor, detection of the disease course prognosis, and the choice of the optimal approach to the disease therapy.

  14. Tumor associated osteoclast-like giant cells promote tumor growth and lymphangiogenesis by secreting vascular endothelial growth factor-C

    International Nuclear Information System (INIS)

    Hatano, Yu; Nakahama, Ken-ichi; Isobe, Mitsuaki; Morita, Ikuo

    2014-01-01

    Highlights: • M-CSF and RANKL expressing HeLa cells induced osteoclastogenesis in vitro. • We established OGC-containing tumor model in vivo. • OGC-containing tumor became larger independent of M-CSF or RANKL effect. • VEGF-C secreted from OGCs was a one of candidates for OGC-containing tumor growth. - Abstract: Tumors with osteoclast-like giant cells (OGCs) have been reported in a variety of organs and exert an invasive and prometastatic phenotype, but the functional role of OGCs in the tumor environment has not been fully clarified. We established tumors containing OGCs to clarify the role of OGCs in tumor phenotype. A mixture of HeLa cells expressing macrophage colony-stimulating factor (M-CSF, HeLa-M) and receptor activator of nuclear factor-κB ligand (RANKL, HeLa-R) effectively supported the differentiation of osteoclast-like cells from bone marrow macrophages in vitro. Moreover, a xenograft study showed OGC formation in a tumor composed of HeLa-M and HeLa-R. Surprisingly, the tumors containing OGCs were significantly larger than the tumors without OGCs, although the growth rates were not different in vitro. Histological analysis showed that lymphangiogenesis and macrophage infiltration in the tumor containing OGCs, but not in other tumors were accelerated. According to quantitative PCR analysis, vascular endothelial growth factor (VEGF)-C mRNA expression increased with differentiation of osteoclast-like cells. To investigate whether VEGF-C expression is responsible for tumor growth and macrophage infiltration, HeLa cells overexpressing VEGF-C (HeLa-VC) were established and transplanted into mice. Tumors composed of HeLa-VC mimicked the phenotype of the tumors containing OGCs. Furthermore, the vascular permeability of tumor microvessels also increased in tumors containing OGCs and to some extent in VEGF-C-expressing tumors. These results suggest that macrophage infiltration and vascular permeability are possible mediators in these tumors. These

  15. Tumor Cells Express FcγRl Which Contributes to Tumor Cell Growth and a Metastatic Phenotype

    Directory of Open Access Journals (Sweden)

    M. Bud Nelson

    2001-01-01

    Full Text Available High levels of circulating immune complexes containing tumor-associated antigens are associated with a poor prognosis for individuals with cancer. The ability of B cells, previously exposed to tumor-associated antigens, to promote both in vitro and in vivo tumor growth formed the rationale to evaluate the mechanism by which immune complexes may promote tumor growth. In elucidating this mechanism, FcγRl expression by tumor cells was characterized by flow cytometry, polymerase chain reaction, and sequence analysis. Immune complexes containing shed tumor antigen and anti-shed tumor antigen Ab cross-linked FcγRl-expressing tumor cells, which resulted in an induction of tumor cell proliferation and of shed tumor antigen production. Use of selective tyrosine kinase inhibitors demonstrated that tumor cell proliferation induced by immune complex cross-linking of FcγRl is dependent on the tyrosine kinase signal transduction pathway. A selective inhibitor of phosphatidylinositol-3 kinase also inhibited this induction of tumor cell proliferation. These findings support a role for immune complexes and FcγRl expression by tumor cells in augmentation of tumor growth and a metastatic phenotype.

  16. Combined human papillomavirus typing and TP53 mutation analysis in distinguishing second primary tumors from lung metastases in patients with head and neck squamous cell carcinoma.

    Science.gov (United States)

    Daher, Tamas; Tur, Mehmet Kemal; Brobeil, Alexander; Etschmann, Benjamin; Witte, Biruta; Engenhart-Cabillic, Rita; Krombach, Gabriele; Blau, Wolfgang; Grimminger, Friedrich; Seeger, Werner; Klussmann, Jens Peter; Bräuninger, Andreas; Gattenlöhner, Stefan

    2018-06-01

    In head and neck squamous cell carcinoma (HNSCC), the occurrence of concurrent lung malignancies poses a significant diagnostic challenge because metastatic HNSCC is difficult to discern from second primary lung squamous cell carcinoma (SCC). However, this differentiation is crucial because the recommended treatments for metastatic HNSCC and second primary lung SCC differ profoundly. We analyzed the origin of lung tumors in 32 patients with HNSCC using human papillomavirus (HPV) typing and targeted next generation sequencing of all coding exons of tumor protein 53 (TP53). Lung tumors were clearly identified as HNSCC metastases or second primary tumors in 29 patients, thus revealing that 16 patients had received incorrect diagnoses based on clinical and morphological data alone. The HPV typing and mutation analysis of all TP53 coding exons is a valuable diagnostic tool in patients with HNSCC and concurrent lung SCC, which can help to ensure that patients receive the most suitable treatment. © 2018 Wiley Periodicals, Inc.

  17. Characterization of testicular germ cell tumors: Whole-lesion histogram analysis of the apparent diffusion coefficient at 3T.

    Science.gov (United States)

    Min, Xiangde; Feng, Zhaoyan; Wang, Liang; Cai, Jie; Yan, Xu; Li, Basen; Ke, Zan; Zhang, Peipei; You, Huijuan

    2018-01-01

    To assess the values of parameters derived from whole-lesion histograms of the apparent diffusion coefficient (ADC) at 3T for the characterization of testicular germ cell tumors (TGCTs). A total of 24 men with TGCTs underwent 3T diffusion-weighted imaging. Fourteen tumors were pathologically confirmed as seminomas, and ten tumors were pathologically confirmed as nonseminomas. Whole-lesion histogram analysis of the ADC values was performed. A Mann-Whitney U test was employed to compare the differences in ADC histogram parameters between seminomas and nonseminomas. Receiver operating characteristic analysis was used to identify the cutoff values for each parameter for differentiating seminomas from nonseminomas; furthermore, the area under the curve (AUC) was calculated to evaluate the diagnostic accuracy. The median of 10th, 25th, 50th, 75th, and 90th percentiles and mean, minimum and maximum ADC values were all significantly reduced for seminomas compared with nonseminomas (phistogram analysis of ADCs might be used for preoperative characterization of TGCTs. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Risk analysis of fatal and incidental lung tumors in wister rats after inhalation of plutonium dioxide

    International Nuclear Information System (INIS)

    Kai, M.; Akahane, K.; Ogiso, Y.

    2000-01-01

    Cancer risk analysis was done in animal studies for inhalation of plutonium dioxide. Female Wister rats were exposed to an aerosol of plutonium with AMAD of 0.4-0.5 μm and followed up until they died. We made some model analyses using their likelihood function. This approach enables us to consider temporal variation in dose-response analysis. Each rat contributes to the total likelihood depending on fatal or incidental tumors. In Weibul model analysis, the logarithm of the hazard function can be linearly modeled with the term of log (dose), log-L model, and additional term of the square of log (dose), log-LQ model. The likelihood ratio statistics gave a significantly better fit of the log-LQ model. However, if data more than 4 Gy were excluded, there was no significant difference between both models. The ratio of hazard function at 1 Gy and 0 Gy, the excess relative risk, showed 30 for total tumors. This result was much different from those in PNL data (Sanders et al.). The difference of pulmonary deposition depending upon particle size would cause different tumor incidence. Our studies indicated significant increase of occurrence of fatal lung cancer at an average dose of 0.5 Gy and thus did not suggest that a life-span effective threshold for death was about 1 Gy to the lung, which is shown in some papers. In contrast PNL, the incidence of adenoma showing the maximum at 0.5 Gy decreased with increasing lung dose from 1.5 Gy or higher, where malignant tumors such as adenocarcinomas increased. This phenomenon was analyzed with carcinogenesis models. (author)

  19. Enhancement of Tumor-Specific T Cell–Mediated Immunity in Dendritic Cell–Based Vaccines by Mycobacterium tuberculosis Heat Shock Protein X

    Science.gov (United States)

    Jung, In Duk; Shin, Sung Jae; Lee, Min-Goo; Kang, Tae Heung; Han, Hee Dong; Lee, Seung Jun; Kim, Woo Sik; Kim, Hong Min; Park, Won Sun; Kim, Han Wool; Yun, Cheol-Heui; Lee, Eun Kyung; Wu, T.-C.

    2014-01-01

    Despite the potential for stimulation of robust antitumor immunity by dendritic cells (DCs), clinical applications of DC-based immunotherapy are limited by the low potency in generating tumor Ag-specific T cell responses. Therefore, optimal conditions for generating potent immunostimulatory DCs that overcome tolerance and suppression are key factors in DC-based tumor immunotherapy. In this study, we demonstrate that use of the Mycobacterium tuberculosis heat shock protein X (HspX) as an immunoadjuvant in DC-based tumor immunotherapy has significant potential in therapeutics. In particular, the treatment aids the induction of tumor-reactive T cell responses, especially tumor-specific CTLs. The HspX protein induces DC maturation and proinflammatory cytokine production (TNF-α, IL-1β, IL-6, and IFN-β) through TLR4 binding partially mediated by both the MyD88 and the TRIF signaling pathways. We employed two models of tumor progression and metastasis to evaluate HspX-stimulated DCs in vivo. The administration of HspX-stimulated DCs increased the activation of naive T cells, effectively polarizing the CD4+ and CD8+ T cells to secrete IFN-γ, as well as enhanced the cytotoxicity of splenocytes against HPV-16 E7 (E7)–expressing TC-1 murine tumor cells in therapeutic experimental animals. Moreover, the metastatic capacity of B16-BL6 melanoma cancer cells toward the lungs was remarkably attenuated in mice that received HspX-stimulated DCs. In conclusion, the high therapeutic response rates with tumor-targeted Th1-type T cell immunity as a result of HspX-stimulated DCs in two models suggest that HspX harnesses the exquisite immunological power and specificity of DCs for the treatment of tumors. PMID:24990079

  20. Optimization of the fractionated irradiation scheme considering physical doses to tumor and organ at risk based on dose–volume histograms

    Energy Technology Data Exchange (ETDEWEB)

    Sugano, Yasutaka [Graduate School of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-ku, Sapporo, Hokkaido 060-0812 (Japan); Mizuta, Masahiro [Laboratory of Advanced Data Science, Information Initiative Center, Hokkaido University, Kita-11, Nishi-5, Kita-ku, Sapporo, Hokkaido 060-0811 (Japan); Takao, Seishin; Shirato, Hiroki; Sutherland, Kenneth L. [Department of Radiation Medicine, Graduate School of Medicine, Hokkaido University, Kita-15, Nishi-5, Kita-ku, Sapporo, Hokkaido 060-8638 (Japan); Date, Hiroyuki, E-mail: date@hs.hokudai.ac.jp [Faculty of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-ku, Sapporo, Hokkaido 060-0812 (Japan)

    2015-11-15

    Purpose: Radiotherapy of solid tumors has been performed with various fractionation regimens such as multi- and hypofractionations. However, the ability to optimize the fractionation regimen considering the physical dose distribution remains insufficient. This study aims to optimize the fractionation regimen, in which the authors propose a graphical method for selecting the optimal number of fractions (n) and dose per fraction (d) based on dose–volume histograms for tumor and normal tissues of organs around the tumor. Methods: Modified linear-quadratic models were employed to estimate the radiation effects on the tumor and an organ at risk (OAR), where the repopulation of the tumor cells and the linearity of the dose-response curve in the high dose range of the surviving fraction were considered. The minimization problem for the damage effect on the OAR was solved under the constraint that the radiation effect on the tumor is fixed by a graphical method. Here, the damage effect on the OAR was estimated based on the dose–volume histogram. Results: It was found that the optimization of fractionation scheme incorporating the dose–volume histogram is possible by employing appropriate cell surviving models. The graphical method considering the repopulation of tumor cells and a rectilinear response in the high dose range enables them to derive the optimal number of fractions and dose per fraction. For example, in the treatment of prostate cancer, the optimal fractionation was suggested to lie in the range of 8–32 fractions with a daily dose of 2.2–6.3 Gy. Conclusions: It is possible to optimize the number of fractions and dose per fraction based on the physical dose distribution (i.e., dose–volume histogram) by the graphical method considering the effects on tumor and OARs around the tumor. This method may stipulate a new guideline to optimize the fractionation regimen for physics-guided fractionation.

  1. Identification of somatic mutations in cancer through Bayesian-based analysis of sequenced genome pairs.

    Science.gov (United States)

    Christoforides, Alexis; Carpten, John D; Weiss, Glen J; Demeure, Michael J; Von Hoff, Daniel D; Craig, David W

    2013-05-04

    The field of cancer genomics has rapidly adopted next-generation sequencing (NGS) in order to study and characterize malignant tumors with unprecedented resolution. In particular for cancer, one is often trying to identify somatic mutations--changes specific to a tumor and not within an individual's germline. However, false positive and false negative detections often result from lack of sufficient variant evidence, contamination of the biopsy by stromal tissue, sequencing errors, and the erroneous classification of germline variation as tumor-specific. We have developed a generalized Bayesian analysis framework for matched tumor/normal samples with the purpose of identifying tumor-specific alterations such as single nucleotide mutations, small insertions/deletions, and structural variation. We describe our methodology, and discuss its application to other types of paired-tissue analysis such as the detection of loss of heterozygosity as well as allelic imbalance. We also demonstrate the high level of sensitivity and specificity in discovering simulated somatic mutations, for various combinations of a) genomic coverage and b) emulated heterogeneity. We present a Java-based implementation of our methods named Seurat, which is made available for free academic use. We have demonstrated and reported on the discovery of different types of somatic change by applying Seurat to an experimentally-derived cancer dataset using our methods; and have discussed considerations and practices regarding the accurate detection of somatic events in cancer genomes. Seurat is available at https://sites.google.com/site/seuratsomatic.

  2. A Bayesian statistical analysis of mouse dermal tumor promotion assay data for evaluating cigarette smoke condensate.

    Science.gov (United States)

    Kathman, Steven J; Potts, Ryan J; Ayres, Paul H; Harp, Paul R; Wilson, Cody L; Garner, Charles D

    2010-10-01

    The mouse dermal assay has long been used to assess the dermal tumorigenicity of cigarette smoke condensate (CSC). This mouse skin model has been developed for use in carcinogenicity testing utilizing the SENCAR mouse as the standard strain. Though the model has limitations, it remains as the most relevant method available to study the dermal tumor promoting potential of mainstream cigarette smoke. In the typical SENCAR mouse CSC bioassay, CSC is applied for 29 weeks following the application of a tumor initiator such as 7,12-dimethylbenz[a]anthracene (DMBA). Several endpoints are considered for analysis including: the percentage of animals with at least one mass, latency, and number of masses per animal. In this paper, a relatively straightforward analytic model and procedure is presented for analyzing the time course of the incidence of masses. The procedure considered here takes advantage of Bayesian statistical techniques, which provide powerful methods for model fitting and simulation. Two datasets are analyzed to illustrate how the model fits the data, how well the model may perform in predicting data from such trials, and how the model may be used as a decision tool when comparing the dermal tumorigenicity of cigarette smoke condensate from multiple cigarette types. The analysis presented here was developed as a statistical decision tool for differentiating between two or more prototype products based on the dermal tumorigenicity. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  3. A semiautomatic CT-based ensemble segmentation of lung tumors: comparison with oncologists' delineations and with the surgical specimen.

    Science.gov (United States)

    Rios Velazquez, Emmanuel; Aerts, Hugo J W L; Gu, Yuhua; Goldgof, Dmitry B; De Ruysscher, Dirk; Dekker, Andre; Korn, René; Gillies, Robert J; Lambin, Philippe

    2012-11-01

    To assess the clinical relevance of a semiautomatic CT-based ensemble segmentation method, by comparing it to pathology and to CT/PET manual delineations by five independent radiation oncologists in non-small cell lung cancer (NSCLC). For 20 NSCLC patients (stages Ib-IIIb) the primary tumor was delineated manually on CT/PET scans by five independent radiation oncologists and segmented using a CT based semi-automatic tool. Tumor volume and overlap fractions between manual and semiautomatic-segmented volumes were compared. All measurements were correlated with the maximal diameter on macroscopic examination of the surgical specimen. Imaging data are available on www.cancerdata.org. High overlap fractions were observed between the semi-automatically segmented volumes and the intersection (92.5±9.0, mean±SD) and union (94.2±6.8) of the manual delineations. No statistically significant differences in tumor volume were observed between the semiautomatic segmentation (71.4±83.2 cm(3), mean±SD) and manual delineations (81.9±94.1 cm(3); p=0.57). The maximal tumor diameter of the semiautomatic-segmented tumor correlated strongly with the macroscopic diameter of the primary tumor (r=0.96). Semiautomatic segmentation of the primary tumor on CT demonstrated high agreement with CT/PET manual delineations and strongly correlated with the macroscopic diameter considered as the "gold standard". This method may be used routinely in clinical practice and could be employed as a starting point for treatment planning, target definition in multi-center clinical trials or for high throughput data mining research. This method is particularly suitable for peripherally located tumors. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  4. Factors affecting the local control of stereotactic body radiotherapy for lung tumors including primary lung cancer and metastatic lung tumors

    International Nuclear Information System (INIS)

    Hamamoto, Yasushi; Kataoka, Masaaki; Yamashita, Motohiro

    2012-01-01

    The purpose of this study was to identify factors affecting local control of stereotactic body radiotherapy (SBRT) for lung tumors including primary lung cancer and metastatic lung tumors. Between June 2006 and June 2009, 159 lung tumors in 144 patients (primary lung cancer, 128; metastatic lung tumor, 31) were treated with SBRT with 48-60 Gy (mean 50.1 Gy) in 4-5 fractions. Higher doses were given to larger tumors and metastatic tumors in principle. Assessed factors were age, gender, tumor origin (primary vs. metastatic), histological subtype, tumor size, tumor appearance (solid vs. ground glass opacity), maximum standardized uptake value of positron emission tomography using 18 F-fluoro-2-deoxy-D-glucose, and SBRT doses. Follow-up time was 1-60 months (median 18 months). The 1-, 2-, and 3-year local failure-free rates of all lesions were 90, 80, and 77%, respectively. On univariate analysis, metastatic tumors (p<0.0001), solid tumors (p=0.0246), and higher SBRT doses (p=0.0334) were the statistically significant unfavorable factors for local control. On multivariate analysis, only tumor origin was statistically significant (p=0.0027). The 2-year local failure-free rates of primary lung cancer and metastatic lung tumors were 87 and 50%, respectively. A metastatic tumor was the only independently significant unfavorable factor for local control after SBRT. (author)

  5. [Meta-analysis of relationship between extranodal tumor deposits and prognosis in patients with colorectal cancer].

    Science.gov (United States)

    Zhang, Xianxiang; Shao, Shihong; Gao, Yuan; Zhang, Maoshen; Lu, Yun

    2016-03-01

    To investigate the relationship between extranodal tumor deposits and prognosis in patients with colorectal cancer. The literatures on extranodal tumor deposits and postoperative survival rate in patients with colorectal cancer published at home and abroad from 1990 to 2014 were retrieved in 15 English literature databases such as MEDLINE/PubMed, Web of Science, Directory of Open Access Journals(DOAJ), SpringerLink and Chinese literature databases such as Chinese Biomedical Literature Database CD-ROM, China National Knowledge Infrastructure (CNKI) Database with the internet platform of Yonsei University Library. After screening for inclusion, data extraction and quality assessment, meta-analysis was conducted by the Review Manager 5.3 software. There were 10 studies meeting the inclusion criteria for meta-analysis. The total sample size of the studies was 4 068 cases with ENTD(+) 727 cases, while ENTD(-) 3 341 cases. Meta analysis showed that 5-year overall survival rate and 5-year relapse-free survival rate were significantly lower in ENTD(+) group than those in ENTD(-) group (OR 0.27, 0.23; 95% CI:0.18 to 0.43, 0.16 to 0.34 respectively, both P=0.000); the 5-year overall survival rates were both significantly lower in ENTD(+) group as compared to ENTD(-) group for patients with N0 and N(+) colorectal cancer (both P<0.05). Extranodal tumor deposits is a poor prognostic factor of patients with colorectal cancer.

  6. Immune response to UV-induced tumors: mediation of progressor tumor rejection by natural killer cells

    International Nuclear Information System (INIS)

    Streeter, P.R.; Fortner, G.W.

    1986-01-01

    Skin tumors induced in mice by chronic ultraviolet (UV) irradiation are highly antigenic and can induce a state of transplantation immunity in syngeneic animals. In the present study, the authors compared the in vitro cytolytic activity of splenic lymphocytes from mice immunized with either regressor or progressor UV-tumors. The results of this comparison implicated tumor-specific cytolytic T (Tc) lymphocytes in rejection of regressor UV-tumors, and revealed that immunization with the progressor UV-tumor 2237 failed to elicit detectable levels of progressor tumor-specific Tc cells even as the tumors rejected. Following in vitro resensitization of spleen cells from either regressor or progressor tumor immune animals, the authors found NK-like lymphocytes with anti-tumor activity. As the authors had not detected cells with this activity in splenic lymphocyte preparations prior to in vitro resensitization, the authors examined lymphocytes from the local tumor environment during the course of progressor tumor rejection for this activity. This analysis revealed NK lymphocytes exhibiting significant levels of cytolytic activity against UV-tumors. These results implicate NK cells as potential effector cells in the rejection of progressor UV-tumors by immune animals, and suggests that these cells may be regulated by T lymphocytes

  7. Cost-effectiveness analysis of optimal strategy for tumor treatment

    International Nuclear Information System (INIS)

    Pang, Liuyong; Zhao, Zhong; Song, Xinyu

    2016-01-01

    We propose and analyze an antitumor model with combined immunotherapy and chemotherapy. Firstly, we explore the treatment effects of single immunotherapy and single chemotherapy, respectively. Results indicate that neither immunotherapy nor chemotherapy alone are adequate to cure a tumor. Hence, we apply optimal theory to investigate how the combination of immunotherapy and chemotherapy should be implemented, for a certain time period, in order to reduce the number of tumor cells, while minimizing the implementation cost of the treatment strategy. Secondly, we establish the existence of the optimality system and use Pontryagin’s Maximum Principle to characterize the optimal levels of the two treatment measures. Furthermore, we calculate the incremental cost-effectiveness ratios to analyze the cost-effectiveness of all possible combinations of the two treatment measures. Finally, numerical results show that the combination of immunotherapy and chemotherapy is the most cost-effective strategy for tumor treatment, and able to eliminate the entire tumor with size 4.470 × 10"8 in a year.

  8. Tumor accumulation of {epsilon}-poly-lysines-based polyamines conjugated with boron clusters

    Energy Technology Data Exchange (ETDEWEB)

    Umano, Masayuki; Uechi, Kazuhiro; Uriuda, Takatoshi; Murayama, Sayuri; Azuma, Hideki [Department of Applied Chemistry and Bioengineering, Graduate School of Engineering, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 5588585 (Japan); Shinohara, Atsuko [Department of Epidemiology and Environmental Health, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 1138421 (Japan); Liu, Young; Ono, Koji [Research Reactor Institute, Kyoto University, 2-1010 Asashiro-nishi, Kumatori 5900494 (Japan); Kirihata, Mitsunori [Department of Bioscience and Informatics, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-1 Gakuen-cho, Sakai 5998531 (Japan); Yanagie, Hironobu [Department of Nuclear Engineering and Management, Graduate School of Engineering, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 1138656 (Japan); Nagasaki, Takeshi, E-mail: nagasaki@bioa.eng.osaka-cu.ac.jp [Department of Applied Chemistry and Bioengineering, Graduate School of Engineering, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 5588585 (Japan)

    2011-12-15

    Boron Neutron Capture Therapy (BNCT) is one of the potent cancer radiotherapies using nuclear reaction between {sup 10}B atoms and the neutron. Whether BNCT will succeed or not depends on tumor selective delivery of {sup 10}B compounds. {epsilon}-Poly-L-lysine is a naturally occurring polyamine characterized by the peptide linkages between the carboxyl and {epsilon}-amino groups of L-lysine. Because of high safety {epsilon}-PLL is applied practically as a food additive due to its strong antimicrobial activity. In this study, we focus on a development of a novel polymeric delivery system for BNCT using biodegradable {epsilon}-PLL conjugated with {sup 10}B-containing clusters (BSH). This polymeric boron carrier will be expected to deliver safely and efficiently into tumor tissues based on Enhanced Permeability and Retention (EPR) effect.

  9. Racial Variations in Prostate Cancer Molecular Subtypes and Androgen Receptor Signaling Reflect Anatomic Tumor Location.

    Science.gov (United States)

    Faisal, Farzana A; Sundi, Debasish; Tosoian, Jeffrey J; Choeurng, Voleak; Alshalalfa, Mohammed; Ross, Ashley E; Klein, Eric; Den, Robert; Dicker, Adam; Erho, Nicholas; Davicioni, Elai; Lotan, Tamara L; Schaeffer, Edward M

    2016-07-01

    Prostate cancer (PCa) subtypes based on ETS gene expression have been described. Recent studies suggest there are racial differences in tumor location, with PCa located anteriorly more often among African-American (AA) compared to Caucasian-American (CA) men. In this retrospective analysis of a multi-institutional cohort treated by radical prostatectomy (179 CA, 121 AA), we evaluated associations among molecular subtype, race, anatomic tumor location, and androgen receptor (AR) signaling. Subtype (m-ERG(+), m-ETS(+), m-SPINK1(+), or triple-negative) was determined using distribution-based outlier analysis. AR signaling was investigated using gene expression profiling of canonical AR targets. m-ERG(+) was more common in CA than AA men (47% vs 22%, pprostate cancer molecular subtypes, and tumor location. Location-specific differences in androgen regulation may further underlie these relationships. Copyright © 2015. Published by Elsevier B.V.

  10. The Prospective External Validation of International Ovarian Tumor Analysis (IOTA) Simple Rules in the Hands of Level I and II Examiners.

    Science.gov (United States)

    Knafel, A; Banas, T; Nocun, A; Wiechec, M; Jach, R; Ludwin, A; Kabzinska-Turek, M; Pietrus, M; Pitynski, K

    2016-10-01

    Objective: To externally validate the International Ovarian Tumor Analysis (IOTA) Simple Rules (SR) by examiners with different levels of sonographic experience defined by the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) and to assess the morphological ultrasound features of the adnexal tumors classified as inconclusive based on IOTA SR. Materials and Methods: In the two-year prospective study adnexal tumors were assessed preoperatively with transvaginal ultrasound by examiners with different levels of experience (level 1- IOTA SR1, level 2-IOTA SR2). Additionally, an expert (level 3) evaluated all tumors by subjective assessment (SA). If the rules could not be applied, the tumors were considered inconclusive. The final diagnosis was based on the histopathological result of the removed mass. The diagnostic performance measures for the assessed model were sensitivity, specificity, negative (LR-) and positive(LR+) likelihood ratios, accuracy (ACC) and diagnostic odds ratio (DOR). Results: 226 women with adnexal tumors scheduled for surgery were included in the stutdy. The prevalence of malignancy was 36.3 % in the group of all studied tumors and was 52.5 % in the inconclusive group (n = 40) (p = 0.215). Fewer tumors were classified as inconclusive by level 2 examiners compared to level 1 examiners [20 (8.8 %) vs. 40 (17.7 %); p = 0.008], resulting from the discrepancy in the evaluation of acoustic shadows and the vascularization within the tumor. For level 1 examiners a diagnostic strategy using IOTA SR1 +MA (assuming malignancy when SR inconclusive) achieved a sensitivity, specificity and DOR of 96.3 %, 81.9 %, 13.624 respectively. For level 2 examiners the diagnostic strategy for IOTA SR2 +MA achieved a sensitivity, specificity and DOR of 95.1 %, 89.6 %, 137,143, respectively. Adding SA by an expert (or level 3 examiner) when IOTA SR were not applicable improved the specificity of the test and

  11. Computer-Aided Detection of Kidney Tumor on Abdominal Computed Tomography Scans

    International Nuclear Information System (INIS)

    Kim, D.Y.; Park, J.W.

    2004-01-01

    Purpose: To implement a computer-aided detection system for kidney segmentation and kidney tumor detection on abdominal computed tomography (CT) scans. Material and Methods: Abdominal CT images were digitized with a film digitizer, and a gray-level threshold method was used to segment the kidney. Based on texture analysis performed on sample images of kidney tumors, a portion of the kidney tumor was selected as seed region for start point of the region-growing process. The average and standard deviations were used to detect the kidney tumor. Starting at the detected seed region, the region-growing method was used to segment the kidney tumor with intensity values used as an acceptance criterion for a homogeneous test. This test was performed to merge the neighboring region as kidney tumor boundary. These methods were applied on 156 transverse images of 12 cases of kidney tumors scanned using a G.E. Hispeed CT scanner and digitized with a Lumisys LS-40 film digitizer. Results: The computer-aided detection system resulted in a kidney tumor detection sensitivity of 85% and no false-positive findings. Conclusion: This computer-aided detection scheme was useful for kidney tumor detection and gave the characteristics of detected kidney tumors

  12. Three-dimensional positron emission tomography image texture analysis of esophageal squamous cell carcinoma: relationship between tumor 18F-fluorodeoxyglucose uptake heterogeneity, maximum standardized uptake value, and tumor stage.

    Science.gov (United States)

    Dong, Xinzhe; Xing, Ligang; Wu, Peipei; Fu, Zheng; Wan, Honglin; Li, Dengwang; Yin, Yong; Sun, Xiaorong; Yu, Jinming

    2013-01-01

    To explore the relationship of a new PET image parameter, (18)F-fluorodeoxyglucose ((18)F-FDG) uptake heterogeneity assessed by texture analysis, with maximum standardized uptake value (SUV(max)) and tumor TNM staging. Forty consecutive patients with esophageal squamous cell carcinoma were enrolled. All patients underwent whole-body preoperative (18)F-FDG PET/CT. Heterogeneity of intratumoral (18)F-FDG uptake was assessed on the basis of the textural features (entropy and energy) of the three-dimensional images using MATLAB software. The correlations between the textural parameters and SUV(max), histological grade, tumor location, and TNM stage were analyzed. Tumors with higher SUV(max) were seen to be more heterogenous on (18)F-FDG uptake. Significant correlations were observed between T stage and SUV(max) (r(s)=0.390, P=0.013), entropy (rs=0.693, Pheterogeneity and the commonly used simplistic parameter of SUV and tumor stage. Our findings suggest a complementary role of these parameters in the staging and prognosis of esophageal squamous cell carcinoma.

  13. CT-Guided Microwave Ablation of 45 Renal Tumors: Analysis of Procedure Complexity Utilizing a Percutaneous Renal Ablation Complexity Scoring System.

    Science.gov (United States)

    Mansilla, Alberto V; Bivins, Eugene E; Contreras, Francisco; Hernandez, Manuel A; Kohler, Nathan; Pepe, Julie W

    2017-02-01

    To develop a scoring system that stratifies complexity of percutaneous ablation of renal tumors. Analysis was performed of 36 consecutive patients (mean age, 64 y; range, 30-89 y) who underwent CT-guided microwave (MW) ablation of 45 renal tumors (mean tumor diameter, 2.4 cm; range, 1.2-4.0 cm). Technical success and effectiveness were determined based on intraprocedural and follow-up imaging studies. The RENAL score and the proposed percutaneous renal ablation complexity (P-RAC) score were calculated for each tumor. Technical success was 93.3% (n = 42). Biopsy of 38 of 45 renal tumors revealed 23 renal cell carcinomas. Median follow-up period was 9.7 months (range, 2.9-46.8 months). There were no tumor recurrences. One major complication, ureteropelvic junction stricture, occurred (2.6%). The P-RAC score was found to differ statistically from the RENAL score (t = 3.754, df = 44, P = .001). A positive correlation was found between the P-RAC score and number of antenna insertions (r = .378, n = 45, P = .011) and procedure duration (r = .328, n = 45, P = .028). No correlation was found between the RENAL score and number of MW antenna insertions (r = .110, n = 45, P = .472) or procedure duration (r = .263, n = 45, P = .081). Hydrodissection was significantly more common in the P-RAC high-complexity category than in low-complexity category (χ 2 = 12.073, df = 2, P = .002). The P-RAC score may be useful in stratifying percutaneous renal ablation complexity. Further studies with larger sample sizes are necessary to validate the P-RAC score and to determine if it can predict risk of complications. Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.

  14. Gene expression analysis of matched ovarian primary tumors and peritoneal metastasis

    Directory of Open Access Journals (Sweden)

    Malek Joel A

    2012-06-01

    Full Text Available Abstract Background Ovarian cancer is the most deadly gynecological cancer due to late diagnosis at advanced stage with major peritoneal involvement. To date most research has focused on primary tumor. However the prognosis is directly related to residual disease at the end of the treatment. Therefore it is mandatory to focus and study the biology of meatastatic disease that is most frequently localized to the peritoneal caivty in ovarian cancer. Methods We used high-density gene expression arrays to investigate gene expression changes between matched primary and metastatic (peritoneal lesions. Results Here we show that gene expression profiles in peritoneal metastasis are significantly different than their matched primary tumor and these changes are affected by underlying copy number variation differences among other causes. We show that differentially expressed genes are enriched in specific pathways including JAK/STAT pathway, cytokine signaling and other immune related pathways. We show that underlying copy number variations significantly affect gene expression. Indeed patients with important differences in copy number variation displayed greater gene expression differences between their primary and matched metastatic lesions. Conclusions Our analysis shows a very specific targeting at both the genomic and transcriptomic level to upregulate certain pathways in the peritoneal metastasis of ovarian cancer. Moreover, while primary tumors use certain pathways we identify distinct differences with metastatic lesions. The variation between primary and metastatic lesions should be considered in personalized treatment of ovarian cancer.

  15. Saponin-based adjuvants create a highly effective anti-tumor vaccine when combined with in situ tumor destruction.

    NARCIS (Netherlands)

    Brok, M.H.M.G.M. den; Nierkens, S.; Wagenaars, J.A.L.; Ruers, T.J.M.; Schrier, C.C.; Rijke, E.O.; Adema, G.J.

    2012-01-01

    Today's most commonly used microbial vaccines are essentially composed of antigenic elements and a non-microbial adjuvant, and induce solid amounts of antibodies. Cancer vaccines mostly aim to induce anti-tumor CTL-responses, which require cross-presentation of tumor-derived antigens by dendritic

  16. Surface-enhanced Raman spectroscopy of saliva proteins for the noninvasive differentiation of benign and malignant breast tumors

    Science.gov (United States)

    Feng, Shangyuan; Huang, Shaohua; Lin, Duo; Chen, Guannan; Xu, Yuanji; Li, Yongzeng; Huang, Zufang; Pan, Jianji; Chen, Rong; Zeng, Haishan

    2015-01-01

    The capability of saliva protein analysis, based on membrane protein purification and surface-enhanced Raman spectroscopy (SERS), for detecting benign and malignant breast tumors is presented in this paper. A total of 97 SERS spectra from purified saliva proteins were acquired from samples obtained from three groups: 33 healthy subjects; 33 patients with benign breast tumors; and 31 patients with malignant breast tumors. Subtle but discernible changes in the mean SERS spectra of the three groups were observed. Tentative assignments of the saliva protein SERS spectra demonstrated that benign and malignant breast tumors led to several specific biomolecular changes of the saliva proteins. Multiclass partial least squares–discriminant analysis was utilized to analyze and classify the saliva protein SERS spectra from healthy subjects, benign breast tumor patients, and malignant breast tumor patients, yielding diagnostic sensitivities of 75.75%, 72.73%, and 74.19%, as well as specificities of 93.75%, 81.25%, and 86.36%, respectively. The results from this exploratory work demonstrate that saliva protein SERS analysis combined with partial least squares–discriminant analysis diagnostic algorithms has great potential for the noninvasive and label-free detection of breast cancer. PMID:25609959

  17. Quantitative analysis of TEM-8 and CEA tumor markers indicating free tumor cells in the peripheral blood of colorectal cancer patients.

    Science.gov (United States)

    Raeisossadati, Reza; Farshchian, Moein; Ganji, Azita; Tavassoli, Alieza; Velayati, Arash; Dadkhah, Ezzat; Chavoshi, Somaye; Mehrabi Bahar, Mostafa; Memar, Bahram; Rajabi Mashhadi, Mohammad Taghi; Naseh, Hossein; Forghanifard, Mohammad Mahdi; Moghbeli, Meysam; Moaven, Omeed; Abbaszadegan, Mohammad Reza

    2011-10-01

    Colorectal cancer (CRC) remains the third most common cancer in the world. Approximately in 50 percent of patients, metastatic disease is a major cause of death. Therefore, early diagnosis of CRC is crucial for a successful outcome. For the detection of circulating cancer cells, this study applied a sensitive method that employed specific tumor markers for early detection. A total of 80 blood samples from 40 CRC patients and 40 age-matched healthy controls were collected for the study. The circulating mRNA levels of two CRC tumor markers, tumor endothelial marker 8 (TEM-8) and carcinoembryogenic antigen (CEA) were evaluated using an absolute quantitative real-time PCR assay in a Stratagene Mx-3000P real-time PCR system. GAPDH was used as the endogenous control. TEM-8 and CEA were primarily detected more in the CRC patients rather than in the controls: 22/40 vs 9/40, p=0.009 and 30/40 vs 11/40, p=0.00054, respectively. In the CRC patients, the mRNA level of these markers was significantly higher in comparison to the normal controls (p=0.018 and 0.01). The overall sensitivity of this panel was 65% with a specificity of 75%. Statistical analysis for demographic variants did not reach significant values. TEM-8 and CEA markers were detected more frequently and in significantly higher levels in the blood samples of patients compared with samples from age-matched healthy controls. The copy number of CEA and TEM-8 mRNA, as detected by a real-time quantitative PCR, appears to be a promising marker for evaluating the risk of tumor spread.

  18. Method of hyperthermia and tumor size influence effectiveness of doxorubicin release from thermosensitive liposomes in experimental tumors.

    Science.gov (United States)

    Willerding, Linus; Limmer, Simone; Hossann, Martin; Zengerle, Anja; Wachholz, Kirsten; Ten Hagen, Timo L M; Koning, Gerben A; Sroka, Ronald; Lindner, Lars H; Peller, Michael

    2016-01-28

    Systemic chemotherapy of solid tumors could be enhanced by local hyperthermia (HT) in combination with thermosensitive liposomes (TSL) as drug carriers. In such an approach, effective HT of the tumor is considered essential for successful triggering local drug release and targeting of the drug to the tumor. To investigate the effect of HT method on the effectiveness of drug delivery, a novel laser-based HT device designed for the use in magnetic resonance imaging (MRI) was compared systematically with the frequently used cold light lamp and water bath HT. Long circulating phosphatidyldiglycerol-based TSL (DPPG2-TSL) with encapsulated doxorubicin (DOX) were used as drug carrier enabling intravascular drug release. Experiments were performed in male Brown Norway rats with a syngeneic soft tissue sarcoma (BN 175) located on both hind legs. One tumor was heated while the second tumor remained unheated as a reference. Six animals were investigated per HT method. DPPG2-TSL were injected i.v. at a stable tumor temperature above 40°C. Thereafter, temperature was maintained for 60min. Total DOX concentration in plasma, tumor tissue and muscle was determined post therapy by HPLC. Finally, the new laser-based device was tested in a MRI environment at 3T using DPPG2-TSL with encapsulated Gd-based contrast agent. All methods showed effective DOX delivery by TSL with 4.5-23.1ng/mg found in the heated tumors. In contrast, DOX concentration in the non-heated tumors was 0.5±0.1ng/mg. Independent of used HT methods, higher DOX levels were found in the smaller tumors. In comparison water bath induced lowest DOX delivery but still showing fourfold higher DOX concentrations compared to the non-heated tumors. With the laser-based applicator, a 13 fold higher DOX deposition was possible for large tumors and a 15 fold higher for the small tumors, respectively. Temperature gradients in the tumor tissue were higher with the laser and cold light lamp (-0.3°C/mm to -0.5°C/mm) compared to

  19. Immunogenic Cell Death Induced by Ginsenoside Rg3: Significance in Dendritic Cell-based Anti-tumor Immunotherapy.

    Science.gov (United States)

    Son, Keum-Joo; Choi, Ki Ryung; Lee, Seog Jae; Lee, Hyunah

    2016-02-01

    Cancer is one of the leading causes of morbidity and mortality worldwide; therefore there is a need to discover new therapeutic modules with improved efficacy and safety. Immune-(cell) therapy is a promising therapeutic strategy for the treatment of intractable cancers. The effectiveness of certain chemotherapeutics in inducing immunogenic tumor cell death thus promoting cancer eradication has been reported. Ginsenoside Rg3 is a ginseng saponin that has antitumor and immunomodulatory activity. In this study, we treated tumor cells with Rg3 to verify the significance of inducing immunogenic tumor cell death in antitumor therapy, especially in DC-based immunotherapy. Rg3 killed the both immunogenic (B16F10 melanoma cells) and non-immunogenic (LLC: Lewis Lung Carcinoma cells) tumor cells by inducing apoptosis. Surface expression of immunogenic death markers including calreticulin and heat shock proteins and the transcription of relevant genes were increased in the Rg3-dying tumor. Increased calreticulin expression was directly related to the uptake of dying tumor cells by dendritic cells (DCs): the proportion of CRT(+) CD11c(+) cells was increased in the Rg3-treated group. Interestingly, tumor cells dying by immunogenic cell death secreted IFN-γ, an effector molecule for antitumor activity in T cells. Along with the Rg3-induced suppression of pro-angiogenic (TNF-α) and immunosuppressive cytokine (TGF-β) secretion, IFN-γ production from the Rg3-treated tumor cells may also indicate Rg3 as an effective anticancer immunotherapeutic strategy. The data clearly suggests that Rg3-induced immunogenic tumor cell death due its cytotoxic effect and its ability to induce DC function. This indicates that Rg3 may be an effective immunotherapeutic strategy.

  20. ADAM12 produced by tumor cells rather than stromal cells accelerates breast tumor progression

    DEFF Research Database (Denmark)

    Frohlich, Camilla; Nehammer, Camilla; Albrechtsen, Reidar

    2011-01-01

    that ADAM12 deficiency reduces breast tumor progression in the PyMT model. However, the catalytic activity of ADAM12 appears to be dispensable for its tumor-promoting effect. Interestingly, we demonstrate that ADAM12 endogenously expressed in tumor-associated stroma in the PyMT model does not influence......Expression of ADAM12 is low in most normal tissues, but is markedly increased in numerous human cancers, including breast carcinomas. We have previously shown that overexpression of ADAM12 accelerates tumor progression in a mouse model of breast cancer (PyMT). In the present study, we found...... hypothesized, however, that the tumor-associated stroma may stimulate ADAM12 expression in tumor cells, based on the fact that TGF-ß1 stimulates ADAM12 expression and is a well-known growth factor released from tumor-associated stroma. TGF-ß1 stimulation of ADAM12-negative Lewis lung tumor cells induced ADAM12...