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Sample records for base tumors analysis

  1. Tumor classification based on orthogonal linear discriminant analysis.

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    Wang, Huiya; Zhang, Shanwen

    2014-01-01

    Gene expression profiles have great potential for accurate tumor diagnosis. It is expected to enable us to diagnose tumors precisely and systematically, and also bring the researchers of machine learning two challenges, the curse of dimensionality and the small sample size problems. We propose a manifold learning based dimensional reduction algorithm named orthogonal local discriminant embedding (O-LDE) and apply it to tumor classification. Comparing with the classical local discriminant embedding (LDE), O-LDE aims to obtain an orthogonal linear projection matrix by solving an optimization problem. After being projected into a low-dimensional subspace by O-LDE, the data points of the same class maintain their intrinsic neighbor relations, whereas the neighboring points of the different classes are far from each other. Experimental results on a public tumor dataset validate the effectiveness and feasibility of the proposed algorithm.

  2. Extent of Endoscopic Resection for Anterior Skull Base Tumors: An MRI-Based Volumetric Analysis.

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    Koszewski, Ian J; Avey, Gregory; Ahmed, Azam; Leonhard, Lucas; Hoffman, Matthew R; McCulloch, Timothy M

    2017-06-01

    Objective  To determine the volume of ventral skull base tumor removed following endoscopic endonasal (EEA) resection using MRI-based volumetric analysis and to evaluate the inter-rater reliability of such analysis. Design  Retrospective case series. Setting  Academic tertiary care hospital. Participants  EEA patients November 2012 to August 2015. Main Outcome Measures  Volumetric analysis of pre- and immediately postoperative MR imaging was performed independently by two investigators. The percentage of total tumor resected was evaluated according to resection goal and tumor type. Results  A total of 39 patients underwent resection. Intraclass correlation coefficients between the raters were 0.9988 for preoperative and 0.9819 for postoperative images. Tumors (and average percentage removed) included 17 nonsecreting pituitary adenomas (95.3%), 8 secreting pituitary adenomas (86.2%), 4 meningiomas (81.6%), 3 olfactory neuroblastomas (100%), 2 craniopharyngiomas (100%), 1 large B-cell lymphoma (90.5%), 1 germ cell neoplasm (48.3), 1 benign fibrous connective tissue mass (93.4%), 1 epidermoid cyst (68.4%), and 1 chordoma (100%). For tumors treated with intent for gross total resection, 96.9 ± 4.8% was removed. Conclusion  EEAs achieved tumor resection rates of ∼97% when total resection was attempted. The radiographic finding of residual tumor is of uncertain clinical significance. The volumetric analysis employed in this study demonstrated high inter-rater reliability and could facilitate further study.

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

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    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.

  4. MR-based volumetric analysis of small tumor volumes: accuracy of phantom examinations of simulated eye tumors

    International Nuclear Information System (INIS)

    Lemke, A.-J.; Kazi, I.; Felix, R.; Hosten, N.; Bechrakis, N.E.; Foerster, M.H.

    2003-01-01

    Purpose: The determination of tumor volume in ocular tumors is very important for the planning and success of radiation therapy. This study uses an animal model to evaluate the accuracy of MR-based volumetry of ocular tumors. Materials and methods: In a total of 25 porcine eyes obtained from the slaughterhouse, ocular tumors were produced by injecting a mixture of hand creme and Gd-DTPA under ophthalmoscopic guidance. The injected volume varied between 0.05 ml and 2.7 ml. The eyes were examined with a 1.5 Tesla scanner and a 4 cm circular surface coil especially developed for ocular MRI. After data transfer to a separate workstation, volumetric analysis was carried out by three independent radiologists using semiautomated software. The determined volume was compared with the injected volume. Results: Of the 25 prepared porcine eyes, 23 were suitable for volumetric analysis. The injection of the mixture of hand creme and GD-DTPA produced two different types of tumors. Ophthalmoscopically, 14 ellipsoid and 9 lobulated to mushroom-shaped tumors were found and confirmed by MRI. Minor deviation was found between injected volume and volume calculated by MRI, with a correlation coefficient of 0.96. Conclusion: Using appropriate technique, MRI is capable of determining small tumor volumes with high accuracy in an animal model. Minor differences can be expected when transferring the results to clinical studies. (orig.) [de

  5. 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)

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

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    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.

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

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    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.

  8. New approach to breast tumor detection based on fluorescence x-ray analysis

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    Okuyama, Fumio

    2010-01-01

    Full Text Available A new technical approach to breast-tumor detection is proposed. The technique is based on fluorescence x-ray analysis, and can identify a miniature malignant tumor within the breast. The primary beam intensity needed in fluorescence x-ray analysis is on a lower order of magnitude than that used in mammography. Thus, the newly-proposed technique would enable detection of a still tiny breast cancer while dramatically lowering the radiation dose. Field-emission x-ray sources might be a key for translating this concept into a medical technique.

  9. Fourier ptychographic microscopy for filtration-based circulating tumor cell enumeration and analysis.

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    Williams, Anthony; Chung, Jaebum; Ou, Xiaoze; Zheng, Guoan; Rawal, Siddarth; Ao, Zheng; Datar, Ram; Yang, Changhuei; Cote, Richard

    2014-06-01

    Circulating tumor cells (CTCs) are recognized as a candidate biomarker with strong prognostic and predictive potential in metastatic disease. Filtration-based enrichment technologies have been used for CTC characterization, and our group has previously developed a membrane microfilter device that demonstrates efficacy in model systems and clinical blood samples. However, uneven filtration surfaces make the use of standard microscopic techniques a difficult task, limiting the performance of automated imaging using commercially available technologies. Here, we report the use of Fourier ptychographic microscopy (FPM) to tackle this challenge. Employing this method, we were able to obtain high-resolution color images, including amplitude and phase, of the microfilter samples over large areas. FPM's ability to perform digital refocusing on complex images is particularly useful in this setting as, in contrast to other imaging platforms, we can focus samples on multiple focal planes within the same frame despite surface unevenness. In model systems, FPM demonstrates high image quality, efficiency, and consistency in detection of tumor cells when comparing corresponding microfilter samples to standard microscopy with high correlation (R² = 0.99932). Based on these results, we believe that FPM will have important implications for improved, high throughput, filtration-based CTC analysis, and, more generally, image analysis of uneven surfaces.

  10. PET-based analysis of tumor glucose metabolism and tumor hypoxia before and during anti-neoplastic treatment

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    Bollineni, Vikram

    2015-01-01

    Tumor hypoxia is an important contributor to chemo-radiotherapy resistance. This has been demonstrated in several tumor types including non-small cell lung cancer and head and neck squamous cell carcinoma. Tumor hypoxia is a dynamic process, some parts of the tumor exhibit higher levels of hypoxia

  11. Skull base tumor model.

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    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

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

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    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.

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

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    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

  14. Image Analysis for MRI Based Brain Tumor Detection and Feature Extraction Using Biologically Inspired BWT and SVM

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    Nilesh Bhaskarrao Bahadure

    2017-01-01

    Full Text Available The segmentation, detection, and extraction of infected tumor area from magnetic resonance (MR images are a primary concern but a tedious and time taking task performed by radiologists or clinical experts, and their accuracy depends on their experience only. So, the use of computer aided technology becomes very necessary to overcome these limitations. In this study, to improve the performance and reduce the complexity involves in the medical image segmentation process, we have investigated Berkeley wavelet transformation (BWT based brain tumor segmentation. Furthermore, to improve the accuracy and quality rate of the support vector machine (SVM based classifier, relevant features are extracted from each segmented tissue. The experimental results of proposed technique have been evaluated and validated for performance and quality analysis on magnetic resonance brain images, based on accuracy, sensitivity, specificity, and dice similarity index coefficient. The experimental results achieved 96.51% accuracy, 94.2% specificity, and 97.72% sensitivity, demonstrating the effectiveness of the proposed technique for identifying normal and abnormal tissues from brain MR images. The experimental results also obtained an average of 0.82 dice similarity index coefficient, which indicates better overlap between the automated (machines extracted tumor region with manually extracted tumor region by radiologists. The simulation results prove the significance in terms of quality parameters and accuracy in comparison to state-of-the-art techniques.

  15. Population based analysis of survival in patients with renal cell carcinoma and venous tumor thrombus.

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    Whitson, Jared M; Reese, Adam C; Meng, Maxwell V

    2013-02-01

    To identify prognostic factors for renal cell carcinoma (RCC) with venous tumor thrombus (VTT) and determine the significance of thrombus level on survival. Patients within the Surveillance, Epidemiology, and End Results (SEER) database with RCC and VTT were identified and included if managed surgically. The Kaplan-Meier method and Cox regression analyses were performed to identify factors associated with disease-specific survival. A total of 1,875 patients met the inclusion criteria. One-year survival for patients undergoing surgery was 60% for patients with metastases and 90% for those without. Factors associated with worse survival included larger tumor size (HR 1.2, 95% CI 1.0-1.4), medullary, collecting duct, or sarcomatoid histology (HR 2.2, 95% CI 1.5-3.3), Fuhrman grade 3 (HR 2.2, 95% CI 1.5-3.3) or grade 4 (HR 2.9, 95% CI 1.8-4.5) tumors, positive lymph nodes (HR 1.5, 95% CI 1.0-2.0), and metastases (HR 3.5, 95% CI 2.6-4.8). Thrombus level above the diaphragm (T3c) was not significantly associated with worse survival (HR 1.4, 95% CI 0.8-2.5). In this large, population-based study of patients with RCC and VTT, we identify several disease-specific factors strongly associated with cancer-specific mortality. After controlling for adverse prognostic factors, thrombus level was not associated with worse outcome. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Image-Based Analysis of Tumor Localization After Intra-Arterial Delivery of Technetium-99m-Labeled SPIO Using SPECT/CT and MRI

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    In Joon Lee MD, PhD

    2017-01-01

    Full Text Available The aim of this study is to evaluate the localization of 99mTc-labeled dextran-coated superparamagnetic iron oxide (SPIO nanoparticles to the liver tumor using image-based analysis. We delivered 99mTc-SPIO intravenously or intra-arterially (IA with/without Lipiodol to compare the tumor localization by gamma scintigraphy, single-photon emission computed tomography (SPECT, and magnetic resonance imaging (MRI in a rabbit liver tumor. The gamma and SPECT image-based analysis shows that the uptake ratio of the tumor to the normal liver parenchyma is highest after delivery of 99mTc-SPIO with Lipiodol IA and that well correlates with the trend of the signal decrease in the liver MRIs. Intra-arterial delivery of SPIO with Lipiodol might be a good drug delivery system targeting the hepatic tumors, as confirmed by image-based analysis.

  17. Pathway-based network analysis of myeloma tumors: monoclonal gammopathy of unknown significance, smoldering multiple myeloma, and multiple myeloma.

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    Dong, L; Chen, C Y; Ning, B; Xu, D L; Gao, J H; Wang, L L; Yan, S Y; Cheng, S

    2015-08-14

    Although many studies have been carried out on monoclonal gammopathy of unknown significances (MGUS), smoldering multiple myeloma (SMM), and multiple myeloma (MM), their classification and underlying pathogenesis are far from elucidated. To discover the relationships among MGUS, SMM, and MM at the transcriptome level, differentially expressed genes in MGUS, SMM, and MM were identified by the rank product method, and then co-expression networks were constructed by integrating the data. Finally, a pathway-network was constructed based on Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and the relationships between the pathways were identified. The results indicated that there were 55, 78, and 138 pathways involved in the myeloma tumor developmental stages of MGUS, SMM, and MM, respectively. The biological processes identified therein were found to have a close relationship with the immune system. Processes and pathways related to the abnormal activity of DNA and RNA were also present in SMM and MM. Six common pathways were found in the whole process of myeloma tumor development. Nine pathways were shown to participate in the progression of MGUS to SMM, and prostate cancer was the sole pathway that was involved only in MGUS and MM. Pathway-network analysis might provide a new indicator for the developmental stage diagnosis of myeloma tumors.

  18. 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

  19. 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

  20. Antibody-Directed Effector Cell Therapy of Tumors: Analysis and Optimization Using a Physiologically Based Pharmacokinetic Model

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    Stuart W. Friedrich

    2002-01-01

    Full Text Available The failure of the cellular immune response to stop solid tumor growth has been the subject of much research. Although the mechanisms for tumor evasion of immune response are poorly understood, one viable explanation is that tumor-killing lymphocytes cannot reach the tumor cells in sufficient quantity to keep the tumor in check. Recently, the use of bifunctional antibodies. (BFAs has been proposed as a way to direct immune cells to the tumor: one arm of the antibody is specific for a known tumor-associated antigen and the other for a lymphocyte marker such as CD3. Injecting this BFA should presumably result in cross-linking of lymphocytes. (either endogenous or adoptively transferred with tumor cells, thereby enhancing therapy. Results from such an approach, however, are often disappointing- frequently there is no benefit gained by using the BFA. We have analyzed the retargeting of endogenous effector cells by BFA using a physiologically based whole-body pharmacokinetic model that accounts for interactions between all relevant species in the various organs and tumor. Our results suggest that the design of the BFA is critical and the binding constants of the antigen and lymphocyte binding epitopes need to be optimized for successful therapy.

  1. Automated brain tumor segmentation in magnetic resonance imaging based on sliding-window technique and symmetry analysis.

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    Lian, Yanyun; Song, Zhijian

    2014-01-01

    Brain tumor segmentation from magnetic resonance imaging (MRI) is an important step toward surgical planning, treatment planning, monitoring of therapy. However, manual tumor segmentation commonly used in clinic is time-consuming and challenging, and none of the existed automated methods are highly robust, reliable and efficient in clinic application. An accurate and automated tumor segmentation method has been developed for brain tumor segmentation that will provide reproducible and objective results close to manual segmentation results. Based on the symmetry of human brain, we employed sliding-window technique and correlation coefficient to locate the tumor position. At first, the image to be segmented was normalized, rotated, denoised, and bisected. Subsequently, through vertical and horizontal sliding-windows technique in turn, that is, two windows in the left and the right part of brain image moving simultaneously pixel by pixel in two parts of brain image, along with calculating of correlation coefficient of two windows, two windows with minimal correlation coefficient were obtained, and the window with bigger average gray value is the location of tumor and the pixel with biggest gray value is the locating point of tumor. At last, the segmentation threshold was decided by the average gray value of the pixels in the square with center at the locating point and 10 pixels of side length, and threshold segmentation and morphological operations were used to acquire the final tumor region. The method was evaluated on 3D FSPGR brain MR images of 10 patients. As a result, the average ratio of correct location was 93.4% for 575 slices containing tumor, the average Dice similarity coefficient was 0.77 for one scan, and the average time spent on one scan was 40 seconds. An fully automated, simple and efficient segmentation method for brain tumor is proposed and promising for future clinic use. Correlation coefficient is a new and effective feature for tumor location.

  2. Novel PDD-PDT system based on spectrophotometric real-time fluorescence monitoring and MALDI-TOF-MS analysis of tumors

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    Yoshida, Takato O.; Kohno, Eiji; Dodeller, Marc; Sakurai, Takashi; Yamamoto, Seiji; Terakawa, Susumu

    2009-06-01

    In the PDT practice for tumor patients, the dose and irradiation time for the treatment are chosen by experience and not by real need. To establish advanced PDD-PDT model system for patients, we developed a method for monitoring the cell-death based on a spectrophotometric real-time change in fluorescence in HeLa-tumors during Photofrin®-PDT and ALA-PDT. Here, we describe the results of application of the new PDD-PDT system to human tumors. The fluorescence spectra obtained from human tumors were analyzed by the differential spectral analysis. The mass-spectral changes of tumor tissues during PDD-PDT were also examined by MALDI-TOF-MS/MS. The first author's seborrheic keratosis was monitored with this system during the PDD-PDT with a topically applied ALA-ointment. The changes in fluorescence spectrum were successfully detected, and the tumor regressed completely within 5 months. The differential spectral analysis of PDD-PDT-fluorescence monitoring spectra of tumors and isolated mitochondria showed a marked decrease of three peaks in the red region indicative of the PDD (600 - 720 nm), and a transient rise followed by a decline of peaks in the green region indicative of the PDT (450 - 580 nm). The MALDI-TOF-MS analysis of PDD-PDT HeLa-tumors showed a consumption of Photofrin-deuteroporphyrin and ALA-PpIX, and decreases in protein mass in the range of 4,000 - 16,000 Da, m/z 4929, 8564, 10089, 15000, and an increase in m/z 7002 in a Photofrin® PDD-PDT monitoring tumor.

  3. Automatic selection of localized region-based active contour models using image content analysis applied to brain tumor segmentation.

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    Ilunga-Mbuyamba, Elisee; Avina-Cervantes, Juan Gabriel; Cepeda-Negrete, Jonathan; Ibarra-Manzano, Mario Alberto; Chalopin, Claire

    2017-12-01

    Brain tumor segmentation is a routine process in a clinical setting and provides useful information for diagnosis and treatment planning. Manual segmentation, performed by physicians or radiologists, is a time-consuming task due to the large quantity of medical data generated presently. Hence, automatic segmentation methods are needed, and several approaches have been introduced in recent years including the Localized Region-based Active Contour Model (LRACM). There are many popular LRACM, but each of them presents strong and weak points. In this paper, the automatic selection of LRACM based on image content and its application on brain tumor segmentation is presented. Thereby, a framework to select one of three LRACM, i.e., Local Gaussian Distribution Fitting (LGDF), localized Chan-Vese (C-V) and Localized Active Contour Model with Background Intensity Compensation (LACM-BIC), is proposed. Twelve visual features are extracted to properly select the method that may process a given input image. The system is based on a supervised approach. Applied specifically to Magnetic Resonance Imaging (MRI) images, the experiments showed that the proposed system is able to correctly select the suitable LRACM to handle a specific image. Consequently, the selection framework achieves better accuracy performance than the three LRACM separately. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. The clinical characteristics and prognostic analysis of Chinese advanced NSCLC patients based on circulating tumor DNA sequencing

    Directory of Open Access Journals (Sweden)

    Rao C

    2018-01-01

    Full Text Available Chuangzhou Rao,1 Liangqin Nie,1 Xiaobo Miao,1 Yunbao Xu,1 Bing Li,2 Tengfei Zhang2 1Radiotherapy & Chemotherapy Dept 2, Ningbo No. 2 Hospital, Zhejiang, 2Burning Rock Biotech, Guangzhou, People’s Republic of China Purpose: Circulating tumor DNA (ctDNA is a noninvasive and real-time marker for tumor diagnosis, prognosis, and prediction. However, further investigations about ctDNA prognostic and predictive value are still needed, and conclusions from several studies were inconsistent.Experimental design: We performed capture-based targeted ultradeep sequencing on liquid biopsies from a cohort of 34 advanced Chinese non-small-cell lung cancer (NSCLC patients and analyzed the clinical use of ctDNA in this study.Results: On the basis of clinical characteristics of the 34 NSCLC patients, we found that brain metastasis correlated with shorter progression-free survival (PFS and is more prone to happen in younger patients. After ctDNA sequencing, we analyzed the prognostic value of baseline ctDNA. In osimertinib-treated group, high max allelic fraction (maxAF correlated with shorter PFS. But for the cohort of 34 patients, no correlation can be observed between maxAF and PFS. We also presented two cases to demonstrate the value of disease progression prediction by ctDNA, which can be detected earlier than clinical response.Conclusion: In this study, we demonstrated that ctDNA is a prognostic marker for evaluating treatment response and predicting recurrence in advanced NSCLC. Further investigations with larger cohort and uniformed patient background are still needed to validate our findings. Keywords: circulating tumor DNA, non-small-cell lung cancer, prognosis 

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

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    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.

  6. Differentiating malignant from benign breast tumors on acoustic radiation force impulse imaging using fuzzy-based neural networks with principle component analysis

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    Liu, Hsiao-Chuan; Chou, Yi-Hong; Tiu, Chui-Mei; Hsieh, Chi-Wen; Liu, Brent; Shung, K. Kirk

    2017-03-01

    Many modalities have been developed as screening tools for breast cancer. A new screening method called acoustic radiation force impulse (ARFI) imaging was created for distinguishing breast lesions based on localized tissue displacement. This displacement was quantitated by virtual touch tissue imaging (VTI). However, VTIs sometimes express reverse results to intensity information in clinical observation. In the study, a fuzzy-based neural network with principle component analysis (PCA) was proposed to differentiate texture patterns of malignant breast from benign tumors. Eighty VTIs were randomly retrospected. Thirty four patients were determined as BI-RADS category 2 or 3, and the rest of them were determined as BI-RADS category 4 or 5 by two leading radiologists. Morphological method and Boolean algebra were performed as the image preprocessing to acquire region of interests (ROIs) on VTIs. Twenty four quantitative parameters deriving from first-order statistics (FOS), fractal dimension and gray level co-occurrence matrix (GLCM) were utilized to analyze the texture pattern of breast tumors on VTIs. PCA was employed to reduce the dimension of features. Fuzzy-based neural network as a classifier to differentiate malignant from benign breast tumors. Independent samples test was used to examine the significance of the difference between benign and malignant breast tumors. The area Az under the receiver operator characteristic (ROC) curve, sensitivity, specificity and accuracy were calculated to evaluate the performance of the system. Most all of texture parameters present significant difference between malignant and benign tumors with p-value of less than 0.05 except the average of fractal dimension. For all features classified by fuzzy-based neural network, the sensitivity, specificity, accuracy and Az were 95.7%, 97.1%, 95% and 0.964, respectively. However, the sensitivity, specificity, accuracy and Az can be increased to 100%, 97.1%, 98.8% and 0.985, respectively

  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. 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 (pautopsy 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.

  9. 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.

  10. 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.

  11. Evaluating the Prognostic Value of microRNA-203 in Solid Tumors Based on a Meta-Analysis and the Cancer Genome Atlas (TCGA Datasets

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    Yingjie Shao

    2017-03-01

    Full Text Available Background: It has been reported that miR-203 expression was aberrant in various types of cancers, and it could be used as a prognostic biomarker. Therefore, in this study, we aimed to evaluate the prognostic value of miR-203 expression in solid tumors by using meta-analysis and The Cancer Genome Atlas (TCGA datasets. Methods: By doing a literature research in PubMed, Embase and the Cochrane Library (last update by December 2016, we were able to identify the studies assessing the prognostic role of miR-203 in various tumors. We then used TCGA datasets to validate the results of meta-analysis. Results:33 studies from 26 articles were qualified and enrolled in this meta-analysis. Pooled analyses showed that higher expression of miR-203 in tissues couldn’t predict poor overall survival (OS and progression-free survival (PFS in solid tumors. However, the results of subgroup analyses revealed that the upregulation of tissue miR-203 expression was associated with poor OS in colorectal cancer (hazard ratio (HR=1.81, 95% confidence intervals (CI 1.31-2.49; P<0.001, pancreatic cancer (HR=1.19, 95% CI 1.09-1.31; P<0.001 and ovarian cancer (HR=1.85, 95% CI 1.45-2.37; P<0.001; but it had opposite association in liver cancer (HR=0.52, 95% CI 0.28-0.97; P=0.040 and esophageal cancer (HR=0.41, 95% CI 0.25-0.66; P<0.001. Based on TCGA datasets, we found the same results for pancreatic cancer and esophageal cancer, but not for colorectal cancer and liver cancer. Moreover, patients with high circulating miR-203 in blood had significantly poor OS and PFS in colorectal cancer and breast cancer. Conclusion: Our study showed that the prognostic values of tissue miR-203 varied in different tumor types. In addition, the upregulation of circulating miR-203 in blood was associated with poor prognosis in colorectal cancer and breast cancer.

  12. Dendritic cell based tumor vaccination in prostate and renal cell cancer: a systematic review and meta-analysis.

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    Andreas Draube

    Full Text Available BACKGROUND: More than 200 clinical trials have been performed using dendritic cells (DC as cellular adjuvants in cancer. Yet the key question whether there is a link between immune and clinical response remains unanswered. Prostate and renal cell cancer (RCC have been extensively studied for DC-based immunotherapeutic interventions and were therefore chosen to address the above question by means of a systematic review and meta-analysis. METHODOLOGY/PRINCIPAL FINDINGS: Data was obtained after a systematic literature search from clinical trials that enrolled at least 6 patients. Individual patient data meta-analysis was performed by means of conditional logistic regression grouped by study. Twenty nine trials involving a total of 906 patients were identified in prostate cancer (17 and RCC (12. Objective response rates were 7.7% in prostate cancer and 12.7% in RCC. The combined percentages of objective responses and stable diseases (SD amounted to a clinical benefit rate (CBR of 54% in prostate cancer and 48% in RCC. Meta-analysis of individual patient data (n = 403 revealed the cellular immune response to have a significant influence on CBR, both in prostate cancer (OR 10.6, 95% CI 2.5-44.1 and in RCC (OR 8.4, 95% CI 1.3-53.0. Furthermore, DC dose was found to have a significant influence on CBR in both entities. Finally, for the larger cohort of prostate cancer patients, an influence of DC maturity and DC subtype (density enriched versus monocyte derived DC as well as access to draining lymph nodes on clinical outcome could be demonstrated. CONCLUSIONS/SIGNIFICANCE: As a 'proof of principle' a statistically significant effect of DC-mediated cellular immune response and of DC dose on CBR could be demonstrated. Further findings concerning vaccine composition, quality control, and the effect of DC maturation status are relevant for the immunological development of DC-based vaccines.

  13. The skull base: tumoral lesions

    International Nuclear Information System (INIS)

    Casselman, Jan W.

    2005-01-01

    Many lesions occur in the anterior, central and posterior skull base. In order to detect and characterise them, one has to apply the best imaging technique. Today MR is the preferred technique, and the use of CT is more and more restricted to evaluate the presence of calcifications and involvement of thin bony walls, foramina and fissures. However, MR is only superior when the right sequences and imaging planes are used. Many lesions can be characterised by their specific signal intensity on different sequences and by their location. Nevertheless some lesions can only be characterised after biopsy. The purpose of imaging in skull base tumours remains in the first place the evaluation of the exact tumour extent, and this is again best achieved with MR. In this paper the imaging technique and the most frequent skull base tumours are discussed. (orig.)

  14. Automatic small bowel tumor diagnosis by using multi-scale wavelet-based analysis in wireless capsule endoscopy images.

    Science.gov (United States)

    Barbosa, Daniel C; Roupar, Dalila B; Ramos, Jaime C; Tavares, Adriano C; Lima, Carlos S

    2012-01-11

    Wireless capsule endoscopy has been introduced as an innovative, non-invasive diagnostic technique for evaluation of the gastrointestinal tract, reaching places where conventional endoscopy is unable to. However, the output of this technique is an 8 hours video, whose analysis by the expert physician is very time consuming. Thus, a computer assisted diagnosis tool to help the physicians to evaluate CE exams faster and more accurately is an important technical challenge and an excellent economical opportunity. The set of features proposed in this paper to code textural information is based on statistical modeling of second order textural measures extracted from co-occurrence matrices. To cope with both joint and marginal non-Gaussianity of second order textural measures, higher order moments are used. These statistical moments are taken from the two-dimensional color-scale feature space, where two different scales are considered. Second and higher order moments of textural measures are computed from the co-occurrence matrices computed from images synthesized by the inverse wavelet transform of the wavelet transform containing only the selected scales for the three color channels. The dimensionality of the data is reduced by using Principal Component Analysis. The proposed textural features are then used as the input of a classifier based on artificial neural networks. Classification performances of 93.1% specificity and 93.9% sensitivity are achieved on real data. These promising results open the path towards a deeper study regarding the applicability of this algorithm in computer aided diagnosis systems to assist physicians in their clinical practice.

  15. Automatic small bowel tumor diagnosis by using multi-scale wavelet-based analysis in wireless capsule endoscopy images

    Directory of Open Access Journals (Sweden)

    Barbosa Daniel C

    2012-01-01

    Full Text Available Abstract Background Wireless capsule endoscopy has been introduced as an innovative, non-invasive diagnostic technique for evaluation of the gastrointestinal tract, reaching places where conventional endoscopy is unable to. However, the output of this technique is an 8 hours video, whose analysis by the expert physician is very time consuming. Thus, a computer assisted diagnosis tool to help the physicians to evaluate CE exams faster and more accurately is an important technical challenge and an excellent economical opportunity. Method The set of features proposed in this paper to code textural information is based on statistical modeling of second order textural measures extracted from co-occurrence matrices. To cope with both joint and marginal non-Gaussianity of second order textural measures, higher order moments are used. These statistical moments are taken from the two-dimensional color-scale feature space, where two different scales are considered. Second and higher order moments of textural measures are computed from the co-occurrence matrices computed from images synthesized by the inverse wavelet transform of the wavelet transform containing only the selected scales for the three color channels. The dimensionality of the data is reduced by using Principal Component Analysis. Results The proposed textural features are then used as the input of a classifier based on artificial neural networks. Classification performances of 93.1% specificity and 93.9% sensitivity are achieved on real data. These promising results open the path towards a deeper study regarding the applicability of this algorithm in computer aided diagnosis systems to assist physicians in their clinical practice.

  16. [Phyllodes tumor of the breast: clinicopathologic analysis of 22 cases].

    Science.gov (United States)

    Velázquez-Dohorn, Magalie; Gamboa-Domínguez, Armando; Medina-Franco, Heriberto

    2013-01-01

    Phyllodes tumors of the breast are uncommon fibroepithelial neoplasms that have potential for recurrence. They are classified as benign, borderline, and malignant, based on a constellation of histologic characteristics that includes the degree of stromal hypercellularity, cytologic atypia and mitotic activity. To analyze the clinical and pathological features of 22 women treated at a referral center in Mexico City. We performed a retrospective analysis of women with phyllodes tumors of the breast treated at our institution between 1998 and 2011. Age, tumor size, surgical method, stromal cellular atypia, mitotic activity, stromal overgrowth, histological classification and surgical margin status were analyzed to determine their possible association with tumor recurrence. Mean patient age at presentation was 42 years. Ten of them (43.5%) had late menarche. Six patients (27.27%) used hormones. Twenty patients (91%) had tumor detected by self-examination. Mean size of the lesion was 7.4 cm. Most lesions were located in the upper outer quadrant (77.3%) and in the left breast (59.1%). Fourteen patients (63.6%) were treated with conservative surgery. Three patients (13.6%) presented local recurrence, two as benign tumors and one patient with two recurrences, first as benign tumor thereafter as malignant phyllodes tumor at 72 and 108 months respectively. . In our study, surgical positive margin status is the main prognostic factor for recurrence.

  17. First epidemiological analysis of breast cancer incidence and tumor characteristics after implementation of population-based digital mammography screening

    International Nuclear Information System (INIS)

    Weigel, Stefanie; Heindel, Walter; Batzler, W.U.; Decker, T.; Hense, H.W.

    2009-01-01

    Purpose: to epidemiologically evaluate the impact of digital mammography screening on incidence rates and tumor characteristics for breast cancer. Materials and methods: the first German digital screening units in the clinical routine were evaluated during the implementation period by using data from the cancer registry to compare the incidence rate of breast cancers and prognostic characteristics. 74% of women aged 50-69 within the region of Muenster/Coesfeld/Warendorf were invited between 10/2005 and 12/2007 for initial screening; 55% participated (n = 35961). Results: in 2002-2004 the average breast cancer incidence rate (per 100000) was 297.9. During the implementation of screening, the rate rose to 532.9 in 2007. Of the 349 cancers detected with screening, 76% (265/349) were invasive compared to 90% (546/608) of cases not detected with screening during the same period. 37% (97/265) of cancers detected in the screening program had a diameter of ≤ 10 mm and 75% (198/265) were node-negative compared to 15% (79/546) and 64% (322/503), respectively, in cancers detected outside the screening program. The distribution of invasive tumor size (pT categories) and the nodal status differed with statistical significance between cancers detected in and outside the program (p = 0.005 and p = 0.004, respectively). (orig.)

  18. 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.

  19. Preoperative predictive factors for gastrointestinal stromal tumors: analysis of 375 surgically resected gastric subepithelial tumors.

    Science.gov (United States)

    Min, Yang Won; Park, Ha Na; Min, Byung-Hoon; Choi, Dongil; Kim, Kyoung-Mee; Kim, Sung

    2015-04-01

    Gastrointestinal stromal tumors (GISTs) and non-GIST subepithelial tumors (SETs) account for about 75 and 25% of gastric hypoechoic SETs ≥2 cm, respectively. Therefore, identifying preoperative predictive factors for GISTs are required to refine surgical indications. We performed a retrospective review of 375 surgically resected gastric hypoechoic SETs ≥2 cm. Demographic data and tumor characteristics based on upper endoscopy and CT findings were compared between GIST and non-GIST SETs originating from muscularis propria layer (leiomyomas, Schwannomas, glomus tumors, and ectopic pancreas). In cardia, leiomyomas were found twice more frequently than GISTs (63.6 versus 31.8%). Perilesional lymph node enlargement (PLNE) was found only in patients with GIST or Schwannomas. Patients with GIST showed a significantly lower rate of PLNE than those with Schwannomas (3.5 versus 29.0%). In multivariate analysis, tumor site outside cardia (odds ratio, 9.157), absence of PLNE (odds ratio, 11.519), old age, large tumor size, exophytic growth pattern, and ulceration or dimpling were identified as independent preoperative predictive factors for GISTs versus non-GIST SETs. The effort for preoperative pathologic diagnosis such as endosonography-guided tissue sampling might be positively considered for SETs at cardia and SETs with PLNE where the possibility of GIST is low.

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

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    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.

  1. 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.

  2. Quantitative MR Image Analysis for Brian Tumor.

    Science.gov (United States)

    Shboul, Zeina A; Reza, Sayed M S; Iftekharuddin, Khan M

    2018-01-01

    This paper presents an integrated quantitative MR image analysis framework to include all necessary steps such as MRI inhomogeneity correction, feature extraction, multiclass feature selection and multimodality abnormal brain tissue segmentation respectively. We first obtain mathematical algorithm to compute a novel Generalized multifractional Brownian motion (GmBm) texture feature. We then demonstrate efficacy of multiple multiresolution texture features including regular fractal dimension (FD) texture, and stochastic texture such as multifractional Brownian motion (mBm) and GmBm features for robust tumor and other abnormal tissue segmentation in brain MRI. We evaluate these texture and associated intensity features to effectively delineate multiple abnormal tissues within and around the tumor core, and stroke lesions using large scale public and private datasets.

  3. Fractionated stereotactic radiotherapy for skull base tumors: analysis of treatment accuracy using a stereotactic mask fixation system

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    Montagnoli Roberto

    2010-01-01

    Full Text Available Abstract Background To assess the accuracy of fractionated stereotactic radiotherapy (FSRT using a stereotactic mask fixation system. Patients and Methods Sixteen patients treated with FSRT were involved in the study. A commercial stereotactic mask fixation system (BrainLAB AG was used for patient immobilization. Serial CT scans obtained before and during FSRT were used to assess the accuracy of patient immobilization by comparing the isocenter position. Daily portal imaging were acquired to establish day to day patient position variation. Displacement errors along the different directions were calculated as combination of systematic and random errors. Results The mean isocenter displacements based on localization and verification CT imaging were 0.1 mm (SD 0.3 mm in the lateral direction, 0.1 mm (SD 0.4 mm in the anteroposterior, and 0.3 mm (SD 0.4 mm in craniocaudal direction. The mean 3D displacement was 0.5 mm (SD 0.4 mm, being maximum 1.4 mm. No significant differences were found during the treatment (P = 0.4. The overall isocenter displacement as calculated by 456 anterior and lateral portal images were 0.3 mm (SD 0.9 mm in the mediolateral direction, -0.2 mm (SD 1 mm in the anteroposterior direction, and 0.2 mm (SD 1.1 mm in the craniocaudal direction. The largest displacement of 2.7 mm was seen in the cranio-caudal direction, with 95% of displacements Conclusions The results indicate that the setup error of the presented mask system evaluated by CT verification scans and portal imaging are minimal. Reproducibility of the isocenter position is in the best range of positioning reproducibility reported for other stereotactic systems.

  4. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  6. 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

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

    Science.gov (United States)

    2012-01-01

    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 (PLC)γ 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/invasion compared with

  8. Tumorer

    DEFF Research Database (Denmark)

    Prause, J.U.; Heegaard, S.

    2005-01-01

    oftalmologi, øjenlågstumorer, conjunctivale tumorer, malignt melanom, retinoblastom, orbitale tumorer......oftalmologi, øjenlågstumorer, conjunctivale tumorer, malignt melanom, retinoblastom, orbitale tumorer...

  9. Epidemiology of malignant cutaneous granular cell tumors: A US population-based cohort analysis using the Surveillance, Epidemiology, and End Results (SEER) database.

    Science.gov (United States)

    Mirza, Fatima N; Tuggle, Charles T; Zogg, Cheryl K; Mirza, Humza N; Narayan, Deepak

    2018-03-01

    Malignant cutaneous granular cell tumors (mcGCTs) are rare and associated with substantial morbidity and mortality. The literature includes single-institution studies. To examine the incidence, secondary malignancies, treatment, overall survival, and disease-specific survival (DSS) of patients with mcGCT. A population-based cohort analysis was conducted in the Surveillance, Epidemiology, and End Results database from 1973 to 2013 for patients with a diagnosis of mcGCT. Risk-adjusted associations between overall survival/DSS and patient characteristics and treatment modalities were assessed by Cox proportional hazard regression. Quantile regression was used to determine median survival times. The 5-year DSS rate was 62.8%. Patients demonstrated an increased risk for renal and pancreatic cancers. In risk-adjusted models, male sex (hazard ratio [HR], 0.21; 95% confidence interval [CI], 0.06-0.82; P = .02), advanced cancer stage (HR, 2.29; 95% CI, 1.40-3.72; P < .01), and surgical resection (HR, 0.06; 95% CI, 0.01-0.59; P = .02) predicted DSS. Median survival time in years increased for males (1.39), earlier stage (0.60), and surgical intervention (5.34). Absent or incorrect reporting in retrospective Surveillance, Epidemiology, and End Results data is possible. The database is more likely to include academic centers. Some subanalyses may be underpowered because of the limited sample size for a rare cancer. Our study presents an in-depth assessment of factors that identify high-risk patients. Residency in a nonmetro area, black race, female sex, and no surgical resection were each associated with poorer DSS. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  10. Quantitation and gompertzian analysis of tumor growth

    DEFF Research Database (Denmark)

    Rygaard, K; Spang-Thomsen, M

    1998-01-01

    to transform the experimental data into useful growth curves. A transformed Gompertz function is used as the basis for calculating relevant parameters pertaining to tumor growth and response to therapy. The calculations are facilitated by use of a computer program which performs the necessary calculations......Human tumor xenografts in immune-deficient animals are used to establish tumor growth curves and for studying the effect of experimental therapy on tumor growth. In this review we describe a method for making serial measurements of tumor size in the nude mouse model as well as methods used...

  11. Quantitation and gompertzian analysis of tumor growth

    DEFF Research Database (Denmark)

    Rygaard, K; Spang-Thomsen, M

    1998-01-01

    Human tumor xenografts in immune-deficient animals are used to establish tumor growth curves and for studying the effect of experimental therapy on tumor growth. In this review we describe a method for making serial measurements of tumor size in the nude mouse model as well as methods used...... to transform the experimental data into useful growth curves. A transformed Gompertz function is used as the basis for calculating relevant parameters pertaining to tumor growth and response to therapy. The calculations are facilitated by use of a computer program which performs the necessary calculations...

  12. 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

    Science.gov (United States)

    2014-01-01

    Background 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. Methods 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. Results 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). Conclusions The analytical performance of NanoString’s Prosigna assay has been validated using FFPE breast tumor specimens across multiple clinical testing laboratories. PMID:24625003

  13. 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

  14. 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

  15. Dynamical analysis of fractional order model of immunogenic tumors

    Directory of Open Access Journals (Sweden)

    Sadia Arshad

    2016-07-01

    Full Text Available In this article, we examine the fractional order model of the cytotoxic T lymphocyte response to a growing tumor cell population. We investigate the long-term behavior of tumor growth and explore the conditions of tumor elimination analytically. We establish the conditions for the tumor-free equilibrium and tumor-infection equilibrium to be asymptotically stable and provide the expression of the basic reproduction number. Existence of physical significant tumor-infection equilibrium points is investigated analytically. We show that tumor growth rate, source rate of immune cells, and death rate of immune cells play vital role in tumor dynamics and system undergoes saddle-node and transcritical bifurcation based on these parameters. Furthermore, the effect of cancer treatment is discussed by varying the values of relevant parameters. Numerical simulations are presented to illustrate the analytical results.

  16. 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

  17. Clinical and radiological profile of ameloblastic fibro-odontoma: an update on an uncommon odontogenic tumor based on a critical analysis of 114 cases.

    Science.gov (United States)

    Buchner, Amos; Kaffe, Israel; Vered, Marilena

    2013-03-01

    Ameloblastic fibro-odontoma is an uncommon benign tumor of the jaws that belongs to the group of mixed odontogenic tumors. The descriptions of its clinical and radiological features in the literature are not always accurate and sometimes even contradictory. The aim of the present study was to critically evaluate their clinical and radiological features as reported in the English-language literature. A total of 114 well-documented cases of ameloblastic fibro-odontomas (103 from publications and 11 of our own new cases) were analyzed. The patients' age ranged from 8 months to 26 years (mean 9.6). There were 74 (65 %) males, with a male-to-female ratio of 1.85:1 (P = 0.001). The mandible was involved in 74 (65 %) cases, and the mandible-to-maxilla ratio was 1.85:1 (P odontomas are significantly more common in males and in the mandible, and that multilocular lesions are uncommon. It also revealed that, based on their clinical and radiological features, some of them are probably true neoplasms while others appear to be developing odontomas (hamartomas).

  18. Nuclear morphometric analysis in gastrointestinal stromal tumors: a preliminary study.

    Science.gov (United States)

    Ozdamar, Sükrü Oğuz; Bektaş, Sibel; Erdem Ozdamar, Sevim; Gedikoğlu, Gökhan; Doğan Gün, Banu; Bahadir, Burak

    2007-06-01

    Gastrointestinal stromal tumors are considered a specialized group of mesenchymal neoplasms. In this study, the histomorphologic and immunohistochemical features of gastrointestinal stromal tumors are compared with nuclear morphometric results. Morphometric nuclear parameters such as mean area, mean roundness factor, mean form ellipse, mean length and mean perimeter were evaluated in hematoxylin and eosin stained slides of 22 gastrointestinal stromal tumors (9 benign and 13 malignant) by using a computer-assisted image analysis system. Morphometric results were compared with tumor behavior and tumor size, the presence of necrosis, mitotic index, and immunohistochemical expressions of p53 and proliferating cell nuclear antigen. We found that tumor necrosis was correlated with mean nuclear roundness factor, mean nuclear form ellipse, mean nuclear length and mean nuclear perimeter (pmorphometric features and gastrointestinal stromal tumor behavior, tumor size, or index of proliferating cell nuclear antigen and p53 expressions (p>0.05). In this preliminary study, the relative concordance of the morphometric results and general histomorphologic data exhibited the importance of nuclear morphometric analysis in gastrointestinal stromal tumors. Studies including larger series of cases investigating detailed nuclear morphometric analysis of gastrointestinal stromal tumors are needed.

  19. 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

  20. Odontogenic tumors: analysis of 706 cases.

    Science.gov (United States)

    Regezi, J A; Kerr, D A; Courtney, R M

    1978-10-01

    From a total of 54,534 oral biopsy specimens, 706 (1.3%) odontogenic tumors were retrieved and reviewed. Odontomas comprised more than 65% of the odontogenic tumors, ameloblastomas about 10%, and the remaining six categories of odontogenic tumors accounted for approximately 25% of the lesions. The distribution by age, sex, and location of these tumors generally supported the data from other previously reported cases. A possible variant of the calcifying epithelial odontogenic tumor was described, and instances of two granular cell ameloblastic fibromas were reported. The myxomas as a group were characterized histologically more by residual bony trabeculae than by the presence of odontogenic rests. Because the clinical, histological, and behavioral features of the ameloblastic fibroma and ameloblastic fibro-odontoma were similar, these lesions were considered to be essentially the same. From limited follow-up information, the ameloblastoma was the only lesion that recurred. With the exception of one ameloblastoma found in the lung, no malignant odontogenic tumors were encountered.

  1. 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 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.

  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. A 3D graphene oxide microchip and a Au-enwrapped silica nanocomposite-based supersandwich cytosensor toward capture and analysis of circulating tumor cells

    Science.gov (United States)

    Li, Na; Xiao, Tingyu; Zhang, Zhengtao; He, Rongxiang; Wen, Dan; Cao, Yiping; Zhang, Weiying; Chen, Yong

    2015-10-01

    Determination of the presence and number of circulating tumor cells (CTCs) in peripheral blood can provide clinically important data for prognosis and therapeutic response patterns. In this study, a versatile supersandwich cytosensor was successfully developed for the highly sensitive and selective analysis of CTCs using Au-enwrapped silica nanocomposites (Si/AuNPs) and three-dimensional (3D) microchips. First, 3D microchips were fabricated by a photolithography method. Then, the prepared substrate was applied to bind graphene oxide, streptavidin and biotinylated epithelial-cell adhesion-molecule antibody, resulting in high stability, bioactivity, and capability for CTCs capture. Furthermore, horseradish peroxidase and anti-CA153 were co-linked to the Si/AuNPs for signal amplification. The performance of the cytosensor was evaluated with MCF7 breast cancer cells. Under optimal conditions, the proposed supersandwich cytosensor showed high sensitivity with a wide range of 101 to 107 cells per mL and a detection limit of 10 cells per mL. More importantly, it could effectively distinguish CTCs from normal cells, which indicated the promising applications of our method for the clinical diagnosis and therapeutic monitoring of cancers.

  4. Social Behavior in Medulloblastoma: Functional Analysis of Tumor-Supporting

    Science.gov (United States)

    2013-07-01

    used MADM to probe into early phases of gliomagenesis, and surprisingly found the lack of overpopulation of mutant NSCs. Among NSC-derived cell types...focus is on brain tumors. Several Berlin-based research groups have specialized on investigating the impact of parenchymal interactions of brain tumor

  5. Tumor-size-based morphological features of metastatic lymph node tumors from primary lung adenocarcinoma.

    Science.gov (United States)

    Yamada, Eiji; Ishii, Genichiro; Aramaki, Nao; Aokage, Keiju; Hishida, Tomoyuki; Yoshida, Junji; Kojima, Motohiro; Nagai, Kanji; Ochiai, Atsushi

    2014-12-01

    Most primary lung adenocarcinomas show histological diversity, however, histological diversity in the metastatic lymph node tumors (LNT) is not well defined. The aim of this study was to explore the histological characteristics of the metastatic LNT based on their sizes. We analyzed 163 primary tumors and 509 metastatic LNTs. When the primary tumor showed papillary-predominant subtype, the most frequent histological subtype in the metastatic LNT that were ≤2 mm in diameter was solid subtype (49%), followed by papillary subtype (35%); on the other hand, in the metastatic LNT measuring >2 mm in size, the frequency of tumors showing papillary-predominant subtype increased significantly to 52% (P = 0.04). When the primary tumor showed acinar-predominant subtype, the most predominant subtype in the ≤2 mm metastatic LN tumors was acinar subtype (55%), followed by solid subtype (40%), with the frequency of acinar subtype increasing significantly to 76% in the metastatic LNT that were >2 mm in diameter (P = 0.04). These results indicate that solid subtype is the characteristic histological subtype in the early phase of the LN metastatic process, and that as the metastatic LNT grow larger, they develop morphological features resembling those in the primary tumor. © 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.

  6. [Clinical analysis of prosthesis replacement for proximal humerus tumors].

    Science.gov (United States)

    Weng, Xiaojun; Liao, Qiande; Li, Xiaosheng; Wang, Jing

    2016-01-01

    To explore surgical strategies, functions and prognosis of artificial prosthesis replacement and soft tissue reconstruction for patients with invasive benign or primary malignant proximal humerus tumor.
 A total of 17 patients with invasive benign or primary malignant proximal humerus tumor underwent prosthetic replacement after segment bone tumor resection and soft tissues reconstruction from April 2007 to April 2014 were enrolled. Based on histological types, tumor stages and surgical procedures, the effects of artificial prosthesis replacement and soft tissue reconstruction on prognosis and shoulder joint function were evaluated.
 All patients were followed up for 8 to 96 months (average time: 58.9 months). Among 11 patients with primary malignant tumor, 5 died of tumor recurrence or metastasis, and 6 showed tumor-free survival for 24 to 91 months (average time: 54.83 months). The 6 patients with aggressive benign tumors survived for 39 to 96 months, with an average of 72.33 months. The shoulder joint function of 17 patients recovered to 64.88% of normal. There were significant differences in the shoulder joint function between the patients who underwent half shoulder replacement and those who underwent total shoulder replacement (56.25% vs 72.56%, Pshoulder joint function between the patients who underwent Type I A excision (retention of abductor muscles and rotator cuff) and those who underwent Type I B excision (68.75% vs 61.44%, Pshoulder joint function is associated with the methods of prosthesis replacement and soft tissue resection.

  7. 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.)

  8. 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.

  9. 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...... with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-aza-CdR) to determine whether this treatment could improve the profile of tumor antigen genes expressed in these cells. In addition, the presence of MAGE-A tumor antigen protein was evaluated in the purified tumor cell lysate used...

  10. Correlation of CCNA1 Promoter Methylation with Malignant Tumors: A Meta-Analysis Introduction

    OpenAIRE

    Yang, Bin; Miao, Shuai; Zhang, Le-Ning; Sun, Hong-Bin; Xu, Zhe-Nan; Han, Chun-Shan

    2015-01-01

    Epigenetic silencing of tumor suppressor genes by promoter methylation plays vital roles in the process of carcinogenesis. The purpose of this meta-analysis was to determine whether the aberrant methylation of cyclin A1 (CCNA1) may be of great significance to human malignant tumors. By searching both English and Chinese language-based electronic databases carefully, we tabulated and analyzed parameters from each study. All human-associated case-control studies were included providing availabl...

  11. 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.

  12. 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.

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

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    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.

  14. 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.

  15. 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.

  16. Comprehensive Quantitative Analysis of Ovarian and Breast Cancer Tumor Peptidomes

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Zhe; Wu, Chaochao; Xie, Fang; Slysz, Gordon W.; Tolic, Nikola; Monroe, Matthew E.; Petyuk, Vladislav A.; Payne, Samuel H.; Fujimoto, Grant M.; Moore, Ronald J.; Fillmore, Thomas L.; Schepmoes, Athena A.; Levine, Douglas; Townsend, Reid; Davies, Sherri; Li, Shunqiang; Ellis, Matthew; Boja, Emily; Rivers, Robert; Rodriguez, Henry; Rodland, Karin D.; Liu, Tao; Smith, Richard D.

    2015-01-02

    Aberrant degradation of proteins is associated with many pathological states, including cancers. Mass spectrometric analysis of tumor peptidomes, the intracellular and intercellular products of protein degradation, has the potential to provide biological insights on proteolytic processing in cancer. However, attempts to use the information on these smaller protein degradation products from tumors for biomarker discovery and cancer biology studies have been fairly limited to date, largely due to the lack of effective approaches for robust peptidomics identification and quantification, and the prevalence of confounding factors and biases associated with sample handling and processing. Herein, we have developed an effective and robust analytical platform for comprehensive analyses of tissue peptidomes, which is suitable for high throughput quantitative studies. The reproducibility and coverage of the platform, as well as the suitability of clinical ovarian tumor and patient-derived breast tumor xenograft samples with post-excision delay of up to 60 min before freezing for peptidomics analysis, have been demonstrated. Moreover, our data also show that the peptidomics profiles can effectively separate breast cancer subtypes, reflecting tumor-associated protease activities. Peptidomics complements results obtainable from conventional bottom-up proteomics, and provides insights not readily obtainable from such approaches.

  17. 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

    -based standardized scoring system for tumor budding in colorectal cancer. The ITBCC included nine sessions with presentations, a pre-meeting survey and an e-book covering the key publications on tumor budding in colorectal cancer. The Grading of Recommendation Assessment, Development and Evaluation' method was used...... colorectal cancer (23/23, 100%). Tumor budding is an independent predictor of survival in stage II colorectal cancer (23/23, 100%). Tumor budding should be taken into account along with other clinicopathological features in a multidisciplinary setting (23/23, 100%). Tumor budding is counted on H&E (19/22, 86...

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. Predictive analysis of optical ablation in several dermatological tumoral tissues

    Science.gov (United States)

    Fanjul-Vélez, F.; Blanco-Gutiérrez, A.; Salas-García, I.; Ortega-Quijano, N.; Arce-Diego, J. L.

    2013-06-01

    Optical techniques for treatment and characterization of biological tissues are revolutionizing several branches of medical praxis, for example in ophthalmology or dermatology. The non-invasive, non-contact and non-ionizing character of optical radiation makes it specially suitable for these applications. Optical radiation can be employed in medical ablation applications, either for tissue resection or surgery. Optical ablation may provide a controlled and clean cut on a biological tissue. This is particularly relevant in tumoral tissue resection, where a small amount of cancerous cells could make the tumor appear again. A very important aspect of tissue optical ablation is then the estimation of the affected volume. In this work we propose a complete predictive model of tissue ablation that provides an estimation of the resected volume. The model is based on a Monte Carlo approach for the optical propagation of radiation inside the tissue, and a blow-off model for tissue ablation. This model is applied to several types of dermatological tumoral tissues, specifically squamous cells, basocellular and infiltrative carcinomas. The parameters of the optical source are varied and the estimated resected volume is calculated. The results for the different tumor types are presented and compared. This model can be used for surgical planning, in order to assure the complete resection of the tumoral tissue.

  3. RNA quality and gene expression analysis of ovarian tumor tissue undergoing repeated thaw-freezing

    DEFF Research Database (Denmark)

    Jochumsen, Kirsten Marie; Tan, Qihua; Dahlgaard, Jesper

    2007-01-01

    undergoes repeated thawing and freezing. We evaluated the influence of repeated division of tumor samples at room temperature, on RNA quality and quantity, in addition to the gene expression profile. Sixteen ovarian tumor samples were divided in three aliquots each, undergoing respectively one, two...... unsupervised, and supervised multivariate statistical methods, reliability analysis, as well as verification using published gene lists in ovarian cancer studies. RNA quality and quantity did not change during the division procedure and microarray data showed insignificant difference in gene expression. Tumor......Gene expression profiles evaluated by microarray-based quantization of RNA are used in studies of differential diagnosis and prognosis in cancer. RNA of good quality is mandatory for this evaluation. The RNA most often comes from tumor banks with limited amount of tissue, and the tissue often...

  4. 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)

  5. [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.

  6. IDH Mutation Analysis in Ewing Sarcoma Family Tumors.

    Science.gov (United States)

    Na, Ki Yong; Noh, Byeong-Joo; Sung, Ji-Youn; Kim, Youn Wha; Santini Araujo, Eduardo; Park, Yong-Koo

    2015-05-01

    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. This study investigated IDH mutations in 61 Ewing sarcoma family tumors (ESFTs), using a pentose nucleic acid clamping method and direct sequencing. 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. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. Hemangiosarcoma in mice administered pregabalin: analysis of genotoxicity, tumor incidence, and tumor genetics.

    Science.gov (United States)

    Pegg, David; Bleavins, Michael; Herman, James; Wojcinski, Zbigniew; Graziano, Michael; Henck, Judith; Criswell, Kay A; Anderson, Timothy; Duddy, Steven

    2012-07-01

    Pregabalin, (S)-3-(aminomethyl)-5-methylhexanoic acid, binds with high affinity to the α(2)δ subunit of voltage-gated calcium channels and exerts analgesic, anxiolytic, and antiseizure activities. Two-year carcinogenicity studies were completed in B6C3F1 and CD-1 mice and two separate studies in Wistar rats. Doses in mice were 200, 1000, and 5000 mg/kg/day, with systemic exposures (AUC(0-24 h)) up to 31 times the mean exposure in humans, given the maximum recommended clinical dose. In rats, doses were 50, 150, and 450 mg/kg/day in males and 100, 300, and 900 mg/kg/day in females; systemic exposures up to 24 times were achieved in clinical trials. In both strains of mice, pregabalin treatment was associated with an increased incidence of hemangiosarcoma primarily in liver, spleen, and bone marrow. The incidence of hemangiosarcoma was higher in B6C3F1 mice than in CD-1 mice, consistent with its spontaneous incidence. Pregabalin did not increase the incidence of any other tumor type in rats and was not genotoxic, based on an extensive battery of in vivo and in vitro tests in bacterial and mammalian systems. Thus, pregabalin is a single-species, single tumor-type, nongenotoxic mouse carcinogen. Hemangiosarcomas occurring in mice treated with pregabalin were genotypically distinct from hemangiosarcomas induced by genotoxic carcinogens in humans with respect to ras and p53 mutation patterns and were similar to spontaneous tumors. Furthermore, there was a strong association between pregabalin treatment and bone marrow changes in these studies in mice, suggesting a possible link between the effects observed in bone marrow and the increase in tumor incidence in pregabalin-treated mice.

  12. 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

  13. Mobile phone use and risk for intracranial tumors and salivary gland tumors – A meta-analysis

    Directory of Open Access Journals (Sweden)

    Alicja Bortkiewicz

    2017-02-01

    Full Text Available Results of epidemiological studies on the association between use of mobile phone and brain cancer are ambiguous, as well as the results of 5 meta-analysis studies published to date. Since the last meta-analysis (2009, new case-control studies have been published, which theoretically could affect the conclusions on this relationship. Therefore, we decided to perform a new meta-analysis. We conducted a systematic review of multiple electronic data bases for relevant publications. The inclusion criteria were: original papers, case-control studies, published till the end of March 2014, measures of association (point estimates as odds ratio and confidence interval of the effect measured, data on individual exposure. Twenty four studies (26 846 cases, 50 013 controls were included into the meta-analysis. A significantly higher risk of an intracranial tumor (all types was noted for the period of mobile phone use over 10 years (odds ratio (OR = 1.324, 95% confidence interval (CI: 1.028–1.704, and for the ipsilateral location (OR = 1.249, 95% CI: 1.022–1.526. The results support the hypothesis that long-term use of mobile phone increases risk of intracranial tumors, especially in the case of ipsilateral exposure. Further studies are needed to confirm this relationship. Int J Occup Med Environ Health 2017;30(1:27–43

  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. Analysis of Mammalian Septin Expression in Human Malignant Brain Tumors

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    Dong-Seok Kim

    2004-03-01

    Full Text Available Septins are a highly conserved subfamily of GTPases that play an important role in the process of cytokinesis. To increase our understanding of the expression and localization of the different mammalian septins in human brain tumors, we used antibodies against septins 2, 3, 4, 5, 6, 7, 9, and 11 in immunofluorescence and Western blot analyses of astrocytomas and medulloblastomas. We then characterized the expression and subcellular distribution of the SEPT2 protein in aphidicolin-synchronized U373 MG astrocytoma cells by immunofluorescence and fluorescenceactivated cell sorter analysis. To determine the role of SEPT2 in astrocytoma cytokinesis, we inducibly expressed a dominant-negative (DN SEPT2 mutant in U373 MG astrocytoma cells. We show variable levels and expression patterns of the different septins in brain tissue, brain tumor specimens, and human brain tumor cell lines. SEPT2 was abundantly expressed in all brain tumor samples and cell lines studied. SEPT3 was expressed in medulloblastoma specimens and cell lines, but not in astrocytoma specimens or cell lines. SEPT2 expression was cell cycle-related, with maximal levels in G2-M. Immunocytochemical analysis showed endogenous levels of the different septins within the perinuclear and peripheral cytoplasmic regions. In mitosis, SEPT2 was concentrated at the cleavage furrow. By immunocytochemistry and flow cytometry, we show that a DN SEPT2 mutant inhibits the completion of cell division and results in the accumulation of multinucleated cells. These results suggest that septins are variably expressed in human brain tumors. Stable expression of the DN SEPT2 mutant leads to a G2-M cell cycle block in astrocytoma cells.

  16. Brainstem tolerance to conformal radiotherapy of skull base tumors

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    Debus, J.; Hug, E.B.; Liebsch, N.J.; O'Farrel, D.; Finkelstein, D.; Efird, J.; Munzenrider, J.E.

    1997-01-01

    Purpose: The aim of this study was to analyze the long-term incidence of brainstem toxicity in patients treated for skull base tumors with high dose conformal radiotherapy. Methods and Materials: 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. Following 3D treatment planning with delineation of target volumes and critical nontarget structures dose distributions and dose-volume histograms were calculated. Radiotherapy was given an 1.8 Gy or CGE (=Cobalt Gray Equivalent) dose per fraction, 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. Results: Follow-up time ranged from 6 months to 21.4 years (mean = 42.5 months). Brainstem toxicity was observed in 17 of 367 patients attributable to treatment, resulting in death of three patients. Actuarial rates of 5 and 10-year high-grade toxicity-free survival were 94 and 88%, respectively. Increased risk of brainstem toxicity was significantly associated with maximum dose to brainstem, volume of brainstem receiving ≥50 CGE, ≥55 CGE, and ≥60 CGE, number of surgical procedures, and prevalence of diabetes or high blood pressure. Multivariate analysis identified three independent factors as important prognosticators: number of surgical procedures (p < 0.001), volume of the brainstem receiving 60 CGE (p < 0.001), and prevalence of diabetes (p < 0.01). Conclusions: Tolerance of brainstem to fractionated radiotherapy appears to be a steep function of tissue volume included in high dose regions rather than the maximum dose of brainstem alone. In addition, presence of predisposing factors as well as extent of surgical manipulation can significantly lower brainstem tolerance in the individual patient

  17. Molecular genetic analysis of tumor suppressor genes in ovarian cancer

    International Nuclear Information System (INIS)

    Lee, Je Ho; Park, Sang Yun

    1992-04-01

    To examine the loci of putative tumor suppressor genes in ovarian cancers, we performed the molecular genetic analysis with fresh human ovarian cancers and observed the following data. Frequent allelic losses were observed on chromosomes 4p(42%), 6p(50%), 7p(43%), 8q(31%), 12p(38%), 12q(33%), 16p(33%), 16q(37%), and 19p(34%) in addition to the previously reported 6q, 11p, and 17p in ovarian caroinomas. we have used an additional probe, TCP10 to narrow down the deleted region on chromosome 6q. TCP10 was reported to be mapped to 6q 25-27. Allelic loss was found to be 40% in epithelial ovarian caroinomas. This finding suggests that chromosome 6q 24-27 is one of putative region haboring the tumor suppressor gene of epithelial ovarian cancer (particularly serous type). To examine the association between FAL(Fractional Allelic Loss) and histopathological features, the FAL value on each phenotypically different tumor was calculated as the ratio of the number of allelic losses versus the number of cases informative in each chromosomal arm. The average FALs for each phenotypically different tumor were: serous cystoadenocarcinomas. FAL=0.31 : mucinous 0.12 : and clear cell carcinoma. FAL=0.20. (Author)

  18. Comprehensive cost analysis of sentinel node biopsy in solid head and neck tumors using a time-driven activity-based costing approach.

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    Crott, Ralph; Lawson, Georges; Nollevaux, Marie-Cécile; Castiaux, Annick; Krug, Bruno

    2016-09-01

    Head and neck cancer (HNC) is predominantly a locoregional disease. Sentinel lymph node (SLN) biopsy offers a minimally invasive means of accurately staging the neck. Value in healthcare is determined by both outcomes and the costs associated with achieving them. Time-driven activity-based costing (TDABC) may offer more precise estimates of the true cost. Process maps were developed for nuclear medicine, operating room and pathology care phases. TDABC estimates the costs by combining information about the process with the unit cost of each resource used. Resource utilization is based on observation of care and staff interviews. Unit costs are calculated as a capacity cost rate, measured as a Euros/min (2014), for each resource consumed. Multiplying together the unit costs and resource quantities and summing across all resources used will produce the average cost for each phase of care. Three time equations with six different scenarios were modeled based on the type of camera, the number of SLN and the type of staining used. Total times for different SLN scenarios vary between 284 and 307 min, respectively, with a total cost between 2794 and 3541€. The unit costs vary between 788€/h for the intraoperative evaluation with a gamma-probe and 889€/h for a preoperative imaging with a SPECT/CT. The unit costs for the lymphadenectomy and the pathological examination are, respectively, 560 and 713€/h. A 10 % increase of time per individual activity generates only 1 % change in the total cost. TDABC evaluates the cost of SLN in HNC. The total costs across all phases which varied between 2761 and 3744€ per standard case.

  19. 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

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

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    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.

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

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    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.

  2. Fuzzy logic-based tumor-marker profiles improved sensitivity in the diagnosis of lung cancer.

    Science.gov (United States)

    Schneider, Joachim; Bitterlich, Norman; Velcovsky, Hans-Georg; Morr, Harald; Katz, Norbert; Eigenbrodt, Erich

    2002-06-01

    The aim of this study was to improve the diagnostic efficiency of tumor markers in the diagnosis of lung cancer, by the mathematical evaluation of a tumor marker profile employing fuzzy logic modelling. A panel of four tumor markers, i.e., carcinoembryonic antigen (CEA), cytokeratin 19 antibody (CYFRA 21-1), neuron-specific enolase (NSE), squamous cell carcinoma-related antigen (SCC) and, additionally, C-reactive protein (CRP), was measured in 175 newly diagnosed lung cancer patients with different histological types and stages. Results were compared with those in 120 control subjects, including 27 with chronic obstructive pulmonary diseases (COPD), 65 with pneumoconiosis, and 11 persons with acute inflammatory lung diseases. A classificator was developed using a fuzzy-logic rule-based system. Application of the fuzzy-logic rule-based system to the tumor marker values of CYFRA 21-1, NSE, and CRP yielded an increase in sensitivity of approximately 20%, i.e., 92%, compared with that of the best single marker, CYFRA 21-1(sensitivity, 72%). The corresponding specificity was 95%. The fuzzy classificator significantly improved the sensitivity of the tumor marker panel in stages I and IIIa for non-small-cell lung cancer, as well as in "limited disease" status for small-cell lung cancer. Also, the diagnosis of other stages of lung cancer was enhanced. Fuzzy-logic analysis was proven to be more powerful than the measurement of single markers alone or combinations using multiple logistic regression analysis of all markers. Therefore, fuzzy logic offers a promising diagnostic tool to improve tumor marker efficiency.

  3. 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.

  4. Photodynamic therapy and imaging based on tumor-targeted nanoprobe, polymer-conjugated zinc protoporphyrin

    Science.gov (United States)

    Fang, Jun; Liao, Long; Yin, Hongzhuan; Nakamura, Hideaki; Subr, Vladimir; Ulbrich, Karel; Maeda, Hiroshi

    2015-01-01

    Aim: To evaluate the potential of tumor-targeted nanoprobe, N-(2-hydroxypropyl)methacrylamide copolymer-conjugated zinc protoporphyrin (PZP) for photodynamic therapy (PDT) and tumor imaging. Materials & Methods: Different tumor models including carcinogen-induced cancer were used, PZP was intravenously injected followed by irradiation with xenon or blue fluorescent light on tumor. Results: One PZP 20 mg/kg (ZnPP equivalent) dose with two or three treatments of light at an intensity of ≥20 J/cm2 caused necrosis and disappearance of most tumors (>70%) in different tumor models. We also confirmed PZP-based tumor imaging in carcinogen-induced breast tumor and colon cancer models. Conclusion: These findings support the potential application of PZP as a tumor-selective nanoprobe for PDT as well as tumor imaging, by virtue of the enhanced permeability and retention effect. PMID:28031879

  5. Dendritic cell-based immunotherapy targeting Wilms' tumor 1 in patients with recurrent malignant glioma.

    Science.gov (United States)

    Sakai, Keiichi; Shimodaira, Shigetaka; Maejima, Shinya; Udagawa, Nobuyuki; Sano, Kenji; Higuchi, Yumiko; Koya, Terutsugu; Ochiai, Takanaga; Koide, Masanori; Uehara, Shunsuke; Nakamura, Midori; Sugiyama, Haruo; Yonemitsu, Yoshikazu; Okamoto, Masato; Hongo, Kazuhiro

    2015-10-01

    Dendritic cell (DC)-based vaccination is considered a potentially effective therapy against advanced cancer. The authors conducted a Phase I study to investigate the safety and immunomonitoring of Wilms' tumor 1 (WT1)-pulsed DC vaccination therapy for patients with relapsed malignant glioma. WT1-pulsed and/or autologous tumor lysate-pulsed DC vaccination therapy was performed in patients with relapsed malignant gliomas. Approximately 1 × 10(7) to 2 × 10(7) pulsed DCs loaded with WT1 peptide antigen and/or tumor lysate were intradermally injected into the axillary areas with OK-432, a streptococcal preparation, at 2-week intervals for at least 5-7 sessions (1 course) during an individual chemotherapy regimen. Ten patients (3 men, 7 women; age range 24-64 years [median 39 years]) with the following tumors were enrolled: glioblastoma (6), anaplastic astrocytoma (2), anaplastic oligoastrocytoma (1), and anaplastic oligodendroglioma (1). Modified WT1 peptide-pulsed DC vaccine was administered to 7 patients, tumor lysate-pulsed DC vaccine to 2 patients, and both tumor lysate-pulsed and WT1-pulsed DC vaccine to 1 patient. The clinical response was stable disease in 5 patients with WT1-pulsed DC vaccination. In 2 of 5 patients with stable disease, neurological findings improved, and MR images showed tumor shrinkage. No serious adverse events occurred except Grade 1-2 erythema at the injection sites. WT1 tetramer analysis detected WT1-reactive cytotoxic T cells after vaccination in patients treated with WT1-pulsed therapy. Positivity for skin reaction at the injection sites was 80% (8 of 10 patients) after the first session, and positivity remained for these 8 patients after the final session. This study of WT1-pulsed DC vaccination therapy demonstrated safety, immunogenicity, and feasibility in the management of relapsed malignant gliomas.

  6. Measurement of Tumor Volumes Improves RECIST-Based Response Assessments in Advanced Lung Cancer1

    Science.gov (United States)

    Mozley, P David; Bendtsen, Claus; Zhao, Binsheng; Schwartz, Lawrence H; Thorn, Matthias; Rong, Yuanxin; Zhang, Luduan; Perrone, Andrea; Korn, René; Buckler, Andrew J

    2012-01-01

    OBJECTIVE: This study was designed to characterize the reproducibility of measurement for tumor volumes and their longest tumor diameters (LDs) and estimate the potential impact of using changes in tumor volumes instead of LDs as the basis for response assessments. METHODS: We studied patients with advanced lung cancer who have been observed longitudinally with x-ray computed tomography in a multinational trial. A total of 71 time points from 10 patients with 13 morphologically complex target lesions were analyzed. A total of 6461 volume measurements and their corresponding LDs were made by seven independent teams using their own work flows and image analysis tools. Interteam agreement and overall interrater concurrence were characterized. RESULTS: Interteam agreement between volume measurements was better than between LD measurements (ı = 0.945 vs 0.734, P = .005). The variability in determining the nadir was lower for volumes than for LDs (P = .005). Use of standard thresholds for the RECIST-based method and use of experimentally determined cutoffs for categorizing responses showed that volume measurements had a significantly greater sensitivity for detecting partial responses and disease progression. Earlier detection of progression would have led to earlier changes in patient management in most cases. CONCLUSIONS: Our findings indicate that measurement of changes in tumor volumes is adequately reproducible. Using tumor volumes as the basis for response assessments could have a positive impact on both patient management and clinical trials. More authoritative work to qualify or discard changes in volume as the basis for response assessments should proceed. PMID:22348172

  7. 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.

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

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    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

  9. Digital image analysis for diagnosis of skin tumors.

    Science.gov (United States)

    Blum, Andreas; Zalaudek, Iris; Argenziano, Giuseppe

    2008-03-01

    Between 1987 and 2007, different groups developed digital image analysis systems for the diagnosis of benign and malignant skin tumors. As the result of significant differences in the technical devices, the number, the nature and benign/malignant ratio of included skin tumors, different variables and statistical methods any comparison of these different systems and their results is difficult. For the use and comparison of the diagnostic performance of different digital image analysis systems in the future, some principle basic conditions are required: All used systems should have a standardized recording system and calibration. First, melanocytic and nonmelanocytic lesions should be included for the development of the diagnostic algorithms. Critical analyses of the results should answer the question if in future only melanocytic lesions should be analyzed or all pigmented and nonpigmented lesions. This will also lead to the answer if only dermatologists or all specialities of medical doctors will use such a system. All artifacts (eg, hairs, air bubbles) should be removed. The number of variables should be chosen according to the number of included melanomas. A high number of benign skin lesions should be included. Of all lesions only 10% or better less should be invasive melanomas. Each system should be developed by a training-set and controlled by an independent test-set. Each system should be controlled by the user with the final decision and responsibility and tested by independent users without any conflict of financial interest.

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

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    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.

  11. A potential new enriching trial design for selecting non-small-cell lung cancer patients with no predictive biomarker for trials based on both histology and early tumor response: further analysis of a thalidomide trial.

    Science.gov (United States)

    Lee, Siow Ming; Hackshaw, Allan

    2013-06-01

    There are few predictive biomarkers for antiangiogenic trials in lung cancer. We examine a potential treatment strategy in which a patient group is enriched using both histology and an early assessment of response during standard chemotherapy, and where a new agent is given for the remainder of chemotherapy and as maintenance. We performed a retrospective analysis of 722 stage IIIB/IV non-small-cell lung cancer patients from a double-blind placebo-controlled trial of thalidomide or placebo 100-200 mg/day, combined with gemcitabine/carboplatin (for up to four cycles), then given as single agent maintenance therapy. There was a significant statistical interaction between treatment and histology, with a possible benefit among squamous cell cancer (SCC) patients. We examined 150 SCC patients who were "nonprogressors" (stable disease or complete/partial response) after completing the second chemotherapy cycle. Endpoints were progression-free survival (PFS) and overall survival (OS). Among the 150 patients nonprogressors after cycle 2 (thalidomide, n = 72; placebo, n = 78; baseline characteristics were similar), the hazard ratios (HRs) were: OS = 0.76 (95% CI: 0.54-1.07) and PFS = 0.69 (95% CI: 0.50-0.97). In 57 patients who had a complete/partial response, the HRs were: OS = 0.63 (95% CI: 0.34-1.15) and PFS = 0.50 (95% CI: 0.28-0.88). SCC patients who were nonprogressors after 2 cycles of standard chemotherapy showed evidence of a benefit from thalidomide when taken for the remainder of chemotherapy and as maintenance. This strategy based on histology and, importantly, early assessment of tumor response, as a means of patient enrichment, could be examined in other lung cancer studies. Such an approach might be suitable for trials where there are no predictive biomarkers.

  12. Nanotechnology based therapeutic modality to boost anti-tumor immunity and collapse tumor defense.

    Science.gov (United States)

    Hu, Xiaomeng; Wu, Tingting; Bao, Yuling; Zhang, Zhiping

    2017-06-28

    Cancer is still the leading cause of death. While traditional treatments such as surgery, chemotherapy and radiotherapy play dominating roles, recent breakthroughs in cancer immunotherapy indicate that the influence of immune system on cancer development is virtually beyond our expectation. Manipulating the immune system to fight against cancer has been thriving in recent years. Further understanding of tumor anatomy provides opportunities to put a brake on immunosuppression by overcoming tumor intrinsic resistance or modulating tumor microenvironment. Nanotechnology which provides versatile engineered approaches to enhance therapeutic effects may potentially contribute to the development of future cancer treatment modality. In this review, we will focus on the application of nanotechnology both in boosting anti-tumor immunity and collapsing tumor defense. Copyright © 2017. Published by Elsevier B.V.

  13. 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.

  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. Analysis of patients with phyllodes tumor of the breast.

    Science.gov (United States)

    Atalay, Can; Kınaş, Volkan; Çelebioğlu, Sait

    2014-01-01

    The diagnosis and management of phyllodes tumors is challenging due to its low incidence. The treatment of these tumors is surgery, however the extent of surgery, the application of adjuvant chemotherapy and radiotherapy are still controversial. Therefore, we aimed to evaluate patients who were treated with a diagnosis of phyllodes tumor of the breast in our clinic. Patients who were treated with a diagnosis of phyllodes tumor of the breast between June 2011 and June 2013 were reviewed retrospectively. Patient demographic characteristics (age, gender), menopausal status, symptoms, radiologic and surgical methods used for diagnosis and treatment, histopathologic features of the tumor and type of adjuvant therapy were evaluated. Patients were grouped as benign or borderline/malignant according to histopathological diagnosis. Patients in these groups were compared in terms of age, menopausal status, tumor size and the number of mitosis within the tumor. The median age was 26 years (17-59), and 30 patients were female. The surgical treatment of choice was wide local excision with tumor-free surgical margins in 29 patients and mastectomy in one patient. Histopathological diagnosis after surgery was benign in 21 patients (70%), borderline in 6 patients (20%) and malignant phyllodes tumor in 3 patients (10%). Patients with borderline and malignant phyllodes tumors were significantly older (p=0.002) and had higher mitotic counts (pphyllodes tumors and menopausal status (p=0.06) or tumor size (p=0.1). Surgery is the treatment of choice for phyllodes tumors, and obtaining tumor-free margins is important. Since phyllodes tumors might recur as borderline/malignant tumors, local control with surgery and adjuvant radiotherapy should be provided when required. In this way, distant metastases and death that may arise due to possible malignant recurrences might be avoided.

  16. Label-free multimodal microspectroscopic differentiation of glioblastoma tumor model cell lines combined with multivariate data analysis

    Science.gov (United States)

    Ostertag, Edwin; Boldrini, Barbara; Luckow, Sabrina; Kessler, Rudolf W.

    2012-06-01

    Glioblastoma multiforme represents a highly lethal brain tumor. A tumor model has been developed based on the U-251 MG cell line from a human explant. The tumor model simulates different malignancies by controlled expression of the tumor suppressor proteins PTEN and TP53 within the cell lines derived from the wild type. The cells from each different malignant cell line are grown on slides, followed by a paraformaldehyde fixation. UV / VIS and IR spectra are recorded in the cell nuclei. For the differentiation of the cell lines a principal component analysis (PCA) is performed. The PCA demonstrates a good separation of the tumor model cell lines both with UV / VIS spectroscopy and with IR spectroscopy.

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

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    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.

  18. 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)

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

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    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.

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

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    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

  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. Diphtheria toxin-based anti-human CD19 immunotoxin for targeting human CD19+tumors.

    Science.gov (United States)

    Zheng, Qian; Wang, Zhaohui; Zhang, Huiping; Huang, Qi; Madsen, Joren C; Sachs, David H; Huang, Christene A; Wang, Zhirui

    2017-05-01

    CD19 is expressed on normal and neoplastic B cells and is a promising target for immunotherapy. However, there is still an unmet need to further develop novel therapeutic drugs for the treatment of the refractory/relapsing human CD19 + tumors. We have developed a diphtheria toxin-based anti-human CD19 immunotoxin for targeting human CD19 + tumors. We have constructed three isoforms of the CD19 immunotoxin: monovalent, bivalent, and foldback diabody. In vitro binding affinity and efficacy analysis demonstrated that the bivalent isoform had the highest binding affinity and in vitro efficacy. The in vivo efficacy of the CD19 immunotoxins was assessed using human CD19 + JeKo-1 tumor-bearing NOD/SCID IL-2 receptor γ -/- (NSG) mouse model. In these animals, CD19 immunotoxins significantly prolonged the median survival from 31 days in controls to 34, 36, and 40 days in animals receiving the monovalent isoform, foldback diabody isoform, and bivalent isoform, respectively. The bivalent CD19 immunotoxin is a promising therapeutic drug candidate for targeting relapsing/refractory human CD19 + tumors. © 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

  3. Immunotherapy of tumor with vaccine based on basic fibroblast growth factor-activated fibroblasts.

    Science.gov (United States)

    Li, Xiuying; Wang, Yongsheng; Zhao, Yuwei; Yang, Hengxiu; Tong, Aiping; Zhao, Chengjian; Shi, Huashan; Li, Yang; Wang, Zhenlin; Wei, Yuquan

    2014-02-01

    Cancer-associated fibroblasts play a key role in tumor progression. It is conceivable that the breaking of immune tolerance of "self-antigens" associated with tumor cells and tumor stromal is an attractive approach for tumor immunotherapy. To test this concept, we used basic fibroblast growth factor (bFGF) to activate normal fibroblasts and used these activated fibroblasts as one vaccine against tumor. Normal fibroblasts were treated with bFGF; their expressions of a-SMA and FAP were assessed by Western blot. We immunized mice with bFGF-activated fibroblasts. Auto-antibodies were assessed by flow cytometric and Western blot analysis. The deposition of auto-antibodies within the tumor tissues was assessed. The inhibition of proliferation of tumor cells and fibroblasts by purified immunoglobulins was investigated. The anti-tumor effects of purified immunoglobulins and lymphocytes of immunized mice were assessed. The bFGF-activated fibroblasts were effective in affording protection from tumor onset, growth, and prolonging survival of tumor-bearing mice. The immunized sera exhibited positive staining for fibroblasts and tumor cells in FCAS and Western blot analysis. The purified immunoglobulins of immunized serum could inhibit the proliferation of tumor cells and fibroblasts in vitro and had the anti-tumor activity in vivo. There was the deposition of auto-antibodies within the tumor tissues. Adoptive transfer of lymphocytes of immunized mice revealed that cellular immune response is also involved. The anti-tumor activity could be abrogated by the depletion of CD4(+), CD8(+) T lymphocytes and NK cells. In summary, bFGF-activated fibroblasts could induce an autoimmune response which was simultaneously against both cancer-associated fibroblasts and tumor cells in a cross-reaction.

  4. Multi-step dimensionality reduction and semi-supervised graph-based tumor classification using gene expression data.

    Science.gov (United States)

    Gui, Jie; Wang, Shu-Lin; Lei, Ying-Ke

    2010-11-01

    Both supervised methods and unsupervised methods have been widely used to solve the tumor classification problem based on gene expression profiles. This paper introduces a semi-supervised graph-based method for tumor classification. Feature extraction plays a key role in tumor classification based on gene expression profiles, and can greatly improve the performance of a classifier. In this paper we propose a novel multi-step dimensionality reduction method for extracting tumor-related features. First the Wilcoxon rank-sum test is used for gene selection. Then gene ranking and discrete cosine transform are combined with principal component analysis for feature extraction. Finally, the performance is evaluated by semi-supervised learning algorithms. To show the validity of the proposed method, we apply it to classify four tumor datasets involving various human normal and tumor tissue samples. The experimental results show that the proposed method is efficient and feasible. Compared with other methods, our method can achieve relatively higher prediction accuracy. Particularly, it is found that semi-supervised method is superior to support vector machines in classification performance. The proposed approach can effectively improve the performance of tumor classification based on gene expression profiles. This work is a meaningful attempt to explore and apply multi-step dimensionality reduction and semi-supervised learning methods in the field of tumor classification. Considering the high classification accuracy, there should be much room for the application of multi-step dimensionality reduction and semi-supervised learning methods to perform tumor classification. Copyright © 2010 Elsevier B.V. All rights reserved.

  5. Molecular cytogenetic analysis of chromosome aberrations in desmoid tumors.

    Science.gov (United States)

    Mayer, Magdalena; Kulig, Andrzej; Sygut, Jacek; Dziki, Adam; Simon, Dorota; Latos-Bieleńska, Anna; Ferenc, Tomasz

    2007-01-01

    To date there are only few reports concerning chromosomal changes in desmoid tumors. To extend the knowledge in this field we examined 19 samples from the patients diagnosed with desmoid tumors. In the present study formalin-fixed and paraffin-embedded desmoid tumors were analyzed using fluorescence in situ hybridization (FISH) with a-satellite probes for chromosomes X, Y, 8 and 20. Chromosomal abnormalities were found in 6 cases, both abdominal and extra-abdominal tumors. FISH studies revealed one case of trisomy 8 and trisomy 20. In four patients we have identified monosomy 20. Our findings confirm earlier reports concerning the diversity of chromosomal changes in desmoid tumors and might suggest that both groups of abdominal and extra-abdominal tumors are genuine neoplasms.

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

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    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.

  7. Radiotherapy alone in breast cancer. I. Analysis of tumor parameters, tumor dose and local control: the experience of the Gustave-Roussy Institute and the Princess Margaret Hospital

    International Nuclear Information System (INIS)

    Arriagada, R.; Mouriesse, H.; Sarrazin, D.; Clark, R.M.; Deboer, G.

    1985-01-01

    This retrospective study involved 463 breast cancer patients treated by radiotherapy alone at the Princess Margaret Hospital and at the Institut Gustave-Roussy. These patients either had operable tumors, but were unfit for general anesthesia, or had inoperable tumors due to local contraindications to surgery. Results were analyzed according to tumor response, local recurrence rate, tumor size, tumor fixation, nodal fixation and tumor dose. Conventional statistical analysis of local control showed two significant factors: tumor dose and tumor size. Multivariate analysis permitted to define an ''individual risk'' (IR) of local recurrence according to three independent factors: tumor size, tumor fixation, and nodal fixation. It was shown that the IR was a good prognostic factor for local control. Increase in tumor dose gave a similar effect in the local recurrence relative risk for all the IR groups. According to the slope of the dose-effect curve, it was deduced that a dose increase of 15 Gy can decrease the relative risk of local recurrence 2-fold. In fact, it was shown that tumor dose was the most significant independent factor on local control, able to produce up to a 10-fold increase compared to 2-fold decrease for tumor size. If the IR of local recurrence is known, a theoretical predictive value on local control, taking into account the tumor dose, can be determined according to the present data

  8. 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

  9. Changing Histopathological Diagnostics by Genome-Based Tumor Classification

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    Michael Kloth

    2014-05-01

    Full Text Available Traditionally, tumors are classified by histopathological criteria, i.e., based on their specific morphological appearances. Consequently, current therapeutic decisions in oncology are strongly influenced by histology rather than underlying molecular or genomic aberrations. The increase of information on molecular changes however, enabled by the Human Genome Project and the International Cancer Genome Consortium as well as the manifold advances in molecular biology and high-throughput sequencing techniques, inaugurated the integration of genomic information into disease classification. Furthermore, in some cases it became evident that former classifications needed major revision and adaption. Such adaptations are often required by understanding the pathogenesis of a disease from a specific molecular alteration, using this molecular driver for targeted and highly effective therapies. Altogether, reclassifications should lead to higher information content of the underlying diagnoses, reflecting their molecular pathogenesis and resulting in optimized and individual therapeutic decisions. The objective of this article is to summarize some particularly important examples of genome-based classification approaches and associated therapeutic concepts. In addition to reviewing disease specific markers, we focus on potentially therapeutic or predictive markers and the relevance of molecular diagnostics in disease monitoring.

  10. 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.

  11. 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.

  12. 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

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

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    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. 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.

  15. Multivariate statistical analysis of Raman spectra to distinguish normal, tumor, lymph nodes and mastitis in mouse mammary tissues

    Science.gov (United States)

    Dai, H.; Thakur, J. S.; Serhatkulu, G. K.; Pandya, A. K.; Auner, G. W.; Naik, R.; Freeman, D. C.; Naik, V. M.; Cao, A.; Klein, M. D.; Rabah, R.

    2006-03-01

    Raman spectra ( > 680) of normal mammary gland, malignant mammary gland tumors, and lymph node tissues from mice injected with 4T1 tumor cells have been recorded using 785 nm excitation laser. The state of the tissues was confirmed by standard pathological tests. The multivariate statistical analysis methods (principle component analysis and discriminant functional analysis) have been used to categorize the Raman spectra. The statistical algorithms based on the Raman spectral peak heights, clearly separated tissues into six distinct classes, including mastitis, which is clearly separated from normal and tumor. This study suggests that the Raman spectroscopy can possibly perform a real-time analysis of the human mammary tissues for the detection of cancer.

  16. Retrospective analysis of oral peripheral nerve sheath tumors in Brazilians

    Directory of Open Access Journals (Sweden)

    Juliana Tito Salla

    2009-03-01

    Full Text Available Traumatic neuroma, neurofibroma, neurilemmoma, palisaded encapsulated neuroma and malignant peripheral nerve sheath tumor (MPNST are peripheral nerve sheath tumors and present neural origin. The goal of this study was to describe the epidemiological data of oral peripheral nerve sheath tumors in a sample of the Brazilian population. Biopsies requested from the Oral Pathology Service, School of Dentistry, Federal University of Minas Gerais (MG, Brazil, between 1966 and 2006 were evaluated. Lesions diagnosed as peripheral nerve sheath tumors were submitted to morphologic and to immunohistochemical analyses. All cases were immunopositive to the S-100 protein. Thirty-five oral peripheral nerve sheath tumors were found, representing 0.16% of all lesions archived in the Oral Pathology Service. Traumatic neuroma (15 cases most frequently affected the mental foramen. Solitary neurofibroma (10 cases was more frequently observed in the palate. Neurofibroma associated with neurofibromatosis type I (2 cases was observed in the gingival and alveolar mucosa. Neurilemmoma (4 cases was more commonly observed in the buccal mucosa. Malignant peripheral nerve sheath tumors (3 cases occurred in the mandible, palate, and tongue. Palisaded encapsulated neuroma (1 case occurred in the buccal mucosa. The data confirmed that oral peripheral nerve sheath tumors are uncommon in the oral region, with some lesions presenting a predilection for a specific gender or site. This study may be useful in clinical dentistry and oral pathology practice and may be used as baseline data regarding oral peripheral nerve sheath tumors in other populations.

  17. Cytogenetic analysis of colorectal adenomas: karyotypic comparisons of synchronous tumors

    DEFF Research Database (Denmark)

    Bomme, L; Bardi, G; Pandis, N

    1998-01-01

    The phenotypic progression of colorectal tumors is driven by their step-by-step acquisition of genomic alterations. These pathogenetically important mutations are at the same time markers of tumor clonality. The aim of this study was to describe the clonal relation among synchronous colorectal ad...

  18. 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.

  19. 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...... frequently (14 of 30 tumors, six of six CSF metastasis specimens); LOH of chromosomes 10q, 16q22, 11, 6, 9q22, and 1q31 was observed in 20.6%, 20%, 14.3%, 12%, 10%, and 0%, respectively. Eight of 32 tumors and CSF specimens showed amplification of c-myc. All tumors with amplification of c-myc were resistant...

  20. Predicting anti-tumor effect of deoxypodophyllotoxin in NCI-H460 tumor-bearing mice based on in vitro pharmacodynamics and physiologically based pharmacokinetic-pharmacodynamic model.

    Science.gov (United States)

    Chen, Yang; Zhao, Kaijing; Liu, Fei; Li, Ying; Zhong, Zeyu; Hong, Shijin; Liu, Xiaodong; Liu, Li

    2018-04-04

    Anti-tumor evaluation in tumor-bearing mouse is time- and energy-consuming. We aimed to investigate whether in vivo anti-tumor efficacy could be predicted based on in vitro pharmacodynamics using deoxypodophyllotoxin (DPT), a developing anti-tumor candidate, as a model compound. Proliferation kinetics of monolayer cultivated NCI-H460 cells under various DPT concentrations was quantitatively investigated accompanied by calibration curves. Koch's two-phase natural growth model combined with sigmoid Emax model, i.e. dM/dt=2λ 0 λ 1 M/(λ 1 +2λ 0 M)-EmaxC γ /(EC 50 γ +C γ )·M, was introduced to describe cell proliferation (M) against time under DPT treatment (C). Estimated in vitro pharmacodynamic parameters were: EC 50 , 8.97 nM; Emax, 0.820 day -1 and γ, 7.13. A physiologically based pharmacokinetic (PBPK) model including tumor compartment was introduced, which could predict DPT disposition in plasma, tumor tissue and main normal tissues of NCI-H460 tumor-bearing mice following single dose. In vivo pharmacodynamic model and parameters were assumed the same as in vitro ones, and linked with simulated tumor pharmacokinetic profiles by PBPK model, to build a physiologically based pharmacokinetic-pharmacodynamic (PBPK-PD) model. After estimating natural growth parameters (λ 0 and λ 1 ), we desirably predicted the tumor growth in NCI-H460 tumor-bearing mice during multi-dose DPT treatment, both in this study and literature, by the PBPK-PD model. The model was further successfully applied to predict tumor growth in SGC-7901 tumor-bearing mice. These data indicated that in vivo anti-tumor efficacy might be predicted based on in vitro cytotoxic assays via PBPK-PD model approach. The approach was demonstrated reasonable and applicable, which might facilitate and accelerate anti-cancer candidate screening and dose regimen design in drug discovery process. The American Society for Pharmacology and Experimental Therapeutics.

  1. 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.

  2. The prognostic value of dividing epithelial ovarian cancer into type I and type II tumors based on pathologic characteristics

    DEFF Research Database (Denmark)

    Prahm, Kira Philipsen; Karlsen, Mona Aarenstrup; Høgdall, Estrid

    2015-01-01

    OBJECTIVE: To investigate the prognostic significance of dividing epithelial ovarian cancer (EOC) in type I and type II tumors based on pathologic variables. METHODS: We used the Danish Gynecologic Cancer Database to identify all patients diagnosed with EOC from 2005 to 2012. Information...... on histologic type and grade were used to classify tumors as either type I or type II. Death, and several prognostic factors were used in the multivariate Cox regression, and Landmark analysis was used to estimate hazard ratios of all-cause mortality. RESULTS: Among 2660 patients diagnosed with EOC, 735 were...... categorized as type I tumors, and 1925 as type II tumors. Patients with type II EOC were more frequently diagnosed in late FIGO stages (stages III-IV) than patients with type I EOC (78.1% vs. 32.1% respectively; P

  3. An integrative CGH, MSI and candidate genes methylation analysis of colorectal tumors.

    Directory of Open Access Journals (Sweden)

    Hassan Brim

    Full Text Available Different DNA aberrations processes can cause colorectal cancer (CRC. Herein, we conducted a comprehensive molecular characterization of 27 CRCs from Iranian patients.Array CGH was performed. The MSI phenotype and the methylation status of 15 genes was established using MSP. The CGH data was compared to two established lists of 41 and 68 cancer genes, respectively, and to CGH data from African Americans. A maximum parsimony cladogram based on global aberrations was established.The number of aberrations seem to depend on the MSI status. MSI-H tumors displayed the lowest number of aberrations. MSP revealed that most markers were methylated, except RNF182 gene. P16 and MLH1 genes were primarily methylated in MSI-H tumors. Seven markers with moderate to high frequency of methylation (SYNE1, MMP2, CD109, EVL, RET, LGR and PTPRD had very low levels of chromosomal aberrations. All chromosomes were targeted by aberrations with deletions more frequent than amplifications. The most amplified markers were CD248, ERCC6, ERGIC3, GNAS, MMP2, NF1, P2RX7, SFRS6, SLC29A1 and TBX22. Most deletions were noted for ADAM29, CHL1, CSMD3, FBXW7, GALNS, MMP2, NF1, PRKD1, SMAD4 and TP53. Aberrations targeting chromosome X were primarily amplifications in male patients and deletions in female patients. A finding similar to what we reported for African American CRC patients.This first comprehensive analysis of CRC Iranian tumors reveals a high MSI rate. The MSI tumors displayed the lowest level of chromosomal aberrations but high frequency of methylation. The MSI-L were predominantly targeted with chromosomal instability in a way similar to the MSS tumors. The global chromosomal aberration profiles showed many similarities with other populations but also differences that might allow a better understanding of CRC's clinico-pathological specifics in this population.

  4. An integrative CGH, MSI and candidate genes methylation analysis of colorectal tumors.

    Science.gov (United States)

    Brim, Hassan; Abu-Asab, Mones S; Nouraie, Mehdi; Salazar, Jose; Deleo, Jim; Razjouyan, Hadi; Mokarram, Pooneh; Schaffer, Alejandro A; Naghibhossaini, Fakhraddin; Ashktorab, Hassan

    2014-01-01

    Different DNA aberrations processes can cause colorectal cancer (CRC). Herein, we conducted a comprehensive molecular characterization of 27 CRCs from Iranian patients. Array CGH was performed. The MSI phenotype and the methylation status of 15 genes was established using MSP. The CGH data was compared to two established lists of 41 and 68 cancer genes, respectively, and to CGH data from African Americans. A maximum parsimony cladogram based on global aberrations was established. The number of aberrations seem to depend on the MSI status. MSI-H tumors displayed the lowest number of aberrations. MSP revealed that most markers were methylated, except RNF182 gene. P16 and MLH1 genes were primarily methylated in MSI-H tumors. Seven markers with moderate to high frequency of methylation (SYNE1, MMP2, CD109, EVL, RET, LGR and PTPRD) had very low levels of chromosomal aberrations. All chromosomes were targeted by aberrations with deletions more frequent than amplifications. The most amplified markers were CD248, ERCC6, ERGIC3, GNAS, MMP2, NF1, P2RX7, SFRS6, SLC29A1 and TBX22. Most deletions were noted for ADAM29, CHL1, CSMD3, FBXW7, GALNS, MMP2, NF1, PRKD1, SMAD4 and TP53. Aberrations targeting chromosome X were primarily amplifications in male patients and deletions in female patients. A finding similar to what we reported for African American CRC patients. This first comprehensive analysis of CRC Iranian tumors reveals a high MSI rate. The MSI tumors displayed the lowest level of chromosomal aberrations but high frequency of methylation. The MSI-L were predominantly targeted with chromosomal instability in a way similar to the MSS tumors. The global chromosomal aberration profiles showed many similarities with other populations but also differences that might allow a better understanding of CRC's clinico-pathological specifics in this population.

  5. Ex vivo brain tumor analysis using spectroscopic optical coherence tomography

    Science.gov (United States)

    Lenz, Marcel; Krug, Robin; Welp, Hubert; Schmieder, Kirsten; Hofmann, Martin R.

    2016-03-01

    A big challenge during neurosurgeries is to distinguish between healthy tissue and cancerous tissue, but currently a suitable non-invasive real time imaging modality is not available. Optical Coherence Tomography (OCT) is a potential technique for such a modality. OCT has a penetration depth of 1-2 mm and a resolution of 1-15 μm which is sufficient to illustrate structural differences between healthy tissue and brain tumor. Therefore, we investigated gray and white matter of healthy central nervous system and meningioma samples with a Spectral Domain OCT System (Thorlabs Callisto). Additional OCT images were generated after paraffin embedding and after the samples were cut into 10 μm thin slices for histological investigation with a bright field microscope. All samples were stained with Hematoxylin and Eosin. In all cases B-scans and 3D images were made. Furthermore, a camera image of the investigated area was made by the built-in video camera of our OCT system. For orientation, the backsides of all samples were marked with blue ink. The structural differences between healthy tissue and meningioma samples were most pronounced directly after removal. After paraffin embedding these differences diminished. A correlation between OCT en face images and microscopy images can be seen. In order to increase contrast, post processing algorithms were applied. Hence we employed Spectroscopic OCT, pattern recognition algorithms and machine learning algorithms such as k-means Clustering and Principal Component Analysis.

  6. A Genomics-Based Classification of Human Lung Tumors

    NARCIS (Netherlands)

    Seidel, Danila; Zander, Thomas; Heukamp, Lukas C.; Peifer, Martin; Bos, Marc; Fernandez-Cuesta, Lynnette; Leenders, Frauke; Lu, Xin; Ansen, Sascha; Gardizi, Masyar; Nguyen, Chau; Berg, Johannes; Russell, Prudence; Wainer, Zoe; Schildhaus, Hans-Ulrich; Rogers, Toni-Maree; Solomon, Benjamin; Pao, William; Carter, Scott L.; Getz, Gad; Hayes, D. Neil; Wilkerson, Matthew D.; Thunnissen, Erik; Travis, William D.; Perner, Sven; Wright, Gavin; Brambilla, Elisabeth; Buettner, Reinhard; Wolf, Juergen; Thomas, Roman; Gabler, Franziska; Wilkening, Ines; Mueller, Christian; Dahmen, Ilona; Menon, Roopika; Koenig, Katharina; Albus, Kerstin; Merkelbach-Bruse, Sabine; Fassunke, Jana; Schmitz, Katja; Kuenstlinger, Helen; Kleine, Michaela; Binot, Elke; Querings, Silvia; Altmueller, Janine; Boessmann, Ingelore; Nuemberg, Peter; Schneider, Peter; Bogus, Magdalena; Buettner, Reinhard; Perner, Sven; Russell, Prudence; Thunnissen, Erik; Travis, William D.; Brambilla, Elisabeth; Soltermann, Alex; Moch, Holger; Brustugun, Odd Terje; Solberg, Steinar; Lund-Iversen, Marius; Helland, Aslaug; Muley, Thomas; Hoffmann, Hans; Schnabel, Philipp A.; Chen, Yuan; Groen, Harry; Timens, Wim; Sietsma, Hannie; Clement, Joachim H.; Weder, Walter; Saenger, Joerg; Stoelben, Erich; Ludwig, Corinna; Engel-Riedel, Walburga; Smit, Egbert; Heideman, Danille A. M.; Snijders, Peter J. F.; Nogova, Lucia; Sos, Martin L.; Mattonet, Christian; Toepelt, Karin; Scheffler, Matthias; Goekkurt, Eray; Kappes, Rainer; Krueger, Stefan; Kambartel, Kato; Behringer, Dirk; Schulte, Wolfgang; Galetke, Wolfgang; Randerath, Winfried; Heldwein, Matthias; Schlesinger, Andreas; Serke, Monika; Hekmat, Khosro; Frank, Konrad F.; Schnell, Roland; Reiser, Marcel; Huenerlituerkoglu, Ali-Nuri; Schmitz, Stephan; Meffert, Lisa; Ko, Yon-Dschun; Litt-Lampe, Markus; Gerigk, Ulrich; Fricke, Rainer; Besse, Benjamin; Brambilla, Christian; Lantuejoul, Sylvie; Lorimier, Philippe; Moro-Sibilot, Denis; Cappuzzo, Federico; Ligorio, Claudia; Damiani, Stefania; Field, John K.; Hyde, Russell; Validire, Pierre; Girard, Philippe; Muscarella, Lucia A.; Fazio, Vito M.; Hallek, Michael; Soria, Jean-Charles; Carter, Scott L.; Getz, Gad; Hayes, D. Neil; Wilkerson, Matthew D.; Achter, Viktor; Lang, Ulrich; Seidel, Danila; Zander, Thomas; Heukamp, Lukas C.; Peifer, Martin; Bos, Marc; Pao, William; Travis, William D.; Brambilla, Elisabeth; Buettner, Reinhard; Wolf, Juergen; Thomas, Roman K.

    2013-01-01

    We characterized genome alterations in 1255 clinically annotated lung tumors of all histological subgroups to identify genetically defined and clinically relevant subtypes. More than 55% of all cases had at least one oncogenic genome alteration potentially amenable to specific therapeutic

  7. Glioblastoma angiogenesis: VEGF resistance solutions and new strategies based on molecular mechanisms of tumor vessel formation.

    Science.gov (United States)

    Takano, Shingo

    2012-04-01

    Glioblastomas are highly vascular tumors. Recent preclinical and clinical investigations have revealed that agents targeting angiogenesis may have efficacy against this type of tumor. Antibodies to vascular endothelial growth factor are being studied in this patient population. Unfortunately, treatment inevitably fails. This review provides an update on recent research on the mechanisms by which tumor cells acquire resistance, and discusses recent preclinical and experimental development of novel new-generation anti-angiogenic agents that overcome this problem, especially those based on the molecular mechanisms of tumor vessel formation. The tumor vasculature not only nourishes glioblastomas, but also provides a specialized microenvironment for tumor stem-like cells and for the brain tumor. The factors, pathways, and interactions described in this review provide information about the cell biology of glioblastomas which may ultimately result in new modes of treatment.

  8. 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.

  9. An artificial neural network (ANN)-based lung-tumor motion predictor for intrafractional MR tumor tracking.

    Science.gov (United States)

    Yun, Jihyun; Mackenzie, Marc; Rathee, Satyapal; Robinson, Don; Fallone, B G

    2012-07-01

    To address practical issues of implementing artificial neural networks (ANN) for lung-tumor motion prediction in MRI-based intrafractional lung-tumor tracking. A feedforward four-layered ANN structure is used to predict future tumor positions. A back-propagation algorithm is used for ANN learning. Adaptive learning is incorporated by continuously updating weights and learning rate during prediction. An ANN training scheme specific for MRI-based tracking is developed. A multiple-ANN structure is developed to reduce tracking failures caused by the lower imaging rates of MRI. We used particle swarm optimization to optimize the ANN structure and initial weights (IW) for each patient and treatment fraction. Prediction accuracy is evaluated using the 1D superior-inferior lung-tumor motions of 29 lung cancer patients for system delays of 120-520 ms, in increments of 80 ms. The result is compared with four different scenarios: (1), (2) ANN structure optimization + with∕without IW optimization, and (3), (4) no ANN structure optimization + with∕without IW optimization, respectively. An additional simulation is performed to assess the value of optimizing the ANN structure for each treatment fraction. For 120-520 ms system delays, mean RMSE values (ranges 0.0-2.8 mm from 29 patients) of 0.5-0.9 mm are observed, respectively. Using patient specific ANN structures, a 30%-60% decrease in mean RMSE values is observed as a result of IW optimization, alone. No significant advantages in prediction performance are observed, however, by optimizing for each fraction. A new ANN-based lung-tumor motion predictor is developed for MRI-based intrafractional tumor tracking. The prediction accuracy of our predictor is evaluated using a realistic simulated MR imaging rate and system delays. For 120-520 ms system delays, mean RMSE values of 0.5-0.9 mm (ranges 0.0-2.8 mm from 29 patients) are achieved. Further, the advantage of patient specific ANN structure and IW in lung-tumor motion

  10. 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

    with 64Cu-ATSM and CT scans with contrast. Irreversible and reversible two-tissue compartment models were fitted to time activity curves (TACs) obtained from whole tumor volumes and compared using the Akaike information criterion (AIC). Based on voxel-wise pharmacokinetic analysis, parametric maps...... of model rate constants k₁, k₃ and Ki were generated and compared to 64Cu-ATSM uptake.RESULTS: Based on the AIC, an irreversible two-tissue compartment model was selected for voxel-wise pharmacokinetic analysis. Of the extracted parameters, k₁ (~perfusion) showed a strong correlation with early tracer...... relevant parameters from voxel-wise pharmacokinetic analysis to be used for preclinical validation of 64Cu-ATSM as a hypoxia-specific PET tracer....

  11. 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

  12. Breast phyllodes tumor: a review of literature and a single center retrospective series analysis.

    Science.gov (United States)

    Spitaleri, Gianluca; Toesca, Antonio; Botteri, Edoardo; Bottiglieri, Luca; Rotmensz, Nicole; Boselli, Sabrina; Sangalli, Claudia; Catania, Chiara; Toffalorio, Francesca; Noberasco, Cristina; Delmonte, Angelo; Luini, Alberto; Veronesi, Paolo; Colleoni, Marco; Viale, Giuseppe; Zurrida, Stefano; Goldhirsch, Aron; Veronesi, Umberto; De Pas, Tommaso

    2013-11-01

    Complete surgical resection is the standard treatment for localized breast phyllodes tumors. Post-surgical treatments are still a matter of debate. We carried out an overview of the literature to investigate the clinical outcome of patients with phyllodes tumor. A retrospective analysis of mono-institutional series has been included as well. We reviewed all the retrospective series reported from 1951 until April 2012. We analyzed cases treated at our institution from 1999 to 2010. Eighty-three articles (5530 patients; 1956 malignant tumors) were reviewed. Local recurrences were independent of histology. Distant recurrences were more frequent in the malignant tumors (22%). A total of 172 phyllodes tumors were included in the retrospective analysis. Prognosis of phyllodes tumors is excellent. There are no convincing data to recommend any adjuvant treatment after surgery. Molecular characterization may well provide new clues to permit identification of active treatments for the rare poor prognosis cases. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  13. Tumor microenvironment in focus: LA-ICP-MS bioimaging of a preclinical tumor model upon treatment with platinum(IV)-based anticancer agents.

    Science.gov (United States)

    Theiner, Sarah; Kornauth, Christoph; Varbanov, Hristo P; Galanski, Markus; Van Schoonhoven, Sushilla; Heffeter, Petra; Berger, Walter; Egger, Alexander E; Keppler, Bernhard K

    2015-08-01

    The selection of drug candidates for entering clinical development relies on in vivo testing in (solid) tumor animal models. However, the heterogeneity of tumor tissue (e.g. in terms of drug uptake or tissue composition) is rarely considered when testing novel drug candidates. Therefore, we used the murine colon cancer CT-26 tumor model to study the spatially-resolved drug distribution in tumor tissue upon repetitive treatment of animals over two weeks with three investigational platinum(IV)-based anticancer agents, oxaliplatin or satraplatin. A quantitative laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) imaging method revealed a heterogeneous platinum distribution, which correlated well with the histologic features of the tumor and surrounding tissue at the microscopic level. In most of the cases, higher amounts of intratumoral platinum were found in the surrounding tissue than in the malignant parts of the sample. This indicates that determination of average platinum amounts (e.g. by microwave-assisted digestion of the sample followed by analysis with ICP-MS) might overestimate the drug uptake in tumor tissue causing misleading conclusions. In addition, we studied the platinum distribution in the kidneys of treated animals to probe if accumulation in the cortex and medulla predict potential nephrotoxicity. A 10-fold increase of platinum in the cortex of the kidney over the medulla was observed for oxaliplatin and satraplatin. Although these findings are similar to those in the platinum distribution of the nephrotoxic anticancer drug cisplatin, treatment with the compounds of our study did not show signs of nephrotoxicity in clinical use or clinical trials (oxaliplatin, satraplatin) and did not result in the alteration of renal structures. Thus, predicting the side effects based on bioimaging data by LA-ICP-MS should be considered with caution. To the best of our knowledge, this is the first LA-ICP-MS study on spatially-resolved platinum

  14. BRAF mutational analysis in ovarian tumors: recent perspectives

    Directory of Open Access Journals (Sweden)

    Wong KK

    2015-09-01

    Full Text Available Kwong-Kwok Wong,1 Ching-Chou Tsai,2 David M Gershenson11Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 2Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan, Republic of ChinaAbstract: BRAF mutations are rare in ovarian cancer and mainly occur in indolent serous borderline tumors (SBTs, also known as serous tumors of low malignant potential or atypical proliferative serous tumors. The reported percentage of BRAF mutations in SBTs varies from 23% to 71%. Although a high percentage of stage II–IV SBTs with noninvasive implants have progressed to invasive low-grade serous carcinomas when patients were observed for 5 years or longer, BRAF mutations are rare in low-grade serous carcinomas as well as in invasive implants associated with SBTs. BRAF mutations in SBTs may prevent SBTs from progressing to invasive carcinomas. On the other hand, the reported percentage of BRAF mutations in mucinous carcinoma (20% is much higher than that of mucinous borderline tumor (5%. Further investigation of the role of BRAF mutations in SBTs and mucinous tumor will shed light on the molecular mechanism underlying the role of BRAF mutations in tumor progression in different cellular context and the clinical utility of BRAF mutations in SBTs as a biomarker of favorable prognosis.Keywords: BRAF V600E, ovarian cancer, COLD-PCR

  15. Dilemmas in Endoscopic Management of Rectal Neuroendocrine Tumors: A Case-Based Discussion

    Directory of Open Access Journals (Sweden)

    Brian P. Rajca

    2015-01-01

    Full Text Available Rectal neuroendocrine tumors are uncommon neoplasms that historically were regarded as having an indolent course. Due to the widespread use of screening colonoscopy neuroendocrine tumors of the rectum are identified with increasing frequency. More recent literature has suggested that rectal neuroendocrine tumors may progress in a more malignant fashion than previously believed. In this case-based discussion we present management dilemmas, analyze current guidelines, and highlight the role of endoscopic ultrasound, endoscopic resection, and surgery.

  16. 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.

  17. 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.

  18. 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.

  19. Malignant tumors of head and neck region - a retrospective analysis

    International Nuclear Information System (INIS)

    Aziz, F.; Ahmed, S.; Malik, A.; Afsar, A.; Yousaf, N.W.

    2001-01-01

    To evaluate the spectrum of malignant tumors of head and neck region. The data of total 375 neoplastic lesions of both the sexes between 8-70 years of age was collected and compared with the findings reported from centers in other parts of the country. Among the total 375 cases of neoplastic lesions, 148 were benign whereas 227 proved to be malignant histologically in 155 male and 72 female patients. Squamous cell carcinoma (SCC) was the most frequently encountered histological category (45.8%) followed by lymphoma (14.5%), basal cell carcinoma (10.5%), carcinoma thyroid (10.5%) and salivary gland tumors (8.80%). These were followed by infrequently encountered tumors including nasopharyngeal carcinoma (n=5), small blue round cell tumors (n=3), undifferentiated carcinoma (n=3), retinoblastoma (n=2) and transitional carcinoma nose (n=1). The anatomical regions involved with this tumor were larynx (53.5% of all SCC) followed by pharynx (18.7%) tongue (10.71%) oral cavity (4.4%) metastasis (5.3%) and skin (2.60%). (author)

  20. Analysis of perfusion, microcirculation and drug transport in tumors. A computational study.

    Science.gov (United States)

    Zunino, Paolo; Cattaneo, Laura

    2013-11-01

    We address blood flow through a network of capillaries surrounded by a porous interstitium. We develop a computational model based on the Immersed Boundary method [C. S. Peskin. Acta Numer. 2002.]. The advantage of such an approach relies in its efficiency, because it does not need a full description of the real geometry allowing for a large economy of memory and CPU time and it facilitates handling fully realistic vascular networks [L. Cattaneo and P. Zunino. Technical report, MOX, Department of Mathematics, Politecnico di Milano, 2013.]. The analysis of perfusion and drug release in vascularized tumors is a relevant application of such techniques. Blood vessels in tumors are substantially leakier than in healthy tissue and they are tortuous. These vascular abnormalities lead to an impaired blood supply and abnormal tumor microenvironment characterized by hypoxia and elevated interstitial fluid pressure that reduces the distribution of drugs through advection [L.T. Baxter and R.K. Jain. Microvascular Research, 1989]. Finally, we discuss the application of the model to deliver nanoparticles. In particular, transport of nanoparticles in the vessels network, their adhesion to the vessel wall and the drug release in the surrounding tissue will be addressed.

  1. 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.

  2. The differentiation of malignant and benign musculoskeletal tumors by F-18 FDG PET/CT studies-determination of maxSUV by analysis of ROC curve

    International Nuclear Information System (INIS)

    Kong, Eun Jung; Cho, Ihn Ho; Chun, Kyung Ah; Won, Kyu Chang; Lee, Hyung Woo; Choi, Jun Heok; Shin, Duk Seop

    2007-01-01

    We evaluated the standard uptake value (SUV) of F-18 FDG at PET/CT for differentiation of benign from malignant tumor in primary musculoskeletal tumors. Forty-six tumors (11 benign and 12 malignant soft tissue tumors, 9 benign and 14 malignant bone tumors) were examined with F-18 FDG PET/CT (Discovery ST, GE) prior to tissue diagnosis. The maxSUV(maximum value of SUV) were calculated and compared between benign and malignant lesions. The lesion analysis was based on the transverse whole body image. The maxSUV with cutoff of 4.1 was used in distinguishing benign from malignant soft tissue tumor and 3.05 was used in bone tumor by ROC curve. There was a statistically significant difference in maxSUV between benign (n = 11; maxSUV 3.4 ± 3.2) and malignant (n = 12; maxSUV 14.8 ± 12.2) lesion in soft tissue tumor (ρ = 0.001). Between benign bone tumor (n = 9; maxSUV 5.4 ± 4.0) and malignant bone tumor (n = 14; maxSUV 7.3 ± 3.2), there was not a significant difference in maxSUV. The sensitivity and specificity for differentiating malignant from benign soft tissue tumor was 83% and 91%, respectively. There were four false positive malignant bone tumor cases to include fibrous dysplasia, Langerhans-cell histiocytosis (n = 2) and osteoid osteoma. Also, one false positive case of malignant soft tissue tumor was nodular fasciitis. The maxSUV was useful for differentiation of benign from malignant lesion in primary soft tissue tumors. In bone tumor, the low maxSUV correlated well with benign lesions but high maxSUV did not always mean malignancy

  3. Mathematical Based Calculation of Drug Penetration Depth in Solid Tumors

    Directory of Open Access Journals (Sweden)

    Hamidreza Namazi

    2016-01-01

    Full Text Available Cancer is a class of diseases characterized by out-of-control cells’ growth which affect cells and make them damaged. Many treatment options for cancer exist. Chemotherapy as an important treatment option is the use of drugs to treat cancer. The anticancer drug travels to the tumor and then diffuses in it through capillaries. The diffusion of drugs in the solid tumor is limited by penetration depth which is different in case of different drugs and cancers. The computation of this depth is important as it helps physicians to investigate about treatment of infected tissue. Although many efforts have been made on studying and measuring drug penetration depth, less works have been done on computing this length from a mathematical point of view. In this paper, first we propose phase lagging model for diffusion of drug in the tumor. Then, using this model on one side and considering the classic diffusion on the other side, we compute the drug penetration depth in the solid tumor. This computed value of drug penetration depth is corroborated by comparison with the values measured by experiments.

  4. Diagnostic accuracy of three-dimensional CT reconstruction and cephalometry for lateral skull base tumors.

    Science.gov (United States)

    Xie, X Z; Huo, X K

    2015-10-01

    To explore the diagnostic accuracy of three-dimensional CT reconstruction and cephalometry in lateral skull base tumors. Fifty-eight patients with lateral skull base tumors were randomly divided into control group (n = 29, examined with conventional diagnostic technique) or study group (n = 29, examined with three-dimensional CT reconstruction and cephalometry). The diagnostic accuracy, tumor distribution and image characteristics were compared between both patient groups. In control group, preoperative tumor diagnosis was consistent with intraoperative diagnosis in 20 patients, similar in 7 patients and discrepant in 2 patients. In study group, there were 24 consistent, 4 similar, and 1 discrepant diagnoses (p cephalometry provides accurate diagnosis of lateral skull base tumors, which is helpful for subsequent surgical treatment.

  5. Analysis of molecular changes during human melanocytic tumor progression.

    NARCIS (Netherlands)

    Wit, N.J. de

    2005-01-01

    Melanoma is one of the most aggressive types of cancer, due to its potency to disseminate early in tumor progression. The incidence is still rising, even though the rate of change has leveled off in the last decade. As melanoma cells are relatively insensitive to classical systemic therapies, like

  6. Cytogenetic analysis of colorectal adenomas: karyotypic comparisons of synchronous tumors

    DEFF Research Database (Denmark)

    Bomme, L; Bardi, G; Pandis, N

    1998-01-01

    , and 3 and loss of chromosome 18. Eight adenomas had subclones as evidence of clonal evolution. Similar clones in separate polyps were seen in tumors from 6 patients; these adenomas were always located in the same part of the large bowel. In 2 patients, both with one rectal adenoma and one adenoma...

  7. Analysis of glycodendrimers effect(s) in tumor mictoenvironment

    Czech Academy of Sciences Publication Activity Database

    Fišerová, Anna; Bezouška, Karel; Švábová, L.; Jedelský, P.; Pucová, S.; Luptovcová, M.; Luksan, O.; Vannucci, Luca; Pospíšil, Miloslav

    2003-01-01

    Roč. 87, č. 1 (2003), s. 24 ISSN 0165-2478 R&D Projects: GA ČR GV312/98/K034; GA AV ČR IAA7020006 Institutional research plan: CEZ:AV0Z5020903 Keywords : glycodendrimers * effect * tumor Subject RIV: EE - Microbiology, Virology Impact factor: 1.710, year: 2003

  8. [Forensic analysis of 74 tumor related medical malpractice cases].

    Science.gov (United States)

    Guo, Ya-Dong; Cai, Ji-Fen; Chang, Yun-Feng; Guan, Peng; Wen, Ji-Fang

    2010-06-01

    To analyze the causes of medical malpractice in patients with tumor, to determine the medical responsibility, and to recommend the related preventions. Seventy four medical malpractice cases, which were involved in tumor and collected from 2000 to 2009 in medicolegal expertise center of west China, were analyzed retrospectively. The medical malpractice cases in the patients with tumor showed an increasing tendency in recent years. The main causes are missed diagnosis, misdiagnosis, improper chemotherapy and neglect of complications. The causes of medical malpractice were different in the different levels of medical services. The occurrence of medical malpractice in surgery and OB-GYN showed more frequent than the others. Forensic pathology autopsy is important to resolve medical malpractice of tumor patients by finding out the cause of death and clarifying the medical responsibility. The occurrence of medical malpractice could be reduced by the clinical doctors through improving serve consciousness, obtaining the patients' trust, improving the medical treatment, following related laws and rules, fulfiling duty of medical careness.

  9. Regulation of Tumor Necrosis Factor Gene Expression in Colorectal Adenocarcinoma: In vivo Analysis by in situ Hybridization

    Science.gov (United States)

    Beissert, Stefan; Bergholz, Michael; Waase, Inge; Lepsien, Gerd; Schauer, Alfred; Pfizenmaier, Klaus; Kronke, Martin

    1989-07-01

    Tumor necrosis factor (TNF) produced by macrophages is thought to contribute to the host defense against development of cancer. However, since tumor cells themselves are able to produce TNF, it is conceivable that TNF may also play an adverse pathological role in carcinogenesis. To better understand the functional significance of TNF in neoplastic disease, we have determined the cellular source of TNF activity produced in 10 patients with colorectal cancer. Northern blot analysis of RNAs extracted from fresh biopsy specimens revealed detectable TNF mRNA levels in all instances. By using in situ hybridization of frozen sections, scattered cells expressing TNF mRNA could be discerned. Based on morphological criteria, these TNF-positive cells most likely belong to the macrophage lineage. Macrophages in normal tissue surrounding the tumor did not express TNF mRNA, suggesting that macrophage activation occurs locally at the site of neoplastic transformation. Immunohistochemistry using anti-TNF monoclonal antibodies revealed that less than 1% of tumor-infiltrating macrophages synthesize TNF protein. Thus we present evidence that in colorectal cancer only a small proportion of tumor-infiltrating macrophages produces TNF, indicating that the microenvironment of the tumor provides adequate, yet suboptimal, conditions for macrophage activation.

  10. Regulation of tumor necrosis factor gene expression in colorectal adenocarcinoma: In vivo analysis by in situ hybridization

    Energy Technology Data Exchange (ETDEWEB)

    Beissert, S.; Bergholz, M.; Waase, I.; Lepsien, G.; Schauer, A.; Pfizenmaier, K.; Kroenke, M. (Max-Planck-Gesellschaft, Goettingen (West Germany))

    1989-07-01

    Tumor necrosis factor (TNF) produced by macrophages is though to contribute to the host defense against development of cancer. However, since tumor cells themselves are able to produce TNF, it is conceivable that TNF may also play an adverse pathological role in carcinogenesis. To better understand the functional significance of TNF in neoplastic disease, they authors have determined the cellular source of TNF activity produced in 10 patients with colorectal cancer. Northern blot analysis of RNAs extracted from fresh biopsy specimens revealed detectable TNF mRNA levels in all instances. By using in situ hybridization of frozen sections, scattered cells expressing TNF mRNA could be discerned. Based on morphological criteria, these TNF-positive cells most likely belong to the macrophage lineage. Macrophages in normal tissue surrounding the tumor did not express TNF mRNA, suggesting that macrophage activation occurs locally at the site of neoplastic transformation. Immunohistochemistry using anti-TNF monoclonal antibodies revealed that less than 1% of tumor-infiltrating macrophages synthesize TNF protein. Thus they present evidence that in colorectal cancer only a small proportion of tumor-infiltrating macrophages produces TNF, indicating that the microenvironment of the tumor provides adequate, yet suboptimal, conditions for macrophage activation.

  11. [Clinicopathologic analysis of 52 cases of thymic epithelial tumor].

    Science.gov (United States)

    Ma, Yu-qing; Miao, Na; Abulajiang, Gulinaer; Li, Qiao-xin; Liu, Xia; Zhang, Wei; Wang, Chao-fu; Wang, Jian

    2010-04-01

    To study the clinicopathologic characteristics of thymic epithelial tumors and to evaluate the diagnostic reproducibility and clinical relevance of the 2004 WHO histologic classification system. The morphology and immunophenotype of 52 cases of thymic epithelial tumor were reviewed. The tumors were classified according to the new WHO classification system and the clinical data were analyzed. Of the 52 cases studied, 45 were thymomas and 7 were thymic carcinomas. Amongst the 45 cases of thymoma, 6 (13.4%) were type A, 15 (33.3%) were type AB, 4 (8.9%) were type B1, 9 (20.0%) were type B2, 9 (20.0%) were type B3 and 2 (4.4%) were metaplastic thymoma. Amongst the 7 cases of thymic carcinoma, 6 were squamous cell carcinomas and 1 was neuroendocrine carcinoma. The commonest presentations were cough and chest pain. Some cases were incidentally discovered by routine physical examination. Thirteen cases (25.0%) of thymoma were associated with myasthenia gravis. CT scan showed that 49 cases (94.2%) were located in the anterior mediastinum. All cases of type A, AB and B1 thymoma and most cases of B2 thymoma appeared as well-defined homogeneous mass, whereas a few cases of type B2 thymoma and most cases of type B3 thymoma and thymic carcinoma were poorly demarcated and heterogeneous. According to Masaoka staging system, 20 cases (41.7%) belonged to stage I, 15 cases (31.3%) stage II, 11 cases (22.9%) stage III and 2 cases (4.1%) stage IV. The histologic subtypes of thymic epithelial tumors significantly correlated with the clinical stages (chi(2) = 32.5, P < 0.01). The 2004 revision of WHO histologic classification system for thymic epithelial tumors shows a high degree of reproducibility. Correlation with the radiologic, clinical and prognostic parameters is helpful in determining the management strategy for individual patients.

  12. Classifying Melanocytic Tumors Based on DNA Copy Number Changes

    OpenAIRE

    Bastian, Boris C.; Olshen, Adam B.; LeBoit, Philip E.; Pinkel, Daniel

    2003-01-01

    Melanoma and benign melanocytic nevi can overlap significantly in their histopathological presentation and misdiagnoses are common. To determine whether genetic criteria can be of diagnostic help we determined DNA copy number changes in 186 melanocytic tumors (132 melanomas and 54 benign nevi) using comparative genomic hybridization. We found highly significant differences between melanomas and nevi. Whereas 127 (96.2%) of the melanomas had some form of chromosomal aberration, only 7 (13.0%) ...

  13. Tumor Dose Response in Yttrium-90 Resin Microsphere Embolization for Neuroendocrine Liver Metastases: A Tumor-Specific Analysis with Dose Estimation Using SPECT-CT.

    Science.gov (United States)

    Chansanti, Orapin; Jahangiri, Younes; Matsui, Yusuke; Adachi, Akira; Geeratikun, Yindee; Kaufman, John A; Kolbeck, Kenneth J; Stevens, Jeffrey S; Farsad, Khashayar

    2017-11-01

    To evaluate dose-response relationship in yttrium-90 ( 90 Y) resin microsphere radioembolization for neuroendocrine tumor (NET) liver metastases using a tumor-specific dose estimation based on technetium-99m-labeled macroaggregated albumin ( 99m Tc MAA) single photon emission computed tomography (SPECT)-CT. Fifty-five tumors (mean size 3.9 cm) in 15 patients (10 women; mean age 57 y) were evaluated. Tumor-specific absorbed dose was estimated using a partition model. Initial (median 2.3 months) follow-up data were available for all tumors; last (median 7.6 months) follow-up data were available for 45 tumors. Tumor response was evaluated using Modified Response Evaluation Criteria in Solid Tumors (mRECIST) on follow-up CT. Tumors with complete or partial response were considered responders. Mean tumor absorbed dose was 231.4 Gy ± 184.3, and mean nontumor liver absorbed dose was 39.0 Gy ± 18.0. Thirty-six (65.5%) and 30 (66.7%) tumors showed response at initial and last follow-up, respectively. Mean absorbed doses in responders and nonresponders at initial and last follow-up were 285.8 Gy ± 191.1 and 128.1 Gy ± 117.1 (P = .0004) and 314.3 Gy ± 195.8 and 115.7 Gy ± 117.4 (P = .0001). Cutoff value of ≥ 191.3 Gy for tumor-specific absorbed dose predicted tumor response with 93% specificity, whereas 90.3 vs 70.0 Gy ± 28.0; P = .007). Tumor-specific absorbed dose, estimated with a partition model, was significantly associated with tumor response in NET liver metastases. An estimated dose ≥ 191.3 Gy predicted treatment response with high sensitivity and specificity. Copyright © 2017 SIR. All rights reserved.

  14. KillerRed protein based in vivo photodynamic therapy and corresponding tumor metabolic imaging

    Directory of Open Access Journals (Sweden)

    Qiaoya Lin

    2016-01-01

    Full Text Available Photodynamic therapy (PDT gains wide attention as a useful therapeutic method for cancer. It is mediated by the oxygen and photosensitizer under the specific light irradiation to produce the reactive oxygen species (ROS, which induce cellular toxicity and regulate the redox potential in tumor cells. Nowadays, genetic photosensitizers of low toxicity and easy production are required to be developed. KillerRed, a unique red fluorescent protein exhibiting excellent phototoxic properties, has the potential to act as a photosensitizer in the application of tumor PDT. Meantime, the course of tumor redox metabolism during this treatment was rarely investigated so far. Thus here, we investigated the effects of KillerRed-based PDT on tumor growth in vivo and examined the subsequent tumor metabolic states including the changes of nicotinamide adenine dinucleotide hydrogen (NADH and flavoprotein (Fp, two important metabolic coenzymes of tumor cells. Results showed the tumor growth had been significantly inhibited by KillerRed-based PDT treatment compared to control groups. A home-made cryo-imaging redox scanner was used to measure intrinsic fluorescence and exogenous KillerRed fluorescence signals in tumors. The Fp signal was elevated by nearly 4.5-fold, while the NADH signal decreased by 66% after light irradiation, indicating that Fp and NADH were oxidized in the course of KillerRed-based PDT. Furthermore, we also observed correlation between the fluorescence distribution of KillerRed and NADH. It suggests that the KillerRed protein based PDT might provide a new approach for tumor therapy accompanied by altering tumor metabolism.

  15. 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.

  16. 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.

  17. Tumor-infiltrating lymphocytes. Cytologic, phenotypic and morphometric analysis.

    Science.gov (United States)

    Oliver, G; Yannelli, J; Solomon, D

    1996-01-01

    To characterize the cytologic, phenotypic and morphometric features of tumor-infiltrating lymphocytes (TILs). Morphology and cell size parameters of 50 TILs and five normal donor peripheral blood lymphocyte (PBL) specimens were compared using light microscopy, manual ocular measurements and digital image processing. Cytologically, all TILs demonstrated similar morphologic findings regardless of the initial tumor type. Changes included large; eccentric nuclei, sometimes hyperlobated; clumped chromatin; and prominent nucleoli. The cytoplasm was abundant and basophilic. Mitotic figures were usually evident. In addition, TIL showed significant increases in cell size parameters as compared to PBLs. The activated morphology of TILs resembles the appearance of high grade lymphoma. Several cell size parameters are increased; that may help to explain differences in previously reported trafficking patterns between TILs and peripheral blood lymphocytes.

  18. Selected Reaction Monitoring (SRM Analysis of Epidermal Growth Factor Receptor (EGFR in Formalin Fixed Tumor Tissue

    Directory of Open Access Journals (Sweden)

    Hembrough Todd

    2012-05-01

    Full Text Available Abstract Background Analysis of key therapeutic targets such as epidermal growth factor receptor (EGFR in clinical tissue samples is typically done by immunohistochemistry (IHC and is only subjectively quantitative through a narrow dynamic range. The development of a standardized, highly-sensitive, linear, and quantitative assay for EGFR for use in patient tumor tissue carries high potential for identifying those patients most likely to benefit from EGFR-targeted therapies. Methods A mass spectrometry-based Selected Reaction Monitoring (SRM assay for the EGFR protein (EGFR-SRM was developed utilizing the Liquid Tissue®-SRM technology platform. Tissue culture cells (n = 4 were analyzed by enzyme-linked immunosorbent assay (ELISA to establish quantitative EGFR levels. Matching formalin fixed cultures were analyzed by the EGFR-SRM assay and benchmarked against immunoassay of the non-fixed cultured cells. Xenograft human tumor tissue (n = 10 of non-small cell lung cancer (NSCLC origin and NSCLC patient tumor tissue samples (n = 23 were microdissected and the EGFR-SRM assay performed on Liquid Tissue lysates prepared from microdissected tissue. Quantitative curves and linear regression curves for correlation between immunoassay and SRM methodology were developed in Excel. Results The assay was developed for quantitation of a single EGFR tryptic peptide for use in FFPE patient tissue with absolute specificity to uniquely distinguish EGFR from all other proteins including the receptor tyrosine kinases, IGF-1R, cMet, Her2, Her3, and Her4. The assay was analytically validated against a collection of tissue culture cell lines where SRM analysis of the formalin fixed cells accurately reflects EGFR protein levels in matching non-formalin fixed cultures as established by ELISA sandwich immunoassay (R2 = 0.9991. The SRM assay was applied to a collection of FFPE NSCLC xenograft tumors where SRM data range from 305amol/μg to 12,860amol/μg and

  19. Molecular Analysis of Medaka Tumors: New Models for Carcinogenicity Testing

    Science.gov (United States)

    1994-07-07

    51 A1 4 INTRODUCTION For over twenty years, tumors in fish and other lower vertebrates and invertebrates have been systematically...class of vertebrates , with over 20,000 described species. Their phylogenetic position relative to the other vertebrates makes them ideal for comparative...provide large numbers of eggs and are easy to culture. The genetics, developmental biology and embryology are well-documented (Yamamoto 1975). Induction

  20. Primary malignant chest wall tumors: analysis of 40 patients.

    Science.gov (United States)

    Bagheri, Reza; Haghi, Seyed Ziaollah; Kalantari, Mahmoud Reza; Sharifian Attar, Alireza; Salehi, Maryam; Tabari, Azadeh; Soudaneh, Maliheh

    2014-06-19

    Primary chest wall tumors originate from different constructions of thoracic wall. We report our multidisciplinary experience on primary thoracic tumor resection and thoracic reconstruction, the need to additional therapy and evaluating prognostic factors affecting survival. We performed a retrospective review of our prospectively maintained database of 40 patients treated for malignant primary chest wall tumor from 1989 to 2009. Patients were evaluated in terms of age, sex, clinical presentation, type of imaging, tissue diagnosis methods, pathology, surgical technique, early complications, hospital mortality, prevalence of recurrence and distant metastases, additional treatment, 3 years survival and factors affecting survival. Male/Female (F/M) = 1, with median age of 43.72 years. Mass was the most common symptoms and the soft tissue sarcoma was the most common pathology. Resection without reconstruction was performed in 5 patients and Thirty-five patients (87.5%) had extensive resection and reconstruction with rotatory muscular flap, prosthetic mesh and/or cement. Overall, 12.5% (5/40) of patients received neoadjuvant therapy and 75% (30/40) of patients were treated with adjuvant therapy. The 3-year survival rate was 65%. Recurrences occurred in 24 patients (60%), 14 developed local recurrences, and 10 developed distant metastases. The primary treatment modality for both local and distant recurrences was surgical resection; among them, 10 underwent repeated resection, 9 adjuvant therapy and 5 were treated with lung metastasectomy. The most common site of distant metastasis was lung (n = 7). Factors that affected survival were type of pathology and evidence of distant metastasis. Surgery with wide margin is the safe and good technique for treatment of primary chest wall tumors with acceptable morbidity and mortality.

  1. Genome wide in silico SNP-tumor association analysis

    International Nuclear Information System (INIS)

    Qiu, Ping; Wang, Luquan; Kostich, Mitch; Ding, Wei; Simon, Jason S; Greene, Jonathan R

    2004-01-01

    Carcinogenesis occurs, at least in part, due to the accumulation of mutations in critical genes that control the mechanisms of cell proliferation, differentiation and death. Publicly accessible databases contain millions of expressed sequence tag (EST) and single nucleotide polymorphism (SNP) records, which have the potential to assist in the identification of SNPs overrepresented in tumor tissue. An in silico SNP-tumor association study was performed utilizing tissue library and SNP information available in NCBI's dbEST (release 092002) and dbSNP (build 106). A total of 4865 SNPs were identified which were present at higher allele frequencies in tumor compared to normal tissues. A subset of 327 (6.7%) SNPs induce amino acid changes to the protein coding sequences. This approach identified several SNPs which have been previously associated with carcinogenesis, as well as a number of SNPs that now warrant further investigation This novel in silico approach can assist in prioritization of genes and SNPs in the effort to elucidate the genetic mechanisms underlying the development of cancer

  2. 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.

  3. 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

  4. Differentiation of multiple types of pancreatico-biliary tumors by molecular analysis of clinical specimens.

    Science.gov (United States)

    Gress, Thomas M; Kestler, Hans A; Lausser, Ludwig; Fiedler, Lisa; Sipos, Bence; Michalski, Christoph W; Werner, Jens; Giese, Nathalia; Scarpa, Aldo; Buchholz, Malte

    2012-04-01

    Timely and accurate diagnosis of pancreatic ductal adenocarcinoma (PDAC) is critical in order to provide adequate treatment to patients. However, the clinical signs and symptoms of PDAC are shared by several types of malignant or benign tumors which may be difficult to differentiate from PDAC with conventional diagnostic procedures. Among others, these include ampullary cancers, solid pseudopapillary tumors, and adenocarcinomas of the distant bile duct, as well as inflammatory masses developing in chronic pancreatitis. Here, we report an approach to accurately differentiate between these different types of pancreatic masses based on molecular analysis of biopsy material. A total of 156 bulk tissue and fine needle aspiration biopsy samples were analyzed using a dedicated diagnostic cDNA array and a composite classification algorithm developed based on linear support vector machines. All five histological subtypes of pancreatic masses were clearly separable with 100% accuracy when using all 156 individual samples for classification. Generalized performance of the classification system was tested by 10 × 10-fold cross validation (100 test runs). Correct classification into the five diagnostic groups was demonstrated for 81.5% of 1,560 test set predictions. Performance increased to 85.3% accuracy when PDAC and distant bile duct carcinomas were combined in a single diagnostic class. Importantly, overall sensitivity of detection of malignant disease was 92.2%. The molecular diagnostic approach presented here is suitable to significantly aid in the differential diagnosis of undetermined pancreatic masses. To our knowledge, this is the first study reporting accurate differentiation between several types of pancreatico-biliary tumors in a single molecular analytical procedure.

  5. Digital image analysis of endoscopic ultrasonography is helpful in diagnosing gastric mesenchymal tumors.

    Science.gov (United States)

    Kim, Gwang Ha; Kim, Kwang Baek; Lee, Seung Hyun; Jeon, Hye Kyung; Park, Do Youn; Jeon, Tae Yong; Kim, Dae Hwan; Song, Geun Am

    2014-01-08

    Endoscopic ultrasonography (EUS) is a valuable imaging tool for evaluating subepithelial lesions in the stomach. However, there are few studies on differentiation between gastrointestinal stromal tumors (GISTs) and benign mesenchymal tumors, such as leiomyoma or schwannoma, with the use of EUS. In addition, there are limitations in the analysis of the characteristic features of such tumors due to poor interobserver agreement as a result of subjective interpretation of EUS images. Therefore, the aim of this study was to evaluate the role of digital image analysis in distinguishing the features of GISTs from those of benign mesenchymal tumors on EUS. We enrolled 65 patients with histopathologically proven gastric GIST, leiomyoma or schwannoma on surgically resected specimens who underwent EUS examination at our endoscopic unit from January 2007 to September 2010. After standardization of the EUS images, brightness values including the mean (Tmean), indicative of echogenicity, and the standard deviation (TSD), indicative of heterogeneity, in the tumors were analyzed. The Tmean and TSD were significantly higher in GIST than in leiomyoma and schwannoma (p schwannoma when the critical values of Tmean and TSD were 65 and 75, respectively. The presence of at least 1 of these 2 findings in a given tumor resulted in a sensitivity of 94%, specificity of 80%, positive predictive value of 94%, negative predictive value of 80%, and accuracy of 90.8% for predicting GIST. Digital image analysis provides objective information on EUS images; thus, it can be useful in diagnosing gastric mesenchymal tumors.

  6. Analysis of histological and immunohistochemical patterns of benign and malignant adrenocortical tumors by computerized morphometry.

    Science.gov (United States)

    Dalino Ciaramella, Paolo; Vertemati, Maurizio; Petrella, Duccio; Bonacina, Edgardo; Grossrubatscher, Erika; Duregon, Eleonora; Volante, Marco; Papotti, Mauro; Loli, Paola

    2017-07-01

    Diagnosis of benign and purely localized malignant adrenocortical lesions is still a complex issue. Moreover, histology-based diagnosis may suffer of a moment of subjectivity due to inter- and intra-individual variations. The aim of the present study was to assess, by computerized morphometry, the morphological features in benign and malignant adrenocortical neoplasms. Eleven adrenocortical adenomas (ACA) were compared with 18 adrenocortical cancers (ACC). All specimens were stained with H&E, cellular proliferation marker Ki-67 and reticulin. We generated a morphometric model based on the analysis of volume fractions occupied by Ki-67 positive and negative cells (nuclei and cytoplasm), vascular and inflammatory compartment; we also analyzed the surface fraction occupied by reticulin. We compared the quantitative data of Ki-67 obtained by morphometry with the quantification resulting from pathologist's visual reading. The volume fraction of Ki-67 positive cells in ACCs was higher than in ACAs. The volume fraction of nuclei in unit volume and the nuclear/cytoplasmic ratio in both Ki-67 negative cells and Ki-67 positive cells were prominent in ACCs. The surface fraction of reticulin was considerably lower in ACCs. Our computerized morphometric model is simple, reproducible and can be used by the pathologist in the histological workup of adrenocortical tumors to achieve precise and reader-independent quantification of several morphological characteristics of adrenocortical tumors. Copyright © 2017 Elsevier GmbH. All rights reserved.

  7. 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

  8. 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.

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

    Science.gov (United States)

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

    2017-02-01

    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.

  10. 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.

  11. 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.

  12. Fractal analysis of nuclear histology integrates tumor and stromal features into a single prognostic factor of the oral cancer microenvironment

    International Nuclear Information System (INIS)

    The lack of prognostic biomarkers in oral squamous cell carcinoma (OSCC) has hampered treatment decision making and survival in OSCC remains poor. Histopathological features are used for prognostication in OSCC and, although useful for predicting risk, manual assessment of histopathology is subjective and labour intensive. In this study, we propose a method that integrates multiple histopathological features of the tumor microenvironment into a single, digital pathology-based biomarker using nuclear fractal dimension (nFD) analysis. One hundred and seven consecutive OSCC patients diagnosed between 1998 and 2006 in Calgary, Canada were included in the study. nFD scores were generated from DAPI-stained images of tissue microarray (TMA) cores. Ki67 protein expression was measured in the tumor using fluorescence immunohistochemistry (IHC) and automated quantitative analysis (AQUA®). Lymphocytic infiltration (LI) was measured in the stroma from haematoxylin-eosin (H&E)-stained TMA slides by a pathologist. Twenty-five (23.4%) and 82 (76.6%) patients were classified as high and low nFD, respectively. nFD was significantly associated with pathological tumor-stage (pT-stage; P = 0.01) and radiation treatment (RT; P = 0.01). High nFD of the total tumor microenvironment (stroma plus tumor) was significantly associated with improved disease-specific survival (DSS; P = 0.002). No association with DSS was observed when nFD of either the tumor or the stroma was measured separately. pT-stage (P = 0.01), pathological node status (pN-status; P = 0.02) and RT (P = 0.03) were also significantly associated with DSS. In multivariate analysis, nFD remained significantly associated with DSS [HR 0.12 (95% CI 0.02-0.89, P = 0.04)] in a model adjusted for pT-stage, pN-status and RT. We also found that high nFD was significantly associated with high tumor proliferation (P < 0.0001) and high LI (P < 0.0001), factors that we and others have shown to be associated with improved survival in OSCC

  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. 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 C; Goldberg, Richard M; Sargent, Daniel J

    2011-10-15

    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. Individual patient data from three North Central Cancer Treatment Group trials (N0026, n = 117; N9741, n = 1,109; and 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 (complete or partial) vs. stable disease 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 postbaseline. Model discrimination was evaluated by the concordance (c) index. The overall best response rates for the three trials were 26%, 45%, and 25%, respectively. Although nearly all metrics were statistically significantly associated with overall survival at the different landmark time points, the concordance indices (c-index) for the traditional response metrics ranged from 0.59 to 0.65; for the continuous metrics from 0.60 to 0.66; and for the TriTR metrics from 0.64 to 0.69. The c-indices for TriTR at 12 weeks were comparable with those at 16 and 24 weeks. 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. ©2011 AACR.

  15. 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.

  16. Machine-learning based comparison of CT-perfusion maps and dual energy CT for pancreatic tumor detection

    Science.gov (United States)

    Goetz, Michael; Skornitzke, Stephan; Weber, Christian; Fritz, Franziska; Mayer, Philipp; Koell, Marco; Stiller, Wolfram; Maier-Hein, Klaus H.

    2016-03-01

    Perfusion CT is well-suited for diagnosis of pancreatic tumors but tends to be associated with a high radiation exposure. Dual-energy CT (DECT) might be an alternative to perfusion CT, offering correlating contrasts while being acquired at lower radiation doses. While previous studies compared intensities of Dual Energy iodine maps and CT-perfusion maps, no study has assessed the combined discriminative power of all information that can be generated from an acquisition of both functional imaging methods. We therefore propose the use of a machine learning algorithm for assessing the amount of information that becomes available by the combination of multiple images. For this, we train a classifier on both imaging methods, using a new approach that allows us to train only from small regions of interests (ROIs). This makes our study comparable to other - ROI-based analysis - and still allows comparing the ability of both classifiers to discriminate between healthy and tumorous tissue. We were able to train classifiers that yield DICE scores over 80% with both imaging methods. This indicates that Dual Energy Iodine maps might be used for diagnosis of pancreatic tumors instead of Perfusion CT, although the detection rate is lower. We also present tumor risk maps that visualize possible tumorous areas in an intuitive way and can be used during diagnosis as an additional information source.

  17. 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.

  18. 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

  19. 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

  20. Boronic acid-tethered amphiphilic hyaluronic acid derivative-based nanoassemblies for tumor targeting and penetration.

    Science.gov (United States)

    Jeong, Jae Young; Hong, Eun-Hye; Lee, Song Yi; Lee, Jae-Young; Song, Jae-Hyoung; Ko, Seung-Hak; Shim, Jae-Seong; Choe, Sunghwa; Kim, Dae-Duk; Ko, Hyun-Jeong; Cho, Hyun-Jong

    2017-04-15

    (3-Aminomethylphenyl)boronic acid (AMPB)-installed hyaluronic acid-ceramide (HACE)-based nanoparticles (NPs), including manassantin B (MB), were fabricated for tumor-targeted delivery. The amine group of AMPB was conjugated to the carboxylic acid group of hyaluronic acid (HA) via amide bond formation, and synthesis was confirmed by spectroscopic methods. HACE-AMPB/MB NPs with a 239-nm mean diameter, narrow size distribution, negative zeta potential, and >90% drug encapsulation efficiency were fabricated. Exposed AMPB in the outer surface of HACE-AMPB NPs (in the aqueous environment) may react with sialic acid of cancer cells. The improved cellular accumulation efficiency, in vitro antitumor efficacy, and tumor penetration efficiency of HACE-AMPB/MB NPs, compared with HACE/MB NPs, in MDA-MB-231 cells (CD44 receptor-positive human breast adenocarcinoma cells) may be based on the CD44 receptor-mediated endocytosis and phenylboronic acid-sialic acid interaction. Enhanced in vivo tumor targetability, infiltration efficiency, and antitumor efficacies of HACE-AMPB NPs, compared with HACE NPs, were observed in a MDA-MB-231 tumor-xenografted mouse model. In addition to passive tumor targeting (based on an enhanced permeability and retention effect) and active tumor targeting (interaction between HA and CD44 receptor), the phenylboronic acid-sialic acid interaction can play important roles in augmented tumor targeting and penetration of HACE-AMPB NPs. STATEMENT OF SIGNIFICANCE: (3-Aminomethylphenyl)boronic acid (AMPB)-tethered hyaluronic acid-ceramide (HACE)-based nanoparticles (NPs), including manassantin B (MB), were fabricated and their tumor targeting and penetration efficiencies were assessed in MDA-MB-231 (CD44 receptor-positive human adenocarcinoma) tumor models. MB, which exhibited antitumor efficacies via the inhibition of angiogenesis and hypoxia inducible factor (HIF)-1, was entrapped in HACE-AMPB NPs in this study. Phenylboronic acid located in the outer surface

  1. Significance of hypoxia for tumor response to radiation: Mathematical modeling and analysis of local control and clonogenic assay data

    International Nuclear Information System (INIS)

    Buffa, Francesca Meteora

    2002-01-01

    Various hypotheses for radiation local tumor control probability (ltcp) were modeled, and assessed against local tumor control (LTC) and clonogenic assay (CA) data. For head-and-neck tumors receiving low-LET external-beam irradiation, the best model was a Poisson ltcp accounting for cell repopulation, hypoxia, and tumor volume dependence of radiosensitivity (α). This confirmed that hypoxia is limiting LTC of these tumors, with the magnitude depending upon tumor volume. However, LTC of cervical carcinoma receiving external-beam irradiation and brachytherapy was well described by a model not accounting for hypoxia. Furthermore, when the survival fraction at 2 Gy (SF 2 ) and colony forming efficiency (CFE) measured for individual patients were incorporated into this model, very good correlation with LTC was seen (p=0.0004). After multivariate analysis, this model was the best independent prognostic factor for LTC and patient survival. Furthermore, no difference in prediction was seen when a model based on birth-and-death stochastic theory was used. Two forms of hypoxia are known to be present in tumors: diffusion-limited, chronic hypoxia (CH), and acute, transient hypoxia (TH). A modeling study on WiDr multicellular spheroids showed that the CH effect on LTC is significantly lower than expected from CA. This could arise from energy charge depletion accompanying CH, reducing the number of proliferating clonogenic cells that can repair radiation damage, and thus mitigating the radioresistance of CH cells. This suggests that TH, rather than CH, may be the limiting factor for in vivo LTC. Finally, by computing ltcp using Monte Carlo calculated dose distributions, it was shown that Monte Carlo statistical noise can cause an underestimation of ltcp, with the magnitude depending upon the model hypotheses

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  4. 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.

  5. Analysis of the contents of German magazines for tumor patients.

    Science.gov (United States)

    Hübner, Jutta; Münstedt, Karsten; Senf, Bianca; Micke, Oliver

    2013-01-01

    Cancer patients have high information needs. Besides direct discussion with the physician, media provide important access to information. In the age of the internet, print media are still being used by many patients. In Germany, several magazines for cancer patients are distributed at no cost to cancer institutions for display. The aim of our study was to assess the content of these magazines. In a first step, a search of the literature concerning patient information needs and evaluation of patient information was done. This search revealed important criteria for evaluation. 2 instruments are recognized internationally as appropriate in evaluating and certifying patient information: HONcode and DISCERN. As we did not find an instrument for the evaluation of patient magazines, we combined the central items from both instruments. With this new instrument, we assessed the 2010 issues of all 5 magazines . The Krebsmagazin offers a vast range of different topics in cancer and thus aims at general patient education, irrespective of the level of knowledge. Befund Krebs offers a wider variety of topics in each issue. Understanding the articles requires basic knowledge. The same applies to Leben? Leben! which specifically addresses the topic of breast cancer. All 3 journals provide information in line with evidence-based medicine. K Journal - Mensch & Krebs provides information on conventional as well as alternative treatments, the latter not being evidence-based. Several issues contained both advertisements and articles by providers of alternative therapies. Signal only deals with alternative medicine in cancer care and does not provide scientifically proven data. As our analysis shows, content and evidence vary greatly in the magazines currently distributed in Germany. Physicians should familiarize themselves with the characteristics of the different journals before recommending them. Copyright © 2013 S. Karger AG, Basel.

  6. 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 (Pfactors 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 McCormick grade and patient received partial resection or

  7. Comparative Analysis of 3D Bladder Tumor Spheroids Obtained by Forced Floating and Hanging Drop Methods for Drug Screening

    OpenAIRE

    Amaral, Robson L. F.; Miranda, Mariza; Marcato, Priscyla D.; Swiech, Kamilla

    2017-01-01

    Introduction: Cell-based assays using three-dimensional (3D) cell cultures may reflect the antitumor activity of compounds more accurately, since these models reproduce the tumor microenvironment better. Methods: Here, we report a comparative analysis of cell behavior in the two most widely employed methods for 3D spheroid culture, forced floating (Ultra-low Attachment, ULA, plates), and hanging drop (HD) methods, using the RT4 human bladder cancer cell line as a model. The morphology para...

  8. 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

  9. 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.

  10. A block matching-based registration algorithm for localization of locally advanced lung tumors.

    Science.gov (United States)

    Robertson, Scott P; Weiss, Elisabeth; Hugo, Geoffrey D

    2014-04-01

    To implement and evaluate a block matching-based registration (BMR) algorithm for locally advanced lung tumor localization during image-guided radiotherapy. 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. 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-right, anterior-posterior, and

  11. 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

  12. 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

  13. Development of diagnostic model of lung cancer based on multiple tumor markers and data mining.

    Science.gov (United States)

    Wang, Zhaoxian; Feng, Feifei; Zhou, Xiaoshan; Duan, Liju; Wang, Jing; Wu, Yongjun; Wang, Na

    2017-11-07

    To develop early intelligent discriminative model of lung cancer and evaluate the efficiency of diagnosis value. Based on the genetic polymorphism profile of CYP1A1-rs1048943, GSTM1, mEH-rs1051740, XRCC1-rs1799782 and XRCC1-rs25489 and the methylations of p16 and RASSF1A gene, and the length of telomere in the peripheral blood from 200 lung cancer patients and 200 health persons, the discriminative model was established through decision tree and ANN technique. ACU of the discriminative model based on multiple tumour markers increased by about 10%; The accuracy rate of decision tree model and ANN model for testing set were 93.00% and 89.62% respectively. The ROC analysis showed the decision tree model's AUC is 0.929 (0.894∼0.964), the ANN model's AUC is 0.894 (0.853∼0.935). However, the classify accuracy rate and AUC of Fisher discriminatory analysis model are all about 0.7. The early intelligent discriminative model of lung cancer based on multiple tumor markers and data mining techniques has a higher accuracy rate and might be useful for early diagnosis of lung cancer.

  14. Wavelet-based 3D reconstruction of microcalcification clusters from two mammographic views: new evidence that fractal tumors are malignant and Euclidean tumors are benign.

    Science.gov (United States)

    Batchelder, Kendra A; Tanenbaum, Aaron B; Albert, Seth; Guimond, Lyne; Kestener, Pierre; Arneodo, Alain; Khalil, Andre

    2014-01-01

    The 2D Wavelet-Transform Modulus Maxima (WTMM) method was used to detect microcalcifications (MC) in human breast tissue seen in mammograms and to characterize the fractal geometry of benign and malignant MC clusters. This was done in the context of a preliminary analysis of a small dataset, via a novel way to partition the wavelet-transform space-scale skeleton. For the first time, the estimated 3D fractal structure of a breast lesion was inferred by pairing the information from two separate 2D projected mammographic views of the same breast, i.e. the cranial-caudal (CC) and mediolateral-oblique (MLO) views. As a novelty, we define the "CC-MLO fractal dimension plot", where a "fractal zone" and "Euclidean zones" (non-fractal) are defined. 118 images (59 cases, 25 malignant and 34 benign) obtained from a digital databank of mammograms with known radiologist diagnostics were analyzed to determine which cases would be plotted in the fractal zone and which cases would fall in the Euclidean zones. 92% of malignant breast lesions studied (23 out of 25 cases) were in the fractal zone while 88% of the benign lesions were in the Euclidean zones (30 out of 34 cases). Furthermore, a Bayesian statistical analysis shows that, with 95% credibility, the probability that fractal breast lesions are malignant is between 74% and 98%. Alternatively, with 95% credibility, the probability that Euclidean breast lesions are benign is between 76% and 96%. These results support the notion that the fractal structure of malignant tumors is more likely to be associated with an invasive behavior into the surrounding tissue compared to the less invasive, Euclidean structure of benign tumors. Finally, based on indirect 3D reconstructions from the 2D views, we conjecture that all breast tumors considered in this study, benign and malignant, fractal or Euclidean, restrict their growth to 2-dimensional manifolds within the breast tissue.

  15. Baculovirus-based gene silencing of Humanin for the treatment of pituitary tumors.

    Science.gov (United States)

    Gottardo, María Florencia; Pidre, Matías L; Zuccato, Camila; Asad, Antonela S; Imsen, Mercedes; Jaita, Gabriela; Candolfi, Marianela; Romanowski, Víctor; Seilicovich, Adriana

    2018-02-01

    Pituitary tumors are the most common primary intracranial neoplasms. Humanin (HN) and Rattin (HNr), a rat homolog of HN, are short peptides with a cytoprotective action. In the present study, we aimed to evaluate whether endogenous HNr plays an antiapoptotic role in pituitary tumor cells. Thus, we used RNA interference based on short-hairpin RNA (shRNA) targeted to HNr (shHNr). A plasmid including the coding sequences for shHNr and dTomato fluorescent reporter gene was developed (pUC-shHNr). Transfection of somatolactotrope GH3 cells with pUC-shHNr increased apoptosis, suggesting that endogenous HNr plays a cytoprotective role in pituitary tumor cells. In order to evaluate the effect of blockade of endogenous HNr expression in vivo, we constructed a recombinant baculovirus (BV) encoding shHNr (BV-shHNr). In vitro, BV-shRNA was capable of transducing more than 80% of GH3 cells and decreased HNr mRNA. Also, BV-shHNr increased apoptosis in transduced GH3 cells. Intratumor injection of BV-shHNr to nude mice bearing s.c. GH3 tumors increased the number of apoptotic cells, delayed tumor growth and enhanced survival rate, suggesting that endogenous HNr may be involved in pituitary tumor progression. These preclinical data suggests that the silencing of HN expression could have a therapeutic impact on the treatment of pituitary tumors.

  16. 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.

  17. 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

  18. 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

  19. Differentiation between Phyllodes Tumors and Fibroadenomas Based on Mammographic Sonographic and MRI Features

    Science.gov (United States)

    Duman, Lale; Gezer, Naciye S.; Balcı, Pınar; Altay, Canan; Başara, Işıl; Durak, Merih G.; Sevinç, Ali İ.

    2016-01-01

    Summary Background This study was performed to compare the mammographic, sonographic, and magnetic resonance imaging (MRI) characteristics of phyllodes tumors and fibroadenomas, which may resemble each other. Methods Preoperative mammograms, B-mode and Doppler sonograms, and dynamic breast MRIs of 72 patients with pathologically proven fibroadenomas and 70 patients with pathologically proven phyllodes tumor were evaluated in this retrospective study. Statistical significance was evaluated using chi-square and Fisher's exact tests. Correlations in lesion size among radiological methods were examined by Pearson's correlation analysis. Results The features that differed on mammogram were size, shape, and margin of the mass. Sonograms showed significant differences in size, shape, margin, echo pattern, and vascularization of the mass. Pearson's correlation analysis showed strong agreement among radiological methods in terms of assessment of size. Tumor size ≥ 3 cm, irregular shape, microlobulated margins, complex internal echo pattern, and hypervascularity were significant findings of phyllodes tumors. Internal cystic areas on MRI were frequently associated with phyllodes tumors. Conclusion Mammographic, sonographic, and MRI findings of fibroadenomas and phyllodes tumors could help radiologists to ascertain imaging-histological concordance and guide clinicians in their decision making regarding adequate follow-up or the necessity of biopsy. PMID:27239174

  20. 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

  1. Pediatric Head and Neck Tumors: An Intra-Demographic Analysis Using the SEER* Database

    OpenAIRE

    Cesmebasi, Alper; Gabriel, Abigail; Niku, Daniel; Bukala, Karolina; Donnelly, Joseph; Fields, Paul J.; Tubbs, R. Shane; Loukas, Marios

    2014-01-01

    Background The aim of this study was to determine the most frequently presenting tumors exclusive to the head and neck within the pediatric population, and to identify racial disparities within the existing incidence rates. Material/Methods The population-based Surveillance, Epidemiology, and End Results (SEER) registry was utilized to identify the frequency and incidence rates of various tumors found exclusively in the head and neck, diagnosed between 1973 and 2008 in pediatric patients. The...

  2. 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.

  3. A kernel-based method for markerless tumor tracking in kV fluoroscopic images.

    Science.gov (United States)

    Zhang, Xiaoyong; Homma, Noriyasu; Ichiji, Kei; Abe, Makoto; Sugita, Norihiro; Takai, Yoshihiro; Narita, Yuichiro; Yoshizawa, Makoto

    2014-09-07

    Markerless tracking of respiration-induced tumor motion in kilo-voltage (kV) fluoroscopic image sequence is still a challenging task in real time image-guided radiation therapy (IGRT). Most of existing markerless tracking methods are based on a template matching technique or its extensions that are frequently sensitive to non-rigid tumor deformation and involve expensive computation. This paper presents a kernel-based method that is capable of tracking tumor motion in kV fluoroscopic image sequence with robust performance and low computational cost. The proposed tracking system consists of the following three steps. To enhance the contrast of kV fluoroscopic image, we firstly utilize a histogram equalization to transform the intensities of original images to a wider dynamical intensity range. A tumor target in the first frame is then represented by using a histogram-based feature vector. Subsequently, the target tracking is then formulated by maximizing a Bhattacharyya coefficient that measures the similarity between the tumor target and its candidates in the subsequent frames. The numerical solution for maximizing the Bhattacharyya coefficient is performed by a mean-shift algorithm. The proposed method was evaluated by using four clinical kV fluoroscopic image sequences. For comparison, we also implement four conventional template matching-based methods and compare their performance with our proposed method in terms of the tracking accuracy and computational cost. Experimental results demonstrated that the proposed method is superior to conventional template matching-based methods.

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

    NARCIS (Netherlands)

    Almendro, Vanessa; Cheng, Yu-Kang; Randles, Amanda; Itzkovitz, Shalev; Marusyk, Andriy; Ametller, Elisabet; Gonzalez-Farre, Xavier; Muñoz, Montse; Russnes, Hege G; Helland, Aslaug; 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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  6. 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.

  7. 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

  8. 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.

  9. Long-term survival in women with borderline ovarian tumors: a population-based survey of borderline ovarian tumors in Sweden 1960-2007.

    Science.gov (United States)

    Kalapotharakos, Grigorios; Högberg, Thomas; Bergfeldt, Kjell; Borgfeldt, Christer

    2016-04-01

    We conducted an evaluation of incidence and survival of women with borderline ovarian tumors in Sweden. All women diagnosed with borderline ovarian tumor in the Swedish Cancer Register 1960-2007 (n = 6252) combined with follow up in the Swedish Death Registry to 1 July 2009 were included. Estimation of age-standardized relative survival rate according to time periods for diagnosis. The incidence of borderline ovarian tumors increased during the study period, with a steep increase during the 1980s. The age standardized 5-year relative survival including all borderline tumors diagnosed 2000-07 was 97% (95% CI 92-99%). In women aged ≤64 years, the 10-year relative survival related to age at diagnosis of borderline tumors ranged from 95 to 98% and was 89% in women aged 65-74 years. In a multivariable analysis including age and decade of diagnosis relative survival for every decade increased. The 10-year relative survival in women with mucinous and serous borderline tumors did not differ significantly (p = 0.121). Results of the present study are reassuring about long-term survival in women with borderline ovarian tumors. The age-standardized relative survival rate increased across time periods for diagnosis. There was no difference in long-term survival between mucinous and serous borderline ovarian tumors. © 2016 Nordic Federation of Societies of Obstetrics and Gynecology.

  10. Selection and Validation of Predictive Models of Radiation Effects on Tumor Growth Based on Noninvasive Imaging Data.

    Science.gov (United States)

    Lima, E A B F; Oden, J T; Wohlmuth, B; Shahmoradi, A; Hormuth, D A; Yankeelov, T E; Scarabosio, L; Horger, T

    2017-12-01

    The use of mathematical and computational models for reliable predictions of tumor growth and decline in living organisms is one of the foremost challenges in modern predictive science, as it must cope with uncertainties in observational data, model selection, model parameters, and model inadequacy, all for very complex physical and biological systems. In this paper, large classes of parametric models of tumor growth in vascular tissue are discussed including models for radiation therapy. Observational data is obtained from MRI of a murine model of glioma and observed over a period of about three weeks, with X-ray radiation administered 14.5 days into the experimental program. Parametric models of tumor proliferation and decline are presented based on the balance laws of continuum mixture theory, particularly mass balance, and from accepted biological hypotheses on tumor growth. Among these are new model classes that include characterizations of effects of radiation and simple models of mechanical deformation of tumors. The Occam Plausibility Algorithm (OPAL) is implemented to provide a Bayesian statistical calibration of the model classes, 39 models in all, as well as the determination of the most plausible models in these classes relative to the observational data, and to assess model inadequacy through statistical validation processes. Discussions of the numerical analysis of finite element approximations of the system of stochastic, nonlinear partial differential equations characterizing the model classes, as well as the sampling algorithms for Monte Carlo and Markov chain Monte Carlo (MCMC) methods employed in solving the forward stochastic problem, and in computing posterior distributions of parameters and model plausibilities are provided. The results of the analyses described suggest that the general framework developed can provide a useful approach for predicting tumor growth and the effects of radiation.

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

    Science.gov (United States)

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

    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 5mg·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 2.5mg·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. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. United States-based practice patterns and resource utilization in advanced neuroendocrine tumor treatment.

    Science.gov (United States)

    Strosberg, Jonathan; Casciano, Roman; Stern, Lee; Parikh, Rohan; Chulikavit, Maruit; Willet, Jacob; Liu, Zhimei; Wang, Xufang; Grzegorzewski, Krzysztof J

    2013-04-21

    To assess advanced neuroendocrine tumor (NET) treatment patterns and resource utilization by tumor progression stage and tumor site in the United States. United States Physicians meeting eligibility criteria were provided with online data extraction forms to collect patient chart data on recent NET patients. Resource utilization and treatment pattern data were collected over a baseline period (after diagnosis and before tumor progression), as well as initial and secondary progression periods, with progression defined according to measureable radiographic evidence of tumor progression. Resource categories used in the analysis include: Treatments (e.g., surgery, chemotherapy, radiotherapy, targeted therapies), hospitalizations and physician visits, diagnostic tests (biomarkers, imaging, laboratory tests). Comparisons between categories of resource utilization and tumor progression status were examined using univariate (by tumor site) and multivariate analyses (across all tumor sites). Fifty-five physicians were included in the study and completed online data extraction forms using the charts of 110 patients. The physician sample showed a relatively even distribution for those affiliated with academic versus community hospitals (46% vs 55%). Forty (36.3%) patients were reported to have pancreatic NET (pNET), while 70 (63.6%) patients had gastrointestinal tract (GI)/Lung as the primary NET site. Univariate analysis showed the proportion of patients hospitalized increased from 32.7% during baseline to 42.1% in the progression stages. While surgeries were performed at similar proportions overall at baseline and progression, pNET patients, were more likely than GI/Lung NET patients to have undergone surgery during the baseline (33.3% vs 25.0%) and any progression periods (26.7% vs 23.4%). While peptide-receptor radionuclide and targeted therapy utilization was low across NET types and tumor stages, GI/Lung types exhibited greater utilization of these technologies compared

  13. Investigation of radiomic signatures for local recurrence using primary tumor texture analysis in oropharyngeal head and neck cancer patients.

    Science.gov (United States)

    2018-01-24

    Radiomics is one such "big data" approach that applies advanced image refining/data characterization algorithms to generate imaging features that can quantitatively classify tumor phenotypes in a non-invasive manner. We hypothesize that certain textural features of oropharyngeal cancer (OPC) primary tumors will have statistically significant correlations to patient outcomes such as local control. Patients from an IRB-approved database dispositioned to (chemo)radiotherapy for locally advanced OPC were included in this retrospective series. Pretreatment contrast CT scans were extracted and radiomics-based analysis of gross tumor volume of the primary disease (GTVp) were performed using imaging biomarker explorer (IBEX) software that runs in Matlab platform. Data set was randomly divided into a training dataset and test and tuning holdback dataset. Machine learning methods were applied to yield a radiomic signature consisting of features with minimal overlap and maximum prognostic significance. The radiomic signature was adapted to discriminate patients, in concordance with other key clinical prognosticators. 465 patients were available for analysis. A signature composed of 2 radiomic features from pre-therapy imaging was derived, based on the Intensity Direct and Neighbor Intensity Difference methods. Analysis of resultant groupings showed robust discrimination of recurrence probability and Kaplan-Meier-estimated local control rate (LCR) differences between "favorable" and "unfavorable" clusters were noted.

  14. 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

  15. 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

  16. 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.

  17. Robotic partial nephrectomy for renal tumors larger than 4 cm: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Liangkuan Bi

    Full Text Available BACKGROUND: With the establishment of minimally invasive surgery in society, the robot has been increasingly widely used in the urologic field, including in partial nephrectomy. This study aimed to comprehensively summarize the currently available evidence on the feasibility and safety of robotic partial nephrectomy for renal tumors of >4 cm. METHOD AND FINDINGS: An electronic database search of PubMed, Scopus, Web of Science, and the Cochrane Library was performed. This systematic review and meta-analysis was based on all relevant studies that assessed robotic partial nephrectomy for renal tumors of >4 cm. Five studies were included. The meta-analysis involved 3 studies from 11 institutions including 154 patients, while the narrative review involved the remaining 2 studies from 5 institutions including 64 patients. In the meta-analysis, the mean ischemic time, operation time, and console time was 28, 319, and 189 minutes, respectively. The estimated blood loss and length of stay was 317 ml and 3.8 days, respectively. The rates of conversion, positive margins, intraoperative complications, postoperative complications, hilar clamping, and collecting system repair were 7.0%, 3.5%, 7.0%, 9.8%, 93.9%, and 47.5%, respectively. The narrative review showed results similar to those of the meta-analysis. CONCLUSIONS: Robotic partial nephrectomy is feasible and safe for renal tumors of >4 cm with an acceptable warm ischemic time, positive margin rate, conversion rate, complication rate, operation time, estimated blood loss, and length of stay.

  18. 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.

  19. Radiation therapy for malignant phyllodes tumor of the breast: An analysis of SEER data.

    Science.gov (United States)

    Kim, Yi-Jun; Kim, Kyubo

    2017-04-01

    Malignant phyllodes tumor of the breast (MPTB) accounts for less than 1% of whole breast neoplasm. Surgery is regarded as the primary treatment of choice in patients with MPTB, but the necessity of postoperative radiation therapy (RT) has been a subject of debate. Our aim was to evaluate effects of postoperative RT for MPTB using a large population database. Using the Surveillance, Epidemiology, and End Results Program (SEER) database (1983-2013), clinico-pathologic prognostic factors were evaluated. Postoperative RT, tumor extent, grade, and lymph node (LN) metastasis were included in the analysis. Univariate and multivariate Cox proportional hazards regressions were performed to evaluate prognostic power of variables on cancer specific survival (CSS). A total of 1974 patients with MPTB were reviewed. Of these, 825 (42%) and 1149 (58%) patients underwent mastectomy and breast conserving surgery (BCS), respectively. In each group, 130 (16%) and 122 (11%) patients received postoperative RT. For patients with adverse risk factors including high grade and large tumor size, postoperative RT was more likely to be performed. In multivariate analysis, age, ethnicity, tumor size, tumor extension and LN status were correlated with prognosis in mastectomy group, while postoperative RT did not affect CSS. In BCS group, age and grade were significant prognostic factors on CSS, meanwhile postoperative RT did not impact CSS in multivariate analysis. Although patients with more adverse prognostic factors underwent postoperative RT, RT groups were not inferior to non-RT group on CSS regardless of surgery (mastectomy or BCS). Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. 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.

  1. Prognostic significance of tumor-associated macrophages in solid tumor: a meta-analysis of the literature.

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    Qiong-wen Zhang

    Full Text Available PURPOSE: Tumor associated macrophages (TAMs are considered with the capacity to have both negative and positive effects on tumor growth. The prognostic value of TAM for survival in patients with solid tumor remains controversial. EXPERIMENTAL DESIGN: We conducted a meta-analysis of 55 studies (n = 8,692 patients that evaluated the correlation between TAM (detected by immunohistochemistry and clinical staging, overall survival (OS and disease free survival (DFS. The impact of M1 and M2 type TAM (n = 5 on survival was also examined. RESULTS: High density of TAM was significantly associated with late clinical staging in patients with breast cancer [risk ratio (RR  = 1.20 (95% confidence interval (CI, 1.14-1.28] and bladder cancer [RR = 3.30 (95%CI, 1.56-6.96] and with early clinical staging in patients with ovarian cancer [RR = 0.52 (95%CI, 0.35-0.77]. Negative effects of TAM on OS was shown in patients with gastric cancer [RR = 1.64 (95%CI, 1.24-2.16], breast cancer [RR = 8.62 (95%CI, 3.10-23.95], bladder cancer [RR = 5.00 (95%CI, 1.98-12.63], ovarian cancer [RR = 2.55 (95%CI, 1.60-4.06], oral cancer [RR = 2.03 (95%CI, 1.47-2.80] and thyroid cancer [RR = 2.72 (95%CI, 1.26-5.86],and positive effects was displayed in patients with colorectal cancer [RR = 0.64 (95%CI, 0.43-0.96]. No significant effect was showed between TAM and DFS. There was also no significant effect of two phenotypes of TAM on survival. CONCLUSIONS: Although some modest bias cannot be excluded, high density of TAM seems to be associated with worse OS in patients with gastric cancer, urogenital cancer and head and neck cancer, with better OS in patients with colorectal cancer.

  2. 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.

  3. AN ANALYSIS OF CLINICOPATHOLOGICAL AND SURGICAL OUTCOME IN SALIVARY GLAND TUMORS OF 178 PATIENTS OF TELANGANA

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    Boda

    2015-10-01

    with a s ensitivity of 63.48%. Facial nerve paralysis was reported in 3.37% and recurrence rate was more with pleomorphic adenomas 6.17%. CONCLUSIONS: The analysis of SGTs from this part of India showed the incidence was higher in females than males. Pleomorphic ad enoma was the commonest tumor observed in the present study. Parotid gland was involved in majority of the tumors followed by hard palate involving minor salivary glands. CT scan and MRI proved to be helpful in the diagnosis and determining the approach wi th a sensitivity of 63.48%. Primary excision of benign tumors resulted in low recurrence rate. Malignant tumors showed better results with surgery and RT combined. Incidence of Facial palsy following SGTs surgery was lowest reported from the center

  4. Nanostructures based on alumina hydroxides inhibit tumor growth

    Science.gov (United States)

    Fomenko, A. N.; Korovin, M. S.

    2017-09-01

    Nanoparticles and nanostructured materials are one of the most promising developments for cancer therapy. Gold nanoparticles, magnetic nanoparticles based on iron and its oxides and other metal oxides have been widely used in diagnosis and treatment of cancer. Much less research attention has been payed to nanoparticles and nanostructures based on aluminum oxides and hydroxides as materials for cancer diagnosis and treatment. However recent investigations have shown promising results regarding these objects. Here, we review the antitumor results obtained with AlOOH nanoparticles.

  5. Tumor size and invasiveness matters for partial nephrectomy: External validation and modification of the arterial based complexity score.

    Science.gov (United States)

    Kriegmair, Maximilian C; Hetjens, Svetlana; Mandel, Philipp; Wadle, Jula; Budjan, Johannes; Michel, Maurice S; Pfalzgraf, Daniel; Wagener, Nina

    2017-05-01

    Outcome of partial nephrectomy (PN) depends on anatomic features of the renal tumor, which can be assessed by nephrometry scores. The aim was to externally validate and refine the Arterial Based Complexity (ABC) score and to compare it to established systems. Tumors of 300 patients undergoing PN were categorized according to the ABC, RENAL, and PADUA score. Size and tumor invasiveness were combined to form the ABCD score. Correlation analysis and multivariate logistic regression was performed to validate and compare the respective scores as predictors of surgical outcome. The ABC score shows significant correlation with ischemia time (IT) (P < 0.01), opening of the collecting system (CS) (P < 0.01), and conversion to nephrectomy (P = 0.01). In the multivariate analysis, the ABC score was predictive for on-clamp excision (P < 0.01) and opening of the CS (P < 0.01) only. The RENAL and ABCD scores were independent predictors for complications (P = 0.02, P = 0.05), IT (P < 0.01, P = 0.03), on clamp excision (P < 0.01, P < 0.01), and opening of the CS (P < 0.01, P < 0.01). The ABC score correlates well with surgical parameters. Expanding the score by tumor diameter gives the ABCD system. It has similar predictive effectiveness to the well-established RENAL score, but features simplicity by only assessing invasiveness and tumor size. © 2017 Wiley Periodicals, Inc.

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

    Science.gov (United States)

    Klement, Rainer J.; Champ, Colin E.; Otto, Christoph; Kämmerer, Ulrike

    2016-01-01

    Background 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. Methods 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]). Conclusions 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. PMID:27159218

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

    Science.gov (United States)

    Klement, Rainer J; Champ, Colin E; Otto, Christoph; Kämmerer, Ulrike

    2016-01-01

    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.

  8. 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.

  9. 3D geometry-based quantification of colocalizations in multichannel 3D microscopy images of human soft tissue tumors.

    Science.gov (United States)

    Wörz, Stefan; Sander, Petra; Pfannmöller, Martin; Rieker, Ralf J; Joos, Stefan; Mechtersheimer, Gunhild; Boukamp, Petra; Lichter, Peter; Rohr, Karl

    2010-08-01

    We introduce a new model-based approach for automatic quantification of colocalizations in multichannel 3D microscopy images. The approach uses different 3D parametric intensity models in conjunction with a model fitting scheme to localize and quantify subcellular structures with high accuracy. The central idea is to determine colocalizations between different channels based on the estimated geometry of the subcellular structures as well as to differentiate between different types of colocalizations. A statistical analysis was performed to assess the significance of the determined colocalizations. This approach was used to successfully analyze about 500 three-channel 3D microscopy images of human soft tissue tumors and controls.

  10. Benign tumors and tumor-like lesions of the oral cavity and jaws: An analysis of 709 cases.

    Science.gov (United States)

    Kilinc, A; Saruhan, N; Gundogdu, B; Yalcin, E; Ertas, U; Urvasizoglu, G

    2017-11-01

    The purpose was to examine the prevalence, gender, age and site(s) of odontogenic and nonodontogenic benign tumors, and tumor-like lesions occurring in the oral cavity and jaws in a Turkish population, particularly, in the Eastern Turkey, and to compare findings of this study with other reports. The data were collected from the files of the Department of Oral and Maxillofacial Surgery and the Department of Oral Pathology, Ataturk University, Turkey, during a 10-year period from January 2005 to January 2015. They were analyzed descriptively regarding prevalence, age, sex, lesion type, and site. A total of 709 benign tumor and tumor-like lesions of the oral cavity, and jaws were selected during a period of 10 years. One hundred and twenty-one of these lesions (17%) were odontogenic benign tumors while 588 (83%) were nonodontogenic benign tumor and tumor-like lesions. This study revealed that the distribution and characteristics of benign tumors and tumor-like lesions of oral cavity and jaws in the Turkish population, particularly including the Eastern region of Turkey have some differences as well as similarities with the findings of studies in different populations.

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

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    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

  12. 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

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

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    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.

  14. 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.

  15. 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

  16. Optimizing a waveguide-based sandwich immunoassay for tumor biomarkers

    Energy Technology Data Exchange (ETDEWEB)

    Mukundan, Harshini [Los Alamos National Laboratory; Swanson, Basil I [Los Alamos National Laboratory; Xie, Hongzhi [Los Alamos National Laboratory; Anderson, Aaron S [Los Alamos National Laboratory; Grace, W Kevin [Los Alamos National Laboratory; Shively, John E [NON LANL

    2008-01-01

    The sensor team at the Los Alamos National Laboratory has developed a waveguide-based optical biosensor for the detection of biomarkers associated with the disease. We have previously demonstrated the application of this technology to the sensitive detection of carcinoembryonic antigen in serum and nipple aspirate fluid from breast cancer patients. In this publication, we report improvements to this technology that will facilitate transition to a point-of-care diagnostic system and/or robust research tool.

  17. 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

  18. Short-term temperature effect on the HRMAS spectra of human brain tumor biopsies and their pattern recognition analysis.

    Science.gov (United States)

    Valverde-Saubí, Daniel; Candiota, Ana Paula; Molins, Maria Antònia; Feliz, Miguel; Godino, Oscar; Dávila, Myriam; Acebes, Juan José; Arús, Carles

    2010-09-01

    To investigate the effect of temperature (0 versus 37 degrees C) in the high-resolution magic angle spinning spectroscopy (HRMAS) pattern of human brain tumor biopsies and its influence in recognition-based tumor type prediction. This proof-of-principle study addressed the bilateral discrimination between meningioma (MM) and glioblastoma multiforme (GBM) cases. Forty-three tumor biopsy samples were collected (20 MM and 23 GBM), kept frozen and later analyzed at 0 degrees C and 37 degrees C by HRMAS. Post-HRMAS histopathology was used to validate the tumor type. Time-course experiments (100 min) at both temperatures were carried out to monitor HRMAS pattern changes. Principal component analysis and linear discriminant analysis were used for classifier development with a training set of 20 biopsies. Temperature-dependent, spectral pattern changes mostly affected mobile lipids and choline-containing compounds resonances and were essentially reversible. Incubation of 3 MM and 3 GBM at 37 degrees C during 100 minutes produced irreversible pattern changes below 13% in a few resonances. Classification performance of an independent test set of 7 biopsies was 100% for the pulse-and-acquire, CPMG at echo times (TE) of 30 ms and 144 ms and Hahn Echo at TE 30 ms at 0 degrees C and 37 degrees C. The performance for Hahn Echo spectra at 136 ms was 83.3% at 0 degrees C and 100% at 37 degrees C. The spectral pattern of mobile lipids changes reversibly with temperature. HRMAS demonstrated potential for automated brain tumor biopsy classification. No advantage was obtained when acquiring spectra at 37 degrees C with respect to 0 degrees C in most of the conditions used for the discrimination addressed.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  20. 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.

  1. 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

  2. A meta-analysis of prognostic value of KIT mutation status in gastrointestinal stromal tumors

    Directory of Open Access Journals (Sweden)

    Jiang Z

    2016-06-01

    Full Text Available Zhiqiang Jiang, Jian Zhang, Zhi Li, Yingjun Liu, Daohai Wang, Guangsen Han Department of General Surgery, Affiliated Tumor Hospital, Zhengzhou University, Zhengzhou, People’s Republic of China Abstract: Numerous types of KIT mutations have been reported in gastrointestinal stromal tumors (GISTs; however, controversy still exists regarding their clinicopathological significance. In this study, we reviewed the publicly available literature to assess the data by a meta-analysis to characterize KIT mutations and different types of KIT mutations in prognostic prediction in patients with GISTs. Twenty-eight studies that included 4,449 patients were identified and analyzed. We found that KIT mutation status was closely correlated with size of tumors and different mitosis indexes, but not with tumor location. KIT mutation was also observed to be significantly correlated with tumor recurrence, metastasis, as well as the overall survival of patients. Interestingly, there was higher risk of progression in KIT exon 9-mutated patients than in exon 11-mutated patients. Five-year relapse-free survival (RFS rate was significantly higher in KIT exon 11-deleted patients than in those with other types of KIT exon 11 mutations. In addition, RFS for 5 years was significantly worse in patients bearing KIT codon 557–558 deletions than in those bearing other KIT exon 11 deletions. Our results strongly support the hypothesis that KIT mutation status is another evaluable factor for prognosis prediction in GISTs. Keywords: KIT, meta-analysis, prognosis, marker, therapy

  3. Treatment of malignant tumors of the skull base with multi-session radiosurgery

    Directory of Open Access Journals (Sweden)

    Gagnon Gregory J

    2009-04-01

    Full Text Available Abstract Objective Malignant tumors that involve the skull base pose significant challenges to the clinician because of the proximity of critical neurovascular structures and limited effectiveness of surgical resection without major morbidity. The purpose of this study was to evaluate the efficacy and safety of multi-session radiosurgery in patients with malignancies of the skull base. Methods Clinical and radiographic data for 37 patients treated with image-guided, multi-session radiosurgery between January 2002 and December 2007 were reviewed retrospectively. Lesions were classified according to involvement with the bones of the base of the skull and proximity to the cranial nerves. Results Our cohort consisted of 37 patients. Six patients with follow-up periods less than four weeks were eliminated from statistical consideration, thus leaving the data from 31 patients to be analyzed. The median follow-up was 37 weeks. Ten patients (32% were alive at the end of the follow-up period. At last follow-up, or the time of death from systemic disease, tumor regression or stable local disease was observed in 23 lesions, representing an overall tumor control rate of 74%. For the remainder of lesions, the median time to progression was 24 weeks. The median progression-free survival was 230 weeks. The median overall survival was 39 weeks. In the absence of tumor progression, there were no cranial nerve, brainstem or vascular complications referable specifically to CyberKnife® radiosurgery. Conclusion Our experience suggests that multi-session radiosurgery for the treatment of malignant skull base tumors is comparable to other radiosurgical techniques in progression-free survival, local tumor control, and adverse effects.

  4. 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.

  5. [Craniofacial resection for tumors of paranasal sinuses involving the anterior skull base].

    Science.gov (United States)

    Burduk, Paweł K; Kaźmierczak, Wojciech; Dalke, Krzysztof; Beuth, Wojciech; Siedlecki, Zygmunt; Prywiński, Maciej

    2012-01-01

    Craniofacial resection is a treatment of choice for paranasal malignant and benign tumors invading the skull base. In this article the authors present the experience in craniofacial resection for malignant tumors invading the anterior skull base. The material consisted of four patients operated in the Department of Otolaryngology and Laryngology Oncology CM UMK between 2007 and 2010. The patients were treated for malignant neoplasms of the paranasal sinuses with anterior skull base involvement. THe age range of the group were between 60 and 75 years. Of these patients three were females and one male. We performed a lateral rhinotomy for laryngological acces for the tumor. The neurosurgeon performed anterior skull base osteotomy at and appropriate site above. The patients recovered uneventfully. The follow up period ranged between 13 and 42 months. The overall 3-year survival for all patients in our series was 66,6%. Combined craniofacial resection of tumors of the anterior skull base is an effective approach for the management of these pathologies. This type of approach in elderly patients over 70 years old could be associated with increased mortality and complications leading to poorer outcome.

  6. Radiological classification of renal angiomyolipomas based on 127 tumors

    Directory of Open Access Journals (Sweden)

    Prando Adilson

    2003-01-01

    Full Text Available PURPOSE: Demonstrate radiological findings of 127 angiomyolipomas (AMLs and propose a classification based on the radiological evidence of fat. MATERIALS AND METHODS: The imaging findings of 85 consecutive patients with AMLs: isolated (n = 73, multiple without tuberous sclerosis (TS (n = 4 and multiple with TS (n = 8, were retrospectively reviewed. Eighteen AMLs (14% presented with hemorrhage. All patients were submitted to a dedicated helical CT or magnetic resonance studies. All hemorrhagic and non-hemorrhagic lesions were grouped together since our objective was to analyze the presence of detectable fat. Out of 85 patients, 53 were monitored and 32 were treated surgically due to large perirenal component (n = 13, hemorrhage (n = 11 and impossibility of an adequate preoperative characterization (n = 8. There was not a case of renal cell carcinoma (RCC with fat component in this group of patients. RESULTS: Based on the presence and amount of detectable fat within the lesion, AMLs were classified in 4 distinct radiological patterns: Pattern-I, predominantly fatty (usually less than 2 cm in diameter and intrarenal: 54%; Pattern-II, partially fatty (intrarenal or exophytic: 29%; Pattern-III, minimally fatty (most exophytic and perirenal: 11%; and Pattern-IV, without fat (most exophytic and perirenal: 6%. CONCLUSIONS: This proposed classification might be useful to understand the imaging manifestations of AMLs, their differential diagnosis and determine when further radiological evaluation would be necessary. Small (< 1.5 cm, pattern-I AMLs tend to be intra-renal, homogeneous and predominantly fatty. As they grow they tend to be partially or completely exophytic and heterogeneous (patterns II and III. The rare pattern-IV AMLs, however, can be small or large, intra-renal or exophytic but are always homogeneous and hyperdense mass. Since no renal cell carcinoma was found in our series, from an evidence-based practice, all renal mass with detectable

  7. 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

  8. Measuring multiple parameters of CD8+ tumor-infiltrating lymphocytes in human cancers by image analysis.

    Science.gov (United States)

    Steele, Keith E; Tan, Tze Heng; Korn, René; Dacosta, Karma; Brown, Charles; Kuziora, Michael; Zimmermann, Johannes; Laffin, Brian; Widmaier, Moritz; Rognoni, Lorenz; Cardenes, Ruben; Schneider, Katrin; Boutrin, Anmarie; Martin, Philip; Zha, Jiping; Wiestler, Tobias

    2018-03-06

    Immuno-oncology and cancer immunotherapies are areas of intense research. The numbers and locations of CD8+ tumor-infiltrating lymphocytes (TILs) are important measures of the immune response to cancer with prognostic, pharmacodynamic, and predictive potential. We describe the development, validation, and application of advanced image analysis methods to characterize multiple immunohistochemistry-derived CD8 parameters in clinical and nonclinical tumor tissues. Commercial resection tumors from nine cancer types, and paired screening/on-drug biopsies of non-small-cell lung carcinoma (NSCLC) patients enrolled in a phase 1/2 clinical trial investigating the PD-L1 antibody therapy durvalumab (NCT01693562), were immunostained for CD8. Additional NCT01693562 samples were immunostained with a CD8/PD-L1 dual immunohistochemistry assay. Whole-slide scanning was performed, tumor regions were annotated by a pathologist, and images were analyzed with customized algorithms using Definiens Developer XD software. Validation of image analysis data used cell-by-cell comparison to pathologist scoring across a range of CD8+ TIL densities of all nine cancers, relying primarily on 95% confidence in having at least moderate agreement regarding Lin concordance correlation coefficient (CCC = 0.88-0.99, CCC_lower = 0.65-0.96). We found substantial variability in CD8+ TILs between individual patients and across the nine types of human cancer. Diffuse large B-cell lymphoma had several-fold more CD8+ TILs than some other cancers. TIL densities were significantly higher in the invasive margin versus tumor center for carcinomas of head and neck, kidney and pancreas, and NSCLC; the reverse was true only for prostate cancer. In paired patient biopsies, there were significantly increased CD8+ TILs 6 weeks after onset of durvalumab therapy (mean of 365 cells/mm 2 over baseline; P = 0.009), consistent with immune activation. Image analysis accurately enumerated CD8+ TILs in PD-L1

  9. Oral mucositis in patients treated with chemotherapy for solid tumors: a retrospective analysis of 150 cases

    NARCIS (Netherlands)

    Raber-Durlacher, J. E.; Weijl, N. I.; Abu Saris, M.; de Koning, B.; Zwinderman, A. H.; Osanto, S.

    2000-01-01

    The incidence and the severity of chemotherapy-associated oral mucositis were determined in a retrospective analysis of 150 patients with various solid tumors. In addition, possible risk factors for the development of mucositis were identified. Patients were treated with chemotherapeutic regimens

  10. 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

    : 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...

  11. Long-term tumor control after brachytherapy for base-of-prostate cancer

    Directory of Open Access Journals (Sweden)

    Seungtaek Choi

    2011-12-01

    Full Text Available Purpose: To evaluate the outcomes of patients presenting with cancer at the base of the prostate after brachytherapyas monotherapy. Material and methods: We retrospectively reviewed the medical records of all patients who had undergone transpe -ri neal ultrasound-guided implantation with 125I or 103Pd seeds as monotherapy between March 1998 and December2006, at our institution. A minimum follow-up interval of 2 years was required for inclusion in our analysis. Dosimetrywas assessed using computed tomography 30 days after the implant. Treatment failure was defined as the appearanceof biopsy-proved tumor after seed implantation, radiographic evidence of metastases, receipt of salvage therapy,or elevation of the prostate-specific antigen level beyond the nadir value plus 2 ng/mL. Results: With a median follow-up interval of 89 months (range 25-128 months, all 52 of the identified patients hadno evidence of disease progression or biochemical failure. The mean number of cores sampled at the prostate base was2.84 (median 2; Gleason scores assigned at central review were 6-8 in all patients. Of the 30 patients (58% for whomdosimetric data were available at day 30, the median V100 values of the right and left base were 92.0% and 93.5%, respectively,and the median D90 values of the right and left base were 148 Gy and 151 Gy, respectively. Conclusion: Permanent prostate brachytherapy as monotherapy results in a high probability of disease-free survivalfor men with cancer at the base of the prostate.

  12. 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.

  13. Thrombocytopenia and craniotomy for tumor: A National Surgical Quality Improvement Program analysis.

    Science.gov (United States)

    Dasenbrock, Hormuzdiyar H; Devine, Christopher A; Liu, Kevin X; Gormley, William B; Claus, Elizabeth B; Smith, Timothy R; Dunn, Ian F

    2016-06-01

    To the authors' knowledge, the current study is the first national analysis of the association between preoperative platelet count and outcomes after craniotomy. Patients who underwent craniotomy for tumor were extracted from the prospective National Surgical Quality Improvement Program registry (2007-2014) and stratified by preoperative thrombocytopenia, defined as mild (125,000-149,000/μL), moderate (100,000-124,000/μL), severe (75,000-99,000/μL), or very severe (craniotomy for tumor. Cancer 2016;122:1708-17. © 2016 American Cancer Society. © 2016 American Cancer Society.

  14. 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.

  15. Locally linear representation Fisher criterion based tumor gene expressive data classification.

    Science.gov (United States)

    Li, Bo; Tian, Bei-Bei; Zhang, Xiao-Long; Zhang, Xiao-Ping

    2014-10-01

    Tumor gene expressive data are characterized by a large amount of genes with only a small amount of observations, which always appear with high dimensionality. So it is necessary to reduce the dimensionality before identifying their genre. In this paper, a discriminant manifold learning method, named locally linear representation Fisher criterion (LLRFC), is applied to extract features from tumor gene expressive data. In LLRFC, an inter-class graph and an intra-class graph are constructed based on their genre information, where any tumor gene expressive data in the inter-class graph should select k nearest neighbors with different class labels and in the intra-class graph the k nearest neighbors for any tumor gene expressive data must be sampled from those with the same class. And then the locally least linear reconstruction is introduced to optimize the corresponding weights in both graphs. Moreover, a Fisher criterion is modeled to explore a low dimensional subspace where the reconstruction errors in the inter-class graph can be maximized and the reconstruction errors in the intra-class graph can be minimized, simultaneously. Experiments on some benchmark tumor gene expressive data have been conducted with some related algorithms, by which the proposed LLRFC has been validated to be efficient. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Nanotechnology-Based Strategies for Early Cancer Diagnosis Using Circulating Tumor Cells as a Liquid Biopsy.

    Science.gov (United States)

    Huang, Qinqin; Wang, Yin; Chen, Xingxiang; Wang, Yimeng; Li, Zhiqiang; Du, Shiming; Wang, Lianrong; Chen, Shi

    2018-01-01

    Circulating tumor cells (CTCs) are cancer cells that shed from a primary tumor and circulate in the bloodstream. As a form of "tumor liquid biopsy", CTCs provide important information for the mechanistic investigation of cancer metastasis and the measurement of tumor genotype evolution during treatment and disease progression. However, the extremely low abundance of CTCs in the peripheral blood and the heterogeneity of CTCs make their isolation and characterization major technological challenges. Recently, nanotechnologies have been developed for sensitive CTC detection; such technologies will enable better cell and molecular characterization and open up a wide range of clinical applications, including early disease detection and evaluation of treatment response and disease progression. In this review, we summarize the nanotechnology-based strategies for CTC isolation, including representative nanomaterials (such as magnetic nanoparticles, gold nanoparticles, silicon nanopillars, nanowires, nanopillars, carbon nanotubes, dendrimers, quantum dots, and graphene oxide) and microfluidic chip technologies that incorporate nanoroughened surfaces and discuss their key challenges and perspectives in CTC downstream analyses, such as protein expression and genetic mutations that may reflect tumor aggressiveness and patient outcome.

  17. Fiber-based time-resolved fluorescence and phosphorescence spectroscopy of tumors

    Science.gov (United States)

    Shirmanova, M.; Lukina, M.; Orlova, A.; Studier, H.; Zagaynova, E.; Becker, W.; Shcheslavskiy, V.

    2017-07-01

    The study of metabolic and oxygen states of cells in a tumor in vivo is crucial for understanding of the mechanisms responsible for the tumor development and provides background for the relevant tumor's treatment. Here, we show that a specially designed implantable fiber-optical 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 nicotinamid adenine dinucleotide (NAD(P)H) and phosphorescence lifetime of an oxygen sensor based on iridium (III) complex of enzothienylpyridine (BTPDM1) are explored both in model experiment in solutions, and in living mice. The luminescence spectroscopy data is substantiated with immunohistochemistry experiments. To the best of our knowledge, the measurements of both metabolic status and oxygenation of tumor in vivo by fluorescence/phosphorescence lifetime spectroscopy with a fiber-optic probe are done for the first time.

  18. KRAS mutational status analysis of peripheral blood isolated circulating tumor cells in metastatic colorectal patients

    OpenAIRE

    GUTI?RREZ, CRISTINA; RODRIGUEZ, JAVIER; PATI?O-GARC?A, ANA; GARC?A-FONCILLAS, JES?S; SALGADO, JOSEFA

    2013-01-01

    The present study describes an optimized method for isolating peripheral blood circulating tumor cells (CTCs) and performing KRAS mutation analysis. The approach combines isolation of peripheral blood mononuclear cells and immunomagnetic labeling with CD45 and CD326 human microbeads with KRAS analysis performed with a Therascreen KRAS kit by quantitative PCR. KRAS mutations were detected in the CTCs of patients with metastatic colorectal cancer (mCRC). CTCs may represent an alternative to inv...

  19. 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

  20. 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<.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

  1. 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.)

  2. 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.)

  3. 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.

  4. 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...... skull base meningiomas and 55 patients treated with FSRT for pituitary adenomas between January 1999 and December 2009 with at least 2 years follow-up were included. Patients were followed up prospectively with magnetic resonance imaging scans, visual acuity and visual field examinations. RION was found...... in four (10%) patients with anterior skull base meningiomas and seven patients (13%) with pituitary adenomas. The five-year actuarial freedom from 25% RION visual field loss was 94% following FSRT. Actuarial 2-, 5- and 10-year tumor control rates were 100, 88.4 and 64.5% for anterior skull base...

  5. Straight sinus: ultrastructural analysis aimed at surgical tumor resection.

    Science.gov (United States)

    Amato, Marcelo Campos Moraes; Tirapelli, Luis Fernando; Carlotti, Carlos Gilberto; Colli, Benedicto Oscar

    2016-08-01

    OBJECTIVE Accurate knowledge of the anatomy of the straight sinus (SS) is relevant for surgical purposes. During one surgical procedure involving the removal of part of the SS wall, the authors observed that the venous blood flow was maintained in the SS, possibly through a vein-like structure within the dural sinus or dural multiple layers. This observation and its divergence from descriptions of the histological features of the SS walls motivated the present study. The authors aimed to investigate whether it is possible to dissect the SS walls while keeping the lumen intact, and to describe the histological and ultrastructural composition of the SS wall. METHODS A total of 22 cadaveric specimens were used. The SS was divided into three portions: anterior, middle, and posterior. The characteristics of the SS walls were analyzed, and the feasibility of dissecting them while keeping the SS lumen intact was assessed. The thickness and the number of collagen fibers and other tissues in the SS walls were compared with the same variables in other venous sinuses. Masson's trichrome and Verhoeff's stains were used to assess collagen and elastic fibers, respectively. The data were analyzed using Zeiss image analysis software (KS400). RESULTS A vein-like structure independent of the SS walls was found in at least one of the portions of the SS in 8 of 22 samples (36.36%). The inferior wall could be delaminated in at least one portion in 21 of 22 samples (95.45%), whereas the lateral walls could seldom be delaminated. The inferior wall of the SS was thicker (p < 0.05) and exhibited less collagen and greater amounts of other tissues-including elastic fibers, connective tissue, blood vessels, and nerve fibers (p < 0.05)-compared with the lateral walls. Transmission electron microscopy revealed the presence of muscle fibers at a level deeper than that of the subendothelial connective tissue in the inferior wall of the SS, extending from its junction with the great cerebral vein

  6. Analysis of Contractility and Invasion Potential of Two Canine Mammary Tumor Cell Lines

    Directory of Open Access Journals (Sweden)

    Kaisa Rajakylä

    2017-09-01

    Full Text Available Cancer cells are surrounded by a mechanically and biochemically distinct microenvironment that undergoes dynamic changes throughout the neoplastic progression. During this progression, some cancer cells acquire abnormal characteristics that potentiate their escape from the primary tumor site, to establish secondary tumors in distant organs. Recent studies with several human cancer cell lines have shown that the altered physical properties of tumor cells, such as their ability to apply high traction forces to the surroundings, are directly linked with their potential to invade and metastasize. To test the hypothetical interconnection between actomyosin-mediated traction forces and invasion potential within 3D-microenvironment, we utilized two canine mammary tumor cell lines with different contractile properties. These cell lines, canine mammary tumor (CMT-U27 and CMT-U309, were found to have distinct expression patterns of lineage-specific markers and organization of actin-based structures. In particular, CMT-U309 carcinoma cells were typified by thick contractile actomyosin bundles that exerted high forces to their environment, as measured by traction force microscopy. These high contractile forces also correlated with the prominent invasiveness of the CMT-U309 cell line. Furthermore, we found high contractility and 3D-invasion potential to be dependent on the activity of 5′AMP-activated protein kinase (AMPK, as blocking AMPK signaling was found to reverse both of these features. Taken together, our findings implicate that actomyosin forces correlate with the invasion potential of the studied cell lines.

  7. 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

  8. 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...

  9. Gamma knife radiosurgery for glomus jugulare tumors: therapeutic advantages of minimalism in the skull base.

    Science.gov (United States)

    Sharma, Manish S; Gupta, A; Kale, S S; Agrawal, D; Mahapatra, A K; Sharma, B S

    2008-01-01

    Glomus jugulare (GJ) tumors are paragangliomas found in the region of the jugular foramen. Surgery with/without embolization and conventional radiotherapy has been the traditional management option. To analyze the efficacy of gamma knife radiosurgery (GKS) as a primary or an adjunctive form of therapy. A retrospective analysis of patients who received GKS at a tertiary neurosurgical center was performed. Of the 1601 patients who underwent GKS from 1997 to 2006, 24 patients with GJ underwent 25 procedures. The average age of the cohort was 46.6 years (range, 22-76 years) and the male to female ratio was 1:2. The most common neurological deficit was IX, X, XI cranial nerve paresis (15/24). Fifteen patients received primary GKS. Mean tumor size was 8.7 cc (range 1.1-17.2 cc). The coverage achieved was 93.1% (range 90-97%) using a mean tumor margin dose of 16.4 Gy (range 12-25 Gy) at a mean isodose of 49.5% (range 45-50%). Thirteen patients (six primary and seven secondary) were available for follow-up at a median interval of 24 months (range seven to 48 months). The average tumor size was 7.9 cc (range 1.1-17.2 cc). Using a mean tumor margin dose of 16.3 Gy (range 12-20 Gy) 93.6% coverage (range 91-97%) was achieved. Six patients improved clinically. A single patient developed transient trigeminal neuralgia. Magnetic resonance imaging follow-up was available for 10 patients; seven recorded a decrease in size. There was no tumor progression. Gamma knife radiosurgery is a safe and effective primary and secondary modality of treatment for GJ.

  10. 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

  11. Prognostic value of high IMP3 expression in solid tumors: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Chen L

    2017-06-01

    Full Text Available Luyao Chen,1,2,* Yongpeng Xie,3,* Xintao Li,1 Liangyou Gu,1 Yu Gao,1 Lu Tang,1 Jianwen Chen,1 Xu Zhang1 1Department of Urology, Chinese PLA General Hospital, Beijing, 2Department of Urology, First Affiliated Hospital of Nanchang University, Nanchang; 3School of Medicine, Nankai University, Tianjin, People’s Republic of China *These authors contributed equally to this work Background: Accumulated studies have investigated the prognostic role of insulin-like growth factor II mRNA-binding protein 3 (IMP3 in various cancers, but inconsistent and controversial results were obtained. Therefore, we performed a systematic review and meta-analysis to investigate the potential value of IMP3 in the prognostic prediction of human solid tumors. Materials and methods: A systematic literature search in the electronic databases PubMed, Embase, Web of Science, and Cochrane library (updated to April 2016 was conducted to identify eligible studies. Pooled hazard ratios (HRs with 95% confidence intervals (CIs for survival outcomes were calculated and gathered using STATA 12.0 software. Results: A total of 53 studies containing 8,937 patients with solid tumors were included in this meta-analysis. High IMP3 expression was significantly associated with worse overall survival (OS of solid tumors (HR =2.08, 95% CI: 1.80–2.42, P<0.001. Similar results were observed in cancer-specific survival (CSS, disease-free survival (DFS, recurrence-free survival (RFS, progression-free survival (PFS, and metastasis-free survival (MFS. Further subgroup analysis stratified by tumor type showed that elevated IMP3 expression was associated with poor OS in renal cell carcinoma (RCC, lung cancer, oral cancer, urothelial carcinoma, hepatocellular carcinoma (HCC, colorectal cancer, pancreatic cancer, gastric cancer, and intrahepatic cholangiocarcinoma (ICC. Conclusion: The current evidence suggests that high IMP3 expression is associated with poor prognosis in most solid tumors. IMP3 is

  12. 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.

  13. [Association rules analysis of Fufang Kushen injection in combination with traditional Chinese medicine or modern medications in treating malignant tumor: real-world retrospective study].

    Science.gov (United States)

    Zhang, Yin; Xie, Yan-Ming; Chen, Cen; Zhang, Chang; Zhuang, Yan

    2017-01-01

    Fufang Kushen injection is used in real world clinical situations to treat different types of malignant tumors. The present study aimed to analyze the association rules of Fufang Kushen injection in combination with other traditional Chinese medicine(TCM) or modern medications in treating malignant tumors based on the electrical medical records extracted from real-world hospital information system. This real world retrospective analysis was based on the clinicians' prescriptions regarding to such treatment by combined TCM and modern medications. Hospital information system data from 22 hospitals, including electrical medical records of 44 588 patients with malignant tumors and Fufang Kushen injection were included in this study, providing useful reference for the development of clinical treatment ideas, and providing reference for clinical rational use of Fufang Kushen injection. High correlation and causal relations were not present in this study, so further exploration and analysis were still needed for the conclusion. Copyright© by the Chinese Pharmaceutical Association.

  14. 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

  15. Concomitant analysis of salivary tumor markers--a new diagnostic tool for oral cancer.

    Science.gov (United States)

    Nagler, Rafael; Bahar, Gideon; Shpitzer, Thomas; Feinmesser, Raphael

    2006-07-01

    Oral squamous cell carcinoma (OSCC) is a common human malignancy. Circulatory epithelial tumor markers were previously investigated in the serum of OSCC patients but almost never in their saliva, in spite of the fact that there is a direct contact between the saliva and the oral cancer lesion. The purpose of the current study was to examine tumor markers in the saliva of OSCC patients. We measured the concentrations of the six most studied epithelial serum circulatory tumor markers in the saliva of OSCC (tongue) patients. Significant increases (of 400%) in salivary concentrations of Cyfra 21-1, tissue polypeptide antigen, and CA125 were shown. Salivary concentrations of CA19-9, SCC, and carcinoembryonic antigen were increased without statistical significance. A concurrent analysis of the three significantly increased markers revealed sensitivity, specificity, and negative and positive predictive values of 71%, 75%, 71%, and 75%, respectively. The increase reported in salivary tumor markers may be used as a diagnostic tool, especially when a concurrent analysis for significantly increased markers is done. Salivary testing is noninvasive, making it an attractive, effective alternative to serum testing, and the possibility of developing home testing kits would further facilitate it as a diagnostic aid, enabling patients to monitor their own health at home and is important for those who live far from their treatment centers and especially for those at risk of developing OSCC.

  16. Comprehensive prognostic analysis in breast cancer integrating clinical, tumoral, micro-environmental and immunohistochemical criteria.

    Science.gov (United States)

    de Mascarel, Isabelle; Debled, Marc; Brouste, Véronique; Mauriac, Louis; Sierankowski, Ghislaine; Velasco, Valérie; Croce, Sabrina; Chibon, Frédéric; Boudeau, Jêrome; Debant, Anne; MacGrogan, Gaëtan

    2015-01-01

    Significant morphological, clinical and biological prognostic factors vary according to molecular subtypes of breast tumors, yet comprehensive analysis of such factors linked to survival in each group is lacking. Clinicopathological and micro-environmental criteria, estrogen (ER), progesterone (PR) receptors, HER2, Ki67, basal markers, CD24, CD44, ALDH1, BCL2, E-Cadherin and Trio were assessed in 1070 primary operable breast cancers from a single center according to five main molecular subtypes and associations with distant metastasis-free survival (DMFS) were examined. There were 682 (64 %) luminal A (LA), 166 (16 %) Luminal B HER2 negative (LBH-), 47 (4 %) Luminal B HER2 positive (LBH+), 108 (10 %) triple negative (TN) and 67 (6 %) HER2-enriched tumors (H2+). Median follow-up was 13.7 years. At 5 years, DMFS in LA (90 %) was better than in LBH- (80.9 %), hazard ratio (HR) = 2.22 [1.44-3.43] P analysis, factors associated with shorter DMFS varied according to molecular subtype, with tumor size being associated with shorter DMFS in the LBH-, LBH+ and TN groups and the Rho GEF Trio and BCL2 phenotypes in TN tumors only. These findings help to define new clinicophenotypic models and to identify new therapeutic strategies in the specific molecular subgroups.

  17. Predicting outcomes in glioblastoma patients using computerized analysis of tumor shape: preliminary data

    Science.gov (United States)

    Mazurowski, Maciej A.; Czarnek, Nicholas M.; Collins, Leslie M.; Peters, Katherine B.; Clark, Kal

    2016-03-01

    Glioblastoma (GBM) is the most common primary brain tumor characterized by very poor survival. However, while some patients survive only a few months, some might live for multiple years. Accurate prognosis of survival and stratification of patients allows for making more personalized treatment decisions and moves treatment of GBM one step closer toward the paradigm of precision medicine. While some molecular biomarkers are being investigated, medical imaging remains significantly underutilized for prognostication in GBM. In this study, we investigated whether computer analysis of tumor shape can contribute toward accurate prognosis of outcomes. Specifically, we implemented applied computer algorithms to extract 5 shape features from magnetic resonance imaging (MRI) for 22 GBM patients. Then, we determined whether each one of the features can accurately distinguish between patients with good and poor outcomes. We found that that one of the 5 analyzed features showed prognostic value of survival. The prognostic feature describes how well the 3D tumor shape fills its minimum bounding ellipsoid. Specifically, for low values (less or equal than the median) the proportion of patients that survived more than a year was 27% while for high values (higher than median) the proportion of patients with survival of more than 1 year was 82%. The difference was statistically significant (p < 0.05) even though the number of patients analyzed in this pilot study was low. We concluded that computerized, 3D analysis of tumor shape in MRI may strongly contribute to accurate prognostication and stratification of patients for therapy in GBM.

  18. 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.

  19. Can Pharmacological Receptor Tyrosine Kinase Inhibitors Sensitize Poor Outcome Breast Tumors to Immune-Based Therapies?

    Directory of Open Access Journals (Sweden)

    Josie eUrsini-Siegel

    2013-02-01

    Full Text Available Receptor tyrosine kinases are known to drive breast cancer progression, particularly in HER2 and basal tumors, the two worst prognosis subtypes. Tumour cells recruit host stromal components, including immune cells, which strongly influence disease progression. This has been studied in human breast cancer and translated to murine models of breast cancer. Stromal immune components including cytotoxic T lymphocytes (CTL and natural killer (NK cells, destroy cancer cells through a process termed immune surveillance. Unfortunately, clinically-detectable tumors escape these immune protective effects through their ability to limit the infiltration, activation and/or survival of CTLs in breast tumors. The immunosuppressed state of established tumors limits the success rate of immune-based therapies, and possibly other therapeutic modalities that depend on host immunity. Published studies demonstrate that receptor tyrosine kinases (RTK facilitate breast cancer progression, in part, by establishing immune suppression. This raises the intriguing possibility that pharmacological RTK inhibitors may be exploited to sensitize breast cancer patients to immune-based therapies.

  20. Malignant sweat gland tumor presenting as an unusual dural-based lesion: case report.

    Science.gov (United States)

    Lee, Jung-Shun; Chang, Kung-Chao; Chen, Hsing-Hong; Sze, Chun-I

    2010-09-01

    Malignant sweat gland tumors are rare neoplasms with high recurrence and metastasis rates of over 50%. Clinically, they are often either not diagnosed or diagnosed improperly and are encountered as a histological surprise. Herein, we report a 50-year-old woman who suffered from chronic headaches and a left-side limping gait. Magnetic resonance imaging revealed a T1 and T2 heterogeneous intense dural-based lesion at right-frontal convexity. The pathological diagnosis of papillary meningioma was rendered at the time. Because there was no evidence of residual tumor, tumor recurrence, or distant metastases during the three-year follow-up, the clinician believed questioning the initial diagnosis was warranted. After pathological review, the final diagnosis was low-grade hidradenocarcinoma. A review of the literature suggests this is the first reported case of dural-based hidradenocarcinoma with local brain invasion. Given the lack of scalp or skull bone involvement, we speculated that the tumor may have arisen from ectopic sweat gland cells entrapped in the dural mater.

  1. 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.

  2. 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.

  3. 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.

  4. Local curvature analysis for classifying breast tumors: Preliminary analysis in dedicated breast CT

    International Nuclear Information System (INIS)

    Lee, Juhun; Nishikawa, Robert M.; Reiser, Ingrid; Boone, John M.; Lindfors, Karen K.

    2015-01-01

    Purpose: The purpose of this study is to measure the effectiveness of local curvature measures as novel image features for classifying breast tumors. Methods: A total of 119 breast lesions from 104 noncontrast dedicated breast computed tomography images of women were used in this study. Volumetric segmentation was done using a seed-based segmentation algorithm and then a triangulated surface was extracted from the resulting segmentation. Total, mean, and Gaussian curvatures were then computed. Normalized curvatures were used as classification features. In addition, traditional image features were also extracted and a forward feature selection scheme was used to select the optimal feature set. Logistic regression was used as a classifier and leave-one-out cross-validation was utilized to evaluate the classification performances of the features. The area under the receiver operating characteristic curve (AUC, area under curve) was used as a figure of merit. Results: Among curvature measures, the normalized total curvature (C T ) showed the best classification performance (AUC of 0.74), while the others showed no classification power individually. Five traditional image features (two shape, two margin, and one texture descriptors) were selected via the feature selection scheme and its resulting classifier achieved an AUC of 0.83. Among those five features, the radial gradient index (RGI), which is a margin descriptor, showed the best classification performance (AUC of 0.73). A classifier combining RGI and C T yielded an AUC of 0.81, which showed similar performance (i.e., no statistically significant difference) to the classifier with the above five traditional image features. Additional comparisons in AUC values between classifiers using different combinations of traditional image features and C T were conducted. The results showed that C T was able to replace the other four image features for the classification task. Conclusions: The normalized curvature measure

  5. Local curvature analysis for classifying breast tumors: Preliminary analysis in dedicated breast CT

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Juhun, E-mail: leej15@upmc.edu; Nishikawa, Robert M. [Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213 (United States); Reiser, Ingrid [Department of Radiology, University of Chicago, Chicago, Illinois 60637 (United States); Boone, John M.; Lindfors, Karen K. [Department of Radiology, University of California Davis Medical Center, Sacramento, California 95817 (United States)

    2015-09-15

    Purpose: The purpose of this study is to measure the effectiveness of local curvature measures as novel image features for classifying breast tumors. Methods: A total of 119 breast lesions from 104 noncontrast dedicated breast computed tomography images of women were used in this study. Volumetric segmentation was done using a seed-based segmentation algorithm and then a triangulated surface was extracted from the resulting segmentation. Total, mean, and Gaussian curvatures were then computed. Normalized curvatures were used as classification features. In addition, traditional image features were also extracted and a forward feature selection scheme was used to select the optimal feature set. Logistic regression was used as a classifier and leave-one-out cross-validation was utilized to evaluate the classification performances of the features. The area under the receiver operating characteristic curve (AUC, area under curve) was used as a figure of merit. Results: Among curvature measures, the normalized total curvature (C{sub T}) showed the best classification performance (AUC of 0.74), while the others showed no classification power individually. Five traditional image features (two shape, two margin, and one texture descriptors) were selected via the feature selection scheme and its resulting classifier achieved an AUC of 0.83. Among those five features, the radial gradient index (RGI), which is a margin descriptor, showed the best classification performance (AUC of 0.73). A classifier combining RGI and C{sub T} yielded an AUC of 0.81, which showed similar performance (i.e., no statistically significant difference) to the classifier with the above five traditional image features. Additional comparisons in AUC values between classifiers using different combinations of traditional image features and C{sub T} were conducted. The results showed that C{sub T} was able to replace the other four image features for the classification task. Conclusions: The normalized

  6. Development and statistical assessment of a paper-based immunoassay for detection of tumor markers

    Energy Technology Data Exchange (ETDEWEB)

    Mazzu-Nascimento, Thiago [Instituto de Química de São Carlos, Universidade de São Paulo, 13566-590, São Carlos, SP (Brazil); Instituto Nacional de Ciência e Tecnologia de Bioanalítica, Campinas, SP (Brazil); Morbioli, Giorgio Gianini [Instituto de Química de São Carlos, Universidade de São Paulo, 13566-590, São Carlos, SP (Brazil); Instituto Nacional de Ciência e Tecnologia de Bioanalítica, Campinas, SP (Brazil); School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332 (United States); Milan, Luis Aparecido [Departamento de Estatística, Universidade Federal de São Carlos, São Carlos, SP (Brazil); Donofrio, Fabiana Cristina [Instituto de Ciências da Saúde, Universidade Federal de Mato Grosso, 78557-267, Sinop, MT (Brazil); Mestriner, Carlos Alberto [Wama Produtos para Laboratório Ltda, 13560-971, São Carlos, SP (Brazil); Carrilho, Emanuel, E-mail: emanuel@iqsc.usp.br [Instituto de Química de São Carlos, Universidade de São Paulo, 13566-590, São Carlos, SP (Brazil); Instituto Nacional de Ciência e Tecnologia de Bioanalítica, Campinas, SP (Brazil)

    2017-01-15

    Paper-based assays are an attractive low-cost option for clinical chemistry testing, due to characteristics such as short time of analysis, low consumption of samples and reagents, and high portability of assays. However, little attention has been given to the evaluation of the performance of these simple tests, which should include the use of a statistical approach to define the choice of best cut-off value for the test. The choice of the cut-off value impacts on the sensitivity and specificity of the bioassay. Here, we developed a paper-based immunoassay for the detection of the carcinoembryonic antigen (CEA) and performed a statistical assessment to establish the assay's cut-off value using the Youden's J index (68.28 A.U.), what allowed for a gain in sensibility (0.86) and specificity (1.0). We also discuss about the importance of defining a gray zone as a safety margin for test (±12% over the cut-off value), eliminating all false positives and false negatives outcomes and avoiding misleading results. The test accuracy was calculated as the area under the curve (AUC) of the receiver operating characteristic (ROC) curve, presenting a value of 0.97, what classifies this test as highly accurate. We propose here a low-cost method capable of detecting carcinoembryonic antigen (CEA) in human serum samples, highlighting the importance of statistical tools to evaluate a new low-cost diagnostic method. - Highlights: • A paper-based sandwich immunoassay protocol for detection of tumor markers. • A statistical approach to define cut-off values and measuring test's sensitivity, specificity and accuracy. • A simple way to create a gray zone, avoiding false positive and false negative outcomes.

  7. Tumor-targeting delivery of herb-based drugs with cell-penetrating/tumor-targeting peptide-modified nanocarriers.

    Science.gov (United States)

    Kebebe, Dereje; Liu, Yuanyuan; Wu, Yumei; Vilakhamxay, Maikhone; Liu, Zhidong; Li, Jiawei

    2018-01-01

    Cancer has become one of the leading causes of mortality globally. The major challenges of conventional cancer therapy are the failure of most chemotherapeutic agents to accumulate selectively in tumor cells and their severe systemic side effects. In the past three decades, a number of drug delivery approaches have been discovered to overwhelm the obstacles. Among these, nanocarriers have gained much attention for their excellent and efficient drug delivery systems to improve specific tissue/organ/cell targeting. In order to enhance targeting efficiency further and reduce limitations of nanocarriers, nanoparticle surfaces are functionalized with different ligands. Several kinds of ligand-modified nanomedicines have been reported. Cell-penetrating peptides (CPPs) are promising ligands, attracting the attention of researchers due to their efficiency to transport bioactive molecules intracellularly. However, their lack of specificity and in vivo degradation led to the development of newer types of CPP. Currently, activable CPP and tumor-targeting peptide (TTP)-modified nanocarriers have shown dramatically superior cellular specific uptake, cytotoxicity, and tumor growth inhibition. In this review, we discuss recent advances in tumor-targeting strategies using CPPs and their limitations in tumor delivery systems. Special emphasis is given to activable CPPs and TTPs. Finally, we address the application of CPPs and/or TTPs in the delivery of plant-derived chemotherapeutic agents.

  8. Multiple malignant extragastrointestinal stromal tumors of the greater omentum and results of immunohistochemistry and mutation analysis: A case report

    OpenAIRE

    Kim, Jong-Han; Boo, Yoon-Jung; Jung, Cheol-Woong; Park, Sung-Soo; Kim, Seung-Joo; Mok, Young-Jae; Kim, Sang-Dae; Chae, Yang-Suk; Kim, Chong-Suk

    2007-01-01

    To report an extragastrointestinal stromal tumor (EGIST) that occurs outside the gastrointestinal tract and shows unique clinicopathologic and immunohistochemical features. In our case, we experienced multiple soft tissue tumors that originate primarily in the greater omentum, and in immunohistochemical analysis, the tumors showed features that correspond to malignant EGIST. Two large omental masses measured 15 cm x 10 cm and 5 cm × 4 cm sized and several small ovoid fragments were attached t...

  9. Risk associated with central catheters for malignant tumor patients: a systematic review and meta-analysis.

    Science.gov (United States)

    Lv, Yajuan; Hou, Yong; Pan, Bo; Ma, Yuwan; Li, Paiyun; Yu, Lili; Xu, Deguo; Song, Juanjuan; Shang, Heli; Wang, Hongyan; Tian, Yuan

    2018-02-23

    The risk of venous thrombosis and mortality associated with central catheter (PICC/CICC) for malignant tumor patients is not definite. So, we carried out a systematic review and meta-analysis to evaluate it. Among patients with comparing PICC with CICC, odds ratio (OR) or risk ratio (RR) was calculated with a random effect model meta-analysis. The result of the stratification analysis of 7 studies (PICC vs CICC) supported the theory that CICCs were associated with a decrease in the odds ratio of thrombosis compared with PICCs. 7 of 15 studies provided the information about the compared mortality rate of the patients. The result showed that CICCs were associated with a decrease in the odds ratio of thrombosis compared with PICCs (OR = 0.45, 95% CI:0.32-0.62, p < 0.0001, I 2 = 0%,Tau 2 = 0.00). Meta-analysis of 8 studies of 2639 patients showed that pharmacological deep vein thrombosis prophylaxis drugs could decrease the risk of mortality of malignant tumor patients with CICCs (RR = 0.58, 95% CI:0.48-0.71, Z = 5.32, p < 0.0001, I 2 = 71%). We found that PICCs are associated with a raised risk of deep vein thrombosis, and pharmacological deep vein thrombosis prophylaxis drugs is a beneficial factor in decreasing the incidence of thrombosis, while warfarin may decrease the risk of mortality of malignant tumor patients with CICCs.

  10. Obesity and Risk for Brain/CNS Tumors, Gliomas and Meningiomas: A Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Theodoros N Sergentanis

    Full Text Available This meta-analysis aims to examine the association between being overweight/obese and risk of meningiomas and gliomas as well as overall brain/central nervous system (CNS tumors.Potentially eligible publications were sought in PubMed up to June 30, 2014. Random-effects meta-analysis and dose-response meta-regression analysis was conducted. Cochran Q statistic, I-squared and tau-squared were used for the assessment of between-study heterogeneity. The analysis was performed using Stata/SE version 13 statistical software.A total of 22 studies were eligible, namely 14 cohort studies (10,219 incident brain/CNS tumor cases, 1,319 meningioma and 2,418 glioma cases in a total cohort size of 10,143,803 subjects and eight case-control studies (1,009 brain/CNS cases, 1,977 meningioma cases, 1,265 glioma cases and 8,316 controls. In females, overweight status/obesity was associated with increased risk for overall brain/CNS tumors (pooled RR = 1.12, 95%CI: 1.03-1.21, 10 study arms, meningiomas (pooled RR = 1.27, 95%CI: 1.13-1.43, 16 study arms and gliomas (pooled RR = 1.17, 95%CI: 1.03-1.32, six arms. Obese (BMI>30 kg/m2 females seemed particularly aggravated in terms of brain/CNS tumor (pooled RR = 1.19, 95%CI: 1.05-1.36, six study arms and meningioma risk (pooled RR = 1.48, 95%CI: 1.28-1.71, seven arms. In males, overweight/obesity status correlated with increased meningioma risk (pooled RR = 1.58, 95%CI: 1.22-2.04, nine study arms, whereas the respective association with overall brain/CNS tumor or glioma risk was not statistically significant. Dose-response meta-regression analysis further validated the findings.Our findings highlight obesity as a risk factor for overall brain/CNS tumors, meningiomas and gliomas among females, as well as for meningiomas among males.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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)

  16. Grating-based phase-contrast imaging of tumor angiogenesis in lung metastases.

    Directory of Open Access Journals (Sweden)

    Huimin Lin

    Full Text Available To assess the feasibility of the grating-based phase-contrast imaging (GPI technique for studying tumor angiogenesis in nude BALB/c mice, without contrast agents.We established lung metastatic models of human gastric cancer by injecting the moderately differentiated SGC-7901 gastric cancer cell line into the tail vein of nude mice. Samples were embedded in a 10% formalin suspension and dried before imaging. Grating-based X-ray phase-contrast images were obtained at the BL13W beamline of the Shanghai Synchrotron Radiation Facility (SSRF and compared with histological sections.Without contrast agents, grating-based X-ray phase-contrast imaging still differentiated angiogenesis within metastatic tumors with high spatial resolution. Vessels, down to tens of microns, showed gray values that were distinctive from those of the surrounding tumors, which made them easily identifiable. The vessels depicted in the imaging study were similar to those identified on histopathology, both in size and shape.Our preliminary study demonstrates that grating-based X-ray phase-contrast imaging has the potential to depict angiogenesis in lung metastases.

  17. 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.

  18. 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.

  19. Hilar bile duct tumors: Endoscopic or percutaneous drainage?: a prospective analysis

    Directory of Open Access Journals (Sweden)

    Martín Alejandro Guidi

    Full Text Available Background and objective: Both the endoscopic and the percutaneous approach are widely accepted for the drainage of hilar tumors. Our primary objective was to report on the effectiveness and complications of these procedures. Methods: Prospective observational analysis of the endoscopic and/or percutaneous management of all hilar tumors treated at a referral hospital from October 2011 until October 2014. Group A included patients treated endoscopically and group B included patients treated with percutaneous drainage. The following variables were assessed: Effective biliary drainage rate, survival time and complications. Results: Group A comprised 40 patients and group B, 22 patients. Overall success rate in achieving effective biliary drainage was 85% in group A and 90.9% in group B (p = 0.78. Five patients required a combined approach. In group A, the rate of effective drainage in patients with Bismuth IV-type tumors was 58.3%, while it was 81.8% in patients in group B (p = 0.44. There was no difference in mean survival between both groups. For group A, complication rate was 11.5%, whereas it was 2.94% for group B (p = 0.41. Conclusions: Endoscopic and percutaneous biliary drainage are both effective methods for the palliative treatment of patients with hilar tumors. However, for Bismuth IV-type strictures, percutaneous drainage proved to be safer and more effective.

  20. Optimizing Chemotherapeutic Anti-cancer Treatment and the Tumor Microenvironment: An Analysis of Mathematical Models.

    Science.gov (United States)

    Ledzewicz, Urszula; Schaettler, Heinz

    2016-01-01

    We review results about the structure of administration of chemotherapeutic anti-cancer treatment that we have obtained from an analysis of minimally parameterized mathematical models using methods of optimal control. This is a branch of continuous-time optimization that studies the minimization of a performance criterion imposed on an underlying dynamical system subject to constraints. The scheduling of anti-cancer treatments has all the features of such a problem: treatments are administered in time and the interactions of the drugs with the tumor and its microenvironment determine the efficacy of therapy. At the same time, constraints on the toxicity of the treatments need to be taken into account. The models we consider are low-dimensional and do not include more refined details, but they capture the essence of the underlying biology and our results give robust and rather conclusive qualitative information about the administration of optimal treatment protocols that strongly correlate with approaches taken in medical practice. We describe the changes that arise in optimal administration schedules as the mathematical models are increasingly refined to progress from models that only consider the cancerous cells to models that include the major components of the tumor microenvironment, namely the tumor vasculature and tumor-immune system interactions.

  1. New Functional Signatures for Understanding Melanoma Biology from Tumor Cell Lineage-Specific Analysis

    Directory of Open Access Journals (Sweden)

    Florian Rambow

    2015-10-01

    Full Text Available Molecular signatures specific to particular tumor types are required to design treatments for resistant tumors. However, it remains unclear whether tumors and corresponding cell lines used for drug development share such signatures. We developed similarity core analysis (SCA, a universal and unsupervised computational framework for extracting core molecular features common to tumors and cell lines. We applied SCA to mRNA/miRNA expression data from various sources, comparing melanoma cell lines and metastases. The signature obtained was associated with phenotypic characteristics in vitro, and the core genes CAPN3 and TRIM63 were implicated in melanoma cell migration/invasion. About 90% of the melanoma signature genes belong to an intrinsic network of transcription factors governing neural development (TFAP2A, DLX2, ALX1, MITF, PAX3, SOX10, LEF1, and GAS7 and miRNAs (211-5p, 221-3p, and 10a-5p. The SCA signature effectively discriminated between two subpopulations of melanoma patients differing in overall survival, and classified MEKi/BRAFi-resistant and -sensitive melanoma cell lines.

  2. [Gastrointestinal stromal tumors: clinical and instrumental diagnosis. Analysis of a review of the literature].

    Science.gov (United States)

    D'Amato, A; Cristaldi, M; Pronio, A M; Montesani, C; Ribotta, G

    1999-01-01

    From a personal experience of 23 treated gastrointestinal stromal tumor (GISTs), this study analyzed both clinical and diagnostic problems of this quite new nosological category. A this literature review provides a rigid selection of papers (scientific basis, statistic inference, type/quality of the journal, etc.); only numerous series have been included (case reports were excluded) and only those published after 1990. Three-hundred-seventy-five cases have therefore been selected. Starting and late symptoms/signs and diagnostic tests employed were analyzed. Results show 1) a relevant GIST quantity (approx. 30%) is casually discovered, during operations carried out for other pathologies or diagnostic tests for other indications; 2) poor correlation between site of the tumor and clinical manifestations; 3) a positive correlation between tumor diameter and presence of symptoms/signs seems to exists. The accuracy of different diagnostic tests is reported. No specific symptoms/signs have been isolated; this kind of tumor is often accidentally found. An analysis of different diagnostic tests available today shows the very important role of endoscopic ultra-sound, together with CT and MRI.

  3. Tumor size and elasticity estimation using Smartphone-based Compression-Induced scope.

    Science.gov (United States)

    Won, C-H; Goldstein, Jesse; Oleksyuk, Vira; Caroline, Dina; Pascarella, Suzanne

    2017-07-01

    A simple-to-use, noninvasive, and risk-free system, which will provide accurate identification of potentially life threatening malignant tumors using tactile pressure, is developed. The Smartphone-based Compression-Induced (SCI) Scope will allow physicians to quickly capture the mechanical properties of a benign or malignant tumor with the convenience of a smartphone platform. The size and elasticity property is described using estimating methods from the pressure-induced images of SCI Scope. The device is based on the Apple iPhone 6. The image will be captured through a waveguide. The image information in combination with the force sensor value will be transmitted wirelessly to a computer for processing. The size and elasticity estimation experiments with SCI Scope showed that the size estimation error of 2.31% and estimated relative elastic modulus error of 23.9%.

  4. Trajectory Based Traffic Analysis

    DEFF Research Database (Denmark)

    Krogh, Benjamin Bjerre; Andersen, Ove; Lewis-Kelham, Edwin

    2013-01-01

    -and-click analysis, due to a novel and efficient indexing structure. With the web-site daisy.aau.dk/its/spqdemo/we will demonstrate several analyses, using a very large real-world data set consisting of 1.9 billion GPS records (1.5 million trajectories) recorded from more than 13000 vehicles, and touching most...

  5. 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.

  6. Length of hospital stay after craniotomy for tumor: a National Surgical Quality Improvement Program analysis.

    Science.gov (United States)

    Dasenbrock, Hormuzdiyar H; Liu, Kevin X; Devine, Christopher A; Chavakula, Vamsidhar; Smith, Timothy R; Gormley, William B; Dunn, Ian F

    2015-12-01

    OBJECT Although the length of hospital stay is often used as a measure of quality of care, data evaluating the predictors of extended hospital stay after craniotomy for tumor are limited. The goals of this study were to use multivariate regression to examine which preoperative characteristics and postoperative complications predict a prolonged hospital stay and to assess the impact of length of stay on unplanned hospital readmission. METHODS Data were extracted from the National Surgical Quality Improvement Program (NSQIP) database from 2007 to 2013. Patients who underwent craniotomy for resection of a brain tumor were included. Stratification was based on length of hospital stay, which was dichotomized by the upper quartile of the interquartile range (IQR) for the entire population. Covariates included patient age, sex, race, tumor histology, comorbidities, American Society of Anesthesiologists (ASA) class, functional status, preoperative laboratory values, preoperative neurological deficits, operative time, and postoperative complications. Multivariate logistic regression with forward prediction was used to evaluate independent predictors of extended hospitalization. Thereafter, hierarchical multivariate logistic regression assessed the impact of length of stay on unplanned readmission. RESULTS The study included 11,510 patients. The median hospital stay was 4 days (IQR 3-8 days), and 27.7% (n = 3185) had a hospital stay of at least 8 days. Independent predictors of extended hospital stay included age greater than 70 years (OR 1.53, 95% CI 1.28%-1.83%, p craniotomy for tumor score was created based on preoperative factors significant in regression models, with a moderate correlation with length of stay (p = 0.43, p craniotomy for tumor, much of the variance in hospital stay was attributable to baseline patient characteristics, suggesting length of stay may be an imperfect proxy for quality. Additionally, longer hospitalizations were not found to be associated

  7. Tumor Marker Detection: Ultrasensitive Luminescent In Vitro Detection for Tumor Markers Based on Inorganic Lanthanide Nano?Bioprobes (Adv. Sci. 11/2016)

    OpenAIRE

    Zheng, Wei; Zhou, Shanyong; Xu, Jin; Liu, Yongsheng; Huang, Ping; Liu, Yan; Chen, Xueyuan

    2016-01-01

    In article 1600197, Xueyuan Chen and co?workers report a novel luminescent bioassay technique, namely, dissolution?enhanced luminescence bioassay based on inorganic lanthanide nanoprobes, for ultrasensitive in?vitro detection of tumor markers in human sera or saliva, such as carcinoembryonic antigen, prostate specific antigen and alpha?fetoprotein, with detection sensitivities several orders of magnitude improvement relative to current commercial bioassays.

  8. 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

  9. 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

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Tatsuya, E-mail: yamatatu_01eik@yahoo.co.jp [Department of Radiology, Faculty of Medical Sciences, University of Fukui, Fukui (Japan); Takeuchi, Hiroaki, E-mail: takeu@u-fukui.ac.jp [Department of Neurosurgery, Faculty of Medical Sciences, University of Fukui, Fukui (Japan); Kinoshita, Kazuyuki, E-mail: kkino@u-fukui.ac.jp [Department of Radiology, Faculty of Medical Sciences, University of Fukui, Fukui (Japan); Kosaka, Nobuyuki, E-mail: nkosaka@u-fukui.ac.jp [Department of Radiology, Faculty of Medical Sciences, University of Fukui, Fukui (Japan); Kimura, Hirohiko, E-mail: kimura@u-fukui.ac.jp [Department of Radiology, Faculty of Medical Sciences, University of Fukui, Fukui (Japan)

    2014-05-15

    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{sub 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{sub s} = 0.89, 0.81, both p < 0.01). There was a weak positive correlation between MVA ratio and mean TBF for schwannomas (r{sub 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.

  10. 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

  11. Evaluating patients for psychosocial distress and supportive care needs based on health-related quality of life in primary brain tumors: a prospective multicenter analysis of patients with gliomas in an outpatient setting.

    Science.gov (United States)

    Hickmann, Anne-Katrin; Hechtner, Marlene; Nadji-Ohl, Minou; Janko, Mareile; Reuter, Ann Katrin; Kohlmann, Karoline; Haug, Markus; Grüninger, Sonja; Deininger, Monika; Ganslandt, Oliver; König, Jochem; Wirtz, Christian Rainer; Coburger, Jan; Renovanz, Mirjam

    2017-01-01

    The association between health-related quality of life (HRQoL), psychosocial distress, and supportive care is in the focus of patient-centered neuro-oncology. We investigated the relationship between the aforementioned in glioma-patients to evaluate the association of these instruments and determine cut-off values for suitable HRQoL scales indicating a potential need for intervention. In an observational multi-center study, outpatients completed the Distress Thermometer (DT), EORTC Quality of Life Questionnaire (EORTC-QLQ-C30/BN20, HRQoL), and Supportive-Care-Needs-Survey-SF34-G (SCNS). Based on nine EORTC-function and selected -symptom scales items of the questionnaires were matched. Convergent validity of related single items and scores across the instruments was estimated. EORTC cut-off values were calculated. Data of 167 patients were analyzed. The strongest correlation of EORTC-QLQ-C30 and DT was found for cognitive function (cogf), global health status (GHS), emotional (emof), role function (rolef), future uncertainty (FU), fatigue, and between EORTC-QLQ-C30 and SCNS for FU, emof, rolef (r = |0.4-0.7|; p care (AUC 0.78, 0.85; p < 0.01). Worse EORTC-C30 scores correlate with higher DT and SCNS scores. With this exploratory assessment, cut-off values for EORTC-C30 subscores to predict distress and pathological SCNS-scores could be determined, which could influence patients' referral to further treatment. However, further prospective clinical trials are needed to confirm the clinical relevance of these cut-off values.

  12. CT imaging spectrum of pancreatic serous tumors: Based on new pathologic classification

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Hye Young [Department of Radiology, Seoul National University Hospital, 101 Daehangno, Jongno-gu, Seoul 110-744 (Korea, Republic of); Kim, Se Hyung, E-mail: shkim@radcom.snu.ac.k [Department of Radiology, Seoul National University Hospital, 101 Daehangno, Jongno-gu, Seoul 110-744 (Korea, Republic of); Institute of Radiation Medicine, Seoul National University Hospital, 101 Daehangno, Jongno-gu, Seoul 110-744 (Korea, Republic of); Kim, Min A. [Department of Pathology, Seoul National University Hospital, 101 Daehangno, Jongno-gu, Seoul 110-744 (Korea, Republic of); Lee, Jae Young; Han, Joon Koo; Choi, Byung Ihn [Department of Radiology, Seoul National University Hospital, 101 Daehangno, Jongno-gu, Seoul 110-744 (Korea, Republic of); Institute of Radiation Medicine, Seoul National University Hospital, 101 Daehangno, Jongno-gu, Seoul 110-744 (Korea, Republic of)

    2010-08-15

    Purpose: The aim of this study is to retrospectively analyze the variety of CT findings based on new pathologic classification. Materials and methods: During a 10-year period, 59 histopathologically proven pancreatic SCTs and 13 SCTs confirmed with typical image findings and strict clinical criteria were enlisted. Two radiologists analyzed CT images for the following items in consensus: location, size, outer margin, tumor shape, the presence of mural nodule, communication with main pancreatic duct (MPD), the presence and extent of MPD dilatation, calcification, central scar, and attenuation on pre- and post-contrast CT images. In addition, typicality of CT findings was determined. A typical finding was defined as a honeycomb appearance without or with oligocystic portion. In the cases with atypical features, the type of atypical features and differential diagnosis were recorded. For the shape of the tumor, tumors were categorized into the following groups: honeycomb without or with oligocystic, pleomorphic, purely oligolocular, unilocular cystic, hypovascular solid, hypervascular solid without or with oligocystic portion, and fingerlike cystic patterns. Results: 28 SCTs (38.9%) presented a honeycomb appearance with (n = 14) or without oligocystic portion (n = 14) and were classified as typical cases. The remaining 44 atypical cases (61.1%) presented the following: purely oligolocular pattern in 18; hypervascular solid without (n = 7) or with oligocystic portion (n = 2) in 9; pleomorphic in 8; unilocular cystic in 7; and fingerlike cystic pattern in 2. Most of the lesions manifesting as hypervascular solid lesions were confused with true solid hypervascular tumors such as neuroendocrine tumors or solid pseudopapillary tumors. For most of the remaining atypical lesions, mucinous cystic neoplasm or branch duct type IPMN were included as a differential diagnosis. Conclusion: Serous cystic tumors of the pancreas can have variable CT appearances ranging from compactly

  13. EPIDEMIOLOGY OF MALIGNANT TUMORS OF LARGE SALIVARY GLANDS (POPULATION-BASED STUDY

    Directory of Open Access Journals (Sweden)

    V. M. Merabishvili

    2016-01-01

    Full Text Available Introduction. Malignant tumors of large salivary glands are a relatively rare malignancy. In 2014 as a whole in Russia 1236 cases of these diseases were registered. According to the latest data of the Interna- tional Agency for Research on Cancer (Volume X the most common standardized incidence rate in various countries ranges from 0.6-0.9 per 100,000 men and 0.4-0.6 per 100,000 women. aim of study. The aim of this study is to carry out for the first time in Russia an estimation of a complex of analytical rates including an evaluation of observed and relative survival rates to assess the effectiveness of cancer control related to patients with a diagnosis of malignant tumors of large salivary glands. material and methods. An estimation of a complex of analytical rates was conducted in accordance with database of the Population-based Cancer Registry of St. Petersburg. There were selected 896 patients with a diagnosis of malignant tumors of large salivary glands from 1994 to 2013. Results. It was found that the most frequent value of the standardized incidence rates of malignant tumors of large salivary glands in different countries of the world community for the male population was 0.6-0.9 per 100,000 population and 0.4-0.6 for the female. These values were 0000 equal to 0.7 and 0.4 0/ in Russia (2014, and 0.6 and 0.5 0/ in St. Petersburg (2014. The vast majority 0000 of recorded cases of malignant tumors of large salivary glands were for S07.9 - of malignant tumors of large salivary glands undefined. 46.6 % of primary patients had early stages (I + II. A relative 5-year survival rate was 61.9 % for men and 69.9 % for women, which was slightly less than the European average (Eurocare. Conclusion. This study for the first time in Russia allowed estimating series of analytical rates character- izing the effectiveness of cancer control related to patients with malignant tumors of large salivary glands in St. Petersburg including estimations of a 5

  14. 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...... blood samples from patients with 6 different solid organ carcinomas and lymphomas. Significantly, CTC-positive rates increased remarkably with tumor progression from N0M0, N+M0 to M1 in each of 5 tested cancers (lung, colon, liver, gastric and pancreatic cancer, and glioma). Among 21 non-small cell lung...

  15. Effects of Strong CYP3A Inhibition and Induction on the Pharmacokinetics of Ixazomib, an Oral Proteasome Inhibitor: Results of Drug-Drug Interaction Studies in Patients With Advanced Solid Tumors or Lymphoma and a Physiologically Based Pharmacokinetic Analysis.

    Science.gov (United States)

    Gupta, Neeraj; Hanley, Michael J; Venkatakrishnan, Karthik; Bessudo, Alberto; Rasco, Drew W; Sharma, Sunil; O'Neil, Bert H; Wang, Bingxia; Liu, Guohui; Ke, Alice; Patel, Chirag; Rowland Yeo, Karen; Xia, Cindy; Zhang, Xiaoquan; Esseltine, Dixie-Lee; Nemunaitis, John

    2018-02-01

    At clinically relevant ixazomib concentrations, in vitro studies demonstrated that no specific cytochrome P450 (CYP) enzyme predominantly contributes to ixazomib metabolism. However, at higher than clinical concentrations, ixazomib was metabolized by multiple CYP isoforms, with the estimated relative contribution being highest for CYP3A at 42%. This multiarm phase 1 study (Clinicaltrials.gov identifier: NCT01454076) investigated the effect of the strong CYP3A inhibitors ketoconazole and clarithromycin and the strong CYP3A inducer rifampin on the pharmacokinetics of ixazomib. Eighty-eight patients were enrolled across the 3 drug-drug interaction studies; the ixazomib toxicity profile was consistent with previous studies. Ketoconazole and clarithromycin had no clinically meaningful effects on the pharmacokinetics of ixazomib. The geometric least-squares mean area under the plasma concentration-time curve from 0 to 264 hours postdose ratio (90%CI) with vs without ketoconazole coadministration was 1.09 (0.91-1.31) and was 1.11 (0.86-1.43) with vs without clarithromycin coadministration. Reduced plasma exposures of ixazomib were observed following coadministration with rifampin. Ixazomib area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration was reduced by 74% (geometric least-squares mean ratio of 0.26 [90%CI 0.18-0.37]), and maximum observed plasma concentration was reduced by 54% (geometric least-squares mean ratio of 0.46 [90%CI 0.29-0.73]) in the presence of rifampin. The clinical drug-drug interaction study results were reconciled well by a physiologically based pharmacokinetic model that incorporated a minor contribution of CYP3A to overall ixazomib clearance and quantitatively considered the strength of induction of CYP3A and intestinal P-glycoprotein by rifampin. On the basis of these study results, the ixazomib prescribing information recommends that patients should avoid concomitant administration of

  16. 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)

  17. 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.

  18. A retrospective analysis of 33 primary intraspinal tumors treated with postoperative radiotherapy

    International Nuclear Information System (INIS)

    Li Li; Xu Changshao; Zhou Juying; Yu Zhiying; Xu Xiaoting

    2005-01-01

    Objective: To describe the clinical characteristics, outcome and prognostic factors of primary intraspinal tumor treated with postoperative radiotherapy. Methods: Thirty-three patients diagnosed as suffering from intraspinal tumor treated with postoperative radiotherapy were analyzed. There were eighteen male and fifteen female, with a median age of 37 years (range 7-64 years). Two patients were treated with grossly total resection, 25 subtotal resection, 2 biopsy only. These patients were treated either with 60 Co (n=18, before 1998) or 6 MV-X ray (n=15, after 1998) to the total dose of 45-68 Gy. The overall response and survival rates were calculated by Kaplan-Meier method and the difference between groups was tested by the log-rank method. The prognostic factors related to the characteristics of patient, tumor, and treatment were determined. Results: The overall response, five-year and disease-free survival rate was 81.3%, 59.4% and 56.3%, respectively. By multivariate analysis, the histological type (P=0.039) and gender (P=0.049) had independent impact on the 5-year survival rate. Ependymoma had a better prognosis compared to other histological subsets and female gained more survival advantage over male. There was no close relationship between survival and other factors, such as age, extent of surgery, initial site, irradiation dose, or the interval between surgery and radiotherapy. Conclusions: Postoperative radiotherapy is safe and effective for primary intraspinal tumor. The histological type and gender are important prognostic factors of survival in primary intraspinal tumors. (authors)

  19. 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

  20. 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

  1. Analytical techniques for boron and boron 10 analysis in a solid experimental tumor EO.771

    International Nuclear Information System (INIS)

    Porschen, W.; Marx, J.; Feinendegen, L.E.

    1987-01-01

    If a tumor can be preferentially loaded with a suitable boron-10 compound and irradiated with thermal neutrons, malignant cells can be selectively destroyed via the α-particle + Li 7-nucleus from the reaction 10 B(n,α) 7 Li. Neutron capture therapy with two boron-10 amino acid analogs of low toxicity has been tested in recent years: (a) trimethylamine carboxyborane, (A3) and (b) amine-carboxyborane, (A7). Now the boron-10 glycineamide analog (A8), amineboryl carboxamide has been synthsized; it contains 13.81% boron (90% Boron 10+10% Boron 11) and shows a very low toxicity in mice. The effects of this compund were tested on the syngeneic solid adenocarcinoma EO 771 on the right hind leg of male C57 BL/6J mice under standard conditions, by measuring tumor volume growth delay and cell cycle changes using flow cytometry. Boron distribution between tumor and muscle was analyzed by emission spectroscopy with inductively coupled plasma (ICP) following injection of a suspension of peanut oil emulsion. In addition, boron-10 concentration in the tumor were analyzed with prompt γ-activation analysis and neutron capture radiography (Kodak-Pathe LR115) at the MRR reactor in Brookhaven after i.p. injection of 0.4 mg/g A8. Application of A8 alone (0.4 mg/g i.p.) or thermal neutron irradiation of the tumor EO. 771 produced a tumor growth delay of 1-2 days for tumor volume doubling. Application of the boron 10 glycine-amide analog A8 i.p. plus 5x10 12 n/cm 2 resulted in a growth delay of 3-6 days. In contrast intratumoral application of A8 plus 4x10 12 n/cm 2 neutrons gave a growth delay of 7-14 days; the fraction of (G2+M) cells rose from 35% (neutrons alone) to 52%, as evaluated from flow cytometry. (orig.)

  2. Comparison of conformal and intensity modulated radiation therapy techniques for treatment of pelvic tumors. Analysis of acute toxicity

    International Nuclear Information System (INIS)

    Ferrigno, Robson; Santos, Adriana; Martins, Lidiane C; Weltman, Eduardo; Chen, Michael J; Sakuraba, Roberto; Lopes, Cleverson P; Cruz, José C

    2010-01-01

    This retrospective analysis reports on the comparative outcome of acute gastrointestinal (GI) and genitourinary (GU) toxicities between conformal radiation therapy (CRT) and intensity modulated radiation therapy (IMRT) techniques in the treatment of patients with pelvic tumors. From January 2002 to December 2008, 69 patients with pelvic tumors underwent whole pelvic CRT and 65 underwent whole pelvic IMRT to treat pelvic lymph nodes and primary tumor regions. Total dose to the whole pelvis ranged from 50 to 50.4 Gy in 25 to 28 daily fractions. Chemotherapy (CT) regimen, when employed, was based upon primary tumor. Acute GI and GU toxicities were graded by RTOG/EORTC acute radiation morbidity criteria. Absence of GI symptoms during radiotherapy (grade 0) was more frequently observed in the IMRT group (43.1% versus 8.7; p < 0.001) and medication for diarrhea (Grade 2) was more frequently used in the CRT group (65.2% versus 38.5%; p = 0.002). Acute GI grade 1 and 3 side effects incidence was similar in both groups (18.5% versus 18.8%; p = 0.95 and 0% versus 7.2%; p = 0.058, respectively). Incidence of GU toxicity was similar in both groups (grade 0: 61.5% versus 66.6%, p = 0.54; grade 1: 20% versus 8.7%, p = 0.06; grade 2: 18.5% versus 23.5%, p = 0.50 and grade 3: 0% versus 1.5%, p > 0.99). This comparative case series shows less grade 2 acute GI toxicity in patients treated with whole pelvic IMRT in comparison with those treated with CRT. Incidence of acute GU toxicity was similar in both groups

  3. Comparative analysis of imaging sensitivity of positron emission mammography and whole-body PET in relation to tumor size.

    Science.gov (United States)

    Yamamoto, Yayoi; Ozawa, Yukihiko; Kubouchi, Kouichi; Nakamura, Seigo; Nakajima, Yasuo; Inoue, Tomio

    2015-01-01

    Positron emission mammography (PEM) consists of a dedicated PET scanner for breast imaging with a higher spatial resolution than whole-body PET (WBPET) scanners. This study compared the imaging sensitivity of PEM with WBPET in relation to tumor size. Fifty-four Japanese women younger than 50 years with histologically confirmed breast lesions were retrospectively enrolled. Positron emission mammography and WBPET were conducted on the same day. Positron emission mammography and WBPET images were blindly evaluated and compared with histopathology. Tumors were classified into 3 groups based on size as follows: group 1, 1 cm or smaller; group 2, 1 to 2 cm; and group 3, larger than 2 cm. The sensitivities of PEM and WBPET were compared in overall subjects and in each size group. In visual analysis, the overall imaging sensitivity was 78.6% (33/42) for PEM and 47.6% (20/42) for WBPET. The overall sensitivity of PEM was significantly higher than that of WBPET (P PEM and WBPET were larger in smaller tumors: group 1 (66.7% vs 13.3%), group 2 (63.4% vs 36.4%), and group 3 (100.0% vs 87.5%). The sensitivity of PEM was significantly higher than that of WBPET in group 1 (P = 0.008); however, no significant differences were seen in group 2 (P = 0.500) or group 3 (P = 0.250). Overall, the imaging specificity of PEM and WEBPET was 90.6% (60/66) and 93.9% (62/66), respectively. The imaging sensitivity of PEM was higher than that of WBPET in Japanese women younger than 50 years. Positron emission mammography showed significant sensitivity in tumors smaller than 1 cm, which has been a weak point for WBPET.

  4. 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.

  5. Update on rare epithelial ovarian cancers: based on the Rare Ovarian Tumors Young Investigator Conference.

    Science.gov (United States)

    Jang, Ji Yon Agnes; Yanaihara, Nozomu; Pujade-Lauraine, Eric; Mikami, Yoshiki; Oda, Katsutoshi; Bookman, Michael; Ledermann, Jonathan; Shimada, Muneaki; Kiyokawa, Takako; Kim, Byoung Gie; Matsumura, Noriomi; Kaku, Tsunehisa; Kuroda, Takafumi; Nagayoshi, Yoko; Kawabata, Ayako; Iida, Yasushi; Kim, Jae Weon; Quinn, Michael; Okamoto, Aikou

    2017-07-01

    There has been significant progress in the understanding of the pathology and molecular biology of rare ovarian cancers, which has helped both diagnosis and treatment. This paper provides an update on recent advances in the knowledge and treatment of rare ovarian cancers and identifies gaps that need to be addressed by further clinical research. The topics covered include: low-grade serous, mucinous, and clear cell carcinomas of the ovary. Given the molecular heterogeneity and the histopathological rarity of these ovarian cancers, the importance of designing adequately powered trials or finding statistically innovative ways to approach the treatment of these rare tumors has been emphasized. This paper is based on the Rare Ovarian Tumors Conference for Young Investigators which was presented in Tokyo 2015 prior to the 5th Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup (GCIG). Copyright © 2017. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.

  6. 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.

  7. Point of care assessment of melanoma tumor signaling and metastatic burden from μNMR analysis of tumor fine needle aspirates and peripheral blood.

    Science.gov (United States)

    Gee, Michael S; Ghazani, Arezou A; Haq, Rizwan; Wargo, Jennifer A; Sebas, Matthew; Sullivan, Ryan J; Lee, Hakho; Weissleder, Ralph

    2017-04-01

    This study evaluates μNMR technology for molecular profiling of tumor fine needle aspirates and peripheral blood of melanoma patients. In vitro assessment of melanocyte (MART-1, HMB45) and MAP kinase signaling (pERK, pS6K) molecule expression was performed in human cell lines, while clinical validation was performed in an IRB-approved study of melanoma patients undergoing biopsy and blood sampling. Tumor FNA and blood specimens were compared with BRAF genetic analysis and cross-sectional imaging. μNMR in vitro analysis showed increased expression of melanocyte markers in melanoma cells as well as increased expression of phosphorylated MAP kinase targets in BRAF-mutant melanoma cells. Melanoma patient FNA samples showed increased pERK and pS6K levels in BRAF mutant compared with BRAF WT melanomas, with μNMR blood circulating tumor cell level increased with higher metastatic burden visible on imaging. These results indicate that μNMR technology provides minimally invasive point-of-care evaluation of tumor signaling and metastatic burden in melanoma patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. System-Wide Analysis Reveals a Complex Network of Tumor-Fibroblast Interactions Involved in Tumorigenicity

    Science.gov (United States)

    Rajaram, Megha; Li, Jinyu; Egeblad, Mikala; Powers, R. Scott

    2013-01-01

    Many fibroblast-secreted proteins promote tumorigenicity, and several factors secreted by cancer cells have in turn been proposed to induce these proteins. It is not clear whether there are single dominant pathways underlying these interactions or whether they involve multiple pathways acting in parallel. Here, we identified 42 fibroblast-secreted factors induced by breast cancer cells using comparative genomic analysis. To determine what fraction was active in promoting tumorigenicity, we chose five representative fibroblast-secreted factors for in vivo analysis. We found that the majority (three out of five) played equally major roles in promoting tumorigenicity, and intriguingly, each one had distinct effects on the tumor microenvironment. Specifically, fibroblast-secreted amphiregulin promoted breast cancer cell survival, whereas the chemokine CCL7 stimulated tumor cell proliferation while CCL2 promoted innate immune cell infiltration and angiogenesis. The other two factors tested had minor (CCL8) or minimally (STC1) significant effects on the ability of fibroblasts to promote tumor growth. The importance of parallel interactions between fibroblasts and cancer cells was tested by simultaneously targeting fibroblast-secreted amphiregulin and the CCL7 receptor on cancer cells, and this was significantly more efficacious than blocking either pathway alone. We further explored the concept of parallel interactions by testing the extent to which induction of critical fibroblast-secreted proteins could be achieved by single, previously identified, factors produced by breast cancer cells. We found that although single factors could induce a subset of genes, even combinations of factors failed to induce the full repertoire of functionally important fibroblast-secreted proteins. Together, these results delineate a complex network of tumor-fibroblast interactions that act in parallel to promote tumorigenicity and suggest that effective anti-stromal therapeutic strategies

  9. 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.

  10. Error analysis of tumor blood flow measurement using dynamic contrast-enhanced data and model-independent deconvolution analysis

    International Nuclear Information System (INIS)

    Murase, Kenya; Miyazaki, Shohei

    2007-01-01

    We performed error analysis of tumor blood flow (TBF) measurement using dynamic contrast-enhanced data and model-independent deconvolution analysis, based on computer simulations. For analysis, we generated a time-dependent concentration of the contrast agent in the volume of interest (VOI) from the arterial input function (AIF) consisting of gamma-variate functions using an adiabatic approximation to the tissue homogeneity model under various plasma flow (F p ), mean capillary transit time (T c ), permeability-surface area product (PS) and signal-to-noise ratio (SNR) values. Deconvolution analyses based on truncated singular value decomposition with a fixed threshold value (TSVD-F), with an adaptive threshold value (TSVD-A) and with the threshold value determined by generalized cross validation (TSVD-G) were used to estimate F p values from the simulated concentration-time curves in the VOI and AIF. First, we investigated the relationship between the optimal threshold value and SNR in TSVD-F, and then derived the equation describing the relationship between the threshold value and SNR for TSVD-A. Second, we investigated the dependences of the estimated F p values on T c , PS, the total duration for data acquisition and the shape of AIF. Although TSVD-F with a threshold value of 0.025, TSVD-A with the threshold value determined by the equation derived in this study and TSVD-G could estimate the F p values in a similar manner, the standard deviation of the estimates was the smallest and largest for TSVD-A and TSVD-G, respectively. PS did not largely affect the estimates, while T c did in all methods. Increasing the total duration significantly improved the variations in the estimates in all methods. TSVD-G was most sensitive to the shape of AIF, especially when the total duration was short. In conclusion, this study will be useful for understanding the reliability and limitation of model-independent deconvolution analysis when applied to TBF measurement using an

  11. 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.

  12. Clinical Outcome of Patients with Breast Phyllodes Tumors: A Retrospective Analysis of 129 Cases in Shiraz, Southern Iran

    Directory of Open Access Journals (Sweden)

    Majid Akrami

    2015-10-01

    Full Text Available Background: Phyllodes tumors are uncommon neoplasms of the breast. Data about their outcome is limited. This study aims to evaluate patients diagnosed with phyllodes tumors in terms of local recurrence, distant metastasis and overall survival. Methods: We retrospectively reviewed the medical records of 129 women with phyllodes tumors who referred to our center from 1999 to 2013. Clinical and pathological features, local and regional recurrence, distant metastasis and overall survival were determined. SPSS 15.0 statistical software was used for analysis. Results:Mean patient age was 39 years (17-67 years. Mean size of the tumor was 5.38 cm. There were 105 (81.4% benign, 8 (6.2% borderline and 16 (12.4% malignant tumors. The mean follow-up period of patients was 28 months (6 to 128 months. The rate of local recurrence among benign tumors was 3.8% (4 cases; in borderline cases the rate was 12.5% (1 case and for malignant cases, it was 18.7% (3 cases. Three patients each recurred twice and one patient had local recurrence for a third time. Two patients died of malignant tumor-related disease - one due to advanced regional recurrence and lung metastasis, and the other to wide-spread metastasis. Another patient died from an unrelated cause (myocardial infarction one year after surgery. For those with malignant phyllodes tumors, the five-year overall survival was 77.8% and disease-free survival rate was 85.7%. Conclusion: Although, the prognosis for phyllodes tumors is good, the malignancy rate is higher in older patients and those with larger tumors. A higher local recurrence rate in malignant phyllodes tumors suggests the importance for adequate resection of margins in surgical management of these tumors.

  13. Splice Expression Variation Analysis (SEVA) for Inter-tumor Heterogeneity of Gene Isoform Usage in Cancer.

    Science.gov (United States)

    Afsari, Bahman; Guo, Theresa; Considine, Michael; Florea, Liliana; Kagohara, Luciane T; Stein-O'Brien, Genevieve L; Kelley, Dylan; Flam, Emily; Zambo, Kristina D; Ha, Patrick K; Geman, Donald; Ochs, Michael F; Califano, Joseph A; Gaykalova, Daria A; Favorov, Alexander V; Fertig, Elana J

    2018-01-12

    Current bioinformatics methods to detect changes in gene isoform usage in distinct phenotypes compare the relative expected isoform usage in phenotypes. These statistics model differences in isoform usage in normal tissues, which have stable regulation of gene splicing. Pathological conditions, such as cancer, can have broken regulation of splicing that increases the heterogeneity of the expression of splice variants. Inferring events with such differential heterogeneity in gene isoform usage requires new statistical approaches. We introduce Splice Expression Variability Analysis (SEVA) to model increased heterogeneity of splice variant usage between conditions (e.g., tumor and normal samples). SEVA uses a rank-based multivariate statistic that compares the variability of junction expression profiles within one condition to the variability within another. Simulated data show that SEVA is unique in modeling heterogeneity of gene isoform usage, and benchmark SEVA's performance against EBSeq, DiffSplice, and rMATS that model differential isoform usage instead of heterogeneity. We confirm the accuracy of SEVA in identifying known splice variants in head and neck cancer and perform cross-study validation of novel splice variants. A novel comparison of splice variant heterogeneity between subtypes of head and neck cancer demonstrated unanticipated similarity between the heterogeneity of gene isoform usage in HPV-positive and HPV-negative subtypes and anticipated increased heterogeneity among HPV-negative samples with mutations in genes that regulate the splice variant machinery. These results show that SEVA accurately models differential heterogeneity of gene isoform usage from RNA-seq data. SEVA is implemented in the R/Bioconductor package GSReg. bahman@jhu.edu, ejfertig@jhmi.edu. Supplementary data are available at Bioinformatics online. © The Author (2018). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  14. Tumor-stroma metabolic relationship based on lactate shuttle can sustain prostate cancer progression

    International Nuclear Information System (INIS)

    Sanità, Patrizia; Capulli, Mattia; Teti, Anna; Galatioto, Giuseppe Paradiso; Vicentini, Carlo; Chiarugi, Paola; Bologna, Mauro; Angelucci, Adriano

    2014-01-01

    Cancer cell adopts peculiar metabolic strategies aimed to sustain the continuous proliferation in an environment characterized by relevant fluctuations in oxygen and nutrient levels. Monocarboxylate transporters MCT1 and MCT4 can drive such adaptation permitting the transport across plasma membrane of different monocarboxylic acids involved in energy metabolism. Role of MCTs in tumor-stroma metabolic relationship was investigated in vitro and in vivo using transformed prostate epithelial cells, carcinoma cell lines and normal fibroblasts. Moreover prostate tissues from carcinoma and benign hypertrophy cases were analyzed for individuating clinical-pathological implications of MCT1 and MCT4 expression. Transformed prostate epithelial (TPE) and prostate cancer (PCa) cells express both MCT1 and MCT4 and demonstrated variable dependence on aerobic glycolysis for maintaining their proliferative rate. In glucose-restriction the presence of L-lactate determined, after 24 h of treatment, in PCa cells the up-regulation of MCT1 and of cytochrome c oxidase subunit I (COX1), and reduced the activation of AMP-activated protein kinase respect to untreated cells. The blockade of MCT1 function, performed by si RNA silencing, determined an appreciable antiproliferative effect when L-lactate was utilized as energetic fuel. Accordingly L-lactate released by high glycolytic human diploid fibroblasts WI-38 sustained survival and growth of TPE and PCa cells in low glucose culture medium. In parallel, the treatment with conditioned medium from PCa cells was sufficient to induce glycolytic metabolism in WI-38 cells, with upregulation of HIF-1a and MCT4. Co-injection of PCa cells with high glycolytic WI-38 fibroblasts determined an impressive increase in tumor growth rate in a xenograft model that was abrogated by MCT1 silencing in PCa cells. The possible interplay based on L-lactate shuttle between tumor and stroma was confirmed also in human PCa tissue where we observed a positive

  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. Designing PDT-based combinations to overcome chemoresistance in heterocellular 3D tumor models (Conference Presentation)

    Science.gov (United States)

    Rizvi, Imran; Briars, Emma A.; Bulin, Anne-Laure; Anbil, Sriram; Vecchio, Daniela; Alkhateeb, Ahmed; Hanna, William R.; Celli, Jonathan P.; Hasan, Tayyaba

    2016-03-01

    A major barrier to treating advanced-stage cancers is heterogeneity in the responsiveness of metastatic disease to conventional therapies leading to resistance and treatment failure. Photodynamic therapy (PDT) has been shown to synergize with conventional agents and to overcome the evasion pathways that cause resistance. Developing PDT-based combinations that target resistant tumor populations and cooperate mechanistically with conventional agents is an increasingly promising approach to improve therapeutic efficacy while minimizing toxicity, particularly in complex disease sites. Identifying the molecular, cellular, and microenvironmental cues that lead to heterogeneity and treatment resistance is critical to developing strategies to target unresponsive regions of stubborn disease. Cell-based research platforms that integrate key microenvironmental cues are emerging as increasingly important tools to improve the translational efficiency of new agents, and to design combination regimens. Among the challenges associated with developing and scaling complex cell-based screening platforms is the need to integrate, and balance, biological relevance with appropriate, high-content imaging routines that provide meaningful quantitative readouts of therapeutic response. The benefits and challenges associated with deriving meaningful insights from complex cell-based models will be presented, with a particular emphasis on overcoming chemoresistance mediated by physical stress and communication with stromal partners (e.g. tumor endothelial cells, which are emerging as dynamic regulators of treatment resistance) using PDT-based combinations.

  17. Utility of the Lateral Base Dural Tacking Method in Cord Tumor Surgery Performed Using Unilateral Hemilaminectomy: A Comparison of Dural Window Widths.

    Science.gov (United States)

    Lee, Seong-Jong; Im, Soo Bin; Jeong, Je Hoon; Chung, Moonyoung; Kim, Bum-Tae; Hwang, Sun-Chul; Shin, Dong-Seong

    2018-02-01

    Unilateral hemilaminectomy, which is used to remove spinal cord tumors, is simpler than laminoplastic laminotomy and affords certain biomechanical advantages. However, both incomplete tumor removal and inadvertent infliction of spinal cord damage attributable to the narrow surgical corridor remain of concern. When a spinal cord tumor is to be removed, it is important to ensure that the dural window along the surgical corridor is of adequate width. This study aimed to determine that the utility of lateral base dural tacking (LBT) method when cord tumor surgery is performed using a unilateral hemilaminectomy-a comparison of dural window widths with a traditional dural tack-up and a suspending-out (DSO) method with the aid of digital image-analysis software. Twenty-one consecutive patients who had intradural-extramedullary spinal cord tumors removed using a unilateral hemilaminectomy were included in the study and analyzed retrospectively. We acquired DSO and LBT dural window images using surgical microscopes under identical conditions in consecutive order and then removed the tumors using the LBT method. We used digital image-analysis software to analyze the images quantitatively. The pixel numbers of LBT and DSO window were compared using a paired t test. Twenty-one tumorous lesions were successfully removed without any major problems using a unilateral hemilaminectomy through LBT windows. The mean pixel numbers of the LBT and DSO windows were 126,787 ± 41,938 and 85,940 ± 21,638. The LBT windows were 46% larger than the DSO windows (P < 0.001). We objectively proved that the utility of the LBT method for widening the surgical corridor created during hemilaminectomy. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Nanoparticle-based sorting of circulating tumor cells by epithelial antigen expression during disease progression in an animal model.

    Science.gov (United States)

    Muhanna, Nidal; Mepham, Adam; Mohamadi, Reza M; Chan, Harley; Khan, Tahsin; Akens, Margarete; Besant, Justin D; Irish, Jonathan; Kelley, Shana O

    2015-10-01

    Circulating tumor cells (CTCs) can be used as markers for the detection, characterization, and targeted therapeutic management of cancer. We recently developed a nanoparticle-mediated approach for capture and sorting of CTCs based on their specific epithelial phenotype. In the current study, we investigate the phenotypic transition of tumor cells in an animal model and show the correlation of this transition with tumor progression. VX2 tumor cells were injected into rabbits, and CTCs were evaluated during tumor progression and correlated with computerized tomography (CT) measurements of tumor volume. The results showed a dramatic increase of CTCs during the four weeks of tumor growth. Following resection, CTC levels dropped but then rebounded, likely due to lymph node metastases. Additionally, CTCs showed a marked loss of the epithelial cell adhesion molecule (EpCAM) relative to precursor cells. In conclusion, the device accurately traces disease progression and CTC phenotypic shift in an animal model. The detection of circulating tumor cells (CTCs) has been used to predict disease prognosis. In this study, the authors developed a nanoparticle-mediated platform based on microfluidics to analyze the differential expressions of epithelial cell adhesion molecule (EpCAM) on CTCs in an animal model. It was found that the loss of EpCAM correlated with disease progression. Hence, the use of this platform may be further applied in other cancer models in the future. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. 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

  20. 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.

  1. Dose to the intracranial arteries in stereotactic and intensity-modulated radiotherapy for skull base tumors

    International Nuclear Information System (INIS)

    Nieder, Carsten; Grosu, Anca L.; Stark, Sybille; Wiedenmann, Nicole; Busch, Raymonde; Kneschaurek, Peter; Molls, Michael

    2006-01-01

    Purpose: To examine retrospectively the maximum dose to the large skull base/intracranial arteries in fractionated stereotactic radiotherapy (FSRT) and intensity-modulated radiotherapy (IMRT), because of the potential risk of perfusion disturbances. Methods and Materials: Overall, 56 patients with tumors adjacent to at least one major artery were analyzed. Our strategy was to perform FSRT with these criteria: 1.8 Gy per fraction, planning target volume (PTV) enclosed by the 95% isodose, maximum dose 107%. Dose limits were applied to established organs at risk, but not the vessels. If FSRT planning failed to meet any of these criteria, IMRT was planned with the same objectives. Results: In 31 patients (median PTV, 23 cm 3 ), the FSRT plan fulfilled all criteria. No artery received a dose ≥105%. Twenty-five patients (median PTV, 39 cm 3 ) needed IMRT planning. In 11 of 25 patients (median PTV, 85 cm 3 ), no plan satisfying all our criteria could be calculated. Only in this group, moderately increased maximum vessel doses were observed (106-110%, n = 7, median PTV, 121 cm 3 ). The median PTV dose gradient was 29% (significantly different from the 14 patients with satisfactory IMRT plans). Three of the four patients in this group had paranasal sinus tumors. Conclusion: The doses to the major arteries should be calculated in IMRT planning for critical tumor locations if a dose gradient >13% within the PTV can not be avoided because the PTV is large or includes air cavities

  2. Real-time temperature feedback for nanoparticles based tumor thermal treatment (Conference Presentation)

    Science.gov (United States)

    Steinberg, Idan; Tamir, Gil; Gannot, Israel

    2017-02-01

    Systemic hyperthermia therapy exploits the fact that cancer cells are more sensitive to elevated temperatures than healthy tissue. Systemic application of hyperthermia externally usually leads to low efficiency treatment. Recently, our group and others have proposed an antibody conjugated magnetic nanoparticles (MNPs) approach to overcome the limitation of systemic hyperthermia. MNPs can bind specifically to the tumor sites, thus delivering internal highly effective targeted hyperthermia. However, such internal mechanism requires more complicated controls and monitoring. This current work presents a deep tissue temperature monitoring method to control hyperthermia effectiveness and minimize collateral damage to surrounding tissues. A low-frequency narrowband modulation of the RF field used for MNP heating leads to the generation of diffused thermal waves which propagate to the tissue surface and captured by a thermal camera. A Fourier domain, analytical heat transfer model is used for temperature monitoring algorithm. The ill-posed thermal inverse problem is solved efficiently by iterating over the source power until both the amplitude and phase match the recorded thermal image sequence. The narrow bandwidth thermal stimulation enables acquiring deep signals with high SNR. We show that thermal transverse resolution improves as the stimulation frequency increases even slightly above DC, enabling better heat source transverse separation and margin identification in the case of distributed tumors. These results can be used as a part of an overall image and treat system for efficient detection of tumors, manipulation of MNPs and monitoring MNP based hyperthermia.

  3. 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.

  4. Probing matrix and tumor mechanics with in situ calibrated optical trap based active microrheology

    Science.gov (United States)

    Staunton, Jack Rory; Vieira, Wilfred; Tanner, Kandice; Tissue Morphodynamics Unit Team

    Aberrant extracellular matrix deposition and vascularization, concomitant with proliferation and phenotypic changes undergone by cancer cells, alter mechanical properties in the tumor microenvironment during cancer progression. Tumor mechanics conversely influence progression, and the identification of physical biomarkers promise improved diagnostic and prognostic power. Optical trap based active microrheology enables measurement of forces up to 0.5 mm within a sample, allowing interrogation of in vitro biomaterials, ex vivo tissue sections, and small organisms in vivo. We fabricated collagen I hydrogels exhibiting distinct structural properties by tuning polymerization temperature Tp, and measured their shear storage and loss moduli at frequencies 1-15k Hz at multiple amplitudes. Lower Tp gels, with larger pore size but thicker, longer fibers, were stiffer than higher Tp gels; decreasing strain increased loss moduli and decreased storage moduli at low frequencies. We subcutanously injected probes with metastatic murine melanoma cells into mice. The excised tumors displayed storage and loss moduli 40 Pa and 10 Pa at 1 Hz, increasing to 500 Pa and 1 kPa at 15 kHz, respectively.

  5. Breast Tumor Classification Based on a Computerized Breast Imaging Reporting and Data System Feature System.

    Science.gov (United States)

    Qiao, Mengyun; Hu, Yuzhou; Guo, Yi; Wang, Yuanyuan; Yu, Jinhua

    2018-02-01

    This work focused on extracting novel and validated digital high-throughput features to present a detailed and comprehensive description of the American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) with the goal of improving the accuracy of ultrasound breast cancer diagnosis. First, the phase congruency approach was used to segment the tumors automatically. Second, high-throughput features were designed and extracted on the basis of each BI-RADS category. Then features were selected based on the basis of a Student t test and genetic algorithm. Finally, the AdaBoost classifier was used to differentiate benign tumors from malignant ones. Experiments were conducted on a database of 138 pathologically proven breast tumors. The system was compared with 6 state-of-art BI-RADS feature extraction methods. By using leave-one-out cross-validation, our system achieved a highest overall accuracy of 93.48%, a sensitivity of 94.20%, a specificity of 92.75%, and an area under the receiver operating characteristic curve of 95.67%, respectively, which were superior to those of other methods. The experiments demonstrated that our computerized BI-RADS feature system was capable of helping radiologists detect breast cancers more accurately and provided more guidance for final decisions. © 2017 by the American Institute of Ultrasound in Medicine.

  6. Segmentation of tumor ultrasound image in HIFU therapy based on texture and boundary encoding

    International Nuclear Information System (INIS)

    Zhang, Dong; Xu, Menglong; Quan, Long; Yang, Yan; Qin, Qianqing; Zhu, Wenbin

    2015-01-01

    It is crucial in high intensity focused ultrasound (HIFU) therapy to detect the tumor precisely with less manual intervention for enhancing the therapy efficiency. Ultrasound image segmentation becomes a difficult task due to signal attenuation, speckle effect and shadows. This paper presents an unsupervised approach based on texture and boundary encoding customized for ultrasound image segmentation in HIFU therapy. The approach oversegments the ultrasound image into some small regions, which are merged by using the principle of minimum description length (MDL) afterwards. Small regions belonging to the same tumor are clustered as they preserve similar texture features. The mergence is completed by obtaining the shortest coding length from encoding textures and boundaries of these regions in the clustering process. The tumor region is finally selected from merged regions by a proposed algorithm without manual interaction. The performance of the method is tested on 50 uterine fibroid ultrasound images from HIFU guiding transducers. The segmentations are compared with manual delineations to verify its feasibility. The quantitative evaluation with HIFU images shows that the mean true positive of the approach is 93.53%, the mean false positive is 4.06%, the mean similarity is 89.92%, the mean norm Hausdorff distance is 3.62% and the mean norm maximum average distance is 0.57%. The experiments validate that the proposed method can achieve favorable segmentation without manual initialization and effectively handle the poor quality of the ultrasound guidance image in HIFU therapy, which indicates that the approach is applicable in HIFU therapy. (paper)

  7. Segmentation of tumor ultrasound image in HIFU therapy based on texture and boundary encoding

    Science.gov (United States)

    Zhang, Dong; Xu, Menglong; Quan, Long; Yang, Yan; Qin, Qianqing; Zhu, Wenbin

    2015-02-01

    It is crucial in high intensity focused ultrasound (HIFU) therapy to detect the tumor precisely with less manual intervention for enhancing the therapy efficiency. Ultrasound image segmentation becomes a difficult task due to signal attenuation, speckle effect and shadows. This paper presents an unsupervised approach based on texture and boundary encoding customized for ultrasound image segmentation in HIFU therapy. The approach oversegments the ultrasound image into some small regions, which are merged by using the principle of minimum description length (MDL) afterwards. Small regions belonging to the same tumor are clustered as they preserve similar texture features. The mergence is completed by obtaining the shortest coding length from encoding textures and boundaries of these regions in the clustering process. The tumor region is finally selected from merged regions by a proposed algorithm without manual interaction. The performance of the method is tested on 50 uterine fibroid ultrasound images from HIFU guiding transducers. The segmentations are compared with manual delineations to verify its feasibility. The quantitative evaluation with HIFU images shows that the mean true positive of the approach is 93.53%, the mean false positive is 4.06%, the mean similarity is 89.92%, the mean norm Hausdorff distance is 3.62% and the mean norm maximum average distance is 0.57%. The experiments validate that the proposed method can achieve favorable segmentation without manual initialization and effectively handle the poor quality of the ultrasound guidance image in HIFU therapy, which indicates that the approach is applicable in HIFU therapy.

  8. Neuropsychological function in adults after high dose fractionated radiation therapy of skull base tumors

    International Nuclear Information System (INIS)

    Glosser, Guila; McManus, Pat; Munzenrider, John; Austin-Seymour, Mary; Fullerton, Barbara; Adams, Judy; Urie, Marcia M.

    1997-01-01

    Purpose: To evaluate the long term effects of high dose fractionated radiation therapy on brain functioning prospectively in adults without primary brain tumors. Methods and Materials: Seventeen patients with histologically confirmed chordomas and low grade chondrosarcomas of the skull base were evaluated with neuropsychological measures of intelligence, language, memory, attention, motor function and mood following surgical resection/biopsy of the tumor prior to irradiation, and then at about 6 months, 2 years and 4 years following completion of treatment. None received chemotherapy. Results: In the patients without tumor recurrence or radiation necrosis, there were no indications of adverse effects on cognitive functioning in the post-acute through the late stages after brain irradiation. Even in patients who received doses of radiation up to 66 Cobalt Gy equivalent through nondiseased (temporal lobe) brain tissue, memory and cognitive functioning remained stable for up to 5 years after treatment. A mild decline in psycho-motor speed was seen in more than half of the patients, and motor slowing was related to higher radiation doses in midline and temporal lobe brain structures. Conclusion: Results suggest that in adults, tolerance for focused radiation is relatively high in cortical brain structures

  9. Base compaction specification feasibility analysis.

    Science.gov (United States)

    2012-12-01

    The objective of this research is to establish the technical engineering and cost : analysis concepts that will enable WisDOT management to objectively evaluate the : feasibility of switching construction specification philosophies for aggregate base...

  10. Analysis of mobile phone use among young patients with brain tumors in Japan.

    Science.gov (United States)

    Sato, Yasuto; Kojimahara, Noriko; Yamaguchi, Naohito

    2017-07-01

    The purpose of this study was to clarify ownership and usage of mobile phones among young patients with brain tumors in Japan. The subjects of this study were patients with brain tumors diagnosed between 2006 and 2010 who were between the ages of 6 and 18 years. The target population for the analysis was 82 patients. Patients were divided into two groups: 16 patients who were mobile phone owners 1 year before diagnosis, and 66 patients who did not own mobile phones (non-owners). Using data on the mobile phone ownership rate obtained from three general-population surveys, we calculated the expected number of mobile phone owners. The three age-adjusted standardized ownership ratios were 0.83 (95% confidence interval [CI]: 0.56-1.22), 0.51 (95% CI: 0.24-1.04), and 0.75 (95% CI: 0.42-1.32). The mobile phone ownership prevalence among the young Japanese patients with brain tumors in the current study does not differ from available estimates for the general population of corresponding age. However, since the use of mobile phones among children is increasing annually, investigations into the health effects of mobile phone use among children should continue. Bioelectromagnetics. 38:349-355, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  11. Survival analysis of colorectal cancer patients with tumor recurrence using global score test methodology

    Science.gov (United States)

    Zain, Zakiyah; Aziz, Nazrina; Ahmad, Yuhaniz; Azwan, Zairul; Raduan, Farhana; Sagap, Ismail

    2014-12-01

    Colorectal cancer is the third and the second most common cancer worldwide in men and women respectively, and the second in Malaysia for both genders. Surgery, chemotherapy and radiotherapy are among the options available for treatment of patients with colorectal cancer. In clinical trials, the main purpose is often to compare efficacy between experimental and control treatments. Treatment comparisons often involve several responses or endpoints, and this situation complicates the analysis. In the case of colorectal cancer, sets of responses concerned with survival times include: times from tumor removal until the first, the second and the third tumor recurrences, and time to death. For a patient, the time to recurrence is correlated to the overall survival. In this study, global score test methodology is used in combining the univariate score statistics for comparing treatments with respect to each survival endpoint into a single statistic. The data of tumor recurrence and overall survival of colorectal cancer patients are taken from a Malaysian hospital. The results are found to be similar to those computed using the established Wei, Lin and Weissfeld method. Key factors such as ethnic, gender, age and stage at diagnose are also reported.

  12. 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.

  13. Survival analysis of colorectal cancer patients with tumor recurrence using global score test methodology

    Energy Technology Data Exchange (ETDEWEB)

    Zain, Zakiyah, E-mail: zac@uum.edu.my; Ahmad, Yuhaniz, E-mail: yuhaniz@uum.edu.my [School of Quantitative Sciences, Universiti Utara Malaysia, UUM Sintok 06010, Kedah (Malaysia); Azwan, Zairul, E-mail: zairulazwan@gmail.com, E-mail: farhanaraduan@gmail.com, E-mail: drisagap@yahoo.com; Raduan, Farhana, E-mail: zairulazwan@gmail.com, E-mail: farhanaraduan@gmail.com, E-mail: drisagap@yahoo.com; Sagap, Ismail, E-mail: zairulazwan@gmail.com, E-mail: farhanaraduan@gmail.com, E-mail: drisagap@yahoo.com [Surgery Department, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, 56000 Bandar Tun Razak, Kuala Lumpur (Malaysia); Aziz, Nazrina, E-mail: nazrina@uum.edu.my

    2014-12-04

    Colorectal cancer is the third and the second most common cancer worldwide in men and women respectively, and the second in Malaysia for both genders. Surgery, chemotherapy and radiotherapy are among the options available for treatment of patients with colorectal cancer. In clinical trials, the main purpose is often to compare efficacy between experimental and control treatments. Treatment comparisons often involve several responses or endpoints, and this situation complicates the analysis. In the case of colorectal cancer, sets of responses concerned with survival times include: times from tumor removal until the first, the second and the third tumor recurrences, and time to death. For a patient, the time to recurrence is correlated to the overall survival. In this study, global score test methodology is used in combining the univariate score statistics for comparing treatments with respect to each survival endpoint into a single statistic. The data of tumor recurrence and overall survival of colorectal cancer patients are taken from a Malaysian hospital. The results are found to be similar to those computed using the established Wei, Lin and Weissfeld method. Key factors such as ethnic, gender, age and stage at diagnose are also reported.

  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. Gait analysis in children treated by surgery followed by adjuvant therapy for posterior fossa tumors.

    Science.gov (United States)

    Fiorillo, Amedeo; Rinaldi, Manuela; Foggia, Luigi

    2010-12-01

    Children affected by posterior fossa tumors show signs and symptoms of neurological dysfunction, associated both to cancer itself and to cancer therapies. Abnormal gait and coordination difficulties are frequent presenting features. Radiation therapy represents the main adjuvant treatment for these patients. However it can produce significant neurologic injury, also manifested as gait disturbance months after treatment. We have analyzed temporo-spatial parameters of gait in sixteen children treated for posterior fossa tumors, mainly medulloblastomas. In all children we found a typical gait pattern of cerebellar ataxia. There were no significant differences between data obtained in children affected by severe neurological impairment and those having slight or even hardly recognizable physical signs. Although the number of patients studied is not large enough to allow definitive conclusions and gait analyses were performed after treatment, our results suggest that most children treated for posterior fossa tumors have gait disturbances and in some of them these are subclinical. Standard gait analysis laboratory methods can thus be a valuable tool for the careful assessment and follow-up of these patients.

  16. Glioma Groups Based on 1p/19q, IDH, and TERT Promoter Mutations in Tumors.

    Science.gov (United States)

    Eckel-Passow, Jeanette E; Lachance, Daniel H; Molinaro, Annette M; Walsh, Kyle M; Decker, Paul A; Sicotte, Hugues; Pekmezci, Melike; Rice, Terri; Kosel, Matt L; Smirnov, Ivan V; Sarkar, Gobinda; Caron, Alissa A; Kollmeyer, Thomas M; Praska, Corinne E; Chada, Anisha R; Halder, Chandralekha; Hansen, Helen M; McCoy, Lucie S; Bracci, Paige M; Marshall, Roxanne; Zheng, Shichun; Reis, Gerald F; Pico, Alexander R; O'Neill, Brian P; Buckner, Jan C; Giannini, Caterina; Huse, Jason T; Perry, Arie; Tihan, Tarik; Berger, Mitchell S; Chang, Susan M; Prados, Michael D; Wiemels, Joseph; Wiencke, John K; Wrensch, Margaret R; Jenkins, Robert B

    2015-06-25

    The prediction of clinical behavior, response to therapy, and outcome of infiltrative glioma is challenging. On the basis of previous studies of tumor biology, we defined five glioma molecular groups with the use of three alterations: mutations in the TERT promoter, mutations in IDH, and codeletion of chromosome arms 1p and 19q (1p/19q codeletion). We tested the hypothesis that within groups based on these features, tumors would have similar clinical variables, acquired somatic alterations, and germline variants. We scored tumors as negative or positive for each of these markers in 1087 gliomas and compared acquired alterations and patient characteristics among the five primary molecular groups. Using 11,590 controls, we assessed associations between these groups and known glioma germline variants. Among 615 grade II or III gliomas, 29% had all three alterations (i.e., were triple-positive), 5% had TERT and IDH mutations, 45% had only IDH mutations, 7% were triple-negative, and 10% had only TERT mutations; 5% had other combinations. Among 472 grade IV gliomas, less than 1% were triple-positive, 2% had TERT and IDH mutations, 7% had only IDH mutations, 17% were triple-negative, and 74% had only TERT mutations. The mean age at diagnosis was lowest (37 years) among patients who had gliomas with only IDH mutations and was highest (59 years) among patients who had gliomas with only TERT mutations. The molecular groups were independently associated with overall survival among patients with grade II or III gliomas but not among patients with grade IV gliomas. The molecular groups were associated with specific germline variants. Gliomas were classified into five principal groups on the basis of three tumor markers. The groups had different ages at onset, overall survival, and associations with germline variants, which implies that they are characterized by distinct mechanisms of pathogenesis. (Funded by the National Institutes of Health and others.).

  17. [Clinical pathological analysis in 14 cases of pancreatic solid-pseudopapillary tumors].

    Science.gov (United States)

    Mei, Fang; DU, Juan; Ma, Xiao-long

    2009-12-18

    To observe clinical and pathological features of pancreatic solid-pseudopapillary tumor (SPPT), and to find some useful immunohistochemical methods for its differential diagnosis. The clinical features of 14 SPPT patients were obtained. Each case underwent microscopic observation and immunohistochemical staining. The primary antibodies were CgA, Syn, E-cadherin, beta-catenin and Cyclin D1. These results were compared with 5 pancreatic well-differentiated tumors and well-differentiated carcinomas (WET/WEC). SPPT mainly involved young women, and the head of pancreas was the commonest location. Tumors were always in solid and cystic gross appearance. Although the tumor's borderlines seemed clear, focal infiltrations could often be identified. The histological features of SPPT were similar in some aspects to those of WET/WEC, especially the solid pattern of WET/WEC. Both of them could express CgA and Syn. But all SPPTs lost E-cadherin membranous signals, and even had some nuclear signals(5/14), while all WET/WECs remained the same staining pattern with normal pancreas cells. beta-catenin positive signals in SPPTs were located both in nuclei and plasmas. WET/WECs' positive signals were all in membranes and plasmas, but negative ones in nuclei. Perinuclear dot-like signals could also be seen in the majority cells, which were similar to normal islet cells' staining pattern. SPPTs' nuclear positive rates of Cyclin D1 were usually more than 70% (12/14). WET/WECs' rates were all lower than 30%. Comprehensive analysis of patients' clinical, pathological features and immunohistochemistry results, including E-cadherin, beta-catenin and Cyclin D1, was helpful to the diagnosis of SPPT and its differential diagnosis of WET/WEC.

  18. Combined analysis of cell growth and apoptosis-regulating proteins in HPVs associated anogenital tumors

    International Nuclear Information System (INIS)

    Mitsuishi, Tsuyoshi; Kawana, Seiji; Ozaki, Kohji; Nakatake, Mayuka; Yamada, Osamu; Iwabu, Yukie; Tokunaga, Kenzo; Sata, Tetsutaro; Kaneko, Takehiko; Ohara, Kuniaki; Ohsawa, Ikuroh; Oda, Fumino; Yamada, Yuko

    2010-01-01

    The clinical course of human papillomavirus (HPV) associated with Bowenoid papulosis and condyloma acuminatum of anogenital tumors are still unknown. Here we evaluated molecules that are relevant to cellular proliferation and regulation of apoptosis in HPV associated anogenital tumors. We investigated the levels of telomerase activity, and inhibitor of apoptosis proteins (IAPs) family (c-IAP1, c-IAP2, XIAP) and c-Myc mRNA expression levels in 20 specimens of Bowenoid papulosis and 36 specimens of condyloma acuminatum in anogenital areas. Overall, phosphorylated (p-) AKT, p-ribosomal protein S6 (S6) and p-4E-binding protein 1 (4EBP1) expression levels were examined by immunohistochemistry in anogenital tumors both with and without positive telomerase activity. Positive telomerase activity was detected in 41.7% of Bowenoid papulosis and 27.3% of condyloma acuminatum compared to normal skin (p < 0.001). In contrast, the expression levels of Bowenoid papulosis indicated that c-IAP1, c-IAP2 and XIAP mRNA were significantly upregulated compared to those in both condyloma acuminatum samples (p < 0.001, p < 0.001, p = 0.022, respectively) and normal skin (p < 0.001, p = 0.002, p = 0.034, respectively). Overall, 30% of Bowenoid papulosis with high risk HPV strongly promoted IAPs family and c-Myc but condyloma acuminatum did not significantly activate those genes. Immunohistochemically, p-Akt and p-S6 expressions were associated with positive telomerase activity but not with p-4EBP1 expression. Combined analysis of the IAPs family, c-Myc mRNA expression, telomerase activity levels and p-Akt/p-S6 expressions may provide clinically relevant molecular markers in HPV associated anogenital tumors

  19. Identification of Potential Therapeutic Targets Among CXC Chemokines in Breast Tumor Microenvironment Using Integrative Bioinformatics Analysis

    Directory of Open Access Journals (Sweden)

    Erbao Chen

    2018-02-01

    Full Text Available Background/Aims: Breast cancer is a common cause of cancer mortality throughout the world. The cross-talk between cancer cells and interstitial cells exerts significant effects on neoplasia and tumor development and is modulated in part by chemokines. CXC is one of four chemokine families involved in mediating survival, angiogenesis, and immunosensitization by chemoattracting leukocytes, and it incentivizes tumor cell growth, invasion and metastasis in the tumor microenvironment. However, the differential expression profiles and prognostic values of these chemokines remains to be elucidated. Methods: In this study, we compared transcriptional CXC chemokines and survival data of patients with breast carcinoma (BC using the ONCOMINE dataset, Kaplan-Meier Plotter, TCGA and cBioPortal. Results: We discovered increased mRNA levels for CXCL8/10/11/16/17, whereas mRNA expression of CXCL1/2/3/4/5/6/7/12/14 was lower in BC patients compared to non-tumor tissues. Kaplan-Meier plots revealed that high mRNA levels of CXCL1/2/3/4/5/6/7/12/14 correlate with relapse-free survival (RFS in all types of BC patients. Conversely, high CXCL8/10/11 predicted worse RFS in BC patients. Significantly, high transcription levels of CXCL9/12/13/14 conferred an overall survival (OS advantage in BC patients, while high levels of CXCL8 demonstrated shorter OS in all BC sufferers. Conclusions: Integrative bioinformatics analysis suggests that CXCL8/12/14 are potential suitable targets for precision therapy in BC patients compared to other CXC chemokines.

  20. Identification of Potential Therapeutic Targets Among CXC Chemokines in Breast Tumor Microenvironment Using Integrative Bioinformatics Analysis.

    Science.gov (United States)

    Chen, Erbao; Qin, Xuan; Peng, Ke; Xu, Xiaojing; Li, Wei; Cheng, Xi; Tang, Cheng; Cui, Yuehong; Wang, Zhiming; Liu, Tianshu

    2018-02-23

    Breast cancer is a common cause of cancer mortality throughout the world. The cross-talk between cancer cells and interstitial cells exerts significant effects on neoplasia and tumor development and is modulated in part by chemokines. CXC is one of four chemokine families involved in mediating survival, angiogenesis, and immunosensitization by chemoattracting leukocytes, and it incentivizes tumor cell growth, invasion and metastasis in the tumor microenvironment. However, the differential expression profiles and prognostic values of these chemokines remains to be elucidated. In this study, we compared transcriptional CXC chemokines and survival data of patients with breast carcinoma (BC) using the ONCOMINE dataset, Kaplan-Meier Plotter, TCGA and cBioPortal. We discovered increased mRNA levels for CXCL8/10/11/16/17, whereas mRNA expression of CXCL1/2/3/4/5/6/7/12/14 was lower in BC patients compared to non-tumor tissues. Kaplan-Meier plots revealed that high mRNA levels of CXCL1/2/3/4/5/6/7/12/14 correlate with relapse-free survival (RFS) in all types of BC patients. Conversely, high CXCL8/10/11 predicted worse RFS in BC patients. Significantly, high transcription levels of CXCL9/12/13/14 conferred an overall survival (OS) advantage in BC patients, while high levels of CXCL8 demonstrated shorter OS in all BC sufferers. Integrative bioinformatics analysis suggests that CXCL8/12/14 are potential suitable targets for precision therapy in BC patients compared to other CXC chemokines. © 2018 The Author(s). Published by S. Karger AG, Basel.

  1. Feasibility of Affibody Molecule-Based PNA-Mediated Radionuclide Pretargeting of Malignant Tumors.

    Science.gov (United States)

    Honarvar, Hadis; Westerlund, Kristina; Altai, Mohamed; Sandström, Mattias; Orlova, Anna; Tolmachev, Vladimir; Karlström, Amelie Eriksson

    2016-01-01

    Affibody molecules are small (7 kDa), non-immunoglobulin scaffold proteins with a potential as targeting agents for radionuclide imaging of cancer. However, high renal re-absorption of Affibody molecules prevents their use for radionuclide therapy with residualizing radiometals. We hypothesized that the use of Affibody-based peptide nucleic acid (PNA)-mediated pretargeting would enable higher accumulation of radiometals in tumors than in kidneys. To test this hypothesis, we designed an Affibody-PNA chimera ZHER2:342-SR-HP1 containing a 15-mer HP1 PNA recognition tag and a complementary HP2 hybridization probe permitting labeling with both (125)I and (111)In. (111)In-ZHER2:342-SR-HP1 bound specifically to HER2-expressing BT474 and SKOV-3 cancer cells in vitro, with a KD of 6±2 pM for binding to SKOV-3 cells. Specific high affinity binding of the radiolabeled complementary PNA probe (111)In-/(125)I-HP2 to ZHER2:342-SR-HP1 pre-treated cells was demonstrated. (111)In-ZHER2:342-SR-HP1 demonstrated specific accumulation in SKOV-3 xenografts in BALB/C nu/nu mice and rapid clearance from blood. Pre-saturation of SKOV-3 with non-labeled anti-HER2 Affibody or the use of HER2-negative Ramos xenografts resulted in significantly lower tumor uptake of (111)In-ZHER2:342-SR-HP1. The complementary PNA probe (111)In/(125)I-HP2 accumulated in SKOV-3 xenografts when ZHER2:342-SR-HP1 was injected 4 h earlier. The tumor accumulation of (111)In/(125)I-HP2 was negligible without ZHER2:342-SR-HP1 pre-injection. The uptake of (111)In-HP2 in SKOV-3 xenografts was 19±2 %ID/g at 1 h after injection. The uptake in blood and kidneys was approximately 50- and 2-fold lower, respectively. In conclusion, we have shown that the use of Affibody-based PNA-mediated pretargeting enables specific delivery of radiometals to tumors and provides higher radiometal concentration in tumors than in kidneys.

  2. Tumors of the foot skeleton

    International Nuclear Information System (INIS)

    Ludwig, K.

    2007-01-01

    About 3-4% of all tumors and tumor-like lesions of the skeleton are located in the foot. Many of these lesions have a predilection for certain locations, so that the spectrum of entities occurring in the foot differs from the rest of the skeleton. Despite the fact that practically any entity can occur in the foot in rare cases, taken together the ten most frequent lesions make up for the vast majority of tumors and tumor-like lesions of the foot. The differential diagnosis of these lesions follows the general principles that apply in the rest of the skeleton. It is based on the analysis of the lesion's X-ray morphology and location, the patient's age, and in certain entities, the MR morphology. This article describes the most important tumors and tumor-like lesions of the foot, their differential diagnosis, and the principles of local staging. (orig.) [de

  3. Performance analysis of a dedicated breast MR-HIFU system for tumor ablation in breast cancer patients

    Science.gov (United States)

    Deckers, R.; Merckel, L. G.; de Senneville, B. Denis; Schubert, G.; Köhler, M.; Knuttel, F. M.; Mali, W. P. Th M.; Moonen, C. T. W.; van den Bosch, M. A. A. J.; Bartels, L. W.

    2015-07-01

    MR-guided HIFU ablation is a promising technique for the non-invasive treatment of breast cancer. A phase I study was performed to assess the safety and treatment accuracy and precision of MR-HIFU ablation in breast cancer patients (n=10 ) using a newly developed MR-HIFU platform dedicated to applications in the breast. In this paper a technical analysis of the performance of the dedicated breast MR-HIFU system during breast tumors ablation is described. The main points of investigation were the spatial targeting accuracy and precision of the system and the performance of real-time respiration-corrected MR thermometry. The mean targeting accuracy was in the range of 2.4-2.6 mm, whereas the mean targeting precision was in the range of 1.5-1.8 mm. To correct for respiration-induced magnetic field fluctuations during MR temperature mapping a look-up-table (LUT)-based correction method was used. An optimized procedural sedation protocol in combination with the LUT-based correction method allowed for precise MR thermometry during the ablation procedure (temperature standard deviation muscle) was detected. The newly developed dedicated breast MR-HIFU system allows for safe, accurate and precise ablation of breast tumors.

  4. Computer-driven quantitative image analysis in the assessment of tumor cell and T cell features in diffuse large B cell lymphomas.

    Science.gov (United States)

    Gaudio, Francesco; Tamma, Roberto; Ingravallo, Giuseppe; Perrone, Tommasina; Laddaga, Filomena Emanuela; De Candia, Mariastella; Maiorano, Eugenio; Ribatti, Domenico; Specchia, Giorgina

    2018-04-01

    Diffuse large B cell lymphoma (DLBCL) is recognized as the most common non-Hodgkin lymphoma subtype. Advanced high-resolution digital scans of pathology slides have enabled the development of computer-based image analysis algorithms that may assist pathologists in quantifying immunohistochemical stains. In this retrospective study, we reviewed data from 29 patients affected by DLBCL. In order to evaluate the number of tumor cells and microenvironment T cells, we performed an analysis of CD20, Ki67, and CD3 counts, assessed with the Positive Pixel Count algorithm embedded in the Aperio ImageScope software. A lower tumor cell count was observed in patients with a non-germinal center immunophenotype, high LDH, splenomegaly and an IPI ≥ 3. A lower number of CD3 was observed in patients with bulky disease, an IPI ≥ 3 and disease stage 3-4. Overall, these data confirm that quantitative analysis of the tumor cells and of the tumor microenvironment by means of computer-driven quantitative image analysis may add new information in DLBCL diagnosis.

  5. Comparative study of contrast-enhanced ultrasound qualitative and quantitative analysis for identifying benign and malignant breast tumor lumps.

    Science.gov (United States)

    Liu, Jian; Gao, Yun-Hua; Li, Ding-Dong; Gao, Yan-Chun; Hou, Ling-Mi; Xie, Ting

    2014-01-01

    To compare the value of contrast-enhanced ultrasound (CEUS) qualitative and quantitative analysis in the identification of breast tumor lumps. Qualitative and quantitative indicators of CEUS for 73 cases of breast tumor lumps were retrospectively analyzed by univariate and multivariate approaches. Logistic regression was applied and ROC curves were drawn for evaluation and comparison. The CEUS qualitative indicator-generated regression equation contained three indicators, namely enhanced homogeneity, diameter line expansion and peak intensity grading, which demonstrated prediction accuracy for benign and malignant breast tumor lumps of 91.8%; the quantitative indicator-generated regression equation only contained one indicator, namely the relative peak intensity, and its prediction accuracy was 61.5%. The corresponding areas under the ROC curve for qualitative and quantitative analyses were 91.3% and 75.7%, respectively, which exhibited a statistically significant difference by the Z test (Pqualitative analysis to identify breast tumor lumps is better than with quantitative analysis.

  6. [Analysis of the pelvic stability after type I resection of iliac tumor].

    Science.gov (United States)

    Jia, Yong-wei; Cheng, Li-ming; Yu, Guang-rong; Yu, Yan; Lou, Yong-jian; Yang, Yun-feng; Ding, Zu-quan

    2008-03-01

    To analyze the pelvic stability after type I resection of iliac tumor. Six adult cadaveric specimens were tested. The iliac subtotal resection models were established according to Ennecking's type I resection. Markers were affixed to the key region of the pelves. Axial loading from the proximal lumbar was applied by MTS load cell in the gradient of 0-500 N in the double feet standing state. Images in front view were obtained using CCD camera. Based on Image J software, displacements of the first sacral vertebrae (S1) of the resected pelves and the intact pelves were calculated using digital marker tracing method with center-of-mass algorithm. Serious instabilities were found in the resected pelves. S1 rotational movements around the normal side femoral head of the resected pelvis were found. The average vertical displacement of S1 of the resected pelvis was (7 +/- 3) mm under vertical load of 500 newtons, which were 8.3 times compared to the intact pelvis. The average angle of S1 rotation around the normal side femoral head of the resected pelvis was (4.0 +/- 1.8) degrees, which were 12.5 times compared to the intact pelvis. Biomechanical model of type I resection of iliac tumor are established. Essential pelvic reconstruction must be introduced because of the serious instability of the bone defection after tumor resection.

  7. 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

  8. MDM2 SNP309, gene-gene interaction, and tumor susceptibility: an updated meta-analysis

    International Nuclear Information System (INIS)

    Wan, Yan; Wu, Wei; Yin, Zhihua; Guan, Peng; Zhou, Baosen

    2011-01-01

    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. 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. 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 in the stratified analysis by p53 mutation status

  9. Meta-analysis of laparoscopic vs. open resection of gastric gastrointestinal stromal tumors.

    Directory of Open Access Journals (Sweden)

    Liangying Ye

    Full Text Available This meta-analysis compared laparoscopic surgery (LAP and open resection (OPEN for the treatment of gastric gastrointestinal stromal tumors (GISTs with regard to feasibility and safety.We searched PubMed, Embase, and Web of Science for studies published before March 2016 comparing the LAP and OPEN procedures for GISTs. RevMan 5.1 software was used for the meta-analysis.In total, 28 studies met the inclusion criteria for the meta-analysis. The mean tumor sizes in the OPEN and LAP groups were 4.54 and 5.67 cm. Compared with the OPEN patients, the LAP patients experienced shorter surgical times (P = 0.05, less blood loss (P5 cm, the present study did not report significant differences in operation time (P = 0.93, postoperative complications (P = 0.30, or recurrence rate (P = 0.61 between the two groups, though LAP was associated with favorable results regarding blood loss (P = 0.03 and hospital stay (P5 cm, no significant difference was detected between LAP and OPEN if patient selection and intraoperative decisions were carefully considered.

  10. Identification of tumor specimens by DNA analysis in a case of histocytological paraffin tissue block swapping

    Science.gov (United States)

    Raina, Anupuma; Yadav, Bhuvnesh; Ali, Sher; Das Dogra, Tirath

    2011-01-01

    We report on a patient who was diagnosed with high-grade breast carcinoma by all the pre-surgery clinical evidence of malignancy, but histopathological reports did not reveal any such tumor residue in the post-surgical tissue block. This raised a suspicion that either exchange of block, labeling error, or a technical error took place during gross examination of the tissue. The mastectomy residue was unprocurable to sort out the problem. So, two doubtful paraffin blocks were sent for DNA fingerprinting analysis. The partial DNA profiles (8-9/15 loci) were obtained from histocytological blocks. The random matching probability for both the paraffin blocks and the patient’s blood were found to be 1 in 4.43E4, 1.89E6, and 8.83E13, respectively for Asian population. Multiplex short tandem repeat analysis applied in this case determined that the cause of tumor absence was an error in gross examination of the post-surgical tissue. Moreover, the analysis helped in justifying the therapy given to the patient. Thus, with DNA fingerprinting technique, it was concluded that there was no exchange of the blocks between the two patients operated on the same day and the treatment given to the concerned patient was in the right direction. PMID:21674839

  11. Risk associated with central catheters for malignant tumor patients: a systematic review and meta-analysis

    Science.gov (United States)

    Lv, Yajuan; Hou, Yong; Pan, Bo; Ma, Yuwan; Li, Paiyun; Yu, Lili; Xu, Deguo; Song, Juanjuan; Shang, Heli; Wang, Hongyan; Tian, Yuan

    2018-01-01

    The risk of venous thrombosis and mortality associated with central catheter (PICC/CICC) for malignant tumor patients is not definite. So, we carried out a systematic review and meta-analysis to evaluate it. Among patients with comparing PICC with CICC, odds ratio (OR) or risk ratio (RR) was calculated with a random effect model meta-analysis. The result of the stratification analysis of 7 studies (PICC vs CICC) supported the theory that CICCs were associated with a decrease in the odds ratio of thrombosis compared with PICCs. 7 of 15 studies provided the information about the compared mortality rate of the patients. The result showed that CICCs were associated with a decrease in the odds ratio of thrombosis compared with PICCs (OR = 0.45, 95% CI:0.32–0.62, p PICCs are associated with a raised risk of deep vein thrombosis, and pharmacological deep vein thrombosis prophylaxis drugs is a beneficial factor in decreasing the incidence of thrombosis, while warfarin may decrease the risk of mortality of malignant tumor patients with CICCs. PMID:29552318

  12. Circulating tumor cells: clinically relevant molecular access based on a novel CTC flow cell.

    Directory of Open Access Journals (Sweden)

    Jessamine P Winer-Jones

    Full Text Available BACKGROUND: Contemporary cancer diagnostics are becoming increasing reliant upon sophisticated new molecular methods for analyzing genetic information. Limiting the scope of these new technologies is the lack of adequate solid tumor tissue samples. Patients may present with tumors that are not accessible to biopsy or adequate for longitudinal monitoring. One attractive alternate source is cancer cells in the peripheral blood. These rare circulating tumor cells (CTC require enrichment and isolation before molecular analysis can be performed. Current CTC platforms lack either the throughput or reliability to use in a clinical setting or they provide CTC samples at purities that restrict molecular access by limiting the molecular tools available. METHODOLOGY/PRINCIPAL FINDINGS: Recent advances in magetophoresis and microfluidics have been employed to produce an automated platform called LiquidBiopsy®. This platform uses high throughput sheath flow microfluidics for the positive selection of CTC populations. Furthermore the platform quantitatively isolates cells useful for molecular methods such as detection of mutations. CTC recovery was characterized and validated with an accuracy (<20% error and a precision (CV<25% down to at least 9 CTC/ml. Using anti-EpCAM antibodies as the capture agent, the platform recovers 78% of MCF7 cells within the linear range. Non specific recovery of background cells is independent of target cell density and averages 55 cells/mL. 10% purity can be achieved with as low as 6 CTCs/mL and better than 1% purity can be achieved with 1 CTC/mL. CONCLUSIONS/SIGNIFICANCE: The LiquidBiopsy platform is an automated validated platform that provides high throughput molecular access to the CTC population. It can be validated and integrated into the lab flow enabling CTC enumeration as well as recovery of consistently high purity samples for molecular analysis such as quantitative PCR and Next Generation Sequencing. This tool opens

  13. PET/CT Based In Vivo Evaluation of 64Cu Labelled Nanodiscs in Tumor Bearing Mice

    DEFF Research Database (Denmark)

    Huda, Pie; Binderup, Tina; Pedersen, Martin Cramer

    2015-01-01

    64Cu radiolabelled nanodiscs based on the 11 α-helix MSP1E3D1 protein and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine lipids were, for the first time, followed in vivo by positron emission tomography for evaluating the biodistribution of nanodiscs. A cancer tumor bearing mouse model...... radiolabelling of proteins via a chelating agent, DOTA, was developed. The reaction was performed at sufficiently mild conditions to be compatible with labelling of the protein part of a lipid-protein particle while fully conserving the particle structure including the amphipathic protein fold....

  14. Esophagus sparing with IMRT in lung tumor irradiation: An EUD-based optimization technique

    International Nuclear Information System (INIS)

    Chapet, Olivier; Thomas, Emma; Kessler, Marc L.; Fraass, Benedick A.; Ten Haken, Randall K.

    2005-01-01

    Purpose: The aim of this study was to evaluate (1) the use of generalized equivalent uniform dose (gEUD) to optimize dose escalation of lung tumors when the esophagus overlaps the planning target volume (PTV) and (2) the potential benefit of further dose escalation in only the part of the PTV that does not overlap the esophagus. Methods and Materials: The treatment-planning computed tomography (CT) scans of patients with primary lung tumors located in different regions of the left and right lung were used for the optimization of beamlet intensity modulated radiation therapy (IMRT) plans. In all cases, the PTV overlapped part of the esophagus. The dose in the PTV was maximized according to 7 different primary cost functions: 2 plans that made use of mean dose (MD) (the reference plan, in which the 95% isodose surface covered the PTV and a second plan that had no constraint on the minimum isodose), 3 plans based on maximizing gEUD for the whole PTV with ever increasing assumptions for tumor aggressiveness, and 2 plans that used different gEUD values in 2 simultaneous, overlapping target volumes (the whole PTV and the PTV minus esophagus). Beam arrangements and NTCP-based costlets for the organs at risk (OARs) were kept identical to the original conformal plan for each case. Regardless of optimization method, the relative ranking of the resulting plans was evaluated in terms of the absence of cold spots within the PTV and the final gEUD computed for the whole PTV. Results: Because the MD-optimized plans lacked a constraint on minimum PTV coverage, they resulted in cold spots that affected approximately 5% of the PTV volume. When optimizing over the whole PTV volume, gEUD-optimized plans resulted in higher equivalent uniform PTV doses than did the reference plan while still maintaining normal-tissue constraints. However, only under the assumption of extremely aggressive tumors could cold spots in the PTV be avoided. Generally, high-level overall results are obtained

  15. Skull Base Clear Cell Carcinoma, Metastasis of Renal Primary Tumor: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Ilson Sepúlveda

    2013-08-01

    Full Text Available We report on a patient who presented with cranial nerve VI bilateral paresis, absence of pharyngeal reflex, dysarthria, right tongue deviation, and right facial paralysis. Imaging studies showed an expansive process in the cranial base with clivus and petrous apex osteolysis. A biopsy confirmed the presence of clear cell adenocarcinoma and suspicion of renal tumor metastases. Abdominal imaging studies revealed a mass in the right kidney. Consequently, radiotherapy was performed, and the patient was enrolled in a palliative care and pain control program.

  16. Parameterization des modeles tumoral bases sur des maillages des donnees experimentaux.

    OpenAIRE

    Jagiella , Nick

    2012-01-01

    In order to establish a predictive model for in-vivo tumor growth and therapy, a multiscale model has to be set-up and calibrated individually in a stepwise process to a targeted cell type and di erent environments (in-vitro and in-vivo). As a proof of principle we will present the process chain of model construction and parametrization from di erent data sources for the avascular growth of the EMT6/Ro and the SK-MES-1 cell line. In a rst step, a multiscale and individual-based model has been...

  17. High-content Analysis of Antibody Phage-display Library Selection Outputs Identifies Tumor Selective Macropinocytosis-dependent Rapidly Internalizing Antibodies*

    Science.gov (United States)

    Ha, Kevin D.; Bidlingmaier, Scott M.; Zhang, Yafeng; Su, Yang; Liu, Bin

    2014-01-01

    Many forms of antibody-based targeted therapeutics, including antibody drug conjugates, utilize the internalizing function of the targeting antibody to gain intracellular entry into tumor cells. Ideal antibodies for developing such therapeutics should be capable of both tumor-selective binding and efficient endocytosis. The macropinocytosis pathway is capable of both rapid and bulk endocytosis, and recent studies have demonstrated that it is selectively up-regulated by cancer cells. We hypothesize that receptor-dependent macropinocytosis can be achieved using tumor-targeting antibodies that internalize via the macropinocytosis pathway, improving potency and selectivity of the antibody-based targeted therapeutic. Although phage antibody display libraries have been utilized to find antibodies that bind and internalize to target cells, no methods have been described to screen for antibodies that internalize specifically via macropinocytosis. We hereby describe a novel screening strategy to identify phage antibodies that bind and rapidly enter tumor cells via macropinocytosis. We utilized an automated microscopic imaging-based, High Content Analysis platform to identify novel internalizing phage antibodies that colocalize with macropinocytic markers from antibody libraries that we have generated previously by laser capture microdissection-based selection, which are enriched for internalizing antibodies binding to tumor cells in situ residing in their tissue microenvironment (Ruan, W., Sassoon, A., An, F., Simko, J. P., and Liu, B. (2006) Identification of clinically significant tumor antigens by selecting phage antibody library on tumor cells in situ using laser capture microdissection. Mol. Cell. Proteomics. 5, 2364–2373). Full-length human IgG molecules derived from macropinocytosing phage antibodies retained the ability to internalize via macropinocytosis, validating our screening strategy. The target antigen for a cross-species binding antibody with a highly

  18. High-content analysis of antibody phage-display library selection outputs identifies tumor selective macropinocytosis-dependent rapidly internalizing antibodies.

    Science.gov (United States)

    Ha, Kevin D; Bidlingmaier, Scott M; Zhang, Yafeng; Su, Yang; Liu, Bin

    2014-12-01

    Many forms of antibody-based targeted therapeutics, including antibody drug conjugates, utilize the internalizing function of the targeting antibody to gain intracellular entry into tumor cells. Ideal antibodies for developing such therapeutics should be capable of both tumor-selective binding and efficient endocytosis. The macropinocytosis pathway is capable of both rapid and bulk endocytosis, and recent studies have demonstrated that it is selectively up-regulated by cancer cells. We hypothesize that receptor-dependent macropinocytosis can be achieved using tumor-targeting antibodies that internalize via the macropinocytosis pathway, improving potency and selectivity of the antibody-based targeted therapeutic. Although phage antibody display libraries have been utilized to find antibodies that bind and internalize to target cells, no methods have been described to screen for antibodies that internalize specifically via macropinocytosis. We hereby describe a novel screening strategy to identify phage antibodies that bind and rapidly enter tumor cells via macropinocytosis. We utilized an automated microscopic imaging-based, High Content Analysis platform to identify novel internalizing phage antibodies that colocalize with macropinocytic markers from antibody libraries that we have generated previously by laser capture microdissection-based selection, which are enriched for internalizing antibodies binding to tumor cells in situ residing in their tissue microenvironment (Ruan, W., Sassoon, A., An, F., Simko, J. P., and Liu, B. (2006) Identification of clinically significant tumor antigens by selecting phage antibody library on tumor cells in situ using laser capture microdissection. Mol. Cell. Proteomics. 5, 2364-2373). Full-length human IgG molecules derived from macropinocytosing phage antibodies retained the ability to internalize via macropinocytosis, validating our screening strategy. The target antigen for a cross-species binding antibody with a highly active

  19. Acute Metabolic Alkalosis Enhances Response of C3H Mouse Mammary Tumors to the Weak Base Mitoxantrone

    Directory of Open Access Journals (Sweden)

    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.

  20. Systemic Distribution and Tumor Localization of Adoptively Transferred Lymphocytes in Mice: Comparison with Physiologically Based Pharmacokinetic Model

    Directory of Open Access Journals (Sweden)

    Robert J. Melder

    2002-01-01

    Full Text Available The mechanisms by which tumors are able to evade cellular immune responses are still largely unknown. It is likely, however, that the initial recruitment of lymphocytes to tumor vessels is limited by cell retention in normal tissue, which results in a low flux of these cells into the tumor vasculature. We grew MCaIV. (20mouse mammary carcinoma tumors in the leg of SCID mice and injected 111In-oxine-labeled, primed T lymphocytes directed against the tumor intravenously. The systemic distribution of cells in normal organs was similar between mice injected with primed and control lymphocyte populations, except for a delayed clearance of primed lymphocytes from the lungs. Kinetics of lymphocyte localization to the tumor were identical between the primed and control lymphocyte populations. Splenectomy before the injection of primed lymphocytes increased delivery of cells to the lungs and liver after 1 hour with no significant improvement in tumor localization. Within 24 to 168 hours after injection, localization of cells in the liver of splenectomized mice was higher than in the control group. However, no significant difference in tumor localization was observed between groups. A physiologically based compartmental model of lymphocyte distribution predicted the compartmental sequestration and identified model parameters critical for experimental planning and therapeutic optimization.

  1. Histopathological analysis of skin adnexal tumors: A three year study of 110 cases at a tertiary care center

    Directory of Open Access Journals (Sweden)

    Kanwalpreet Kaur

    2017-01-01

    Full Text Available Background: Skin adnexal tumors (SAT encompass wide spectrum of benign and malignant tumors that differentiate toward one or more adnexal structures found in normal skin. Overall incidence of SATs is low yet they can be challenging to diagnose. Aims: The aim of this study is to study the spectrum and microscopic features of SATs. Materials and Methods: It was a retrospective cross-sectional, descriptive study conducted over a period of 3 years. Formalin fixed, paraffin-embedded sections were stained with hematoxylin and eosin for histopathological analysis. Results: Out of the total 34,400 biopsies, 110 cases were diagnosed as SATs comprising 39.09% of tumors with follicular differentiation followed by tumors showing sweat gland differentiation (37.27%, and sebaceous differentiation (23.63%. The age ranged from 5 years to 85 years and male:female ratio was 1.03:1. Most of the tumors were benign (82.73% while only 17.27% were malignant. Pilomatricoma (28.2% was the most common benign tumor while sebaceous carcinoma (11.8% was the most common malignant tumor. Conclusion: Architectural features are of great importance in differentiating benign tumors from malignant.

  2. 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.

  3. 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

  4. 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

  5. Molecular analysis of urothelial cancer cell lines for modeling tumor biology and drug response.

    Science.gov (United States)

    Nickerson, M L; Witte, N; Im, K M; Turan, S; Owens, C; Misner, K; Tsang, S X; Cai, Z; Wu, S; Dean, M; Costello, J C; Theodorescu, D

    2017-01-05

    The utility of tumor-derived cell lines is dependent on their ability to recapitulate underlying genomic aberrations and primary tumor biology. Here, we sequenced the exomes of 25 bladder cancer (BCa) cell lines and compared mutations, copy number alterations (CNAs), gene expression and drug response to BCa patient profiles in The Cancer Genome Atlas (TCGA). We observed a mutation pattern associated with altered CpGs and APOBEC-family cytosine deaminases similar to mutation signatures derived from somatic alterations in muscle-invasive (MI) primary tumors, highlighting a major mechanism(s) contributing to cancer-associated alterations in the BCa cell line exomes. Non-silent sequence alterations were confirmed in 76 cancer-associated genes, including mutations that likely activate oncogenes TERT and PIK3CA, and alter chromatin-associated proteins (MLL3, ARID1A, CHD6 and KDM6A) and established BCa genes (TP53, RB1, CDKN2A and TSC1). We identified alterations in signaling pathways and proteins with related functions, including the PI3K/mTOR pathway, altered in 60% of lines; BRCA DNA repair, 44%; and SYNE1-SYNE2, 60%. Homozygous deletions of chromosome 9p21 are known to target the cell cycle regulators CDKN2A and CDKN2B. This loci was commonly lost in BCa cell lines and we show the deletions extended to the polyamine enzyme methylthioadenosine (MTA) phosphorylase (MTAP) in 36% of lines, transcription factor DMRTA1 (27%) and antiviral interferon epsilon (IFNE, 19%). Overall, the BCa cell line genomic aberrations were concordant with those found in BCa patient tumors. We used gene expression and copy number data to infer pathway activities for cell lines, then used the inferred pathway activities to build a predictive model of cisplatin response. When applied to platinum-treated patients gathered from TCGA, the model predicted treatment-specific response. Together, these data and analysis represent a valuable community resource to model basic tumor biology and to study

  6. Mosaic zebrafish transgenesis for functional genomic analysis of candidate cooperative genes in tumor pathogenesis.

    Science.gov (United States)

    Ung, Choong Yong; Guo, Feng; Zhang, Xiaoling; Zhu, Zhihui; Zhu, Shizhen

    2015-03-31

    Comprehensive genomic analysis has uncovered surprisingly large numbers of genetic alterations in various types of cancers. To robustly and efficiently identify oncogenic "drivers" among these tumors and define their complex relationships with concurrent genetic alterations during tumor pathogenesis remains a daunting task. Recently, zebrafish have emerged as an important animal model for studying human diseases, largely because of their ease of maintenance, high fecundity, obvious advantages for in vivo imaging, high conservation of oncogenes and their molecular pathways, susceptibility to tumorigenesis and, most importantly, the availability of transgenic techniques suitable for use in the fish. Transgenic zebrafish models of cancer have been widely used to dissect oncogenic pathways in diverse tumor types. However, developing a stable transgenic fish model is both tedious and time-consuming, and it is even more difficult and more time-consuming to dissect the cooperation of multiple genes in disease pathogenesis using this approach, which requires the generation of multiple transgenic lines with overexpression of the individual genes of interest followed by complicated breeding of these stable transgenic lines. Hence, use of a mosaic transient transgenic approach in zebrafish offers unique advantages for functional genomic analysis in vivo. Briefly, candidate transgenes can be coinjected into one-cell-stage wild-type or transgenic zebrafish embryos and allowed to integrate together into each somatic cell in a mosaic pattern that leads to mixed genotypes in the same primarily injected animal. This permits one to investigate in a faster and less expensive manner whether and how the candidate genes can collaborate with each other to drive tumorigenesis. By transient overexpression of activated ALK in the transgenic fish overexpressing MYCN, we demonstrate here the cooperation of these two oncogenes in the pathogenesis of a pediatric cancer, neuroblastoma that has

  7. Parameter estimation of brain tumors using intraoperative thermal imaging based on artificial tactile sensing in conjunction with artificial neural network

    Science.gov (United States)

    Sadeghi-Goughari, M.; Mojra, A.; Sadeghi, S.

    2016-02-01

    Intraoperative Thermal Imaging (ITI) is a new minimally invasive diagnosis technique that can potentially locate margins of brain tumor in order to achieve maximum tumor resection with least morbidity. This study introduces a new approach to ITI based on artificial tactile sensing (ATS) technology in conjunction with artificial neural networks (ANN) and feasibility and applicability of this method in diagnosis and localization of brain tumors is investigated. In order to analyze validity and reliability of the proposed method, two simulations were performed. (i) An in vitro experimental setup was designed and fabricated using a resistance heater embedded in agar tissue phantom in order to simulate heat generation by a tumor in the brain tissue; and (ii) A case report patient with parafalcine meningioma was presented to simulate ITI in the neurosurgical procedure. In the case report, both brain and tumor geometries were constructed from MRI data and tumor temperature and depth of location were estimated. For experimental tests, a novel assisted surgery robot was developed to palpate the tissue phantom surface to measure temperature variations and ANN was trained to estimate the simulated tumor’s power and depth. Results affirm that ITI based ATS is a non-invasive method which can be useful to detect, localize and characterize brain tumors.

  8. Parameter estimation of brain tumors using intraoperative thermal imaging based on artificial tactile sensing in conjunction with artificial neural network

    International Nuclear Information System (INIS)

    Sadeghi-Goughari, M; Mojra, A; Sadeghi, S

    2016-01-01

    Intraoperative Thermal Imaging (ITI) is a new minimally invasive diagnosis technique that can potentially locate margins of brain tumor in order to achieve maximum tumor resection with least morbidity. This study introduces a new approach to ITI based on artificial tactile sensing (ATS) technology in conjunction with artificial neural networks (ANN) and feasibility and applicability of this method in diagnosis and localization of brain tumors is investigated. In order to analyze validity and reliability of the proposed method, two simulations were performed. (i) An in vitro experimental setup was designed and fabricated using a resistance heater embedded in agar tissue phantom in order to simulate heat generation by a tumor in the brain tissue; and (ii) A case report patient with parafalcine meningioma was presented to simulate ITI in the neurosurgical procedure. In the case report, both brain and tumor geometries were constructed from MRI data and tumor temperature and depth of location were estimated. For experimental tests, a novel assisted surgery robot was developed to palpate the tissue phantom surface to measure temperature variations and ANN was trained to estimate the simulated tumor’s power and depth. Results affirm that ITI based ATS is a non-invasive method which can be useful to detect, localize and characterize brain tumors. (paper)

  9. 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.)

  10. 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

  11. ANALYSIS OF 2,3,7,8-TCDD TUMOR PROMOTION ACTIVITY ...

    Science.gov (United States)

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has a high estimated cancer potency in animals which has been reasoned to imply that TCDD might be carcinogenic to man. The animal cancer data show that TCDD can act in a solitary manner causing tumors without the participation of other known factors. owever, there exist animal cancer data indicating that TCDD can act as a tumor-promoting compound. This analysis examines which type of carcinogen and which mechanism best characterize TCDD cancer activity. It is suggested that TCDD acts by a hormonal mechanism to cause cancer in solitary manner, at low doses, in two species, and in a number of different organs, including rare sites. These observations in toto characterize TCDD as a complete carcinogen, which by definition encompasses both initiation and promotion carcinogenic activities. This analysis examines which type of carcinogen and which mechanism best characterize TCDD cancer activity. It is suggested that TCDD acts by a hormonal mechanism to cause cancer in solitary manner, at low doses, in two species, and in a number of different organs, including rare sites

  12. [Impact of technical and morphological factors on the precision of software-based MR tumor volumetry: a phantom study].

    Science.gov (United States)

    Rohde, S; Massberg, M; Reinhardt, J; Sartor, K; Heiland, S

    2008-07-01

    To investigate the impact of technical and morphological parameters on the precision of software-based MR tumor volumetry (SBV) in an in-vitro experimental setting. Tumor models were formed from a silicone compound in three different sizes with a max. diameter 4 cm (large). For each size a spherical, an elliptic and an irregular shaped model was produced. The true volume of the tumor models was established by water displacement. Tumor models were examined with a high-field MRI (TRIO, 3 Tesla, Siemens) with T 2-weighted sequences under optimized contrast conditions. Slice thickness was 1, 3 and 5 mm. The volume of the tumor models was then calculated using (1). manually driven volumetric software (SBVmanual) and (2). automatic volumetric software (SBVauto). The influence of the following parameters on the precision of SBV was analyzed: Size and shape of the tumor models, manual/automatic SBV, segmentation technique and slice thickness. In general, SBVauto measurements showed less deviation than measurements with SBVmanual (p technical factors. Using a "minimal" segmentation technique (e. g. excluding partial volume effects), volumes were underestimated in all cases, whereas volumes of middle and large tumor models were slightly overestimated when using a "maximum" segmentation technique (e. g. including partial volume effects; p = 0.01). Deviation of SBVmanual increased with slice thickness from 15.9 +/- 12.7 % (1 mm slices) to 27.1 +/- 21.3 % (5 mm-slices). In general, SBVauto measurements yielded smaller deviations than SBVmanual. However, both methods showed major inaccuracy in the volumetric estimation of small and irregular shaped tumor models, thus the tumor volumetry of these tumors has to be considered inappropriate for clinical practice. Moreover, the exactness of SBVmanual depended significantly on segmentation technique and slice thickness.

  13. Technical Note: A deep learning based auto segmentation of rectal tumors in MR images.

    Science.gov (United States)

    Wang, Jiazhou; Lu, Jiayu; Qin, Gan; Shen, Lijun; Sun, Yiqun; Ying, Hongmei; Zhang, Zhen; Hu, Weigang

    2018-04-16

    Manual contouring of gross tumor volumes (GTV) is a crucial and time-consuming process in rectum cancer radiotherapy. This study aims to develop a simple deep learning based auto segmentation algorithm to segment rectal tumors on T2 weighted MR images. MRI scans (3T, T2-weighted) of 93 patients with locally advanced (cT3-4 and/or cN1-2) rectal cancer treated with neoadjuvant chemoradiotherapy followed by surgery were enrolled in this study. A 2D U-net similar network was established as a training model. The model was trained in two phases to increase efficiency. These phases were tumor recognition and tumor segmentation. An opening (erosion and dilation) process was implemented to smooth contours after segmentation. Data were randomly separated into training (90%) and validation (10%) datasets for a 10-folder cross-validation. Additionally, 20 patients were double contoured for performance evaluation. Four indices were calculated to evaluate the similarity of automated and manual segmentation, including Hausdorff distance (HD), average surface distance (ASD), Dice index (DSC), and Jaccard index (JSC). The DSC, JSC, HD, ASD (mean±SD) were 0.74±0.14, 0.60±0.16, 20.44±13.35 and 3.25±1.69mm for validation dataset; and these indices were 0.71±0.13, 0.57±0.15, 14.91±7.62 and 2.67±1.46mm between two human radiation oncologists, respectively. No significant difference has been observed between automated segmentation and manual segmentation considering DSC (p=0.42), JSC (p=0.35), HD (p=0.079) and ASD (p=0.16). However, significant difference was found for HD (p=0.0027) without opening process. This study showed that a simple deep learning neural network can perform segmentation for rectum cancer based on MRI T2 images with results comparable to a human. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  14. Exon array analysis reveals neuroblastoma tumors have distinct alternative splicing patterns according to stage and MYCN amplification status

    Directory of Open Access Journals (Sweden)

    Wei Jun S

    2011-04-01

    Full Text Available Abstract Background Neuroblastoma (NB tumors are well known for their pronounced clinical and molecular heterogeneity. The global gene expression and DNA copy number alterations have been shown to have profound differences in tumors of low or high stage and those with or without MYCN amplification. RNA splicing is an important regulatory mechanism of gene expression, and differential RNA splicing may be associated with the clinical behavior of a tumor. Methods In this study, we used exon array profiling to investigate global alternative splicing pattern of 47 neuroblastoma samples in stage 1 and stage 4 with normal or amplified MYCN copy number (stage 1-, 4- and 4+. The ratio of exon-level expression to gene-level expression was used to detect alternative splicing events, while the gene-level expression was applied to characterize whole gene expression change. Results Principal component analysis (PCA demonstrated distinct splicing pattern in three groups of samples. Pairwise comparison identified genes with splicing changes and/or whole gene expression changes in high stage tumors. In stage 4- compared with stage 1- tumors, alternatively spliced candidate genes had little overlap with genes showing whole gene expression changes, and most of them were involved in different biological processes. In contrast, a larger number of genes exhibited either exon-level splicing, gene-level expression or both changes in stage 4+ versus stage 1- tumors. Those biological processes involved in stage 4- tumors were disrupted to a greater extent by both splicing and transcription regulations in stage 4+ tumors. Conclusions Our results demonstrated a significant role of alternative splicing in high stage neuroblastoma, and suggested a MYCN-associated splicing regulation pathway in stage 4+ tumors. The identification of differentially spliced genes and pathways in neuroblastoma tumors of different stages and molecular subtypes may be important to the

  15. Molecular analysis of desmoid tumors with a high-density single-nucleotide polymorphism array identifies new molecular candidate lesions

    OpenAIRE

    Erben, Philipp; Nowak, Daniel; Sauer, Christian; Ströbel, Philipp; Hofmann, Wolf-Karsten; Hofheinz, Ralf-Dieter; Hohenberger, Peter; Kasper, Bernd

    2012-01-01

    Background: Desmoid tumors are neoplastic proliferations of connective tissues. The mutation status of the gene coding for catenin (cadherin-associated protein) beta 1 (CTNNB1) and trisomy 8 on the chromosomal level have been described to have prognostic relevance. Patients and Methods: In order to elucidate new molecular mechanisms underlying these tumors, we carried out a molecular analysis with a genome-wide human high-density single-nucleotide polymorphism (SNP) array, in 9 patients. Resu...

  16. Cytogenetic analysis of tumoral thyroid tissues of thyroid glands of people from Gomel region as against Brest one

    International Nuclear Information System (INIS)

    Polonetskaya, S.N.; Demidchik, Yu.E.

    2001-01-01

    The analysis in vivo of histologically normal and tumoral thyroid tissues has shown that in organism of examined patients with thyroid cancer mutation process taken place not only in tumor but in histologically normal tissue. As a result of investigations pursued a significant increase in the level of aberrant cells in thyroid cell populations was revealed in people from Gomel regions as against Brest one

  17. Classification of 27 Tumor-Associated Antigens by Histochemical Analysis of 36 Freshly Resected Lung Cancer Tissues

    Directory of Open Access Journals (Sweden)

    Gene Kurosawa

    2016-11-01

    Full Text Available In previous studies, we identified 29 tumor-associated antigens (TAAs and isolated 488 human monoclonal antibodies (mAbs that specifically bind to one of the 29 TAAs. In the present study, we performed histochemical analysis of 36 freshly resected lung cancer tissues by using 60 mAbs against 27 TAAs. Comparison of the staining patterns of tumor cells, bronchial epithelial cells, and normal pulmonary alveolus cells and interalveolar septum allowed us to determine the type and location of cells that express target molecules, as well as the degree of expression. The patterns were classified into 7 categories. While multiple Abs were used against certain TAAs, the differences observed among them should be derived from differences in the binding activity and/or the epitope. Thus, such data indicate the versatility of respective clones as anti-cancer drugs. Although the information obtained was limited to the lung and bronchial tube, bronchial epithelial cells represent normal growing cells, and therefore, the data are informative. The results indicate that 9 of the 27 TAAs are suitable targets for therapeutic Abs. These 9 Ags include EGFR, HER2, TfR, and integrin α6β4. Based on our findings, a pharmaceutical company has started to develop anti-cancer drugs by using Abs to TfR and integrin α6β4. HGFR, PTP-LAR, CD147, CDCP1, and integrin αvβ3 are also appropriate targets for therapeutic purposes.

  18. Monte Carlo based dosimetry and treatment planning for neutron capture therapy of brain tumors

    International Nuclear Information System (INIS)

    Zamenhof, R.G.; Clement, S.D.; Harling, O.K.; Brenner, J.F.; Wazer, D.E.; Madoc-Jones, H.; Yanch, J.C.

    1990-01-01

    Monte Carlo based dosimetry and computer-aided treatment planning for neutron capture therapy have been developed to provide the necessary link between physical dosimetric measurements performed on the MITR-II epithermal-neutron beams and the need of the radiation oncologist to synthesize large amounts of dosimetric data into a clinically meaningful treatment plan for each individual patient. Monte Carlo simulation has been employed to characterize the spatial dose distributions within a skull/brain model irradiated by an epithermal-neutron beam designed for neutron capture therapy applications. The geometry and elemental composition employed for the mathematical skull/brain model and the neutron and photon fluence-to-dose conversion formalism are presented. A treatment planning program, NCTPLAN, developed specifically for neutron capture therapy, is described. Examples are presented illustrating both one and two-dimensional dose distributions obtainable within the brain with an experimental epithermal-neutron beam, together with beam quality and treatment plan efficacy criteria which have been formulated for neutron capture therapy. The incorporation of three-dimensional computed tomographic image data into the treatment planning procedure is illustrated. The experimental epithermal-neutron beam has a maximum usable circular diameter of 20 cm, and with 30 ppm of B-10 in tumor and 3 ppm of B-10 in blood, it produces a beam-axis advantage depth of 7.4 cm, a beam-axis advantage ratio of 1.83, a global advantage ratio of 1.70, and an advantage depth RBE-dose rate to tumor of 20.6 RBE-cGy/min (cJ/kg-min). These characteristics make this beam well suited for clinical applications, enabling an RBE-dose of 2,000 RBE-cGy/min (cJ/kg-min) to be delivered to tumor at brain midline in six fractions with a treatment time of approximately 16 minutes per fraction

  19. Antiproliferative Activity and Cellular Uptake of Evodiamine and Rutaecarpine Based on 3D Tumor Models

    Directory of Open Access Journals (Sweden)

    Hui Guo

    2016-07-01

    Full Text Available Evodiamine (EVO and rutaecarpine (RUT are promising anti-tumor drug candidates. The evaluation of the anti-proliferative activity and cellular uptake of EVO and RUT in 3D multicellular spheroids of cancer cells would better recapitulate the native situation and thus better reflect an in vivo response to the treatment. Herein, we employed the 3D culture of MCF-7 and SMMC-7721 cells based on hanging drop method and evaluated the anti-proliferative activity and cellular uptake of EVO and RUT in 3D multicellular spheroids, and compared the results with those obtained from 2D monolayers. The drugs’ IC50 values were significantly increased from the range of 6.4–44.1 μM in 2D monolayers to 21.8–138.0 μM in 3D multicellular spheroids, which may be due to enhanced mass barrier and reduced drug penetration in 3D models. The fluorescence of EVO and RUT was measured via fluorescence spectroscopy and the cellular uptake of both drugs was characterized in 2D tumor models. The results showed that the cellular uptake concentrations of RUT increased with increasing drug concentrations. However, the EVO concentrations uptaken by the cells showed only a small change with increasing drug concentrations, which may be due to the different solubility of EVO and Rut in solvents. Overall, this study provided a new vision of the anti-tumor activity of EVO and RUT via 3D multicellular spheroids and cellular uptake through the fluorescence of compounds.

  20. Gold-nanoparticle-based theranostic agents for radiotherapy of malignant solid tumors

    Science.gov (United States)