Estimation of lung tumor position from multiple anatomical features on 4D-CT using multiple regression analysis.

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Ono, Tomohiro; Nakamura, Mitsuhiro; Hirose, Yoshinori; Kitsuda, Kenji; Ono, Yuka; Ishigaki, Takashi; Hiraoka, Masahiro

2017-09-01

To estimate the lung tumor position from multiple anatomical features on four-dimensional computed tomography (4D-CT) data sets using single regression analysis (SRA) and multiple regression analysis (MRA) approach and evaluate an impact of the approach on internal target volume (ITV) for stereotactic body radiotherapy (SBRT) of the lung. Eleven consecutive lung cancer patients (12 cases) underwent 4D-CT scanning. The three-dimensional (3D) lung tumor motion exceeded 5 mm. The 3D tumor position and anatomical features, including lung volume, diaphragm, abdominal wall, and chest wall positions, were measured on 4D-CT images. The tumor position was estimated by SRA using each anatomical feature and MRA using all anatomical features. The difference between the actual and estimated tumor positions was defined as the root-mean-square error (RMSE). A standard partial regression coefficient for the MRA was evaluated. The 3D lung tumor position showed a high correlation with the lung volume (R = 0.92 ± 0.10). Additionally, ITVs derived from SRA and MRA approaches were compared with ITV derived from contouring gross tumor volumes on all 10 phases of the 4D-CT (conventional ITV). The RMSE of the SRA was within 3.7 mm in all directions. Also, the RMSE of the MRA was within 1.6 mm in all directions. The standard partial regression coefficient for the lung volume was the largest and had the most influence on the estimated tumor position. Compared with conventional ITV, average percentage decrease of ITV were 31.9% and 38.3% using SRA and MRA approaches, respectively. The estimation accuracy of lung tumor position was improved by the MRA approach, which provided smaller ITV than conventional ITV. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

A case of parotid tumor showing remarkable regression following hyperthermo-chemo-radiotherapy

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Fujimura, Takashi; Yonemura, Yutaka; Kamata, Toru

1987-01-01

A 72-year-old woman developed adenocarcinoma of the left parotid gland. Because of the excessive size of her tumor and the fact that she suffered from severe liver dysfunction, she was treated by hyperthermo-chemo-radiotherapy (HCR therapy). After ten sessions of radiofrequency hyperthermia with HEH 500 (13.56 MHz radiofrequency wave), 50-Gy irradiation from a linac and administration of 33.0 g of tegafur in suppository form, the tumor mass showed remarkable regression decreasing in size by as much as 84 % on computed tomography. Histologically, the tumor which was resected under local anesthesia, showed almost total necrosis. The multidisciplinary HCR therapy was well tolerated and effective as a therapy for cancer in this case. (author)

Hapten-Induced Contact Hypersensitivity, Autoimmune Reactions, and Tumor Regression: Plausibility of Mediating Antitumor Immunity

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Dan A. Erkes

2014-01-01

Full Text Available Haptens are small molecule irritants that bind to proteins and elicit an immune response. Haptens have been commonly used to study allergic contact dermatitis (ACD using animal contact hypersensitivity (CHS models. However, extensive research into contact hypersensitivity has offered a confusing and intriguing mechanism of allergic reactions occurring in the skin. The abilities of haptens to induce such reactions have been frequently utilized to study the mechanisms of inflammatory bowel disease (IBD to induce autoimmune-like responses such as autoimmune hemolytic anemia and to elicit viral wart and tumor regression. Hapten-induced tumor regression has been studied since the mid-1900s and relies on four major concepts: (1 ex vivo haptenation, (2 in situ haptenation, (3 epifocal hapten application, and (4 antigen-hapten conjugate injection. Each of these approaches elicits unique responses in mice and humans. The present review attempts to provide a critical appraisal of the hapten-mediated tumor treatments and offers insights for future development of the field.

Targeting Nanomedicine to Brain Tumors: Latest Progress and Achievements.

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Van't Root, Moniek; Lowik, Clemens; Mezzanotte, Laura

2017-01-01

Targeting nanomedicine to brain tumors is hampered by the heterogeneity of brain tumors and the blood brain barrier. These represent the main reasons of unsuccessful treatments. Nanomedicine based approaches hold promise for improved brain tissue distribution of drugs and delivery of combination therapies. In this review, we describe the recent advancements and latest achievements in the use of nanocarriers, virus and cell-derived nanoparticles for targeted therapy of brain tumors. We provide successful examples of nanomedicine based approaches for direct targeting of receptors expressed in brain tumor cells or modulation of pathways involved in cell survival as well as approaches for indirect targeting of cells in the tumor stroma and immunotherapies. Although the field is at its infancy, clinical trials involving nanomedicine based approaches for brain tumors are ongoing and many others will start in the near future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

YKL-40/c-Met expression in rectal cancer biopsies predicts tumor regression following neoadjuvant chemoradiotherapy: a multi-institutional study.

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Senetta, Rebecca; Duregon, Eleonora; Sonetto, Cristina; Spadi, Rossella; Mistrangelo, Massimiliano; Racca, Patrizia; Chiusa, Luigi; Munoz, Fernando H; Ricardi, Umberto; Arezzo, Alberto; Cassenti, Adele; Castellano, Isabella; Papotti, Mauro; Morino, Mario; Risio, Mauro; Cassoni, Paola

2015-01-01

Neoadjuvant chemo-radiotherapy (CRT) followed by surgical resection is the standard treatment for locally advanced rectal cancer, although complete tumor pathological regression is achieved in only up to 30% of cases. A clinicopathological and molecular predictive stratification of patients with advanced rectal cancer is still lacking. Here, c-Met and YKL-40 have been studied as putative predictors of CRT response in rectal cancer, due to their reported involvement in chemoradioresistance in various solid tumors. A multicentric study was designed to assess the role of c-Met and YKL-40 expression in predicting chemoradioresistance and to correlate clinical and pathological features with CRT response. Immunohistochemistry and fluorescent in situ hybridization for c-Met were performed on 81 rectal cancer biopsies from patients with locally advanced rectal adenocarcinoma. All patients underwent standard (50.4 gy in 28 fractions + concurrent capecitabine 825 mg/m2) neoadjuvant CRT or the XELOXART protocol. CRT response was documented on surgical resection specimens and recorded as tumor regression grade (TRG) according to the Mandard criteria. A significant correlation between c-Met and YKL-40 expression was observed (R = 0.43). The expressions of c-Met and YKL-40 were both significantly associated with a lack of complete response (86% and 87% of c-Met and YKL-40 positive cases, prectal cancer. Targeted therapy protocols could take advantage of prior evaluations of c-MET and YKL-40 expression levels to increase therapeutic efficacy.

Canine transmissible venereal tumor and seminoma: a cytohistopathology and chemotherapy study of tumors in the growth phase and during regression after chemotherapy.

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Javanbakht, J; Pedram, B; Taheriyan, M R; Khadivar, F; Hosseini, S H; Abdi, F S; Hosseini, E; Moloudizargari, M; Aghajanshakeri, S H; Javaherypour, S; Shafiee, R; Emrani Bidi, R

2014-06-01

In this study, 12 dogs affected by canine transmissible venereal tumor (CTVT) and testicular seminoma tumor were studied retrospectively. The cytological sample was smeared onto a glass slide and either air-dried for May-Grünwald-stain, and masses were surgically removed. The tumors were grossly examined, and sections of 4-μm thick were obtained from each sample and stained with H&E. For chemotherapy, vincristine sulfate was administered weekly as an infusion over 3 min via the cephalic vein at a dose of 0.025 mg/kg after diluting with physiological saline to a total amount of 10 ml. If no remission was observed after 8 weeks, chemotherapy was continued with weekly doxorubicin infusion at a dose of 1 mg/kg. All the tumor samples were divided into four cytohistopathologic groups, namely: multilobular (six cases), papillary (two cases), pedunculated (two cases), and tubular (two cases of seminoma). The most frequently represented tumor type was multilobular (6/10, 60 %) followed by pedunculated (2/10, 20 %), papillary (2/10, 20 %), and tubular (two cases of seminoma, 100 %). Cytological smears from eight tumors in regression after chemotherapy were poorly cellular, and many cells were fragmented. In two progressive tumors, there was an average of 1,406 ± 972 CTVT 200 cells/μl or 96.71 % of total cells counted. Thus, tumor cells represented 96.71 % of total cells within the biopsy specimens and the leukocytes 4.29 % (leukocyte, tumor cell ratio=0.062 ± 0.031). In eight regressive tumors, there was an average of 1,245 ± 1,032 CTVT 200 cells/μl or 97.31 % of total cells counted. Thus, tumor cells represented 97.31 % of total cells and leukocytes 2.69 % (leukocyte, tumor cell ratio=0.071 ± 0.174). Our data suggested that combination treatment with vincristine and doxorubicin in the future could be an excellent therapeutic alternative for the treatment of TVT for probably reducing the resistance to vincristine, and also, treatment success could easily be followed

Logistic Regression and Path Analysis Method to Analyze Factors influencing Students’ Achievement

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Noeryanti, N.; Suryowati, K.; Setyawan, Y.; Aulia, R. R.

2018-04-01

Students' academic achievement cannot be separated from the influence of two factors namely internal and external factors. The first factors of the student (internal factors) consist of intelligence (X1), health (X2), interest (X3), and motivation of students (X4). The external factors consist of family environment (X5), school environment (X6), and society environment (X7). The objects of this research are eighth grade students of the school year 2016/2017 at SMPN 1 Jiwan Madiun sampled by using simple random sampling. Primary data are obtained by distributing questionnaires. The method used in this study is binary logistic regression analysis that aims to identify internal and external factors that affect student’s achievement and how the trends of them. Path Analysis was used to determine the factors that influence directly, indirectly or totally on student’s achievement. Based on the results of binary logistic regression, variables that affect student’s achievement are interest and motivation. And based on the results obtained by path analysis, factors that have a direct impact on student’s achievement are students’ interest (59%) and students’ motivation (27%). While the factors that have indirect influences on students’ achievement, are family environment (97%) and school environment (37).

Comprehensive modulation of tumor progression and regression with periodic fasting and refeeding circles via boosting IGFBP-3 loops and NK responses.

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Chen, Xiancheng; Lin, Xiaojuan; Li, Meng

2012-10-01

Progressive tumor-bearing patients deserve to benefit from more realistic approaches. Here, a study revealed the impact of modified periodic fasting and refeeding regimen on tumor progression or regression with little or no loss of food intake and body weight. Human A549 lung, HepG-2 liver, and SKOV-3 ovary progressive tumor-bearing mice were established and subjected to 4 wk of periodic fasting/refeeding cycles (PFRC), including periodic 1-d fasting/6-d refeeding weekly (protocol 1) and periodic 2-d fasting/5-d refeeding weekly (P2DF/5DR, protocol 2), with ad libitum (AL)-fed hosts as controls. Afterwards, PFRC groups exhibited tumor growth arrest with some tendency towards regression; especially, complete regression of progressive tumors and metastases comprised between 43.75 and 56.25% of tumor-challenged hosts in P2DF/5DR group (P fasting/6-d refeeding weekly groups survived a 4-month study period vs. only 31.25-37.5% in AL control group. Immunological assays and Luminex microarray revealed that tumor growth remission is mainly via natural killer cell (NK) reactivity and cross-regulation of IGF-binding protein-3, IGF/IGF-receptor, and megakaryocyte growth and development factor autocrine and paracrine loops. In vivo cellular and humoral assays indicated that tumor-regressive induction by PFRC protocols could be partly terminated by NK cell and IGF-binding protein-3 blockade or replenishment of IGF-I/-II and megakaryocyte growth and development factor. These findings offer a better understanding of comprehensive modulation of periodic fasting/refeeding strategy on the balance between tumor progression and regression.

Multiple injections of electroporated autologous T cells expressing a chimeric antigen receptor mediate regression of human disseminated tumor.

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Zhao, Yangbing; Moon, Edmund; Carpenito, Carmine; Paulos, Chrystal M; Liu, Xiaojun; Brennan, Andrea L; Chew, Anne; Carroll, Richard G; Scholler, John; Levine, Bruce L; Albelda, Steven M; June, Carl H

2010-11-15

Redirecting T lymphocyte antigen specificity by gene transfer can provide large numbers of tumor-reactive T lymphocytes for adoptive immunotherapy. However, safety concerns associated with viral vector production have limited clinical application of T cells expressing chimeric antigen receptors (CAR). T lymphocytes can be gene modified by RNA electroporation without integration-associated safety concerns. To establish a safe platform for adoptive immunotherapy, we first optimized the vector backbone for RNA in vitro transcription to achieve high-level transgene expression. CAR expression and function of RNA-electroporated T cells could be detected up to a week after electroporation. Multiple injections of RNA CAR-electroporated T cells mediated regression of large vascularized flank mesothelioma tumors in NOD/scid/γc(-/-) mice. Dramatic tumor reduction also occurred when the preexisting intraperitoneal human-derived tumors, which had been growing in vivo for >50 days, were treated by multiple injections of autologous human T cells electroporated with anti-mesothelin CAR mRNA. This is the first report using matched patient tumor and lymphocytes showing that autologous T cells from cancer patients can be engineered to provide an effective therapy for a disseminated tumor in a robust preclinical model. Multiple injections of RNA-engineered T cells are a novel approach for adoptive cell transfer, providing flexible platform for the treatment of cancer that may complement the use of retroviral and lentiviral engineered T cells. This approach may increase the therapeutic index of T cells engineered to express powerful activation domains without the associated safety concerns of integrating viral vectors. Copyright © 2010 AACR.

SU-E-J-137: Incorporating Tumor Regression Into Robust Plan Optimization for Head and Neck Radiotherapy

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Zhang, P; Hu, J; Tyagi, N; Mageras, G; Lee, N; Hunt, M

2014-01-01

Purpose: To develop a robust planning paradigm which incorporates a tumor regression model into the optimization process to ensure tumor coverage in head and neck radiotherapy. Methods: Simulation and weekly MR images were acquired for a group of head and neck patients to characterize tumor regression during radiotherapy. For each patient, the tumor and parotid glands were segmented on the MR images and the weekly changes were formulated with an affine transformation, where morphological shrinkage and positional changes are modeled by a scaling factor, and centroid shifts, respectively. The tumor and parotid contours were also transferred to the planning CT via rigid registration. To perform the robust planning, weekly predicted PTV and parotid structures were created by transforming the corresponding simulation structures according to the weekly affine transformation matrix averaged over patients other than him/herself. Next, robust PTV and parotid structures were generated as the union of the simulation and weekly prediction contours. In the subsequent robust optimization process, attainment of the clinical dose objectives was required for the robust PTV and parotids, as well as other organs at risk (OAR). The resulting robust plans were evaluated by looking at the weekly and total accumulated dose to the actual weekly PTV and parotid structures. The robust plan was compared with the original plan based on the planning CT to determine its potential clinical benefit. Results: For four patients, the average weekly change to tumor volume and position was −4% and 1.2 mm laterally-posteriorly. Due to these temporal changes, the robust plans resulted in an accumulated PTV D95 that was, on average, 2.7 Gy higher than the plan created from the planning CT. OAR doses were similar. Conclusion: Integration of a tumor regression model into target delineation and plan robust optimization is feasible and may yield improved tumor coverage. Part of this research is supported

Pitfalls in the assessment of radioresponse as determined by tumor regression. Consideration based on the location and histologic constitution of tumors

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Ohara, Kiyoshi; Shimizu, Wakako; Itai, Yuji [Tsukuba Univ., Ibaraki (Japan). Inst. of Clinical Medicine

2000-05-01

To prove the following hypotheses regarding tumor shrinkage after radiotherapy. Tumors located on an outer tissue surface, e.g. esophageal tumors shrink faster than parenchymal tumors, e.g. lymph-node metastasis, because two clearance mechanisms, exfoliation and absorption, can operate in the former type of tumors whereas only absorption can function in the latter. Tumors which are being controlled do not necessarily respond completely, because tumors are constituted not only of tumor cells but also stromal tissues that are difficult to be absorbed. Long-term shrinkage patterns of a parenchymal tumor were determined by using 18 curatively irradiated hepatomas. Preoperatively irradiated thymomas (10) and lymph-node metastases (37) from head and neck cancers were examined histopathologically. Twenty-one esophageal cancers were used for intra-patient response comparison between the primary disease and the lymph-node metastases. Shrinkage patterns were generally biphasic: rapid exponential regression followed by a plateau phase. Histologically, thymomas generally consisted of predominant fibrous tissues and few remaining tumor cells. Radioresponse did not predict the presence of remaining cancer cells in the lymph nodes. Esophageal-cancer radiorespone was always higher for the primary disease than the lymph-node metastases. The location and histologic constitution of tumors must be taken into account in predicting radiocurability using radioresponse. (author)

Regression of conjunctival tumor during dietary treatment of celiac disease

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Tuncer Samuray

2010-01-01

Full Text Available A 3-year-old girl presented with a hemorrhagic conjunctival lesion in the right eye. The medical history revealed premature cessation of breast feeding, intolerance to the ingestion of baby foods, anorexia, and abdominal distention. Prior to her referral, endoscopic small intestinal biopsy had been carried out under general anesthesia with a possible diagnosis of Celiac Disease (CD. Her parents did not want their child to undergo general anesthesia for the second time for the excisional biopsy. We decided to follow the patient until all systemic investigations were concluded. In evaluation, the case was diagnosed with CD and the conjunctival tumor showed complete regression during gluten-free dietary treatment. The clinical fleshy appearance of the lesion with spider-like vascular extensions and subconjunctival hemorrhagic spots, possible association with an acquired immune system dysfunction due to CD, and spontaneous regression by a gluten-free diet led us to make a presumed diagnosis of conjunctival Kaposi sarcoma.

A histological evaluation and in vivo assessment of intratumoral near infrared photothermal nanotherapy-induced tumor regression

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Green HN

2014-11-01

Full Text Available Hadiyah N Green,1,2 Stephanie D Crockett,3 Dmitry V Martyshkin,1 Karan P Singh,2,4 William E Grizzle,2,5 Eben L Rosenthal,2,6 Sergey B Mirov11Department of Physics, Center for Optical Sensors and Spectroscopies, 2Comprehensive Cancer Center, 3Department of Pediatrics, Division of Neonatology, 4Department of Medicine, Division of Preventive Medicine, Biostatistics and Bioinformatics Shared Facility, 5Department of Pathology, 6Department of Surgery, Division of Otolaryngology, Head and Neck Surgery, The University of Alabama at Birmingham, Birmingham, AL, USAPurpose: Nanoparticle (NP-enabled near infrared (NIR photothermal therapy has realized limited success in in vivo studies as a potential localized cancer therapy. This is primarily due to a lack of successful methods that can prevent NP uptake by the reticuloendothelial system, especially the liver and kidney, and deliver sufficient quantities of intravenously injected NPs to the tumor site. Histological evaluation of photothermal therapy-induced tumor regression is also neglected in the current literature. This report demonstrates and histologically evaluates the in vivo potential of NIR photothermal therapy by circumventing the challenges of intravenous NP delivery and tumor targeting found in other photothermal therapy studies.Methods: Subcutaneous Cal 27 squamous cell carcinoma xenografts received photothermal nanotherapy treatments, radial injections of polyethylene glycol (PEG-ylated gold nanorods and one NIR 785 nm laser irradiation for 10 minutes at 9.5 W/cm2. Tumor response was measured for 10–15 days, gross changes in tumor size were evaluated, and the remaining tumors or scar tissues were excised and histologically analyzed.Results: The single treatment of intratumoral nanorod injections followed by a 10 minute NIR laser treatment also known as photothermal nanotherapy, resulted in ~100% tumor regression in ~90% of treated tumors, which was statistically significant in a

Tumor regression with a combination of drugs interfering with the tumor metabolism: efficacy of hydroxycitrate, lipoic acid and capsaicin.

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Schwartz, Laurent; Guais, Adeline; Israël, Maurice; Junod, Bernard; Steyaert, Jean-Marc; Crespi, Elisabetta; Baronzio, Gianfranco; Abolhassani, Mohammad

2013-04-01

Cellular metabolic alterations are now well described as implicated in cancer and some strategies are currently developed to target these different pathways. In previous papers, we demonstrated that a combination of molecules (namely alpha-lipoic acid and hydroxycitrate, i.e. Metabloc™) targeting the cancer metabolism markedly decreased tumor cell growth in mice. In this work, we demonstrate that the addition of capsaicin further delays tumor growth in mice in a dose dependant manner. This is true for the three animal model tested: lung (LLC) cancer, bladder cancer (MBT-2) and melanoma B16F10. There was no apparent side effect of this ternary combination. The addition of a fourth drug (octreotide) is even more effective resulting in tumor regression in mice bearing LLC cancer. These four compounds are all known to target the cellular metabolism not its DNA. The efficacy, the apparent lack of toxicity, the long clinical track records of these medications in human medicine, all points toward the need for a clinical trial. The dramatic efficacy of treatment suggests that cancer may simply be a disease of dysregulated cellular metabolism.

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

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

2018-02-01

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

Translating Response During Therapy into Ultimate Treatment Outcome: A Personalized 4-Dimensional MRI Tumor Volumetric Regression Approach in Cervical Cancer

International Nuclear Information System (INIS)

Mayr, Nina A.; Wang, Jian Z.; Lo, Simon S.; Zhang Dongqing; Grecula, John C.; Lu Lanchun; Montebello, Joseph F.; Fowler, Jeffrey M.; Yuh, William T.C.

2010-01-01

Purpose: To assess individual volumetric tumor regression pattern in cervical cancer during therapy using serial four-dimensional MRI and to define the regression parameters' prognostic value validated with local control and survival correlation. Methods and Materials: One hundred and fifteen patients with Stage IB 2 -IVA cervical cancer treated with radiation therapy (RT) underwent serial MRI before (MRI 1) and during RT, at 2-2.5 weeks (MRI 2, at 20-25 Gy), and at 4-5 weeks (MRI 3, at 40-50 Gy). Eighty patients had a fourth MRI 1-2 months post-RT. Mean follow-up was 5.3 years. Tumor volume was measured by MRI-based three-dimensional volumetry, and plotted as dose(time)/volume regression curves. Volume regression parameters were correlated with local control, disease-specific, and overall survival. Results: Residual tumor volume, slope, and area under the regression curve correlated significantly with local control and survival. Residual volumes ≥20% at 40-50 Gy were independently associated with inferior 5-year local control (53% vs. 97%, p <0.001) and disease-specific survival rates (50% vs. 72%, p = 0.009) than smaller volumes. Patients with post-RT residual volumes ≥10% had 0% local control and 17% disease-specific survival, compared with 91% and 72% for <10% volume (p <0.001). Conclusion: Using more accurate four-dimensional volumetric regression analysis, tumor response can now be directly translated into individual patients' outcome for clinical application. Our results define two temporal thresholds critically influencing local control and survival. In patients with ≥20% residual volume at 40-50 Gy and ≥10% post-RT, the risk for local failure and death are so high that aggressive intervention may be warranted.

Molecular Genetic Changes Associated With Colorectal Carcinogenesis Are Not Prognostic for Tumor Regression Following Preoperative Chemoradiation of Rectal Carcinoma

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Zauber, N. Peter; Marotta, Steven P.; Berman, Errol; Grann, Alison; Rao, Maithili; Komati, Naga; Ribiero, Kezia; Bishop, D. Timothy

2009-01-01

Purpose: Preoperative chemotherapy and radiation has become the standard of care for many patients with rectal cancer. The therapy may have toxicity and delays definitive surgery. It would therefore be desirable to identify those cancers that will not regress with preoperative therapy. We assessed a series of rectal cancers for the molecular changes of loss of heterozygosity of the APC and DCC genes, K-ras mutations, and microsatellite instability, changes that have clearly been associated with rectal carcinogenesis. Methods and Materials: Diagnostic colonoscopic biopsies from 53 patients who received preoperative chemotherapy and radiation were assayed using polymerase chain reaction techniques followed by single-stranded conformation polymorphism and DNA sequencing. Regression of the primary tumor was evaluated using the surgically removed specimen. Results: Twenty-three lesions (45%) were found to have a high degree of regression. None of the molecular changes were useful as indicators of regression. Conclusions: Recognized molecular changes critical for rectal carcinogenesis including APC and DCC loss of heterozygosity, K-ras mutations, and microsatellite instability are not useful as indicators of tumor regression following chemoradiation for rectal carcinoma.

Serial megavoltage CT imaging during external beam radiotherapy for non-small-cell lung cancer: Observations on tumor regression during treatment

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Kupelian, Patrick A.; Ramsey, Chester; Meeks, Sanford L.; Willoughby, Twyla R.; Forbes, Alan; Wagner, Thomas H.; Langen, Katja M.

2005-01-01

Purpose: The ability to obtain soft-tissue imaging in the treatment room, such as with megavoltage CT imaging, enables the observation of tumor regression during a course of external beam radiation therapy. In this current study, we report on the most extensive study looking at the rate of regression of non-small-cell lung cancers during a course of external beam radiotherapy by analyzing serial megavoltage CT images obtained on 10 patients. Methods and Materials: The analysis is performed on 10 patients treated with the Helical Tomotherapy Hi*Art device. All 10 patients had non-small-cell lung cancer. A total of 274 megavoltage CT sets were obtained on the 10 patients (average, 27 scans per patient; range, 9-35). All patients had at least a scan at beginning and at the end of treatment. The frequency of scanning was determined by the treating physician. The treatment was subsequently delivered with the Tomotherapy Hi*Art system. The gross tumor volumes (GTVs) were later contoured on each megavoltage CT scan, and tumor volumes were calculated. Although some patients were treated to draining nodal areas in addition to the primary tumor, only the primary GTVs were tracked. Response to treatment was quantified by the relative decrease in tumor volume over time, i.e., elapsed days from the first day of therapy. The individual GTVs ranged from 5.9 to 737.2 cc in volume at the start of treatment. In 6 of the 10 patients, dose recalculations were also performed to document potential variations in delivered doses within the tumors. The megavoltage CT scans were used, and the planned treatment was recalculated on the daily images. The hypothesis was that dose deposited in the target would increase throughout the course of radiotherapy because of tumor shrinkage and subsequent decreasing attenuation. Specifically, the dose received by 95% of the GTV (D 95 ) was monitored over time for each of the 6 patients treated at M.D. Anderson Cancer Center Orlando. Results: Regression

Analysis of animal experiments of radiation dependent tumor regression in relation to different parameters

International Nuclear Information System (INIS)

Heinzel, F.; Mueller-Duysing, W.; Blattman, H.; Bacesa, L.; Rao, K.R.; Mindek, G.

In order to be able to test the therapeutic value of the pions in comparison with conventional X-rays, analyses of animal experiments with induced tumors, transplantation tumors, and comparative cellular kinetic studies of tissue cultures will be performed. So that differences in radiation effect and a possible superiority of the pion therapy be objectively acknowledged, the reaction systems to be tested must be as homogenous as possible. For this purpose, the dependence of the radiation related regression on various parameters such as sex, age of hosts, environmental factors radiation conditions (intensity, fractionation, and so on), tumor size, and so on, must be investigated on sterile animals in a sterile environment. The experiments should be conducted under conditions as close as possible to clinical ones. For comparison, the reaction of normal tissue (in vitro and in vivo) and of malignant cells in short-time tissue cultures will be analysed. Cellular kinetics, alteration of chromosomes and metabolic activity of the cells will be studied

Role of Immunomodulators in Tumor Regression in Mice Exposed to Fractionated Low Dose of Gamma Radiation

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Rokaya Elsayed Maaroaf Elsayed

2015-01-01

Immunotherapy is one of the most promising approaches of cancer treatment. The present study was designed to examine the role of irradiated tumor cell lysate vaccine, IFNα-2b and low dose of gamma irradiation as immunomodulators either alone or combined in tumor regression. Ehrlich ascite carcinoma (EAC) cells and 9 groups of female mice were used. Mice were immunized intramuscularly by tumor cell lysate vaccine one time/week for 3 weeks in the right thigh of mice. After two weeks from last immunization, all mice were challenged with normal viable EAC cells at count of 2.5 ×10 6 /mouse in the opposite left thigh for Ehrlich carcinoma (EC) production. Mice were subcutaneously injected with 10.000 units of IFNα-2b 3 times/week for 4 weeks and others were exposed to fractionated dose of γ- radiation (0.5 Gy/day x 4, day after day). Tumor size, serum tumor markers (TNF-α and CEA), tumor DNA fragmentation and Caspase-3 were evaluated. Oxidative stress (MDA and NO) markers and antioxidants (GSH, GPX and SOD) were determined in spleen and tumor tissues. Histopathological examinations, apoptosis and necrosis in spleen and tumor tissues were also examined. The results revealed significant inhibition in tumor size throughout the observation period either for treatments with vaccine or IFNα-2b either alone or combined with γ-irradiation. DNA fragmentation and Caspase-3 enzyme activities were significantly elevated in immunized mice as compared with EC group along with diminished tumor size while, tumor markers were significantly decreased. MDA and NO were significantly increased in tumor tissue.while, tumor GSH content, GPX and SOD activities were significantly decreased. Combined treatments of female mice bearing EC with IFN-α-2b, tumor cell lysate vaccine and low dose of γ-radiation cause a highly significant decrease in serum TNF-α and CEA levels, increase in Cas-3 activity, no DNA fragmentation, significant increase in MDA, decrease in SOD activity and decreased

Regression and local control rates after radiotherapy for jugulotympanic paragangliomas: Systematic review and meta-analysis

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Hulsteijn, Leonie T. van; Corssmit, Eleonora P.M.; Coremans, Ida E.M.; Smit, Johannes W.A.; Jansen, Jeroen C.; Dekkers, Olaf M.

2013-01-01

The primary treatment goal of radiotherapy for paragangliomas of the head and neck region (HNPGLs) is local control of the tumor, i.e. stabilization of tumor volume. Interestingly, regression of tumor volume has also been reported. Up to the present, no meta-analysis has been performed giving an overview of regression rates after radiotherapy in HNPGLs. The main objective was to perform a systematic review and meta-analysis to assess regression of tumor volume in HNPGL-patients after radiotherapy. A second outcome was local tumor control. Design of the study is systematic review and meta-analysis. PubMed, EMBASE, Web of Science, COCHRANE and Academic Search Premier and references of key articles were searched in March 2012 to identify potentially relevant studies. Considering the indolent course of HNPGLs, only studies with ⩾12 months follow-up were eligible. Main outcomes were the pooled proportions of regression and local control after radiotherapy as initial, combined (i.e. directly post-operatively or post-embolization) or salvage treatment (i.e. after initial treatment has failed) for HNPGLs. A meta-analysis was performed with an exact likelihood approach using a logistic regression with a random effect at the study level. Pooled proportions with 95% confidence intervals (CI) were reported. Fifteen studies were included, concerning a total of 283 jugulotympanic HNPGLs in 276 patients. Pooled regression proportions for initial, combined and salvage treatment were respectively 21%, 33% and 52% in radiosurgery studies and 4%, 0% and 64% in external beam radiotherapy studies. Pooled local control proportions for radiotherapy as initial, combined and salvage treatment ranged from 79% to 100%. Radiotherapy for jugulotympanic paragangliomas results in excellent local tumor control and therefore is a valuable treatment for these types of tumors. The effects of radiotherapy on regression of tumor volume remain ambiguous, although the data suggest that regression can

A Tumor-stroma Targeted Oncolytic Adenovirus Replicated in Human Ovary Cancer Samples and Inhibited Growth of Disseminated Solid Tumors in Mice

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Lopez, M Veronica; Rivera, Angel A; Viale, Diego L; Benedetti, Lorena; Cuneo, Nicasio; Kimball, Kristopher J; Wang, Minghui; Douglas, Joanne T; Zhu, Zeng B; Bravo, Alicia I; Gidekel, Manuel; Alvarez, Ronald D; Curiel, David T; Podhajcer, Osvaldo L

2012-01-01

Targeting the tumor stroma in addition to the malignant cell compartment is of paramount importance to achieve complete tumor regression. In this work, we modified a previously designed tumor stroma-targeted conditionally replicative adenovirus (CRAd) based on the SPARC promoter by introducing a mutated E1A unable to bind pRB and pseudotyped with a chimeric Ad5/3 fiber (Ad F512v1), and assessed its replication/lytic capacity in ovary cancer in vitro and in vivo. AdF512v1 was able to replicate in fresh samples obtained from patients: (i) with primary human ovary cancer; (ii) that underwent neoadjuvant treatment; (iii) with metastatic disease. In addition, we show that four intraperitoneal (i.p.) injections of 5 × 1010 v.p. eliminated 50% of xenografted human ovary tumors disseminated in nude mice. Moreover, AdF512v1 replication in tumor models was enhanced 15–40-fold when the tumor contained a mix of malignant and SPARC-expressing stromal cells (fibroblasts and endothelial cells). Contrary to the wild-type virus, AdF512v1 was unable to replicate in normal human ovary samples while the wild-type virus can replicate. This study provides evidence on the lytic capacity of this CRAd and highlights the importance of targeting the stromal tissue in addition to the malignant cell compartment to achieve tumor regression. PMID:22948673

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

International Nuclear Information System (INIS)

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

1997-01-01

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

T cell receptor (TCR-transgenic CD8 lymphocytes rendered insensitive to transforming growth factor beta (TGFβ signaling mediate superior tumor regression in an animal model of adoptive cell therapy

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Quatromoni Jon G

2012-06-01

Full Text Available Abstract Tumor antigen-reactive T cells must enter into an immunosuppressive tumor microenvironment, continue to produce cytokine and deliver apoptotic death signals to affect tumor regression. Many tumors produce transforming growth factor beta (TGFβ, which inhibits T cell activation, proliferation and cytotoxicity. In a murine model of adoptive cell therapy, we demonstrate that transgenic Pmel-1 CD8 T cells, rendered insensitive to TGFβ by transduction with a TGFβ dominant negative receptor II (DN, were more effective in mediating regression of established B16 melanoma. Smaller numbers of DN Pmel-1 T cells effectively mediated tumor regression and retained the ability to produce interferon-γ in the tumor microenvironment. These results support efforts to incorporate this DN receptor in clinical trials of adoptive cell therapy for cancer.

Locoregional control of non-small cell lung cancer in relation to automated early assessment of tumor regression on cone beam computed tomography

DEFF Research Database (Denmark)

Brink, Carsten; Bernchou, Uffe; Bertelsen, Anders

2014-01-01

was estimated on the basis of the first one third and two thirds of the scans. The concordance between estimated and actual relative volume at the end of radiation therapy was quantified by Pearson's correlation coefficient. On the basis of the estimated relative volume, the patients were stratified into 2...... for other clinical characteristics. RESULTS: Automatic measurement of the tumor regression from standard CBCT images was feasible. Pearson's correlation coefficient between manual and automatic measurement was 0.86 in a sample of 9 patients. Most patients experienced tumor volume regression, and this could...

PSMA-targeted polyinosine/polycytosine vector induces prostate tumor regression and invokes an antitumor immune response in mice.

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Langut, Yael; Talhami, Alaa; Mamidi, Samarasimhareddy; Shir, Alexei; Zigler, Maya; Joubran, Salim; Sagalov, Anna; Flashner-Abramson, Efrat; Edinger, Nufar; Klein, Shoshana; Levitzki, Alexander

2017-12-26

There is an urgent need for an effective treatment for metastatic prostate cancer (PC). Prostate tumors invariably overexpress prostate surface membrane antigen (PSMA). We designed a nonviral vector, PEI-PEG-DUPA (PPD), comprising polyethylenimine-polyethyleneglycol (PEI-PEG) tethered to the PSMA ligand, 2-[3-(1, 3-dicarboxy propyl)ureido] pentanedioic acid (DUPA), to treat PC. The purpose of PEI is to bind polyinosinic/polycytosinic acid (polyIC) and allow endosomal release, while DUPA targets PC cells. PolyIC activates multiple pathways that lead to tumor cell death and to the activation of bystander effects that harness the immune system against the tumor, attacking nontargeted neighboring tumor cells and reducing the probability of acquired resistance and disease recurrence. Targeting polyIC directly to tumor cells avoids the toxicity associated with systemic delivery. PPD selectively delivered polyIC into PSMA-overexpressing PC cells, inducing apoptosis, cytokine secretion, and the recruitment of human peripheral blood mononuclear cells (PBMCs). PSMA-overexpressing tumors in nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice with partially reconstituted immune systems were significantly shrunken following PPD/polyIC treatment, in all cases. Half of the tumors showed complete regression. PPD/polyIC invokes antitumor immunity, but unlike many immunotherapies does not need to be personalized for each patient. The potent antitumor effects of PPD/polyIC should spur its development for clinical use.

A note on modeling of tumor regression for estimation of radiobiological parameters

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Zhong, Hualiang; Chetty, Indrin

2014-01-01

Purpose: Accurate calculation of radiobiological parameters is crucial to predicting radiation treatment response. Modeling differences may have a significant impact on derived parameters. In this study, the authors have integrated two existing models with kinetic differential equations to formulate a new tumor regression model for estimation of radiobiological parameters for individual patients. Methods: A system of differential equations that characterizes the birth-and-death process of tumor cells in radiation treatment was analytically solved. The solution of this system was used to construct an iterative model (Z-model). The model consists of three parameters: tumor doubling time T d , half-life of dead cells T r , and cell survival fraction SF D under dose D. The Jacobian determinant of this model was proposed as a constraint to optimize the three parameters for six head and neck cancer patients. The derived parameters were compared with those generated from the two existing models: Chvetsov's model (C-model) and Lim's model (L-model). The C-model and L-model were optimized with the parameter T d fixed. Results: With the Jacobian-constrained Z-model, the mean of the optimized cell survival fractions is 0.43 ± 0.08, and the half-life of dead cells averaged over the six patients is 17.5 ± 3.2 days. The parameters T r and SF D optimized with the Z-model differ by 1.2% and 20.3% from those optimized with the T d -fixed C-model, and by 32.1% and 112.3% from those optimized with the T d -fixed L-model, respectively. Conclusions: The Z-model was analytically constructed from the differential equations of cell populations that describe changes in the number of different tumor cells during the course of radiation treatment. The Jacobian constraints were proposed to optimize the three radiobiological parameters. The generated model and its optimization method may help develop high-quality treatment regimens for individual patients

Adenoviral vaccination combined with CD40 stimulation and CTLA-4 blockage can lead to complete tumor regression in a murine melanoma model

DEFF Research Database (Denmark)

Sørensen, Maria Rathmann; Holst, Peter J; Steffensen, Maria Abildgaard

2010-01-01

that the delay in tumor growth can be converted to complete regression and long-term survival in 30-40% of the mice by a booster vaccination plus combinational treatment with agonistic anti-CD40 monoclonal antibodies (mAb) and anti-CTLA-4 mAb. Regarding the mechanism underlying the improved clinical effect......, analysis of the tumor-specific response revealed a significantly prolonged tumor-specific CD8 T cell response in spleens of the mice receiving the combinational treatment compared with mice receiving either treatment individually. Matching this, CD8 T cell depletion completely prevented tumor control...

Gender Gaps in Mathematics, Science and Reading Achievements in Muslim Countries: A Quantile Regression Approach

Science.gov (United States)

Shafiq, M. Najeeb

2013-01-01

Using quantile regression analyses, this study examines gender gaps in mathematics, science, and reading in Azerbaijan, Indonesia, Jordan, the Kyrgyz Republic, Qatar, Tunisia, and Turkey among 15-year-old students. The analyses show that girls in Azerbaijan achieve as well as boys in mathematics and science and overachieve in reading. In Jordan,…

Tumor regression induced by intratumor therapy with a disabled infectious single cycle (DISC) herpes simplex virus (HSV) vector, DISC/HSV/murine granulocyte-macrophage colony-stimulating factor, correlates with antigen-specific adaptive immunity.

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Ali, Selman A; Lynam, June; McLean, Cornelia S; Entwisle, Claire; Loudon, Peter; Rojas, José M; McArdle, Stephanie E B; Li, Geng; Mian, Shahid; Rees, Robert C

2002-04-01

Direct intratumor injection of a disabled infectious single cycle HSV-2 virus encoding the murine GM-CSF gene (DISC/mGM-CSF) into established murine colon carcinoma CT26 tumors induced a significant delay in tumor growth and complete tumor regression in up to 70% of animals. Pre-existing immunity to HSV did not reduce the therapeutic efficacy of DISC/mGM-CSF, and, when administered in combination with syngeneic dendritic cells, further decreased tumor growth and increased the incidence of complete tumor regression. Direct intratumor injection of DISC/mGM-CSF also inhibited the growth of CT26 tumor cells implanted on the contralateral flank or seeded into the lungs following i.v. injection of tumor cells (experimental lung metastasis). Proliferation of splenocytes in response to Con A was impaired in progressor and tumor-bearer, but not regressor, mice. A potent tumor-specific CTL response was generated from splenocytes of all mice with regressing, but not progressing tumors following in vitro peptide stimulation; this response was specific for the gp70 AH-1 peptide SPSYVYHQF and correlated with IFN-gamma, but not IL-4 cytokine production. Depletion of CD8(+) T cells from regressor splenocytes before in vitro stimulation with the relevant peptide abolished their cytolytic activity, while depletion of CD4(+) T cells only partially inhibited CTL generation. Tumor regression induced by DISC/mGM-CSF virus immunotherapy provides a unique model for evaluating the immune mechanism(s) involved in tumor rejection, upon which tumor immunotherapy regimes may be based.

Radiotherapy in glomus jugulare and glomus tympanicum tumors

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Feyerabend, T.; Richter, E.; Kapp, B.; Bohndorf, W.; Ptok, M.

1989-01-01

Glomus jugulare tumors are difficult to manage therapeutically due to their localisation. Operation may be successful in small tumors but can be hazardous in larger lesions mainly because of bleeding and palsy of cranial nerves. In these cases there should be used radiation therapy under the condition that it is planned by use of computed tomography. Moreover reproducibility of radiation treatment set-up is vital. In this way tumor regression may be achieved. Four own illustrative cases are demonstrated. According to the stage of disease a modified treatment strategy is presented which integrates surgical procedures, angiographic embolisation and radiotherapy. (orig.) [de

SU-F-J-64: Comparison of Dosimetric Robustness Between Proton Therapy and IMRT Plans Following Tumor Regression for Locally Advanced Non-Small Cell Lung Cancer (NSCLC)

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Teng, C; Ainsley, C; Teo, B; Burgdorf, B; Berman, A; Levin, W; Xiao, Y; Lin, L; Simone, C; Solberg, T [University of Pennsylvania, Philadelphia, PA (United States); Janssens, G [IBA, Louvain-la-Neuve (Belgium)

2016-06-15

Purpose: In the light of tumor regression and normal tissue changes, dose distributions can deviate undesirably from what was planned. As a consequence, replanning is sometimes necessary during treatment to ensure continued tumor coverage or to avoid overdosing organs at risk (OARs). Proton plans are generally thought to be less robust than photon plans because of the proton beam’s higher sensitivity to changes in tissue composition, suggesting also a higher likely replanning rate due to tumor regression. The purpose of this study is to compare dosimetric deviations between forward-calculated double scattering (DS) proton plans with IMRT plans upon tumor regression, and assesses their impact on clinical replanning decisions. Methods: Ten consecutive locally advanced NSCLC patients whose tumors shrank > 50% in volume and who received four or more CT scans during radiotherapy were analyzed. All the patients received proton radiotherapy (6660 cGy, 180 cGy/fx). Dosimetric robustness during therapy was characterized by changes in the planning objective metrics as well as by point-by-point root-mean-squared differences for the entire PTV, ITV, and OARs (heart, cord, esophagus, brachial plexus and lungs) DVHs. Results: Sixty-four pairs of DVHs were reviewed by three clinicians, who requested a replanning rate of 16.7% and 18.6% for DS and IMRT plans, respectively, with a high agreement between providers. Robustness of clinical indicators was found to depend on the beam orientation and dose level on the DVH curve. Proton dose increased most in OARs distal to the PTV along the beam path, but these changes were primarily in the mid to low dose levels. In contrast, the variation in IMRT plans occurred primarily in the high dose region. Conclusion: Robustness of clinical indicators depends where on the DVH curves comparisons are made. Similar replanning rates were observed for DS and IMRT plans upon large tumor regression.

Tumor dose-volume response in image-guided adaptive brachytherapy for cervical cancer: A meta-regression analysis.

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Mazeron, Renaud; Castelnau-Marchand, Pauline; Escande, Alexandre; Rivin Del Campo, Eleonor; Maroun, Pierre; Lefkopoulos, Dimitri; Chargari, Cyrus; Haie-Meder, Christine

2016-01-01

Image-guided adaptive brachytherapy is a high precision technique that allows dose escalation and adaptation to tumor response. Two monocentric studies reported continuous dose-volume response relationships, however, burdened by large confidence intervals. The aim was to refine these estimations by performing a meta-regression analysis based on published series. Eligibility was limited to series reporting dosimetric parameters according to the Groupe Européen de Curiethérapie-European SocieTy for Radiation Oncology recommendations. The local control rates reported at 2-3 years were confronted to the mean D90 clinical target volume (CTV) in 2-Gy equivalent using the probit model. The impact of each series on the relationships was pondered according to the number of patients reported. An exhaustive literature search retrieved 13 series reporting on 1299 patients. D90 high-risk CTV ranged from 70.9 to 93.1 Gy. The probit model showed a significant correlation between the D90 and the probability of achieving local control (p < 0.0001). The D90 associated to a 90% probability of achieving local control was 81.4 Gy (78.3-83.8 Gy). The planning aim of 90 Gy corresponded to a 95.0% probability (92.8-96.3%). For the intermediate-risk CTV, less data were available, with 873 patients from eight institutions. Reported mean D90 intermediate-risk CTV ranged from 61.7 to 69.1 Gy. A significant dose-volume effect was observed (p = 0.009). The D90 of 60 Gy was associated to a 79.4% (60.2-86.0%) local control probability. Based on published data from a high number of patients, significant dose-volume effect relationships were confirmed and refined between the D90 of both CTV and the probability of achieving local control. Further studies based on individual data are required to develop nomograms including nondosimetric prognostic criteria. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Preclinical experiments for analysis of tumor regression due to negative pions

International Nuclear Information System (INIS)

Blattmann, H.; Cabeza, L.; Fritz-Niggli, H.

To test the potential therapeutic value of negative pions in comparison with conventional x-rays, cobalt-60 γ rays, and high energy electrons and photons (Betatron), experimental analyses with induced tumors (transplant tumors) after irradiation are to be performed in vivo and in vitro (tumor cell suspensions, cell cultures, spontaneous tumors, carcinoma in ascites form); in addition to tumors primarily of mice, human cell tumors will be used; studies will also be made of cell kinetics with various cell types (normal cells, transformed (malignant) cells, beam-resistant, beam-sensitive types) using cell cultures from Chinese hamsters. An attempt will be made to compare slow- and fast-growing tumors. In a second phase, human tumors in conditioned animals will be tested in situ or as cell cultures. Skin, small intestine, regenerating liver and kidney, together with cell cultures, will serve as normal reaction systems

Primary tumor regression speed after radiotherapy and its prognostic significance in nasopharyngeal carcinoma: a retrospective study

International Nuclear Information System (INIS)

Zhang, Ning; Liu, Dong-Sheng; Chen, Yong; Liang, Shao-Bo; Deng, Yan-Ming; Lu, Rui-Liang; Chen, Hai-Yang; Zhao, Hai; Lv, Zhi-Qian; Liang, Shao-Qiang; Yang, Lin

2014-01-01

To observe the primary tumor (PT) regression speed after radiotherapy (RT) in nasopharyngeal carcinoma (NPC) and evaluate its prognostic significance. One hundred and eighty-eight consecutive newly diagnosed NPC patients were reviewed retrospectively. All patients underwent magnetic resonance imaging and fiberscope examination of the nasopharynx before RT, during RT when the accumulated dose was 46–50 Gy, at the end of RT, and 3–4 months after RT. Of 188 patients, 40.4% had complete response of PT (CRPT), 44.7% had partial response of PT (PRPT), and 14.9% had stable disease of PT (SDPT) at the end of RT. The 5-year overall survival (OS) rates for patients with CRPT, PRPT, and SDPT at the end of RT were 84.0%, 70.7%, and 44.3%, respectively (P < 0.001, hazard ratio [HR] = 2.177, 95% confidence interval [CI] = 1.480-3.202). The 5-year failure-free survival (FFS) and distant metastasis-free survival (DMFS) rates also differed significantly (87.8% vs. 74.3% vs. 52.7%, P = 0.001, HR = 2.148, 95% CI, 1.384-3.333; 91.7% vs. 84.7% vs. 66.1%, P = 0.004, HR = 2.252, 95% CI = 1.296-3.912). The 5-year local relapse–free survival (LRFS) rates were not significantly different (95.8% vs. 86.0% vs. 81.8%, P = 0.137, HR = 1.975, 95% CI, 0.976-3.995). By multivariate analyses, the PT regression speed at the end of RT was the only independent prognostic factor of OS, FFS, and DMFS (P < 0.001, P = 0.001, and P = 0.004, respectively). The 5-year FFS rates for patients with CRPT during RT and CRPT only at the end of RT were 80.2% and 97.1%, respectively (P = 0.033). For patients with persistent PT at the end of RT, the 5-year LRFS rates of patients without and with boost irradiation were 87.1% and 84.6%, respectively (P = 0.812). PT regression speed at the end of RT was an independent prognostic factor of OS, FFS, and DMFS in NPC patients. Immediate strengthening treatment may be provided to patients with poor tumor regression at the end of RT

Regression trees for predicting mortality in patients with cardiovascular disease: What improvement is achieved by using ensemble-based methods?

Science.gov (United States)

Austin, Peter C; Lee, Douglas S; Steyerberg, Ewout W; Tu, Jack V

2012-01-01

In biomedical research, the logistic regression model is the most commonly used method for predicting the probability of a binary outcome. While many clinical researchers have expressed an enthusiasm for regression trees, this method may have limited accuracy for predicting health outcomes. We aimed to evaluate the improvement that is achieved by using ensemble-based methods, including bootstrap aggregation (bagging) of regression trees, random forests, and boosted regression trees. We analyzed 30-day mortality in two large cohorts of patients hospitalized with either acute myocardial infarction (N = 16,230) or congestive heart failure (N = 15,848) in two distinct eras (1999–2001 and 2004–2005). We found that both the in-sample and out-of-sample prediction of ensemble methods offered substantial improvement in predicting cardiovascular mortality compared to conventional regression trees. However, conventional logistic regression models that incorporated restricted cubic smoothing splines had even better performance. We conclude that ensemble methods from the data mining and machine learning literature increase the predictive performance of regression trees, but may not lead to clear advantages over conventional logistic regression models for predicting short-term mortality in population-based samples of subjects with cardiovascular disease. PMID:22777999

[Regression and therapy-resistance of primary liver tumors and liver metastases after regional chemotherapy and local tumor ablation].

Science.gov (United States)

Fischer, H-P

2005-05-01

High dosage regional chemotherapy, chemoembolization and other methods of regional treatment are commonly used to treat unresectable primary liver malignancies and liver metastases. In liver malignancies of childhood neoadjuvant chemotherapy is successfully combined with surgical treatment. Chemotherapy and local tumor ablation lead to characteristic histomorphologic changes: Complete destruction of the tumor tissue and its vascular bed is followed by encapsulated necroses. After selective eradication of the tumor cells under preservation of the fibrovasular bed the tumor is replaced by hypocellular edematous and fibrotic tissue. If completely damaged tumor tissue is absorbed quickly, the tumor area is replaced by regenerating liver tissue. Obliterating fibrohyalinosis of tumor vessels, and perivascular edema or necrosis indicate tissue damage along the vascular bed. Degenerative pleomorphism of tumor cells, steatosis, hydropic swelling and Malloryhyalin in HCC can represent cytologic findings of cytotoxic cellular damage. Macroscopic type of HCC influences significantly the response to treatment. Multinodular HCC often contain viable tumor nodules close to destroyed nodules after treatment. Encapsulated uninodular tumors undergo complete necrosis much easier. Large size and a tumor capsule limitate the effect of percutaneous injection of ethanol into HCC. In carcinomas with an infiltrating border, especially in metastases of adenocarcinomas and hepatic cholangiocarcinoma cytostatic treatment damages the tumor tissue mainly in the periphery. Nevertheless the infiltrating rim, portal veins, lymphatic spaces and bile ducts as well as the angle between liver capsule, tumor nodule and bordering parenchyma are the main refugees of viable tumor tissue even after high dosage regional chemotherapy. This local resistance is caused by special local conditions of vascularization and perfusion. These residues are the source of local tumor progression and distant metastases

YAP Inhibition Restores Hepatocyte Differentiation in Advanced HCC, Leading to Tumor Regression

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Julien Fitamant

2015-03-01

Full Text Available Defective Hippo/YAP signaling in the liver results in tissue overgrowth and development of hepatocellular carcinoma (HCC. Here, we uncover mechanisms of YAP-mediated hepatocyte reprogramming and HCC pathogenesis. YAP functions as a rheostat in maintaining metabolic specialization, differentiation, and quiescence within the hepatocyte compartment. Increased or decreased YAP activity reprograms subsets of hepatocytes to different fates associated with deregulation of the HNF4A, CTNNB1, and E2F transcriptional programs that control hepatocyte quiescence and differentiation. Importantly, treatment with small interfering RNA-lipid nanoparticles (siRNA-LNPs targeting YAP restores hepatocyte differentiation and causes pronounced tumor regression in a genetically engineered mouse HCC model. Furthermore, YAP targets are enriched in an aggressive human HCC subtype characterized by a proliferative signature and absence of CTNNB1 mutations. Thus, our work reveals Hippo signaling as a key regulator of the positional identity of hepatocytes, supports targeting of YAP using siRNA-LNPs as a paradigm of differentiation-based therapy, and identifies an HCC subtype that is potentially responsive to this approach.

Efficient tumor regression by adoptively transferred CEA-specific CAR-T cells associated with symptoms of mild cytokine release syndrome.

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Wang, Linan; Ma, Ning; Okamoto, Sachiko; Amaishi, Yasunori; Sato, Eiichi; Seo, Naohiro; Mineno, Junichi; Takesako, Kazutoh; Kato, Takuma; Shiku, Hiroshi

2016-01-01

Carcinoembryonic antigen (CEA) is a cell surface antigen highly expressed in various cancer cell types and in healthy tissues. It has the potential to be a target for chimeric antigen receptor (CAR)-modified T-cell therapy; however, the safety of this approach in terms of on-target/off-tumor effects needs to be determined. To address this issue in a clinically relevant model, we used a mouse model in which the T cells expressing CEA-specific CAR were transferred into tumor-bearing CEA-transgenic (Tg) mice that physiologically expressed CEA as a self-antigen. The adoptive transfer in conjunction with lymphodepleting and myeloablative preconditioning mediated significant tumor regression but caused weight loss in CEA-Tg, but not in wild-type mice. The weight loss was not associated with overt inflammation in the CEA-expressing gastrointestinal tract but was associated with malnutrition, reflected in elevated systemic levels of cytokines linked to anorexia, which could be controlled by the administration of an anti-IL-6 receptor monoclonal antibody without compromising efficacy. The apparent relationship between lymphodepleting and myeloablative preconditioning, efficacy, and off-tumor toxicity of CAR-T cells would necessitate the development of CEA-specific CAR-T cells with improved signaling domains that require less stringent preconditioning for their efficacy. Taken together, these results suggest that CEA-specific CAR-based adoptive T-cell therapy may be effective for patients with CEA + solid tumors. Distinguishing the fine line between therapeutic efficacy and off-tumor toxicity would involve further modifications of CAR-T cells and preconditioning regimens.

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

Science.gov (United States)

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

2010-10-01

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

Retrospective feasibility study of simultaneous integrated boost in cervical cancer using Tomotherapy: the impact of organ motion and tumor regression.

Science.gov (United States)

Herrera, Fernanda G; Callaway, Sharon; Delikgoz-Soykut, Ela; Coskun, Mehtap; Porta, Laetitia; Meuwly, Jean-Yves; Soares-Rodrigues, Joao; Heym, Leonie; Moeckli, Raphael; Ozsahin, Mahmut

2013-01-03

Whole pelvis intensity modulated radiotherapy (IMRT) is increasingly being used to treat cervical cancer aiming to reduce side effects. Encouraged by this, some groups have proposed the use of simultaneous integrated boost (SIB) to target the tumor, either to get a higher tumoricidal effect or to replace brachytherapy. Nevertheless, physiological organ movement and rapid tumor regression throughout treatment might substantially reduce any benefit of this approach. To evaluate the clinical target volume - simultaneous integrated boost (CTV-SIB) regression and motion during chemo-radiotherapy (CRT) for cervical cancer, and to monitor treatment progress dosimetrically and volumetrically to ensure treatment goals are met. Ten patients treated with standard doses of CRT and brachytherapy were retrospectively re-planned using a helical Tomotherapy - SIB technique for the hypothetical scenario of this feasibility study. Target and organs at risk (OAR) were contoured on deformable fused planning-computed tomography and megavoltage computed tomography images. The CTV-SIB volume regression was determined. The center of mass (CM) was used to evaluate the degree of motion. The Dice's similarity coefficient (DSC) was used to assess the spatial overlap of CTV-SIBs between scans. A cumulative dose-volume histogram modeled estimated delivered doses. The CTV-SIB relative reduction was between 31 and 70%. The mean maximum CM change was 12.5, 9, and 3 mm in the superior-inferior, antero-posterior, and right-left dimensions, respectively. The CTV-SIB-DSC approached 1 in the first week of treatment, indicating almost perfect overlap. CTV-SIB-DSC regressed linearly during therapy, and by the end of treatment was 0.5, indicating 50% discordance. Two patients received less than 95% of the prescribed dose. Much higher doses to the OAR were observed. A multiple regression analysis showed a significant interaction between CTV-SIB reduction and OAR dose increase. The CTV-SIB had important

Retrospective feasibility study of simultaneous integrated boost in cervical cancer using tomotherapy: the impact of organ motion and tumor regression

International Nuclear Information System (INIS)

Herrera, Fernanda G; Ozsahin, Mahmut; Callaway, Sharon; Delikgoz-Soykut, Ela; Coskun, Mehtap; Porta, Laetitia; Meuwly, Jean-Yves; Soares-Rodrigues, Joao; Heym, Leonie; Moeckli, Raphael

2013-01-01

Whole pelvis intensity modulated radiotherapy (IMRT) is increasingly being used to treat cervical cancer aiming to reduce side effects. Encouraged by this, some groups have proposed the use of simultaneous integrated boost (SIB) to target the tumor, either to get a higher tumoricidal effect or to replace brachytherapy. Nevertheless, physiological organ movement and rapid tumor regression throughout treatment might substantially reduce any benefit of this approach. To evaluate the clinical target volume - simultaneous integrated boost (CTV-SIB) regression and motion during chemo-radiotherapy (CRT) for cervical cancer, and to monitor treatment progress dosimetrically and volumetrically to ensure treatment goals are met. Ten patients treated with standard doses of CRT and brachytherapy were retrospectively re-planned using a helical Tomotherapy - SIB technique for the hypothetical scenario of this feasibility study. Target and organs at risk (OAR) were contoured on deformable fused planning-computed tomography and megavoltage computed tomography images. The CTV-SIB volume regression was determined. The center of mass (CM) was used to evaluate the degree of motion. The Dice’s similarity coefficient (DSC) was used to assess the spatial overlap of CTV-SIBs between scans. A cumulative dose-volume histogram modeled estimated delivered doses. The CTV-SIB relative reduction was between 31 and 70%. The mean maximum CM change was 12.5, 9, and 3 mm in the superior-inferior, antero-posterior, and right-left dimensions, respectively. The CTV-SIB-DSC approached 1 in the first week of treatment, indicating almost perfect overlap. CTV-SIB-DSC regressed linearly during therapy, and by the end of treatment was 0.5, indicating 50% discordance. Two patients received less than 95% of the prescribed dose. Much higher doses to the OAR were observed. A multiple regression analysis showed a significant interaction between CTV-SIB reduction and OAR dose increase. The CTV-SIB had important

Retrospective feasibility study of simultaneous integrated boost in cervical cancer using tomotherapy: the impact of organ motion and tumor regression

Directory of Open Access Journals (Sweden)

Herrera Fernanda G

2013-01-01

Full Text Available Abstract Background Whole pelvis intensity modulated radiotherapy (IMRT is increasingly being used to treat cervical cancer aiming to reduce side effects. Encouraged by this, some groups have proposed the use of simultaneous integrated boost (SIB to target the tumor, either to get a higher tumoricidal effect or to replace brachytherapy. Nevertheless, physiological organ movement and rapid tumor regression throughout treatment might substantially reduce any benefit of this approach. Purpose To evaluate the clinical target volume - simultaneous integrated boost (CTV-SIB regression and motion during chemo-radiotherapy (CRT for cervical cancer, and to monitor treatment progress dosimetrically and volumetrically to ensure treatment goals are met. Methods and materials Ten patients treated with standard doses of CRT and brachytherapy were retrospectively re-planned using a helical Tomotherapy - SIB technique for the hypothetical scenario of this feasibility study. Target and organs at risk (OAR were contoured on deformable fused planning-computed tomography and megavoltage computed tomography images. The CTV-SIB volume regression was determined. The center of mass (CM was used to evaluate the degree of motion. The Dice’s similarity coefficient (DSC was used to assess the spatial overlap of CTV-SIBs between scans. A cumulative dose-volume histogram modeled estimated delivered doses. Results The CTV-SIB relative reduction was between 31 and 70%. The mean maximum CM change was 12.5, 9, and 3 mm in the superior-inferior, antero-posterior, and right-left dimensions, respectively. The CTV-SIB-DSC approached 1 in the first week of treatment, indicating almost perfect overlap. CTV-SIB-DSC regressed linearly during therapy, and by the end of treatment was 0.5, indicating 50% discordance. Two patients received less than 95% of the prescribed dose. Much higher doses to the OAR were observed. A multiple regression analysis showed a significant interaction

Engineering a prostate-specific membrane antigen-activated tumor endothelial cell prodrug for cancer therapy

DEFF Research Database (Denmark)

Denmeade, Samuel R; Mhaka, Annastasiah M; Rosen, D Marc

2012-01-01

adenosine triphosphatase (SERCA) pump, whose proper function is required by all cell types for viability. To achieve targeted inhibition, we took advantage of the unique expression of the carboxypeptidase prostate-specific membrane antigen (PSMA) by tumor endothelial cells within the microenvironment...... of solid tumors. We generated a prodrug, G202, consisting of a PSMA-specific peptide coupled to an analog of the potent SERCA pump inhibitor thapsigargin. G202 produced substantial tumor regression against a panel of human cancer xenografts in vivo at doses that were minimally toxic to the host...

Tumor regression following intravenous administration of lactoferrin- and lactoferricin-bearing dendriplexes.

Science.gov (United States)

Lim, Li Ying; Koh, Pei Yin; Somani, Sukrut; Al Robaian, Majed; Karim, Reatul; Yean, Yi Lyn; Mitchell, Jennifer; Tate, Rothwelle J; Edrada-Ebel, RuAngelie; Blatchford, David R; Mullin, Margaret; Dufès, Christine

2015-08-01

The possibility of using gene therapy for the treatment of cancer is limited by the lack of safe, intravenously administered delivery systems able to selectively deliver therapeutic genes to tumors. In this study, we investigated if the conjugation of the polypropylenimine dendrimer to lactoferrin and lactoferricin, whose receptors are overexpressed on cancer cells, could result in a selective gene delivery to tumors and a subsequently enhanced therapeutic efficacy. The conjugation of lactoferrin and lactoferricin to the dendrimer significantly increased the gene expression in the tumor while decreasing the non-specific gene expression in the liver. Consequently, the intravenous administration of the targeted dendriplexes encoding TNFα led to the complete suppression of 60% of A431 tumors and up to 50% of B16-F10 tumors over one month. The treatment was well tolerated by the animals. These results suggest that these novel lactoferrin- and lactoferricin-bearing dendrimers are promising gene delivery systems for cancer therapy. Specific targeting of cancer cells should enhance the delivery of chemotherapeutic agents. This is especially true for gene delivery. In this article, the authors utilized a dendrimer-based system and conjugated this with lactoferrin and lactoferricin to deliver anti-tumor genes. The positive findings in animal studies should provide the basis for further clinical studies. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Facile synthesis of soybean phospholipid-encapsulated MoS2 nanosheets for efficient in vitro and in vivo photothermal regression of breast tumor

Directory of Open Access Journals (Sweden)

Li X

2016-04-01

Full Text Available Xiang Li,1 Yun Gong,2,3 Xiaoqian Zhou,1 Hui Jin,1 Huanhuan Yan,1 Shige Wang,2 Jun Liu11Department of Breast-Thyroid Surgery, Shanghai General Hospital of Nanjing Medical University, Shanghai, People’s Republic of China; 2College of Science, University of Shanghai for Science and Technology, 3Shanghai Publishing and Printing College, Shanghai, People’s Republic of ChinaAbstract: Two-dimensional MoS2 nanosheet has been extensively explored as a photothermal agent for tumor regression; however, its surface modification remains a great challenge. Herein, as an alternative to surface polyethylene glycol modification (PEGylation, a facile approach based on “thin-film” strategy has been proposed for the first time to produce soybean phospholipid-encapsulated MoS2 (SP-MoS2 nanosheets. By simply vacuum-treating MoS2 nanosheets/soybean phospholipid/chloroform dispersion in a rotary evaporator, SP-MoS2 nanosheet was successfully constructed. Owing to the steric hindrance of polymer chains, the surface-coated soybean phospholipid endowed MoS2 nanosheets with excellent colloidal stability. Without showing detectable in vitro and in vivo hemolysis, coagulation, and cyto-/histotoxicity, the constructed SP-MoS2 nanosheets showed good photothermal conversion performance and photothermal stability. SP-MoS2 nanosheet was shown to be a promising platform for in vitro and in vivo breast tumor photothermal therapy. The produced SP-MoS2 nanosheets featured low cost, simple fabrication, and good in vivo hemo-/histocompatibility and hold promising potential for future clinical tumor therapy.Keywords: soybean phospholipid, MoS2 nanosheets, in vivo, photothermal regression, breast tumor

Clinical study of combined radio-thermotherapy for radioresistant tumors, 1

International Nuclear Information System (INIS)

Hiraoka, Masahiro; Ri, Nariyoshi; Ono, Kouji; Nishidai, Takehiro; Takahashi, Masaji

1981-01-01

Seventeen cases of superficial malignant tumors considered to be refractory to conventional treatment modalities were treated by thermotherapy in combination with radiation. Heat was generated by a microwave apparatus of 2450MHz. Fourteen cases which received complete thermotherapy were analysed and the following results were obtained. 1. Intratumor temperature of over 41 0 C was obtained in all cases and temperature of over 42.5 0 C was achieved in ten cases (71%). 2. In five out of fourteen cases, both intratumor and adjacent normal tissue temperatures were measured and intratumor temperature was approximately 1 0 C higher on the average than normal tissue temperature. 3. Phantom and clinical examinations demonstrated that effective heating depth obtained by this apparatus was approximately 3 cm from the surface. 4. Of eleven cases who hadn't received any radiotherapy, five cases showed complete regression (46%), three cases partial regression (27%) and no regression was observed in three cases (27%). Of three cases who had received full course of radiotherapy, two cases showed partial regression (67%) and one demonstrated no regression (33%). It was concluded that this heating unit was applicable to the thermotherapy for superficial malignant tumors. Radiosensitizing effect of heat was suggested, however more clinical experiences are needed to evaluate the definite usefulness of this treatment. (author)

Assessment of diagnostic value of tumor markers for colorectal neoplasm by logistic regression and ROC curve

International Nuclear Information System (INIS)

Ping, G.

2007-01-01

Full text: Objective: To assess the diagnostic value of CEA CA199 and CA50 for colorectal neoplasm by logistic regression and ROC curve. Methods: The subjects include 75 patients of colorectal cancer, 35 patients of benign intestinal disease and 49 health controls. CEA CA199 and CA50 are measured by CLIA ECLIA and IRMA respectively. The area under the curve (AUC) of CEA CA 199 CA50 and logistic regression results are compared. [Result] In the cancer-benign group, the AUC of CA50 is larger than the AUC of CA199 Compared with the AUC of combination of CEA CA199 and CA50 (0.604),the AUC of combination of CEA and CA50 (0.875) is larger and it is also larger than any other AUC of CEA CA199 or CA50 alone. In the cancerhealth group, the AUC of combination of CEA CA199 and CA50 is larger than any other AUC of CEA CA199 or CA50 alone. No matter in the cancer-benign group or cancerhealth group. The AUC of CEA is larger than the AUC of CA199 or CA50. Conclusion: CEA is useful in the diagnosis of colorectal cancer. In the process of differential diagnosis, the combination of CEA and CA50 can give more information, while the combination of three tumor markers does not perform well. Furthermore, as a statistical method, logistic regression can improve the diagnostic sensitivity and specificity. (author)

Clinical features and treatment outcomes of vasoproliferative tumors in Indian participants

Directory of Open Access Journals (Sweden)

Jaydeep Avinash Walinjkar

2018-01-01

Full Text Available Purpose: The aim of the study was to describe the clinical features and treatment outcomes of vasoproliferative tumors (VPT in Indian participants. Methods: This study design was a retrospective case series in a tertiary eye care center. Case records of patients diagnosed with VPT from 2011 to 2015 were reviewed, and their demographic details, clinical presentation, and treatment outcomes were documented. Baseline and follow-up visual acuity and tumor dimensions were statistically compared by applying paired t-test. Statistical analysis used SPSS version 14. Results: Twenty-two tumors from 19 eyes of 17 patients were included. Mean age at presentation was 43.5 years (range: 15–68 years. Mean presenting best-corrected visual acuity (BCVA was + 1.10 logMAR. Sixty-eight percent eyes had secondary tumors. Most common association of secondary VPT was Coats disease followed by retinal vasculitis, polypoidal choroidal vasculopathy, familial exudative vitreoretinopathy, and traumatic chorioretinopathy. Ten tumors (45% involved the inferior quadrant. Tumor-associated features were intra/subretinal exudates, vitritis, subretinal fluid, vitreous hemorrhage, preretinal fibrosis, epiretinal membrane, and subretinal blood. Treatment included cryotherapy, intravitreal or oral steroids, laser photocoagulation, cryotherapy with encirclage, cryotherapy with anti-vascular endothelial growth factor, and observation. Complications included tumor recurrence, retinal detachment, raised intraocular pressure, neovascularization of iris, and cataract. Ninety-five percent VPT regressed at mean 21 months (Median: 17 months; Range: 3–64 months. Mean final BCVA was + 1.21 logMAR. Conclusion: VPTs are commonly unilateral, unifocal, and located anterior to equator in inferior fundus. Secondary tumors are more common than primary tumors. Treatment achieves tumor regression in majority of cases.

Radiation regression patterns after cobalt plaque insertion for retinoblastoma

International Nuclear Information System (INIS)

Buys, R.J.; Abramson, D.H.; Ellsworth, R.M.; Haik, B.

1983-01-01

An analysis of 31 eyes of 30 patients who had been treated with cobalt plaques for retinoblastoma disclosed that a type I radiation regression pattern developed in 15 patients; type II, in one patient, and type III, in five patients. Nine patients had a regression pattern characterized by complete destruction of the tumor, the surrounding choroid, and all of the vessels in the area into which the plaque was inserted. This resulting white scar, corresponding to the sclerae only, was classified as a type IV radiation regression pattern. There was no evidence of tumor recurrence in patients with type IV regression patterns, with an average follow-up of 6.5 years, after receiving cobalt plaque therapy. Twenty-nine of these 30 patients had been unsuccessfully treated with at least one other modality (ie, light coagulation, cryotherapy, external beam radiation, or chemotherapy)

Radiation regression patterns after cobalt plaque insertion for retinoblastoma

Energy Technology Data Exchange (ETDEWEB)

Buys, R.J.; Abramson, D.H.; Ellsworth, R.M.; Haik, B.

1983-08-01

An analysis of 31 eyes of 30 patients who had been treated with cobalt plaques for retinoblastoma disclosed that a type I radiation regression pattern developed in 15 patients; type II, in one patient, and type III, in five patients. Nine patients had a regression pattern characterized by complete destruction of the tumor, the surrounding choroid, and all of the vessels in the area into which the plaque was inserted. This resulting white scar, corresponding to the sclerae only, was classified as a type IV radiation regression pattern. There was no evidence of tumor recurrence in patients with type IV regression patterns, with an average follow-up of 6.5 years, after receiving cobalt plaque therapy. Twenty-nine of these 30 patients had been unsuccessfully treated with at least one other modality (ie, light coagulation, cryotherapy, external beam radiation, or chemotherapy).

The likelihood of achieving quantified road safety targets: a binary logistic regression model for possible factors.

Science.gov (United States)

Sze, N N; Wong, S C; Lee, C Y

2014-12-01

In past several decades, many countries have set quantified road safety targets to motivate transport authorities to develop systematic road safety strategies and measures and facilitate the achievement of continuous road safety improvement. Studies have been conducted to evaluate the association between the setting of quantified road safety targets and road fatality reduction, in both the short and long run, by comparing road fatalities before and after the implementation of a quantified road safety target. However, not much work has been done to evaluate whether the quantified road safety targets are actually achieved. In this study, we used a binary logistic regression model to examine the factors - including vehicle ownership, fatality rate, and national income, in addition to level of ambition and duration of target - that contribute to a target's success. We analyzed 55 quantified road safety targets set by 29 countries from 1981 to 2009, and the results indicate that targets that are in progress and with lower level of ambitions had a higher likelihood of eventually being achieved. Moreover, possible interaction effects on the association between level of ambition and the likelihood of success are also revealed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Radiotherapy in glomus jugulare and glomus tympanicum tumors. Zur Radiotherapie der Glomus-jugulare-et-tympanicum-Tumoren

Energy Technology Data Exchange (ETDEWEB)

Feyerabend, T; Richter, E; Kapp, B; Bohndorf, W [Wuerzburg Univ. (Germany, F.R.). Klinik und Poliklinik fuer Strahlentherapie; Ptok, M [Wuerzburg Univ. (Germany, F.R.). Klinik und Poliklinik fuer Hals-, Nasen- und Ohrenkranke

1989-09-01

Glomus jugulare tumors are difficult to manage therapeutically due to their localisation. Operation may be successful in small tumors but can be hazardous in larger lesions mainly because of bleeding and palsy of cranial nerves. In these cases there should be used radiation therapy under the condition that it is planned by use of computed tomography. Moreover reproducibility of radiation treatment set-up is vital. In this way tumor regression may be achieved. Four own illustrative cases are demonstrated. According to the stage of disease a modified treatment strategy is presented which integrates surgical procedures, angiographic embolisation and radiotherapy. (orig.).

Immunotherapy with neuraminidase-treated tumor cells after radiotherapy

International Nuclear Information System (INIS)

Song, C.W.; Levitt, S.H.

1975-01-01

The effect of active immunotherapy with Vibrio cholerae neuraminidase-treated syngeneic tumor cells (VCN-cells) following radiotherapy has been studied with 3-methylcholanthrene-induced fibrosarcoma, M-79, transplanted to the thigh of C3H/HeJ mice. When the tumors reached 4 to 8 mm in diameter, various treatments were started. X-irradiation with 2000 rad in a single dose induced a complete regression of 24 out of 103 tumors (23.3 percent). The inoculation of 1 x 10 6 of VCN-cells to the tumor-bearing animals, every other day for a total of three doses, caused a complete regression of 6 out of 57 tumors (10.5 percent). Treatments of animals with the immunotherapy starting 1 day after X-irradiation of tumors with 2000 rad resulted in a complete regression of 22 out of 58 tumors (37.9 percent). The median survival time of animals that received combined radiotherapy and immunotherapy was longer than that observed after either treatment alone

Neonatal umbilical inflammatory myofibroblastic tumor

African Journals Online (AJOL)

antenatal scan. The preferred treatment option is resection of the tumor. Spontaneous regression has been described. Ann Pediatr Surg 13:160–162 c 2017 Annals of Pediatric. Surgery. ... Keywords: inflammatory myofibroblastic tumor, neonatal tumor, surgical resection ... Other anatomical regions were the brain, the.

Purging of the neuroblastoma stem cell compartment and tumor regression on exposure to hypoxia or cytotoxic treatment.

Science.gov (United States)

Marzi, Ilaria; D'Amico, Massimo; Biagiotti, Tiziana; Giunti, Serena; Carbone, Maria Vittoria; Fredducci, David; Wanke, Enzo; Olivotto, Massimo

2007-03-15

We worked out an experimental protocol able to purge the stem cell compartment of the SH-SY5Y neuroblastoma clone. This protocol was based on the prolonged treatment of the wild-type cell population with either hypoxia or the antiblastic etoposide. Cell fate was monitored by immunocytochemical and electrophysiologic (patch-clamp) techniques. Both treatments produced the progressive disappearance of neuronal type (N) cells (which constitute the bulk of the tumor), leaving space for a special category of epithelial-like substrate-adherent cells (S(0)). The latter represent a minimal cell component of the untreated population and are endowed with immunocytochemical markers (p75, c-kit, and CD133) and the electrophysiologic "nude" profile, typical of the neural crest stem cells. S(0) cells displayed a highly clonogenic potency and a substantial plasticity, generating both the N component and an alternative subpopulation terminally committed to the fibromuscular lineage. Unlike the N component, this lineage was highly insensitive to the apoptotic activity of hypoxia and etoposide and developed only when the neuronal option was abolished. Under these conditions, the fibromuscular progeny of S(0) expanded and progressed up to the exhaustion of the staminal compartment and to the extinction of the tumor. When combined, hypoxia and etoposide cooperated in abolishing the N cell generation and promoting the conversion of the tumor described. This synergy might mirror a natural condition in the ischemic areas occurring in cancer. These results have relevant implications for the understanding of the documented tendency of neuroblastomas to regress from a malignant to a benign phenotype, either spontaneously or on antiblastic treatment.

Regression Patterns of Iris Melanoma after Palladium-103 (103Pd) Plaque Brachytherapy.

Science.gov (United States)

Chaugule, Sonal S; Finger, Paul T

2017-07-01

To evaluate the patterns of regression of iris melanoma after treatment with palladium-103 ( 103 Pd) plaque brachytherapy. Retrospective, nonrandomized, interventional case series. Fifty patients with primary malignant melanoma of the iris. Palladium-103 plaque brachytherapy. Changes in tumor size, pigmentation, and vascularity; incidence of iris neovascularization; and radiation-related complications. The mean age in the case series was 61.2±14.9 years. The mean tumor thickness was 1.4±0.6 mm. According to the American Joint Committee on Cancer, eighth edition, staging criteria for iris melanoma, 21 tumors (42%) were T1a, 5 tumors (10%) were T1b, and 24 tumors (48%) were T2a. The tumor was melanotic in 37 cases (74%) and amelanotic in 13 cases (26%); of these, 13 tumors (26%) showed variable pigmentation. After brachytherapy, mean tumor thickness decreased to 0.9±0.2 mm. Pigmentation increased in 32 tumors (64%), decreased in 11 tumors (22%), and was unchanged in 6 tumors (12%). For intrinsic vascularity (n = 19), 12 tumors (63%) showed decrease and 7 tumors (37%) showed complete resolution. Appearance of ectropion uveae showed diminution in 15 tumors (43%); newly present corectopia was observed in 6 patients (12%). On high-frequency ultrasound imaging, of the 42 tumors (84%) with low to moderate internal reflectivity, 30 tumors (60%) showed an increase in internal reflectivity on regression. Iris stromal atrophy was noted in 26 patients (52%), progression or new-onset cataract was noted in 22 patients (44%), neovascular glaucoma was noted in 1 patient (2%), and there were no cases of corneal opacity. There was no clinical evidence (0%) of radiation-induced retinopathy, maculopathy, or optic neuropathy. Mean follow-up in this series was 5.2 years (range, 0.5-17 years). The most common findings related to iris melanoma regression after 103 Pd plaque brachytherapy included decreased intrinsic tumor vascularity, increased tumor pigmentation, and decreased tumor

Simultaneous administration of glucose and hyperoxic gas achieves greater improvement in tumor oxygenation than hyperoxic gas alone

International Nuclear Information System (INIS)

Snyder, Stacey A.; Lanzen, Jennifer L.; Braun, Rod D.; Rosner, Gary; Secomb, Timothy W.; Biaglow, John; Brizel, David M.; Dewhirst, Mark W.

2001-01-01

Purpose: To test the feasibility of hyperglycemic reduction of oxygen consumption combined with oxygen breathing (O 2 ), to improve tumor oxygenation. Methods and Materials: Fischer-344 rats bearing 1 cm R3230Ac flank tumors were anesthetized with Nembutal. Mean arterial pressure, heart rate, tumor blood flow ([TBF], laser Doppler flowmetry), pH, and pO 2 were measured before, during, and after glucose (1 or 4 g/kg) and/or O 2 . Results: Mean arterial pressure and heart rate were unaffected by treatment. Glucose at 1 g/kg yielded maximum blood glucose of 400 mg/dL, no change in TBF, reduced tumor pH (0.17 unit), and 3 mm Hg pO 2 rise. Glucose at 4 g/kg yielded maximum blood glucose of 900 mg/dL, pH drop of 0.6 unit, no pO 2 change, and reduced TBF (31%). Oxygen tension increased by 5 mm Hg with O 2 . Glucose (1 g/Kg) + O 2 yielded the largest change in pO 2 (27 mm Hg); this is highly significant relative to baseline or either treatment alone. The effect was positively correlated with baseline pO 2 , but 6 of 7 experiments with baseline pO 2 2 to improve tumor oxygenation. However, some cell lines are not susceptible to the Crabtree effect, and the magnitude is dependent on baseline pO 2 . Additional or alternative manipulations may be necessary to achieve more uniform improvement in pO 2

Automated Processing of Dynamic Contrast-Enhanced MRI: Correlation of Advanced Pharmacokinetic Metrics with Tumor Grade in Pediatric Brain Tumors.

Science.gov (United States)

Vajapeyam, S; Stamoulis, C; Ricci, K; Kieran, M; Poussaint, T Young

2017-01-01

Pharmacokinetic parameters from dynamic contrast-enhanced MR imaging have proved useful for differentiating brain tumor grades in adults. In this study, we retrospectively reviewed dynamic contrast-enhanced perfusion data from children with newly diagnosed brain tumors and analyzed the pharmacokinetic parameters correlating with tumor grade. Dynamic contrast-enhanced MR imaging data from 38 patients were analyzed by using commercially available software. Subjects were categorized into 2 groups based on pathologic analyses consisting of low-grade (World Health Organization I and II) and high-grade (World Health Organization III and IV) tumors. Pharmacokinetic parameters were compared between the 2 groups by using linear regression models. For parameters that were statistically distinct between the 2 groups, sensitivity and specificity were also estimated. Eighteen tumors were classified as low-grade, and 20, as high-grade. Transfer constant from the blood plasma into the extracellular extravascular space (K trans ), rate constant from extracellular extravascular space back into blood plasma (K ep ), and extracellular extravascular volume fraction (V e ) were all significantly correlated with tumor grade; high-grade tumors showed higher K trans , higher K ep , and lower V e . Although all 3 parameters had high specificity (range, 82%-100%), K ep had the highest specificity for both grades. Optimal sensitivity was achieved for V e , with a combined sensitivity of 76% (compared with 71% for K trans and K ep ). Pharmacokinetic parameters derived from dynamic contrast-enhanced MR imaging can effectively discriminate low- and high-grade pediatric brain tumors. © 2017 by American Journal of Neuroradiology.

Radiation therapy of brain tumor

International Nuclear Information System (INIS)

Sung, K. J.; Lee, D. H.; Park, C. Y.

1980-01-01

One hundred and six cases of brain tumors were treated at the Yonsei Cancer Center from January 1972 to August 1978 by Co-60 teletherapy unit. We analyses their clinical findings, histopathological findings, treatment and results. In those cases which computerized tomography had been used before and after radiation therapy, changes in tumor size and the presence of edema or necrosis following treatment was evaluated. 1. Among 106 cases, 90 cases were primary brain tumors and 16 cases were metastatic brain tumors. Pituitary tumors (38), glioma (34) and pinealoma (10) composed of most of primary brain tumors. 2. Post treatment follow-up was possible in 38 cases more than 1 years. Four among 11 cases of giloma expired and survivors had considerable neurological symptoms except 2 cases. Sixty five percent (12/20) of pituitary tumors showed improvement of visual symptoms and all cases (7) of pinealoma which post treatment follow-up was possible, showed remarkable good response. 3. Findings of CT scan after radiation treatment were compatible with results of clinical findings and post treatment follow-up. It showed complete regression of tumor mass in one case of pinealoma and medulloblastoma. One case of pituitary tumor showed almost complete regression of tumor mass. It also showed large residual lesion in cases of glioblastoma multiforme and cystic astrocytoma.

Longitudinal Studies of Angiogenesis in Hormone-Dependent Shionogi Tumors

Directory of Open Access Journals (Sweden)

Trevor P. Wade

2007-07-01

Full Text Available Vessel size imaging was used to assess changes in the average vessel size of Shionogi tumors throughout the tumor growth cycle. Changes in R2 and R2* relaxivities caused by the injection of a superparamagnetic contrast agent (ferumoxtran-10 were measured using a 2.35-T animal magnetic resonance imaging system, and average vessel size index (VSI was calculated for each stage of tumor progression: growth, regression, and relapse. Statistical analysis using Spearman rank correlation test showed no dependence between vessel size and tumor volume at any stage of the tumor growth cycle. Paired Student's t test was used to assess the statistical significance of the differences in average vessel size for the three stages of the tumor growth cycle. The average VSI for regressing tumors (15.1 ± 6.6 wm was significantly lower than that for growing tumors (35.2 ± 25.5 μm; P < .01. Relapsing tumors also had an average VSI (45.4 ± 41.8 μm higher than that of regressing tumors, although the difference was not statistically significant (P = .067. This study shows that VSI imaging is a viable method for the noninvasive monitoring of angiogenesis during the progression of a Shionogi tumor from androgen dependence to androgen independence.

Tumor Volume Reduction Rate Measured by Magnetic Resonance Volumetry Correlated With Pathologic Tumor Response of Preoperative Chemoradiotherapy for Rectal Cancer

International Nuclear Information System (INIS)

Yeo, Seung-Gu; Kim, Dae Yong; Kim, Tae Hyun; Jung, Kyung Hae; Hong, Yong Sang; Chang, Hee Jin; Park, Ji Won; Lim, Seok-Byung; Choi, Hyo Seong; Jeong, Seung-Yong

2010-01-01

Purpose: To determine whether the tumor volume reduction rate (TVRR) measured using three-dimensional region-of-interest magnetic resonance volumetry correlates with the pathologic tumor response after preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer. Methods and Materials: The study included 405 patients with locally advanced rectal cancer (cT3-T4) who had undergone preoperative CRT and radical proctectomy. The tumor volume was measured using three-dimensional region-of-interest magnetic resonance volumetry before and after CRT but before surgery. We analyzed the correlation between the TVRR and the pathologic tumor response in terms of downstaging and tumor regression grade (TRG). Downstaging was defined as ypStage 0-I (ypT0-T2N0M0), and the TRG proposed by Dworak et al. was used. Results: The mean TVRR was 65.0% ± 22.3%. Downstaging and complete regression occurred in 167 (41.2%) and 58 (14.3%) patients, respectively. The TVRRs according to ypT classification (ypT0-T2 vs. ypT3-T4), ypN classification (ypN0 vs. ypN1-N2), downstaging (ypStage 0-I vs. ypStage II-III), good regression (TRG 3-4 vs. TRG 1-2), and complete regression (TRG 4 vs. TRG 1-3) were all significantly different (p 80%), the rates of ypT0-T2, ypN0, downstaging, and good regression were all significantly greater for patients with a TVRR of ≥60%, as was the complete regression rate for patients with a TVRR >80% (p <.05). Conclusion: The TVRR measured using three-dimensional region-of-interest magnetic resonance volumetry correlated significantly with the pathologic tumor response in terms of downstaging and TRG after preoperative CRT for locally advanced rectal cancer.

TU-AB-202-07: A Novel Method for Registration of Mid-Treatment PET/CT Images Under Conditions of Tumor Regression for Patients with Locally Advanced Lung Cancers

Energy Technology Data Exchange (ETDEWEB)

Sharifi, Hoda [Department of Radiation Oncology, Henry Ford Health System, Detroit, MI (United States); Department of Physics, Oakland University, Rochester, MI (United States); Zhang, Hong; Jin, Jian-Yyue; Kong, Feng-Ming [Department of Radiation Oncology, GRU Cancer Center, Augusta GA (United States); Chetty, Indrin J [Department of Radiation Oncology, Henry Ford Health System, Detroit, MI (United States); Zhong, Hualiang

2016-06-15

Purpose: In PET-guided adaptive radiotherapy (RT), changes in the metabolic activity at individual voxels cannot be derived until the duringtreatment CT images are appropriately registered to pre-treatment CT images. However, deformable image registration (DIR) usually does not preserve tumor volume. This may induce errors when comparing to the target. The aim of this study was to develop a DIR-integrated mechanical modeling technique to track radiation-induced metabolic changes on PET images. Methods: Three patients with non-small cell lung cancer (NSCLC) were treated with adaptive radiotherapy under RTOG 1106. Two PET/CT image sets were acquired 2 weeks before RT and 18 fractions after the start of treatment. DIR was performed to register the during-RT CT to the pre-RT CT using a B-spline algorithm and the resultant displacements in the region of tumor were remodeled using a hybrid finite element method (FEM). Gross tumor volume (GTV) was delineated on the during-RT PET/CT image sets and deformed using the 3D deformation vector fields generated by the CT-based registrations. Metabolic tumor volume (MTV) was calculated using the pre- and during–RT image set. The quality of the PET mapping was evaluated based on the constancy of the mapped MTV and landmark comparison. Results: The B-spline-based registrations changed MTVs by 7.3%, 4.6% and −5.9% for the 3 patients and the correspondent changes for the hybrid FEM method −2.9%, 1% and 6.3%, respectively. Landmark comparisons were used to evaluate the Rigid, B-Spline, and hybrid FEM registrations with the mean errors of 10.1 ± 1.6 mm, 4.4 ± 0.4 mm, and 3.6 ± 0.4 mm for three patients. The hybrid FEM method outperforms the B-Spline-only registration for patients with tumor regression Conclusion: The hybrid FEM modeling technique improves the B-Spline registrations in tumor regions. This technique may help compare metabolic activities between two PET/CT images with regressing tumors. The author gratefully

Engineering a prostate-specific membrane antigen-activated tumor endothelial cell prodrug for cancer therapy.

Science.gov (United States)

Denmeade, Samuel R; Mhaka, Annastasiah M; Rosen, D Marc; Brennen, W Nathaniel; Dalrymple, Susan; Dach, Ingrid; Olesen, Claus; Gurel, Bora; Demarzo, Angelo M; Wilding, George; Carducci, Michael A; Dionne, Craig A; Møller, Jesper V; Nissen, Poul; Christensen, S Brøgger; Isaacs, John T

2012-06-27

Heterogeneous expression of drug target proteins within tumor sites is a major mechanism of resistance to anticancer therapies. We describe a strategy to selectively inhibit, within tumor sites, the function of a critical intracellular protein, the sarcoplasmic/endoplasmic reticulum calcium adenosine triphosphatase (SERCA) pump, whose proper function is required by all cell types for viability. To achieve targeted inhibition, we took advantage of the unique expression of the carboxypeptidase prostate-specific membrane antigen (PSMA) by tumor endothelial cells within the microenvironment of solid tumors. We generated a prodrug, G202, consisting of a PSMA-specific peptide coupled to an analog of the potent SERCA pump inhibitor thapsigargin. G202 produced substantial tumor regression against a panel of human cancer xenografts in vivo at doses that were minimally toxic to the host. On the basis of these data, a phase 1 dose-escalation clinical trial has been initiated with G202 in patients with advanced cancer.

In-vivo luminescence model for the study of tumor regression and regrowth following combination regimens with differentiation-promoting agents and photodynamic therapy

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Rollakanti, K.; Anand, S.; Maytin, E. V.

2013-03-01

Photodynamic therapy with aminolevulinic acid can be modified by pretreatment regimens with drugs such as 5- Fluorouracil (5-FU) or Vitamin D (calcitriol) that enhance accumulation of protoporphyrin IX (PpIX) within tumor tissue which presumably will enhance the therapeutic response to light. However, histological approaches for monitoring therapeutic responses are poorly suited for studying long term survival because large numbers of mice need to be sacrificed. To address this limitation, a non-invasive model to monitor tumor regression and regrowth has been established. Breast cancer cells, stably transfected with firefly luciferase (MDA-Luc cell line), are implanted orthotopically in nude mice (0.25 - 1 x 106 cells/site), and monitored 0-60 min after s.c. injection of luciferin, with Xenogen in-vivo imaging system. Luminescence is detectable at day 1 post-implantation. Tumors are suitable for experimentation on day 6, when daily injections of pretreatment agents (5-FU, 300 mg/kg; calcitriol, 1 μg/kg) begin. On day 9, ALA (75 mg/kg i.p.) is given for 4 hr, followed by illumination (633 nm, 100 J/cm2). Tumor luminescence post- PDT is monitored daily and compared with caliper measurements. Pretreatments (5-FU, calcitriol) by themselves do not inhibit luciferase expression, and all tumors grow at a similar rate during the pretreatment period. Results from in vivo survival experiments can be correlated to survival responses of MDA-Luc cells grown in monolayer cultures +/- PDT and +/- pretreatments, and additional mechanistic information (e.g. Ki67 and E-cadherin expression) obtained. In summary, this noninvasive model will permit testing of the therapeutic survival advantages of various pretreatments during cPDT.

Exploiting tumor shrinkage through temporal optimization of radiotherapy

International Nuclear Information System (INIS)

Unkelbach, Jan; Craft, David; Hong, Theodore; Papp, Dávid; Wolfgang, John; Bortfeld, Thomas; Ramakrishnan, Jagdish; Salari, Ehsan

2014-01-01

In multi-stage radiotherapy, a patient is treated in several stages separated by weeks or months. This regimen has been motivated mostly by radiobiological considerations, but also provides an approach to reduce normal tissue dose by exploiting tumor shrinkage. The paper considers the optimal design of multi-stage treatments, motivated by the clinical management of large liver tumors for which normal liver dose constraints prohibit the administration of an ablative radiation dose in a single treatment. We introduce a dynamic tumor model that incorporates three factors: radiation induced cell kill, tumor shrinkage, and tumor cell repopulation. The design of multi-stage radiotherapy is formulated as a mathematical optimization problem in which the total dose to the normal tissue is minimized, subject to delivering the prescribed dose to the tumor. Based on the model, we gain insight into the optimal administration of radiation over time, i.e. the optimal treatment gaps and dose levels. We analyze treatments consisting of two stages in detail. The analysis confirms the intuition that the second stage should be delivered just before the tumor size reaches a minimum and repopulation overcompensates shrinking. Furthermore, it was found that, for a large range of model parameters, approximately one-third of the dose should be delivered in the first stage. The projected benefit of multi-stage treatments in terms of normal tissue sparing depends on model assumptions. However, the model predicts large dose reductions by more than a factor of 2 for plausible model parameters. The analysis of the tumor model suggests that substantial reduction in normal tissue dose can be achieved by exploiting tumor shrinkage via an optimal design of multi-stage treatments. This suggests taking a fresh look at multi-stage radiotherapy for selected disease sites where substantial tumor regression translates into reduced target volumes. (paper)

Research on the psychological gap, personality and achievement of in-school youth based on regression analysis

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Lei Zhou

2017-02-01

Full Text Available Although our society is in rapid development, the psychological problems among in-school university students are increasingly obvious. According to this problem, this thesis applied the Psychological Gap Scale made by Caixia Ma with EPQ and AMS, and made random questionnaire survey among 400 students in a comprehensive university. The survey found out that the average scores of all psychological gap dimensions exceeded the critical value 3, showing most students in that university have psychological gap. Their personality stability, introversion and extroversion are all above the national norm level while their stubbornness is lower than it. Besides, the students’ motivation in pursuing success is stronger than their motivation in avoiding failure. In the last part, this thesis reached the conclusion that personality leaves a great impact in the students’ psychology through regression analysis model and study of the quantitative relations among personality, achievement and psychological gap.

Differentiation between benign and malignant palatal tumors using conventional MRI: a retrospective analysis of 130 cases.

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Zheng, Yingyan; Xiao, Zebin; Zhang, Hua; She, Dejun; Lin, Xuehua; Lin, Yu; Cao, Dairong

2018-04-01

To evaluate the discriminative value of conventional magnetic resonance imaging between benign and malignant palatal tumors. Conventional magnetic resonance imaging features of 130 patients with palatal tumors confirmed by histopathologic examination were retrospectively reviewed. Clinical data and imaging findings were assessed between benign and malignant tumors and between benign and low-grade malignant salivary gland tumors. The variables that were significant in differentiating benign from malignant lesions were further identified using logistic regression analysis. Moreover, imaging features of each common palatal histologic entity were statistically analyzed with the rest of the tumors to define their typical imaging features. Older age, partially defined and ill-defined margins, and absence of a capsule were highly suggestive of malignant palatal tumors, especially ill-defined margins (β = 6.400). The precision in determining malignant palatal tumors achieved a sensitivity of 92.8% and a specificity of 85.6%. In addition, irregular shape, ill-defined margins, lack of a capsule, perineural spread, and invasion of surrounding structures were more often associated with low-grade malignant salivary gland tumors. Conventional magnetic resonance imaging is useful for differentiating benign from malignant palatal tumors as well as benign salivary gland tumors from low-grade salivary gland malignancies. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Tumor residual pós-quimioterapia neoadjuvante para câncer de mama: impacto sobre o tratamento cirúrgico conservador Residual tumor after neoadjuvant chemotherapy for breast cancer: impact on conservative surgical treatment

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Edison Mantovani Barbosa

1999-05-01

Full Text Available Objetivo: analisar as alterações histopatológicas provocadas pela ação da quimioterapia neoadjuvante (fluoracil, epirrubicina e ciclofosfamida; FEC -- 4 ciclos na área tumoral, no tecido mamário adjacente e nos linfonodos homolaterais, em peças cirúrgicas obtidas de pacientes portadoras de carcinomas primários da mama. Método: estudo histológico detalhado de 30 peças cirúrgicas obtidas por mastectomia radical (Patey de pacientes portadoras de carcinomas primários da mama, previamente submetidas a esse tipo de terapêutica sistêmica. Resultados: observamos regressão tumoral, de grau variável, em todas as peças analisadas. Esta regressão ocorreu de forma irregular, restando inúmeros focos refratários na área ocupada pelo tumor primário. Observamos focos celulares resistentes independentes do tumor primário no tecido mamário. Detalhamos outros achados histopatológicos decorrentes da ação quimioterápica nos tecidos tumoral e mamário, como calcificações e fibrose, e nos linfonodos axilares homolaterais. Conclusão: concluímos que a ação da quimioterapia neoadjuvante não é uniforme, restando focos tumorais refratários, tanto na área do tumor inicial, quanto à distância. A regressão do tumor independe da resposta de regressão dos linfonodos axilares metastáticos. A utilização da cirurgia conservadora pós-quimioterapia neoadjuvante (FEC deve ser evitada.Purpose: analysis of histopathologic alterations caused by neoadjuvant chemotherapy (fluorouracil, epirubicine, cyclophosphamide; FEC - 4 cycles at the tumor site, adjacent mammary tissue and homolateral lymph nodes, as observed in sections of patients with primary breast carcinomas. Method: histological studies performed on 30 surgical sections obtained from radical mastectomy (Patey of patients with primary breast carcinomas, who underwent prior neoadjuvant systemic therapy. Results: all sections showed tumor regression with variable intensity. This

Merkel Cell Carcinoma with Spontaneous Regression: A Case Report and Immunohistochemical Study

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Hitoshi Terui

2016-02-01

Full Text Available Merkel cell carcinoma (MCC is an aggressive neuroendocrine carcinoma that only rarely regresses spontaneously. Since little is known about the immunological mechanisms involved in the spontaneous regression of MCC, we describe a case of MCC with spontaneous regression and employed immunohistochemical staining for cytotoxic and immunosuppressive molecules to investigate possible mechanisms involved in the spontaneous regression of MCC. Interestingly, compared to conventional MCC, tumor-infiltrating lymphocytes in MCC with spontaneous regression contained higher numbers of CD8+ cells and granulysin-bearing cells and lower numbers of CD206+ cells. Our present study suggests one of the possible reasons for the spontaneous regression of MCC.

Differences in the effects of host suppression on the adoptive immunotherapy of subcutaneous and visceral tumors

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Chang, A.E.; Shu, S.Y.; Chou, T.; Lafreniere, R.; Rosenberg, S.A.

1986-01-01

A syngeneic transplantable sarcoma induced in C57BL/6 mice, MCA 105, was used in studies to examine host suppression on the adoptive immunotherapy of established intradermal and experimentally induced pulmonary and hepatic metastases. Fresh immune splenocytes were generated from mice immunized to the MCA 105 tumor by a mixture of viable tumor cells and Corynebacterium parvum. The adoptive immunotherapy of intradermal MCA 105 tumor with immune cells required prior immunosuppression of the recipient by sublethal irradiation with 500 R or T-cell depletion. The effect of whole-body sublethal irradiation appeared to eliminate a systemic host suppression mechanism, since partialbody irradiation involving the tumor-bearing area did not permit successful immunotherapy. Host irradiation was not required to achieve successful immunotherapy of experimentally induced pulmonary or hepatic metastases. In nonirradiated recipients bearing both intradermal and pulmonary tumors, host suppression did not affect the function of transferred immune cells to induce regression of pulmonary metastases. Thus, suppression of adoptive immunotherapy appears to be relevant to tumors confined to the skin and subcutaneous tissue but not to tumor in visceral sites, such as the lung and liver

Brain stem tumors in children - therapeutic results in patients of the University Children's Hospital of Cracow in Poland

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Korab-Chrzanowska, E.; Bartoszewska, J.; Kwiatkowski, S.

2005-01-01

To analyse the treatment results achieved in children treated for brain stem tumours at one institution between the years 1990 and 2004. Material. 20 patients (10 girls, 10 boys) aged 2.8-15.6 years were treated for brain stem tumors at the University Children's Hospital of Cracow (UCHC) in the years 1990-2004. The tumour type was defined basing on imaging studies (CT, MRI), and, in the case of 7 patients, additionally basing on histopathological results. In the collected material the predominant tumor type was benign glioma, detected in 17 patients. Malignant gliomas were diagnosed in 3 children. 7 children were treated by radiotherapy only. Surgical procedures and adjuvant radiotherapy were employed in 3 patients. 6 children underwent radiotherapy and chemotherapy. Combined surgical treatment followed by radiotherapy and chemotherapy was employed in 4 patients. Of the 20 patients 6 have died (30%). The surviving group (70%) includes 1 patient with tumor progression (5%), 5 - with stable tumors (25%), and 8 (40%) - with tumor regression. The probability of three-year overall survival for the entire group as calculated by the Kaplan-Meier method was 70% while the probability of three-year progression-free survival was 65%. Conclusions. Diffuse brain stem tumors, mostly those involving the pons, and malignant gliomas have poor prognosis. In the presented material we achieved the best treatment results in patients with exophytic or focal tumors, treated surgically with adjuvant therapy. (author)

The microbiome modulates the tumor macroenvironment.

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Erdman, Susan E; Poutahidis, Theofilos

2014-01-01

Earlier investigations of the tumor microenvironment unveiled systemic networks presenting novel therapeutic opportunities. It has been recently shown that gut microbes modulate whole host immune and neuroendocrine factors impacting the fate of distant preneoplastic lesions toward malignancy or regression. These findings establish a new paradigm of holobiont therapeutic engineering in emerging tumor macroenvironments.

Determinates of tumor response to radiation: Tumor cells, tumor stroma and permanent local control

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Li, Wende; Huang, Peigen; Chen, David J.; Gerweck, Leo E.

2014-01-01

Background and purpose: The causes of tumor response variation to radiation remain obscure, thus hampering the development of predictive assays and strategies to decrease resistance. The present study evaluates the impact of host tumor stromal elements and the in vivo environment on tumor cell kill, and relationship between tumor cell radiosensitivity and the tumor control dose. Material and methods: Five endpoints were evaluated and compared in a radiosensitive DNA double-strand break repair-defective (DNA-PKcs −/− ) tumor line, and its DNA-PKcs repair competent transfected counterpart. In vitro colony formation assays were performed on in vitro cultured cells, on cells obtained directly from tumors, and on cells irradiated in situ. Permanent local control was assessed by the TCD 50 assay. Vascular effects were evaluated by functional vascular density assays. Results: The fraction of repair competent and repair deficient tumor cells surviving radiation did not substantially differ whether irradiated in vitro, i.e., in the absence of host stromal elements and factors, from the fraction of cells killed following in vivo irradiation. Additionally, the altered tumor cell sensitivity resulted in a proportional change in the dose required to achieve permanent local control. The estimated number of tumor cells per tumor, their cloning efficiency and radiosensitivity, all assessed by in vitro assays, were used to predict successfully, the measured tumor control doses. Conclusion: The number of clonogens per tumor and their radiosensitivity govern the permanent local control dose

Active specific immunotherapy using the immune reaction of a low-dose irradiated tumor tissue

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Ogawa, Y.; Imanaka, K.; Ashida, C.; Takashima, H.; Imajo, Y.; Kimura, S.

1983-01-01

Active specific immunotherapy using the immune reaction of a low-dose irradiated tumor tissue was studied on the transplanted MM46 tumor of female C3H/He mice after radiotherapy. MM46 tumor cells were inoculated into the right hind paws of mice. On the 5th day, irradiation with the dose irradiated tumor tissue (2000 rad on the fifth day), were injected into the left hind paws of the tumor-bearing mice. Effectiveness of this active specific immunotherapy against tumor was evaluated by the regression of tumor and survival rate of mice. Tumor was markedly regressed and survival rate was significantly increased by the active specific immunitherapy

Therapeutic T cells induce tumor-directed chemotaxis of innate immune cells through tumor-specific secretion of chemokines and stimulation of B16BL6 melanoma to secrete chemokines

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Fox Bernard A

2007-11-01

Full Text Available Abstract Background The mechanisms by which tumor-specific T cells induce regression of established metastases are not fully characterized. In using the poorly immunogenic B16BL6-D5 (D5 melanoma model we reported that T cell-mediated tumor regression can occur independently of perforin, IFN-γ or the combination of both. Characterization of regressing pulmonary metastases identified macrophages as a major component of the cells infiltrating the tumor after adoptive transfer of effector T cells. This led us to hypothesize that macrophages played a central role in tumor regression following T-cell transfer. Here, we sought to determine the factors responsible for the infiltration of macrophages at the tumor site. Methods These studies used the poorly immunogenic D5 melanoma model. Tumor-specific effector T cells, generated from tumor vaccine-draining lymph nodes (TVDLN, were used for adoptive immunotherapy and in vitro analysis of chemokine expression. Cellular infiltrates into pulmonary metastases were determined by immunohistochemistry. Chemokine expression by the D5 melanoma following co-culture with T cells, IFN-γ or TNF-α was determined by RT-PCR and ELISA. Functional activity of chemokines was confirmed using a macrophage migration assay. T cell activation of macrophages to release nitric oxide (NO was determined using GRIES reagent. Results We observed that tumor-specific T cells with a type 1 cytokine profile also expressed message for and secreted RANTES, MIP-1α and MIP-1β following stimulation with specific tumor. Unexpectedly, D5 melanoma cells cultured with IFN-γ or TNF-α, two type 1 cytokines expressed by therapeutic T cells, secreted Keratinocyte Chemoattractant (KC, MCP-1, IP-10 and RANTES and expressed mRNA for MIG. The chemokines released by T cells and cytokine-stimulated tumor cells were functional and induced migration of the DJ2PM macrophage cell line. Additionally, tumor-specific stimulation of wt or perforin

On Solving Lq-Penalized Regressions

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Tracy Zhou Wu

2007-01-01

Full Text Available Lq-penalized regression arises in multidimensional statistical modelling where all or part of the regression coefficients are penalized to achieve both accuracy and parsimony of statistical models. There is often substantial computational difficulty except for the quadratic penalty case. The difficulty is partly due to the nonsmoothness of the objective function inherited from the use of the absolute value. We propose a new solution method for the general Lq-penalized regression problem based on space transformation and thus efficient optimization algorithms. The new method has immediate applications in statistics, notably in penalized spline smoothing problems. In particular, the LASSO problem is shown to be polynomial time solvable. Numerical studies show promise of our approach.

Gamma radiosurgery combined with trans-sphenoidal surgery for pituitary tumor involved to the cavernous sinus

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Ikeda, Hidetoshi; Yoshimoto, Takashi; Shirokura, Hidefumi.

1995-01-01

Ten patients (2 males and 8 females with an average age of 39 years) were treated with combined trans-sphenoidal surgery and gamma radiosurgery for pituitary tumor involved to the cavernous sinus. A Follow-up period ranged from 7 to 29 months, with a mean of 21 months. Therapeutic effects were assessed using magnetic resonance imaging (MRI) every 3 months, endocrine examination, optical examination for visual field, and auditory test. Pituitary tumor after radiosurgery was shown as hypointensity on T1-weighted images and hyperintensity on T2-weighted images. Tumor response could be classified on MRI into (1) a remarkably decreased tumor in size with increased contrast enhancement (n=6), (2) a remarkably decreased tumor in size with unchanged contrast enhancement (n=one), (3) a slightly decreased tumor in size with increased spotted contrast enhancement (n=2), and (4) unchanged tumor in size with decreased contrast enhancement (n=one). Of 6 Type 1 patients, 5 had growth hormone production. Growth hormone production tended to be associated with favorable response to radiosurgery. In 3 patients who showed endocrinologically favorable response (such as increased growth hormone in blood and somatomedin C value), complete regression of tumor was achieved at a 20-month follow-up period. Radiosurgery also seemed to be useful for treating hormone active tumors. (N.K.)

Assessment of diagnostic value of various tumors markers (CEA, CA199, CA50) for colorectal neoplasm with logistic regression and ROC curve

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Gu Ping; Huang Gang; Han Yuan

2007-01-01

Objective: To assess the diagnostic value of CEA, CA199 and CA50 for colorectal neoplasm by logistic regression and ROC curve. Methods: Serum CEA (with CLIA), CA199 (with ECLIA) and CA50 (with IRMA) levels were measured in 75 patients with colorectal cancer, 35 patients with benign colorectal disorders and 49 controls. The area under the ROC curve (AUC)s of CEA, CA199, CA50 from logistic regression results were compared. Results: In the cancer-benign disorder group, the AUC of CA50 was larger than the AUC of CA199. AUC of combined CEA, CA50 was largest: not only larger than any AUC of CEA, CA50, CA199 alone but also larger than the AUC of the combined three markers (0.875 vs 0.604). In cancer-control group, the AUC of combination of CEA, CA199 and CA50 was larger than any AUC of CEA, CA199 or CA50 alone. Both in the cancer-benign disorder group or cancer-control group, the AUC of CEA was larger than the AUC of CA199 or CA50. Conclusion: CEA is of definite value in the diagnosis of colorectal cancer. For differential diagnosis, the combination of CEA and CA50 can give more information, while the combination of three tumor markers is less helpful. As an advanced statistical method, logistic regression can improve the diagnostic sensitivity and specificity. (authors)

Paradoxical action of fulvestrant in estradiol-induced regression of tamoxifen-stimulated breast cancer.

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Osipo, Clodia; Gajdos, Csaba; Liu, Hong; Chen, Bin; Jordan, V Craig

2003-11-05

Long-term tamoxifen treatment of breast cancer can result in tamoxifen-stimulated breast cancer, in which estrogen inhibits tumor growth after tamoxifen withdrawal. We investigated the molecular mechanism(s) of estradiol-induced tumor regression by using an in vivo model of tamoxifen-stimulated human breast cancer. Growth of parental estradiol-stimulated MCF-7E2 and long-term tamoxifen-stimulated MCF-7TAMLT xenografts in athymic mice was measured during treatment with vehicle, estradiol, estradiol plus tamoxifen, tamoxifen alone, estradiol plus fulvestrant, or fulvestrant alone. Apoptosis was detected by the terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay. Protein expression was assessed by western blot analysis. mRNA expression was assessed by real-time reverse transcription-polymerase chain reaction. All statistical tests were two-sided. MCF-7E2 tumor growth was stimulated by estradiol (cross-sectional area at week 13 = 1.06 cm2, 95% confidence interval [CI] = 0.82 to 1.30 cm2; Pestradiol-induced regression to 0.18 cm2 (95% CI = 0.15 to 0.21 cm2; P<.001), and tamoxifen or estradiol plus fulvestrant enhanced tumor growth to 1.00 cm2 (95% CI = 0.88 to 1.22 cm2). Estradiol increased the number of apoptotic cells in tumors by 23% (95% CI = 20% to 26%; P<.001) compared with all other treatments, decreased estrogen receptor alpha(ERalpha) protein expression, increased the expression of Fas mRNA and protein, decreased the expression of HER2/neu mRNA and protein and nuclear factor kappaB (NF-kappaB) protein but did not affect Fas ligand protein expression compared with control. Paradoxically, fulvestrant reversed this effect and stimulated MCF-7TAMLT tumor growth apparently through ERalpha-mediated regulation of Fas, HER2/neu, and NF-kappaB. Physiologic levels of estradiol induced regression of tamoxifen-stimulated breast cancer tumors, apparently by inducing the death receptor Fas and suppressing the antiapoptotic

Central nervous system tumors

International Nuclear Information System (INIS)

Curran, W.J. Jr.

1991-01-01

Intrinsic tumors of the central nervous system (CNS) pose a particularly challenging problem to practicing oncologists. These tumors rarely metastasize outside the CNS, yet even histologically benign tumors can be life-threatening due to their local invasiveness and strategic location. The surrounding normal tissues of the nervous system is often incapable of full functional regeneration, therefore prohibiting aggressive attempts to use either complete surgical resection or high doses of irradiation. Despite these limitations, notable achievements have recently been recorded in the management of these tumors

Outcome and histopathologic regression in oral squamous cell carcinoma after preoperative radiochemotherapy

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Driemel, Oliver; Ettl, Tobias; Reichert, Torsten E.; Koelbl, Oliver; Dresp, Bernd V.; Reuther, Juergen; Pistner, Hans

2009-01-01

Background and purpose: preoperative radiochemotherapy has been reported to enhance tumor response and to improve long-term survival in advanced squamous cell carcinoma of the head and neck. This retrospective study evaluates regression rate and long-term survival in 228 patients with primary oral squamous cell carcinoma treated by neoadjuvant radiochemotherapy and radical surgery. Patients and methods: all patients with biopsy-proven, resectable oral squamous cell carcinoma - TNM stages II-IV without distant metastasis - received preoperative treatment consisting of fractioned irradiation of the primary and the regional lymph nodes with a total dose of 40 Gy and additional cisplatin (n = 160) or carboplatin (n = 68) during the 1st week of treatment. Radical surgery and neck dissection followed after a delay of 10-14 days. The study only included cases with histologically negative resection margins. Results: after a median follow-up of 5.2 years, 53 patients (23.2%) had experienced local-regional recurrence. The median 2-year disease-specific survival (DSS) rate was 86.2%. 5-year DSS and 10-year DSS were 76.3% and 66.7%, respectively. Complete histological local tumor regression after surgery (ypTO) was observed in 50 patients (21.9%) and was independent of pretreatment tumor classification. Uni- and multivariate survival analysis revealed that ypT- and ypN-stage were the most decisive predictors for DSS. Conclusion: preoperative radiochemotherapy with cisplatin/carboplatin followed by radical surgery attains favorable long-term survival rates. This applies especially to cases with complete histological tumor regression after radiochemotherapy, which can be assumed for one of five patients. (orig.)

Applied regression analysis a research tool

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Pantula, Sastry; Dickey, David

1998-01-01

Least squares estimation, when used appropriately, is a powerful research tool. A deeper understanding of the regression concepts is essential for achieving optimal benefits from a least squares analysis. This book builds on the fundamentals of statistical methods and provides appropriate concepts that will allow a scientist to use least squares as an effective research tool. Applied Regression Analysis is aimed at the scientist who wishes to gain a working knowledge of regression analysis. The basic purpose of this book is to develop an understanding of least squares and related statistical methods without becoming excessively mathematical. It is the outgrowth of more than 30 years of consulting experience with scientists and many years of teaching an applied regression course to graduate students. Applied Regression Analysis serves as an excellent text for a service course on regression for non-statisticians and as a reference for researchers. It also provides a bridge between a two-semester introduction to...

Imaging of pancreatic tumors

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Brambs, Hans-Juergen; Juchems, Markus

2010-01-01

Ductal adenocarcinoma is the most frequent solid tumor of the pancreas. This tumor has distinct features including early obstruction of the pancreatic duct, diminished enhancement after administration of contrast material due to desmoplastic growth, high propensity to infiltrate adjacent structures and to metastasize into the liver and the peritoneum. Hormone active endocrine tumors cause specific clinical symptoms. Imaging is aimed at localization of these hypervascular tumors. Non hormone active tumors are most frequently malignant and demonstrate very varying features. Cystic pancreatic tumors are increasingly detected by means of cross sectional imaging. Exact classification can be achieved with knowledge of the macropathology and considering clinical presentation as well as age and gender of the patients. (orig.)

Burned-Out Testicular Tumor: A Case Report

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N. Balalaa

2011-01-01

Full Text Available Germ cell tumors constitute the majority of all testicular tumors, which are relatively rare overall and are mainly encountered in young adults and teenagers. The term ‘burned-out’ germ cell tumor refers to the presence of a metastatic germ cell tumor with histological regression of the primary testicular lesion. Clinical examination of the testes and scrotal sonography is pivotal in the initial diagnosis of such neoplasms. We present a case of a 31-year-old male with a retroperitoneal mass and no palpable lesion on testicular examination.

TH-E-BRF-01: Exploiting Tumor Shrinkage in Split-Course Radiotherapy

International Nuclear Information System (INIS)

Unkelbach, J; Craft, D; Hong, T; Papp, D; Wolfgang, J; Bortfeld, T; Ramakrishnan, J; Salari, E

2014-01-01

Purpose: In split-course radiotherapy, a patient is treated in several stages separated by weeks or months. This regimen has been motivated by radiobiological considerations. However, using modern image-guidance, it also provides an approach to reduce normal tissue dose by exploiting tumor shrinkage. In this work, we consider the optimal design of split-course treatments, motivated by the clinical management of large liver tumors for which normal liver dose constraints prohibit the administration of an ablative radiation dose in a single treatment. Methods: We introduce a dynamic tumor model that incorporates three factors: radiation induced cell kill, tumor shrinkage, and tumor cell repopulation. The design of splitcourse radiotherapy is formulated as a mathematical optimization problem in which the total dose to the liver is minimized, subject to delivering the prescribed dose to the tumor. Based on the model, we gain insight into the optimal administration of radiation over time, i.e. the optimal treatment gaps and dose levels. Results: We analyze treatments consisting of two stages in detail. The analysis confirms the intuition that the second stage should be delivered just before the tumor size reaches a minimum and repopulation overcompensates shrinking. Furthermore, it was found that, for a large range of model parameters, approximately one third of the dose should be delivered in the first stage. The projected benefit of split-course treatments in terms of liver sparing depends on model assumptions. However, the model predicts large liver dose reductions by more than a factor of two for plausible model parameters. Conclusion: The analysis of the tumor model suggests that substantial reduction in normal tissue dose can be achieved by exploiting tumor shrinkage via an optimal design of multi-stage treatments. This suggests taking a fresh look at split-course radiotherapy for selected disease sites where substantial tumor regression translates into reduced

TH-E-BRF-01: Exploiting Tumor Shrinkage in Split-Course Radiotherapy

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Unkelbach, J; Craft, D; Hong, T; Papp, D; Wolfgang, J; Bortfeld, T [Massachusetts General Hospital, Boston, MA (United States); Ramakrishnan, J [University of Wisconsin, Madison, Wisconsin (United States); Salari, E [Wichita State University, Wichita, KS (United States)

2014-06-15

Purpose: In split-course radiotherapy, a patient is treated in several stages separated by weeks or months. This regimen has been motivated by radiobiological considerations. However, using modern image-guidance, it also provides an approach to reduce normal tissue dose by exploiting tumor shrinkage. In this work, we consider the optimal design of split-course treatments, motivated by the clinical management of large liver tumors for which normal liver dose constraints prohibit the administration of an ablative radiation dose in a single treatment. Methods: We introduce a dynamic tumor model that incorporates three factors: radiation induced cell kill, tumor shrinkage, and tumor cell repopulation. The design of splitcourse radiotherapy is formulated as a mathematical optimization problem in which the total dose to the liver is minimized, subject to delivering the prescribed dose to the tumor. Based on the model, we gain insight into the optimal administration of radiation over time, i.e. the optimal treatment gaps and dose levels. Results: We analyze treatments consisting of two stages in detail. The analysis confirms the intuition that the second stage should be delivered just before the tumor size reaches a minimum and repopulation overcompensates shrinking. Furthermore, it was found that, for a large range of model parameters, approximately one third of the dose should be delivered in the first stage. The projected benefit of split-course treatments in terms of liver sparing depends on model assumptions. However, the model predicts large liver dose reductions by more than a factor of two for plausible model parameters. Conclusion: The analysis of the tumor model suggests that substantial reduction in normal tissue dose can be achieved by exploiting tumor shrinkage via an optimal design of multi-stage treatments. This suggests taking a fresh look at split-course radiotherapy for selected disease sites where substantial tumor regression translates into reduced

Heterogeneity index evaluated by slope of linear regression on 18F-FDG PET/CT as a prognostic marker for predicting tumor recurrence in pancreatic ductal adenocarcinoma

International Nuclear Information System (INIS)

Kim, Yong-il; Kim, Yong Joong; Paeng, Jin Chul; Cheon, Gi Jeong; Lee, Dong Soo; Chung, June-Key; Kang, Keon Wook

2017-01-01

18 F-Fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) has been investigated as a method to predict pancreatic cancer recurrence after pancreatic surgery. We evaluated the recently introduced heterogeneity indices of 18 F-FDG PET/CT used for predicting pancreatic cancer recurrence after surgery and compared them with current clinicopathologic and 18 F-FDG PET/CT parameters. A total of 93 pancreatic ductal adenocarcinoma patients (M:F = 60:33, mean age = 64.2 ± 9.1 years) who underwent preoperative 18 F-FDG PET/CT following pancreatic surgery were retrospectively enrolled. The standardized uptake values (SUVs) and tumor-to-background ratios (TBR) were measured on each 18 F-FDG PET/CT, as metabolic parameters. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were examined as volumetric parameters. The coefficient of variance (heterogeneity index-1; SUVmean divided by the standard deviation) and linear regression slopes (heterogeneity index-2) of the MTV, according to SUV thresholds of 2.0, 2.5 and 3.0, were evaluated as heterogeneity indices. Predictive values of clinicopathologic and 18 F-FDG PET/CT parameters and heterogeneity indices were compared in terms of pancreatic cancer recurrence. Seventy patients (75.3%) showed recurrence after pancreatic cancer surgery (mean recurrence = 9.4 ± 8.4 months). Comparing the recurrence and no recurrence patients, all of the 18 F-FDG PET/CT parameters and heterogeneity indices demonstrated significant differences. In univariate Cox-regression analyses, MTV (P = 0.013), TLG (P = 0.007), and heterogeneity index-2 (P = 0.027) were significant. Among the clinicopathologic parameters, CA19-9 (P = 0.025) and venous invasion (P = 0.002) were selected as significant parameters. In multivariate Cox-regression analyses, MTV (P = 0.005), TLG (P = 0.004), and heterogeneity index-2 (P = 0.016) with venous invasion (P < 0.001, 0.001, and 0.001, respectively) demonstrated significant results

Predictive Treatment Management: Incorporating a Predictive Tumor Response Model Into Robust Prospective Treatment Planning for Non-Small Cell Lung Cancer

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Zhang, Pengpeng, E-mail: zhangp@mskcc.org [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Yorke, Ellen; Hu, Yu-Chi; Mageras, Gig [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Rimner, Andreas [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Deasy, Joseph O. [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

2014-02-01

Purpose: We hypothesized that a treatment planning technique that incorporates predicted lung tumor regression into optimization, predictive treatment planning (PTP), could allow dose escalation to the residual tumor while maintaining coverage of the initial target without increasing dose to surrounding organs at risk (OARs). Methods and Materials: We created a model to estimate the geometric presence of residual tumors after radiation therapy using planning computed tomography (CT) and weekly cone beam CT scans of 5 lung cancer patients. For planning purposes, we modeled the dynamic process of tumor shrinkage by morphing the original planning target volume (PTV{sub orig}) in 3 equispaced steps to the predicted residue (PTV{sub pred}). Patients were treated with a uniform prescription dose to PTV{sub orig}. By contrast, PTP optimization started with the same prescription dose to PTV{sub orig} but linearly increased the dose at each step, until reaching the highest dose achievable to PTV{sub pred} consistent with OAR limits. This method is compared with midcourse adaptive replanning. Results: Initial parenchymal gross tumor volume (GTV) ranged from 3.6 to 186.5 cm{sup 3}. On average, the primary GTV and PTV decreased by 39% and 27%, respectively, at the end of treatment. The PTP approach gave PTV{sub orig} at least the prescription dose, and it increased the mean dose of the true residual tumor by an average of 6.0 Gy above the adaptive approach. Conclusions: PTP, incorporating a tumor regression model from the start, represents a new approach to increase tumor dose without increasing toxicities, and reduce clinical workload compared with the adaptive approach, although model verification using per-patient midcourse imaging would be prudent.

Pathological assessment of liver fibrosis regression

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WANG Bingqiong

2017-03-01

Full Text Available Hepatic fibrosis is the common pathological outcome of chronic hepatic diseases. An accurate assessment of fibrosis degree provides an important reference for a definite diagnosis of diseases, treatment decision-making, treatment outcome monitoring, and prognostic evaluation. At present, many clinical studies have proven that regression of hepatic fibrosis and early-stage liver cirrhosis can be achieved by effective treatment, and a correct evaluation of fibrosis regression has become a hot topic in clinical research. Liver biopsy has long been regarded as the gold standard for the assessment of hepatic fibrosis, and thus it plays an important role in the evaluation of fibrosis regression. This article reviews the clinical application of current pathological staging systems in the evaluation of fibrosis regression from the perspectives of semi-quantitative scoring system, quantitative approach, and qualitative approach, in order to propose a better pathological evaluation system for the assessment of fibrosis regression.

Basal cell carcinoma: PD-L1/PD-1 checkpoint expression and tumor regression after PD-1 blockade.

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Lipson, Evan J; Lilo, Mohammed T; Ogurtsova, Aleksandra; Esandrio, Jessica; Xu, Haiying; Brothers, Patricia; Schollenberger, Megan; Sharfman, William H; Taube, Janis M

2017-01-01

Monoclonal antibodies that block immune regulatory proteins such as programmed death-1 (PD-1) have demonstrated remarkable efficacy in controlling the growth of multiple tumor types. Unresectable or metastatic basal cell carcinoma, however, has largely gone untested. Because PD-Ligand-1 (PD-L1) expression in other tumor types has been associated with response to anti-PD-1, we investigated the expression of PD-L1 and its association with PD-1 expression in the basal cell carcinoma tumor microenvironment. Among 40 basal cell carcinoma specimens, 9/40 (22%) demonstrated PD-L1 expression on tumor cells, and 33/40 (82%) demonstrated PD-L1 expression on tumor-infiltrating lymphocytes and associated macrophages. PD-L1 was observed in close geographic association to PD-1+ tumor infiltrating lymphocytes. Additionally, we present, here, the first report of an objective anti-tumor response to pembrolizumab (anti-PD-1) in a patient with metastatic PD-L1 (+) basal cell carcinoma, whose disease had previously progressed through hedgehog pathway-directed therapy. The patient remains in a partial response 14 months after initiation of therapy. Taken together, our findings provide a rationale for testing anti-PD-1 therapy in patients with advanced basal cell carcinoma, either as initial treatment or after acquired resistance to hedgehog pathway inhibition.

Commensal bacteria modulate the tumor microenvironment.

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Poutahidis, Theofilos; Erdman, Susan E

2016-09-28

It has been recently shown that gut microbes modulate whole host immune and hormonal factors impacting the fate of distant preneoplastic lesions toward malignancy or regression. This raises the possibility that the tumor microenvironment interacts with broader systemic microbial-immune networks. These accumulated findings suggest novel therapeutic opportunities for holobiont engineering in emerging tumor microenvironments. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

IL-7 and CCL19 expression in CAR-T cells improves immune cell infiltration and CAR-T cell survival in the tumor.

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Adachi, Keishi; Kano, Yosuke; Nagai, Tomohiko; Okuyama, Namiko; Sakoda, Yukimi; Tamada, Koji

2018-04-01

Infiltration, accumulation, and survival of chimeric antigen receptor T (CAR-T) cells in solid tumors is crucial for tumor clearance. We engineered CAR-T cells to express interleukin (IL)-7 and CCL19 (7 × 19 CAR-T cells), as these factors are essential for the maintenance of T-cell zones in lymphoid organs. In mice, 7 × 19 CAR-T cells achieved complete regression of pre-established solid tumors and prolonged mouse survival, with superior anti-tumor activity compared to conventional CAR-T cells. Histopathological analyses showed increased infiltration of dendritic cells (DC) and T cells into tumor tissues following 7 × 19 CAR-T cell therapy. Depletion of recipient T cells before 7 × 19 CAR-T cell administration dampened the therapeutic effects of 7 × 19 CAR-T cell treatment, suggesting that CAR-T cells and recipient immune cells collaborated to exert anti-tumor activity. Following treatment of mice with 7 × 19 CAR-T cells, both recipient conventional T cells and administered CAR-T cells generated memory responses against tumors.

Sparse reduced-rank regression with covariance estimation

KAUST Repository

Chen, Lisha

2014-12-08

Improving the predicting performance of the multiple response regression compared with separate linear regressions is a challenging question. On the one hand, it is desirable to seek model parsimony when facing a large number of parameters. On the other hand, for certain applications it is necessary to take into account the general covariance structure for the errors of the regression model. We assume a reduced-rank regression model and work with the likelihood function with general error covariance to achieve both objectives. In addition we propose to select relevant variables for reduced-rank regression by using a sparsity-inducing penalty, and to estimate the error covariance matrix simultaneously by using a similar penalty on the precision matrix. We develop a numerical algorithm to solve the penalized regression problem. In a simulation study and real data analysis, the new method is compared with two recent methods for multivariate regression and exhibits competitive performance in prediction and variable selection.

Sparse reduced-rank regression with covariance estimation

KAUST Repository

Chen, Lisha; Huang, Jianhua Z.

2014-01-01

Improving the predicting performance of the multiple response regression compared with separate linear regressions is a challenging question. On the one hand, it is desirable to seek model parsimony when facing a large number of parameters. On the other hand, for certain applications it is necessary to take into account the general covariance structure for the errors of the regression model. We assume a reduced-rank regression model and work with the likelihood function with general error covariance to achieve both objectives. In addition we propose to select relevant variables for reduced-rank regression by using a sparsity-inducing penalty, and to estimate the error covariance matrix simultaneously by using a similar penalty on the precision matrix. We develop a numerical algorithm to solve the penalized regression problem. In a simulation study and real data analysis, the new method is compared with two recent methods for multivariate regression and exhibits competitive performance in prediction and variable selection.

Expression of LIGHT/TNFSF14 Combined with Vaccination against Human Papillomavirus Type 16 E7 Induces Significant Tumor Regression

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Kanodia, Shreya; Da Silva, Diane M.; Karamanukyan, Tigran; Bogaert, Lies; Fu, Yang-Xin; Kast, W. Martin

2010-01-01

LIGHT, a ligand for the lymphotoxin-beta receptor, establishes lymphoid-like tissues inside tumor sites and recruits naïve T-cells into the tumor. However, whether these infiltrating T-cells are specific for tumor antigens is not known. We hypothesized that therapy with LIGHT can expand functional tumor-specific CD8+ T-cells that can be boosted using HPV16E6E7-Venezuelan Equine Encephalitis Virus Replicon Particles (HPV16-VRP) and that this combined therapy can eradicate HPV16-induced tumors. Our data show that forced expression of LIGHT in tumors results in an increase in expression of interferon gamma (IFNg) and chemottractant cytokines such as IL-1a, MIG and MIP-2 within the tumor and that this tumor microenvironment correlates with an increase in frequency of tumor-infiltrating CD8+ T-cells. Forced expression of LIGHT also results in the expansion of functional T-cells that recognize multiple tumor-antigens, including HPV16 E7, and these T-cells prevent the outgrowth of tumors upon secondary challenge. Subsequent boosting of E7-specific T-cells by vaccination with HPV16-VRP significantly increases their frequency in both the periphery and the tumor, and leads to the eradication of large well-established tumors, for which either treatment alone is not successful. These data establish the safety of Ad-LIGHT as a therapeutic intervention in pre-clinical studies and suggest that patients with HPV16+ tumors may benefit from combined immunotherapy with LIGHT and antigen-specific vaccination. PMID:20460520

Comparison of logistic regression and neural models in predicting the outcome of biopsy in breast cancer from MRI findings

International Nuclear Information System (INIS)

Abdolmaleki, P.; Yarmohammadi, M.; Gity, M.

2004-01-01

Background: We designed an algorithmic model based on regression analysis and a non-algorithmic model based on the Artificial Neural Network. Materials and methods: The ability of these models was compared together in clinical application to differentiate malignant from benign breast tumors in a study group of 161 patient's records. Each patient's record consisted of 6 subjective features extracted from MRI appearance. These findings were enclosed as features extracted for an Artificial Neural Network as well as a logistic regression model to predict biopsy outcome. After both models had been trained perfectly on samples (n=100), the validation samples (n=61) were presented to the trained network as well as the established logistic regression models. Finally, the diagnostic performance of models were compared to the that of the radiologist in terms of sensitivity, specificity and accuracy, using receiver operating characteristic curve analysis. Results: The average out put of the Artificial Neural Network yielded a perfect sensitivity (98%) and high accuracy (90%) similar to that one of an expert radiologist (96% and 92%) while specificity was smaller than that (67%) verses 80%). The output of the logistic regression model using significant features showed improvement in specificity from 60% for the logistic regression model using all features to 93% for the reduced logistic regression model, keeping the accuracy around 90%. Conclusion: Results show that Artificial Neural Network and logistic regression model prove the relationship between extracted morphological features and biopsy results. Using statistically significant variables reduced logistic regression model outperformed of Artificial Neural Network with remarkable specificity while keeping high sensitivity is achieved

Solid tumor models for the assessment of different treatment modalities. XIV. The evaluation of host and tumor response to cyclophosphamide and radiation

International Nuclear Information System (INIS)

Looney, W.B.; Hopkins, H.A.; MacLeod, M.S.; Ritenour, E.R.

1979-01-01

The effect of increasing doses of cyclophosphamide (50 to 250 mg/kg) on the time of occurrence of maximal and minimal tumor growth rates, tumor volume reduction, and linear doubling times (LDT) on the solid tumor model H-4-II-E has been determined. Tumor response to cyclophosphamide was classified as class I, tumor regression; class II, pseudo-regression; and class III, slow-down. The overall treatment efficiency (OTE) has been used to assess the magnitude of tumor volume changes after treatment. The maximum OTE occurred after 150 mg/kg of cyclophosphamide. Increasing the dose to 200 and 250 mg/kg of cyclophosphamide resulted in a decrease in OTE. Similar parameters were utilized to measure the effectiveness of increasing doses of local tumor radiation (750, 1500, 2000, 2500, 3000 and 3500R). The major increase in OTE occurs when the radiation dose is increased from 750R to 2000R. Increasing the dose further to 3500R results in smaller incremental increases in the OTE. Results of the study indicate that increasing the cyclophosphamide dose beyond a certain level (i.e., 150 mg/kg) increases mortality and morbidity without concomitant therapeutic benefit. The effects of increasing the dose of local tumor radiation on life span have given results which suggest that increasing the total radiation dose beyond a certain limit is less effective in increasing life span

Brown tumor of secondary hyperparathyroidism: surgical approach and clinical outcome.

Science.gov (United States)

Queiroz, Isaac Vieira; Queiroz, Samara Pereira; Medeiros, Rui; Ribeiro, Rodolfo Bonfim; Crusoé-Rebello, Iêda Margarida; Leão, Jair Carneiro

2016-12-01

Secondary hyperparathyroidism is a frequent complication of chronic renal failure. The brown tumor is an unusual presentation of fibrous osteitis that represents a serious complication of renal osteodystrophy, affecting predominantly the hands, feet, skull, and facial bones. The aim of this paper is to describe the case of a 53-year-old female patient, with renal failure who has been on dialysis for 6 years and developed severe secondary hyperparathyroidism and brown tumor of the maxilla and mandible, confirmed by incisional biopsy. Parathyroidectomy was indicated as a result of rapid growth of the tumor and the maintenance of laboratory findings. Despite the normalization of serum parathyroid hormone and alkaline phosphatase, tumor regression was slow and patient's important functional and esthetic deficits persisted. Excision of the mandible tumor was conservative. Osteoplasty was recommended because during a 5-year follow-up there was regression of the lesion, decreased pain, bleeding, and tooth mobility.

Heterogeneity index evaluated by slope of linear regression on {sup 18}F-FDG PET/CT as a prognostic marker for predicting tumor recurrence in pancreatic ductal adenocarcinoma

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Kim, Yong-il [CHA University, Department of Nuclear Medicine, CHA Bundang Medical Center, Seongnam (Korea, Republic of); Seoul National University Hospital, Department of Nuclear Medicine, Seoul (Korea, Republic of); Kim, Yong Joong [Veterans Health Service Medical Center, Seoul (Korea, Republic of); Paeng, Jin Chul; Cheon, Gi Jeong; Lee, Dong Soo [Seoul National University Hospital, Department of Nuclear Medicine, Seoul (Korea, Republic of); Chung, June-Key [Seoul National University Hospital, Department of Nuclear Medicine, Seoul (Korea, Republic of); Seoul National University, Cancer Research Institute, Seoul (Korea, Republic of); Kang, Keon Wook [Seoul National University Hospital, Department of Nuclear Medicine, Seoul (Korea, Republic of); Seoul National University, Cancer Research Institute, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Biomedical Sciences, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of)

2017-11-15

{sup 18}F-Fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) has been investigated as a method to predict pancreatic cancer recurrence after pancreatic surgery. We evaluated the recently introduced heterogeneity indices of {sup 18}F-FDG PET/CT used for predicting pancreatic cancer recurrence after surgery and compared them with current clinicopathologic and {sup 18}F-FDG PET/CT parameters. A total of 93 pancreatic ductal adenocarcinoma patients (M:F = 60:33, mean age = 64.2 ± 9.1 years) who underwent preoperative {sup 18}F-FDG PET/CT following pancreatic surgery were retrospectively enrolled. The standardized uptake values (SUVs) and tumor-to-background ratios (TBR) were measured on each {sup 18}F-FDG PET/CT, as metabolic parameters. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were examined as volumetric parameters. The coefficient of variance (heterogeneity index-1; SUVmean divided by the standard deviation) and linear regression slopes (heterogeneity index-2) of the MTV, according to SUV thresholds of 2.0, 2.5 and 3.0, were evaluated as heterogeneity indices. Predictive values of clinicopathologic and {sup 18}F-FDG PET/CT parameters and heterogeneity indices were compared in terms of pancreatic cancer recurrence. Seventy patients (75.3%) showed recurrence after pancreatic cancer surgery (mean recurrence = 9.4 ± 8.4 months). Comparing the recurrence and no recurrence patients, all of the {sup 18}F-FDG PET/CT parameters and heterogeneity indices demonstrated significant differences. In univariate Cox-regression analyses, MTV (P = 0.013), TLG (P = 0.007), and heterogeneity index-2 (P = 0.027) were significant. Among the clinicopathologic parameters, CA19-9 (P = 0.025) and venous invasion (P = 0.002) were selected as significant parameters. In multivariate Cox-regression analyses, MTV (P = 0.005), TLG (P = 0.004), and heterogeneity index-2 (P = 0.016) with venous invasion (P < 0.001, 0.001, and 0

Dietary rice bran component γ-oryzanol inhibits tumor growth in tumor-bearing mice.

Science.gov (United States)

Kim, Sung Phil; Kang, Mi Young; Nam, Seok Hyun; Friedman, Mendel

2012-06-01

We investigated the effects of rice bran and components on tumor growth in mice. Mice fed standard diets supplemented with rice bran, γ-oryzanol, Ricetrienol®, ferulic acid, or phytic acid for 2 weeks were inoculated with CT-26 colon cancer cells and fed the same diet for two additional weeks. Tumor mass was significantly lower in the γ-oryzanol and less so in the phytic acid group. Tumor inhibition was associated with the following biomarkers: increases in cytolytic activity of splenic natural killer (NK) cells; partial restoration of nitric oxide production and phagocytosis in peritoneal macrophages increases in released the pro-inflammatory cytokines tumor necrosis factor-α, IL-1β, and IL-6 from macrophages; and reductions in the number of blood vessels inside the tumor. Pro-angiogenic biomarkers vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), and 5-lipoxygenase-5 (5-LOX) were also significantly reduced in mRNA and protein expression by tumor genes. ELISA of tumor cells confirmed reduced expression of COX-2 and 5-LOX up to 30%. Reduced COX-2 and 5-LOX expression downregulated VEGF and inhibited neoangiogenesis inside the tumors. Induction of NK activity, activation of macrophages, and inhibition of angiogenesis seem to contribute to the inhibitory mechanism of tumor regression by γ-oryzanol. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Computer-aided diagnosis of liver tumors on computed tomography images.

Science.gov (United States)

Chang, Chin-Chen; Chen, Hong-Hao; Chang, Yeun-Chung; Yang, Ming-Yang; Lo, Chung-Ming; Ko, Wei-Chun; Lee, Yee-Fan; Liu, Kao-Lang; Chang, Ruey-Feng

2017-07-01

Liver cancer is the tenth most common cancer in the USA, and its incidence has been increasing for several decades. Early detection, diagnosis, and treatment of the disease are very important. Computed tomography (CT) is one of the most common and robust imaging techniques for the detection of liver cancer. CT scanners can provide multiple-phase sequential scans of the whole liver. In this study, we proposed a computer-aided diagnosis (CAD) system to diagnose liver cancer using the features of tumors obtained from multiphase CT images. A total of 71 histologically-proven liver tumors including 49 benign and 22 malignant lesions were evaluated with the proposed CAD system to evaluate its performance. Tumors were identified by the user and then segmented using a region growing algorithm. After tumor segmentation, three kinds of features were obtained for each tumor, including texture, shape, and kinetic curve. The texture was quantified using 3 dimensional (3-D) texture data of the tumor based on the grey level co-occurrence matrix (GLCM). Compactness, margin, and an elliptic model were used to describe the 3-D shape of the tumor. The kinetic curve was established from each phase of tumor and represented as variations in density between each phase. Backward elimination was used to select the best combination of features, and binary logistic regression analysis was used to classify the tumors with leave-one-out cross validation. The accuracy and sensitivity for the texture were 71.82% and 68.18%, respectively, which were better than for the shape and kinetic curve under closed specificity. Combining all of the features achieved the highest accuracy (58/71, 81.69%), sensitivity (18/22, 81.82%), and specificity (40/49, 81.63%). The Az value of combining all features was 0.8713. Combining texture, shape, and kinetic curve features may be able to differentiate benign from malignant tumors in the liver using our proposed CAD system. Copyright © 2017 Elsevier B.V. All

William Bradley Coley, MD, and the phenomenon of spontaneous regression

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Vernon LF

2018-04-01

Full Text Available Leonard F Vernon Sherman College of Chiropractic, Spartanburg, SC, USA Abstract: The standard definition of spontaneous regression (SR of cancer is as follows, “…when a malignant tumor partially or completely disappears without treatment or in the presence of therapy which is considered inadequate to exert a significant influence on neoplastic disease.” SR is also known as Saint Peregrine tumor, the name taken from a young priest, Peregrine Laziosi (1260 [5]–1345, exact date is unknown, who had been diagnosed with a tumor of the tibia. The mass eventually grew so large that it broke through the skin and became severely infected. The available treatment for this condition was limited to amputation. Historical records report that on the day of surgery, physicians found that the tumor had disappeared and reportedly never returned. To date, the medical literature consists only of individual case studies and overviews of this phenomenon. The most cited work on the subject was done by surgeons Tilden Everson and Warren Cole who reviewed 176 published cases of SR from 1900 to 1960. While a percentage of these were found not to be cases of SR, there remained a number of unexplained cases. A frequent theme in many cases of SR is the co-occurrence of infection. Given the current interest in immunotherapy in the treatment of cancer, this article discusses one of the very early pioneers of this theory, William Bradley Coley, MD, a surgeon who was clearly ahead of his time. Ostracized by colleagues for his belief that stimulation of the immune system could in fact produce a regression of cancer, Coley remained convinced that his theory was right and, while he was not familiar with cytokines such as tumor necrosis factor (TNF, interferons, and streptokinase, he knew instinctively that an innate immune response was taking place. Keywords: autoimmunity, cancer, fever, infection, immunotherapy, tumor, cytokines

PET measurements of hyperthermia-induced suppression of protein synthesis in tumors in relation to effects on tumor growth

International Nuclear Information System (INIS)

Daemen, B.J.; Elsinga, P.H.; Mooibroek, J.; Paans, A.M.; Wieringa, A.R.; Konings, A.W.; Vaalburg, W.

1991-01-01

Hyperthermia-induced metabolic changes in tumor tissue have been monitored by PET. Uptake of L-[1-11C]tyrosine in rhabdomyosarcoma tissue of Wag/Rij rats was dose-dependently reduced after local hyperthermia treatment at 42, 45, or 47 degrees C. Tumor blood flow, as measured by PET with 13NH3, appeared to be unchanged. The L-[1-11C]tyrosine uptake data were compared to uptake data of L-[1-14C]tyrosine and with data on the incorporation of L-[1-14C]tyrosine into tumor proteins. After intravenous injection, the 14C data were obtained from dissected tumor tissue. Heat-induced inhibition of the incorporation of L-[1-14C]tyrosine into tumor proteins tallied with the L-[1-11C]tyrosine uptake data. Heat-induced inhibition of amino acid uptake in the tumor correlated well with regression of tumor growth. It is concluded that PET using L-[1-11C]tyrosine is eligible for monitoring the effect of hyperthermia on tumor growth

Antitumor effectiveness of different amounts of electrical charge in Ehrlich and fibrosarcoma Sa-37 tumors

International Nuclear Information System (INIS)

Ciria, HC; Quevedo, MS; Cabrales, LB; Bruzón, RP; Salas, MF; Pena, OG; González, TR; López, DS; Flores, JM

2004-01-01

In vivo studies were conducted to quantify the effectiveness of low-level direct electric current for different amounts of electrical charge and the survival rate in fibrosarcoma Sa-37 and Ehrlich tumors, also the effect of direct electric in Ehrlich tumor was evaluate through the measurements of tumor volume and the peritumoral and tumoral findings. BALB/c male mice, 7–8 week old and 20–22 g weight were used. Ehrlich and fibrosarcoma Sa-37 cell lines, growing in BALB/c mice. Solid and subcutaneous Ehrlich and fibrosarcoma Sa-37 tumors, located dorsolaterally in animals, were initiated by the inoculation of 5 × 10 6 and 1 × 10 5 viable tumor cells, respectively. For each type of tumor four groups (one control group and three treated groups) consisting of 10 mice randomly divided were formed. When the tumors reached approximately 0.5 cm 3 , four platinum electrodes were inserted into their bases. The electric charge delivered to the tumors was varied in the range of 5.5 to 110 C/cm 3 for a constant time of 45 minutes. An additional experiment was performed in BALB/c male mice bearing Ehrlich tumor to examine from a histolological point of view the effects of direct electric current. A control group and a treated group with 77 C/cm 3 (27.0 C in 0.35 cm 3 ) and 10 mA for 45 min were formed. In this experiment when the tumor volumes reached 0.35 cm 3 , two anodes and two cathodes were inserted into the base perpendicular to the tumor long axis. Significant tumor growth delay and survival rate were achieved after electrotherapy and both were dependent on direct electric current intensity, being more marked in fibrosarcoma Sa-37 tumor. Complete regressions for fibrosarcoma Sa-37 and Ehrlich tumors were observed for electrical charges of 80 and 92 C/cm 3 , respectively. Histopathological and peritumoral findings in Ehrlich tumor revealed in the treated group marked tumor necrosis, vascular congestion, peritumoral neutrophil infiltration, an acute inflammatory

The dual PI3K/mTOR inhibitor NVP-BEZ235 induces tumor regression in a genetically engineered mouse model of PIK3CA wild-type colorectal cancer.

Directory of Open Access Journals (Sweden)

Jatin Roper

Full Text Available To examine the in vitro and in vivo efficacy of the dual PI3K/mTOR inhibitor NVP-BEZ235 in treatment of PIK3CA wild-type colorectal cancer (CRC.PIK3CA mutant and wild-type human CRC cell lines were treated in vitro with NVP-BEZ235, and the resulting effects on proliferation, apoptosis, and signaling were assessed. Colonic tumors from a genetically engineered mouse (GEM model for sporadic wild-type PIK3CA CRC were treated in vivo with NVP-BEZ235. The resulting effects on macroscopic tumor growth/regression, proliferation, apoptosis, angiogenesis, and signaling were examined.In vitro treatment of CRC cell lines with NVP-BEZ235 resulted in transient PI3K blockade, sustained decreases in mTORC1/mTORC2 signaling, and a corresponding decrease in cell viability (median IC(50 = 9.0-14.3 nM. Similar effects were seen in paired isogenic CRC cell lines that differed only in the presence or absence of an activating PIK3CA mutant allele. In vivo treatment of colonic tumor-bearing mice with NVP-BEZ235 resulted in transient PI3K inhibition and sustained blockade of mTORC1/mTORC2 signaling. Longitudinal tumor surveillance by optical colonoscopy demonstrated a 97% increase in tumor size in control mice (p = 0.01 vs. a 43% decrease (p = 0.008 in treated mice. Ex vivo analysis of the NVP-BEZ235-treated tumors demonstrated a 56% decrease in proliferation (p = 0.003, no effects on apoptosis, and a 75% reduction in angiogenesis (p = 0.013.These studies provide the preclinical rationale for studies examining the efficacy of the dual PI3K/mTOR inhibitor NVP-BEZ235 in treatment of PIK3CA wild-type CRC.

Marginal longitudinal semiparametric regression via penalized splines

KAUST Repository

Al Kadiri, M.

2010-08-01

We study the marginal longitudinal nonparametric regression problem and some of its semiparametric extensions. We point out that, while several elaborate proposals for efficient estimation have been proposed, a relative simple and straightforward one, based on penalized splines, has not. After describing our approach, we then explain how Gibbs sampling and the BUGS software can be used to achieve quick and effective implementation. Illustrations are provided for nonparametric regression and additive models.

Marginal longitudinal semiparametric regression via penalized splines

KAUST Repository

Al Kadiri, M.; Carroll, R.J.; Wand, M.P.

2010-01-01

We study the marginal longitudinal nonparametric regression problem and some of its semiparametric extensions. We point out that, while several elaborate proposals for efficient estimation have been proposed, a relative simple and straightforward one, based on penalized splines, has not. After describing our approach, we then explain how Gibbs sampling and the BUGS software can be used to achieve quick and effective implementation. Illustrations are provided for nonparametric regression and additive models.

Diltiazem enhances tumor blood flow: MRI study in a murine tumor

International Nuclear Information System (INIS)

Muruganandham, M.; Kasiviswanathan, A.; Jagannathan, N.R.; Raghunathan, P.; Jain, P.C.; Jain, V.

1999-01-01

Purpose: Diltiazem, a calcium-channel blocker, is known to differentially influence the radiation responses of normal and murine tumor tissues. To elucidate the underlying mechanisms, the effects of diltiazem on the radiation response of Ehrlich ascites tumor (EAT) in mice have been investigated, and the hemodynamic changes induced by diltiazem in tumor and normal muscle have been studied using magnetic resonance imaging (MRI) techniques. Methods and Materials: Ehrlich ascites tumors were grown subcutaneously in Swiss albino strain A mice. Dynamic gadodiamide and blood oxygen level dependent (BOLD) contrast enhanced 1 H MR imaging studies of EAT and normal muscle were performed after administration of diltiazem in mice using a 4.7 Tesla MR scanner. Tumor radiotherapy experiments (total dose = 10 Gy, 0.4-0.5 Gy/min, single fraction) were carried out with 30 min preadministration of diltiazem (27.5 or 55 mg/kg i.p.) to EAT-bearing mice using a teletherapy machine. Results: The diltiazem+ radiation treated group showed significant tumor regression (in congruent with 65% of the animals) and enhanced animal survival. MR-gadodiamide contrast kinetics revealed a higher magnitude of signal enhancement in diltiazem treated groups as compared to the controls. The observed changes in the magnitude of kinetic parameters were the same for both tumor and normal muscle. BOLD-MR images at 30 min after diltiazem administration showed a 25% and 8% (average) intensity enhancement from their basal values in tumor and normal muscle regions, respectively. The control group showed no significant changes. Conclusion: The present studies demonstrate the radiosensitization potential of diltiazem in the mice EAT model. The enhanced radiation response observed with diltiazem correlates with the diltiazem-induced increase in tumor blood flow (TBF) and tumor oxygenation. The present results also demonstrate the applications of BOLD-MR measurements in investigating the alterations in tumor

Photodynamic Therapy of the Murine LM3 Tumor Using Meso-Tetra (4-N,N,N-Trimethylanilinium) Porphine.

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Colombo, L L; Juarranz, A; Cañete, M; Villanueva, A; Stockert, J C

2007-12-01

Photodynamic therapy (PDT) of cancer is based on the cytotoxicity induced by a photosensitizer in the presence of oxygen and visible light, resulting in cell death and tumor regression. This work describes the response of the murine LM3 tumor to PDT using meso-tetra (4-N,N,N-trimethylanilinium) porphine (TMAP). BALB/c mice with intradermal LM3 tumors were subjected to intravenous injection of TMAP (4 mg/kg) followed 24 h later by blue-red light irradiation (λmax: 419, 457, 650 nm) for 60 min (total dose: 290 J/cm(2)) on depilated and glycerol-covered skin over the tumor of anesthetized animals. Control (drug alone, light alone) and PDT treatments (drug + light) were performed once and repeated 48 h later. No significant differences were found between untreated tumors and tumors only treated with TMAP or light. PDT-treated tumors showed almost total but transitory tumor regression (from 3 mm to less than 1 mm) in 8/9 animals, whereas no regression was found in 1/9. PDT response was heterogeneous and each tumor showed different regression and growth delay. The survival of PDT-treated animals was significantly higher than that of TMAP and light controls, showing a lower number of lung metastasis but increased tumor-draining lymph node metastasis. Repeated treatment and reduction of tissue light scattering by glycerol could be useful approaches in studies on PDT of cancer.

Poisson Mixture Regression Models for Heart Disease Prediction.

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Mufudza, Chipo; Erol, Hamza

2016-01-01

Early heart disease control can be achieved by high disease prediction and diagnosis efficiency. This paper focuses on the use of model based clustering techniques to predict and diagnose heart disease via Poisson mixture regression models. Analysis and application of Poisson mixture regression models is here addressed under two different classes: standard and concomitant variable mixture regression models. Results show that a two-component concomitant variable Poisson mixture regression model predicts heart disease better than both the standard Poisson mixture regression model and the ordinary general linear Poisson regression model due to its low Bayesian Information Criteria value. Furthermore, a Zero Inflated Poisson Mixture Regression model turned out to be the best model for heart prediction over all models as it both clusters individuals into high or low risk category and predicts rate to heart disease componentwise given clusters available. It is deduced that heart disease prediction can be effectively done by identifying the major risks componentwise using Poisson mixture regression model.

Poisson Mixture Regression Models for Heart Disease Prediction

Science.gov (United States)

Erol, Hamza

2016-01-01

Early heart disease control can be achieved by high disease prediction and diagnosis efficiency. This paper focuses on the use of model based clustering techniques to predict and diagnose heart disease via Poisson mixture regression models. Analysis and application of Poisson mixture regression models is here addressed under two different classes: standard and concomitant variable mixture regression models. Results show that a two-component concomitant variable Poisson mixture regression model predicts heart disease better than both the standard Poisson mixture regression model and the ordinary general linear Poisson regression model due to its low Bayesian Information Criteria value. Furthermore, a Zero Inflated Poisson Mixture Regression model turned out to be the best model for heart prediction over all models as it both clusters individuals into high or low risk category and predicts rate to heart disease componentwise given clusters available. It is deduced that heart disease prediction can be effectively done by identifying the major risks componentwise using Poisson mixture regression model. PMID:27999611

Regression of a vaginal leiomyoma after ovariohysterectomy in a dog: a case report.

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Sathya, Suresh; Linn, Kathleen

2014-01-01

An 11 yr old female mixed-breed Siberian husky was presented with a history of sanguineous vaginal discharge, swelling of the perineal area, decreased appetite, and lethargy. A single, large vaginal leiomyoma and multiple mammary tumors were diagnosed. Mastectomy and ovariohysterectomy were performed. The vaginal leiomyoma regressed completely after ovariohysterectomy. This is the first reported case of spontaneous regression of a vaginal leiomyoma after ovariohysterectomy in a dog.

Preoperative intraluminal irradiation of the extrahepatic bile duct tumor

International Nuclear Information System (INIS)

Kamada, Tadashi; Tsujii, Hirohiko; Arimoto, Takuro; Irie, Goro.

1991-01-01

From 1984 through 1986, six patients with extrahepatic bile duct tumor were treated preoperatively with intraluminal irradiation of the bile duct. There were no unresectable cases and pathological examination of the surgical specimens showed moderate to remarkable tumor regression in all cases. Postoperative biliary tract hemorrhage occurred in 2 of 3 patients who received 60 Gy at a point 7.5 mm from the center of the source. With accurate preoperative diagnosis of the tumor extent and careful setting of the target area of intraluminal irradiation, improved local tumor control of extrahepatic bile duct tumor can be expected with this method. (author)

A case of intracranial malignant lymphoma with pure akinesia and repeated regression on CT scans

International Nuclear Information System (INIS)

Suzuki, Takeo; Yamamoto, Mari; Saitoh, Mitsunori; Aoki, Akira; Imai, Hisamasa; Narabayashi, Hirotaro.

1984-01-01

In a case of primary reticulum cell sarcoma in the brain, histologically verified by biopsy, the tumor regressed twice on a CT scan without radiotherapy. The systemic freezing phenomenon was seen as a main clinical symptom. The patient, a 44 year-old male, first complained of decreased livido and festinating speech. He also showed frozen gait, micrographia, a decrease in spontaneity and urinary incontinence. Four months after onset he was hospitalized. Neurological findings on admission revealed freezing of gait, writing, and speech, but there was no weakness of muscles with normal tendon reflexes, and normal muscular tone. In the CT scan on admission, there were high density areas mainly in the head of the right caudate nucleus, the medial deep portion of the right frontal lobe, the right side of the hypothalamus, the anterior thalamus, the globus pallidus. There were also nodular-type enhanced effects in the same areas. Regression of the tumor was seen on the CT scans after administration of betamethasone. The tumor which had again incrased in size regressed spontaneously without the use of steroids after 3 months. Thereafter, the tumor gradually became larger and an open biopsy was perfomed. Histopathological findings showed a reticulum cell sarcoma. There were no findings of systemic malignant lymphoma. Such intracrainal malignant lymphomas showing repeated regression including spontaneous one are very rare in the literature. The freezing phenomenon in this case started with festinating speech and spread to writing and gait. L-DOPA had no effect. This systemic freezing phenomenon was considered to be the same as that in the cases of pure akinesia without rigidity and tremor reported by Narabayashi and Imai, which did not respond to L-DOPA at all. But on the other hand, L-Threo-3, 4-Dihydroxyphenylserine was effective to the frozen gait of this patient. (J.P.N.)

Cell proliferation markers in the transplanted canine transmissible venereal tumor

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F.G.A. Santos

2011-12-01

Full Text Available Adult male mongrel dogs were subcutaneously transplanted with the canine transmissible venereal tumor (TVT on the hypogastric region. Twelve specimens of tumors were collected, half during the proliferative phase and the other half during the regressive phase. Fragments of the tumor were fixed in 10% buffered formalin and routinely processed for light microscopy. Sections of 4µm were stained by Schorr or AgNOR or either immunostained for MIB1 (Ki67. Schorr stain, AgNOR and MIB1 showed an increased proliferative activity through mitotic index, nuclear argyrophilic protein stain and cycling tumoral cells in the growing tumors, respectively. All of the three cell proliferation markers were able to distinguish the TVT in both evolution phases. MIB1 monoclonal antibody was the best in the morphologic evaluation of growth and regression of TVT. This resulted in higher values than AgNORs counting and mitotic index. MIB1 immunostaining was the most effective parameter of the proliferative activity of TVT. However, a significant correlation has been detected only between mitosis counting and AgNORs.

Monte Carlo calculation of the maximum therapeutic gain of tumor antivascular alpha therapy

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Huang, Chen-Yu; Oborn, Bradley M.; Guatelli, Susanna; Allen, Barry J. [Centre for Experimental Radiation Oncology, St. George Clinical School, University of New South Wales, Kogarah, New South Wales 2217 (Australia); Illawarra Cancer Care Centre, Wollongong, New South Wales 2522, Australia and Centre for Medical Radiation Physics, University of Wollongong, New South Wales 2522 (Australia); Centre for Medical Radiation Physics, University of Wollongong, New South Wales 2522 (Australia); Centre for Experimental Radiation Oncology, St. George Clinical School, University of New South Wales, Kogarah, New South Wales 2217 (Australia)

2012-03-15

Purpose: Metastatic melanoma lesions experienced marked regression after systemic targeted alpha therapy in a phase 1 clinical trial. This unexpected response was ascribed to tumor antivascular alpha therapy (TAVAT), in which effective tumor regression is achieved by killing endothelial cells (ECs) in tumor capillaries and, thus, depriving cancer cells of nutrition and oxygen. The purpose of this paper is to quantitatively analyze the therapeutic efficacy and safety of TAVAT by building up the testing Monte Carlo microdosimetric models. Methods: Geant4 was adapted to simulate the spatial nonuniform distribution of the alpha emitter {sup 213}Bi. The intraluminal model was designed to simulate the background dose to normal tissue capillary ECs from the nontargeted activity in the blood. The perivascular model calculates the EC dose from the activity bound to the perivascular cancer cells. The key parameters are the probability of an alpha particle traversing an EC nucleus, the energy deposition, the lineal energy transfer, and the specific energy. These results were then applied to interpret the clinical trial. Cell survival rate and therapeutic gain were determined. Results: The specific energy for an alpha particle hitting an EC nucleus in the intraluminal and perivascular models is 0.35 and 0.37 Gy, respectively. As the average probability of traversal in these models is 2.7% and 1.1%, the mean specific energy per decay drops to 1.0 cGy and 0.4 cGy, which demonstrates that the source distribution has a significant impact on the dose. Using the melanoma clinical trial activity of 25 mCi, the dose to tumor EC nucleus is found to be 3.2 Gy and to a normal capillary EC nucleus to be 1.8 cGy. These data give a maximum therapeutic gain of about 180 and validate the TAVAT concept. Conclusions: TAVAT can deliver a cytotoxic dose to tumor capillaries without being toxic to normal tissue capillaries.

Descriptor Learning via Supervised Manifold Regularization for Multioutput Regression.

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Zhen, Xiantong; Yu, Mengyang; Islam, Ali; Bhaduri, Mousumi; Chan, Ian; Li, Shuo

2017-09-01

Multioutput regression has recently shown great ability to solve challenging problems in both computer vision and medical image analysis. However, due to the huge image variability and ambiguity, it is fundamentally challenging to handle the highly complex input-target relationship of multioutput regression, especially with indiscriminate high-dimensional representations. In this paper, we propose a novel supervised descriptor learning (SDL) algorithm for multioutput regression, which can establish discriminative and compact feature representations to improve the multivariate estimation performance. The SDL is formulated as generalized low-rank approximations of matrices with a supervised manifold regularization. The SDL is able to simultaneously extract discriminative features closely related to multivariate targets and remove irrelevant and redundant information by transforming raw features into a new low-dimensional space aligned to targets. The achieved discriminative while compact descriptor largely reduces the variability and ambiguity for multioutput regression, which enables more accurate and efficient multivariate estimation. We conduct extensive evaluation of the proposed SDL on both synthetic data and real-world multioutput regression tasks for both computer vision and medical image analysis. Experimental results have shown that the proposed SDL can achieve high multivariate estimation accuracy on all tasks and largely outperforms the algorithms in the state of the arts. Our method establishes a novel SDL framework for multioutput regression, which can be widely used to boost the performance in different applications.

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

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

2012-04-01

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

Oleuropein, a non-toxic olive iridoid, is an anti-tumor agent and cytoskeleton disruptor

International Nuclear Information System (INIS)

Hamdi, Hamdi K.; Castellon, Raquel

2005-01-01

Oleuropein, a non-toxic secoiridoid derived from the olive tree, is a powerful antioxidant and anti-angiogenic agent. Here, we show it to be a potent anti-cancer compound, directly disrupting actin filaments in cells and in a cell-free assay. Oleuropein inhibited the proliferation and migration of advanced-grade tumor cell lines in a dose-responsive manner. In a novel tube-disruption assay, Oleuropein irreversibly rounded cancer cells, preventing their replication, motility, and invasiveness; these effects were reversible in normal cells. When administered orally to mice that developed spontaneous tumors, Oleuropein completely regressed tumors in 9-12 days. When tumors were resected prior to complete regression, they lacked cohesiveness and had a crumbly consistency. No viable cells could be recovered from these tumors. These observations elevate Oleuropein from a non-toxic antioxidant into a potent anti-tumor agent with direct effects against tumor cells. Our data may also explain the cancer-protective effects of the olive-rich Mediterranean diet

Assessment of tumor control following definitive radiotherapy in carcinoma of the prostate: A continuing dilemma

International Nuclear Information System (INIS)

Pilepich, M.V.

1987-01-01

Evaluation of tumor response and tumor control after definitive radiotherapy is a relatively simple task in most malignancies arising at sites amenable to clinical examination (inspection and palpation). The rates of tumor regression following irradiation are quite variable. While some types of cancer regress completely during the radiotherapy course, some may take weeks or months to resolve. Occasionally, residual induration or a residual mass may persist for prolonged periods (many months), prompting the clinician to consider a biopsy for evaluation of the tumor status. In these circumstances histological examination may show necrotic tumor or residual fibrotic tissue. Finding viable-appearing tumor cells beyond the immediate postirradiation period (several weeks to a few months after completion of the radiotherapy course) is generally accepted as an equivalent of failure to eradicate the tumor. However, in a few types of cancer, presence of histologically identifiable and apparently viable tumor cells over protracted periods does not necessarily imply treatment failure

NUC041, a Prodrug of the DNA Methytransferase Inhibitor 5-aza-2′,2′-Difluorodeoxycytidine (NUC013, Leads to Tumor Regression in a Model of Non-Small Cell Lung Cancer

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Richard Daifuku

2018-04-01

Full Text Available 5-aza-2′,2′-difluorodeoxycytidine (NUC013 has been shown to be significantly safer and more effective than decitabine in xenograft models of human leukemia and colon cancer. However, it suffers from a similar short half-life as other DNA methyltransferase inhibitors with a 5-azacytosine base, which is problematic for nucleosides that primarily target tumor cells in S phase. Because of the relative instability of 5-azanucleosides, a prodrug approach was developed to improve the pharmacology of NUC013. NUC013 was conjugated with trimethylsilanol (TMS at the 3′ and 5′ position of the sugar, rendering the molecule hydrophobic and producing 3′,5′-di-trimethylsilyl-2′,2′-difluoro-5-azadeoxycytidine (NUC041. NUC041 was designed to be formulated in a hydrophobic vehicle, protecting it from deamination and hydrolysis. In contact with blood, the TMS moieties are readily hydrolyzed to release NUC013. The half-life of NUC013 administered intravenously in mice is 20.1 min, while that of NUC013 derived from intramuscular NUC041 formulated in a pegylated-phospholipid depot is 3.4 h. In a NCI-H460 xenograft of non-small cell lung cancer, NUC013 was shown to significantly inhibit tumor growth and improve survival. Treatment with NUC041 also led to significant tumor growth inhibition. However, NUC041-treated mice had significantly more tumors ulcerate than either NUC013 treated mice or saline control mice, and such ulceration occurred at significantly lower tumor volumes. In these nude mice, tumor regression was likely mediated by the derepression of the tumor suppressor gene p53 and resultant activation of natural killer (NK cells.

Occurrence of mammary tumors in beagls given radium-226

International Nuclear Information System (INIS)

Bruenger, F.W.; Lloyd, R.D.; Miller, S.C.; Taylor, G.N.; Angus, W.; Huth, D.A.

1994-01-01

A total of 128 primary mammary tumors (66 of them malignant) occurred in 35 female beagles injected with 226 Ra at eight dose levels ranging from 0.2 to 440 kBq/kg body mass as young adults, while a total of 156 mammary tumors (57 of them malignant) were seen in 46 female control beagles not given any radioactivity. Sixty-three of 65 control dogs and 59 of 61 dogs given 226 Ra survived the minimum age for diagnosis of mammary tumors of 3.75 years. Based on the observed age-dependent tumor incidence rates in the controls and on the corresponding number of dog-years at risk, the total number of observed malignant tumors in the radium group was statistically greater than the number of expected malignant tumors (66 observed vs 34 expected, P < 0.005). There was no such difference for the benign tumors. Cox regression analysis indicated no increased risk for the first tumor occurrence in irradiated dogs. Cox regression analysis of the multivariate risk sets showed no significantly increased risk for the occurrence of benign tumors but a statistically higher risk of 1.66 with a confidence interval of 1.15-2.40 for the occurrence of malignant tumors. The increased risk was dependent on dose, but a dependence on the frequency of previous occurrence of mammary tumors could not be confirmed. Censoring ovariectomized dogs at time of surgery decreased the relative risks slightly but did not alter the significance. Exposure to diagnostic X rays with cumulative exposures below 0.2 Gy had no effect on tumor formation. It is unknown whether the increased risk for malignant mammary tumors was due to some initial deposition of radium in sensitive tissue, a possible irradiation of fatty mammary tissue from transient radon → polonium deposition, or a general effect of the overall radium deposition on the immune system of the dogs that lowered their resistance to formation of mammary tumors. 27 refs., 5 figs., 4 tabs

Differentiating regressed melanoma from regressed lichenoid keratosis.

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Chan, Aegean H; Shulman, Kenneth J; Lee, Bonnie A

2017-04-01

Distinguishing regressed lichen planus-like keratosis (LPLK) from regressed melanoma can be difficult on histopathologic examination, potentially resulting in mismanagement of patients. We aimed to identify histopathologic features by which regressed melanoma can be differentiated from regressed LPLK. Twenty actively inflamed LPLK, 12 LPLK with regression and 15 melanomas with regression were compared and evaluated by hematoxylin and eosin staining as well as Melan-A, microphthalmia transcription factor (MiTF) and cytokeratin (AE1/AE3) immunostaining. (1) A total of 40% of regressed melanomas showed complete or near complete loss of melanocytes within the epidermis with Melan-A and MiTF immunostaining, while 8% of regressed LPLK exhibited this finding. (2) Necrotic keratinocytes were seen in the epidermis in 33% regressed melanomas as opposed to all of the regressed LPLK. (3) A dense infiltrate of melanophages in the papillary dermis was seen in 40% of regressed melanomas, a feature not seen in regressed LPLK. In summary, our findings suggest that a complete or near complete loss of melanocytes within the epidermis strongly favors a regressed melanoma over a regressed LPLK. In addition, necrotic epidermal keratinocytes and the presence of a dense band-like distribution of dermal melanophages can be helpful in differentiating these lesions. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Regression of left ventricular hypertrophy and microalbuminuria changes during antihypertensive treatment.

Science.gov (United States)

Rodilla, Enrique; Pascual, Jose Maria; Costa, Jose Antonio; Martin, Joaquin; Gonzalez, Carmen; Redon, Josep

2013-08-01

The objective of the present study was to assess the regression of left ventricular hypertrophy (LVH) during antihypertensive treatment, and its relationship with the changes in microalbuminuria. One hundred and sixty-eight previously untreated patients with echocardiographic LVH, 46 (27%) with microalbuminuria, were followed during a median period of 13 months (range 6-23 months) and treated with lifestyle changes and antihypertensive drugs. Twenty-four-hour ambulatory blood pressure monitoring, echocardiography and urinary albumin excretion were assessed at the beginning and at the end of the study period. Left ventricular mass index (LVMI) was reduced from 137 [interquartile interval (IQI), 129-154] to 121 (IQI, 104-137) g/m (P 50%) had the same odds of achieving regression of LVH as patients with normoalbuminuria (ORm 1.1; 95% CI 0.38-3.25; P = 0.85). However, those with microalbuminuria at baseline, who did not regress, had less probability of achieving LVH regression than the normoalbuminuric patients (OR 0.26; 95% CI 0.07-0.90; P = 0.03) even when adjusted for age, sex, initial LVMI, GFR, blood pressure and angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB) treatment during the follow-up. Patients who do not have a significant reduction in microalbuminuria have less chance of achieving LVH regression, independent of blood pressure reduction.

Reactivity of p53 protein in canine transmissible venereal tumor Reatividade da proteína P53 no tumor venéreo transmissível canino

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J.V. Moro

2010-04-01

Full Text Available The expression of p53 protein was evaluated in canine transmissible venereal tumor (CTVT, as following: natural occurrence (n=8; resistant to chemotherapy (n=4; and allogeneic transplanted in progression (n=8, stable (n=8, and regression (n=8stages. The collected specimens were submitted to GM1 immunohistochemical reaction. Results showed a mean percentage of immunomarked cells around 18.6% in CTVT of natural occurrence, 23.8% in CTVT resistant to chemotherapy, 22.9% in allogeneic transplanted CTVT in both progression and stable stages, and 35.8% in transplanted CTVT in regression stage. The results suggest that there is a functional abnormality in p53 gene and its products in the studied tumors; although, it is not possible to correlate the percentage of cells marked by p53 and a prognosis.A expressão da proteína p53 foi avaliada em espécimes de tumor venéreo transmissível canino (TVT de ocorrência natural (n=8; resistente à quimioterapia (n=4 e transplantado em cão nas fases de progressão tumoral (n=8, de latência (n=8 e de regressão (n=8. Os espécimes foram submetidos à reação de imunoistoquímica. Os resultados mostraram porcentagem média de células imunomarcadas de 18,6% no TVT de ocorrência natural, de 23,8% no TVT refratário, 22,9% nos TVTs transplantados nas fases de progressão e latência e de 35,8% na fase de regressão. Os resultados sugerem que há uma anormalidade funcional no gene P53 e seus produtos nos tumores estudados, apesar de não ser possível correlacionar a porcentagem de células marcadas pelo p53 ao prognóstico.

Adult Wilms tumor with inferior vena cava thrombus and distal deep vein thrombosis - a case report and literature review.

Science.gov (United States)

Ratajczyk, Krzysztof; Czekaj, Adrian; Rogala, Joanna; Kowal, Pawel

2018-02-23

Adult Wilms tumor (WT, nephroblastoma) is a rare, but well-described renal neoplasm. Although inferior vena cava tumor thrombosis is present in up to 10% of Wilms tumors in childhood, only few cases of this clinical manifestation in adults have been reported. To the best of our knowledge, this is the first case of adult WT infiltrating into inferior vena cava (IVC) with concomitant distal deep vein thrombosis. A 28-year-old male patient with gross hematuria and right flank pain was diagnosed with right kidney tumor penetrating to IVC. Preoperatively, acute distal thrombosis in inferior vena cava and lower extremities veins occurred. Right radical nephrectomy with tumor thrombectomy via cavotomy was performed. In order to prevent pulmonary embolism, IVC was ligated below left renal vein level. Histopathological examination revealed a triphasic nephroblastoma without anaplastic features. Postoperatively, patient was diagnosed with metastatic liver disease, which was treated with two lines of chemotherapy followed by radiotherapy with achievement of complete response. Adult WT occurs usually in young patients, under 40 years of age. Neoadjuvant chemotherapy proved to be effective in children, resulting with tumor shrinkage and venous tumor thrombus regression. Therefore, percutaneous biopsy should be always considered in young patients presenting with renal tumor invading venous system. IVC ligation is a safe treatment option in the event of complete inferior vena cava occlusion due to distal thrombosis concomitant to tumor thrombus, provided collateral venous pathways are well-developed.

ASSOCIATION BETWEEN EMOTIONAL VARIABLES AND SCHOOL ACHIEVEMENT

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Christoph Randler

2009-07-01

Full Text Available Recent psychological studies highlight emotional aspects, and they show an important role within individual learning processes. Hereby, positive emotions were supposed to positively influence learning and achievement processes and negative ones do the contrary. In this study, an educational unit “ecosystem lake” was used during which achievement (three tests and emotional variables (interest, well-being, anxiety and boredom; measured at the end of three pre-selected lessons were monitored. The research question was to explore correlations between emotional variables and the learning outcome of the teaching unit. Prior knowledge was regressed against the subsequent tests to account for its confounding effect. Regressions showed a highly significant influence of prior knowledge on the subsequent measurements of achievement. However, after accounting for prior knowledge, a positive correlation between interest/well-being and achievement and a negative correlation between anxiety/boredom and achievement was found. Further research and interventions should try to enhance positive emotions in biology lessons to positively influence achievement.

Correlation between dose and tumor response in the radiotherapy of lung cancer of various histological types

International Nuclear Information System (INIS)

Koga, Kenji; Kusuhara, Toshiyuki; Nishikawa, Kiyoshi; Asada, Keiko; Watanabe, Katsushi

1984-01-01

Correlation between dose and tumor response by cell types was determined in 50 patients with lung cancer in order to predict the possibility of further tumor regression. The TDF (time-dose-fractionation) concept was used as dose factor. The radiation source was a cobalt-60 γ-ray or linear accelerator 10 MV X-ray. As a routine regime a fraction dose of 2 Gy five times per week was given to 39 of the 50 patients, but a dose of 2 Gy three times per week or of 1.5 Gy five times per week was given to seven and four patients, respectively. Radiation response was the best in small cell carcinoma and better in adenocarcinoma than in squamous cell carcinoma, showing a tumor regression rate of 50% or more in 90%, 80% and 58% of the patients, respectively. The correlation between tumor regression rate and TDF values was good in squamous cell carcinoma (r = 0.73) and small cell carcinoma (r = - 0.72), but poor in adenocarcinoma (r = - 0.10). These results suggest that in squamous cell carcinoma improvement of tumor regression can be expected by increasing TDF values, and in adenocarcinoma and small cell carcinoma the optimal TDF values are about 100 and 60 to 80, respectively. (author)

Novel Antitumor Strategy Utilizing a Plasmid Expressing a Mycobacterium tuberculosis Antigen as a “Danger Signal” to Block Immune Escape of Tumor Cells

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Yoshiyuki Koyama

2015-07-01

Full Text Available Immune escape of tumor cells is one of the main obstacles hindering the effectiveness of cancer immunotherapy. We developed a novel strategy to block immune escape by transfecting tumor cells in vivo with genes of pathogenic antigens from Mycobacterium tuberculosis (TB. This induces presentation of the TB antigen on tumor cell surfaces, which can be recognized by antigen presenting cells (APCs as a “danger signal” to stimulate antitumor immune response. This strategy is also expected to amplify the immune response against tumor-associated antigens, and block immune escape of the tumor. DNA/PEI/chondroitin sulfate ternary complex is a highly effective non-viral gene vector system for in vivo transfection. A therapeutic complex was prepared using a plasmid encoding the TB antigen, early secretory antigenic target-6 (ESAT-6. This was injected intratumorally into syngeneic tumor-bearing mice, and induced significant tumor growth suppression comparable to or higher than similar complexes expressing cytokines such as interleukin-2 (IL-2 and interleukin-12 (IL-12. Co-transfection of the cytokine-genes and the ESAT-6-gene enhanced the antitumor efficacy of either treatment alone. In addition, complete tumor regression was achieved with the combination of ESAT-6 and IL-2 genes.

Malignancy risk prediction for primary jejunum-ileal tumors

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MARQUES Ruy Garcia

2000-01-01

Full Text Available This work is aimed at identifying factors associated with primary jejunum-ileal tumors malignancy, defining a prediction model with sensitivity, specificity and accuracy to distinguish malign from benign neoplasms. These tumors are rare, have highly unspecific presentation and, frequently, are diagnosed late. We reviewed the charts of 42 patients with primary jejunum-ileal tumors treated in the Department of General Surgery of Rio de Janeiro State University Hospital, Rio de Janeiro, RJ, Brazil, from 1969 to 1998. We performed bivariate analyses, based on chi² test, searching associations between tumors malignancy and demographic and clinical variables. Then logistic regression was employed to consider the independent effect of variables previously identified on malignancy risk. The malign tumors included 11 adenocarcinomas, 7 leiomyosarcomas, 5 carcinoids and 4 lymphomas; the benign tumors included 10 leiomyomas, 2 hamartomas, and single cases of adenoma, multiple neurilemoma and choristoma. The bivariate analyses indicated the association between malignancy and palpable abdominal mass (P = 0.003, period from signs and symptoms onset to diagnosis (P = 0.016, anemia (P = 0.020, anorexia (P = 0.003, abdominal pain (P = 0.031, weight loss (P = 0.001, nausea and vomit (P = 0.094, and intestinal obstruction (P = 0.066; no association with patients demographic characteristics were found. In the final logistic regression model, weight loss, anemia and intestinal obstruction were statistically associated with the dependent variable of interest. Based only on three variables -- weight loss, anemia and intestinal obstruction -- the model defined was able to predict primary jejunum-ileal tumors malignancy with sensitivity of 85.2%, specificity of 80.0%, and accuracy of 83.3%.

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.

Utility of MRI versus tumor markers for post-treatment surveillance of marker-positive CNS germ cell tumors.

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Cheung, Victoria; Segal, Devorah; Gardner, Sharon L; Zagzag, David; Wisoff, Jeffrey H; Allen, Jeffrey C; Karajannis, Matthias A

2016-09-01

Patients with marker-positive central nervous system (CNS) germ cell tumors are typically monitored for tumor recurrence with both tumor markers (AFP and b-hCG) and MRI. We hypothesize that the recurrence of these tumors will always be accompanied by an elevation in tumor markers, and that surveillance MRI may not be necessary. We retrospectively identified 28 patients with CNS germ cell tumors treated at our institution that presented with an elevated serum or cerebrospinal fluid (CSF) tumor marker at the time of diagnosis. We then identified those who had a tumor recurrence after having been in remission and whether each recurrence was detected via MRI changes, elevated tumor markers, or both. Four patients suffered a tumor recurrence. Only one patient had simultaneously elevated tumor markers and MRI evidence of recurrence. Two patients had evidence of recurrence on MRI without corresponding elevations in serum or CSF tumor markers. One patient had abnormal tumor markers with no evidence of recurrence on MRI until 6 months later. We conclude that in patients with marker-positive CNS germ cell tumors who achieve complete remission, continued surveillance imaging in addition to measurement of tumor markers is indicated to detect recurrences.

Photodynamic therapy-generated vaccines prevent tumor recurrence after radiotherapy

International Nuclear Information System (INIS)

Korbelik, M.; Sun, J.

2003-01-01

Photodynamic therapy (PDT), an established clinical modality for a variety of malignant and non-malignant diseases, inflicts photoreactive drug-mediated oxidative stress that prompts the engagement of host inflammatory and immune responses which contribute to the therapy outcome. Recently, it has become evident that in vitro PDT-treated tumor cells or their lysates can be utilized as an effective vaccine against established tumors of the same origin. The mechanism underlying the vaccine action appears to be based on eliciting immune recognition of the tumor and developing an efficient immune response even against poorly immunogenic tumors. This study examined whether PDT-generated vaccines can be effectively combined with radiotherapy. Subcutaneous SCCVII tumors (squamous cell carcinomas) growing in syngeneic C3H/HeN mice were treated by radiotherapy (60 Gy x-ray dose). PDT-vaccine treatment, done by peritumoral injection of in vitro PDT-treated SCCVII cells (20 million/mouse), was performed either immediately after radiotherapy or ten days later. The mice were then observed for tumor regression/recurrence. The tumors treated with radiotherapy alone shrunk and became impalpable for a brief period after which they all recurred. In contrast, vaccination performed at 10 days post radiotherapy delayed tumor recurrence and prevented it in one of six mice. Even better results were obtained with mice vaccinated immediately after radiotherapy, with mice showing not only a delayed tumor recurrence but also no sign of tumor in 50% of mice. The PDT-vaccine treatment without radiotherapy produced in this trial a significant tumor growth retardation but no complete regressions. These results indicate that PDT-generated vaccines can ensure immune rejection of cancer once the lesion size is reduced by radiotherapy. Even without obtaining a systemic immunity for the elimination of disseminated malignant deposits, these findings suggest that PDT-vaccines can improve local control

Tumor response to ionizing radiation and combined 2-deoxy-D-glucose application in EATC tumor bearing mice: monitoring of tumor size and microscopic observations

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Latz, D.; Thonke, A.; Jueling-Pohlit, L.; Pohlit, W.

1993-01-01

The present study deals with the changes induced by two fractionation schedules (5x9 Gy and 10x4.5 Gy; 30 MeV-electrons) of ionizing radiations and 2-Deoxy-D-Glucose (2-DG) application on EATC tumor bearing swiss albino mice. The monitoring of tumor response was carried out by means of calliper measurement on the macroscopic level and by histopathological examination of tumor preparations stained with hematoxiline and eosine on the microscopic level. The tumor material was assessed at suitable intervals after treatment by killing the animals. The tumor response was analysed in the histological preparations and the thickness of the tumor band was determined quantitatively by an ocularmicrometric technique. Tumor damage was most extensive in the combined treated animals (5x9 Gy + 2-DG). Only in this group local tumor control was achievable. The histological analysis of tumor preparations revealed additional data about treatment-induced changes in the tumor compared to the measurement of the tumor volume with mechanical callipers. We also found that the treatment outcome could be predicted from the histopathological analysis. It is concluded that studies involving histopathological examinations may give some insight into the way cancer is controlled by radiotherapy and may be of value in prognosis and selection of treatment in patients. (orig.) [de

Recommendations for reporting tumor budding in colorectal cancer based on the International Tumor Budding Consensus Conference (ITBCC) 2016

DEFF Research Database (Denmark)

Lugli, Alessandro; Kirsch, Richard; Ajioka, Yoichi

2017-01-01

to determine the strength of recommendations and quality of evidence. The following 10 statements achieved consensus: Tumor budding is defined as a single tumor cell or a cell cluster consisting of four tumor cells or less (22/22, 100%). Tumor budding is an independent predictor of lymph node metastases in pT1......%). Intratumoral budding exists in colorectal cancer and has been shown to be related to lymph node metastasis (22/22, 100%). Tumor budding is assessed in one hotspot (in a field measuring 0.785 mm 2) at the invasive front (22/22, 100%). A three-tier system should be used along with the budding count in order...

BPA and BSH accumulation in experimental tumors

International Nuclear Information System (INIS)

Patel, H.; Sedgwick, E.M.

2000-01-01

The accumulation of boronated compounds into tumors is a critical component to the success of BNCT. To date, great variability has been demonstrated in the tumor:blood ratio achieved in samples both from different patients and within samples taken from the same patient. The factors that probably influence the level of uptake include the vascular perfusion within the tumor, the permeability of these vessels and the viability of the tumor cells themselves. These experiments were designed to measure these various factors in different experimental tumor models and to relate these measurements to the uptake of both BPA (Boronophenylalanine) and BSH (Sodiumborocaptate). They demonstrate that within different tumors there can be wide variations in the vascular parameters. In addition, the viability of the tumor cells may also be an important determinant of tumor uptake. (author)

Refractive regression after laser in situ keratomileusis.

Science.gov (United States)

Yan, Mabel K; Chang, John Sm; Chan, Tommy Cy

2018-04-26

Uncorrected refractive errors are a leading cause of visual impairment across the world. In today's society, laser in situ keratomileusis (LASIK) has become the most commonly performed surgical procedure to correct refractive errors. However, regression of the initially achieved refractive correction has been a widely observed phenomenon following LASIK since its inception more than two decades ago. Despite technological advances in laser refractive surgery and various proposed management strategies, post-LASIK regression is still frequently observed and has significant implications for the long-term visual performance and quality of life of patients. This review explores the mechanism of refractive regression after both myopic and hyperopic LASIK, predisposing risk factors and its clinical course. In addition, current preventative strategies and therapies are also reviewed. © 2018 Royal Australian and New Zealand College of Ophthalmologists.

Sparse Regression by Projection and Sparse Discriminant Analysis

KAUST Repository

Qi, Xin

2015-04-03

© 2015, © American Statistical Association, Institute of Mathematical Statistics, and Interface Foundation of North America. Recent years have seen active developments of various penalized regression methods, such as LASSO and elastic net, to analyze high-dimensional data. In these approaches, the direction and length of the regression coefficients are determined simultaneously. Due to the introduction of penalties, the length of the estimates can be far from being optimal for accurate predictions. We introduce a new framework, regression by projection, and its sparse version to analyze high-dimensional data. The unique nature of this framework is that the directions of the regression coefficients are inferred first, and the lengths and the tuning parameters are determined by a cross-validation procedure to achieve the largest prediction accuracy. We provide a theoretical result for simultaneous model selection consistency and parameter estimation consistency of our method in high dimension. This new framework is then generalized such that it can be applied to principal components analysis, partial least squares, and canonical correlation analysis. We also adapt this framework for discriminant analysis. Compared with the existing methods, where there is relatively little control of the dependency among the sparse components, our method can control the relationships among the components. We present efficient algorithms and related theory for solving the sparse regression by projection problem. Based on extensive simulations and real data analysis, we demonstrate that our method achieves good predictive performance and variable selection in the regression setting, and the ability to control relationships between the sparse components leads to more accurate classification. In supplementary materials available online, the details of the algorithms and theoretical proofs, and R codes for all simulation studies are provided.

Malignant progressive tumor cell clone exhibits significant up-regulation of cofilin-2 and 27-kDa modified form of cofilin-1 compared to regressive clone.

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Kuramitsu, Yasuhiro; Wang, Yufeng; Okada, Futoshi; Baron, Byron; Tokuda, Kazuhiro; Kitagawa, Takao; Akada, Junko; Nakamura, Kazuyuki

2013-09-01

QR-32 is a regressive murine fibrosarcoma cell clone which cannot grow when they are transplanted in mice; QRsP-11 is a progressive malignant tumor cell clone derived from QR-32 which shows strong tumorigenicity. A recent study showed there to be differentially expressed up-regulated and down-regulated proteins in these cells, which were identified by proteomic differential display analyses by using two-dimensional gel electrophoresis and mass spectrometry. Cofilins are small proteins of less than 20 kDa. Their function is the regulation of actin assembly. Cofilin-1 is a small ubiquitous protein, and regulates actin dynamics by means of binding to actin filaments. Cofilin-1 plays roles in cell migration, proliferation and phagocytosis. Cofilin-2 is also a small protein, but it is mainly expressed in skeletal and cardiac muscles. There are many reports showing the positive correlation between the level of cofilin-1 and cancer progression. We have also reported an increased expression of cofilin-1 in pancreatic cancer tissues compared to adjacent paired normal tissues. On the other hand, cofilin-2 was significantly less expressed in pancreatic cancer tissues. Therefore, the present study investigated the comparison of the levels of cofilin-1 and cofilin-2 in regressive QR-32 and progressive QRsP-11cells by western blotting. Cofilin-2 was significantly up-regulated in QRsP-11 compared to QR-32 cells (p<0.001). On the other hand, the difference of the intensities of the bands of cofilin-1 (18 kDa) in QR-32 and QRsP-11 was not significant. However, bands of 27 kDa showed a quite different intensity between QR-32 and QRsP-11, with much higher intensities in QRsP-11 compared to QR-32 (p<0.001). These results suggested that the 27-kDa protein recognized by the antibody against cofilin-1 is a possible biomarker for progressive tumor cells.

Therapeutic Non-Toxic Doses of TNF Induce Significant Regression in TNFR2-p75 Knockdown Lewis Lung Carcinoma Tumor Implants

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Sasi, Sharath P.; Bae, Sanggyu; Song, Jin; Perepletchikov, Aleksandr; Schneider, Douglas; Carrozza, Joseph; Yan, Xinhua; Kishore, Raj; Enderling, Heiko; Goukassian, David A.

2014-01-01

Tumor necrosis factor-alpha (TNF) binds to two receptors: TNFR1/p55-cytotoxic and TNFR2/p75-pro-survival. We have shown that tumor growth in p75 knockout (KO) mice was decreased more than 2-fold in Lewis lung carcinoma (LLCs). We hypothesized that selective blocking of TNFR2/p75 LLCs may sensitize them to TNF-induced apoptosis and affect the tumor growth. We implanted intact and p75 knockdown (KD)-LLCs (>90%, using shRNA) into wild type (WT) mice flanks. On day 8 post-inoculation, recombinant murine (rm) TNF-α (12.5 ng/gr of body weight) or saline was injected twice daily for 6 days. Tumor volumes (tV) were measured daily and tumor weights (tW) on day 15, when study was terminated due to large tumors in LLC+TNF group. Tubular bones, spleens and peripheral blood (PB) were examined to determine possible TNF toxicity. There was no significant difference in tV or tW between LLC minus (-) TNF and p75KD/LLC-TNF tumors. Compared to 3 control groups, p75KD/LLC+TNF showed >2-5-fold decreases in tV (ptumors were 100% necrotic, the remaining revealed 40-60% necrosis. No toxicity was detected in bone marrow, spleen and peripheral blood. We concluded that blocking TNFR2/p75 in LLCs combined with intra-tumoral rmTNF injections inhibit LLC tumor growth. This could represent a novel and effective therapy against lung neoplasms and a new paradigm in cancer therapeutics. PMID:24664144

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

Multiple brown tumors of the orbital walls: case report Tumor marrom múltiplo das paredes orbitárias: relato de caso

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Mário Luiz Ribeiro Monteiro

2009-02-01

Full Text Available We report the case of a 40-year-old woman with chronic renal failure and secondary hyperparathyroidism that presented with slowly progressive proptosis of the right eye and mass sensation in the temporal and frontal orbital margins. Computerized tomography scan revealed two separate hyperdense and well-circumscribed lesions in the right orbital walls. A biopsy followed by histopathologic study revealed a dense lesion, with fibrous proliferation associated with osseous metaplasia and osteoclastic activity in the tumor, compatible with the diagnosis of brown tumor. The patient was submitted to surgical removal of the parathyroid glands that resulted in marked improvement in her condition and regression of the orbital tumors. Although the occurrence of more than one separate bone lesion in the orbit usually suggests metastasis, our case shows that brown tumors should also be included in the differential diagnosis of such lesions, particularly in patients with hyperparathyroidism.Este trabalho relata o caso de uma paciente de 40 anos, com insuficiência renal crônica e hiperparatireoidismo secundário que se apresentou com proptose progressiva e tumoração nas regiões lateral da órbita e superior da órbita. Tomografia computadorizada revelou duas lesões ósseas separadas, bem delimitadas e hiperdensas nas paredes orbitárias. Uma biópsia seguida de estudo histopatológico revelou um tumor denso, com proliferação fibrosa associada a metaplasia óssea e atividade osteoclástica no tumor, características compatíveis com tumor marrom. A paciente foi submetida a remoção das glândulas paratiróides que resultou em melhora dramática do seu estado geral e regressão dos tumores orbitais. Embora a presença de mais de uma lesão óssea separada na órbita geralmente sugira o diagnóstico de lesões metastáticas, nosso caso evidencia que tumores marrons devem também ser incluídos no diagnóstico diferencial, particularmente em pacientes com

A polyethylenimine-modified carboxyl-poly(styrene/acrylamide copolymer nanosphere for co-delivering of CpG and TGF-β receptor I inhibitor with remarkable additive tumor regression effect against liver cancer in mice

Directory of Open Access Journals (Sweden)

Liang SY

2016-12-01

Full Text Available Shuyan Liang,* Jun Hu,* Yuanyuan Xie, Qing Zhou, Yanhong Zhu, Xiangliang Yang National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, People’s Republic of China *These authors contributed equally to this work Abstract: Cancer immunotherapy based on nanodelivery systems has shown potential for treatment of various malignancies, owing to the benefits of tumor targeting of nanoparticles. However, induction of a potent T-cell immune response against tumors still remains a challenge. In this study, polyethylenimine-modified carboxyl-styrene/acrylamide (PS copolymer nanospheres were developed as a delivery system of unmethylated cytosine-phosphate-guanine (CpG oligodeoxynucleotides and transforming growth factor-beta (TGF-β receptor I inhibitors for cancer immunotherapy. TGF-β receptor I inhibitors (LY2157299, LY were encapsulated to the PS via hydrophobic interaction, while CpG oligodeoxynucleotides were loaded onto the PS through electrostatic interaction. Compared to the control group, tumor inhibition in the PS-LY/CpG group was up to 99.7% without noticeable toxicity. The tumor regression may be attributed to T-cell activation and amplification in mouse models. The results highlight the additive effect of CpG and TGF-β receptor I inhibitors co-delivered in cancer immunotherapy. Keywords: CpG, TGF-β receptor I inhibitor, Pst-AAm copolymer nanosphere, immunotherapy

Targeting Autophagy in the Tumor Microenvironment: New Challenges and Opportunities for Regulating Tumor Immunity

Directory of Open Access Journals (Sweden)

Bassam Janji

2018-04-01

Full Text Available Cancer cells evolve in the tumor microenvironment, which is now well established as an integral part of the tumor and a determinant player in cancer cell adaptation and resistance to anti-cancer therapies. Despite the remarkable and fairly rapid progress over the past two decades regarding our understanding of the role of the tumor microenvironment in cancer development, its precise contribution to cancer resistance is still fragmented. This is mainly related to the complexity of the “tumor ecosystem” and the diversity of the stromal cell types that constitute the tumor microenvironment. Emerging data indicate that several factors, such as hypoxic stress, activate a plethora of resistance mechanisms, including autophagy, in tumor cells. Hypoxia-induced autophagy in the tumor microenvironment also activates several tumor escape mechanisms, which effectively counteract anti-tumor immune responses mediated by natural killer and cytotoxic T lymphocytes. Therefore, strategies aiming at targeting autophagy in cancer cells in combination with other therapeutic strategies have inspired significant interest to overcome immunological tolerance and promote tumor regression. However, a number of obstacles still hamper the application of autophagy inhibitors in clinics. First, the lack of selectivity of the current pharmacological inhibitors of autophagy makes difficult to draw a clear statement about its effective contribution in cancer. Second, autophagy has been also described as an important mechanism in tumor cells involved in presentation of antigens to T cells. Third, there is a circumstantial evidence that autophagy activation in some innate immune cells may support the maturation of these cells, and it is required for their anti-tumor activity. In this review, we will address these aspects and discuss our current knowledge on the benefits and the drawbacks of targeting autophagy in the context of anti-tumor immunity. We believe that it is

Complete Spontaneous Regression of Merkel Cell Carcinoma After Biopsy: A Case Report and Review of the Literature.

Science.gov (United States)

Ahmadi Moghaddam, Parnian; Cornejo, Kristine M; Hutchinson, Lloyd; Tomaszewicz, Keith; Dresser, Karen; Deng, April; OʼDonnell, Patrick

2016-11-01

Merkel cell carcinoma (MCC) is a rare primary cutaneous neuroendocrine tumor that typically occurs on the head and neck of the elderly and follows an aggressive clinical course. Merkel cell polyomavirus (MCPyV) has been identified in up to 80% of cases and has been shown to participate in MCC tumorigenesis. Complete spontaneous regression of MCC has been rarely reported in the literature. We describe a case of a 79-year-old man that presented with a rapidly growing, 3-cm mass on the left jaw. An incisional biopsy revealed MCC. Additional health issues were discovered in the preoperative workup of this patient which delayed treatment. One month after the biopsy, the lesion showed clinical regression in the absence of treatment. Wide excision of the biopsy site with sentinel lymph node dissection revealed no evidence of MCC 2 months later. The tumor cells in the patient's biopsy specimen were negative for MCPyV by polymerase chain reaction and immunohistochemistry (CM2B4 antibody, Santa Cruz, CA). The exact mechanism for complete spontaneous regression in MCC is unknown. To our knowledge, only 2 previous studies evaluated the presence of MCPyV by polymerase chain reaction in MCC with spontaneous regression. Whether the presence or absence of MCPyV correlates with spontaneous regression warrants further investigation.

Quality of life in breast cancer patients--a quantile regression analysis.

Science.gov (United States)

Pourhoseingholi, Mohamad Amin; Safaee, Azadeh; Moghimi-Dehkordi, Bijan; Zeighami, Bahram; Faghihzadeh, Soghrat; Tabatabaee, Hamid Reza; Pourhoseingholi, Asma

2008-01-01

Quality of life study has an important role in health care especially in chronic diseases, in clinical judgment and in medical resources supplying. Statistical tools like linear regression are widely used to assess the predictors of quality of life. But when the response is not normal the results are misleading. The aim of this study is to determine the predictors of quality of life in breast cancer patients, using quantile regression model and compare to linear regression. A cross-sectional study conducted on 119 breast cancer patients that admitted and treated in chemotherapy ward of Namazi hospital in Shiraz. We used QLQ-C30 questionnaire to assessment quality of life in these patients. A quantile regression was employed to assess the assocciated factors and the results were compared to linear regression. All analysis carried out using SAS. The mean score for the global health status for breast cancer patients was 64.92+/-11.42. Linear regression showed that only grade of tumor, occupational status, menopausal status, financial difficulties and dyspnea were statistically significant. In spite of linear regression, financial difficulties were not significant in quantile regression analysis and dyspnea was only significant for first quartile. Also emotion functioning and duration of disease statistically predicted the QOL score in the third quartile. The results have demonstrated that using quantile regression leads to better interpretation and richer inference about predictors of the breast cancer patient quality of life.

Reconstruction of segmental bone defect of long bones after tumor resection by devitalized tumor-bearing bone.

Science.gov (United States)

Qu, Huayi; Guo, Wei; Yang, Rongli; Li, Dasen; Tang, Shun; Yang, Yi; Dong, Sen; Zang, Jie

2015-09-24

The reconstruction of an intercalary bone defect after a tumor resection of a long bone remains a challenge to orthopedic surgeons. Though several methods have been adopted to enhance the union of long segmental allografts or retrieved segmental autografts to the host bones, still more progresses are required to achieve a better union rate. Several methods have been adopted to devitalize tumor bone for recycling usage, and the results varied. We describe our experiences of using devitalized tumor-bearing bones for the repairing of segmental defects after tumor resection. Twenty-seven eligible patients treated from February 2004 to May 2012 were included. The segmental tumor bone (mean length, 14 cm) was resected, and then devitalized in 20% sterile saline at 65 °C for 30 min after the tumor tissue was removed. The devitalized bone was implanted back into the defect by using nails or plates. Complete healing of 50 osteotomy ends was achieved at a median time of 11 months (interquartile range (IQR) 9-13 months). Major complications included bone nonunion in four bone junctions (7.4%), devitalized bone fracture in one patient (3.7%), deep infection in three patients (11.1%), and fixation failure in two patients (7.4%). The bone union rates at 1 and 2 years were 74.1 and 92.6%, respectively. The average functional score according to the Musculoskeletal Tumor Society (MSTS) 93 scoring system was 93 % (IQR 80-96.7%). Incubation in 20% sterile saline at 65 °C for 30 min is an effective method of devitalization of tumor-bearing bone. The retrieved bone graft may provide as a less expensive alternative for limb salvage. The structural bone and the preserved osteoinductivity of protein may improve bone union.

Tumor-induced rickets in a child with a central giant cell granuloma: a case report.

Science.gov (United States)

Fernández-Cooke, Elisa; Cruz-Rojo, Jaime; Gallego, Carmen; Romance, Ana Isabel; Mosqueda-Peña, Rocio; Almaden, Yolanda; Sánchez del Pozo, Jaime

2015-06-01

Tumor-induced osteomalacia/rickets is a rare paraneoplastic disorder associated with a tumor-producing fibroblast growth factor 23 (FGF23). We present a child with symptoms of rickets as the first clinical sign of a central giant cell granuloma (CGCG) with high serum levels of FGF23, a hormone associated with decreased phosphate resorption. A 3-year-old boy presented with a limp and 6 months later with painless growth of the jaw. On examination gingival hypertrophy and genu varum were observed. Investigations revealed hypophosphatemia, normal 1,25 and 25 (OH) vitamin D, and high alkaline phosphatase. An MRI showed an osteolytic lesion of the maxilla. Radiographs revealed typical rachitic findings. Incisional biopsy of the tumor revealed a CGCG with mesenchymal matrix. The CGCG was initially treated with calcitonin, but the lesions continued to grow, making it necessary to perform tracheostomy and gastrostomy. One year after onset the hyperphosphaturia worsened, necessitating increasing oral phosphate supplements up to 100 mg/kg per day of elemental phosphorus. FGF23 levels were extremely high. Total removal of the tumor was impossible, and partial reduction was achieved after percutaneous computed tomography-guided radiofrequency, local instillation of triamcinolone, and oral propranolol. Compassionate use of cinacalcet was unsuccessful in preventing phosphaturia. The tumor slowly regressed after the third year of disease; phosphaturia improved, allowing the tapering of phosphate supplements, and FGF23 levels normalized. Tumor-induced osteomalacia/rickets is uncommon in children and is challenging for physicians to diagnose. It should be suspected in patients with intractable osteomalacia or rickets. A tumor should be ruled out if FGF23 levels are high. Copyright © 2015 by the American Academy of Pediatrics.

Face Alignment via Regressing Local Binary Features.

Science.gov (United States)

Ren, Shaoqing; Cao, Xudong; Wei, Yichen; Sun, Jian

2016-03-01

This paper presents a highly efficient and accurate regression approach for face alignment. Our approach has two novel components: 1) a set of local binary features and 2) a locality principle for learning those features. The locality principle guides us to learn a set of highly discriminative local binary features for each facial landmark independently. The obtained local binary features are used to jointly learn a linear regression for the final output. This approach achieves the state-of-the-art results when tested on the most challenging benchmarks to date. Furthermore, because extracting and regressing local binary features are computationally very cheap, our system is much faster than previous methods. It achieves over 3000 frames per second (FPS) on a desktop or 300 FPS on a mobile phone for locating a few dozens of landmarks. We also study a key issue that is important but has received little attention in the previous research, which is the face detector used to initialize alignment. We investigate several face detectors and perform quantitative evaluation on how they affect alignment accuracy. We find that an alignment friendly detector can further greatly boost the accuracy of our alignment method, reducing the error up to 16% relatively. To facilitate practical usage of face detection/alignment methods, we also propose a convenient metric to measure how good a detector is for alignment initialization.

Cish actively silences TCR signaling in CD8+ T cells to maintain tumor tolerance.

Science.gov (United States)

Palmer, Douglas C; Guittard, Geoffrey C; Franco, Zulmarie; Crompton, Joseph G; Eil, Robert L; Patel, Shashank J; Ji, Yun; Van Panhuys, Nicholas; Klebanoff, Christopher A; Sukumar, Madhusudhanan; Clever, David; Chichura, Anna; Roychoudhuri, Rahul; Varma, Rajat; Wang, Ena; Gattinoni, Luca; Marincola, Francesco M; Balagopalan, Lakshmi; Samelson, Lawrence E; Restifo, Nicholas P

2015-11-16

Improving the functional avidity of effector T cells is critical in overcoming inhibitory factors within the tumor microenvironment and eliciting tumor regression. We have found that Cish, a member of the suppressor of cytokine signaling (SOCS) family, is induced by TCR stimulation in CD8(+) T cells and inhibits their functional avidity against tumors. Genetic deletion of Cish in CD8(+) T cells enhances their expansion, functional avidity, and cytokine polyfunctionality, resulting in pronounced and durable regression of established tumors. Although Cish is commonly thought to block STAT5 activation, we found that the primary molecular basis of Cish suppression is through inhibition of TCR signaling. Cish physically interacts with the TCR intermediate PLC-γ1, targeting it for proteasomal degradation after TCR stimulation. These findings establish a novel targetable interaction that regulates the functional avidity of tumor-specific CD8(+) T cells and can be manipulated to improve adoptive cancer immunotherapy.

Breast pathology after cryotherapy. Histological regression of breast cancer after cryotherapy.

Science.gov (United States)

Gajda, Mieczyslaw R; Mireskandari, Masoud; Baltzer, Pascal A; Pfleiderer, Stefan O; Camara, Oumar; Runnebaum, Ingo B; Kaiser, Werner A; Petersen, Iver

2014-03-01

A breast saving treatment is contemporary the preferred method of treatment with comparable results in comparing with mastectomy. In this study were evaluated the effects of cryotherapy by histological verification of changes in post treatment resection specimens. Fifty-three patients in age of 38-81 year with histologically confirmed breast cancer in needle biopsies were managed by cryotherapy between 1999 and 2007. The patients were operated between day 1 and 35 after cryotherapy. The histologic examination of operation materials showed in all cases at least partial tumor destruction. In general in 54.7% of all handled cases (29 patient) there was no residual tumor. In 6 cases (22.2%) from group 1 and in 23 cases (88.5%) of group 2 no tumor rest was found. Cryotherapy can lead to complete destruction of tumoral tissue. In our study all 29 (54.7%) of tumor-free cases after cryotherapy were those with cT1 stage. The experience of operator and the correct selection of appropriate patients (primarily taking the tumor size into account) play the most important role for achieving the best results.

Method and timing of tumor volume measurement for outcome prediction in cervical cancer using magnetic resonance imaging

International Nuclear Information System (INIS)

Mayr, Nina A.; Taoka, Toshiaki; Yuh, William T.C.; Denning, Leah M.; Zhen, Weining K.; Paulino, Arnold C.; Gaston, Robert C.; Sorosky, Joel I.; Meeks, Sanford L.; Walker, Joan L.; Mannel, Robert S.; Buatti, John M.

2002-01-01

Purpose: Recently, imaging-based tumor volume before, during, and after radiation therapy (RT) has been shown to predict tumor response in cervical cancer. However, the effectiveness of different methods and timing of imaging-based tumor size assessment have not been investigated. The purpose of this study was to compare the predictive value for treatment outcome derived from simple diameter-based ellipsoid tumor volume measurement using orthogonal diameters (with ellipsoid computation) with that derived from more complex contour tracing/region-of-interest (ROI) analysis 3D tumor volumetry. Methods and Materials: Serial magnetic resonance imaging (MRI) examinations were prospectively performed in 60 patients with advanced cervical cancer (Stages IB 2 -IVB/recurrent) at the start of RT, during early RT (20-25 Gy), mid-RT (45-50 Gy), and at follow-up (1-2 months after RT completion). ROI-based volumetry was derived by tracing the entire tumor region in each MR slice on the computer work station. For the diameter-based surrogate ''ellipsoid volume,'' the three orthogonal diameters (d 1 , d 2 , d 3 ) were measured on film hard copies to calculate volume as an ellipsoid (d 1 x d 2 x d 3 x π/6). Serial tumor volumes and regression rates determined by each method were correlated with local control, disease-free and overall survival, and the results were compared between the two measuring methods. Median post-therapy follow-up was 4.9 years (range, 2.0-8.2 years). Results: The best method and time point of tumor size measurement for the prediction of outcome was the tumor regression rate in the mid-therapy MRI examination (at 45-50 Gy) using 3D ROI volumetry. For the pre-RT measurement both the diameter-based method and ROI volumetry provided similar predictive accuracy, particularly for patients with small ( 3 ) and large (≥100 cm 3 ) pre-RT tumor size. However, the pre-RT tumor size measured by either method had much less predictive value for the intermediate-size (40

Retro-regression--another important multivariate regression improvement.

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Randić, M

2001-01-01

We review the serious problem associated with instabilities of the coefficients of regression equations, referred to as the MRA (multivariate regression analysis) "nightmare of the first kind". This is manifested when in a stepwise regression a descriptor is included or excluded from a regression. The consequence is an unpredictable change of the coefficients of the descriptors that remain in the regression equation. We follow with consideration of an even more serious problem, referred to as the MRA "nightmare of the second kind", arising when optimal descriptors are selected from a large pool of descriptors. This process typically causes at different steps of the stepwise regression a replacement of several previously used descriptors by new ones. We describe a procedure that resolves these difficulties. The approach is illustrated on boiling points of nonanes which are considered (1) by using an ordered connectivity basis; (2) by using an ordering resulting from application of greedy algorithm; and (3) by using an ordering derived from an exhaustive search for optimal descriptors. A novel variant of multiple regression analysis, called retro-regression (RR), is outlined showing how it resolves the ambiguities associated with both "nightmares" of the first and the second kind of MRA.

Modified Regression Correlation Coefficient for Poisson Regression Model

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Kaengthong, Nattacha; Domthong, Uthumporn

2017-09-01

This study gives attention to indicators in predictive power of the Generalized Linear Model (GLM) which are widely used; however, often having some restrictions. We are interested in regression correlation coefficient for a Poisson regression model. This is a measure of predictive power, and defined by the relationship between the dependent variable (Y) and the expected value of the dependent variable given the independent variables [E(Y|X)] for the Poisson regression model. The dependent variable is distributed as Poisson. The purpose of this research was modifying regression correlation coefficient for Poisson regression model. We also compare the proposed modified regression correlation coefficient with the traditional regression correlation coefficient in the case of two or more independent variables, and having multicollinearity in independent variables. The result shows that the proposed regression correlation coefficient is better than the traditional regression correlation coefficient based on Bias and the Root Mean Square Error (RMSE).

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.

NMR characteristics of rat mammary tumors

International Nuclear Information System (INIS)

Osbakken, M.; Kreider, J.; Taczanowsky, P.

1984-01-01

12 rats were injected intradermally with 13762A rat mammary adenocarcinoma (1 x 10/sup 6/ cells). 3 rats died before completion of the study and 2 rat had tumor regression; the first 3 were excluded from data analysis. NMR imaging with a 1.5K gauss resistive magnet at 2, 3, 4, and 5 weeks after injection demonstrated increasing tumor mass. Saturation recovery (SR), inversion recovery (IR), and spin echo (SE) pulse sequence images and T/sub 1/ calculation were done for tumor characterization. (Tumor size was too small to identify at 2 weeks.) 3 rats were sacrificed after the last 3 imaging periods for histological studies, done to distinguish solid tumor mass from necrosis. Planimetry of tumor areas showed that as tumors grew in size, the ratio of necrotic area to area of solid tumor increased (week 3 = .3 +- .11; week 4 = .45 +- .07; week 5 = .51 +- 05); simultaneous calculated T/sub 1/ values also increased (week 3 = .35 +- .15; week 4 = .45 +- .06; week 5 = .42 +- 03). Qualitative NMR image T/sub 1/ values also increased as evidenced by progression of SR and IR tumor image intensity from very bright compared to the rest of the body at week 3 to less intense than other structures at week 5. These findings indicate that change in T/sub 1/ may be secondary to the pathophysiological change in the tumor (the increasing in necrosis, associated with increased free water). Thus, the range of T/sub 1/ values obtained in tumors in this study (and in previous studies) may be due to change in tumor physiology and anatomy. Careful correlation of histological with NMR data may allow ultimate use of NMR relaxation characteristics for determination of the physiological state of tumors

Dimethyl phenyl piperazine iodide (DMPP) induces glioma regression by inhibiting angiogenesis

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He, Yan-qing; Li, Yan; Wang, Xiao-yu; He, Xiao-dong; Jun, Li; Chuai, Manli; Lee, Kenneth Ka Ho; Wang, Ju; Wang, Li-jing; Yang, Xuesong

2014-01-01

1,1-Dimethyl-4-phenyl piperazine iodide (DMPP) is a synthetic nicotinic acetylcholine receptor (nAChR) agonist that could reduce airway inflammation. In this study, we demonstrated that DMPP could dramatically inhibit glioma size maintained on the chick embryonic chorioallantoic membrane (CAM). We first performed MTT and BrdU incorporation experiments on U87 glioma cells in vitro to understand the mechanism involved. We established that DMPP did not significantly affect U87 cell proliferation and survival. We speculated that DMPP directly caused the tumor to regress by affecting the vasculature in and around the implanted tumor on our chick CAM model. Hence, we conducted detailed analysis of DMPP's inhibitory effects on angiogenesis. Three vasculogenesis and angiogenesis in vivo models were used in the study which included (1) early chick blood islands formation, (2) chick yolk-sac membrane (YSW) and (3) CAM models. The results revealed that DMPP directly suppressed all developmental stages involved in vasculogenesis and angiogenesis – possibly by acting through Ang-1 and HIF-2α signaling. In sum, our results show that DMPP could induce glioma regression grown on CAM by inhibiting vasculogenesis and angiogenesis. - Highlights: ●We demonstrated that DMPP inhibited the growth of glioma cells on chick CAM. ●DMPP did not significantly affect the proliferation and survival of U87 cells. ●We revealed that DMPP suppressed vasculogenesis and angiogenesis in chick embryo. ●Angiogenesis in chick CAM was inhibited by DMPP via most probably Ang-1 and HIF-2α. ●DMPP could be potentially developed as an anti-tumor drug in the future

Echosonography and surgical therapy of facial skin tumors

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Pešić Zoran U.

2002-01-01

Full Text Available In the second half of the 20 century, echosonography has been used in many medical specialties. In 1992 and 1993 highfrequencies echosonography was used in the examination of irritant and allergic skin lesions in order to examine the effects of different therapeuthical agents on the skin lesions [1-4]. Hoffmann used highfrequencies echosonography in the examination of healing of skin lesions [3]. By their incidence skin tumors are the largest group of newly discovered tumors, and their usual location is on the face [5-7]. By clinical examination it is not possible to precisely determine the depth of tumor border; therefore, the radically performed surgical excision is the only correct surgical treatment. The aim of this study was to estimate the results of preoperatively performed high frequencies echosonography in order to reduce the number of incorrectly performed surgical excisions of skin tumors. The group was composed of 40 patients with 45 tumors, who first underwent echosonographic diagnostic procedure (20 MHz, Hadsund electronic, Hadsund Technology, Denmark and then surgical excision; patients in control group (45 patients with 45 tumors were only subjected to surgical excision. Excised tumors were then pathohistologically analyzed, and measurements of tumor depth progression were performed. Margins of pathohistological specimen were controlled for the presence of tumor cells. Results of measurements of tumor depth obtained by echosonography and pathohistological measurements were compared. By Jate's modification of c2 test results regarding correct and incorrect surgical excision in patients and control group were compared. By linear regression analysis results of tumor depth obtained by echosonographic and pathohistologic examinations were compared. Hypoechogen zone echosonographic results were used like criteria for tumor expansion. Results of tumor depth measurements are presented in Table 1. Linear regression analysis showed (R = 0

Magnetic Resonance Fingerprinting of Adult Brain Tumors: Initial Experience

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Badve, Chaitra; Yu, Alice; Dastmalchian, Sara; Rogers, Matthew; Ma, Dan; Jiang, Yun; Margevicius, Seunghee; Pahwa, Shivani; Lu, Ziang; Schluchter, Mark; Sunshine, Jeffrey; Griswold, Mark; Sloan, Andrew; Gulani, Vikas

2016-01-01

Background Magnetic resonance fingerprinting (MRF) allows rapid simultaneous quantification of T1 and T2 relaxation times. This study assesses the utility of MRF in differentiating between common types of adult intra-axial brain tumors. Methods MRF acquisition was performed in 31 patients with untreated intra-axial brain tumors: 17 glioblastomas, 6 WHO grade II lower-grade gliomas and 8 metastases. T1, T2 of the solid tumor (ST), immediate peritumoral white matter (PW), and contralateral white matter (CW) were summarized within each region of interest. Statistical comparisons on mean, standard deviation, skewness and kurtosis were performed using univariate Wilcoxon rank sum test across various tumor types. Bonferroni correction was used to correct for multiple comparisons testing. Multivariable logistic regression analysis was performed for discrimination between glioblastomas and metastases and area under the receiver operator curve (AUC) was calculated. Results Mean T2 values could differentiate solid tumor regions of lower-grade gliomas from metastases (mean±sd: 172±53ms and 105±27ms respectively, p =0.004, significant after Bonferroni correction). Mean T1 of PW surrounding lower-grade gliomas differed from PW around glioblastomas (mean±sd: 1066±218ms and 1578±331ms respectively, p=0.004, significant after Bonferroni correction). Logistic regression analysis revealed that mean T2 of ST offered best separation between glioblastomas and metastases with AUC of 0.86 (95% CI 0.69–1.00, p<0.0001). Conclusion MRF allows rapid simultaneous T1, T2 measurement in brain tumors and surrounding tissues. MRF based relaxometry can identify quantitative differences between solid-tumor regions of lower grade gliomas and metastases and between peritumoral regions of glioblastomas and lower grade gliomas. PMID:28034994

Improved Tumor-Specific Drug Accumulation by Polymer Therapeutics with pH-Sensitive Drug Release Overcomes Chemotherapy Resistance.

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Heinrich, Anne-Kathrin; Lucas, Henrike; Schindler, Lucie; Chytil, Petr; Etrych, Tomáš; Mäder, Karsten; Mueller, Thomas

2016-05-01

The success of chemotherapy is limited by poor selectivity of active drugs combined with occurrence of tumor resistance. New star-like structured N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-based drug delivery systems containing doxorubicin attached via a pH-sensitive hydrazone bond were designed and investigated for their ability to overcome chemotherapy resistance. These conjugates combine two strategies to achieve a high drug concentration selectively at the tumor site: (I) high accumulation by passive tumor targeting based on enhanced permeability and retention effect and (II) pH-sensitive site-specific drug release due to an acidic tumor microenvironment. Mice bearing doxorubicin-resistant xenograft tumors were treated with doxorubicin, PBS, poly HPMA (pHPMA) precursor or pHPMA-doxorubicin conjugate at different equivalent doses of 5 mg/kg bodyweight doxorubicin up to a 7-fold total dose using different treatment schedules. Intratumoral drug accumulation was analyzed by fluorescence imaging utilizing intrinsic fluorescence of doxorubicin. Free doxorubicin induced significant toxicity but hardly any tumor-inhibiting effects. Administering at least a 3-fold dose of pHPMA-doxorubicin conjugate was necessary to induce a transient response, whereas doses of about 5- to 6-fold induced strong regressions. Tumors completely disappeared in some cases. The onset of response was differential delayed depending on the tumor model, which could be ascribed to distinct characteristics of the microenvironment. Further fluorescence imaging-based analyses regarding underlying mechanisms of the delayed response revealed a related switch to a more supporting intratumoral microenvironment for effective drug release. In conclusion, the current study demonstrates that the concept of tumor site-restricted high-dose chemotherapy is able to overcome therapy resistance. Mol Cancer Ther; 15(5); 998-1007. ©2016 AACR. ©2016 American Association for Cancer Research.

Salvage Reirradiaton With Stereotactic Body Radiotherapy for Locally Recurrent Head-and-Neck Tumors

International Nuclear Information System (INIS)

Cengiz, Mustafa; Ozyigit, Goekhan; Yazici, Goezde; Dogan, Ali; Yildiz, Ferah; Zorlu, Faruk; Guerkaynak, Murat; Gullu, Ibrahim H.; Hosal, Sefik; Akyol, Fadil

2011-01-01

Purpose: In this study, we present our results of reirradiation of locally recurrent head-and-neck cancer with image-guided, fractionated, frameless stereotactic body radiotherapy technique. Methods and Materials: From July 2007 to February 2009, 46 patients were treated using the CyberKnife (Accuray, Sunnyvale, CA) at the Department of Radiation Oncology, Hacettepe University, Ankara, Turkey. All patients had recurrent, unresectable, and previously irradiated head-and-neck cancer. The most prominent site was the nasopharynx (32.6%), and the most common histopathology was epidermoid carcinoma. The planning target volume was defined as the gross tumor volume identified on magnetic resonance imaging and computed tomography. There were 22 female and 24 male patients. Median age was 53 years (range, 19-87 years). The median tumor dose with stereotactic body radiotherapy was 30 Gy (range, 18-35 Gy) in a median of five (range, one to five) fractions. Results: Of 37 patients whose response to therapy was evaluated, 10 patients (27%) had complete tumor regression, 11 (29.8%) had partial response, and 10 (27%) had stable disease. Ultimate local disease control was achieved in 31 patients (83.8%). The overall survival was 11.93 months in median (ranged, 11.4 - 17.4 months), and the median progression free survival was 10.5 months. One-year progression-free survival and overall survival were 41% and 46%, respectively. Grade II or greater long-term complications were observed in 6 (13.3%) patients. On follow-up, 8 (17.3%) patients had carotid blow-out syndrome, and 7 (15.2%) patients died of bleeding from carotid arteries. We discovered that this fatal syndrome occurred only in patients with tumor surrounding carotid arteries and carotid arteries receiving all prescribed dose. Conclusions: Stereotactic body radiotherapy is an appealing treatment option for patients with recurrent head-and-neck cancer previously treated with radiation to high doses. Good local control with

Comparison of the effect between an active specific immunotherapy using the immune reaction of a low-dose irradiated tumor tissue and that using irradiated tumor cells

International Nuclear Information System (INIS)

Ogawa, Yasuhiro; Maeda, Tomoho; Yoshida, Shoji; Yamamoto, Yoichi; Morita, Masaru

1983-01-01

The effect of the active specific immunotherapy using the immune reaction of a low-dose irradiated tumor tissue was compared with that of irradiated (10,000 rads) tumor cells on the transplanted MM46 tumor of female C3H/He mice after radiotherapy. MM46 tumor cells were inoculated into the right hind paws of mice. On the 6th day, irradiation with a dose of 3,000 rads was performed. On the 14th day, tumor cells and concomitant mononuclear cells which were separated from the low-dose irradiated tumor tissue (2,000 rads on the 6th day) were injected into the left hind paws of one group of the tumor-bearing mice. On the same day, irradiated MM46 tumor cells were injected into the left hind paws of another group of the tumor-bearing mice. Effectiveness of these two methods of active specific immunotherapy against tumor was evaluated by the regression of tumor and survival rate of mice. The active specific immunotherapy using the immune reaction of a low-dose irradiated tumor tissue was far more effective than irradiated tumor cells on this tumor system involved. (author)

Diffusion-weighted imaging of tumor recurrencies and posttherapeutical soft-tissue changes in humans

International Nuclear Information System (INIS)

Baur, A.; Huber, A.; Reiser, M.; Arbogast, S.; Duerr, H.R.; Zysk, S.; Wendtner, C.; Deimling, M.

2001-01-01

The aim of this study was to examine soft tissue tumor recurrences and posttherapeutic soft tissue changes in humans with a diffusion-weighted steady-state free precession (SSFP) sequence. Twenty-four patients with 29 pathologies of the pelvis or the extremities were examined. The lesions were classified as follows: group 1, recurrent viable tumors (n = 10); group 2, postoperative hygromas (n = 7); and group 3, posttherapeutic reactive inflammatory muscle changes (n = 12). The sequence protocol in these patients consisted of short tau inversion recovery images, T2-weighted spin-echo (SE), pre- and postcontrast T1-weighted SE images and the diffusion-weighted SSFP sequence. The signal loss on diffusion-weighting was evaluated visually on a four-grade scale and quantitatively. The signal intensities were measured in regions of interest and a regression analysis was performed. Statistical analyses was performed utilizing the Student's t-test. The signal loss was significantly higher for hygromas and edematous muscle changes than for recurrent tumors (p < 0.001) indicating higher diffusion of water protons. The regression coefficient was -0.11 (mean) for tumors. Hygromas had a significantly higher signal loss than inflammatory edematous muscle changes (p < 0.01). The regression coefficients were -0.29 (mean) for hygromas and -0.22 (mean) for edematous muscle changes. The SSFP sequence seems to be a suitable method for diffusion-weighted imaging of the musculoskeletal system in humans. These preliminary results suggest that the signal loss and the regression coefficients can be used to characterize different types of tissue. (orig.)

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

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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.

Tumor-specific CD4+ T cells develop cytotoxic activity and eliminate virus-induced tumor cells in the absence of regulatory T cells.

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Akhmetzyanova, Ilseyar; Zelinskyy, Gennadiy; Schimmer, Simone; Brandau, Sven; Altenhoff, Petra; Sparwasser, Tim; Dittmer, Ulf

2013-02-01

The important role of tumor-specific cytotoxic CD8(+) T cells is well defined in the immune control of the tumors, but the role of effector CD4(+) T cells is poorly understood. In the current research, we have used a murine retrovirus-induced tumor cell line of C57BL/6 mouse origin, namely FBL-3 cells, as a model to study basic mechanisms of immunological control and escape during tumor formation. This study shows that tumor-specific CD4(+) T cells are able to protect against virus-induced tumor cells. We show here that there is an expansion of tumor-specific CD4(+) T cells producing cytokines and cytotoxic molecule granzyme B (GzmB) in the early phase of tumor growth. Importantly, we demonstrate that in vivo depletion of regulatory T cells (Tregs) and CD8(+) T cells in FBL-3-bearing DEREG transgenic mice augments IL-2 and GzmB production by CD4(+) T cells and increases FV-specific CD4(+) T-cell effector and cytotoxic responses leading to the complete tumor regression. Therefore, the capacity to reject tumor acquired by tumor-reactive CD4(+) T cells largely depends on the direct suppressive activity of Tregs. We suggest that a cytotoxic CD4(+) T-cell immune response may be induced to enhance resistance against oncovirus-associated tumors.

Spontaneous regression of transverse colon cancer: a case report.

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Chida, Keigo; Nakanishi, Kazuaki; Shomura, Hiroki; Homma, Shigenori; Hattori, Atsuo; Kazui, Keizo; Taketomi, Akinobu

2017-12-01

Spontaneous regression (SR) of many malignant tumors has been well documented, with an approximate incidence of one per 60,000-100,000 cancer patients. However, SR of colorectal cancer (CRC) is very rare, accounting for less than 2% of such cases. We report a case of SR of transverse colon cancer in an 80-year-old man undergoing outpatient follow-up after surgical treatment of early gastric cancer. Colonoscopy (CS) revealed a Borrmann type II tumor in the transverse colon measuring 30 × 30 mm. Because the patient underwent anticoagulant therapy, we did not perform a biopsy at that time. A second CS was performed 1 week after the initial examination and revealed tumor shrinkage to a diameter of 20 mm and a shift to the Borrmann type III morphology. Biopsy revealed a poorly differentiated adenocarcinoma. One week after the second CS, we performed a partial resection of the transverse colon and D2 lymph node dissection. Histopathology revealed inflammatory cell infiltration and fibrosis from the submucosal to muscularis propria layers in the absence of cancer cells, leading to pathological staging of pStage 0 (T0N0). The patient had an uneventful recovery, and CS performed at 5 months postoperatively revealed the absence of a tumor in the colon and rectum. The patient continues to be followed up as an outpatient at 12 months postoperatively, and no recurrence has been observed.

A Unique Cellular and Molecular Microenvironment Is Present in Tertiary Lymphoid Organs of Patients with Spontaneous Prostate Cancer Regression

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María de la Luz García-Hernández

2017-05-01

Full Text Available ObjectiveMultiple solid cancers contain tertiary lymphoid organs (TLO. However, it is unclear whether they promote tumor rejection, facilitate tumor evasion, or simply whether they are a byproduct of chronic inflammation. We hypothesize that although chronic inflammation induces TLO formation, the tumor milieu can modulate TLO organization and functions in prostate cancer. Therefore, our study seeks to elucidate the cellular and molecular signatures in unique prostatectomy specimens from evanescent carcinoma patients to identify markers of cancer regression, which could be harnessed to modulate local immunosuppression or potentially enhance TLO function.MethodsWe used multicolor immunofluorescence to stain prostate tissues, collected at different stages of cancer progression (prostatic intraepithelial neoplasia, intermediate and advanced cancer or from patients with evanescent prostate carcinoma. Tissues were stained with antibodies specific for pro-inflammatory molecules (cyclooxygenase 2, CXCL10, IL17, tumor-infiltrating immune cells (mature DC-LAMP+ dendritic cells, CD3+ T cells, CD3+Foxp3+ regulatory T cells (Treg, T bet+ Th1 cells, granzyme B+ cytotoxic cells, and stromal cell populations (lymphatic vessels, tumor neovessels, high endothelial venules (HEV, stromal cells, which promote prostate tumor growth or are critical components of tumor-associated TLO.ResultsGenerally, inflammatory cells are located at the margins of tumors. Unexpectedly, we found TLO within prostate tumors from patients at different stages of cancer and in unique samples from patients with spontaneous cancer remission. In evanescent prostate carcinomas, accumulation of Treg was compromised, while Tbet+ T cells and CD8 T cells were abundant in tumor-associated TLO. In addition, we found a global decrease in tumor neovascularization and the coverage by cells positive for cyclooxygenase 2 (COX2. Finally, consistent with tumor regression, prostate stem cell antigen was

Spontaneous regression of pulmonary bullae

International Nuclear Information System (INIS)

Satoh, H.; Ishikawa, H.; Ohtsuka, M.; Sekizawa, K.

2002-01-01

The natural history of pulmonary bullae is often characterized by gradual, progressive enlargement. Spontaneous regression of bullae is, however, very rare. We report a case in which complete resolution of pulmonary bullae in the left upper lung occurred spontaneously. The management of pulmonary bullae is occasionally made difficult because of gradual progressive enlargement associated with abnormal pulmonary function. Some patients have multiple bulla in both lungs and/or have a history of pulmonary emphysema. Others have a giant bulla without emphysematous change in the lungs. Our present case had treated lung cancer with no evidence of local recurrence. He had no emphysematous change in lung function test and had no complaints, although the high resolution CT scan shows evidence of underlying minimal changes of emphysema. Ortin and Gurney presented three cases of spontaneous reduction in size of bulla. Interestingly, one of them had a marked decrease in the size of a bulla in association with thickening of the wall of the bulla, which was observed in our patient. This case we describe is of interest, not only because of the rarity with which regression of pulmonary bulla has been reported in the literature, but also because of the spontaneous improvements in the radiological picture in the absence of overt infection or tumor. Copyright (2002) Blackwell Science Pty Ltd

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

International Nuclear Information System (INIS)

Sposto, R.; Preston, D.L.

1993-05-01

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

Lapatinib Plasma and Tumor Concentrations and Effects on HER Receptor Phosphorylation in Tumor.

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Neil L Spector

Full Text Available The paradigm shift in cancer treatment from cytotoxic drugs to tumor targeted therapies poses new challenges, including optimization of dose and schedule based on a biologically effective dose, rather than the historical maximum tolerated dose. Optimal dosing is currently determined using concentrations of tyrosine kinase inhibitors in plasma as a surrogate for tumor concentrations. To examine this plasma-tumor relationship, we explored the association between lapatinib levels in tumor and plasma in mice and humans, and those effects on phosphorylation of human epidermal growth factor receptors (HER in human tumors.Mice bearing BT474 HER2+ human breast cancer xenografts were dosed once or twice daily (BID with lapatinib. Drug concentrations were measured in blood, tumor, liver, and kidney. In a randomized phase I clinical trial, 28 treatment-naïve female patients with early stage HER2+ breast cancer received lapatinib 1000 or 1500 mg once daily (QD or 500 mg BID before evaluating steady-state lapatinib levels in plasma and tumor.In mice, lapatinib levels were 4-fold higher in tumor than blood with a 4-fold longer half-life. Tumor concentrations exceeded the in vitro IC90 (~ 900 nM or 500 ng/mL for inhibition of HER2 phosphorylation throughout the 12-hour dosing interval. In patients, tumor levels were 6- and 10-fold higher with QD and BID dosing, respectively, compared to plasma trough levels. The relationship between tumor and plasma concentration was complex, indicating multiple determinants. HER receptor phosphorylation varied depending upon lapatinib tumor concentrations, suggestive of changes in the repertoire of HER homo- and heterodimers.Plasma lapatinib concentrations underestimated tumor drug levels, suggesting that optimal dosing should be focused on the site of action to avoid to inappropriate dose escalation. Larger clinical trials are required to determine optimal dose and schedule to achieve tumor concentrations that maximally

Radiotherapy for a cystadenolymphoma of the parotid gland (Warthin's tumor)

International Nuclear Information System (INIS)

Stallmann, C.; Vacha, P.; Vesely, H.; Richter, E.; Feyerabend, T.

2001-01-01

Background: With 17.6% of all primary parotid neoformations the benign Warthin's tumor (cystadenolymphoma) is the second common parotid gland tumor. Males > 50 years are affected predominantly. After surgery the recurrence rate is less than 5%. Histomorphologically the tumor is characterized by cystoid ducts lined by epithelial cells as well as lymphoid stroma. The lymphoid component has been described as radioresponsive whereas the epithelial parts are less radiosensitive. Since 1960 only one patient treated by primary radiotherapy has been published. Case report: A 77-year-old woman suffered from cystadenolymphoma (maximal diameter 7 cm). Because of its extension and the reduced performance status of the patient surgery was no option. Radiotherapy was performed with a total dose of 50 Gy. Clinically, the tumor regressed completely after 30 Gy, which was confirmed by CT at 6 weeks after completion of radiotherapy. After 6 and 12 months the patient stayed free of tumor. Epicrisis: In our case the cystadenolymphoma was unusually large (7 cm). Radiotherapy with 50 Gy induced complete tumor regression. The good clinical response after 30 Gy suggests that the necessary dose may be lower for less extended cystadenolymphomas. Conclusion: We present a case of cystadenolymphoma treated by radiotherapy with 50 Gy resulting in a complete remission. Due to missing published experiences no common recommendation for the total dose can be given. In the following situations radiotherapy should be considered: 1. high surgical risk of damage to the facial nerve, 2. unfavorable cosmetic outcome after surgery, 3. inoperability for internal risks, 4. refusal of operation. (orig.) [de

Dual Regression

OpenAIRE

Spady, Richard; Stouli, Sami

2012-01-01

We propose dual regression as an alternative to the quantile regression process for the global estimation of conditional distribution functions under minimal assumptions. Dual regression provides all the interpretational power of the quantile regression process while avoiding the need for repairing the intersecting conditional quantile surfaces that quantile regression often produces in practice. Our approach introduces a mathematical programming characterization of conditional distribution f...

Intraoperative MRI to control the extent of brain tumor surgery

International Nuclear Information System (INIS)

Knauth, M.; Sartor, K.; Wirtz, C.R.; Tronnier, V.M.; Staubert, A.; Kunze, S.

1998-01-01

Intraoperative MRI definitely showed residual tumor in 6 of the 18 patients and resulted in ambiguous findings in 3 patients. In 7 patients surgery was continued. Early postoperative MRI showed residual tumor in 3 patients and resulted in uncertain findings in 2 patients. The rate of patients in whom complete removal of enhancing tumor could be achieved was 50% at the time of the intraoperative MR examination and 72% at the time of the early postoperative MR control. The difference in proportion of patients with 'complete tumor removal' between the groups who had been operated on using neuronavigation (NN) and intraoperative MRI (ioMRI) and those who had been operated on using only modern neurosurgical techniques except NN and ioMRI was statistically highly significant (Fisher exact test; P=0.008). Four different types of surgically induced contrast enhancement were observed. These phenomena carry different confounding potentials with residual tumor. Conclusion: Our preliminary experience with intraoperative MRI in patients with enhancing intraaxial tumors is encouraging. Combined use of neuronavigation and intraoperative MRI was able to increase the proportion of patients in whom complete removal of the enhancing parts of the tumor was achieved. Surgically induced enhancement requires careful analysis of the intraoperative MRI in order not to confuse it with residual tumor. (orig.) [de

Experimental study on active specific immunotherapy utilizing the immunotherapy utilizing the immune reaction of low-dose irradiated tumor tissue, 3

International Nuclear Information System (INIS)

Ogawa, Yasuhiro; Imanaka, Kazufumi; Gose, Kyuhei; Imajo, Yoshinari; Kimura, Shuji

1982-01-01

We have already demonstrated the remarkable effect of the active specific immunotherapy utilizing tumor cells and infiltrating lymphocytes prepared from a low-dose irradiated tumor tissue after cytoreductive radiotherapy. In the present study, the active specific immunotherapy using the tumor cells and infiltrating lymphocytes which were cryopreserved at -196 0 C in liquid nitrogen was investigated in female C3H/He mice inoculated MM46 tumor. Irradiation with the dose of 3,000 rads was performed on the sixth day. The tumor cells and lymphocytes which were separated from 2,000 rads-irradiated tumor tissue were frozen by the program freezer to be preserved at -196 0 C for two months and were thawed to inject into the tumor-bearing mice on the thirteenth day. Anti-tumor effect was evaluated by the regression of the tumor and survival curves. The remarkable regression of the tumor (p < 0.01) and significant elongation of the survival period (p < 0.1) were observed in the group which received the active specific immunotherapy using the cryopreserved tumor cells and lymphocytes as well as the group using the fresh tumor cells and lymphocytes prepared from a low-dose irradiated tumor tissue. (author)

Reconstruction of segmental bone defect of long bones after tumor resection by devitalized tumor-bearing bone

OpenAIRE

Qu, Huayi; Guo, Wei; Yang, Rongli; Li, Dasen; Tang, Shun; Yang, Yi; Dong, Sen; Zang, Jie

2015-01-01

Background The reconstruction of an intercalary bone defect after a tumor resection of a long bone remains a challenge to orthopedic surgeons. Though several methods have been adopted to enhance the union of long segmental allografts or retrieved segmental autografts to the host bones, still more progresses are required to achieve a better union rate. Several methods have been adopted to devitalize tumor bone for recycling usage, and the results varied. We describe our experiences of using de...

Tumor Hypoxia is Independent of Hemoglobin and Prognostic for Loco-regional Tumor Control after Primary Radiotherapy in Advanced Head and Neck Cancer

International Nuclear Information System (INIS)

Nordsmark, Marianne; Overgaard, Jens

2004-01-01

There is evidence that tumor hypoxia adversely affects loco-regional tumor control and survival in head and neck cancer. The aim of the current study was to compare pretreatment tumor oxygenation measured by Eppendorf pO2 electrodes with known prognostic factors in advanced head and neck tumors after definitive radiotherapy, and to evaluate the prognostic significance of these parameters on loco-regional tumor control. Sixty-seven patients, median age 56 years (22-82), all with primary stage III-IV squamous cell carcinoma were available for survival analysis. Tumor oxygenation was described as the fraction of pO2 values=2.5 mmHg (HP2.5) and the median tumor pO2. By regression analysis HP2.5 was independent of known prognostic factors including stage, pretreatment hemoglobin (Hb) and the largest tumor diameter at the site of pO2 measurement. By Kaplan-Meier analysis loco-regional tumor control at 5 years was in favor of less hypoxic tumors using either HP2.5 or median tumor pO2 as descriptors and stratifying by the median values. Also, Hb was prognostic of loco-regional tumor control at 5 years using the median value as cut off. HP2.5 as continuous parameter was highly significant for loco-regional tumor control in a multivariate analysis. In conclusion both HP2.5 and total Hb were prognostic for loco-regional tumor control, but HP2.5 as continuous variable was independently the strongest prognostic indicator for loco-regional tumor control after definitive primary radiotherapy in advanced head and neck tumors

Neurosurgical treatment of extracerebral tumors

International Nuclear Information System (INIS)

Antoniadis, G.; Kretschmer, T.; Braun, V.; Rath, S.; Richter, H.P.

1998-01-01

Extracerebral tumors represent 29-30% of the intracranial tumors. Meningiomas rank first in incidence with 13-19%, followed by neurinomas and pituitary adenomas, 6-8% each. Due to their slow growth rate, meningiomas in the initial stages do not produce symptoms. Complete recovery can be achieved by complete removal of the tumor, which in general is possible in case of tumor sites at the convexity. Meningiomas at the basis, or meningiomas spreading into the sinus sagittalis superior often cannot be totally removed, so that for treatment of remaining or recurrent tumors and anaplastic meningiomas, post-operative radiation therapy is recommended. Neurinomas of the nervus acusticus originate at the N. vestibularis and may spread from the Meatus acusticus internus into the brain stem. With the modern methods of microsurgery combined with intraoperative monitoring it is possible to preserve the Nn. facialis and cochlearis and their functions. As an alternative to surgery, radiosurgery techniques have been on trial in the last few years. Via transsphenoidal approach, intra- and suprasellar pituitary adenomas can be completely destroyed. Parasellar tumors can be resected by transcranial approach only. Remaining tumors in the Sinus cavernosus, or recurrent adenomas, should receive post-surgery radiation treatment. (orig./CB) [de

Dimethyl phenyl piperazine iodide (DMPP) induces glioma regression by inhibiting angiogenesis

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He, Yan-qing; Li, Yan; Wang, Xiao-yu [Key Laboratory for Regenerative Medicine of the Ministry of Education, Division of Histology and Embryology, Medical College, Jinan University, Guangzhou 510632 (China); He, Xiao-dong [Institute of Vascular Biological Sciences, Guangdong Pharmaceutical University, Guangzhou 510006 (China); Jun, Li [Guangdong Provincial Key Laboratory of Bioengineering Medicine, National Engineering Research Centre of Genetic Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632 (China); Chuai, Manli [Division of Cell and Developmental Biology, University of Dundee, Dundee, DD1 5EH (United Kingdom); Lee, Kenneth Ka Ho [Key Laboratory for Regenerative Medicine of the Ministry of Education, School of Biomedical Sciences, Chinese University of Hong Kong, Shatin (Hong Kong); Wang, Ju [Guangdong Provincial Key Laboratory of Bioengineering Medicine, National Engineering Research Centre of Genetic Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632 (China); Wang, Li-jing, E-mail: wanglijing62@163.com [Institute of Vascular Biological Sciences, Guangdong Pharmaceutical University, Guangzhou 510006 (China); Yang, Xuesong, E-mail: yang_xuesong@126.com [Key Laboratory for Regenerative Medicine of the Ministry of Education, Division of Histology and Embryology, Medical College, Jinan University, Guangzhou 510632 (China)

2014-01-15

1,1-Dimethyl-4-phenyl piperazine iodide (DMPP) is a synthetic nicotinic acetylcholine receptor (nAChR) agonist that could reduce airway inflammation. In this study, we demonstrated that DMPP could dramatically inhibit glioma size maintained on the chick embryonic chorioallantoic membrane (CAM). We first performed MTT and BrdU incorporation experiments on U87 glioma cells in vitro to understand the mechanism involved. We established that DMPP did not significantly affect U87 cell proliferation and survival. We speculated that DMPP directly caused the tumor to regress by affecting the vasculature in and around the implanted tumor on our chick CAM model. Hence, we conducted detailed analysis of DMPP's inhibitory effects on angiogenesis. Three vasculogenesis and angiogenesis in vivo models were used in the study which included (1) early chick blood islands formation, (2) chick yolk-sac membrane (YSW) and (3) CAM models. The results revealed that DMPP directly suppressed all developmental stages involved in vasculogenesis and angiogenesis – possibly by acting through Ang-1 and HIF-2α signaling. In sum, our results show that DMPP could induce glioma regression grown on CAM by inhibiting vasculogenesis and angiogenesis. - Highlights: ●We demonstrated that DMPP inhibited the growth of glioma cells on chick CAM. ●DMPP did not significantly affect the proliferation and survival of U87 cells. ●We revealed that DMPP suppressed vasculogenesis and angiogenesis in chick embryo. ●Angiogenesis in chick CAM was inhibited by DMPP via most probably Ang-1 and HIF-2α. ●DMPP could be potentially developed as an anti-tumor drug in the future.

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

The Relationship between The Level of Intelligence, Achievement Motivation, Mathematics Learning Habits and Learning Achievement

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Farkhatu Sikhah

2017-03-01

correlative so data were analyzed to describe the relationship between the level of intelligence, achievement motivation and study habits mathematics with mathematics learning achievement of students. Instrument documentation and data retrieval using a questionnaire and analyzed using simple linear regression and correlation, as well as multiple linear regression and correlation. The results showed that there is a significant relationship between: (1 the level of intelligence with mathematics learning achievement of students, (2 achievement motivation and academic achievement of student mathematics, (3 study habits and academic achievement of student mathematics (4 the level of intelligence, achievement motivation and study habits mathematics with mathematics learning achievement of students.

Coefficient shifts in geographical ecology: an empirical evaluation of spatial and non-spatial regression

DEFF Research Database (Denmark)

Bini, L. M.; Diniz-Filho, J. A. F.; Rangel, T. F. L. V. B.

2009-01-01

A major focus of geographical ecology and macroecology is to understand the causes of spatially structured ecological patterns. However, achieving this understanding can be complicated when using multiple regression, because the relative importance of explanatory variables, as measured by regress...

Potential pitfalls when denoising resting state fMRI data using nuisance regression.

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Bright, Molly G; Tench, Christopher R; Murphy, Kevin

2017-07-01

In resting state fMRI, it is necessary to remove signal variance associated with noise sources, leaving cleaned fMRI time-series that more accurately reflect the underlying intrinsic brain fluctuations of interest. This is commonly achieved through nuisance regression, in which the fit is calculated of a noise model of head motion and physiological processes to the fMRI data in a General Linear Model, and the "cleaned" residuals of this fit are used in further analysis. We examine the statistical assumptions and requirements of the General Linear Model, and whether these are met during nuisance regression of resting state fMRI data. Using toy examples and real data we show how pre-whitening, temporal filtering and temporal shifting of regressors impact model fit. Based on our own observations, existing literature, and statistical theory, we make the following recommendations when employing nuisance regression: pre-whitening should be applied to achieve valid statistical inference of the noise model fit parameters; temporal filtering should be incorporated into the noise model to best account for changes in degrees of freedom; temporal shifting of regressors, although merited, should be achieved via optimisation and validation of a single temporal shift. We encourage all readers to make simple, practical changes to their fMRI denoising pipeline, and to regularly assess the appropriateness of the noise model used. By negotiating the potential pitfalls described in this paper, and by clearly reporting the details of nuisance regression in future manuscripts, we hope that the field will achieve more accurate and precise noise models for cleaning the resting state fMRI time-series. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Four-dimensional treatment planning and fluoroscopic real-time tumor tracking radiotherapy for moving tumor

International Nuclear Information System (INIS)

Shirato, Hiroki; Shimizu, Shinichi; Kitamura, Kei; Nishioka, Takeshi; Kagei, Kenji; Hashimoto, Seiko; Aoyama, Hidefumi; Kunieda, Tatsuya; Shinohara, Nobuo; Dosaka-Akita, Hirotoshi; Miyasaka, Kazuo

2000-01-01

Purpose: To achieve precise three-dimensional (3D) conformal radiotherapy for mobile tumors, a new radiotherapy system and its treatment planning system were developed and used for clinical practice. Methods and Materials: We developed a linear accelerator synchronized with a fluoroscopic real-time tumor tracking system by which 3D coordinates of a 2.0-mm gold marker in the tumor can be determined every 0.03 second. The 3D relationships between the marker and the tumor at different respiratory phases are evaluated using CT image at each respiratory phase, whereby the optimum phase can be selected to synchronize with irradiation (4D treatment planning). The linac is triggered to irradiate the tumor only when the marker is located within the region of the planned coordinates relative to the isocenter. Results: The coordinates of the marker were detected with an accuracy of ± 1 mm during radiotherapy in the phantom experiment. The time delay between recognition of the marker position and the start or stop of megavoltage X-ray irradiation was 0.03 second. Fourteen patients with various tumors were treated by conformal radiotherapy with a 'tight' planning target volume (PTV) margin. They were surviving without relapse or complications with a median follow-up of 6 months. Conclusion: Fluoroscopic real-time tumor tracking radiotherapy following 4D treatment planning was developed and shown to be feasible to improve the accuracy of the radiotherapy for mobile tumors

18F-fluorodeoxyglucose positron emission tomography for predicting tumor response to radiochemotherapy in nasopharyngeal carcinoma

International Nuclear Information System (INIS)

Su, Meng; Wei, Hangping; Lin, Ruifang; Zhang, Xuebang; Zou, Changlin; Zhao, Liang

2015-01-01

The aim of this study was to evaluate the value of 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in predicting tumor response to radiochemotherapy in nasopharyngeal carcinoma (NPC). From July 2012 to March 2014, 46 NPC patients who had undergone PET scanning before receiving definitive intensity-modulated radiotherapy (IMRT) treatment in our hospital were enrolled. Factors potentially affecting tumor response to treatment were studied by multiple logistic regression analysis. After radiochemotherapy, 32 patients had a clinical complete response (CR), making the CR rate 69.6 %. Multiple logistic regression analysis demonstrated that the maximal standard uptake value (SUV max ) of the primary tumor was the only factor related to tumor response (p = 0.001), and that the logistic model had a high positive predictive value (90.6 %). The area under the receiver operating characteristic (ROC) curve was 0.809, with a best cutoff threshold at 10.05. Patients with SUV max ≤ 10 had a higher CR rate than those with SUV max > 10 (p < 0.001). The SUV max of the primary tumor before treatment is an independent predictor of tumor response in NPC. (orig.) [de

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

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

2015-01-01

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

Multiparametric MR assessment of pediatric brain tumors

International Nuclear Information System (INIS)

Tzika, A.A.; Astrakas, L.G.; Zarifi, M.K.; Petridou, N.; Young-Poussaint, T.; Goumnerova, L.; Black, P.McL.; Zurakowski, D.; Anthony, D.C.

2003-01-01

MR assessment of pediatric brain tumors has expanded to include physiologic information related to cellular metabolites, hemodynamic and diffusion parameters. The purpose of this study was to investigate the relationship between MR and proton MR spectroscopic imaging in children with primary brain tumors. Twenty-one patients (mean age 9 years) with histologically verified brain tumors underwent conventional MR imaging, hemodynamic MR imaging (HMRI) and proton MR spectroscopic imaging (MRSI). Fourteen patients also had diffusion-weighted MR imaging (DWMRI). Metabolic indices including choline-containing compounds (Cho), total creatine (tCr) and lipids/lactate (L) were derived by proton MRSI, relative cerebral blood volume (rCBV) by HMRI, and apparent tissue water diffusion coefficients (ADC) by DWMRI. Variables were examined by linear regression and correlation as well as by ANOVA. Cho (suggestive of tumor cellularity and proliferative activity) correlated positively with rCBV, while the relationship between Cho and ADC (suggestive of cellular density) was inverse (P<0.001). The relationship between rCBV and ADC was also inverse (P=0.004). Cho and lipids (suggestive of necrosis and/or apoptosis) were not significantly correlated (P=0.51). A positive relationship was found between lipids and ADC (P=0.002). The relationships between Cho, rCBV, ADC and lipids signify that tumor physiology is influenced by the tumor's physical and chemical environment. Normalized Cho and lipids distinguished high-grade from low-grade tumors (P<0.05). Multiparametric MR imaging using MRSI, HMRI and DWMRI enhances assessment of brain tumors in children and improves our understanding of tumor physiology while promising to distinguish higher- from lower-malignancy tumors, a distinction that is particularly clinically important among inoperable tumors. (orig.)

Feasibility of boron neutron capture therapy for malignant spinal tumors

International Nuclear Information System (INIS)

Nakai, Kei; Kumada, Hiroaki; Yamamoto, Tetsuya; Tsurubuchi, Takao; Zaboronok, Alexander; Matsumura, Akira

2009-01-01

Treatment of malignant spinal cord tumors is currently ineffective. The characteristics of the spine are its seriality, small volume, and vulnerability: severe QOL impairment can be brought about by small neuronal damage. The present study aimed to investigate the feasibility of BNCT as a tumor-selective charged particle therapy for spinal cord tumors from the viewpoint of protecting the normal spine. A previous report suggested the tolerance dose of the spinal cord was 13.8 Gy-Eq for radiation myelopathy; a dose as high as 11 Gy-Eq demonstrated no spinal cord damage in an experimental animal model. We calculated the tumor dose and the normal spinal cord dose on a virtual model of a spinal cord tumor patient with a JAEA computational dosimetry system (JCDS) treatment planning system. The present study made use of boronophenylalanine (BPA). In these calculations, conditions were set as follows: tumor/normal (T/N) ratio of 3.5, blood boron concentration of 12 ppm, tumor boron concentration of 42 ppm, and relative biological effectiveness (RBE) values for tumor and normal spinal cord of 3.8 and 1.35, respectively. We examined how to optimize neutron irradiation by changing the beam direction and number. In our theoretical example, simple opposed two-field irradiation achieved 28.0 Gy-Eq as a minimum tumor dose and 7.3 Gy-Eq as a maximum normal spinal dose. The BNCT for the spinal cord tumor was therefore feasible when a sufficient T/N ratio could be achieved. The use of F-BPA PET imaging for spinal tumor patients is supported by this study.

Fractional laser exposure induces neutrophil infiltration (N1 phenotype into the tumor and stimulates systemic anti-tumor immune response.

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Masayoshi Kawakubo

Full Text Available Ablative fractional photothermolysis (aFP using a CO2 laser generates multiple small diameter tissue lesions within the irradiation field. aFP is commonly used for a wide variety of dermatological indications, including treatment of photodamaged skin and dyschromia, drug delivery and modification of scars due to acne, surgical procedures and burns. In this study we explore the utility of aFP for treating oncological indications, including induction of local tumor regression and inducing anti-tumor immunity, which is in marked contrast to current indications of aFP.We used a fractional CO2 laser to treat a tumor established by BALB/c colon carcinoma cell line (CT26.CL25, which expressed a tumor antigen, beta-galactosidase (beta-gal. aFP treated tumors grew significantly slower as compared to untreated controls. Complete remission after a single aFP treatment was observed in 47% of the mice. All survival mice from the tumor inoculation rejected re-inoculation of the CT26.CL25 colon carcinoma cells and moreover 80% of the survival mice rejected CT26 wild type colon carcinoma cells, which are parental cells of CT26.CL25 cells. Histologic section of the FP-treated tumors showed infiltrating neutrophil in the tumor early after aFP treatment. Flow cytometric analysis of tumor-infiltrating lymphocytes showed aFP treatment abrogated the increase in regulatory T lymphocyte (Treg, which suppresses anti-tumor immunity and elicited the expansion of epitope-specific CD8+ T lymphocytes, which were required to mediate the tumor-suppressing effect of aFP.We have demonstrated that aFP is able to induce a systemic anti-tumor adaptive immunity preventing tumor recurrence in a murine colon carcinoma in a mouse model. This study demonstrates a potential role of aFP treatments in oncology and further studies should be performed.

Experimental study on active specific immunotherapy utilizing the immune reaction of low-dose irradiated tumor tissue, 8

International Nuclear Information System (INIS)

Imanaka, Kazufumi; Gose, Kyuhei; Ichiyanagi, Akihiro

1983-01-01

The effectiveness of active specific immunotherapy prepared from a low-dose irradiated tumor tissue has already reported. The present study was designed to investigate the effect of Mitomycin C-treated active specific immunotherapy. Twelve-week-aged female C3H/He mice transplanted with MM 46 tumors were exposed to local electron radiotherapy with a dose of 3,000 rad on the 5th day after tumor inoculation. Tumor cells prepared for active specific immunotherapy were pretreated with Mitomycin C at concentration of 20 μg/10 7 cells in Eagle MEM Earle containing 100 IU/ml penicillin. The cell suspension was incubated at 37 0 C for 15 minutes. Mitomycin C-treated active specific immunotherapy was performed on the 12th day. Antitumor effect was evaluated by the regression of the tumor and survival curve. The remarkable regression of the tumor and significant elongation of the survival period were observed in the group which received Mitomycin C-treated active specific immunotherapy and the group which received active specific immunotherapy without the treatment of Mitomycin C. (author)

Tumor size and prognosis in patients with Wilms tumor

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Valentina Oliveira Provenzi

2015-03-01

Full Text Available OBJECTIVE: Investigate the relationship of the tumor volume after preoperative chemotherapy (TVAPQ and before preoperative chemotherapy (TVBPQ with overall survival at two and at five years, and lifetime. METHODS: Our sample consisted of consecutive patients evaluated in the period from 1989 to 2009 in an Onco-Hematology Service. Clinical, histological and volumetric data were collected from the medical records. For analysis, chi-square, Kaplan-Meier, log-rank and Cox regression tests were used. RESULTS: The sample consisted of 32 patients, 53.1% were male with a median age at diagnosis of 43 months. There was a significant association between TVAPQ>500mL and the difference between the TVBPQ and TVAPQ (p=0.015 and histologic types of risk (p=0.008. It was also verified an association between the difference between the TVBPQ and TVAPQ and the predominant stromal tumor (p=0.037. When assessing the TVAPQ of all patients, without a cutoff, there was an association of the variable with lifetime (p=0.013, i.e., for each increase of 10mL in TVAPQ there was an average increase of 2% in the risk of death. CONCLUSIONS: Although our results indicate that the TVAPQ could be considered alone as a predictor of poor prognosis regardless of the cutoff suggested in the literature, more studies are needed to replace the histology and staging by tumor size as best prognostic variable.

Spontaneous regression in an ulcerated CK7 positive Merkel cell carcinoma

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Anza Khader

2015-01-01

Full Text Available Merkel cell carcinoma is an aggressive and frequently lethal tumor of the elderly, associated with sun exposure and immunosuppression which is less common in the dark-skinned. We report the case of a 40-year-old woman who presented with multiple slowly progressive, mildly itchy ulcerated plaques of size ranging from 2 × 3 cm to 5 × 7 cm on the left knee of 1 year duration. Skin biopsy showed diffuse dermal infiltration by small round cells with molding of cells and lymphocyte infiltration. The cells stained positive for cytokeratin (CK 20, CK7, neuron-specific enolase, and chromogranin. The skin lesions underwent spontaneous regression within 1 month of skin biopsy and have not recurred during the past 2 years. The immune mechanisms triggered by biopsy possibly explain the spontaneous regression.

Fetal Primary Cardiac Tumors During Perinatal Period

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Shi-Min Yuan

2017-06-01

Full Text Available Fetal primary cardiac tumors are rare, but they may cause complications, which are sometimes life threatening, including arrhythmias, hydrops fetalis, ventricular outflow/inflow obstruction, cardiac failure, and even sudden death. Among fetal primary cardiac tumors, rhabdomyomas are most common, followed by teratomas, fibromas, hemangiomas, and myxomas. Everolimus, a mammalian target of rapamycin inhibitor, has been reported to be an effective drug to cause tumor remission in three neonates with multiple cardiac rhabdomyomas. Neonatal cardiac surgery for the resection of primary cardiac tumors found by fetal echocardiography has been reported sporadically. However, open fetal surgery for pericardial teratoma resection, which was performed successfully via a fetal median sternotomy in one case report, could be a promising intervention to rescue these patients with large pericardial effusions. These recent achievements undoubtedly encourage further development in early management of fetal cardiac tumors. Owing to the rarity of fetal primary cardiac tumors, relevant information in terms of prenatal diagnosis, treatment, and prognosis remains to be clarified.

Treatment of natural mammary gland tumors in canines and felines using gold nanorods-assisted plasmonic photothermal therapy to induce tumor apoptosis.

Science.gov (United States)

Ali, Moustafa R K; Ibrahim, Ibrahim M; Ali, Hala R; Selim, Salah A; El-Sayed, Mostafa A

Plasmonic photothermal therapy (PPTT) is a cancer therapy in which gold nanorods are injected at the site of a tumor before near-infrared light is transiently applied to the tumor causing localized cell death. Previously, PPTT studies have been carried out on xenograft mice models. Herein, we report a study showing the feasibility of PPTT as applied to natural tumors in the mammary glands of dogs and cats, which more realistically represent their human equivalents at the molecular level. We optimized a regime of three low PPTT doses at 2-week intervals that ablated tumors mainly via apoptosis in 13 natural mammary gland tumors from seven animals. Histopathology, X-ray, blood profiles, and comprehensive examinations were used for both the diagnosis and the evaluation of tumor statuses before and after treatment. Histopathology results showed an obvious reduction in the cancer grade shortly after the first treatment and a complete regression after the third treatment. Blood tests showed no obvious change in liver and kidney functions. Similarly, X-ray diffraction showed no metastasis after 1 year of treatment. In conclusion, our study suggests the feasibility of applying the gold nanorods-PPTT on natural tumors in dogs and cats without any relapse or toxicity effects after 1 year of treatment.

Regression: A Bibliography.

Science.gov (United States)

Pedrini, D. T.; Pedrini, Bonnie C.

Regression, another mechanism studied by Sigmund Freud, has had much research, e.g., hypnotic regression, frustration regression, schizophrenic regression, and infra-human-animal regression (often directly related to fixation). Many investigators worked with hypnotic age regression, which has a long history, going back to Russian reflexologists.…

Combined tumor therapy

International Nuclear Information System (INIS)

Wrba, H.

1990-01-01

This comprehensive survey of current methods and achievements first takes a look at the two basic therapies, devoting a chapter each to the surgery and radiotherapy of tumors. The principal subjects of the book, however, are the systemic, adjuvant therapy, biological therapies, hyperthermia and various other therapies (as e.g. treatment with ozone, oxygen, or homeopathic means), and psychotherapy. (MG) With 54 figs., 86 tabs [de

Multitask Quantile Regression under the Transnormal Model.

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Fan, Jianqing; Xue, Lingzhou; Zou, Hui

2016-01-01

We consider estimating multi-task quantile regression under the transnormal model, with focus on high-dimensional setting. We derive a surprisingly simple closed-form solution through rank-based covariance regularization. In particular, we propose the rank-based ℓ 1 penalization with positive definite constraints for estimating sparse covariance matrices, and the rank-based banded Cholesky decomposition regularization for estimating banded precision matrices. By taking advantage of alternating direction method of multipliers, nearest correlation matrix projection is introduced that inherits sampling properties of the unprojected one. Our work combines strengths of quantile regression and rank-based covariance regularization to simultaneously deal with nonlinearity and nonnormality for high-dimensional regression. Furthermore, the proposed method strikes a good balance between robustness and efficiency, achieves the "oracle"-like convergence rate, and provides the provable prediction interval under the high-dimensional setting. The finite-sample performance of the proposed method is also examined. The performance of our proposed rank-based method is demonstrated in a real application to analyze the protein mass spectroscopy data.

[Establishment of EL4 tumor-bearing mouse models and investigation on immunological mechanisms of anti-tumor effect of melphalan].

Science.gov (United States)

Li, Mo-lin; Li, Chuan-gang; Shu, Xiao-hong; Jia, Yu-jie; Qin, Zhi-hai

2006-03-01

To establish mouse lymphoma EL4 tumor-bearing mouse models in wild type C57BL/6 mice and nude C57BL/6 mice respectively, and to further investigate the immunological mechanisms of anti-tumor effect of melphalan. Mouse lymphoma EL4 cells were inoculated subcutaneously into wild type C57BL/6 mice (immune-competent mice). Twelve days later, melphalan of different doses were administered intraperitoneally to treat these wild type C57BL/6 tuomr-bearing mice. Tumor sizes were observed and recorded subsequently to find out the minimal dose of melphalan that could cure the tuomr-bearing mice. Then the same amount of EL4 tumor cells were inoculated subcutaneously into wild type C57BL/6 mice and nude C57BL/6 mice (T cell-deficient mice) simultaneously, which had the same genetic background of C57BL/6. Twelve days later, melphalan of the minimal dose was given intraperitoneally to treat both the wild type and nude C57BL/6 tuomr-bearing mice. Tumor sizes were observed and recorded in these two different types of mice subsequently. A single dose of melphalan (7.5 mg/kg) could cure EL4 tumor-bearing wild type C57BL/6 mice, but could not induce tumor regression in EL4 tumor-bearing nude C57BL/6 mice. A single dose of melphalan has obvious anti-tumor effect on mouse lymphoma EL4 tumor-bearing wild type C57BL/6mice, which requires the involvement of T lymphocytes in the host probably related to their killing functions.

Wilms' tumor: past, present and (possibly) future.

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Spreafico, Filippo; Bellani, Franca Fossati

2006-02-01

Wilms' tumor is one of the successes of pediatric oncology, with an overall cure rate of over 85%, using relatively simple therapies. This excellent outcome has been the result of collaborative efforts among surgeons, pediatricians, pathologists and radiation oncologists. The results that have been achieved in children with Wilms' tumors support the strong value of the multidisciplinary team approach to cancer. The two largest cooperative groups that have studied the optimum treatment for Wilms' tumor are the National Wilms' Tumor Study group in North America and the International Society of Pediatric Oncology, involving European and other countries. The National Wilms' Tumor Study group recommends primary surgery before any adjuvant treatment, whereas the International Society of Pediatric Oncology trials are based on the use of preoperative chemotherapy. The debate on primary chemotherapy versus primary nephrectomy appears to have been overcome, in the sense that the advantages and disadvantages of these two diverse methods have emerged from large and well-performed clinical trials, and comparably low doses of anthracyclines and radiotherapy are now used. Challenges remain in identifying novel molecular, histological and clinical risk factors for stratification of treatment intensity. This could allow a safe reduction in therapy for patients known to have an excellent chance of cure with the current therapy, while identifying, at diagnosis, the minority of children at risk of relapse, who will necessitate more aggressive treatments. Another positive factor is the substantial progress that has been made in the cure for recurrent patients, with long-term survivals shifting from 30 to almost 60% in more recently treated patients with intensive-dose chemotherapy regimens. The combination of lower relapses and higher salvage rates translated into significantly improved overall survival for Wilms' tumor patients as a whole. This review covers current concepts on

CS2164, a novel multi-target inhibitor against tumor angiogenesis, mitosis and chronic inflammation with anti-tumor potency.

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Zhou, You; Shan, Song; Li, Zhi-Bin; Xin, Li-Jun; Pan, De-Si; Yang, Qian-Jiao; Liu, Ying-Ping; Yue, Xu-Peng; Liu, Xiao-Rong; Gao, Ji-Zhou; Zhang, Jin-Wen; Ning, Zhi-Qiang; Lu, Xian-Ping

2017-03-01

Although inhibitors targeting tumor angiogenic pathway have provided improvement for clinical treatment in patients with various solid tumors, the still very limited anti-cancer efficacy and acquired drug resistance demand new agents that may offer better clinical benefits. In the effort to find a small molecule potentially targeting several key pathways for tumor development, we designed, discovered and evaluated a novel multi-kinase inhibitor, CS2164. CS2164 inhibited the angiogenesis-related kinases (VEGFR2, VEGFR1, VEGFR3, PDGFRα and c-Kit), mitosis-related kinase Aurora B and chronic inflammation-related kinase CSF-1R in a high potency manner with the IC 50 at a single-digit nanomolar range. Consequently, CS2164 displayed anti-angiogenic activities through suppression of VEGFR/PDGFR phosphorylation, inhibition of ligand-dependent cell proliferation and capillary tube formation, and prevention of vasculature formation in tumor tissues. CS2164 also showed induction of G2/M cell cycle arrest and suppression of cell proliferation in tumor tissues through the inhibition of Aurora B-mediated H3 phosphorylation. Furthermore, CS2164 demonstrated the inhibitory effect on CSF-1R phosphorylation that led to the suppression of ligand-stimulated monocyte-to-macrophage differentiation and reduced CSF-1R + cells in tumor tissues. The in vivo animal efficacy studies revealed that CS2164 induced remarkable regression or complete inhibition of tumor growth at well-tolerated oral doses in several human tumor xenograft models. Collectively, these results indicate that CS2164 is a highly selective multi-kinase inhibitor with potent anti-tumor activities against tumor angiogenesis, mitosis and chronic inflammation, which may provide the rationale for further clinical assessment of CS2164 as a therapeutic agent in the treatment of cancer. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Advanced statistics: linear regression, part I: simple linear regression.

Science.gov (United States)

Marill, Keith A

2004-01-01

Simple linear regression is a mathematical technique used to model the relationship between a single independent predictor variable and a single dependent outcome variable. In this, the first of a two-part series exploring concepts in linear regression analysis, the four fundamental assumptions and the mechanics of simple linear regression are reviewed. The most common technique used to derive the regression line, the method of least squares, is described. The reader will be acquainted with other important concepts in simple linear regression, including: variable transformations, dummy variables, relationship to inference testing, and leverage. Simplified clinical examples with small datasets and graphic models are used to illustrate the points. This will provide a foundation for the second article in this series: a discussion of multiple linear regression, in which there are multiple predictor variables.

Tumor boards and the quality of cancer care.

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Keating, Nancy L; Landrum, Mary Beth; Lamont, Elizabeth B; Bozeman, Samuel R; Shulman, Lawrence N; McNeil, Barbara J

2013-01-16

Despite the widespread use of tumor boards, few data on their effects on cancer care exist. We assessed whether the presence of a tumor board, either general or cancer specific, was associated with recommended cancer care, outcomes, or use in the Veterans Affairs (VA) health system. We surveyed 138 VA medical centers about the presence of tumor boards and linked cancer registry and administrative data to assess receipt of stage-specific recommended care, survival, or use for patients with colorectal, lung, prostate, hematologic, and breast cancers diagnosed in the period from 2001 to 2004 and followed through 2005. We used multivariable logistic regression to assess associations of tumor boards with the measures, adjusting for patient sociodemographic and clinical characteristics. All statistical tests were two-sided. Most facilities (75%) had at least one tumor board, and many had several cancer-specific tumor boards. Presence of a tumor board was associated with only seven of 27 measures assessed (all P < .05), and several associations were not in expected directions. Rates of some recommended care (eg, white blood cell growth factors with cyclophosphamide, adriamycin, vincristine, and prednisone in diffuse large B-cell lymphoma) were lower in centers with hematologic-specialized tumor boards (39.4%) than in centers with general tumor boards (61.3%) or no tumor boards (56.4%; P = .002). Only one of 27 measures was statistically significantly associated with tumor boards after applying a Bonferroni correction for multiple comparisons. We observed little association of multidisciplinary tumor boards with measures of use, quality, or survival. This may reflect no effect or an effect that varies by structural and functional components and participants' expertise.

Predicting location of recurrence using FDG, FLT, and Cu-ATSM PET in canine sinonasal tumors treated with radiotherapy

International Nuclear Information System (INIS)

Bradshaw, Tyler; Jeraj, Robert; Fu, Rau; Zhu, Jun; Bowen, Stephen; Forrest, Lisa

2015-01-01

Dose painting relies on the ability of functional imaging to identify resistant tumor subvolumes to be targeted for additional boosting. This work assessed the ability of FDG, FLT, and Cu-ATSM PET imaging to predict the locations of residual FDG PET in canine tumors following radiotherapy. Nineteen canines with spontaneous sinonasal tumors underwent PET/CT imaging with radiotracers FDG, FLT, and Cu-ATSM prior to hypofractionated radiotherapy. Therapy consisted of 10 fractions of 4.2 Gy to the sinonasal cavity with or without an integrated boost of 0.8 Gy to the GTV. Patients had an additional FLT PET/CT scan after fraction 2, a Cu-ATSM PET/CT scan after fraction 3, and follow-up FDG PET/CT scans after radiotherapy. Following image registration, simple and multiple linear and logistic voxel regressions were performed to assess how well pre- and mid-treatment PET imaging predicted post-treatment FDG uptake. R 2 and pseudo R 2 were used to assess the goodness of fits. For simple linear regression models, regression coefficients for all pre- and mid-treatment PET images were significantly positive across the population (P < 0.05). However, there was large variability among patients in goodness of fits: R 2 ranged from 0.00 to 0.85, with a median of 0.12. Results for logistic regression models were similar. Multiple linear regression models resulted in better fits (median R 2 = 0.31), but there was still large variability between patients in R 2 . The R 2 from regression models for different predictor variables were highly correlated across patients (R ≈ 0.8), indicating tumors that were poorly predicted with one tracer were also poorly predicted by other tracers. In conclusion, the high inter-patient variability in goodness of fits indicates that PET was able to predict locations of residual tumor in some patients, but not others. This suggests not all patients would be good candidates for dose painting based on a single biological target. (paper)

Surgery of malignant pancreatic tumors

International Nuclear Information System (INIS)

Loos, M.; Friess, H.; Kleeff, J.

2009-01-01

Ductal adenocarcinoma is the most common malignant tumor of the pancreas. Despite great efforts in basic and clinical pancreatic cancer research, the prognosis remains poor with an overall 5-year survival rate of less than 5%. Complete surgical resection represents the only curative treatment option and 5-year survival rates of 20-25% can be achieved following curative resection and adjuvant chemotherapy. Although pancreatic surgery is considered one of the most technically demanding and challenging procedures, there has been constant progress in surgical techniques and advances in perioperative care with a modern interdisciplinary approach including anesthesiology, oncology, radiology and nursing. This has reduced morbidity and especially mortality rates in high-volume centers. Among extended resection procedures multivisceral and venous resections are technically feasible and should be considered if a complete tumor resection can be achieved. Multimodal regimens have shown promising results, however, only adjuvant chemotherapy is supported by solid evidence from randomized controlled trials. (orig.) [de

Prognostic value of tumor burden measurement using the number of tumors in non-surgical patients with non-small cell lung cancer

International Nuclear Information System (INIS)

Zhang, Hao; Wroblewski, Kristen; Pu, Yonglin

2012-01-01

Background: No study to test the feasibility and prognostic value of the number of primary tumors, the number of positive lymph nodes, and the total number of tumors in the whole body as tumor burden measurements on FDG PET/CT imaging has been reported. Purpose: To determine whether the number of tumors seen in 18F-FDG PET scans can be a prognostic factor in non-surgical patients with non-small cell lung cancer (NSCLC). Material and Methods: One hundred and forty patients with histologically proven NSCLC and baseline 18F-FDG PET scan before therapy were identified in this retrospective analysis. The total number of tumors (TTn) in the whole body, the number of primary tumors (Tn), positive lymph nodes (Nn), and distant metastases (Mn), along with the maximum standardized uptake values (SUVmax) of the tumors were measured. Inter-observer variability of the total number of tumors, counted by two radiologists, was assessed. Survival analyses were performed to determine the prognostic value of the number of tumors. Results: Concordance correlation coefficients for the TTn, Tn, Nn, and Mn were all greater than 0.85. TTn and Nn were strong prognostic factors of NSCLC patients' overall survival (OS). In univariate Cox regression models, gender, stage, TTn, Nn, and Mn were statistically significant factors (P = 0.016, 0.032, 4. Conclusion: Measuring the number of tumors on FDG PET imaging is easy to perform with minimal inter-observer variability. The total number of tumors and number of nodal metastases, as metabolic tumor burden measurements in 18F-FDG PET/CT, are prognostic markers independent of clinical stage, age, gender, and SUV measurement in non-surgical patients with NSCLC

Breast mass detection in mammography and tomosynthesis via fully convolutional network-based heatmap regression

Science.gov (United States)

Zhang, Jun; Cain, Elizabeth Hope; Saha, Ashirbani; Zhu, Zhe; Mazurowski, Maciej A.

2018-02-01

Breast mass detection in mammography and digital breast tomosynthesis (DBT) is an essential step in computerized breast cancer analysis. Deep learning-based methods incorporate feature extraction and model learning into a unified framework and have achieved impressive performance in various medical applications (e.g., disease diagnosis, tumor detection, and landmark detection). However, these methods require large-scale accurately annotated data. Unfortunately, it is challenging to get precise annotations of breast masses. To address this issue, we propose a fully convolutional network (FCN) based heatmap regression method for breast mass detection, using only weakly annotated mass regions in mammography images. Specifically, we first generate heat maps of masses based on human-annotated rough regions for breast masses. We then develop an FCN model for end-to-end heatmap regression with an F-score loss function, where the mammography images are regarded as the input and heatmaps for breast masses are used as the output. Finally, the probability map of mass locations can be estimated with the trained model. Experimental results on a mammography dataset with 439 subjects demonstrate the effectiveness of our method. Furthermore, we evaluate whether we can use mammography data to improve detection models for DBT, since mammography shares similar structure with tomosynthesis. We propose a transfer learning strategy by fine-tuning the learned FCN model from mammography images. We test this approach on a small tomosynthesis dataset with only 40 subjects, and we show an improvement in the detection performance as compared to training the model from scratch.

N-end rule pathway inhibition assists colon tumor regression via necroptosis

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Pritha Agarwalla

2016-01-01

Full Text Available Recent study has shown that N-end rule pathway, an ubiquitin dependent proteolytic system, counteracts cell death by degrading many antisurvival protein fragments like BCLxL, BRCA1, RIPK1, etc. Inhibition of the N-end rule pathway can lead to metabolic stabilization of proapoptotic protein fragments like RIPK1, thereby sensitizing cells to programmed cell death. Receptor interacting serine-threonine protein kinase-1 (RIPK1 is one of the upstream regulators of programmed necrosis known as necroptosis. Necroptosis is particularly gaining attention of cancer biologists as it provides an alternate therapeutic modality to kill cancer cells, which often evolve multiple strategies to circumvent growth inhibition by apoptosis. Utilizing the over expression of biotin receptor in cancer cells, herein, we report that coadministration of synthetic hetero-bivalent N-end rule inhibitor RFC11 and anticancer drug shikonin solubilized in a stable biotin receptor-targeted liposome exhibited significant synergistic antitumor effect in both subcutaneous and orthotopic mouse colon tumor model through induction of necroptosis with distinctive upregulation of RIPK1. Besides developing a newly targeted formulation for necroptosis induction, this report is the first in vivo evidence demonstrating that potent inhibition of N-end rule pathway can enhance therapeutic efficacy of conventional chemotherapeutics.

Targeted drug delivery and penetration into solid tumors.

Science.gov (United States)

Corti, Angelo; Pastorino, Fabio; Curnis, Flavio; Arap, Wadih; Ponzoni, Mirco; Pasqualini, Renata

2012-09-01

Delivery and penetration of chemotherapeutic drugs into tumors are limited by a number of factors related to abnormal vasculature and altered stroma composition in neoplastic tissues. Coupling of chemotherapeutic drugs with tumor vasculature-homing peptides or administration of drugs in combination with biological agents that affect the integrity of the endothelial lining of tumor vasculature is an appealing strategy to improve drug delivery to tumor cells. Promising approaches to achieve this goal are based on the use of Asn-Gly-Arg (NGR)-containing peptides as ligands for drug delivery and of NGR-TNF, a peptide-tumor necrosis factor-α fusion protein that selectively alters drug penetration barriers and that is currently tested in a randomized Phase III trial in patients with malignant pleural mesothelioma. © 2011 Wiley Periodicals, Inc.

Quality of life and performance status in patients with pancreatic and periampullary tumors

International Nuclear Information System (INIS)

Velanovich, V.; Wollner, I.

2011-01-01

The background of this study was to determine if pretreatment quality of life is associated with performance status in patients with pancreatic and periampullary tumors. Eighty consecutive patients evaluated for surgical treatment of pancreatic or periampullary tumors completed the social functioning SF-36, a generic quality of life instrument. This instrument measures 8 domains of quality of life: physical functioning (PF), role-physical (RP), role-emotional, bodily pain, vitality, mental health, social functioning, and general health (GH). The best possible score is 100 and the worst possible score is 0. Each patient was then assigned a Karnofsky performance score (KPS), with the best possible score of 100 (normal, no complaints, no evidence of disease) and worst score of 0 (dead). Data recorded included age, gender, pathology, stage, resection, use of chemotherapy, and radiation therapy. Statistical analysis was done using single and multiple linear regression analysis, correlation coefficients (r) and coefficient of determination (r 2 ). KPS was significantly associated with all domains of the SF-36 by single linear regression. By multiple linear regression, KPS was significantly associated with the PF domain (p 2 values) suggest that there are additional factors determining both quality of life and performance status in patients with pancreatic and periampullary tumors. (author)

Radioguided surgery with MIBI in brain tumors: on the subject of a case

International Nuclear Information System (INIS)

Martín Escuela, Juan Miguel

2016-01-01

Many efforts are directed towards better intraoperative detection and delimitation of brain tumors, in order to achieve better resection. A recent technique, implemented is radioguided surgery in which the tumor tissue is marked with a radiotracer (MIBI) and through the use of a probe and / or gamma camera to differentiate it from healthy brain tissue, in vivo, in the surgery room. : Evaluate the feasibility of radioguided surgery and optimize the procedures with the purpose of developing a clinical protocol for the reception of brain tumors. MATERIALS AND METHODS: A patient with a high grade glioma was submitted to MIBI, confirming that gamma camera facilitated the intraoperative detection of the tumor and indicated a small piece of residual tumor that was subsequently resected, Achieving total resection of the lesion. Conclusion: Radio-guided surgery with MIBI, showed, in this case, that it is a safe and reliable technique, not only for the detection and delimitation of brain tumors, but also for confirmation of presence or absence of residual tumor, facilitating total resection of the lesion.

Multiple Imputation of a Randomly Censored Covariate Improves Logistic Regression Analysis.

Science.gov (United States)

Atem, Folefac D; Qian, Jing; Maye, Jacqueline E; Johnson, Keith A; Betensky, Rebecca A

2016-01-01

Randomly censored covariates arise frequently in epidemiologic studies. The most commonly used methods, including complete case and single imputation or substitution, suffer from inefficiency and bias. They make strong parametric assumptions or they consider limit of detection censoring only. We employ multiple imputation, in conjunction with semi-parametric modeling of the censored covariate, to overcome these shortcomings and to facilitate robust estimation. We develop a multiple imputation approach for randomly censored covariates within the framework of a logistic regression model. We use the non-parametric estimate of the covariate distribution or the semiparametric Cox model estimate in the presence of additional covariates in the model. We evaluate this procedure in simulations, and compare its operating characteristics to those from the complete case analysis and a survival regression approach. We apply the procedures to an Alzheimer's study of the association between amyloid positivity and maternal age of onset of dementia. Multiple imputation achieves lower standard errors and higher power than the complete case approach under heavy and moderate censoring and is comparable under light censoring. The survival regression approach achieves the highest power among all procedures, but does not produce interpretable estimates of association. Multiple imputation offers a favorable alternative to complete case analysis and ad hoc substitution methods in the presence of randomly censored covariates within the framework of logistic regression.

Selective anti-tumor activity of the novel fluoropyrimidine polymer F10 towards G48a orthotopic GBM tumors.

Science.gov (United States)

Gmeiner, William H; Lema-Tome, Carla; Gibo, Denise; Jennings-Gee, Jamie; Milligan, Carol; Debinski, Waldemar

2014-02-01

F10 is a novel anti-tumor agent with minimal systemic toxicity in vivo and which displays strong cytotoxicity towards glioblastoma (GBM) cells in vitro. Here we investigate the cytotoxicity of F10 towards GBM cells and evaluate the anti-tumor activity of locally-administered F10 towards an orthotopic xenograft model of GBM. The effects of F10 on thymidylate synthase (TS) inhibition and Topoisomerase 1 (Top1) cleavage complex formation were evaluated using TS activity assays and in vivo complex of enzyme bioassays. Cytotoxicity of F10 towards normal brain was evaluated using cortices from embryonic (day 18) mice. F10 displays minimal penetrance of the blood-brain barrier and was delivered by intra-cerebral (i.c.) administration and prospective anti-tumor response towards luciferase-expressing G48a human GBM tumors in nude mice was evaluated using IVIS imaging. Histological examination of tumor and normal brain tissue was used to assess the selectivity of anti-tumor activity. F10 is cytotoxic towards G48a, SNB-19, and U-251 MG GBM cells through dual targeting of TS and Top1. F10 is not toxic to murine primary neuronal cultures. F10 is well-tolerated upon i.c. administration and induces significant regression of G48a tumors that is dose-dependent. Histological analysis from F10-treated mice revealed tumors were essentially completely eradicated in F10-treated mice while vehicle-treated mice displayed substantial infiltration into normal tissue. F10 displays strong efficacy for GBM treatment with minimal toxicity upon i.c. administration establishing F10 as a promising drug-candidate for treating GBM in human patients.

Design of radiation dose tumor response assays

International Nuclear Information System (INIS)

Suit, H.D.; Hwang, T.; Hsieh, C.; Thames, H.

1985-01-01

The efficient utilization of animals in a radiation dose response assay for tumor control requires a definition of the goal, e.g., TCD50 or slope. A series of computer modelled ''experiments'' have been performed for each of a number of allocations of dose levels (DL) and number of animals/DL. The authors stipulated that the assumed TCD50 was .85 of true value; assumed slope was correct. They stipulated a binominal distribution of observed tumor control results at each dose level. A pilot assay used 6 tumors at 7 DL (from TCD1-TCD97). The second assay used 30 tumors assigned to 2,3,5 or 9 DL and to selected tumor control probabilities (TCP derived from the pilot run. Results from 100 test runs were combined with the pilot run for each of the combination of DL and TCP values. Logit regression lines were fitted through these ''data'' and the 95% CL around the TCD50 and the TCD37 values and the variances of the slopes were computed. These experiments were repeated using the method suggested by Porter (1980). Results show that a different strategy is needed depending upon the goal, viz. TCD50 or TCD37 vs slope. The differences between the two approaches are discussed

Determinants of successful CD8+ T-cell adoptive immunotherapy for large established tumors in mice.

Science.gov (United States)

Klebanoff, Christopher A; Gattinoni, Luca; Palmer, Douglas C; Muranski, Pawel; Ji, Yun; Hinrichs, Christian S; Borman, Zachary A; Kerkar, Sid P; Scott, Christopher D; Finkelstein, Steven E; Rosenberg, Steven A; Restifo, Nicholas P

2011-08-15

Adoptive cell transfer (ACT) of tumor infiltrating or genetically engineered T cells can cause durable responses in patients with metastatic cancer. Multiple clinically modifiable parameters can comprise this therapy, including cell dose and phenotype, in vivo antigen restimulation, and common gamma-chain (γ(c)) cytokine support. However, the relative contributions of each these individual components to the magnitude of the antitumor response have yet to be quantified. To systematically and quantitatively appraise each of these variables, we employed the Pmel-1 mouse model treating large, established B16 melanoma tumors. In addition to cell dose and magnitude of in vivo antigen restimulation, we also evaluated the relative efficacy of central memory (T(CM)), effector memory (T(EM)), and stem cell memory (T(SCM)) subsets on the strength of tumor regression as well as the dose and type of clinically available γ(c) cytokines, including IL-2, IL-7, IL-15, and IL-21. We found that cell dose, T-cell differentiation status, and viral vaccine titer each were correlated strongly and significantly with the magnitude of tumor regression. Surprisingly, although the total number of IL-2 doses was correlated with tumor regression, no significant benefit to prolonged (≥6 doses) administration was observed. Moreover, the specific type and dose of γ(c) cytokine only moderately correlated with response. Collectively, these findings elucidate some of the key determinants of successful ACT immunotherapy for the treatment of cancer in mice and further show that γ(c) cytokines offer a similar ability to effectively drive antitumor T-cell function in vivo. ©2011 AACR.

Spontaneous regression of multiple pulmonary metastatic nodules of hepatocarcinoma: a case report

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Bahk, Yong Whee; Park, Seog Hee; Kim, Sun Moo [St. Mary' s Hospital, Catholic Medical College, Seoul (Korea, Republic of)

1981-09-15

Although are spontaneous regression of either primary or metastatic malignant tumor in the absence of or inadequate therapy has been well documented. Since the earliest day of this century various malignant tumors have been reported to spontaneously disappear or to be arrested of their growth, but the cases of hepatocarcinoma has been very rare. From the literature, we were able to find out 5 previously reported cases of hepatocarcinoma which showed spontaneous regression at the primary site. Recently we have seen a case of multiple pulmonary metastatic nodules of hepatocarcinoma which completely regressed spontaneously and this forms the basis of the present case report. The patient was 55-year-old male admitted to St. Mary's Hospital, Catholic Medical College because of a hard palpable mass in the epigastrium on April 26, 1978. The admission PA chest roentgenogram revealed multiple small nodular densities scattered throughout both lung field especially in lower zones and toward the peripheral portion. A hepatoscintigram revealed a large cold area involving the left lobe and inermediate zone of the liver. Alfa-fetoprotein and hepatitis B serum antigen test were positive whereas many other standard liver function tests turned out to be negative. A needle biopsy of the tumor revealed well differentiated hepatocellular carcinoma. The patient was put under chemotherapy which consisted of 5 FU 500 mg intravenously for 6 days from April 28 to May 3, 1978. The patient was discharged after this single course of 5 FU treatment and was on a herb medicine, the nature and quantity of which obscure. No other specific treatment was given. The second admission took place on Dec. 3, 1980 because of irregularity in bowel habits and dyspepsia. A follow up PA chest roentgenogram obtained on the second admission revealed complete disappearance of previously noted multiple pulmonary nodular lesions (Fig. 3). Follow up liver scan revealed persistence of the cold area in the left lobe

Spontaneous regression of multiple pulmonary metastatic nodules of hepatocarcinoma: a case report

International Nuclear Information System (INIS)

Bahk, Yong Whee; Park, Seog Hee; Kim, Sun Moo

1981-01-01

Although are spontaneous regression of either primary or metastatic malignant tumor in the absence of or inadequate therapy has been well documented. Since the earliest day of this century various malignant tumors have been reported to spontaneously disappear or to be arrested of their growth, but the cases of hepatocarcinoma has been very rare. From the literature, we were able to find out 5 previously reported cases of hepatocarcinoma which showed spontaneous regression at the primary site. Recently we have seen a case of multiple pulmonary metastatic nodules of hepatocarcinoma which completely regressed spontaneously and this forms the basis of the present case report. The patient was 55-year-old male admitted to St. Mary's Hospital, Catholic Medical College because of a hard palpable mass in the epigastrium on April 26, 1978. The admission PA chest roentgenogram revealed multiple small nodular densities scattered throughout both lung field especially in lower zones and toward the peripheral portion. A hepatoscintigram revealed a large cold area involving the left lobe and inermediate zone of the liver. Alfa-fetoprotein and hepatitis B serum antigen test were positive whereas many other standard liver function tests turned out to be negative. A needle biopsy of the tumor revealed well differentiated hepatocellular carcinoma. The patient was put under chemotherapy which consisted of 5 FU 500 mg intravenously for 6 days from April 28 to May 3, 1978. The patient was discharged after this single course of 5 FU treatment and was on a herb medicine, the nature and quantity of which obscure. No other specific treatment was given. The second admission took place on Dec. 3, 1980 because of irregularity in bowel habits and dyspepsia. A follow up PA chest roentgenogram obtained on the second admission revealed complete disappearance of previously noted multiple pulmonary nodular lesions (Fig. 3). Follow up liver scan revealed persistence of the cold area in the left lobe

Enhancement of 67Ga tumor-to-blood ratios by chelating agent

International Nuclear Information System (INIS)

Saji, Hideo; Yokoyama, Akira; Hata, Naotaka; Misaki, Atsushi; Tanaka, Hisashi.

1980-01-01

Chelating agent, such as, CaEDTA, CaDTPA, D-penicillamine, DMSA, desferoxamine, NTA, cysteine ethyl ester, BAL, α-MPG, phthalein complexone, were tested as a possible contrast enhancing agent for tumor imaging with 67 Ga-citrate. The intravenous administration of a chelating agent to Ehrlich's tumor bearing mice, one hour after the injection of 67 Ga-citrate, accelerated the blood clearance with only a very slight change of activity in the target, increasing the tumor-to-blood ratio, and consequently achieving a better visualization. Among the tested chelating agents, D-penicillamine showed the highest target-to-nontarget ratio at a shorter time: a good tumor-to-blood ratio, performed after 24 hr with non-treated animals, was achieved in only 1-3 hr with post-treated animals. Thus, D-penicillamine hold a considerable promise as a contrast enhancing agent for future clinical use. (author)

Tumor tracking and motion compensation with an adaptive tumor tracking system (ATTS): System description and prototype testing

International Nuclear Information System (INIS)

Wilbert, Juergen; Meyer, Juergen; Baier, Kurt; Guckenberger, Matthias; Herrmann, Christian; Hess, Robin; Janka, Christian; Ma Lei; Mersebach, Torben; Richter, Anne; Roth, Michael; Schilling, Klaus; Flentje, Michael

2008-01-01

A novel system for real-time tumor tracking and motion compensation with a robotic HexaPOD treatment couch is described. The approach is based on continuous tracking of the tumor motion in portal images without implanted fiducial markers, using the therapeutic megavoltage beam, and tracking of abdominal breathing motion with optical markers. Based on the two independently acquired data sets the table movements for motion compensation are calculated. The principle of operation of the entire prototype system is detailed first. In the second part the performance of the HexaPOD couch was investigated with a robotic four-dimensional-phantom capable of simulating real patient tumor trajectories in three-dimensional space. The performance and limitations of the HexaPOD table and the control system were characterized in terms of its dynamic behavior. The maximum speed and acceleration of the HexaPOD were 8 mm/s and 34.5 mm/s 2 in the lateral direction, and 9.5 mm/s and 29.5 mm/s 2 in longitudinal and anterior-posterior direction, respectively. Base line drifts of the mean tumor position of realistic lung tumor trajectories could be fully compensated. For continuous tumor tracking and motion compensation a reduction of tumor motion up to 68% of the original amplitude was achieved. In conclusion, this study demonstrated that it is technically feasible to compensate breathing induced tumor motion in the lung with the adaptive tumor tracking system

Photodynamic therapy (PDT) of malignant tumors by photosensitzer photosens: results of 45 clinical cases

Science.gov (United States)

Sokolov, Victor V.; Chissov, Valery I.; Yakubovskaya, Raisa I.; Aristarkhova, E. I.; Filonenko, E. V.; Belous, T. A.; Vorozhtsov, Georgy N.; Zharkova, Natalia N.; Smirnov, V. V.; Zhitkova, Margarita B.

1996-01-01

Photosensitizer Photosens is a mixture of sulphonated Al-phthalocyanines with a different number of substituents per phthalocyanine molecule. In the beginning of 1994, this photosensitizer was approved for clinical trials. Since that time till May 1995, 45 patients with 120 tumors were treated by PDT-Photosens. The main tumor localizations were lung (5/6), head and neck (4/4), esophagus (8/8), stomach (2/2), vulva (2/2), bladder (1/1), breast cancer (3/3), skin (basalioma, melanoma, sarcoma Kaposi, mts breast cancer) (20 patients/94 tumors). The lesions were photoirradiated 48-72 h after intravenous injection of Photosens in doses from 0.5 to 2.0 mg/kg b.w. (1.0 mg/kg b.w., on average). PDT was performed by laser power density from 20 to 1400 mW/sq cm (300 mW/sq.cm, on average), energy density varying from 15 to 200 J/sq cm (100 J/sq.cm, on average). The therapeutical effect of PDT was evaluated histologically, endoscopically, roentgenologically and sonographically 3 - 4 weeks after the treatment. Complete regression of tumors was reached in 56%, significant remission was reached in 34%, and partial remission was observed in 10% of cases. The follow-up of patients with complete tumor regression was to 15 months.

Ordinary least square regression, orthogonal regression, geometric mean regression and their applications in aerosol science

International Nuclear Information System (INIS)

Leng Ling; Zhang Tianyi; Kleinman, Lawrence; Zhu Wei

2007-01-01

Regression analysis, especially the ordinary least squares method which assumes that errors are confined to the dependent variable, has seen a fair share of its applications in aerosol science. The ordinary least squares approach, however, could be problematic due to the fact that atmospheric data often does not lend itself to calling one variable independent and the other dependent. Errors often exist for both measurements. In this work, we examine two regression approaches available to accommodate this situation. They are orthogonal regression and geometric mean regression. Comparisons are made theoretically as well as numerically through an aerosol study examining whether the ratio of organic aerosol to CO would change with age

Accelerated regression of brain metastases in patients receiving whole brain radiation and the topoisomerase II inhibitor, lucanthone

International Nuclear Information System (INIS)

Rowe, John D. del; Bello, Jacqueline; Mitnick, Robin; Sood, Brij; Filippi, Christopher; Moran, Justin Ph.D.; Freeman, Katherine; Mendez, Frances; Bases, Robert

1999-01-01

Purpose: To determine if lucanthone crossed the blood-brain barrier in experimental animals; and to determine accelerated tumor regression of human brain metastases treated jointly with lucanthone and whole brain radiation. Methods and Materials: The organ distribution of 3 H lucanthone in mice and 125 I lucanthone in rats was determined to learn if lucanthone crossed the blood-brain barrier. Size determinations were made of patients' brain metastases from magnetic resonance images or by computed tomography before and after treatment with 30 Gy whole brain radiation alone or with lucanthone. Results: The time course of lucanthone's distribution in brain was identical to that in muscle and heart after intraperitoneal or intravenous administration in experimental animals. Lucanthone, therefore, readily crossed the blood-brain barrier in experimental animals. Conclusion: Compared with radiation alone, the tumor regression in patients with brain metastases treated with lucanthone and radiation was accelerated, approaching significance using a permutation test at p = 0.0536

Development of an acellular tumor extracellular matrix as a three-dimensional scaffold for tumor engineering.

Directory of Open Access Journals (Sweden)

Wei-Dong Lü

Full Text Available Tumor engineering is defined as the construction of three-dimensional (3D tumors in vitro with tissue engineering approaches. The present 3D scaffolds for tumor engineering have several limitations in terms of structure and function. To get an ideal 3D scaffold for tumor culture, A549 human pulmonary adenocarcinoma cells were implanted into immunodeficient mice to establish xenotransplatation models. Tumors were retrieved at 30-day implantation and sliced into sheets. They were subsequently decellularized by four procedures. Two decellularization methods, Tris-Trypsin-Triton multi-step treatment and sodium dodecyl sulfate (SDS treatment, achieved complete cellular removal and thus were chosen for evaluation of histological and biochemical properties. Native tumor tissues were used as controls. Human breast cancer MCF-7 cells were cultured onto the two 3D scaffolds for further cell growth and growth factor secretion investigations, with the two-dimensional (2D culture and cells cultured onto the Matrigel scaffolds used as controls. Results showed that Tris-Trypsin-Triton multi-step treated tumor sheets had well-preserved extracellular matrix structures and components. Their porosity was increased but elastic modulus was decreased compared with the native tumor samples. They supported MCF-7 cell repopulation and proliferation, as well as expression of growth factors. When cultured within the Tris-Trypsin-Triton treated scaffold, A549 cells and human colorectal adenocarcinoma cells (SW-480 had similar behaviors to MCF-7 cells, but human esophageal squamous cell carcinoma cells (KYSE-510 had a relatively slow cell repopulation rate. This study provides evidence that Tris-Trypsin-Triton treated acellular tumor extracellular matrices are promising 3D scaffolds with ideal spatial arrangement, biomechanical properties and biocompatibility for improved modeling of 3D tumor microenvironments.

Theory of Regression Apple Professional Cooperation Organization Research

OpenAIRE

Ouyang Bin

2013-01-01

In view of the enterprise ecological apple manor a variety of problems of existence, put forward to the enterprise management transformation, achieve enterprise, collective, individual integrated operation management and the use of regression mathematical model on apple professional cooperation organization analysis. Through the example, Apple professional economic cooperation organization innovation model of the input output ratio than the rural economic cooperation organization is much high...

Linear regression methods a ccording to objective functions

OpenAIRE

Yasemin Sisman; Sebahattin Bektas

2012-01-01

The aim of the study is to explain the parameter estimation methods and the regression analysis. The simple linear regressionmethods grouped according to the objective function are introduced. The numerical solution is achieved for the simple linear regressionmethods according to objective function of Least Squares and theLeast Absolute Value adjustment methods. The success of the appliedmethods is analyzed using their objective function values.

Assessment of perfusion by dynamic contrast-enhanced imaging using a deconvolution approach based on regression and singular value decomposition.

Science.gov (United States)

Koh, T S; Wu, X Y; Cheong, L H; Lim, C C T

2004-12-01

The assessment of tissue perfusion by dynamic contrast-enhanced (DCE) imaging involves a deconvolution process. For analysis of DCE imaging data, we implemented a regression approach to select appropriate regularization parameters for deconvolution using the standard and generalized singular value decomposition methods. Monte Carlo simulation experiments were carried out to study the performance and to compare with other existing methods used for deconvolution analysis of DCE imaging data. The present approach is found to be robust and reliable at the levels of noise commonly encountered in DCE imaging, and for different models of the underlying tissue vasculature. The advantages of the present method, as compared with previous methods, include its efficiency of computation, ability to achieve adequate regularization to reproduce less noisy solutions, and that it does not require prior knowledge of the noise condition. The proposed method is applied on actual patient study cases with brain tumors and ischemic stroke, to illustrate its applicability as a clinical tool for diagnosis and assessment of treatment response.

Visual grading characteristics and ordinal regression analysis during optimisation of CT head examinations.

Science.gov (United States)

Zarb, Francis; McEntee, Mark F; Rainford, Louise

2015-06-01

To evaluate visual grading characteristics (VGC) and ordinal regression analysis during head CT optimisation as a potential alternative to visual grading assessment (VGA), traditionally employed to score anatomical visualisation. Patient images (n = 66) were obtained using current and optimised imaging protocols from two CT suites: a 16-slice scanner at the national Maltese centre for trauma and a 64-slice scanner in a private centre. Local resident radiologists (n = 6) performed VGA followed by VGC and ordinal regression analysis. VGC alone indicated that optimised protocols had similar image quality as current protocols. Ordinal logistic regression analysis provided an in-depth evaluation, criterion by criterion allowing the selective implementation of the protocols. The local radiology review panel supported the implementation of optimised protocols for brain CT examinations (including trauma) in one centre, achieving radiation dose reductions ranging from 24 % to 36 %. In the second centre a 29 % reduction in radiation dose was achieved for follow-up cases. The combined use of VGC and ordinal logistic regression analysis led to clinical decisions being taken on the implementation of the optimised protocols. This improved method of image quality analysis provided the evidence to support imaging protocol optimisation, resulting in significant radiation dose savings. • There is need for scientifically based image quality evaluation during CT optimisation. • VGC and ordinal regression analysis in combination led to better informed clinical decisions. • VGC and ordinal regression analysis led to dose reductions without compromising diagnostic efficacy.

The Impact of Induction Chemotherapy and the Associated Tumor Response on Subsequent Radiation-Related Changes in Lung Function and Tumor Response

International Nuclear Information System (INIS)

Mao Jingfang; Kocak, Zafer; Zhou Sumin; Garst, Jennifer; Evans, Elizabeth S.; Zhang Junan; Larrier, Nicole A.; Hollis, Donna R.; Folz, Rodney J.; Marks, Lawrence B.

2007-01-01

Purpose: To assess the impact of induction chemotherapy, and associated tumor shrinkage, on the subsequent radiation-related changes in pulmonary function and tumor response. Methods and Materials: As part of a prospective institutional review board-approved study, 91 evaluable patients treated definitively with thoracic radiation therapy (RT) for unresectable lung cancer were analyzed. The rates of RT-associated pulmonary toxicity and tumor response were compared in the patients with and without pre-RT chemotherapy. In the patients receiving induction chemotherapy, the rates of RT-associated pulmonary toxicity and tumor response were compared in the patients with and without a response (modified Response Evaluation Criteria in Solid Tumor criteria) to the pre-RT chemotherapy. Comparisons of the rates of improvements in pulmonary function tests (PFTs) post-RT, dyspnea requiring steroids, and percent declines in PFTs post-RT were compared in patient subgroups using Fisher's exact test, analysis of variance, and linear or logistic regression. Results: The use of pre-RT chemotherapy appears to increase the rate of radiation-induced pneumonitis (p = 0.009-0.07), but has no consistent impact on changes in PFTs. The degree of induction chemotherapy-associated tumor shrinkage is not associated with the rate of subsequent RT-associated pulmonary toxicity. The degree of tumor response to chemotherapy is not related to the degree of tumor response to RT. Conclusions: Additional study is needed to better clarify the impact of chemotherapy on radiation-associated disfunction

Value of gamma knife radiosurgery for tumors invading cavernous sinus

International Nuclear Information System (INIS)

Jokura, Hidefumi; Yoshimoto, Takashi

1999-01-01

The usefulness of radiosurgery for cavernous sinus tumors was evaluated based on our experience and recent published reports from other institutes. Twenty-six meningiomas involving the cavernous sinus were treated by radiosurgery. The length of follow-up average 3 years. Tumors regressed in 40% and remained stable in 56% of cases. A total of 96% of the tumors were controlled with only a few minor complications. We believe surgical resection to reduce the volume of the tumor without causing new neurological deficits, followed by radiosurgery on the tumor located in the cavernous sinus is the best choice in many cases. Twenty-five pituitary adenomas with cavernous sinus invasion were treated by a combination of transsphenoidal removal and radiosurgery. All the tumors are controlled in terms of volume during the follow-up (average of 34 months). There were no new neurological deficits, including visual disturbance. Hormone elevation was able to be corrected at an early stage without pituitary insufficiency more by radiosurgery than by fractionated radiation. However, to obtain good results by radiosurgery, it must be preceded by complete surgical decompression of optic nerves and chiasma from the tumor. (author)

Detection of brain tumor margins using optical coherence tomography

Science.gov (United States)

Juarez-Chambi, Ronald M.; Kut, Carmen; Rico-Jimenez, Jesus; Campos-Delgado, Daniel U.; Quinones-Hinojosa, Alfredo; Li, Xingde; Jo, Javier

2018-02-01

In brain cancer surgery, it is critical to achieve extensive resection without compromising adjacent healthy, non-cancerous regions. Various technological advances have made major contributions in imaging, including intraoperative magnetic imaging (MRI) and computed tomography (CT). However, these technologies have pros and cons in providing quantitative, real-time and three-dimensional (3D) continuous guidance in brain cancer detection. Optical Coherence Tomography (OCT) is a non-invasive, label-free, cost-effective technique capable of imaging tissue in three dimensions and real time. The purpose of this study is to reliably and efficiently discriminate between non-cancer and cancer-infiltrated brain regions using OCT images. To this end, a mathematical model for quantitative evaluation known as the Blind End- Member and Abundances Extraction method (BEAE). This BEAE method is a constrained optimization technique which extracts spatial information from volumetric OCT images. Using this novel method, we are able to discriminate between cancerous and non-cancerous tissues and using logistic regression as a classifier for automatic brain tumor margin detection. Using this technique, we are able to achieve excellent performance using an extensive cross-validation of the training dataset (sensitivity 92.91% and specificity 98.15%) and again using an independent, blinded validation dataset (sensitivity 92.91% and specificity 86.36%). In summary, BEAE is well-suited to differentiate brain tissue which could support the guiding surgery process for tissue resection.

A Percutaneous Transtubular Middle Fossa Approach for Intracanalicular Tumors.

Science.gov (United States)

Bernardo, Antonio; Evins, Alexander I; Tsiouris, Apostolos J; Stieg, Philip E

2015-07-01

In cases of small intracanalicular tumors (≤ 1.5 cm), the middle fossa approach (MFA) provides the ability for adequate tumor removal with preservation of existing auditory function. Application of a minimally invasive tubular retractor in this approach may help mitigate the risk of postoperative seizures, aphasia, and venous complications by minimizing intraoperative retraction of the temporal lobe. We propose a minimally invasive microscopic and/or endoscopic percutaneous transtubular MFA for the management of intracanalicular tumors. Subtemporal keyhole craniectomies were performed on 5 preserved cadaveric heads (10 sides), with 6 sides previously injected with a synthetic tumor model. A ViewSite Brain Access System tubular retractor (Vycor Medical, Inc., Boca Raton, Florida, USA) was used to provide minimal temporal retraction and protection of the surrounding anatomy. An extradural dissection of the internal auditory canal was performed under microscopic and endoscopic visualization with a minimally invasive surgical drill and tube shaft instruments, the intracanalicular tumors were removed, and degree of resection was assessed. All 10 approaches were completed successfully through the tubular retractor with minimal retraction of the temporal lobe. Excellent visualization of the structures within the internal auditory canal was achieved with both the microscope and 3-dimensional endoscope. On the 6 synthetic intracanalicular tumors resected, 5 gross total (Grade I) and 1 near total (Grade II) resections were achieved. A percutaneous transtubular MFA is a feasible minimally invasive option for resection of small intracanalicular tumors with potential preservation of auditory function, reduced temporal retraction, and enhanced protection of surrounding structures. Copyright © 2015 Elsevier Inc. All rights reserved.

A Solution to Separation and Multicollinearity in Multiple Logistic Regression.

Science.gov (United States)

Shen, Jianzhao; Gao, Sujuan

2008-10-01

In dementia screening tests, item selection for shortening an existing screening test can be achieved using multiple logistic regression. However, maximum likelihood estimates for such logistic regression models often experience serious bias or even non-existence because of separation and multicollinearity problems resulting from a large number of highly correlated items. Firth (1993, Biometrika, 80(1), 27-38) proposed a penalized likelihood estimator for generalized linear models and it was shown to reduce bias and the non-existence problems. The ridge regression has been used in logistic regression to stabilize the estimates in cases of multicollinearity. However, neither solves the problems for each other. In this paper, we propose a double penalized maximum likelihood estimator combining Firth's penalized likelihood equation with a ridge parameter. We present a simulation study evaluating the empirical performance of the double penalized likelihood estimator in small to moderate sample sizes. We demonstrate the proposed approach using a current screening data from a community-based dementia study.

Polynomial regression analysis and significance test of the regression function

International Nuclear Information System (INIS)

Gao Zhengming; Zhao Juan; He Shengping

2012-01-01

In order to analyze the decay heating power of a certain radioactive isotope per kilogram with polynomial regression method, the paper firstly demonstrated the broad usage of polynomial function and deduced its parameters with ordinary least squares estimate. Then significance test method of polynomial regression function is derived considering the similarity between the polynomial regression model and the multivariable linear regression model. Finally, polynomial regression analysis and significance test of the polynomial function are done to the decay heating power of the iso tope per kilogram in accord with the authors' real work. (authors)

Diagnostic radiation and its prognosis of pineal region tumor

International Nuclear Information System (INIS)

Momose, Toshimitsu; Aoki, Yukimasa; Akanuma, Atsuo; Machida, Tohru; Iio, Masahiro; Takakura, Kimitomo

1984-01-01

20 Gy of local irradiation was performed for the patients with pineal region tumor. We evaluated the tumor volume on X-CT in the pre-radiation and 20 Gy of post-radiation state. If tumor is sensitive enough to radiation therapy, we add 40 Gy of whole brain and 30 to 40 Gy of whole spine irradiation. If not, we transfer patients to neurosurgeons for the purpose of tumor ressection. We call this procedure ''Diagnostic Radiation.'' We proposed the concept of TRR (Tumor Regression Ratio) in order to evaluate our protocol more objctively. TRR is as follows: TRR (%) = [1-Total Tumor Volume (at each dose) / Total Tumor Volume (at o Gy)] x 100 (%) Total Tumor Volume(mm 3 ) = slice thickness(mm) x siguma HDA (mm 2 ) on each slice: where HDA is high density area on enhanced CT. Eleven patients were studied and TRR of each patients was calculated. The relations between TRR, tumor markers, CSF seeding and prognoiss was discussed. From our study, (1) TRR at 20Gy was important and might predict approximate prognosis of each cae case. A) TRR = 100 → very good B) TRR < 20 → poor C) 20 <= TRR < 100 → high possibility (2) Majority of TRR < 100 cases have turned out to be histologically in teratoma category. (3) Good correlation between the level of tumor markers and prognosis was observed. Cases with elevated level of AFP and/or HCG were radio- resistant and had poor prognosis. (4) Distant metastasis must also be kept in mind in the treatment of pineal region tumor. (author)

[Neuronavigator-guided microsurgery for resection of brain tumors].

Science.gov (United States)

Zhang, Xiang; Zhang, Jianning; Fei, Zhou; Wu, Jingwen; Fu, Luoan; Qu, Yan; Liu, Weiping; Wang, Zhanxiang; Yang, Lisun; He, Xiaosheng; Zhen, Haining; Gao, Dakuan; Cao, Weidong; Liang, Jingwen

2002-02-25

To study locating accuracy for the brain tumors and their peri-structures by the neuronavigator and elucidate the microsurgical effects. 65 patients with intracranial tumors were microsurgically treated by the application of Stealth Station and Vector Vision system. The treatment effects were summarized and the neuronavigational accuracy was discussed. After mean fiducial error (MFE) and sustained accuracy (SA) were satisfied. Total tumor removal was achieved in 63 cases (97.0%), subtotal removal in 2 cases (3.0%). The neurological functions were improved in 56 cases (86.2%), unchanged obviously in 9 cases (13.8%). No case deteriorated and died in the group. Navigation systems are reliable and accurate in making microneurosurgical plans for brain tumors. And they can provide tracing of the tumor in the operation and guide the operator's manipulation. The techniques, which help total removal of the tumors and reduce the postoperative complications, are very useful in guarantee operation effects.

Glioma Surgery: Technological Advances to Achieve a Maximal Safe Resection.

Science.gov (United States)

Altieri, Roberto; Zenga, Francesco; Fontanella, Marco Maria; Cofano, Fabio; Agnoletti, Alessandro; Spena, Giannantonio; Crobeddu, Emanuela; Fornaro, Riccardo; Ducati, Alessandro; Garbossa, Diego

2015-11-01

Glioblastoma multiforme (GBM) is the most frequent primary central nervous system (CNS) tumor. Despite the best treatment and advances in therapy, prognosis remains poor. One of the mainstays of therapy in GBM is surgical excision. Several studies have confirmed that the extent of resection (EOR) positively influences overall survival (OS) in patients with high-grade gliomas (HGGs). A literature search was performed using PubMed to assess the useful neurosurgical tools to achieve the best neurosurgical performance. In order to achieve the major extent of resection, preserving neurological function, many tools are now available, especially neuronavigation, intraoperative fluorescence, intraoperative ultrasound, and neuromonitoring. In addition to the maximal excision of tumor, the neurosurgeon can use photodynamic therapy (PTD) and local drug delivery (LDD) to improve the local control and bridge conventional radio and chemotherapy. EOR improves OS in patients with HGGs. There are technological possibilities for achieving a complete resection preserving neurological function, and it is not acceptable to perform only biopsy of these lesions.

[Predictive value of Hodgkin's lymphoma tumor burden in present].

Science.gov (United States)

Kulyova, S A; Karitsky, A P

2014-01-01

Today approximately 70% of patients with Hodgkin lymphoma can be cured with the combined-modality therapy. Tumor burden, the importance of which was demonstrated 15 years ago for the first time, is a powerful prognostic factor. Data of literature of representations on predictive value of Hodgkin's lymphoma tumor burden are shown in the article. The difficult immunological relations between tumor cells and reactive ones lead to development of the main symptoms. Nevertheless, the collective sign of tumor burden shows the greatest influence on survival and on probability of resistance, which relative risk can be predicted on this variable and treatment program. Patients with bulky disease need escalated therapy with high-dose chemotherapy. Integration into predictive models of the variable will change an expected contribution of clinical and laboratory parameters in the regression analyses constructed on patients with Hodgkin's lymphoma. Today the role of diagnostic functional methods, in particular a positron emission tomography, for metabolic active measurement is conducted which allows excluding a reactive component.

Congenital tumors of the central nervous system

International Nuclear Information System (INIS)

Severino, Mariasavina; Schwartz, Erin S.; Thurnher, Majda M.; Rydland, Jana; Nikas, Ioannis; Rossi, Andrea

2010-01-01

Congenital tumors of the central nervous system (CNS) are often arbitrarily divided into ''definitely congenital'' (present or producing symptoms at birth), ''probably congenital'' (present or producing symptoms within the first week of life), and ''possibly congenital'' (present or producing symptoms within the first 6 months of life). They represent less than 2% of all childhood brain tumors. The clinical features of newborns include an enlarged head circumference, associated hydrocephalus, and asymmetric skull growth. At birth, a large head or a tense fontanel is the presenting sign in up to 85% of patients. Neurological symptoms as initial symptoms are comparatively rare. The prenatal diagnosis of congenital CNS tumors, while based on ultrasonography, has significantly benefited from the introduction of prenatal magnetic resonance imaging studies. Teratomas constitute about one third to one half of these tumors and are the most common neonatal brain tumor. They are often immature because of primitive neural elements and, rarely, a component of mixed malignant germ cell tumors. Other tumors include astrocytomas, choroid plexus papilloma, primitive neuroectodermal tumors, atypical teratoid/rhabdoid tumors, and medulloblastomas. Less common histologies include craniopharyngiomas and ependymomas. There is a strong predilection for supratentorial locations, different from tumors of infants and children. Differential diagnoses include spontaneous intracranial hemorrhage that can occur in the presence of coagulation factor deficiency or underlying vascular malformations, and congenital brain malformations, especially giant heterotopia. The prognosis for patients with congenital tumors is generally poor, usually because of the massive size of the tumor. However, tumors can be resected successfully if they are small and favorably located. The most favorable outcomes are achieved with choroid plexus tumors, where aggressive surgical treatment leads to disease

Reduced Rank Regression

DEFF Research Database (Denmark)

Johansen, Søren

2008-01-01

The reduced rank regression model is a multivariate regression model with a coefficient matrix with reduced rank. The reduced rank regression algorithm is an estimation procedure, which estimates the reduced rank regression model. It is related to canonical correlations and involves calculating...

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.)

Proton therapy for tumors of the skull base

International Nuclear Information System (INIS)

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

1999-01-01

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

Risk of Recurrence in Operated Parasagittal Meningiomas: A Logistic Binary Regression Model.

Science.gov (United States)

Escribano Mesa, José Alberto; Alonso Morillejo, Enrique; Parrón Carreño, Tesifón; Huete Allut, Antonio; Narro Donate, José María; Méndez Román, Paddy; Contreras Jiménez, Ascensión; Pedrero García, Francisco; Masegosa González, José

2018-02-01

Parasagittal meningiomas arise from the arachnoid cells of the angle formed between the superior sagittal sinus (SSS) and the brain convexity. In this retrospective study, we focused on factors that predict early recurrence and recurrence times. We reviewed 125 patients with parasagittal meningiomas operated from 1985 to 2014. We studied the following variables: age, sex, location, laterality, histology, surgeons, invasion of the SSS, Simpson removal grade, follow-up time, angiography, embolization, radiotherapy, recurrence and recurrence time, reoperation, neurologic deficit, degree of dependency, and patient status at the end of follow-up. Patients ranged in age from 26 to 81 years (mean 57.86 years; median 60 years). There were 44 men (35.2%) and 81 women (64.8%). There were 57 patients with neurologic deficits (45.2%). The most common presenting symptom was motor deficit. World Health Organization grade I tumors were identified in 104 patients (84.6%), and the majority were the meningothelial type. Recurrence was detected in 34 cases. Time of recurrence was 9 to 336 months (mean: 84.4 months; median: 79.5 months). Male sex was identified as an independent risk for recurrence with relative risk 2.7 (95% confidence interval 1.21-6.15), P = 0.014. Kaplan-Meier curves for recurrence had statistically significant differences depending on sex, age, histologic type, and World Health Organization histologic grade. A binary logistic regression was made with the Hosmer-Lemeshow test with P > 0.05; sex, tumor size, and histologic type were used in this model. Male sex is an independent risk factor for recurrence that, associated with other factors such tumor size and histologic type, explains 74.5% of all cases in a binary regression model. Copyright © 2017 Elsevier Inc. All rights reserved.

Advance MRI for pediatric brain tumors with emphasis on clinical benefits

Energy Technology Data Exchange (ETDEWEB)

Goo, Hyun Woo; Ra, Young Shin [Asan Medical Center, University of Ulsan College of Medicine, Seoul(Korea, Republic of)

2017-01-15

Conventional anatomic brain MRI is often limited in evaluating pediatric brain tumors, the most common solid tumors and a leading cause of death in children. Advanced brain MRI techniques have great potential to improve diagnostic performance in children with brain tumors and overcome diagnostic pitfalls resulting from diverse tumor pathologies as well as nonspecific or overlapped imaging findings. Advanced MRI techniques used for evaluating pediatric brain tumors include diffusion-weighted imaging, diffusion tensor imaging, functional MRI, perfusion imaging, spectroscopy, susceptibility-weighted imaging, and chemical exchange saturation transfer imaging. Because pediatric brain tumors differ from adult counterparts in various aspects, MRI protocols should be designed to achieve maximal clinical benefits in pediatric brain tumors. In this study, we review advanced MRI techniques and interpretation algorithms for pediatric brain tumors.

Demonstration of tumor-associated antigens in dogs

International Nuclear Information System (INIS)

Warren, R.P.; Tsoi, M.S.; Henderson, B.H.; Weiden, P.L.; Storb, R.

1975-01-01

Procedures for the 51 Cr release assay using labeled L cells or lymphocytes and the indirect leukocyte migration test are described. These assays appear capable of detecting cellular immunity against tumor associated antigens in dogs. In 8 of 14 instances, lymphocyte-mediated cytotoxicity to autochthonous L cells was found as measured by 51 Cr release, and lymphocytes from 12 of 24 dogs produced the migration inhibition factor (MIF) when cultured with autochthonous tumor cells. Chromium-51 release occurred with 4 h of exposure of effector cells to target cells, suggesting that the immunity detected in the tumor dogs against their tumors is also present in vivo. With the leukocyte migration test, however, consistent MIF production was achieved only after 3 to 6 days in culture, suggesting that in vitro sensitization may result in increased MIF production

Simultaneous inhibition of key growth pathways in melanoma cells and tumor regression by a designed bidentate constrained helical peptide.

Science.gov (United States)

Dhar, Amlanjyoti; Mallick, Shampa; Ghosh, Piya; Maiti, Atanu; Ahmed, Israr; Bhattacharya, Seemana; Mandal, Tapashi; Manna, Asit; Roy, Koushik; Singh, Sandeep; Nayak, Dipak Kumar; Wilder, Paul T; Markowitz, Joseph; Weber, David; Ghosh, Mrinal K; Chattopadhyay, Samit; Guha, Rajdeep; Konar, Aditya; Bandyopadhyay, Santu; Roy, Siddhartha

2014-07-01

Protein-protein interactions are part of a large number of signaling networks and potential targets for drug development. However, discovering molecules that can specifically inhibit such interactions is a major challenge. S100B, a calcium-regulated protein, plays a crucial role in the proliferation of melanoma cells through protein-protein interactions. In this article, we report the design and development of a bidentate conformationally constrained peptide against dimeric S100B based on a natural tight-binding peptide, TRTK-12. The helical conformation of the peptide was constrained by the substitution of α-amino isobutyric acid--an amino acid having high helical propensity--in positions which do not interact with S100B. A branched bidentate version of the peptide was bound to S100B tightly with a dissociation constant of 8 nM. When conjugated to a cell-penetrating peptide, it caused growth inhibition and rapid apoptosis in melanoma cells. The molecule exerts antiproliferative action through simultaneous inhibition of key growth pathways, including reactivation of wild-type p53 and inhibition of Akt and STAT3 phosphorylation. The apoptosis induced by the bidentate constrained helix is caused by direct migration of p53 to mitochondria. At moderate intravenous dose, the peptide completely inhibits melanoma growth in a mouse model without any significant observable toxicity. The specificity was shown by lack of ability of a double mutant peptide to cause tumor regression at the same dose level. The methodology described here for direct protein-protein interaction inhibition may be effective for rapid development of inhibitors against relatively weak protein-protein interactions for de novo drug development. © 2014 Wiley Periodicals, Inc.

Tumor Architecture and Notch Signaling Modulate Drug Response in Basal Cell Carcinoma.

Science.gov (United States)

Eberl, Markus; Mangelberger, Doris; Swanson, Jacob B; Verhaegen, Monique E; Harms, Paul W; Frohm, Marcus L; Dlugosz, Andrzej A; Wong, Sunny Y

2018-02-12

Hedgehog (Hh) pathway inhibitors such as vismodegib are highly effective for treating basal cell carcinoma (BCC); however, residual tumor cells frequently persist and regenerate the primary tumor upon drug discontinuation. Here, we show that BCCs are organized into two molecularly and functionally distinct compartments. Whereas interior Hh + /Notch + suprabasal cells undergo apoptosis in response to vismodegib, peripheral Hh +++ /Notch - basal cells survive throughout treatment. Inhibiting Notch specifically promotes tumor persistence without causing drug resistance, while activating Notch is sufficient to regress already established lesions. Altogether, these findings suggest that the three-dimensional architecture of BCCs establishes a natural hierarchy of drug response in the tumor and that this hierarchy can be overcome, for better or worse, by modulating Notch. Copyright © 2017 Elsevier Inc. All rights reserved.

The problem: Tumor radioresistance in clinical radiotherapy

International Nuclear Information System (INIS)

Peters, L.J.; Withers, H.R.; Thames, H.D.; Fletcher, G.H.; M.D. Anderson Hospital and Tumor Inst., Houston, TX)

1983-01-01

Tumor radioresistance in clinical radiotherapy implies failure to achieve local-regional disease control with radiation doses producing an acceptable degree of morbidity. Such radioresistance may be due to many different causes (biological and technical) which are reviewed in terms of possible remedial actions. Dose-response relationships for human cancers suggest that, in many sites, tumors are heterogeneous with respect to their cure-limiting characteristics. The case is developed that unless the predominant cure-limiting factor can be predicted, little benefit may be seen in trials of new treatment strategies using heterogeneous tumor populations. The fundamental problem of clinical radioresistance is therefore perceived as the inability to identify predictively its cause in the individual patient

Risk interrelationship among multiple primary tumors

Science.gov (United States)

Safi, Mohammed; Sun, Xiuhua; Wang, Lifen; Zhang, Xinwei; Song, Jicheng; Ameen, Mohammed

2018-01-01

Abstract Rationale: Along with advanced management in oncology, great progress has been recently achieved in the studies of multiple primary tumors. Several reports have studied the coexistence between lymphoma and either renal cell carcinoma (RCC) or Warthin tumor. However, the level of coexistence between these cases remains unclear due to the absence of a distinct link between them. Patient concerns: We present a unique case of multiple primary tumors (lymphoma, RCC, and Warthin tumor) in an 80-year-old man and a review of the literature on the coexistence of RCC with lymphoma and lymphoma with Warthin tumor. Diagnosis: With a history of RCC, the patient had a freely movable lump under his left ear, and the pathological report indicated Hodgkin lymphoma and Warthin tumor. Intervention: RCC and Warthin tumor of the patient were surgically treated, followed by 2 cycles (14 days per cycle) of Epirubicin 40 mg day 1, Bleomycin 8 mg day 1, Vincristine 2 mg day 1, and Dacarbazine 500 mg day 1. The chemotherapy protocol was then changed to Epirubicin 40 mg day 1, Vincristine 2 mg day 1, and Dacarbazine 500 mg day 1 for 7 cycles. Outcomes: After the last day of chemotherapy, the patient showed a complete response. Lessons: To the best of our knowledge, this paper is the first to report a case of multiple primary tumors with a complete response. For their early detection, favorable prognosis, and correlation identification, we suggest a transitive relation between these coexisting tumors. Therefore, similar studies should be conducted. PMID:29642151

Quantile Regression Methods

DEFF Research Database (Denmark)

Fitzenberger, Bernd; Wilke, Ralf Andreas

2015-01-01

if the mean regression model does not. We provide a short informal introduction into the principle of quantile regression which includes an illustrative application from empirical labor market research. This is followed by briefly sketching the underlying statistical model for linear quantile regression based......Quantile regression is emerging as a popular statistical approach, which complements the estimation of conditional mean models. While the latter only focuses on one aspect of the conditional distribution of the dependent variable, the mean, quantile regression provides more detailed insights...... by modeling conditional quantiles. Quantile regression can therefore detect whether the partial effect of a regressor on the conditional quantiles is the same for all quantiles or differs across quantiles. Quantile regression can provide evidence for a statistical relationship between two variables even...

Calcium antagonist radioprotectors do not reduce radiotherapeutic efficacy in three human tumor xenografts

International Nuclear Information System (INIS)

Floersheim, G.L.; Racine, C.

1995-01-01

One Ewing's sarcoma and 2 colon carcinomas were grown as xenografts in immunosuppressed mice. The mice were treated with diltiazem, nifedipine, nimodipine and nitrendipine. The effect of whole body γ-radiation on the growth of the subcutaneously implanted tumors was assessed. Growth delay or regression of the tumors in mice treated with the calcium antagonists prior to irradiation was not reduced as compared to only irradiated controls. (orig.) [de

Radiofrequency ablation of liver tumors (II): clinical application and outcomes.

Science.gov (United States)

Vanagas, Tomas; Gulbinas, Antanas; Pundzius, Juozas; Barauskas, Giedrius

2010-01-01

Radiofrequency ablation is one of the alternatives in the management of liver tumors, especially in patients who are not candidates for surgery. The aim of this article is to review applicability of radiofrequency ablation achieving complete tumor destruction, utility of imaging techniques for patients' follow-up, indications for local ablative procedures, procedure-associated morbidity and mortality, and long-term results in patients with different tumors. The success of local thermal ablation consists in creating adequate volumes of tissue destruction with adequate "clear margin," depending on improved delivery of radiofrequency energy and modulated tissue biophysiology. Different volumes of coagulation necrosis are achieved applying different types of electrodes, pulsing energy sources, utilizing sophisticated ablation schemes. Some additional methods are used to increase the overall deposition of energy through alterations in tissue electrical conductivity, to improve heat retention within the tissue, and to modulate tolerance of tumor tissue to hyperthermia. Contrast-enhanced computed tomography, magnetic resonance imaging, ultrasound or positron emission tomography are applied to control the effectiveness of radiofrequency ablation. The long-term results of radiofrequency ablation are controversial.

Achievements and challenges of adoptive T cell therapy with tumor-infiltrating or blood-derived lymphocytes for metastatic melanoma

DEFF Research Database (Denmark)

Svane, Inge Marie; Verdegaal, Els M

2014-01-01

Adoptive cell therapy (ACT) based on autologous T cell derived either from tumor as tumor-infiltrating lymphocytes (TILs) or from peripheral blood is developing as a key area of future personalized cancer therapy. TIL-based ACT is defined as the infusion of T cells harvested from autologous fresh...

Validation of Heat Shock Protein 70 as a Tumor-Specific Biomarker for Monitoring the Outcome of Radiation Therapy in Tumor Mouse Models

Energy Technology Data Exchange (ETDEWEB)

Bayer, Christine; Liebhardt, Michael E.; Schmid, Thomas E. [Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich (Germany); Trajkovic-Arsic, Marija [II Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich (Germany); Hube, Kathrin; Specht, Hanno M. [Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich (Germany); Schilling, Daniela [Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich (Germany); Clinical Kooperation Group, Innate Immunity in Tumor Biology, HelmholtzZentrum München, Munich (Germany); Gehrmann, Mathias; Stangl, Stefan [Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich (Germany); Siveke, Jens T. [II Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich (Germany); Wilkens, Jan J. [Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich (Germany); Multhoff, Gabriele, E-mail: Gabriele.multhoff@lrz.tum.de [Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich (Germany); Clinical Kooperation Group, Innate Immunity in Tumor Biology, HelmholtzZentrum München, Munich (Germany)

2014-03-01

Purpose: Tumor cells, in contrast to normal cells, frequently overexpress heat shock protein 70 (Hsp70) in the cytosol, present it on their cell surface, and actively release it. Therefore, soluble Hsp70 (sHsp70) was investigated as a potential tumor biomarker for monitoring the outcome of radiation therapy. Methods and Materials: Plasma from mice bearing membrane Hsp70 (mHsp70)-positive FaDu human squamous cell carcinoma of the head and neck and spontaneous pancreatic ductal adenocarcinoma (PDAC) was investigated. A cohort of mice with FaDu tumors (0.32 cm{sup 3}) was irradiated with 30 Gy, and plasma was collected 24 hours after irradiation, after the tumors had shrunk to 50% of their starting volume and after complete remission. sHsp70 levels in the plasma were quantified by enzyme-linked immunosorbent assay. Results: sHsp70 levels were significantly higher in the blood of tumor-bearing mice than that of control animals. A correlation between increasing sHsp70 plasma levels and tumor volume in the range of 0.01 cm{sup 3} to 0.66 cm{sup 3} was observed. Radiation-induced regression of the tumors was associated with significantly decreased sHsp70 levels, which returned to the level of control animals after complete remission. Conclusion: We propose sHsp70 as an innovative biomarker for detecting tumors and for monitoring the clinical outcome of radiation therapy in cancer patients.

Maxillary brown tumor as initial presentation of parathyroid adenoma: A case report

Directory of Open Access Journals (Sweden)

Hon-Ke Sia

2012-07-01

Full Text Available Brown tumor is a rare late-stage skeletal change caused by long-term stimulation of excess parathyroid hormone. It is not neoplastic, but a reparative cellular process. Common sites of brown tumor are the ribs, clavicle, long bones and pelvic girdle. Solitary maxillary brown tumor as initial presentation of primary hyperparathyroidism is rare; it is often accompanied by brown tumors of the other facial bones. Here, we present the first case of solitary maxillary brown tumor in a 29-year-old ethnic Chinese woman with initial presentation of a large tumor filling the left maxillary sinus. Underlying long-standing primary hyperparathyroidism caused by a large parathyroid adenoma was finally diagnosed. Brown tumor tends to be misdiagnosed as malignancy, and delayed diagnosis of the underlying hyperparathyroidism is common. Our case validates the suggestion that young women have a higher probability of brown tumor. Biopsy of the suspicious bone tumor and blood tests for calcium and parathyroid hormone level are crucial and essential to reach the correct diagnosis. Most brown tumors show spontaneous regression after parathyroidectomy. However, direct excision of the brown tumor may be indicated to avoid the risk of facial deformity and orbital compression at a special anatomical site, as in our case.

DRREP: deep ridge regressed epitope predictor.

Science.gov (United States)

Sher, Gene; Zhi, Degui; Zhang, Shaojie

2017-10-03

The ability to predict epitopes plays an enormous role in vaccine development in terms of our ability to zero in on where to do a more thorough in-vivo analysis of the protein in question. Though for the past decade there have been numerous advancements and improvements in epitope prediction, on average the best benchmark prediction accuracies are still only around 60%. New machine learning algorithms have arisen within the domain of deep learning, text mining, and convolutional networks. This paper presents a novel analytically trained and string kernel using deep neural network, which is tailored for continuous epitope prediction, called: Deep Ridge Regressed Epitope Predictor (DRREP). DRREP was tested on long protein sequences from the following datasets: SARS, Pellequer, HIV, AntiJen, and SEQ194. DRREP was compared to numerous state of the art epitope predictors, including the most recently published predictors called LBtope and DMNLBE. Using area under ROC curve (AUC), DRREP achieved a performance improvement over the best performing predictors on SARS (13.7%), HIV (8.9%), Pellequer (1.5%), and SEQ194 (3.1%), with its performance being matched only on the AntiJen dataset, by the LBtope predictor, where both DRREP and LBtope achieved an AUC of 0.702. DRREP is an analytically trained deep neural network, thus capable of learning in a single step through regression. By combining the features of deep learning, string kernels, and convolutional networks, the system is able to perform residue-by-residue prediction of continues epitopes with higher accuracy than the current state of the art predictors.

Evaluation for intravenous, arterial and local infusion of a hypoxic cell radiosensitizer RK28 on rabbit VX2 tumor system

International Nuclear Information System (INIS)

Kuramitsu, Tatsuya

1993-01-01

We evaluated the radiosensitizing effect of intraarterial, intravenous and local infusion of a hypoxic cell radiosensitizer RK28 on rabbit VX2 tumor system. Six rabbits were treated in each infusion group. VX2 tumor was implanted in the left hind leg. Tumor grown up to 3 cm in diameter was treated with 15 Gy of X-ray irradiation just after infusion of radiosensitizer RK28 (80 mg/kg.b.w.). Intratumoral and serum mean concentration of RK28 and its metabolites were measured. Tumor regression curve and survival time were analyzed. The following results were obtained. Mean concentration of RK28 was about 2.5 times greater in local infusion and 1.5 times in intraarterial infusion than in intravenous infusion. Significant regression of tumor was obtained in intraarterial infusion (p<0.01). There was no significant difference in survival time. These data suggest that the usefulness of intraarterial infusion of RK28 for local control using intraoperative radiation therapy and brachytherapy. (author)

Antibody-radioisotope conjugates for tumor localization and treatment

International Nuclear Information System (INIS)

Larson, S.M.; Carrasquillo, J.A.

1985-01-01

In principle, anti-tumor antibodies can be used to carry radioactivity to tumors for in-vivo diagnosis and treatment of cancer. First, for diagnostic purposes, an antibody that targets a specific antigen (for example, the p97 antigen of human melanoma tumor), is labeled with a tracer amount of radioactivity. When this antibody-radioisotope conjugate is injected into the blood stream, the antibody carries the radioactivity throughout the body and in time, percolates through all the tissues of the body. Because the tumor has specific antigens to which the antibody can bind, the antibody conjugate progressively accumulates in the tumor. Using conventional nuclear medicine imaging equipment, the body of the patient is scanned for radioactivity content, and a map of the distribution of the radioactivity is displayed on photographic film. The tumor shows up as a dense area of radio-activity. These same antibody-radioisotope conjugates may be used for therapy of tumors, except that in this case large amounts of radioactivity are loaded on the antibody. After localization of the conjugate there is sufficient radiation deposited in the tumor of radiotherapy. The success of this approach in the clinic is determined in large measure by the concentration gradient that can be achieved between tissue antibody conjugate in tumor versus normal tissue

A Monte Carlo simulation study comparing linear regression, beta regression, variable-dispersion beta regression and fractional logit regression at recovering average difference measures in a two sample design.

Science.gov (United States)

Meaney, Christopher; Moineddin, Rahim

2014-01-24

In biomedical research, response variables are often encountered which have bounded support on the open unit interval--(0,1). Traditionally, researchers have attempted to estimate covariate effects on these types of response data using linear regression. Alternative modelling strategies may include: beta regression, variable-dispersion beta regression, and fractional logit regression models. This study employs a Monte Carlo simulation design to compare the statistical properties of the linear regression model to that of the more novel beta regression, variable-dispersion beta regression, and fractional logit regression models. In the Monte Carlo experiment we assume a simple two sample design. We assume observations are realizations of independent draws from their respective probability models. The randomly simulated draws from the various probability models are chosen to emulate average proportion/percentage/rate differences of pre-specified magnitudes. Following simulation of the experimental data we estimate average proportion/percentage/rate differences. We compare the estimators in terms of bias, variance, type-1 error and power. Estimates of Monte Carlo error associated with these quantities are provided. If response data are beta distributed with constant dispersion parameters across the two samples, then all models are unbiased and have reasonable type-1 error rates and power profiles. If the response data in the two samples have different dispersion parameters, then the simple beta regression model is biased. When the sample size is small (N0 = N1 = 25) linear regression has superior type-1 error rates compared to the other models. Small sample type-1 error rates can be improved in beta regression models using bias correction/reduction methods. In the power experiments, variable-dispersion beta regression and fractional logit regression models have slightly elevated power compared to linear regression models. Similar results were observed if the

Long term results after fractionated stereotactic radiotherapy (FSRT) in patients with craniopharyngioma: maximal tumor control with minimal side effects.

Science.gov (United States)

Harrabi, Semi B; Adeberg, Sebastian; Welzel, Thomas; Rieken, Stefan; Habermehl, Daniel; Debus, Jürgen; Combs, Stephanie E

2014-09-16

There are already numerous reports about high local control rates in patients with craniopharyngioma but there are only few studies with follow up times of more than 10 years. This study is an analysis of long term control, tumor response and side effects after fractionated stereotactic radiotherapy (FSRT) for patients with craniopharyngioma. 55 patients who were treated with FSRT for craniopharyngioma were analyzed. Median age was 37 years (range 6-70 years), among them eight children craniopharyngioma. Overall treatment was tolerated well with almost no severe acute or chronic side effects. One patient developed complete anosmia, another one's initially impaired vision deteriorated further. In 83.6% of the cases with radiological follow up a regression of irradiated tumor residues was monitored, in 7 cases complete response was achieved. 44 patients presented themselves initially with endocrinologic dysfunction none of them showed signs of further deterioration during follow up. No secondary malignancies were observed. Long term results for patients with craniopharyngioma after stereotactic radiotherapy are with respect to low treatment related side effects as well as to local control and overall survival excellent.

Evaluation of [1-11C]-α-aminoisobutyric acid for tumor detection and amino acid transport measurement: Spontaneous canine tumor studies

International Nuclear Information System (INIS)

Bigler, R.E.; Zanzonico, P.B.; Schmall, B.; Conti, P.S.; Dahl, J.R.; Rothman, L.; Sgouros, G.

1985-01-01

Alpha-aminoisobutyric acid (AIB) or α-methyl alanine, is a nonmetabolized amino acid treansported into cells particularly malignant cells, predominantly by the ''A'' amino acid transport system. Since it is not metabolized, [1- 11 C]-AIB can be used to quantify A-type amino acid transport into cells using a relatively simple compartmental model and quantitative imaging procedures (e.g. positron tomography). The tissue distribution of [1- 11 C]-AIB was determined in six dogs bearing spontaneous tumors, including lymphosarcoma, osteogenic sarcoma, mammary carcinoma, and adenocarcinoma. Quantitative imaging with tissue radioassay confirmation at necropsy showed poor to excellent tumor localization. However, in all cases the concentrations achieved appear adequate for amino acid transport measurement at known tumor locations. The observed low normal brain (due to blood-brain barrier exclusion) and high (relative to brain) tumor concentrations of [1- 11 C]-AIB suggest that this agent may prove effective for the early detection of human brain tumors. (orig.)

Congenital tumors of the central nervous system

Energy Technology Data Exchange (ETDEWEB)

Severino, Mariasavina [G. Gaslini Children' s Hospital, Department of Neuroradiology, Genoa (Italy); Schwartz, Erin S. [The Children' s Hospital of Philadelphia, Department of Radiology, Philadelphia, PA (United States); Thurnher, Majda M. [Medical University of Vienna, Department of Radiology, Vienna (Austria); Rydland, Jana [MR Center, St. Olav' s Hospital HF, Trondheim (Norway); Nikas, Ioannis [Agia Sophia Children' s Hospital, Imaging Department, Athens (Greece); Rossi, Andrea [G. Gaslini Children' s Hospital, Department of Neuroradiology, Genoa (Italy); G. Gaslini Children' s Hospital, Department of Pediatric Neuroradiology, Genoa (Italy)

2010-06-15

Congenital tumors of the central nervous system (CNS) are often arbitrarily divided into ''definitely congenital'' (present or producing symptoms at birth), ''probably congenital'' (present or producing symptoms within the first week of life), and ''possibly congenital'' (present or producing symptoms within the first 6 months of life). They represent less than 2% of all childhood brain tumors. The clinical features of newborns include an enlarged head circumference, associated hydrocephalus, and asymmetric skull growth. At birth, a large head or a tense fontanel is the presenting sign in up to 85% of patients. Neurological symptoms as initial symptoms are comparatively rare. The prenatal diagnosis of congenital CNS tumors, while based on ultrasonography, has significantly benefited from the introduction of prenatal magnetic resonance imaging studies. Teratomas constitute about one third to one half of these tumors and are the most common neonatal brain tumor. They are often immature because of primitive neural elements and, rarely, a component of mixed malignant germ cell tumors. Other tumors include astrocytomas, choroid plexus papilloma, primitive neuroectodermal tumors, atypical teratoid/rhabdoid tumors, and medulloblastomas. Less common histologies include craniopharyngiomas and ependymomas. There is a strong predilection for supratentorial locations, different from tumors of infants and children. Differential diagnoses include spontaneous intracranial hemorrhage that can occur in the presence of coagulation factor deficiency or underlying vascular malformations, and congenital brain malformations, especially giant heterotopia. The prognosis for patients with congenital tumors is generally poor, usually because of the massive size of the tumor. However, tumors can be resected successfully if they are small and favorably located. The most favorable outcomes are achieved with choroid plexus tumors

Novel radiosensitizers for locally advanced epithelial tumors: inhibition of the PI3K/Akt survival pathway in tumor cells and in tumor-associated endothelial cells as a novel treatment strategy?

International Nuclear Information System (INIS)

Riesterer, Oliver; Tenzer, Angela; Zingg, Daniel; Hofstetter, Barbara; Vuong, Van; Pruschy, Martin; Bodis, Stephan

2004-01-01

In locally advanced epithelial malignancies, local control can be achieved with high doses of radiotherapy (RT). Concurrent chemoradiotherapy can improve tumor control in selected solid epithelial adult tumors; however, treatment-related toxicity is of major concern and the therapeutic window often small. Therefore, novel pharmacologic radiosensitizers with a tumor-specific molecular target and a broad therapeutic window are attractive. Because of clonal heterogeneity and the high mutation rate of these tumors, combined treatment with single molecular target radiosensitizers and RT are unlikely to improve sustained local tumor control substantially. Therefore, radiosensitizers modulating entire tumor cell survival pathways in epithelial tumors are of potential clinical use. We discuss the preclinical efficacy and the mechanism of three different, potential radiosensitizers targeting the PTEN/PI3K/Akt survival pathway. These compounds were initially thought to act as single-target agents against growth factor receptors (PKI 166 and PTK 787) or protein kinase C isoforms (PKC 412). We describe an additional target for these compounds. PKI 166 (an epidermal growth factor [EGF] receptor inhibitor) and PKC 412, target the PTEN/PI3K/Akt pathway mainly in tumor cells, and PTK 787 (a vascular endothelial growth factor [VEGF] receptor inhibitor) in endothelial cells. Even for these broader range molecular radiosensitizers, the benefit could be restricted to human epithelial tumor cell clones with a distinct molecular profile. Therefore, these potential radiosensitizers have to be carefully tested in specific model systems before introduction in early clinical trials

ANALYSIS OF THE FINANCIAL PERFORMANCES OF THE FIRM, BY USING THE MULTIPLE REGRESSION MODEL

Directory of Open Access Journals (Sweden)

Constantin Anghelache

2011-11-01

Full Text Available The information achieved through the use of simple linear regression are not always enough to characterize the evolution of an economic phenomenon and, furthermore, to identify its possible future evolution. To remedy these drawbacks, the special literature includes multiple regression models, in which the evolution of the dependant variable is defined depending on two or more factorial variables.

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

Optimized support vector regression for drilling rate of penetration estimation

Science.gov (United States)

Bodaghi, Asadollah; Ansari, Hamid Reza; Gholami, Mahsa

2015-12-01

In the petroleum industry, drilling optimization involves the selection of operating conditions for achieving the desired depth with the minimum expenditure while requirements of personal safety, environment protection, adequate information of penetrated formations and productivity are fulfilled. Since drilling optimization is highly dependent on the rate of penetration (ROP), estimation of this parameter is of great importance during well planning. In this research, a novel approach called `optimized support vector regression' is employed for making a formulation between input variables and ROP. Algorithms used for optimizing the support vector regression are the genetic algorithm (GA) and the cuckoo search algorithm (CS). Optimization implementation improved the support vector regression performance by virtue of selecting proper values for its parameters. In order to evaluate the ability of optimization algorithms in enhancing SVR performance, their results were compared to the hybrid of pattern search and grid search (HPG) which is conventionally employed for optimizing SVR. The results demonstrated that the CS algorithm achieved further improvement on prediction accuracy of SVR compared to the GA and HPG as well. Moreover, the predictive model derived from back propagation neural network (BPNN), which is the traditional approach for estimating ROP, is selected for comparisons with CSSVR. The comparative results revealed the superiority of CSSVR. This study inferred that CSSVR is a viable option for precise estimation of ROP.

Differential diagnosis between benign and malignant soft tissue tumors utilizing ultrasound parameters.

Science.gov (United States)

Morii, Takeshi; Kishino, Tomonori; Shimamori, Naoko; Motohashi, Mitsue; Ohnishi, Hiroaki; Honya, Keita; Aoyagi, Takayuki; Tajima, Takashi; Ichimura, Shoichi

2018-01-01

Preoperative discrimination between benign and malignant soft tissue tumors is critical for the prevention of excess application of magnetic resonance imaging and biopsy as well as unplanned resection. Although ultrasound, including power Doppler imaging, is an easy, noninvasive, and cost-effective modality for screening soft tissue tumors, few studies have investigated reliable discrimination between benign and malignant soft tissue tumors. To establish a modality for discrimination between benign and malignant soft tissue tumors using ultrasound, we extracted the significant risk factors for malignancy based on ultrasound information from 40 malignant and 56 benign pathologically diagnosed soft tissue tumors and established a scoring system based on these risk factors. The maximum size, tumor margin, and vascularity evaluated using ultrasound were extracted as significant risk factors. Using the odds ratio from a multivariate regression model, a scoring system was established. Receiver operating characteristic analyses revealed a high area under the curve value (0.85), confirming the accuracy of the scoring system. Ultrasound is a useful modality for establishing the differential diagnosis between benign and malignant soft tissue tumors.

Regression Phalanxes

OpenAIRE

Zhang, Hongyang; Welch, William J.; Zamar, Ruben H.

2017-01-01

Tomal et al. (2015) introduced the notion of "phalanxes" in the context of rare-class detection in two-class classification problems. A phalanx is a subset of features that work well for classification tasks. In this paper, we propose a different class of phalanxes for application in regression settings. We define a "Regression Phalanx" - a subset of features that work well together for prediction. We propose a novel algorithm which automatically chooses Regression Phalanxes from high-dimensi...

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

Directory of Open Access Journals (Sweden)

Maryam Azimi

2012-01-01

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

A noninvasive multimodal technique to monitor brain tumor vascularization

Science.gov (United States)

Saxena, Vishal; Gonzalez-Gomez, Ignacio; Laug, Walter E.

2007-09-01

Determination of tumor oxygenation at the microvascular level will provide important insight into tumor growth, angiogenesis, necrosis and therapeutic response and will facilitate to develop protocols for studying tumor behavior. The non-ionizing near infrared spectroscopy (NIRS) technique has the potential to differentiate lesion and hemoglobin dynamics; however, it has a limited spatial resolution. On the other hand, magnetic resonance imaging (MRI) has achieved high spatial resolution with excellent tissue discrimination but is more susceptible to limited ability to monitor the hemoglobin dynamics. In the present work, the vascular status and the pathophysiological changes that occur during tumor vascularization are studied in an orthotopic brain tumor model. A noninvasive multimodal approach based on the NIRS technique, namely steady state diffuse optical spectroscopy (SSDOS) along with MRI, is applied for monitoring the concentrations of oxyhemoglobin, deoxyhemoglobin and water within tumor region. The concentrations of oxyhemoglobin, deoxyhemoglobin and water within tumor vasculature are extracted at 15 discrete wavelengths in a spectral window of 675-780 nm. We found a direct correlation between tumor size, intratumoral microvessel density and tumor oxygenation. The relative decrease in tumor oxygenation with growth indicates that though blood vessels infiltrate and proliferate the tumor region, a hypoxic trend is clearly present.

A noninvasive multimodal technique to monitor brain tumor vascularization

International Nuclear Information System (INIS)

Saxena, Vishal; Gonzalez-Gomez, Ignacio; Laug, Walter E

2007-01-01

Determination of tumor oxygenation at the microvascular level will provide important insight into tumor growth, angiogenesis, necrosis and therapeutic response and will facilitate to develop protocols for studying tumor behavior. The non-ionizing near infrared spectroscopy (NIRS) technique has the potential to differentiate lesion and hemoglobin dynamics; however, it has a limited spatial resolution. On the other hand, magnetic resonance imaging (MRI) has achieved high spatial resolution with excellent tissue discrimination but is more susceptible to limited ability to monitor the hemoglobin dynamics. In the present work, the vascular status and the pathophysiological changes that occur during tumor vascularization are studied in an orthotopic brain tumor model. A noninvasive multimodal approach based on the NIRS technique, namely steady state diffuse optical spectroscopy (SSDOS) along with MRI, is applied for monitoring the concentrations of oxyhemoglobin, deoxyhemoglobin and water within tumor region. The concentrations of oxyhemoglobin, deoxyhemoglobin and water within tumor vasculature are extracted at 15 discrete wavelengths in a spectral window of 675-780 nm. We found a direct correlation between tumor size, intratumoral microvessel density and tumor oxygenation. The relative decrease in tumor oxygenation with growth indicates that though blood vessels infiltrate and proliferate the tumor region, a hypoxic trend is clearly present

Tumor RNA disruption predicts survival benefit from breast cancer chemotherapy.

Science.gov (United States)

Parissenti, Amadeo M; Guo, Baoqing; Pritzker, Laura B; Pritzker, Kenneth P H; Wang, Xiaohui; Zhu, Mu; Shepherd, Lois E; Trudeau, Maureen E

2015-08-01

In a prior substudy of the CAN-NCIC-MA.22 clinical trial (ClinicalTrials.gov identifier NCT00066443), we observed that neoadjuvant chemotherapy reduced tumor RNA integrity in breast cancer patients, a phenomenon we term "RNA disruption." The purpose of the current study was to assess in the full patient cohort the relationship between mid-treatment tumor RNA disruption and both pCR post-treatment and, subsequently, disease-free survival (DFS) up to 108 months post-treatment. To meet these objectives, we developed the RNA disruption assay (RDA) to quantify RNA disruption and stratify it into 3 response zones of clinical importance. Zone 1 is a level of RNA disruption inadequate for pathologic complete response (pCR); Zone 2 is an intermediate level, while Zone 3 has high RNA disruption. The same RNA disruption cut points developed for pCR response were then utilized for DFS. Tumor RDA identified >fourfold more chemotherapy non-responders than did clinical response by calipers. pCR responders were clustered in RDA Zone 3, irrespective of tumor subtype. DFS was about 2-fold greater for patients with tumors in Zone 3 compared to Zone 1 patients. Kaplan-Meier survival curves corroborated these findings that high tumor RNA disruption was associated with increased DFS. DFS values for patients in zone 3 that did not achieve a pCR were similar to that of pCR recipients across tumor subtypes, including patients with hormone receptor positive tumors that seldom achieve a pCR. RDA appears superior to pCR as a chemotherapy response biomarker, supporting the prospect of its use in response-guided chemotherapy.

Using an external surrogate for predictor model training in real-time motion management of lung tumors

Energy Technology Data Exchange (ETDEWEB)

Rottmann, Joerg; Berbeco, Ross [Brigham and Women’s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115 (United States)

2014-12-15

Purpose: Precise prediction of respiratory motion is a prerequisite for real-time motion compensation techniques such as beam, dynamic couch, or dynamic multileaf collimator tracking. Collection of tumor motion data to train the prediction model is required for most algorithms. To avoid exposure of patients to additional dose from imaging during this procedure, the feasibility of training a linear respiratory motion prediction model with an external surrogate signal is investigated and its performance benchmarked against training the model with tumor positions directly. Methods: The authors implement a lung tumor motion prediction algorithm based on linear ridge regression that is suitable to overcome system latencies up to about 300 ms. Its performance is investigated on a data set of 91 patient breathing trajectories recorded from fiducial marker tracking during radiotherapy delivery to the lung of ten patients. The expected 3D geometric error is quantified as a function of predictor lookahead time, signal sampling frequency and history vector length. Additionally, adaptive model retraining is evaluated, i.e., repeatedly updating the prediction model after initial training. Training length for this is gradually increased with incoming (internal) data availability. To assess practical feasibility model calculation times as well as various minimum data lengths for retraining are evaluated. Relative performance of model training with external surrogate motion data versus tumor motion data is evaluated. However, an internal–external motion correlation model is not utilized, i.e., prediction is solely driven by internal motion in both cases. Results: Similar prediction performance was achieved for training the model with external surrogate data versus internal (tumor motion) data. Adaptive model retraining can substantially boost performance in the case of external surrogate training while it has little impact for training with internal motion data. A minimum

Imitation-tumor targeting based on continuous-wave near-infrared tomography.

Science.gov (United States)

Liu, Dan; Liu, Xin; Zhang, Yan; Wang, Qisong; Lu, Jingyang; Sun, Jinwei

2017-12-01

Continuous-wave Near-Infrared (NIR) optical spectroscopy has shown great diagnostic capability in the early tumor detection with advantages of low-cost, portable, non-invasive, and non-radiative. In this paper, Modified Lambert-Beer Theory is deployed to address the low-resolution issues of the NIR technique and to design the tumor detecting and imaging system. Considering that tumor tissues have features such as high blood flow and hypoxia, the proposed technique can detect the location, size, and other information of the tumor tissues by comparing the absorbance between pathological and normal tissues. Finally, the tumor tissues can be imaged through tomographic method. The simulation experiments prove that the proposed technique and designed system can efficiently detect the tumor tissues, achieving imaging precision within 1 mm. The work of the paper has shown great potential in the diagnosis of tumor close to body surface.

Statistical approach for selection of regression model during validation of bioanalytical method

Directory of Open Access Journals (Sweden)

Natalija Nakov

2014-06-01

Full Text Available The selection of an adequate regression model is the basis for obtaining accurate and reproducible results during the bionalytical method validation. Given the wide concentration range, frequently present in bioanalytical assays, heteroscedasticity of the data may be expected. Several weighted linear and quadratic regression models were evaluated during the selection of the adequate curve fit using nonparametric statistical tests: One sample rank test and Wilcoxon signed rank test for two independent groups of samples. The results obtained with One sample rank test could not give statistical justification for the selection of linear vs. quadratic regression models because slight differences between the error (presented through the relative residuals were obtained. Estimation of the significance of the differences in the RR was achieved using Wilcoxon signed rank test, where linear and quadratic regression models were treated as two independent groups. The application of this simple non-parametric statistical test provides statistical confirmation of the choice of an adequate regression model.

eTumorType, An Algorithm of Discriminating Cancer Types for Circulating Tumor Cells or Cell-free DNAs in Blood

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Jinfeng Zou

2017-04-01

Full Text Available With the technology development on detecting circulating tumor cells (CTCs and cell-free DNAs (cfDNAs in blood, serum, and plasma, non-invasive diagnosis of cancer becomes promising. A few studies reported good correlations between signals from tumor tissues and CTCs or cfDNAs, making it possible to detect cancers using CTCs and cfDNAs. However, the detection cannot tell which cancer types the person has. To meet these challenges, we developed an algorithm, eTumorType, to identify cancer types based on copy number variations (CNVs of the cancer founding clone. eTumorType integrates cancer hallmark concepts and a few computational techniques such as stochastic gradient boosting, voting, centroid, and leading patterns. eTumorType has been trained and validated on a large dataset including 18 common cancer types and 5327 tumor samples. eTumorType produced high accuracies (0.86–0.96 and high recall rates (0.79–0.92 for predicting colon, brain, prostate, and kidney cancers. In addition, relatively high accuracies (0.78–0.92 and recall rates (0.58–0.95 have also been achieved for predicting ovarian, breast luminal, lung, endometrial, stomach, head and neck, leukemia, and skin cancers. These results suggest that eTumorType could be used for non-invasive diagnosis to determine cancer types based on CNVs of CTCs and cfDNAs.

Limited Margin Radiation Therapy for Children and Young Adults With Ewing Sarcoma Achieves High Rates of Local Tumor Control

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Talleur, Aimee C.; Navid, Fariba [Department of Oncology, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Spunt, Sheri L. [Department of Pediatrics, Stanford University School of Medicine, Stanford, California (United States); McCarville, M. Beth [Department of Diagnostic Imaging, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Wu, John; Mao, Shenghua [Department of Biostatistics, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Davidoff, Andrew M. [Department of Surgery, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Department of Surgery, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee (United States); Neel, Michael D. [Department of Surgery, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Krasin, Matthew J., E-mail: matthew.krasin@stjude.org [Department of Radiation Oncology, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States)

2016-09-01

Purpose: To determine the rate of local failure using focal conformal, limited margin radiation therapy (RT) and dose escalation for tumors ≥8 cm (greatest dimension at diagnosis) in children and young adults with Ewing sarcoma (EWS). Methods and Materials: Eligible patients with EWS were treated on a phase 2 institutional trial of focal conformal, limited margin RT using conformal or intensity modulated techniques. The treatment volume incorporated a 1-cm constrained margin around the gross tumor. Unresected tumors, <8 cm at diagnosis, received a standard dose of 55.8 Gy and tumors ≥8 cm, an escalated dose to 64.8 Gy. Patients with microscopic residual disease after resection received adjuvant RT to 50.4 Gy. Adjuvant brachytherapy was permitted in selected patients. Results: Forty-five patients were enrolled: 26 with localized and 19 with metastatic disease. Median (range) age, tumor size, and follow-up were 13.0 years (2.9-24.7 years), 9.0 cm (2.4-17.0 cm), and 54.5 months (1.9-122.2 months), respectively. All patients received systemic chemotherapy. The median (range) RT dose for all patients was 56.1 Gy (45-65.5 Gy). Seventeen patients received adjuvant, 16 standard-dose, and 12 escalated-dose RT. Failures included 1 local, 10 distant, and 1 local/distant. The estimated 10-year cumulative incidence of local failure was 4.4% ± 3.1%, with no statistical difference seen between RT treatment groups and no local failures in the escalated-dose RT treatment group. Conclusions: Treatment with focal conformal, limited margin RT, including dose escalation for larger tumors, provides favorable local tumor control in EWS.

Limited Margin Radiation Therapy for Children and Young Adults With Ewing Sarcoma Achieves High Rates of Local Tumor Control

International Nuclear Information System (INIS)

Talleur, Aimee C.; Navid, Fariba; Spunt, Sheri L.; McCarville, M. Beth; Wu, John; Mao, Shenghua; Davidoff, Andrew M.; Neel, Michael D.; Krasin, Matthew J.

2016-01-01

Purpose: To determine the rate of local failure using focal conformal, limited margin radiation therapy (RT) and dose escalation for tumors ≥8 cm (greatest dimension at diagnosis) in children and young adults with Ewing sarcoma (EWS). Methods and Materials: Eligible patients with EWS were treated on a phase 2 institutional trial of focal conformal, limited margin RT using conformal or intensity modulated techniques. The treatment volume incorporated a 1-cm constrained margin around the gross tumor. Unresected tumors, <8 cm at diagnosis, received a standard dose of 55.8 Gy and tumors ≥8 cm, an escalated dose to 64.8 Gy. Patients with microscopic residual disease after resection received adjuvant RT to 50.4 Gy. Adjuvant brachytherapy was permitted in selected patients. Results: Forty-five patients were enrolled: 26 with localized and 19 with metastatic disease. Median (range) age, tumor size, and follow-up were 13.0 years (2.9-24.7 years), 9.0 cm (2.4-17.0 cm), and 54.5 months (1.9-122.2 months), respectively. All patients received systemic chemotherapy. The median (range) RT dose for all patients was 56.1 Gy (45-65.5 Gy). Seventeen patients received adjuvant, 16 standard-dose, and 12 escalated-dose RT. Failures included 1 local, 10 distant, and 1 local/distant. The estimated 10-year cumulative incidence of local failure was 4.4% ± 3.1%, with no statistical difference seen between RT treatment groups and no local failures in the escalated-dose RT treatment group. Conclusions: Treatment with focal conformal, limited margin RT, including dose escalation for larger tumors, provides favorable local tumor control in EWS.

Living donor liver transplantation for hepatocellular carcinoma achieves better outcomes.

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Lin, Chih-Che; Chen, Chao-Long

2016-10-01

Liver transplantation (LT) for hepatocellular carcinoma (HCC) at Kaohsiung Chang Gung Memorial Hospital mainly relies on live donor LT (LDLT). Owing to taking the risk of LD, we are obligated to adopt strict selection criteria for HCC patients and optimize the pre-transplant conditions to ensure a high disease-free survival similar to those without HCC, even better than deceased donor LT (DDLT). Better outcomes are attributed to excellent surgical results and optimal patient selection. The hospital mortality of primary and salvage LDLT are lower than 2% in our center. Although Taiwan Health Insurance Policy extended the Milan to University of California, San Francisco (UCSF) criteria in 2006, selection criteria will not be consolidated to take into account only by the morphologic size/number of tumors but also by their biology. The criteria are divided into modifiable image morphology, alpha fetoprotein (AFP), and positron emission tomography (PET) scan with standard uptake value (SUV) and unmodifiable unfavorable pathology such as HCC combined with cholangiocarcinoma (CC), sarcomatoid type, and poor differentiation. Downstaging therapy is necessary for HCC patients beyond criteria to fit all modifiable standards. The upper limit of downstaging treatment seems to be extended by more effective drug eluting transarterial chemoembolization in cases without absolute contraindications. In contrast, the pitfall of unmodifiable tumor pathology should be excluded by the findings of pretransplant core biopsy/resection if possible. More recently, achieving complete tumor necrosis in explanted liver could almost predict no recurrence after transplant. Necrotizing therapy is advised if possible before transplant even the tumor status within criteria to minimize the possibility of tumor recurrence. LDLT with low surgical mortality in experienced centers provides the opportunities of optimizing the pre-transplant tumor conditions and timing of transplant to achieve better

Ascorbate availability affects tumor implantation-take rate and increases tumor rejection in Gulo–/– mice

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Campbell EJ

2016-04-01

Full Text Available Elizabeth J Campbell,1 Margreet CM Vissers,2 Gabi U Dachs1 1Mackenzie Cancer Research Group, 2Centre for Free Radical Research, Department of Pathology, University of Otago, Christchurch, New Zealand Abstract: In solid tumors, HIF1 upregulates the expression of hundreds of genes involved in cell survival, tumor growth, and adaptation to the hypoxic microenvironment. HIF1 stabilization and activity are suppressed by prolyl and asparagine hydroxylases, which require oxygen as a substrate and ascorbate as a cofactor. This has led us to hypothesize that intracellular ascorbate availability could modify the hypoxic HIF1 response and influence tumor growth. In this study, we investigated the effect of variable intracellular ascorbate levels on HIF1 induction in cancer cells in vitro, and on tumor-take rate and growth in the Gulo–/– mouse. These mice depend on dietary ascorbate, and were supplemented with 3,300 mg/L, 330 mg/L, or 33 mg/L ascorbate in their drinking water, resulting in saturating, medium, or low plasma and tissue ascorbate levels, respectively. In Lewis lung carcinoma cells (LL/2 in culture, optimal ascorbate supplementation reduced HIF1 accumulation under physiological but not pathological hypoxia. LL/2, B16-F10 melanoma, or CMT-93 colorectal cancer cells were implanted subcutaneously into Gulo–/– mice at a range of cell inocula. Establishment of B16-F10 tumors in mice supplemented with 3,300 mg/L ascorbate required an increased number of cancer cells to initiate tumor growth compared with the number of cells required in mice on suboptimal ascorbate intake. Elevated ascorbate intake was also associated with decreased tumor ascorbate levels and a reduction in HIF1α expression and transcriptional activity. Following initial growth, all CMT-93 tumors regressed spontaneously, but mice supplemented with 33 mg/L ascorbate had lower plasma ascorbate levels and grew larger tumors than optimally supplemented mice. The data from this

Depth-weighted robust multivariate regression with application to sparse data

KAUST Repository

Dutta, Subhajit; Genton, Marc G.

2017-01-01

A robust method for multivariate regression is developed based on robust estimators of the joint location and scatter matrix of the explanatory and response variables using the notion of data depth. The multivariate regression estimator possesses desirable affine equivariance properties, achieves the best breakdown point of any affine equivariant estimator, and has an influence function which is bounded in both the response as well as the predictor variable. To increase the efficiency of this estimator, a re-weighted estimator based on robust Mahalanobis distances of the residual vectors is proposed. In practice, the method is more stable than existing methods that are constructed using subsamples of the data. The resulting multivariate regression technique is computationally feasible, and turns out to perform better than several popular robust multivariate regression methods when applied to various simulated data as well as a real benchmark data set. When the data dimension is quite high compared to the sample size it is still possible to use meaningful notions of data depth along with the corresponding depth values to construct a robust estimator in a sparse setting.

Robust Face Recognition via Multi-Scale Patch-Based Matrix Regression.

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Guangwei Gao

Full Text Available In many real-world applications such as smart card solutions, law enforcement, surveillance and access control, the limited training sample size is the most fundamental problem. By making use of the low-rank structural information of the reconstructed error image, the so-called nuclear norm-based matrix regression has been demonstrated to be effective for robust face recognition with continuous occlusions. However, the recognition performance of nuclear norm-based matrix regression degrades greatly in the face of the small sample size problem. An alternative solution to tackle this problem is performing matrix regression on each patch and then integrating the outputs from all patches. However, it is difficult to set an optimal patch size across different databases. To fully utilize the complementary information from different patch scales for the final decision, we propose a multi-scale patch-based matrix regression scheme based on which the ensemble of multi-scale outputs can be achieved optimally. Extensive experiments on benchmark face databases validate the effectiveness and robustness of our method, which outperforms several state-of-the-art patch-based face recognition algorithms.

Depth-weighted robust multivariate regression with application to sparse data

KAUST Repository

Dutta, Subhajit

2017-04-05

A robust method for multivariate regression is developed based on robust estimators of the joint location and scatter matrix of the explanatory and response variables using the notion of data depth. The multivariate regression estimator possesses desirable affine equivariance properties, achieves the best breakdown point of any affine equivariant estimator, and has an influence function which is bounded in both the response as well as the predictor variable. To increase the efficiency of this estimator, a re-weighted estimator based on robust Mahalanobis distances of the residual vectors is proposed. In practice, the method is more stable than existing methods that are constructed using subsamples of the data. The resulting multivariate regression technique is computationally feasible, and turns out to perform better than several popular robust multivariate regression methods when applied to various simulated data as well as a real benchmark data set. When the data dimension is quite high compared to the sample size it is still possible to use meaningful notions of data depth along with the corresponding depth values to construct a robust estimator in a sparse setting.

Forced LIGHT expression in prostate tumors overcomes Treg mediated immunosuppression and synergizes with a prostate tumor therapeutic vaccine by recruiting effector T lymphocytes.

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Yan, Lisa; Da Silva, Diane M; Verma, Bhavna; Gray, Andrew; Brand, Heike E; Skeate, Joseph G; Porras, Tania B; Kanodia, Shreya; Kast, W Martin

2015-02-15

LIGHT, a ligand for lymphotoxin-β receptor (LTβR) and herpes virus entry mediator, is predominantly expressed on activated immune cells and LTβR signaling leads to the recruitment of lymphocytes. The interaction between LIGHT and LTβR has been previously shown to activate immune cells and result in tumor regression in a virally-induced tumor model, but the role of LIGHT in tumor immunosuppression or in a prostate cancer setting, where self antigens exist, has not been explored. We hypothesized that forced expression of LIGHT in prostate tumors would shift the pattern of immune cell infiltration toward an anti-tumoral milieu, would inhibit T regulatory cells (Tregs) and would induce prostate cancer tumor associated antigen (TAA) specific T cells that would eradicate tumors. Real Time PCR was used to evaluate expression of forced LIGHT and other immunoregulatory genes in prostate tumors samples. For in vivo studies, adenovirus encoding murine LIGHT was injected intratumorally into TRAMP-C2 prostate cancer cell tumor bearing mice. Chemokine and cytokine concentrations were determined by multiplex ELISA. Flow cytometry was used to phenotype tumor infiltrating lymphocytes and expression of LIGHT on the tumor cell surface. Tumor-specific lymphocytes were quantified via ELISpot assay. Treg induction and Treg suppression assays determined Treg functionality after LIGHT treatment. LIGHT in combination with a therapeutic vaccine, PSCA TriVax, reduced tumor burden. LIGHT expression peaked within 48 hr of infection, recruited effector T cells that recognized mouse prostate stem cell antigen (PSCA) into the tumor microenvironment, and inhibited infiltration of Tregs. Tregs isolated from tumor draining lymph nodes had impaired suppressive capability after LIGHT treatment. Forced LIGHT treatment combined with PSCA TriVax therapeutic vaccination delays prostate cancer progression in mice by recruiting effector T lymphocytes to the tumor and inhibiting Treg mediated

Investigation of the effects of long-term infusion of 125I-iododeoxyuridine on tumor growth in mice (solid mouse tumor sarcoma-180)

International Nuclear Information System (INIS)

Wirtz, F.

1987-05-01

The present experiments were designed to test the therapeutic qualification of 125 I incorporated in DNA of tumor cells. The tumor-host system used was the solid mouse tumor sarcoma-180 growing on female albino mice (NMRI). A device was built which makes it possible to intravenously infuse tumor bearing mice with solutions of 125 IUdR for several weeks. Three or, respectively, 5 days before the onset of the infusions the mice were inocculated into the right hind leg with 3x10 5 tumor cells in 0.1 ml physiological salt solution. The total activity administered per mouse was 100 μCi infused during a period of 10 days. After termination of the infusions tumor sizes and retained radioactivities were measured every 5 days until death of the animals occured. In comparison with tumors of control animals tumors of mice infused with 125 IUdR showed a mean retardation in growth of about 27% of the volumes of control tumors during the total period of post-infusion observation (25 days). Extension of life expectancy and an increase of the rate of final tumor regression did not occur. Likewise, no significant differences were observed between tumors which were 3 or 5 days old on the first day of infusion. After termination of the infusions the residual whole-body radioactivity per mouse was about 1% of the total activity infused per animal. This was in good agreement with calculations considering rates of incorporation and excretion and confirmed earlier assumptions that only about 5% of the administered IUdR is incorporated initially. The number further confirmed that, during the first 10 days after incorporation, the daily loss of activity - due to cell death - is about 30%. Control animals without tumors showed a faster decrease of incorporated activity or, respectively, loss of cells than tumor bearing mice. This difference could in part be explained by an exhaution of the short-lived cell populations of the reticulo-endothelial system of tumor bearing animals. (orig

Massive hematemesis after radiofrequency ablation of metastatic liver tumor with successful hemostasis achieved through transarterial embolization.

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Liu, Chien-An; Chiu, Nai-Chi; Chiou, Yi-You

2018-03-03

Hemorrhagic complications are the most common major complications that occur after radiofrequency ablation, but hematemesis as a complication after radiofrequency ablation for hepatic tumor has not been mentioned before. A hepatogastric fistula as a delayed complication is also rare. We present the case of a 77-year-old man with severe hematemesis that occurred 2 months after radiofrequency ablation of a liver metastasis of gastric cancer. A ruptured hepatic artery pseudoaneurysm and a hepatogastric fistula were confirmed through serial imaging examinations. The current case is reported in combination with 2 rare major complications after radiofrequency ablation of a liver tumor. Copyright © 2018. Published by Elsevier Inc.

Pulsed terahertz imaging of breast cancer in freshly excised murine tumors

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Bowman, Tyler; Chavez, Tanny; Khan, Kamrul; Wu, Jingxian; Chakraborty, Avishek; Rajaram, Narasimhan; Bailey, Keith; El-Shenawee, Magda

2018-02-01

This paper investigates terahertz (THz) imaging and classification of freshly excised murine xenograft breast cancer tumors. These tumors are grown via injection of E0771 breast adenocarcinoma cells into the flank of mice maintained on high-fat diet. Within 1 h of excision, the tumor and adjacent tissues are imaged using a pulsed THz system in the reflection mode. The THz images are classified using a statistical Bayesian mixture model with unsupervised and supervised approaches. Correlation with digitized pathology images is conducted using classification images assigned by a modal class decision rule. The corresponding receiver operating characteristic curves are obtained based on the classification results. A total of 13 tumor samples obtained from 9 tumors are investigated. The results show good correlation of THz images with pathology results in all samples of cancer and fat tissues. For tumor samples of cancer, fat, and muscle tissues, THz images show reasonable correlation with pathology where the primary challenge lies in the overlapping dielectric properties of cancer and muscle tissues. The use of a supervised regression approach shows improvement in the classification images although not consistently in all tissue regions. Advancing THz imaging of breast tumors from mice and the development of accurate statistical models will ultimately progress the technique for the assessment of human breast tumor margins.

Tumor metabolism, the ketogenic diet and β-hydroxybutyrate: novel approaches to adjuvant brain tumor therapy

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Eric C. Woolf

2016-11-01

Full Text Available Malignant brain tumors are devastating despite aggressive treatments such as surgical resection, chemotherapy and radiation therapy. The average life expectancy of patients with newly diagnosed glioblastoma is approximately ~18 months. It is clear that increased survival of brain tumor patients requires the design of new therapeutic modalities, especially those that enhance currently available treatments and/or limit tumor growth. One novel therapeutic arena is the metabolic dysregulation that results in an increased need for glucose in tumor cells. This phenomenon suggests that a reduction in tumor growth could be achieved by decreasing glucose availability, which can be accomplished through pharmacological means or through the use of a high-fat, low-carbohydrate ketogenic diet (KD. The KD, as the name implies, also provides increased blood ketones to support the energy needs of normal tissues. Preclinical work from a number of laboratories has shown that the KD does indeed reduce tumor growth in vivo. In addition, the KD has been shown to reduce angiogenesis, inflammation, peri-tumoral edema, migration and invasion. Furthermore, this diet can enhance the activity of radiation and chemotherapy in a mouse model of glioma, thus increasing survival. Additional studies in vitro have indicated that increasing ketones such as β-hydroxybutyrate in the absence of glucose reduction can also inhibit cell growth and potentiate the effects of chemotherapy and radiation. Thus, while we are only beginning to understand the pluripotent mechanisms through which the KD affects tumor growth and response to conventional therapies, the emerging data provide strong support for the use of a KD in the treatment of malignant gliomas. This has led to a limited number of clinical trials investigating the use of a KD in patients with primary and recurrent glioma.

Energy-Driven Image Interpolation Using Gaussian Process Regression

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Lingling Zi

2012-01-01

Full Text Available Image interpolation, as a method of obtaining a high-resolution image from the corresponding low-resolution image, is a classical problem in image processing. In this paper, we propose a novel energy-driven interpolation algorithm employing Gaussian process regression. In our algorithm, each interpolated pixel is predicted by a combination of two information sources: first is a statistical model adopted to mine underlying information, and second is an energy computation technique used to acquire information on pixel properties. We further demonstrate that our algorithm can not only achieve image interpolation, but also reduce noise in the original image. Our experiments show that the proposed algorithm can achieve encouraging performance in terms of image visualization and quantitative measures.

Postoperative Stereotactic Radiosurgery Without Whole-Brain Radiation Therapy for Brain Metastases: Potential Role of Preoperative Tumor Size

International Nuclear Information System (INIS)

Hartford, Alan C.; Paravati, Anthony J.; Spire, William J.; Li, Zhongze; Jarvis, Lesley A.; Fadul, Camilo E.; Rhodes, C. Harker; Erkmen, Kadir; Friedman, Jonathan; Gladstone, David J.; Hug, Eugen B.; Roberts, David W.; Simmons, Nathan E.

2013-01-01

Purpose: Radiation therapy following resection of a brain metastasis increases the probability of disease control at the surgical site. We analyzed our experience with postoperative stereotactic radiosurgery (SRS) as an alternative to whole-brain radiotherapy (WBRT), with an emphasis on identifying factors that might predict intracranial disease control and overall survival (OS). Methods and Materials: We retrospectively reviewed all patients through December 2008, who, after surgical resection, underwent SRS to the tumor bed, deferring WBRT. Multiple factors were analyzed for time to intracranial recurrence (ICR), whether local recurrence (LR) at the surgical bed or “distant” recurrence (DR) in the brain, for time to WBRT, and for OS. Results: A total of 49 lesions in 47 patients were treated with postoperative SRS. With median follow-up of 9.3 months (range, 1.1-61.4 months), local control rates at the resection cavity were 85.5% at 1 year and 66.9% at 2 years. OS rates at 1 and 2 years were 52.5% and 31.7%, respectively. On univariate analysis (preoperative) tumors larger than 3.0 cm exhibited a significantly shorter time to LR. At a cutoff of 2.0 cm, larger tumors resulted in significantly shorter times not only for LR but also for DR, ICR, and salvage WBRT. While multivariate Cox regressions showed preoperative size to be significant for times to DR, ICR, and WBRT, in similar multivariate analysis for OS, only the graded prognostic assessment proved to be significant. However, the number of intracranial metastases at presentation was not significantly associated with OS nor with other outcome variables. Conclusions: Larger tumor size was associated with shorter time to recurrence and with shorter time to salvage WBRT; however, larger tumors were not associated with decrements in OS, suggesting successful salvage. SRS to the tumor bed without WBRT is an effective treatment for resected brain metastases, achieving local control particularly for tumors up to

The Association between Educational Achievements, Career ...

African Journals Online (AJOL)

Chi-square test and multivariate logistic regression tests were used in data analysis. Confidence level and level of ... Tooth brushing frequency, time and replacement time of tooth brush were found to be significantly associated with career aspiration (p=0.007; p=0.002; p=0.00 respectively). Achievement motives did not ...

Brown tumor of the maxilla in patient with secondary hyperparathyroidism

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Jović Nebojša

2004-01-01

Full Text Available Brown tumor or parathyroid osteopathy is a kind of bony lesion caused by hyperparathyroidism. It appears as an expansive osteolytic lesion mostly in mandible, ribs, pelvis and femur, but rarely in the upper jaw. Bone resorption is the result of osteoclastic activity due to an increased activity of parathyroid hormone. A 25-years-old male patient was operated on due to clinicaly and radiographicaly obvious maxillary tumor and increased values of parathyroid hormon (PTH - 1 050 ng/l. The level of calcium in blood was normal (Ca 2.34 mEq/L. The patient was dialyzed for years because of the chronic renal failure. Histopathologic analysis confirmed brown tumor, that appeared as bony lesion of secondary hyperparathyroidism due to the chronic renal failure. The operation of the upper jaw had been performed before parathyroidectomy, due to an excessive growth of tumor followed by heavy epistaxes. The subsequent parathyroidectomy was followed by the regression of remaining bony lesions.

A pan-inhibitor of DASH family enzymes induces immune-mediated regression of murine sarcoma and is a potent adjuvant to dendritic cell vaccination and adoptive T-cell therapy.

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Duncan, Brynn B; Highfill, Steven L; Qin, Haiying; Bouchkouj, Najat; Larabee, Shannon; Zhao, Peng; Woznica, Iwona; Liu, Yuxin; Li, Youhua; Wu, Wengen; Lai, Jack H; Jones, Barry; Mackall, Crystal L; Bachovchin, William W; Fry, Terry J

2013-10-01

Multimodality therapy consisting of surgery, chemotherapy, and radiation will fail in approximately 40% of patients with pediatric sarcomas and result in substantial long-term morbidity in those who are cured. Immunotherapeutic regimens for the treatment of solid tumors typically generate antigen-specific responses too weak to overcome considerable tumor burden and tumor suppressive mechanisms and are in need of adjuvant assistance. Previous work suggests that inhibitors of DASH (dipeptidyl peptidase IV activity and/or structural homologs) enzymes can mediate tumor regression by immune-mediated mechanisms. Herein, we demonstrate that the DASH inhibitor, ARI-4175, can induce regression and eradication of well-established solid tumors, both as a single agent and as an adjuvant to a dendritic cell (DC) vaccine and adoptive cell therapy (ACT) in mice implanted with the M3-9-M rhabdomyosarcoma cell line. Treatment with effective doses of ARI-4175 correlated with recruitment of myeloid (CD11b) cells, particularly myeloid DCs, to secondary lymphoid tissues and with reduced frequency of intratumoral monocytic (CD11bLy6-CLy6-G) myeloid-derived suppressor cells. In immunocompetent mice, combining ARI-4175 with a DC vaccine or ACT with tumor-primed T cells produced significant improvements in tumor responses against well-established M3-9-M tumors. In M3-9-M-bearing immunodeficient (Rag1) mice, ACT combined with ARI-4175 produced greater tumor responses and significantly improved survival compared with either treatment alone. These studies warrant the clinical investigation of ARI-4175 for treatment of sarcomas and other malignancies, particularly as an adjuvant to tumor vaccines and ACT.

Advanced statistics: linear regression, part II: multiple linear regression.

Science.gov (United States)

Marill, Keith A

2004-01-01

The applications of simple linear regression in medical research are limited, because in most situations, there are multiple relevant predictor variables. Univariate statistical techniques such as simple linear regression use a single predictor variable, and they often may be mathematically correct but clinically misleading. Multiple linear regression is a mathematical technique used to model the relationship between multiple independent predictor variables and a single dependent outcome variable. It is used in medical research to model observational data, as well as in diagnostic and therapeutic studies in which the outcome is dependent on more than one factor. Although the technique generally is limited to data that can be expressed with a linear function, it benefits from a well-developed mathematical framework that yields unique solutions and exact confidence intervals for regression coefficients. Building on Part I of this series, this article acquaints the reader with some of the important concepts in multiple regression analysis. These include multicollinearity, interaction effects, and an expansion of the discussion of inference testing, leverage, and variable transformations to multivariate models. Examples from the first article in this series are expanded on using a primarily graphic, rather than mathematical, approach. The importance of the relationships among the predictor variables and the dependence of the multivariate model coefficients on the choice of these variables are stressed. Finally, concepts in regression model building are discussed.

Enhanced tumor responses through therapies combining CCNU, MISO and radiation

International Nuclear Information System (INIS)

Siemann, D.W.; Hill, S.A.

1984-01-01

Studies were performed to determine whether the radiation sensitizer misonidazole (MISO) could enhance the tumor control probability in a treatment strategy combining radiation and the nitrosourea 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU). In initial experiments KHT sarcoma-bearing mice were injected with 1.0 mg/g of MISO simultaneously with a 20 mg/kg dose of CCNU 30-40 min prior to irradiation (1500 rad). With this treatment protocol approximately 60% of the mice were found to be tumor-free 100 days post treatment. By comparison all 2 agent combinations led to 0% cures. To evaluate the relative importance of chemopotentiation versus radiosensitization in the 3 agent protocol, tumors were treated with MISO plus one anti-tumor agent (either radiation of CCNU) and then at times ranging from 0 to 24 hr later exposed to the other agent. When the time between treatments was 0 to 6 hr, a 60 to 80% tumor control rate was achieved for both MISO plus radiation followed by CCNU and MISO plus CCNU followed by radiation. However if the time interval was increased to 18 or 24 hr, the cure rate in the former treatment regimen dropped to 10% while that of the latter remained high at 40%. The data therefore indicate that (1) improved tumor responses may be achieved when MISO is added to a radiation-chemotherapy combination and (2) MISO may be more effective in such a protocol when utilized as a chemopotentiator

The use of sonographic subjective tumor assessment, IOTA logistic regression model 1, IOTA Simple Rules and GI-RADS system in the preoperative prediction of malignancy in women with adnexal masses.

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Koneczny, Jarosław; Czekierdowski, Artur; Florczak, Marek; Poziemski, Paweł; Stachowicz, Norbert; Borowski, Dariusz

2017-01-01

Sonography based methods with various tumor markers are currently used to discriminate the type of adnexal masses. To compare the predictive value of selected sonography-based models along with subjective assessment in ovarian cancer prediction. We analyzed data of 271 women operated because of adnexal masses. All masses were verified by histological examination. Preoperative sonography was performed in all patients and various predictive models includ¬ing IOTA group logistic regression model LR1 (LR1), IOTA simple ultrasound-based rules by IOTA (SR), GI-RADS and risk of malignancy index (RMI3) were used. ROC curves were constructed and respective AUC's with 95% CI's were compared. Of 271 masses 78 proved to be malignant including 6 borderline tumors. LR1 had sensitivity of 91.0%, specificity of 91.2%, AUC = 0.95 (95% CI: 0.92-0.98). Sensitivity for GI-RADS for 271 patients was 88.5% with specificity of 85% and AUC = 0.91 (95% CI: 0.88-0.95). Subjective assessment yielded sensitivity and specificity of 85.9% and 96.9%, respectively with AUC = 0.97 (95% CI: 0.94-0.99). SR were applicable in 236 masses and had sensitivity of 90.6% with specificity of 95.3% and AUC = 0.93 (95% CI 0.89-0.97). RMI3 was calculated only in 104 women who had CA125 available and had sensitivity of 55.3%, specificity of 94% and AUC = 0.85 (95% CI: 0.77-0.93). Although subjective assessment by the ultrasound expert remains the best current method of adnexal tumors preoperative discrimination, the simplicity and high predictive value favor the IOTA SR method, and when not applicable, the IOTA LR1 or GI-RADS models to be primarily and effectively used.

Boosted beta regression.

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Matthias Schmid

Full Text Available Regression analysis with a bounded outcome is a common problem in applied statistics. Typical examples include regression models for percentage outcomes and the analysis of ratings that are measured on a bounded scale. In this paper, we consider beta regression, which is a generalization of logit models to situations where the response is continuous on the interval (0,1. Consequently, beta regression is a convenient tool for analyzing percentage responses. The classical approach to fit a beta regression model is to use maximum likelihood estimation with subsequent AIC-based variable selection. As an alternative to this established - yet unstable - approach, we propose a new estimation technique called boosted beta regression. With boosted beta regression estimation and variable selection can be carried out simultaneously in a highly efficient way. Additionally, both the mean and the variance of a percentage response can be modeled using flexible nonlinear covariate effects. As a consequence, the new method accounts for common problems such as overdispersion and non-binomial variance structures.

Prognostic value of lymph node-to-primary tumor standardized uptake value ratio in endometrioid endometrial carcinoma

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Chung, Hyun Hoon; Kim, Jae-Weon; Park, Noh-Hyun; Song, Yong Sang [Seoul National University College of Medicine, Department of Obstetrics and Gynecology, Cancer Research Institute, Seoul (Korea, Republic of); Cheon, Gi Jeong [Seoul National University College of Medicine, Department of Nuclear Medicine, Cancer Research Institute, Seoul (Korea, Republic of)

2018-01-15

To determine whether the relative metabolic activity of pelvic or para-aortic LN compared with that of primary tumor measured by preoperative [{sup 18}F]FDG PET/CT scan has prognostic value in patients with endometrioid endometrial carcinoma. We retrospectively reviewed patients with endometrioid endometrial carcinoma who underwent preoperative [{sup 18}F]FDG PET/CT scans. Prognostic values of PET/CT-derived metabolic variables such as maximum standardized uptake value (SUV) of the primary endometrial carcinoma (SUV{sub Tumor}) and LN (SUV{sub LN}), and the LN-to-endometrial carcinoma SUV ratio (SUV{sub LN} / SUV{sub Tumor}) were assessed. Clinico-pathological data, imaging data, and treatment results were reviewed for 107 eligible patients. Median post-surgical follow-up was 23 months (range, 6-60), and 7 (6.5%) patients experienced recurrence. Regression analysis showed that SUV{sub LN} / SUV{sub Tumor} (P < 0.001), SUV{sub LN} (P = 0.003), International Federation of Gynecology and Obstetrics (FIGO) stage (P = 0.006), and tumor grade (P = 0.011) were risk factors of recurrence. Multivariate regression analysis revealed that FIGO stage (P = 0.034) was the independent risk factor of recurrence. SUV{sub LN} / SUV{sub Tumor} showed significant correlation with FIGO stage (P < 0.001), LN metastasis (P < 0.001), lymphovascular space invasion (P < 0.001), recurrence (P = 0.001), tumor grade (P < 0.001), and deep myometrial invasion of tumor (P = 0.022). Patient groups categorized by SUV{sub LN} / SUV{sub Tumor} showed significant difference in progression-free survival (Log-rank test, P = 0.001). Preoperative SUV{sub LN} / SUV{sub Tumor} measured by [{sup 18}F]FDG PET/CT was significantly associated with recurrence, and may become a novel prognostic factor in patients with endometrioid endometrial carcinoma. (orig.)

Activated STAT5 promotes long-lived cytotoxic CD8+ T cells that induce regression of autochthonous melanoma.

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Grange, Magali; Buferne, Michel; Verdeil, Grégory; Leserman, Lee; Schmitt-Verhulst, Anne-Marie; Auphan-Anezin, Nathalie

2012-01-01

Immunotherapy based on adoptive transfer of tumor antigen-specific CD8(+) T cell (TC) is generally limited by poor in vivo expansion and tumor infiltration. In this study, we report that activated STAT5 transcription factors (STAT5CA) confer high efficiency on CD8(+) effector T cells (eTC) for host colonization after adoptive transfer. Engineered expression of STAT5CA in antigen-experienced TCs with poor replicative potential was also sufficient to convert them into long-lived antigen-responsive eTCs. In transplanted mastocytoma- or melanoma-bearing hosts, STAT5CA greatly enhanced the ability of eTCs to accumulate in tumors, become activated by tumor antigens, and to express the cytolytic factor granzyme B. Taken together, these properties contributed to an increase in tumor regression by STAT5CA-transduced, as compared with untransduced, TCs including when the latter control cells were combined with infusion of interleukin (IL)-2/anti-IL-2 complexes. In tumors arising in the autochthonous TiRP transgenic model of melanoma associated with systemic chronic inflammation, endogenous CD8(+) TCs were nonfunctional. In this setting, adoptive transfer of STAT5CA-transduced TCs produced superior antitumor effects compared with nontransduced TCs. Our findings imply that STAT5CA expression can render TCs resistant to the immunosuppressive environment of melanoma tumors, enhancing their ability to home to tumors and to maintain high granzyme B expression, as well as their capacity to stimulate granzyme B expression in endogenous TCs. ©2011 AACR.

Laser ablation of tumors: current concepts and recent developments

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Stroszczynski, C.; Gaffke, G.; Gnauck, M.; Ricke, J.; Felix, R.; Puls, R.; Speck, U.; Hosten, N.; Oettle, H.; Hohenberger, P.

2004-01-01

Purpose. The purpose of this paper is to present technical innovations and clinical results of percutaneous interventional laser ablation of tumors using new techniques. Methods. Laser ablation was performed in 182 patients (liver tumors: 131, non hepatic tumors - bone, lung, others: 51) after interdisciplinary consensus was obtained. The procedure was done using a combination of imaging modalities (CT/MRI, CT/US) or only closed high field MRI (1.5 T). All patients received an MRI-scan immediately after laser ablation. Results. In 90.9% of the patients with liver tumors, a complete ablation was achieved. Major events occurred in 5.4%. The technical success rate of laser ablation in non-hepatic tumors was high, clinical results differed depending on the treated organ. Conclusions. The treatment of tumors of the liver and other organs up to 5 cm by laser ablation was a safe procedure with a low rate of complications and side effects. Image guidance by MRI is advantageous for precise tumor visualization in all dimensions, therapy monitoring, and control of laser ablation results. (orig.) [de

Regression to Causality : Regression-style presentation influences causal attribution

DEFF Research Database (Denmark)

Bordacconi, Mats Joe; Larsen, Martin Vinæs

2014-01-01

of equivalent results presented as either regression models or as a test of two sample means. Our experiment shows that the subjects who were presented with results as estimates from a regression model were more inclined to interpret these results causally. Our experiment implies that scholars using regression...... models – one of the primary vehicles for analyzing statistical results in political science – encourage causal interpretation. Specifically, we demonstrate that presenting observational results in a regression model, rather than as a simple comparison of means, makes causal interpretation of the results...... more likely. Our experiment drew on a sample of 235 university students from three different social science degree programs (political science, sociology and economics), all of whom had received substantial training in statistics. The subjects were asked to compare and evaluate the validity...

Hallazgo de antígenos en un tumor murino espontáneo no inmunogénico mediante el uso de una vacuna basada en células dendríticas Unveiling antigens in a non-immunogenic spontaneous murine tumor using a dendritic cell-based vaccine

Directory of Open Access Journals (Sweden)

Verónica L. Reffo

2008-08-01

Full Text Available La inmunoterapia sería un tratamiento ideal contra el cáncer porque combina eficacia y especificidad, pero hasta hoy no ha dado resultados exitosos contra tumores establecidos. En este trabajo abordamos el problema de la falta de inmunogenicidad de los tumores espontáneos como una posible causa del fracaso de la inmunoterapia. Nos preguntamos si esta falta de inmunogenicidad se debe a la ausencia de antígenos o a la existencia de mecanismos tolerogénicos que impiden a esos antígenos iniciar una respuesta inmune. Para deslindar entre ambas alternativas, utilizamos dos tumores murinos -uno espontáneo y no inmunogénico (linfoma LB y otro inducido por metilcolantreno y fuertemente inmunogénico (fibrosarcoma MC-C- y la técnica de inmunización con células dendríticas (DC estimuladas con extracto acelular de tumor. Al estimular DC in vitro con extracto de LB, las DC no exhibieron maduración ni inmunizaron in vivo contra implantes de LB. Por otro lado, extractos de MC-C, hicieron madurar las DC y las convirtieron en poderosas vacunas contra implantes de MC-C pero no de LB, indicando que MC-C y LB no tienen antígenos compartidos. Por último, cuando DC fueron estimuladas con una mezcla de los extractos de LB y MC-C, expresaron marcadores de maduración y exhibieron capacidad vacunante contra LB. Estos resultados sugieren que el tumor LB tiene antígenos específicos de tumor pero carece de otras señales necesarias para la maduración de las DC. Estas señales serían aportadas por el extracto de MC-C, permitiendo de este modo iniciar una respuesta inmune contra LB.Up to date, most attempts to use immunotherapy to cause the regression of animal and human established tumors have not been successful. Former experiments have postulated that this failure could be attributed, at least in part, to a lack of immunogenicity of spontaneous tumors. In this paper, we have investigated whether this lack of immunogenicity can be attributed to the

Comparison of cell uptake, biodistribution and tumor retention of folate-coated and PEG-coated gadolinium nanoparticles in tumor-bearing mice.

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Oyewumi, Moses O; Yokel, Robert A; Jay, Michael; Coakley, Tricia; Mumper, Russell J

2004-03-24

The purpose of these studies was to compare the cell uptake, biodistribution and tumor retention of folate-coated and PEG-coated gadolinium (Gd) nanoparticles. Gd is a potential agent for neutron capture therapy (NCT) of tumors. Gd nanoparticles were engineered from oil-in-water microemulsion templates. To obtain folate-coated nanoparticles, a folate ligand [folic acid chemically linked to distearoylphosphatidylethanolamine (DSPE) via a PEG spacer MW 3350] was included in nanoparticle preparations. Similarly, control nanoparticles were coated with DSPE-PEG-MW 3350 (PEG-coated). Nanoparticles were characterized based on size, size distribution, morphology, biocompatibility and tumor cell uptake. In vivo studies were carried out in KB (human nasopharyngeal carcinoma) tumor-bearing athymic mice. Biodistribution and tumor retention studies were carried out at pre-determined time intervals after injection of nanoparticles (10 mg/kg). Gd nanoparticles did not aggregate platelets or activate neutrophils. The retention of nanoparticles in the blood 8, 16 and 24 h post-injection was 60%, 13% and 11% of the injected dose (ID), respectively. A maximum Gd tumor localization of 33+/-7 microg Gd/g was achieved. Both folate-coated and PEG-coated nanoparticles had comparable tumor accumulation. However, the cell uptake and tumor retention of folate-coated nanoparticles was significantly enhanced over PEG-coated nanoparticles. Thus, the benefits of folate ligand coating were to facilitate tumor cell internalization and retention of Gd-nanoparticles in the tumor tissue. The engineered nanoparticles may have potential in tumor-targeted delivery of Gd thereby enhancing the therapeutic success of NCT.

Chondroitin sulfate-functionalized polyamidoamine as a tumor-targeted carrier for miR-34a delivery.

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Chen, Wenqi; Liu, Yong; Liang, Xiao; Huang, Yu; Li, Quanshun

2017-07-15

Chondroitin sulfate (CS) was modified on a polyamidoamine dendrimer (PAMAM) through Michael addition to construct a tumor-targeted carrier CS-PAMAM for miR-34a delivery. The derivative CS-PAMAM was demonstrated to achieve an efficient cellular uptake of miR-34a in a CD44-dependent endocytosis way and further facilitate the endosomal escape of miR-34a after 4h. Through the miR-34a delivery, obvious inhibition of cell proliferation could be detected which was attributed to the enhancement of cell apoptosis and cell cycle arrest, and meanwhile the cell migration and invasion has been observed to be inhibited. Finally, the intravenous injection of CS-PAMAM/miR-34a formulation into mice bearing human lung adenocarcinoma cell A549 xenografts could efficiently inhibit the tumor growth and induce the tumor apoptosis owing to the enhanced accumulation of miR-34a in tumor tissue. Overall, CS-PAMAM is potential to be used as a tumor-targeted oligonucleotide carrier for achieving tumor gene therapy. The cationic dendrimer PAMAM was modified by chondroitin sulfate (CS) through Michael addition to construct a tumor-targeted carrier CS-PAMAM for miR-34a delivery. The introduction of CS could achieve an efficient cellular uptake and intracellular transfection of miR-34a in a CD44-dependent endocytosis manner. The miR-34a delivery could execute the anti-proliferation activity by simultaneously inducing cell apoptosis and cell cycle arrest, and also the anti-migration activity. The CS-PAMAM-mediated systemic delivery of miR-34a showed significant inhibition of tumor growth and induction of tumor apoptosis using a mice model of subcutaneously implanted tumors. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

[Diagnosis and surgical management in gastrointestinal neuroendocrine tumors].

Science.gov (United States)

Tomulescu, V; Stănciulea, O; Dima, S; Herlea, V; Stoica Mustafa, E; Dumitraşcu, T; Pechianu, C; Popescu, I

2011-01-01

Neuroendocrine tumors, known as carcinoid tumors constitute a heterogeneous group of neoplasms that present many clinical challenges. They secrete peptides and neuroamines that cause specific clinical syndromes. Assessment of specific or general tumors markers offers high sensitivity in establishing the diagnosis and they also have prognostic significance. Management strategies include curative surgery, whenever possible-that can be rarely achieved, palliative surgery, chemotherapy, radiologic therapy, such as radiofrequency ablation and chemoembolisations and somatostatin analogues therapy in order to control the symptoms. The aim of this paper is to review recent publications in this field and to give recommendations that take into account current advances in order to facilitate improvement in management and outcome.

Enhanced tumor imaging with pokeweed mitogen

International Nuclear Information System (INIS)

Bitner, D.M.; Mann, P.L.; D'Souza, P.; Wenk, R.; Baughman, D.G.; Quesada, S.M.; Purvis, R.; Born, J.L.; Matwiyoff, N.A.; Eshima, D.

1993-01-01

Traditional tumor imaging with biotracer techniques relies solely on the target specificity of the biomolecule. We hypothesize that specific imaging is possible by altering the rate of tissue clearance of any given radiotracer. Pokeweed mitogen (PWM) as a biomodulator, represents a class of molecules which regulate cellular differentiation and cell-cell interactions and, as part of these mechanisms alter tissue clearance rates. Utilizing the B-16/C57BL/6 model, 7 days post-transplantation, 10 animals were imaged following an i.v. injection of 1-2 mCi 99m Tc-PWM in order to visualize the tumors and determine the optimal imaging kinetics. A specific tumor image is achieved between 120 and 240 min post-injection. In addition, tumor imaging studies using a non-tumor-specific biomolecule were conducted by injecting 19 animals i.v. with 1-2 mCi of 99m Tc-human serum albumin (HSA). Twelve of these animals were given 10 μg of PWM i.p. at various intervals prior to the 99m Tc-HAS administration. Imaging and biodistribution studies were performed at various intervals up to 2 h post- 99m Tc-HSA injection. A 32-59% increase in the tumor-to-muscle ratio was observed in the PWM-treated animals relative to the non-treated controls. To further investigate the PWM-induced tissue clearance alteration hypothesis, tissue clearance studies using 99m Tc-diethylenetriaminepentaacetic acid (DTPA) were conducted in non-tumor bearing ICR mice and the B-16/C57BL/6 tumor bearing animals. 99m Tc-DTPA normal tissue clearance rates were significantly increased in the PWM treated animals relative to the non-treated controls. (author)

Oligodeoxynucleotides Expressing Polyguanosine Motifs Promote Anti-Tumor Activity through the Up-Regulation of IL-2

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Kobayashi, Nobuaki; Hong, Choongman; Klinman, Dennis M.; Shirota, Hidekazu

2012-01-01

The primary goal of cancer immunotherapy is to elicit an immune response capable of eliminating the tumor. One approach towards accomplishing that goal utilizes general (rather than tumor-specific) immunomodulatory agents to boost the number and activity of pre-existing cytotoxic T lymphocytes. We find that the intra-tumoral injection of poly-G ODN has such an effect, boosting anti-tumor immunity and promoting tumor regression. The anti-tumor activity of polyguanosine (poly-G) oligonucleotides (ODN) was mediated through CD8 T cells in a TLR9 independent manner. Mechanistically, poly-G ODN directly induced the phosphorylation of Lck (an essential element of the T cell signaling pathway), thereby enhancing the production of IL-2 and CD8 T cell proliferation. These findings establish poly-G ODN as a novel type of cancer immunotherapy. PMID:23296706

Trastuzumab anti-tumor efficacy in patient-derived esophageal squamous cell carcinoma xenograft (PDECX mouse models

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Wu Xianhua

2012-08-01

Full Text Available Abstract Background Trastuzumab is currently approved for the clinical treatment of breast and gastric cancer patients with HER-2 positive tumors, but not yet for the treatment of esophageal carcinoma patients, whose tumors typically show 5 ~ 35% HER-2 gene amplification and 0 ~ 56% HER-2 protein expression. This study aimed to investigate the therapeutic efficacy of Trastuzumab in patient-derived esophageal squamous cell carcinoma xenograft (PDECX mouse models. Methods PDECX models were established by implanting patient esophageal squamous cell carcinoma (ESCC tissues into immunodeficient (SCID/nude mice. HER-2 gene copy number (GCN and protein expression were determined in xenograft tissues and corresponding patient EC samples by FISH and IHC analysis. Trastuzumab anti-tumor efficacy was evaluated within these PDECX models (n = 8 animals/group. Furthermore, hotspot mutations of EGFR, K-ras, B-raf and PIK3CA genes were screened for in the PDECX models and their corresponding patient’s ESCC tissues. Similarity between the PDECX models and their corresponding patient’s ESCC tissue was confirmed by histology, morphology, HER-2 GCN and mutation. Results None of the PDECX models (or their corresponding patient’s ESCC tissues harbored HER-2 gene amplification. IHC staining showed HER-2 positivity (IHC 2+ in 2 PDECX models and negativity in 3 PDECX models. Significant tumor regression was observed in the Trastuzumab-treated EC044 HER-2 positive model (IHC 2+. A second HER-2 positive (IHC 2+ model, EC039, harbored a known PIK3CA mutation and showed strong activation of the AKT signaling pathway and was insensitive to Trastuzumab treatment, but could be resensitised using a combination of Trastuzumab and AKT inhibitor AZD5363. In summary, we established 5 PDECX mouse models and demonstrated tumor regression in response to Trastuzumab treatment in a HER-2 IHC 2+ model, but resistance in a HER-2 IHC 2+/PIK3CA mutated model. Conclusions

Family History of Cancer in Benign Brain Tumor Subtypes Versus Gliomas

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Ostrom, Quinn T. [Department of Anthropology, Case Western Reserve University, Cleveland, OH (United States); McCulloh, Christopher [Case Western Reserve University School of Medicine, Cleveland, OH (United States); Chen, Yanwen; Devine, Karen; Wolinsky, Yingli, E-mail: qto@case.edu [Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH (United States)

2012-02-28

Purpose: Family history is associated with gliomas, but this association has not been established for benign brain tumors. Using information from newly diagnosed primary brain tumor patients, we describe patterns of family cancer histories in patients with benign brain tumors and compare those to patients with gliomas. Methods: Newly diagnosed primary brain tumor patients were identified as part of the Ohio Brain Tumor Study. Each patient was asked to participate in a telephone interview about personal medical history, family history of cancer, and other exposures. Information was available from 33 acoustic neuroma (65%), 78 meningioma (65%), 49 pituitary adenoma (73.1%), and 152 glioma patients (58.2%). The association between family history of cancer and each subtype was compared with gliomas using unconditional logistic regression models generating odds ratios (ORs) and 95% confidence intervals. Results: There was no significant difference in family history of cancer between patients with glioma and benign subtypes. Conclusion: The results suggest that benign brain tumor may have an association with family history of cancer. More studies are warranted to disentangle the potential genetic and/or environmental causes for these diseases.

Family History of Cancer in Benign Brain Tumor Subtypes Versus Gliomas

International Nuclear Information System (INIS)

Ostrom, Quinn T.; McCulloh, Christopher; Chen, Yanwen; Devine, Karen; Wolinsky, Yingli

2012-01-01

Purpose: Family history is associated with gliomas, but this association has not been established for benign brain tumors. Using information from newly diagnosed primary brain tumor patients, we describe patterns of family cancer histories in patients with benign brain tumors and compare those to patients with gliomas. Methods: Newly diagnosed primary brain tumor patients were identified as part of the Ohio Brain Tumor Study. Each patient was asked to participate in a telephone interview about personal medical history, family history of cancer, and other exposures. Information was available from 33 acoustic neuroma (65%), 78 meningioma (65%), 49 pituitary adenoma (73.1%), and 152 glioma patients (58.2%). The association between family history of cancer and each subtype was compared with gliomas using unconditional logistic regression models generating odds ratios (ORs) and 95% confidence intervals. Results: There was no significant difference in family history of cancer between patients with glioma and benign subtypes. Conclusion: The results suggest that benign brain tumor may have an association with family history of cancer. More studies are warranted to disentangle the potential genetic and/or environmental causes for these diseases.

Family history of cancer in benign brain tumor subtypes versus gliomas

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Quinn eOstrom

2012-02-01

Full Text Available Purpose: Family history is associated with gliomas, but this association has not ben established for benign brain tumors. Using information from newly diagnosed primary brain tumor patients, we describe patterns of family cancer histories in patients with benign brain tumors and compare those to patients with gliomas. Methods: Newly diagnosed primary brain tumor patients were identified as part of the Ohio Brain Tumor Study (OBTS. Each patient was asked to participate in a telephone interview about personal medical history, family history of cancer, and other exposures. Information was available from 33 acoustic neuroma (65%, 78 meningioma (65%, 49 pituitary adenoma (73.1% and 152 glioma patients (58.2%. The association between family history of cancer and each subtype was compared with gliomas using unconditional logistic regression models generating odds ratios (ORs and 95% confidence intervals (95% CI. Results: There was no significant difference in family history of cancer between patients with glioma and benign subtypes. Conclusions: The results suggest that benign brain tumor may have an association with family history of cancer. More studies are warranted to disentangle the potential genetic and/or environmental causes for these diseases.

Effect of Emotional Intelligence on Student Learning Achievement

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Hendra Hadiwijaya

2017-08-01

Full Text Available The Effect of Emotional Intelligence Against Student Achievement aims to determine the effect of emotional intelligence which consists of self awareness, self management, Motivation, social awareness, relationship management partially and simultaneously on learning achievement. Respondents are students of SMP Negeri 4 Lalan Bumi Agung  Vilage Musi Banyuasin Regency to be 135 people. Methods of data analysis using regression analysis techniques. Partial assay results (t-test showed emotional intelligence consists of Self awareness, self management, Motivation, social awareness, relationship management positive and significant effect on learning achievement. Simultaneous Test Results (Test-F emotional intelligence consists of Self awareness, self management, motivation, social awareness, relationship management and significant positive effect on learning achievement. Social awareness is more dominant influence on learning achievement.

Combining miRNA and mRNA Expression Profiles in Wilms Tumor Subtypes

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Nicole Ludwig

2016-03-01

Full Text Available Wilms tumor (WT is the most common childhood renal cancer. Recent findings of mutations in microRNA (miRNA processing proteins suggest a pivotal role of miRNAs in WT genesis. We performed miRNA expression profiling of 36 WTs of different subtypes and four normal kidney tissues using microarrays. Additionally, we determined the gene expression profile of 28 of these tumors to identify potentially correlated target genes and affected pathways. We identified 85 miRNAs and 2107 messenger RNAs (mRNA differentially expressed in blastemal WT, and 266 miRNAs and 1267 mRNAs differentially expressed in regressive subtype. The hierarchical clustering of the samples, using either the miRNA or mRNA profile, showed the clear separation of WT from normal kidney samples, but the miRNA pattern yielded better separation of WT subtypes. A correlation analysis of the deregulated miRNA and mRNAs identified 13,026 miRNA/mRNA pairs with inversely correlated expression, of which 2844 are potential interactions of miRNA and their predicted mRNA targets. We found significant upregulation of miRNAs-183, -301a/b and -335 for the blastemal subtype, and miRNAs-181b, -223 and -630 for the regressive subtype. We found marked deregulation of miRNAs regulating epithelial to mesenchymal transition, especially in the blastemal subtype, and miRNAs influencing chemosensitivity, especially in regressive subtypes. Further research is needed to assess the influence of preoperative chemotherapy and tumor infiltrating lymphocytes on the miRNA and mRNA patterns in WT.

The dual role of tumor necrosis factor (TNF) in cancer biology.

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Bertazza, Loris; Mocellin, Simone

2010-01-01

Tumor necrosis factor (TNF) is a cytokine with well known anticancer properties and is being utilized as anticancer agent for the treatment of patients with locally advanced solid tumors. However, TNF role in cancer biology is debated. In fact, in spite of the wealth of evidence supporting its antitumor activity, the cascade of molecular events underlying TNF-mediated tumor regression observed in vivo is still incompletely elucidated. Furthermore, some preclinical findings suggest that TNF may even promote cancer development and progression. With this work we intend to summarize the molecular biology of TNF (with particular regard to its tumor-related activities) and review the experimental and clinical evidence currently available describing the complex and sometime apparently conflicting relationship between this cytokine, cancer biology and antitumor therapy. We also propose a model to explain the dual effect of TNF based on the exposure time and cytokine levels reached within the tumor microenvironment. Finally, we overview recent research findings that might lead to new ways for exploiting the anticancer potential of TNF in the clinical setting.

Filipino students' reported parental socialization of academic achievement by socioeconomic group.

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Bernardo, Allan B I

2009-10-01

Academic achievement of students differs by socioeconomic group. Parents' socialization of academic achievement in their children was explored in self-reports of 241 students from two socioeconomic status (SES) groups in the Philippines, using a scale developed by Bempechat, et al. Students in the upper SES group had higher achievement than their peers in the middle SES group, but had lower scores on most dimensions of parental socialization of academic achievement. Regression analyses indicate that reported parental attempts to encourage more effort to achieve was associated with lower achievement in students with upper SES.

Optimal factors of diffusion tensor imaging predicting cortico spinal tract injury in patients with brain tumors

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Min, Zhi Gang; Niu, Chen; Zhang, Qiu Li; Zhang, Ming [Dept. of Radiology, First Affiliated Hospital of Xi' an Jiaotong University, Xi' an (China); Qian, Yu Cheng [Dept. of Medical Imaging, School of Medicine, Jiangsu University, Zhenjiang (China)

2017-09-15

To identify the optimal factors in diffusion tensor imaging for predicting corticospinal tract (CST) injury caused by brain tumors. This prospective study included 33 patients with motor weakness and 64 patients with normal motor function. The movement of the CST, minimum distance between the CST and the tumor, and relative fractional anisotropy (rFA) of the CST on diffusion tensor imaging, were compared between patients with motor weakness and normal function. Logistic regression analysis was used to obtain the optimal factor predicting motor weakness. In patients with motor weakness, the displacement (8.44 ± 6.64 mm) of the CST (p = 0.009), minimum distance (3.98 ± 7.49 mm) between the CST and tumor (p < 0.001), and rFA (0.83 ± 0.11) of the CST (p < 0.001) were significantly different from those of the normal group (4.64 ± 6.65 mm, 14.87 ± 12.04 mm, and 0.98 ± 0.05, respectively) (p = 0.009, p < 0.001, and p < 0.001). The frequencies of patients with the CST passing through the tumor (6%, p = 0.002), CST close to the tumor (23%, p < 0.001), CST close to a malignant tumor (high grade glioma, metastasis, or lymphoma) (19%, p < 0.001), and CST passing through infiltrating edema (19%, p < 0.001) in the motor weakness group, were significantly different from those of the patients with normal motor function (0, 8, 1, and 10%, respectively). Logistic regression analysis showed that decreased rFA and CST close to a malignant tumor were effective variables related to motor weakness. Decreased fractional anisotropy, combined with closeness of a malignant tumor to the CST, is the optimal factor in predicting CST injury caused by a brain tumor.

Regression Levels of Selected Affective Factors on Science Achievement: A Structural Equation Model with TIMSS 2011 Data

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Akilli, Mustafa

2015-01-01

The aim of this study is to demonstrate the science success regression levels of chosen emotional features of 8th grade students using Structural Equation Model. The study was conducted by the analysis of students' questionnaires and science success in TIMSS 2011 data using SEM. Initially, the factors that are thought to have an effect on science…

The c-Met Inhibitor MSC2156119J Effectively Inhibits Tumor Growth in Liver Cancer Models

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Bladt, Friedhelm, E-mail: Friedhelm.Bladt@merckgroup.com; Friese-Hamim, Manja; Ihling, Christian; Wilm, Claudia; Blaukat, Andree [EMD Serono, and Merck Serono Research and Development, Merck KGaA, Darmstadt 64293 (Germany)

2014-08-19

The mesenchymal-epithelial transition factor (c-Met) is a receptor tyrosine kinase with hepatocyte growth factor (HGF) as its only high-affinity ligand. Aberrant activation of c-Met is associated with many human malignancies, including hepatocellular carcinoma (HCC). We investigated the in vivo antitumor and antimetastatic efficacy of the c-Met inhibitor MSC2156119J (EMD 1214063) in patient-derived tumor explants. BALB/c nude mice were inoculated with MHCC97H cells or with tumor fragments of 10 patient-derived primary liver cancer explants selected according to c-Met/HGF expression levels. MSC2156119J (10, 30, and 100 mg/kg) and sorafenib (50 mg/kg) were administered orally as single-agent treatment or in combination, with vehicle as control. Tumor response, metastases formation, and alpha fetoprotein (AFP) levels were measured. MSC2156119J inhibited tumor growth and induced complete regression in mice bearing subcutaneous and orthotopic MHCC97H tumors. AFP levels were undetectable after 5 weeks of MSC2156119J treatment, and the number of metastatic lung foci was reduced. Primary liver explant models with strong c-Met/HGF activation showed increased responsiveness to MSC2156119J, with MSC2156119J showing similar or superior activity to sorafenib. Tumors characterized by low c-Met expression were less sensitive to MSC2156119J. MSC2156119J was better tolerated than sorafenib, and combination therapy did not improve efficacy. These findings indicate that selective c-Met/HGF inhibition with MSC2156119J is associated with marked regression of c-Met high-expressing tumors, supporting its clinical development as an antitumor treatment for HCC patients with active c-Met signaling.

In vivo cation exchange in quantum dots for tumor-specific imaging.

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Liu, Xiangyou; Braun, Gary B; Qin, Mingde; Ruoslahti, Erkki; Sugahara, Kazuki N

2017-08-24

In vivo tumor imaging with nanoprobes suffers from poor tumor specificity. Here, we introduce a nanosystem, which allows selective background quenching to gain exceptionally tumor-specific signals. The system uses near-infrared quantum dots and a membrane-impermeable etchant, which serves as a cation donor. The etchant rapidly quenches the quantum dots through cation exchange (ionic etching), and facilitates renal clearance of metal ions released from the quantum dots. The quantum dots are intravenously delivered into orthotopic breast and pancreas tumors in mice by using the tumor-penetrating iRGD peptide. Subsequent etching quenches excess quantum dots, leaving a highly tumor-specific signal provided by the intact quantum dots remaining in the extravascular tumor cells and fibroblasts. No toxicity is noted. The system also facilitates the detection of peritoneal tumors with high specificity upon intraperitoneal tumor targeting and selective etching of excess untargeted quantum dots. In vivo cation exchange may be a promising strategy to enhance specificity of tumor imaging.The imaging of tumors in vivo using nanoprobes has been challenging due to the lack of sufficient tumor specificity. Here, the authors develop a tumor-specific quantum dot system that permits in vivo cation exchange to achieve selective background quenching and high tumor-specific imaging.

Clinical results of BNCT for malignant brain tumors in children

International Nuclear Information System (INIS)

Nakagawa, Yoshinobu; Kageji, Teruyoshi; Mizobuchi, Yoshifumi; Kumada, Hiroaki; Nakagawa, Yoshiaki

2009-01-01

It is very difficult to treat the patients with malignant brain tumor in children, especially under 3 years, because the conventional irradiation cannot be applied due to the damage of normal brain tissue. However, boron neutron capture therapy (BNCT) has tumor selectivity such that it can make damage only in tumor cells. We evaluated the clinical results and courses in patients with malignant glioma under 15 years. Among 183 patients with brain tumors treated by our group using BSH-based intra-operative BNCT, 23 patients were under 15 years. They included 4 patients under 3 years. There were 3 glioblastomas (GBM), 6 anaplastic astrocytomas(AAS), 7 primitive neuroectodermal tumors (PNET), 6 pontine gliomas and 1 anaplastic ependymoma. All GBM and PNET patients died due to CSF and/or CNS dissemination without local tumor regrowth. All pontine glioma patients died due to regrowth of the tumor. Four of 6 anaplastic astrocytoma and 1 anaplastic ependymoma patients alive without tumor recurrence. BNCT can be applied to malignant brain tumors in children, especially under 3 years instead of conventional radiation. Although it can achieve the local control in the primary site, it cannot prevent CSF dissemination in patients with glioblastoma.

Immune Suppression in Tumors as a Surmountable Obstacle to Clinical Efficacy of Cancer Vaccines

International Nuclear Information System (INIS)

Wieërs, Grégoire; Demotte, Nathalie; Godelaine, Danièle; Bruggen, Pierre van der

2011-01-01

Human tumors are usually not spontaneously eliminated by the immune system and therapeutic vaccination of cancer patients with defined antigens is followed by tumor regressions only in a small minority of the patients. The poor vaccination effectiveness could be explained by an immunosuppressive tumor microenvironment. Because T cells that infiltrate tumor metastases have an impaired ability to lyse target cells or to secrete cytokine, many researchers are trying to decipher the underlying immunosuppressive mechanisms. We will review these here, in particular those considered as potential therapeutic targets. A special attention will be given to galectins, a family of carbohydrate binding proteins. These lectins have often been implicated in inflammation and cancer and may be useful targets for the development of new anti-cancer therapies

Rank-Optimized Logistic Matrix Regression toward Improved Matrix Data Classification.

Science.gov (United States)

Zhang, Jianguang; Jiang, Jianmin

2018-02-01

While existing logistic regression suffers from overfitting and often fails in considering structural information, we propose a novel matrix-based logistic regression to overcome the weakness. In the proposed method, 2D matrices are directly used to learn two groups of parameter vectors along each dimension without vectorization, which allows the proposed method to fully exploit the underlying structural information embedded inside the 2D matrices. Further, we add a joint [Formula: see text]-norm on two parameter matrices, which are organized by aligning each group of parameter vectors in columns. This added co-regularization term has two roles-enhancing the effect of regularization and optimizing the rank during the learning process. With our proposed fast iterative solution, we carried out extensive experiments. The results show that in comparison to both the traditional tensor-based methods and the vector-based regression methods, our proposed solution achieves better performance for matrix data classifications.

Role of a Cyclooxygenase Inhibitor and Luteolin in the Regression of Colon Tumors in Irradiated Rats

International Nuclear Information System (INIS)

Ahmed, E.S.A.

2015-01-01

Colon carcinogenesis is a devastating problem leading to morbidity and mortality in developed countries. Colon cancer is a complex multi-step process involving progressive disruption of homeostatic mechanisms controlling intestinal epithelial proliferation/inflammation, differentiation and programmed cell death. Colon cancer is the third most common malignant neoplasm worldwide. Its incidence strongly varies globally and is closely linked to elements of a so-called western lifestyle. In Egypt reports showed that colon cancer was detected in 11–15% of patients who underwent colonoscopy and diagnosed in 29–31% of patients aged 40 years or younger. The present study was planned to evaluate the effect of a cyclooxygenase inhibitor (aspirin) and a natural product (luteolin) and on colon cancer induced by 1, 2 dimethylhydrazine (DMH), beside studying the effects of luteolin and aspirin either alone or combined with fractionated low doses of γ- irradiation as a route of cancer therapy. Seventy adult male Wistar rats were divided into seven groups 10 animals each and treated as follows: 1. Control group (G1): rats of this group received distilled water via gavages for 15 weeks. 2. Colon tumor induction group (G2): rats of this group were injected subcutaneously with DMH (20 mg/kg body weight) once a week for 15 weeks. 3. Colon tumor + irradiation group (G3): these rats were injected subcutaneously with DMH (20 mg/kg body weight) once a week for 15 weeks then at the beginning of the 8th week they were exposed to γ-radiation at a dose level of 0.5 Gy/week x 8 and continued during DMH treatment. 4. Colon tumor + aspirin treatment group (G4): rats of this group gavaged aspirin (50 mg/kg/ week) and injected subcutaneously with DMH for 15 weeks. 5. Colon tumor + luteolin treatment group (G5): these rats were treated orally with LUT (0.2 mg/kg body weight/ day) and injected subcutaneously with DMH (20 mg/kg body weight/ week) for 15 weeks. 6. Colon tumor + aspirin

Systematic review, meta-analysis, and meta-regression: Successful second-line treatment for Helicobacter pylori.

Science.gov (United States)

Muñoz, Neus; Sánchez-Delgado, Jordi; Baylina, Mireia; Puig, Ignasi; López-Góngora, Sheila; Suarez, David; Calvet, Xavier

2018-06-01

Multiple Helicobacter pylori second-line schedules have been described as potentially useful. It remains unclear, however, which are the best combinations, and which features of second-line treatments are related to better cure rates. The aim of this study was to determine that second-line treatments achieved excellent (>90%) cure rates by performing a systematic review and when possible a meta-analysis. A meta-regression was planned to determine the characteristics of treatments achieving excellent cure rates. A systematic review for studies evaluating second-line Helicobacter pylori treatment was carried out in multiple databases. A formal meta-analysis was performed when an adequate number of comparative studies was found, using RevMan5.3. A meta-regression for evaluating factors predicting cure rates >90% was performed using Stata Statistical Software. The systematic review identified 115 eligible studies, including 203 evaluable treatment arms. The results were extremely heterogeneous, with 61 treatment arms (30%) achieving optimal (>90%) cure rates. The meta-analysis favored quadruple therapies over triple (83.2% vs 76.1%, OR: 0.59:0.38-0.93; P = .02) and 14-day quadruple treatments over 7-day treatments (91.2% vs 81.5%, OR; 95% CI: 0.42:0.24-0.73; P = .002), although the differences were significant only in the per-protocol analysis. The meta-regression did not find any particular characteristics of the studies to be associated with excellent cure rates. Second-line Helicobacter pylori treatments achieving>90% cure rates are extremely heterogeneous. Quadruple therapy and 14-day treatments seem better than triple therapies and 7-day ones. No single characteristic of the treatments was related to excellent cure rates. Future approaches suitable for infectious diseases-thus considering antibiotic resistances-are needed to design rescue treatments that consistently achieve excellent cure rates. © 2018 John Wiley & Sons Ltd.

Antitumor effect of intra-arterial tumor necrosis factor-{alpha} in rats with transplanted intracerebral glioma and its evaluation by MRI

Energy Technology Data Exchange (ETDEWEB)

Harada, Kunyu; Yoshida, Jun; Wakabayashi, Toshihiko; Sugita, Kenichiro [Nagoya Univ. (Japan). School of Medicine; Kurisu, Kaoru; Uozumi, Tohru; Zieroth, B.F.; Takahashi, Masaya; Yamanaka, Tsuyoshi

1995-12-01

Recombinant human TNF-{alpha} was administrated intra-arterially to rats with transplanted intracerebral glioma. 1 x 10{sup 6} of T9 rat glioma cells were transplanted into Fisher 344 rat brain stereotaxically and 1000 units of TNF-{alpha} was administrated at a rate of 100{mu}l/min via an internal carotid artery 1 or 3 weeks after the transplantation. The effects of TNF-{alpha} were evaluated by MRI and histopathological examinations. Neurological symptoms, i.e. hemiparesis, appeared after 9.0{+-}0.63 days and all rats died of tumor overloading 14.5{+-}0.84 days after the transplantation. Single injection of TNF-{alpha} on 7th day after the transplantation induced regression of the tumor size in one of six rats. The tumors were detected 3 days after transplantation by MRI and they were revealed as low/iso intensity mass in T1WI, iso/high intensity in T2WI, and were enhanced by Gd-DTPA heterogenously. On 7/14 days after the transplantation, the tumor grew approximately 7/10 mm in diameter. The single 1000 units of TNF-{alpha} were administrated via an internal carotid artery. Three days after the administration or TNF-{alpha}, regression of the tumor size was seen in one of six rats and decrease of peritumoral edema was seen in three. These effects of TNF-{alpha} were, however, transient and they were not demonstrated on day 7. Single injection of TNF-{alpha} was not effective for large tumors more than 10 mm in diameter seen 14 days after the transplantation. These data suggest that intra-arterial TNF-{alpha} should be administrated at an early stage of the tumor growth and several injections are needed to cause regression in the size of the gliomas. (author).

Incidence and Curability of Tumors in Childhood in Slovakia

International Nuclear Information System (INIS)

Kaiserova, E.; Subova, Z.; Bubanska, E.; Stancokova, T.; Oravkinova, I.; Plank, L.

2006-01-01

Annual incidence of cancer in Slovak Republic for children 0 - 14 years old in 1991 - 2002 was 115,2 - 143 per million and for adolescents 15 - 19 years old 156 - 196 per million, in which mild increase was observed. Most often malignancies in children have been acute lymphoblastic leukemia and tumors of central nervous system. For children 0 - 4 years old have been characteristic also embryonal tumors (neuroblastoma, Wilms' tumor, retinoblastoma). In older than 10 years incidence of Hodgkins' lymphoma, osteosarcoma and carcinomas has been increasing. All children and adolescents 0 - 18 years have been treated exclusively in the last 10 years in three pediatric oncological centers. The survival significantly improved in last 10 years. Overall 4-years survival has been 76 % in years 2000 - 2003 in comparison with 5-years survival 63 % in 1990 - 1994. More than 75 % survival was achieved in acute lymphoblastic leukemia, Hodgkins' and non-Hodgkins' lymphomas, retinoblastoma, Wilms' tumor, germinal cell tumors and soft-tissue sarcomas. The worst survival was observed in acute non-lymphoblastic leukemia (56 %) and liver tumors (41 %). (author)

Early prediction of therapy response and disease free survival after induction chemotherapy in stage III non-small cell lung cancer by FDG-PET: Correlation between tumor FDG-metabolism and morphometric tumor response

International Nuclear Information System (INIS)

Baum, R.P.; Schmuecking, M.; Niesen, A.; Przetak, C.; Griesinger, F.

2002-01-01

Aim: Chemotherapy with Docetaxel and Carboplatin (DC) has shown high response rates in advanced non-small cell lung cancer (NSCLC). Histologic tumor response after chemotherapy or combined chemoradiotherapy is strongly associated with systemic tumor control and potentially cure. Metabolic tumor response assessed by FDG-PET after induction VIP-chemotherapy has been shown to be predictive of outcome in NSCLC. The aim of the present study was to correlate the tumor FDG metabolism as measured by F-18 FDG-PET with morphometric findings after DC induction chemotherapy plus Erythropoietin (10,000 IU Epo s.c. three times a week). Material and Methods: In this prospective multicenter study, 54 patients with NSCLC stage IIIA (9 patients) or IIIB (45 patients) were enrolled and received neoadjuvant treatment with D 100 mg/m 2 d1 and C AUC 7.5 d2 q21 days for 4 cycles prior to surgery. Postoperatively, all patients received adjuvant radiotherapy. WB-PET-studies (ECAT Exact 47) were obtained p.i. of 400 MBq F-18 FDG. Standardized uptake values (SUV), metabolic tumor diameter (MTD) and metabolic tumor index (MTI SUV x MTD) were assessed. Image fusion of PET and CT data was applied on a HERMES computer. Results: Of 54 enrolled patients, 46 were evaluable for response by CT. 30/46 patients (65%) achieved complete remission (CR, 1 patient) or partial remission (PR 29 patients.). Of the 46 patients, 37 patients completed neoadjuvant chemotherapy (Chx) and were studied before and after Chx by FDG-PET. 14 (30% of the 46 evaluable patients) had SUV < 2.5, corresponding to metabolic complete remission (mCR), 23 had PR or stable disease (non-mCR); in 9 patients, PET was not performed because of progressive disease demonstrated by CT. The R0-resection rate was 56% (27/48 evaluable patients). Of the 14 patients with metabolic CR, 9 were evaluated by morphometry. All had regression grades III (no vital tumor cells) or grade IIB (< 10% vital tumor cells and induced apoptosis). With a median

Adaptive radiotherapy strategies for pelvic tumors - a systematic review of clinical implementations

DEFF Research Database (Denmark)

Thörnqvist, Sara; Hysing, Liv B; Tuomikoski, Laura

2016-01-01

Med. For each tumor site, the identified papers were screened independently by two researches for selection of studies describing all processes of an ART workflow: treatment monitoring and evaluation, decision and execution of adaptations. Both brachytherapy and external beam studies were eligible for review...... patients were treated with offline re-planning, all to account for tumor regression detected by magnetic resonance imaging (MRI)/computed tomography (CT). For bladder and gyne, 161 and 64 patients, respectively, were treated with library-based online plan selection to account for target volume and shape...

Explicit hypoxia targeting with tumor suppression by creating an "obligate" anaerobic Salmonella Typhimurium strain.

Science.gov (United States)

Yu, Bin; Yang, Mei; Shi, Lei; Yao, Yandan; Jiang, Qinqin; Li, Xuefei; Tang, Lei-Han; Zheng, Bo-Jian; Yuen, Kwok-Yung; Smith, David K; Song, Erwei; Huang, Jian-Dong

2012-01-01

Using bacteria as therapeutic agents against solid tumors is emerging as an area of great potential in the treatment of cancer. Obligate and facultative anaerobic bacteria have been shown to infiltrate the hypoxic regions of solid tumors, thereby reducing their growth rate or causing regression. However, a major challenge for bacterial therapy of cancer with facultative anaerobes is avoiding damage to normal tissues. Consequently the virulence of bacteria must be adequately attenuated for therapeutic use. By placing an essential gene under a hypoxia conditioned promoter, SalmonellaTyphimurium strain SL7207 was engineered to survive only in anaerobic conditions (strain YB1) without otherwise affecting its functions. In breast tumor bearing nude mice, YB1 grew within the tumor, retarding its growth, while being rapidly eliminated from normal tissues. YB1 provides a safe bacterial vector for anti-tumor therapies without compromising the other functions or tumor fitness of the bacterium as attenuation methods normally do.

Early Indicators of Treatment Success After Percutaneous Radiofrequency of Pulmonary Tumors

International Nuclear Information System (INIS)

Anderson, Ewan Mark; Lees, W. R.; Gillams, A. R.

2009-01-01

We retrospectively reviewed the imaging of patients after radiofrequency ablation (RFA) of lung metastases performed at our institution to assess the usefulness of ground glass opacification (GGO) margin for the prediction of complete tumor ablation. From January 2004 to March 2007, patients were identified where there was a postprocedure thin collimation scan to allow multiplanar reformatting, either immediately or at 24 h and at least 6 months of imaging follow-up. Thirty-six tumors in 22 patients were identified. The scans were assessed for the presence and width of GGO margin, and minimal and maximal dimensions were measured. A second reviewer, blinded to the outcome of the postprocedure assessment, reviewed the follow-up imaging for recurrence. The recurrence group had larger tumors (p = 0.045) and smaller mean minimal GGO margin width (p = 0.0001). Multivariate binary regression analysis confirmed that the minimal GGO margin was significantly (p 5 mm is the minimal margion required to ensure complete tumor ablation.

Taming dendritic cells with TIM-3: Another immunosuppressive strategy by tumors

Science.gov (United States)

Patel, Jaina; Bozeman, Erica N.; Selvaraj, Periasamy

2013-01-01

The identification of TIM-3 expression on tumor associated dendritic cells (TADCs) provides insight into another aspect of tumor-mediated immunosuppression. The role of TIM-3 has been well characterized on tumor-infiltrating T cells, however its role on TADCs was not previously known. The current paper demonstrated that TIM-3 was predominantly expressed by TADCs and its interaction with the nuclear protein HMGB1 suppressed nucleic acid mediated activation of an effective antitumor immune response. The authors were able to show that TIM-3 interaction with HMGB1 prevented the localization of nucleic acids into endosomal vesicles. Furthermore, chemotherapy was found to be more effective in anti-TIM-3 mAb treated mice or mice depleted of all DCs which indicated that significant role played by TADCs inhibiting tumor regression. Taken together, these findings identify TIM-3 as a potential target for inducing antitumor immunity in conjunction with DNA vaccines and/or immunogenic chemotherapy in clinical settings. PMID:23240746

Histogenesis and progression of ultraviolet light-induced tumors in hairless mice

International Nuclear Information System (INIS)

Kligman, L.H.; Kligman, A.M.

1981-01-01

Tumor histogenesis and progression were studied in UV-irradiated albino (Skh:hairless-1) and lightly pigmented (Skh:hairless-2) hairless mice. A strongly carcinogenic dose of UV light was used, producing 100% tumor incidence by 35 weeks. The light source emitted mainly UV radiation in the range of 280-320 nm and the less energetic UV radiation up to 400 nm. The resulting epidermal changes and neoplasms resembled those seen in the actinically damaged skin of humans. Microscopic lesions included benign hyperplasia, actinic keratoses, and squamous cell carcinoma in situ and with microinvasion. Clinical tumors were epithelial papillomas, fibropapillomas, keratoacanthomas, cystic keratomas, benign pigmented macules, cutaneous hornlike growths, exophytic and endophytic squamous cell carcinomas of several cytologic types, and fibrosarcomas. Even with this high dose of UV radiation, not all of the small tumors progressed to cancer. Many regressed, including some keratoacanthomas, whereas others remained small and benign for the lifetime of the mouse

Boron compounds in neutron capture therapy of tumors

International Nuclear Information System (INIS)

Strouf, O.; Gregor, V.

1986-01-01

In the selective incorporation of a sufficient amount of a compound containing boron isotope 10 B in the tumor tissue for neutron capture therapy, high efficiency is achieved in tumor destruction while sparing the surrounding tissues. In the treatment of brain tumors, 4-carboxy phenylboric acid and the disodium salt of mercaptoundecahydrododecaborate were successfully tested. The use of the compounds minimizes radiation damage to the blood stream of the brain. In case of melanomas the L-DOPA-borate complex, boronophenylalanine and chlorpromazine preparations containing 10 B are used. In the treatment of cancer of the reproductive organs, boron derivatives of estradiol and testosterone have been proven. The immunobiological procedure, i.e., the use of antibodies with bound boron compounds, is being intensively studied. (M.D.)

Treatment of natural mammary gland tumors in canines and felines using gold nanorods-assisted plasmonic photothermal therapy to induce tumor apoptosis

Directory of Open Access Journals (Sweden)

Ali MRK

2016-09-01

Full Text Available Moustafa R K Ali,1 Ibrahim M Ibrahim,2,† Hala R Ali,2,3 Salah A Selim,2 Mostafa A El-Sayed1,4 1School of Chemistry and Biochemistry, Georgia Institute of Technology, and Laser Dynamics Laboratory, Atlanta, GA, USA; 2Department of Veterinary Medicine, Cairo University, Giza, Cairo, Egypt; 3Department of Bacteriology and Immunology, Animal Health Research Institute (AHRI, Dokki, Giza, Egypt; 4School of Chemistry, King Abdul Aziz University, Jeddah, Saudi Arabia †Ibrahim M Ibrahim passed away on August 23, 2015 Abstract: Plasmonic photothermal therapy (PPTT is a cancer therapy in which gold nanorods are injected at the site of a tumor before near-infrared light is transiently applied to the tumor causing localized cell death. Previously, PPTT studies have been carried out on xenograft mice models. Herein, we report a study showing the feasibility of PPTT as applied to natural tumors in the mammary glands of dogs and cats, which more realistically represent their human equivalents at the molecular level. We optimized a regime of three low PPTT doses at 2-week intervals that ablated tumors mainly via apoptosis in 13 natural mammary gland tumors from seven animals. Histopathology, X-ray, blood profiles, and comprehensive examinations were used for both the diagnosis and the evaluation of tumor statuses before and after treatment. Histopathology results showed an obvious reduction in the cancer grade shortly after the first treatment and a complete regression after the third treatment. Blood tests showed no obvious change in liver and kidney functions. Similarly, X-ray diffraction showed no metastasis after 1 year of treatment. In conclusion, our study suggests the feasibility of applying the gold nanorods-PPTT on natural tumors in dogs and cats without any relapse or toxicity effects after 1 year of treatment. Keywords: gold nanorods, natural mammary tumors, plasmonic photothermal therapy, canine, feline

Reduction of the radiogenic tumor incidence by stimulation with lyophilized fetal cells

International Nuclear Information System (INIS)

Bause, R.; Gros, C.J.; Landsberger, A.; Renner, H.; Klinikum Nuernberg

1983-01-01

The effect of an immunization treatment with lyophilized xenogenic fetal cells was studied in 7 months old, female albino rats (strain Wistar). The tumor incidence was measured after a sublethal whole-body irradiation with 600 cGy. Furthermore, the spleen of the individual animals was histologically examined. 3,5 to 6 months after a whole-body irradiation with 600 cGy, the tumor incidence was 55%. The tumors found were tubular adenocarcinomas of the thyroid gland. A significant reduction of the tumor incidence can be achieved by an immunostimulation with xenogenic, lyophilized, fetal cells (connective tissue and bone marrow, respectively) administered twice, namely eight days before and four days after the whole-body irradiation. The tumor incidence measured after 3,5 months was 10% and 15%, respectively, and after 6 months 15% and 25%, respectively. No significant tumor protection is achieved, however, by a single stimulation before whole-body irradiation and by a stimulation performed one or two times after whole-body irradiation. Histologic examinations of the spleen show in the immunostimulized animals a strong regeneration of the immune system with a significantly increased number of follicles and a significant increase of lumphocytes in the red pulp. The authors stress the possible clinical importance for radio-oncology of an immunostimulation with lyophilized, xenogenic, fetal cells. (orig.) [de

Radiation therapy of thoracic and abdominal tumors

International Nuclear Information System (INIS)

LaRue, S.M.; Gillette, S.M.; Poulson, J.M.

1995-01-01

Until recently, radiotherapy of thoracic and abdominal tumors in animals has been limited. However, the availability of computerized tomography and other imaging techniques to aid in determining the extent of tumor, an increase in knowledge of dose tolerance of regional organs, the availability of isocentrically mounted megavoltage machines, and the willingness of patients to pursue more aggressive treatment is making radiation therapy of tumors in these regions far more common. Tumor remission has been reported after radiation therapy of thymomas. Radiation therapy has been used to treat mediastinal lymphoma refractory to chemotherapy, and may be beneficial as part of the initial treatment regimen for this disease. Chemodectomas are responsive to radiation therapy in human patients, and favorable response has also been reported in dogs. Although primary lung tumors in dogs are rare, in some cases radiation therapy could be a useful primary or adjunctive therapy. Lung is the dose-limiting organ in the thorax. Bladder and urethral tumors in dogs have been treated using intraoperative and external-beam radiation therapy combined with chemotherapy. These tumors are difficult to control locally with surgery alone, although the optimal method of combining treatment modalities has not been established. Local control of malignant perianal tumors is also difficult to achieve with surgery alone, and radiation therapy should be used. Intraoperative radiation therapy combined with external-beam radiation therapy has been used for the management of metastatic carcinoma to the sublumbar lymph nodes. Tolerance of retroperitoneal tissues may be decreased by disease or surgical manipulation

Novel real-time tumor-contouring method using deep learning to prevent mistracking in X-ray fluoroscopy.

Science.gov (United States)

Terunuma, Toshiyuki; Tokui, Aoi; Sakae, Takeji

2018-03-01

Robustness to obstacles is the most important factor necessary to achieve accurate tumor tracking without fiducial markers. Some high-density structures, such as bone, are enhanced on X-ray fluoroscopic images, which cause tumor mistracking. Tumor tracking should be performed by controlling "importance recognition": the understanding that soft-tissue is an important tracking feature and bone structure is unimportant. We propose a new real-time tumor-contouring method that uses deep learning with importance recognition control. The novelty of the proposed method is the combination of the devised random overlay method and supervised deep learning to induce the recognition of structures in tumor contouring as important or unimportant. This method can be used for tumor contouring because it uses deep learning to perform image segmentation. Our results from a simulated fluoroscopy model showed accurate tracking of a low-visibility tumor with an error of approximately 1 mm, even if enhanced bone structure acted as an obstacle. A high similarity of approximately 0.95 on the Jaccard index was observed between the segmented and ground truth tumor regions. A short processing time of 25 ms was achieved. The results of this simulated fluoroscopy model support the feasibility of robust real-time tumor contouring with fluoroscopy. Further studies using clinical fluoroscopy are highly anticipated.

Adaptive kernel regression for freehand 3D ultrasound reconstruction

Science.gov (United States)

Alshalalfah, Abdel-Latif; Daoud, Mohammad I.; Al-Najar, Mahasen

2017-03-01

Freehand three-dimensional (3D) ultrasound imaging enables low-cost and flexible 3D scanning of arbitrary-shaped organs, where the operator can freely move a two-dimensional (2D) ultrasound probe to acquire a sequence of tracked cross-sectional images of the anatomy. Often, the acquired 2D ultrasound images are irregularly and sparsely distributed in the 3D space. Several 3D reconstruction algorithms have been proposed to synthesize 3D ultrasound volumes based on the acquired 2D images. A challenging task during the reconstruction process is to preserve the texture patterns in the synthesized volume and ensure that all gaps in the volume are correctly filled. This paper presents an adaptive kernel regression algorithm that can effectively reconstruct high-quality freehand 3D ultrasound volumes. The algorithm employs a kernel regression model that enables nonparametric interpolation of the voxel gray-level values. The kernel size of the regression model is adaptively adjusted based on the characteristics of the voxel that is being interpolated. In particular, when the algorithm is employed to interpolate a voxel located in a region with dense ultrasound data samples, the size of the kernel is reduced to preserve the texture patterns. On the other hand, the size of the kernel is increased in areas that include large gaps to enable effective gap filling. The performance of the proposed algorithm was compared with seven previous interpolation approaches by synthesizing freehand 3D ultrasound volumes of a benign breast tumor. The experimental results show that the proposed algorithm outperforms the other interpolation approaches.

Tumor prevalence and biomarkers of genotoxicity in brown bullhead (Ameiurus nebulosus) in Chesapeake Bay tributaries

Energy Technology Data Exchange (ETDEWEB)

Pinkney, Alfred E., E-mail: Fred_Pinkney@fws.gov [U.S. Fish and Wildlife Service, Chesapeake Bay Field Office, 177 Admiral Cochrane Drive, Annapolis, MD 21401 (United States); Harshbarger, John C., E-mail: jcharshbarger@verizon.net [Department of Pathology, George Washington University Medical Center, 2300 I Street, NW, Washington, DC 20037 (United States); Karouna-Renier, Natalie K., E-mail: nkarouna@usgs.gov [U.S. Geological Survey, Patuxent Wildlife Research Center, BARC, Bldg. 308, Beltsville, MD 20705 (United States); Jenko, Kathryn [U.S. Geological Survey, Patuxent Wildlife Research Center, BARC, Bldg. 308, Beltsville, MD 20705 (United States); Balk, Lennart, E-mail: lennart.balk@itm.su.se [Department of Applied Environmental Science (ITM), Stockholm University SE-106 91, Stockholm (Sweden); Skarphe Latin-Small-Letter-Eth insdottir, Halldora; Liewenborg, Birgitta [Department of Applied Environmental Science (ITM), Stockholm University SE-106 91, Stockholm (Sweden); Rutter, Michael A., E-mail: mar36@psu.edu [Department of Mathematics, Penn State Erie, The Behrend College, 5091 Station Road, Erie, PA 16563 (United States)

2011-12-01

We surveyed four Chesapeake Bay tributaries for skin and liver tumors in brown bullhead (Ameiurus nebulosus). We focused on the South River, where the highest skin tumor prevalence (53%) in the Bay watershed had been reported. The objectives were to 1) compare tumor prevalence with nearby rivers (Severn and Rhode) and a more remote river (Choptank); 2) investigate associations between tumor prevalence and polynuclear aromatic hydrocarbons (PAHs) and alkylating agents; and 3) statistically analyze Chesapeake Bay bullhead tumor data from 1992 through 2008. All four South River collections exhibited high skin tumor prevalence (19% to 58%), whereas skin tumor prevalence was 2%, 10%, and 52% in the three Severn collections; 0% and 2% in the Choptank collections; and 5.6% in the Rhode collection. Liver tumor prevalence was 0% to 6% in all but one South River collection (20%) and 0% to 6% in the three other rivers. In a subset of samples, PAH-like biliary metabolites and {sup 32}P-DNA adducts were used as biomarkers of exposure and response to polycyclic aromatic compounds (PACs). Adducts from alkylating agents were detected as O6-methyl-2 Prime -deoxyguanosine (O6Me-dG) and O6-ethyl-2 Prime -deoxyguanosine (O6Et-dG) modified DNA. Bullheads from the contaminated Anacostia River were used as a positive control for DNA adducts. {sup 32}P-DNA adduct concentrations were significantly higher in Anacostia bullhead livers compared with the other rivers. We identified alkyl DNA adducts in bullhead livers from the South and Anacostia, but not the Choptank. Neither the PAH-like bile metabolite data, sediment PAH data, nor the DNA adduct data suggest an association between liver or skin tumor prevalence and exposure to PACs or alkylating agents in the South, Choptank, Severn, or Rhode rivers. Logistic regression analysis of the Chesapeake Bay database revealed that sex and length were significant covariates for liver tumors and length was a significant covariate for skin tumors

Tumor prevalence and biomarkers of genotoxicity in brown bullhead (Ameiurus nebulosus) in Chesapeake Bay tributaries

International Nuclear Information System (INIS)

Pinkney, Alfred E.; Harshbarger, John C.; Karouna-Renier, Natalie K.; Jenko, Kathryn; Balk, Lennart; Skarphéðinsdóttir, Halldóra; Liewenborg, Birgitta; Rutter, Michael A.

2011-01-01

We surveyed four Chesapeake Bay tributaries for skin and liver tumors in brown bullhead (Ameiurus nebulosus). We focused on the South River, where the highest skin tumor prevalence (53%) in the Bay watershed had been reported. The objectives were to 1) compare tumor prevalence with nearby rivers (Severn and Rhode) and a more remote river (Choptank); 2) investigate associations between tumor prevalence and polynuclear aromatic hydrocarbons (PAHs) and alkylating agents; and 3) statistically analyze Chesapeake Bay bullhead tumor data from 1992 through 2008. All four South River collections exhibited high skin tumor prevalence (19% to 58%), whereas skin tumor prevalence was 2%, 10%, and 52% in the three Severn collections; 0% and 2% in the Choptank collections; and 5.6% in the Rhode collection. Liver tumor prevalence was 0% to 6% in all but one South River collection (20%) and 0% to 6% in the three other rivers. In a subset of samples, PAH-like biliary metabolites and 32 P-DNA adducts were used as biomarkers of exposure and response to polycyclic aromatic compounds (PACs). Adducts from alkylating agents were detected as O6-methyl-2′-deoxyguanosine (O6Me-dG) and O6-ethyl-2′-deoxyguanosine (O6Et-dG) modified DNA. Bullheads from the contaminated Anacostia River were used as a positive control for DNA adducts. 32 P-DNA adduct concentrations were significantly higher in Anacostia bullhead livers compared with the other rivers. We identified alkyl DNA adducts in bullhead livers from the South and Anacostia, but not the Choptank. Neither the PAH-like bile metabolite data, sediment PAH data, nor the DNA adduct data suggest an association between liver or skin tumor prevalence and exposure to PACs or alkylating agents in the South, Choptank, Severn, or Rhode rivers. Logistic regression analysis of the Chesapeake Bay database revealed that sex and length were significant covariates for liver tumors and length was a significant covariate for skin tumors. - Highlights: ► We

Regression analysis with categorized regression calibrated exposure: some interesting findings

Directory of Open Access Journals (Sweden)

Hjartåker Anette

2006-07-01

Full Text Available Abstract Background Regression calibration as a method for handling measurement error is becoming increasingly well-known and used in epidemiologic research. However, the standard version of the method is not appropriate for exposure analyzed on a categorical (e.g. quintile scale, an approach commonly used in epidemiologic studies. A tempting solution could then be to use the predicted continuous exposure obtained through the regression calibration method and treat it as an approximation to the true exposure, that is, include the categorized calibrated exposure in the main regression analysis. Methods We use semi-analytical calculations and simulations to evaluate the performance of the proposed approach compared to the naive approach of not correcting for measurement error, in situations where analyses are performed on quintile scale and when incorporating the original scale into the categorical variables, respectively. We also present analyses of real data, containing measures of folate intake and depression, from the Norwegian Women and Cancer study (NOWAC. Results In cases where extra information is available through replicated measurements and not validation data, regression calibration does not maintain important qualities of the true exposure distribution, thus estimates of variance and percentiles can be severely biased. We show that the outlined approach maintains much, in some cases all, of the misclassification found in the observed exposure. For that reason, regression analysis with the corrected variable included on a categorical scale is still biased. In some cases the corrected estimates are analytically equal to those obtained by the naive approach. Regression calibration is however vastly superior to the naive method when applying the medians of each category in the analysis. Conclusion Regression calibration in its most well-known form is not appropriate for measurement error correction when the exposure is analyzed on a

Radiotherapy for a cystadenolymphoma of the parotid gland (Warthin's tumor); Radiotherapie bei einem Zystadenolymphom der Parotis (Warthin-Tumor)

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Stallmann, C; Vacha, P; Vesely, H; Richter, E; Feyerabend, T [Medizinische Univ., Luebeck (Germany). Klinik fuer Strahlentherapie und Nuklearmedizin

2001-05-01

Background: With 17.6% of all primary parotid neoformations the benign Warthin's tumor (cystadenolymphoma) is the second common parotid gland tumor. Males > 50 years are affected predominantly. After surgery the recurrence rate is less than 5%. Histomorphologically the tumor is characterized by cystoid ducts lined by epithelial cells as well as lymphoid stroma. The lymphoid component has been described as radioresponsive whereas the epithelial parts are less radiosensitive. Since 1960 only one patient treated by primary radiotherapy has been published. Case report: A 77-year-old woman suffered from cystadenolymphoma (maximal diameter 7 cm). Because of its extension and the reduced performance status of the patient surgery was no option. Radiotherapy was performed with a total dose of 50 Gy. Clinically, the tumor regressed completely after 30 Gy, which was confirmed by CT at 6 weeks after completion of radiotherapy. After 6 and 12 months the patient stayed free of tumor. Epicrisis: In our case the cystadenolymphoma was unusually large (7 cm). Radiotherapy with 50 Gy induced complete tumor regression. The good clinical response after 30 Gy suggests that the necessary dose may be lower for less extended cystadenolymphomas. Conclusion: We present a case of cystadenolymphoma treated by radiotherapy with 50 Gy resulting in a complete remission. Due to missing published experiences no common recommendation for the total dose can be given. In the following situations radiotherapy should be considered: 1. high surgical risk of damage to the facial nerve, 2. unfavorable cosmetic outcome after surgery, 3. inoperability for internal risks, 4. refusal of operation. (orig.) [German] Hintergrund: Mit einem Anteil von 17,6% an allen primaeren Parotisneubildungen ist das gutartige Warthin-Tumor (Zystadenolymphom) der zweithaeufigste Ohrspeicheldruesentumor. Es erkranken ueberwiegend Maenner ab 50 Jahren. Nach Operation liegt die Rezidivrate unter 5%. Histomorphologische Kennzeichen

Proton magnetic spectroscopic imaging of the child's brain: the response of tumors to treatment

International Nuclear Information System (INIS)

Tzika, A.A.; Young Poussaint, T.; Astrakas, L.G.; Barnes, P.D.; Goumnerova, L.; Scott, R.M.; Black, P.McL.; Anthony, D.C.; Billett, A.L.; Tarbell, N.J.

2001-01-01

Our aim was to determine and/or predict response to treatment of brain tumors in children using proton magnetic resonance spectroscopic imaging (MRSI). We studied 24 patients aged 10 months to 24 years, using MRI and point-resolved spectroscopy (PRESS; TR 2000 TE 65 ms) with volume preselection and phase-encoding in two dimensions on a 1.5 T imager. Multiple logistic regression was used to establish independent predictors of active tumor growth. Biologically vital cell metabolites, such as N-acetyl aspartate and choline-containing compounds (Cho), were significantly different between tumor and control tissues (P<0.001). The eight brain tumors which responded to radiation or chemotherapy, exhibited lower Cho (P=0.05), higher total creatine (tCr) (P=0.02) and lower lactate and lipid (L) (P=0.04) than16 tumors which were not treated (except by surgery) or did not respond to treatment. The only significant independent predictor of active tumor growth was tCr (P<0.01). We suggest that tCr is useful in assessing response of brain tumors to treatment. (orig.)

eTumorType, An Algorithm of Discriminating Cancer Types for Circulating Tumor Cells or Cell-free DNAs in Blood.

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Zou, Jinfeng; Wang, Edwin

2017-04-01

With the technology development on detecting circulating tumor cells (CTCs) and cell-free DNAs (cfDNAs) in blood, serum, and plasma, non-invasive diagnosis of cancer becomes promising. A few studies reported good correlations between signals from tumor tissues and CTCs or cfDNAs, making it possible to detect cancers using CTCs and cfDNAs. However, the detection cannot tell which cancer types the person has. To meet these challenges, we developed an algorithm, eTumorType, to identify cancer types based on copy number variations (CNVs) of the cancer founding clone. eTumorType integrates cancer hallmark concepts and a few computational techniques such as stochastic gradient boosting, voting, centroid, and leading patterns. eTumorType has been trained and validated on a large dataset including 18 common cancer types and 5327 tumor samples. eTumorType produced high accuracies (0.86-0.96) and high recall rates (0.79-0.92) for predicting colon, brain, prostate, and kidney cancers. In addition, relatively high accuracies (0.78-0.92) and recall rates (0.58-0.95) have also been achieved for predicting ovarian, breast luminal, lung, endometrial, stomach, head and neck, leukemia, and skin cancers. These results suggest that eTumorType could be used for non-invasive diagnosis to determine cancer types based on CNVs of CTCs and cfDNAs. Copyright © 2017 Beijing Institute of Genomics, Chinese Academy of Sciences and Genetics Society of China. Production and hosting by Elsevier B.V. All rights reserved.

Tumor-Associated Macrophages and Neutrophils in Tumor Microenvironment

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Jaehong Kim

2016-01-01

Full Text Available Distinct tumor microenvironment forms in each progression step of cancer and has diverse capacities to induce both adverse and beneficial consequences for tumorigenesis. It is now known that immune cells can be activated to favor tumor growth and progression, most probably influenced by the tumor microenvironment. Tumor-associated macrophages and tumor-associated neutrophils can exert protumoral functions, enhancing tumor cell invasion and metastasis, angiogenesis, and extracellular matrix remodeling, while inhibiting the antitumoral immune surveillance. Considering that neutrophils in inflammatory environments recruit macrophages and that recruited macrophages affect neutrophil functions, there may be various degrees of interaction between tumor-associated macrophages and tumor-associated neutrophils. Platelets also play an important role in the recruitment and regulation of monocytic and granulocytic cells in the tumor tissues, suggesting that platelet function may be essential for generation of tumor-associated macrophages and tumor-associated neutrophils. In this review, we will explore the biology of tumor-associated macrophages and tumor-associated neutrophils and their possible interactions in the tumor microenvironment. Special attention will be given to the recruitment and activation of these tumor-associated cells and to the roles they play in maintenance of the tumor microenvironment and progression of tumors.

Measurement of some tumor markers by IRMA in vietnam

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Tran Xuan Truong

2004-01-01

As we known that a perfect tumor markers could be used in five different ways : for population screening, for diagnose, for monitoring therapy and for follow-up early evidence of cancer recurrence. In order to achieve perfect status a tumor markers would require total negativity in healthy subject, total positivity for single tumor type and close correlation between plasma tumor marker concentration and tumor size . The advance of monoclonal antibodies has had dramatic impact in oncology, where new tumor markers have been discovered and assay methods for all tumor markers have been improved commercially . Analytical performance of these new methods are potentially as good as that of the best Immunoradiometric assay for others analytes. In Vietnam, the first time we use immunoradiometric assay (IRMA) for the measurement of some tumor markers in normal subject and cancer diseases. These are Thyroglobulin (TG) of thyroid cancer, cancer-antigen 15-3 (CA15-3) of breast cancer and cancer-antigen 72-4 (CA72-4) of stomach cancer. We would like applying the CA72-4 in the indication of stomach cancer, CA15-3 in the differential diagnosis of breast cancer, and TG in the differential diagnosis of thyroid cancer. And all of these tumor markers were also used in the clinical follow-up and early detection of recurrence and metastatic Cancer of them. We could try researching on them much more. (authors)

Acellular organ scaffolds for tumor tissue engineering

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Guller, Anna; Trusova, Inna; Petersen, Elena; Shekhter, Anatoly; Kurkov, Alexander; Qian, Yi; Zvyagin, Andrei

2015-12-01

Rationale: Tissue engineering (TE) is an emerging alternative approach to create models of human malignant tumors for experimental oncology, personalized medicine and drug discovery studies. Being the bottom-up strategy, TE provides an opportunity to control and explore the role of every component of the model system, including cellular populations, supportive scaffolds and signalling molecules. Objectives: As an initial step to create a new ex vivo TE model of cancer, we optimized protocols to obtain organ-specific acellular matrices and evaluated their potential as TE scaffolds for culture of normal and tumor cells. Methods and results: Effective decellularization of animals' kidneys, ureter, lungs, heart, and liver has been achieved by detergent-based processing. The obtained scaffolds demonstrated biocompatibility and growthsupporting potential in combination with normal (Vero, MDCK) and tumor cell lines (C26, B16). Acellular scaffolds and TE constructs have been characterized and compared with morphological methods. Conclusions: The proposed methodology allows creation of sustainable 3D tumor TE constructs to explore the role of organ-specific cell-matrix interaction in tumorigenesis.

Dual antibody therapy to harness the innate anti-tumor immune response to enhance antibody targeting of tumors.

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Chester, Cariad; Marabelle, Aurelien; Houot, Roch; Kohrt, Holbrook E

2015-04-01

Cancer immunotherapy is a rapidly evolving field that offers a novel paradigm for cancer treatment: therapies focus on enhancing the immune system's innate and adaptive anti-tumor response. Early immunotherapeutics have achieved impressive clinical outcomes and monoclonal antibodies are now integral to therapeutic strategies in a variety of cancers. However, only recently have antibodies targeting innate immune cells entered clinical development. Innate immune effector cells play important roles in generating and maintaining antitumor immunity. Antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) are important innate immune mechanisms for tumor eradication. These cytolytic processes are initiated by the detection of a tumor-targeting antibody and can be augmented by activating co-stimulatory pathways or blocking inhibitory signals on innate immune cells. The combination of FDA-approved monoclonal antibodies with innate effector-targeting antibodies has demonstrated potent preclinical therapeutic synergy and early-phase combinatorial clinical trials are ongoing. Copyright © 2015 Elsevier Ltd. All rights reserved.

Prognostic value of PET/CT in lung cancer. Study of survival and tumor metabolic characterization

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Ladron de Guevara, David; Fuentes Anibal; Farina, Ciro; Corral, Camilo; Pefaur, Raul

2013-01-01

PET/CT (Positron emission tomography/computed tomography) is a hybrid image modality widely used in oncology, for staging, therapy evaluation or follow up. Aim: To evaluate the prognostic value of PET/CT in lung cancer. Material and Methods: Retrospective review of PET/CT records, selecting 51 patients with a lung malignancy, mass or nodule referred for PET/CT between December 2008 and December 2010. All had pathological confirmation of malignancy and had not been treated previously. Age, gender, body mass index, radiological features of lung tumor and metastases, and lung tumor 18 F-fluoro-2-deoxy-d-glucose uptake using the SUV (Standardized uptake value) index were recorded. Survival was analyzed using Kaplan-Meier curves and a Cox proportional regression analysis. Results: Pathology confirmed the presence of lung cancer in 47 patients aged 30 to 88 years. Four patients (7.8%) had other type of tumors such as carcinoid or lymphoma. Fifty percent of lung cancer patients died during a mean observation lapse of 18 months (range: 2-34 months). Patients with metastases, local lymph node involvement, a lung tumor size ≥ 3 cm and high tumor uptake (SUVmax > 6) had significantly lower survival. Occurrence of metastases was the only independent prognostic factor in the Cox regression. A lung lesion with a SUVmax ≥ 12 was always associated to hilar/mediastinal lymph node involvement. Conclusions: PET/CT imaging gives important prognostic information in lung cancer patients

TumorTracer: a method to identify the tissue of origin from the somatic mutations of a tumor specimen

DEFF Research Database (Denmark)

Marquard, Andrea Marion; Birkbak, Nicolai Juul; Thomas, Cecilia Engel

2015-01-01

A substantial proportion of cancer cases present with a metastatic tumor and require further testing to determine the primary site; many of these are never fully diagnosed and remain cancer of unknown primary origin (CUP). It has been previously demonstrated that the somatic point mutations......-copy-number classifier on three independent data sets: 1669 newly available public tumors of various types, a cohort of 91 breast metastases, and a set of 24 specimens from 9 lung cancer patients subjected to multiregion sequencing. The cross-validation accuracy was highest when all three types of information were used...... detected in a tumor can be used to identify its site of origin with limited accuracy. We hypothesized that higher accuracy could be achieved by a classification algorithm based on the following feature sets: 1) the number of nonsynonymous point mutations in a set of 232 specific cancer-associated genes, 2...

The Potential Biomarkers and Immunological Effects of Tumor-Derived Exosomes in Lung Cancer

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Shamila D. Alipoor

2018-04-01

Full Text Available Lung cancer remains the leading cause of cancer-related deaths worldwide. Despite considerable achievements in lung cancer diagnosis and treatment, the global control of the disease remains problematic. In this respect, greater understanding of the disease pathology is crucially needed for earlier diagnosis and more successful treatment to be achieved. Exosomes are nano-sized particles secreted from most cells, which allow cross talk between cells and their surrounding environment via transferring their cargo. Tumor cells, just like normal cells, also secrete exosomes that are termed Tumor-Derived Exosome or tumor-derived exosome (TEX. TEXs have gained attention for their immuno-modulatory activities, which strongly affect the tumor microenvironment and antitumor immune responses. The immunological activity of TEX influences both the innate and adaptive immune systems including natural killer cell activity and regulatory T-cell maturation as well as numerous anti-inflammatory responses. In the context of lung cancer, TEXs have been studied in order to better understand the mechanisms underlying tumor metastasis and progression. As such, TEX has the potential to act both as a biomarker for lung cancer diagnosis as well as the response to therapy.

Endoscopic resection of subepithelial tumors.

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Schmidt, Arthur; Bauder, Markus; Riecken, Bettina; Caca, Karel

2014-12-16

Management of subepithelial tumors (SETs) remains challenging. Endoscopic ultrasound (EUS) has improved differential diagnosis of these tumors but a definitive diagnosis on EUS findings alone can be achieved in the minority of cases. Complete endoscopic resection may provide a reasonable approach for tissue acquisition and may also be therapeutic in case of malignant lesions. Small SET restricted to the submucosa can be removed with established basic resection techniques. However, resection of SET arising from deeper layers of the gastrointestinal wall requires advanced endoscopic methods and harbours the risk of perforation. Innovative techniques such as submucosal tunneling and full thickness resection have expanded the frontiers of endoscopic therapy in the past years. This review will give an overview about endoscopic resection techniques of SET with a focus on novel methods.

Endocrine tumors other than thyroid tumors

International Nuclear Information System (INIS)

Takeichi, Norio; Dohi, Kiyohiko

1992-01-01

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

The review of the achieved degree of sustainable development in South Eastern Europe - The use of linear regression method

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Golusin, Mirjana [Educons University, Vojvode Putnika st. bb, 21013 Sremska Kamnica (RS); Ivanovic, Olja Munitlak [Faculty of Business in Services, Vojvode Putnik st. bb, 21013 Sremska Kamenica (RS); Teodorovic, Natasa [Faculty of Entrepreneurial Management, Modene st. 5, 21000 Novi Sad (RS)

2011-01-15

The need for preservation and adequate management of the quality of environment requires the development of new methods and techniques by which the achieved degree of sustainable development can be defined as well as the laws regarding the relationship among its subsystems. Main objective of research is to point to a strong contradiction between the development of ecological and economic subsystems. In order to improve previous research, this study suggests the use of linear evaluation, by which it is possible to determine the exact degree of contradiction between these two subsystems and to define the regularities as well as the deviations. Authors present the essential steps that were used. Conducted by the method of linear regression this research shows a significant negative correlation between ecological and economic subsystem indicators, whereas its value R{sup 2} 0.58 proves the expected contradiction that exists between the two previously mentioned subsystems. By observing the sustainable development as a two-dimensional system that includes ecological and economic indicators, the authors suggest the methodology to modelling the relationship between economic and ecological development as an orthogonal distance between the degree of the current state measured by the relation between economic and ecological indicators of sustainable development and the degree which was obtained in a traditional way. The method used in this research proved to be extremely suitable for modelling the relationship between ecological and economic subsystems of sustainable development. This research was conducted on a repeated sample of countries of South East Europe by including the data for France and Germany, being two countries on the highest level of development in the European Union. (author)

Radiofrequency hyperthermia for advanced malignant liver tumors

International Nuclear Information System (INIS)

Nagata, Y.; Okuno, Y.; Mitsumori, M.; Akuta, K.; Nishimura, Y.; Masunaga, S.; Kanamori, S.; Fujishiro, M.; Hiraoka, M.; Takahashi, M.; Abe, M.

1996-01-01

, average tumor temperature, and minimal tumor temperature in HCC were 41.2±0.2 deg. C Mean±SE), 40.3±1.3 deg. C and 40.1±0.2 deg. C respectively. The same thermometery results for non-HCC were 42.3±0.2 deg. C41.2±0.2 deg. C and 40.9±0.2 deg. C, respectively. The maximal and minimal temperatures (41.8±0.2 deg. C, 40.3±.0.4 deg. C in the responders (CR+PR) were higher than those (41.3±0.5 deg. C39.8± 0.4 deg. C in non-responders (NC+PD), but the difference was not significant. Of the 73 cases with HCC who were evaluated by CT, CR was achieved in (7(73))(10%), PR in (15(73))(21%), NC in (37(73))(51%), and PD in (14(73)) (19%). Of the 45 cases involving liver metastases evaluated by CT, CR was achieved in (3(45))(7%), PR in(17(45)) (38%), NC in (12(45))(27%), and PD in(13(45)) (29%). The one-year cumulative survival rate for HCC patients was 30.0%, and the five-year survival rate was 17.5%. The median survival was 5 months, and the longest survival was 144 months. The one-year survival of non-HCC was 32.5%, and the longest survival was 30 months. Conclusion: Even though the thermometry results for liver tumors were not satisfactory, the treatment result is promising. Further clinical trials of RF capacitive hyperthermia for the treatment of advanced liver tumors should be encouraged

Chemotherapy-Induced Regression of an Adrenocorticotropin-Secreting Pituitary Carcinoma Accompanied by Secondary Adrenal Insufficiency

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Robert Frank Cornell

2013-01-01

Full Text Available Purpose. Adrenocorticotropin- (ACTH- secreting pituitary carcinomas are rare and require multimodality treatment. The aim of this study was to report the response to various therapies and discuss the potential development of secondary adrenal insufficiency with cytotoxic chemotherapy. Methods. This report describes a man with a large silent corticotroph adenoma progressing to endogenous hypercortisolism and metastatic ACTH-secreting pituitary carcinoma over a period of 14 years. Results. Seven years after initial presentation, progressive tumor enlargement associated with the development of hypercortisolism mandated multiple pituitary tumor debulking procedures and radiotherapy. Testing of the Ki-67 proliferation index was markedly high and he developed a hepatic metastasis. Combination therapy with cisplatin and etoposide resulted in a substantial reduction in tumor size, near-complete regression of his liver metastasis, and dramatic decrease in ACTH secretion. This unexpectedly resulted in symptomatic secondary adrenal insufficiency. Conclusions. This is the first reported case of secondary adrenal insufficiency after use of cytotoxic chemotherapy for metastatic ACTH-secreting pituitary carcinoma. High proliferative indices may be predictive of dramatic responses to chemotherapy. Given the potential for such responses, the development of secondary adrenal insufficiency may occur and patients should be monitored accordingly.

Expectancy as a mediator of the relation between learning strategies and academic achievement among university students

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Shurbanovska Orhideja

2013-01-01

Full Text Available The aim of this study was to explore the mediation role of the expectancy component of motivation (self-efficacy and control beliefs for learning in the relationship between learning strategies (cognitive, meta-cognitive, resource management strategies and academic achievement. The sample consisted of 155 university students (85 psychology students and 70 architecture students. Learning strategies section from the MSLQ (Motivated Strategies for Learning Questionnaire was taken to assess the extent of learning strategies usage during exam preparation. Motivation for learning was measured by the Expectancy scale as a part of the Motivation section of the MSLQ. Mediation analysis was used for data processing. Following the proposed steps for mediation effect testing, a series of regression analyses was conducted: first, the expectancy component of motivation was regressed on learning strategies; second, academic achievement was regressed on learning strategies; and third, academic achievement was regressed on the expectancy component of motivation. It was found that learning strategies influence academic achievement indirectly through the expectancy component of motivation (Sobel test=2.18; p=.029. It is emphasized that students should be encouraged to use learning strategies in knowledge acquisition.

The study on linac stereotactic radiosurgery for acoustic tumors

International Nuclear Information System (INIS)

Ohishi, Hitoshi

1995-01-01

We have designed and manufactured a new type of device for stereotactic radiosurgery characterized by the combined use of a rotatory chair and a linear accelerator. In this study, 20 acoustic tumors treated by our modality were evaluated by serial neuroimaging, neurofunctional outcome and, in a few cases, pathological findings of surgical specimens. Because tumor size usually changed very slowly after radiosurgery, 12 cases that had a minimum of 12 months of follow-up were employed in the analysis of tumor size. Serial neuroimaging studies revealed the reduction of tumor size in 3 cases and prevention of tumor growth in 7 cases, therefore, the rate of tumor control was evaluated as 83%. Growth of tumor size occurred in 3 cases, two were cases harbouring a large cyst in the tumor and another was a case of neurofibromatosis type 2. In 13 cases (68%), loss of the gadolinium enhancement effect inside the tumor was observed. This is a characteristic change after radiosurgery for acoustic tumors, and attributable to a necrotic change. Cranial nerve neuropathies as a complication also occurred (facial nerve palsy in 2 and trigeminal nerve dysfunction in 1). Adjacent parenchymal change appeared in 1 case. This patient had two prior operations and the tumor had an irregular shape, therefore, planning for radiosurgery encountered some difficulty. Hydrocephalus occurred in 1 case. Surgical specimens in 2 cases in which microsurgery was undertaken for growing tumors, revealed a necrotic tumor tissue and proliferation of fibrous tissue. In conclusion, our new device for stereotactic radiosurgery is particularly useful for the treatment of acoustic tumors. Similar therapeutic results of the gamma knife have been achieved. Radiosurgery is a recommendable treatment for acoustic tumors. However, the superiority of radiosurgery over microsurgery is still controversial and needs a longer term follow-up and multivariate analysis for a final conclusion. (author)

Self-Concept Predicts Academic Achievement Across Levels of the Achievement Distribution: Domain Specificity for Math and Reading.

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Susperreguy, Maria Ines; Davis-Kean, Pamela E; Duckworth, Kathryn; Chen, Meichu

2017-09-18

This study examines whether self-concept of ability in math and reading predicts later math and reading attainment across different levels of achievement. Data from three large-scale longitudinal data sets, the Avon Longitudinal Study of Parents and Children, National Institute of Child Health and Human Development-Study of Early Child Care and Youth Development, and Panel Study of Income Dynamics-Child Development Supplement, were used to answer this question by employing quantile regression analyses. After controlling for demographic variables, child characteristics, and early ability, the findings indicate that self-concept of ability in math and reading predicts later achievement in each respective domain across all quantile levels of achievement. These results were replicated across the three data sets representing different populations and provide robust evidence for the role of self-concept of ability in understanding achievement from early childhood to adolescence across the spectrum of performance (low to high). © 2017 The Authors. Child Development © 2017 Society for Research in Child Development, Inc.

Response of the primary tumor in symptomatic and asymptomatic stage IV colorectal cancer to combined interventional endoscopy and palliative chemotherapy

International Nuclear Information System (INIS)

Cameron, Silke; Hünerbein, Diana; Mansuroglu, Tümen; Armbrust, Thomas; Scharf, Jens-Gerd; Schwörer, Harald; Füzesi, László; Ramadori, Giuliano

2009-01-01

The treatment of the primary tumor in advanced metastatic colorectal cancer (CRC) is still a matter of discussion. Little attention has thus far been paid to the endoscopically observable changes of the primary in non-curatively resectable stage IV disease. 20 patients [14 men, 6 women, median age 67 (39–82) years] were observed after initial diagnosis of non-curatively resectable metastasized symptomatic (83%) or asymptomatic (17%) CRC, from June 2002 to April 2009. If necessary, endoscopic tumor debulking was performed. 5-FU based chemotherapy was given immediately thereafter. In 10 patients, chemotherapy was combined with antibody therapy. Response of the primary was observed in all patients. Local symptoms were treated endoscopically whenever necessary (obstruction or bleeding), and further improved after chemotherapy was started: Four patients showed initial complete endoscopic disappearance of the primary. In an additional 6 patients, only adenomatous tissue was histologically detected. In both these groups, two patients revealed local tumor relapse after interruption of therapy. Local tumor regression or stable disease was achieved in the remaining 10 patients. 15 patients died during the observation time. In 13 cases, death was related to metastatic disease progression. The mean overall survival time was 19.6 (3–71) months. No complications due to the primary were observed. This study shows that modern anti-cancer drugs combined with endoscopic therapy are an effective and safe treatment of the symptomatic primary and ameliorate local complaints without the need for surgical intervention in advanced UICC stage IV CRC

Tumor cell-derived microparticles polarize M2 tumor-associated macrophages for tumor progression.

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Ma, Ruihua; Ji, Tiantian; Chen, Degao; Dong, Wenqian; Zhang, Huafeng; Yin, Xiaonan; Ma, Jingwei; Liang, Xiaoyu; Zhang, Yi; Shen, Guanxin; Qin, Xiaofeng; Huang, Bo

2016-04-01

Despite identification of macrophages in tumors (tumor-associated macrophages, TAM) as potential targets for cancer therapy, the origin and function of TAM in the context of malignancy remain poorly characterized. Here, we show that microparticles (MPs), as a by-product, released by tumor cells act as a general mechanism to mediate M2 polarization of TAM. Taking up tumor MPs by macrophages is a very efficient process, which in turn results in the polarization of macrophages into M2 type, not only leading to promoting tumor growth and metastasis but also facilitating cancer stem cell development. Moreover, we demonstrate that the underlying mechanism involves the activation of the cGAS/STING/TBK1/STAT6 pathway by tumor MPs. Finally, in addition to murine tumor MPs, we show that human counterparts also possess consistent effect on human M2 polarization. These findings provide new insights into a critical role of tumor MPs in remodeling of tumor microenvironment and better understanding of the communications between tumors and macrophages.

Detecting overdispersion in count data: A zero-inflated Poisson regression analysis

Science.gov (United States)

Afiqah Muhamad Jamil, Siti; Asrul Affendi Abdullah, M.; Kek, Sie Long; Nor, Maria Elena; Mohamed, Maryati; Ismail, Norradihah

2017-09-01

This study focusing on analysing count data of butterflies communities in Jasin, Melaka. In analysing count dependent variable, the Poisson regression model has been known as a benchmark model for regression analysis. Continuing from the previous literature that used Poisson regression analysis, this study comprising the used of zero-inflated Poisson (ZIP) regression analysis to gain acute precision on analysing the count data of butterfly communities in Jasin, Melaka. On the other hands, Poisson regression should be abandoned in the favour of count data models, which are capable of taking into account the extra zeros explicitly. By far, one of the most popular models include ZIP regression model. The data of butterfly communities which had been called as the number of subjects in this study had been taken in Jasin, Melaka and consisted of 131 number of subjects visits Jasin, Melaka. Since the researchers are considering the number of subjects, this data set consists of five families of butterfly and represent the five variables involve in the analysis which are the types of subjects. Besides, the analysis of ZIP used the SAS procedure of overdispersion in analysing zeros value and the main purpose of continuing the previous study is to compare which models would be better than when exists zero values for the observation of the count data. The analysis used AIC, BIC and Voung test of 5% level significance in order to achieve the objectives. The finding indicates that there is a presence of over-dispersion in analysing zero value. The ZIP regression model is better than Poisson regression model when zero values exist.

Time-adaptive quantile regression

DEFF Research Database (Denmark)

Møller, Jan Kloppenborg; Nielsen, Henrik Aalborg; Madsen, Henrik

2008-01-01

and an updating procedure are combined into a new algorithm for time-adaptive quantile regression, which generates new solutions on the basis of the old solution, leading to savings in computation time. The suggested algorithm is tested against a static quantile regression model on a data set with wind power......An algorithm for time-adaptive quantile regression is presented. The algorithm is based on the simplex algorithm, and the linear optimization formulation of the quantile regression problem is given. The observations have been split to allow a direct use of the simplex algorithm. The simplex method...... production, where the models combine splines and quantile regression. The comparison indicates superior performance for the time-adaptive quantile regression in all the performance parameters considered....

Explicit hypoxia targeting with tumor suppression by creating an “obligate” anaerobic Salmonella Typhimurium strain

Science.gov (United States)

Yu, Bin; Yang, Mei; Shi, Lei; Yao, Yandan; Jiang, Qinqin; Li, Xuefei; Tang, Lei-Han; Zheng, Bo-Jian; Yuen, Kwok-Yung; Smith, David K.; Song, Erwei; Huang, Jian-Dong

2012-01-01

Using bacteria as therapeutic agents against solid tumors is emerging as an area of great potential in the treatment of cancer. Obligate and facultative anaerobic bacteria have been shown to infiltrate the hypoxic regions of solid tumors, thereby reducing their growth rate or causing regression. However, a major challenge for bacterial therapy of cancer with facultative anaerobes is avoiding damage to normal tissues. Consequently the virulence of bacteria must be adequately attenuated for therapeutic use. By placing an essential gene under a hypoxia conditioned promoter, Salmonella Typhimurium strain SL7207 was engineered to survive only in anaerobic conditions (strain YB1) without otherwise affecting its functions. In breast tumor bearing nude mice, YB1 grew within the tumor, retarding its growth, while being rapidly eliminated from normal tissues. YB1 provides a safe bacterial vector for anti-tumor therapies without compromising the other functions or tumor fitness of the bacterium as attenuation methods normally do. PMID:22666539

TU-CD-304-06: Using FFF Beams Improves Tumor Control in Radiotherapy of Lung Cancers

Energy Technology Data Exchange (ETDEWEB)

Vassiliev, O [Mary Bird Perkins Cancer Center, Baton Rouge, LA (United States); Wang, H [UT MD Anderson Cancer Center, Houston, TX (United States)

2015-06-15

Purpose: Electron disequilibrium at the lung-tumor interface results in an under-dosage of tumor regions close to its surface. This under-dosage is known to be significant and can compromise tumor control. Previous studies have shown that in FFF beams, disequilibrium effects are less pronounced, which is manifested in an increased skin dose. In this study we investigate the improvement in tumor dose coverage that can be achieved with FFF beams. The significance of this improvement is evaluated by comparing tumor control probabilities of FFF beams and conventional flattened beams. Methods: The dosimetric coverage was investigated in a virtual phantom representing the chest wall, lung tissue and the tumor. A range of tumor sizes was investigated, and two tumor locations – central and adjacent to the chest wall. Calculations were performed with BEAMnrc Monte Carlo code. Parallel-opposed and multiple coplanar 6-MV beams were simulated. The tumor control probabilities were calculated using the logistic model with parameters derived from clinical data for non-small lung cancer patients. Results: FFF beams were not entirely immune to disequilibrium effects. They nevertheless consistently delivered more uniform dose distribution throughout the volume of the tumor, and eliminated up to ∼15% of under-dosage in the most affected by disequilibrium 1-mm thick surface region of the tumor. A voxel-by-voxel comparison of tumor control probabilities between FFF and conventional flattened beams showed an advantage of FFF beams that, depending on the set up, was from a few to ∼9 percent. Conclusion: A modest improvement in tumor control probability on the order of a few percent can be achieved by replacing conventional flattened beams with FFF beams. However, given the large number of lung cancer patients undergoing radiotherapy, these few percent can potentially prevent local tumor recurrence for a significant number of patients.

[Inflammatory myofibroblastic tumor of the lymph node with paraneoplastic thrombosis and eosinophilia].

Science.gov (United States)

Behzad, Ali; Müller, Andrea; Rösler, Wolf; Amann, Kerstin; Linke, Rainer; Mackensen, Andreas

2010-04-01

A 52-year-old female patient was admitted to hospital because of progressive thrombosis despite therapeutic anticoagulation as well as leukocytosis with eosinophilia and thrombocytopenia. On examination, the patient presented with dyspnea and swelling oft her left leg and arm. The laboratory findings revealed leukocytosis (31,000/microl) with eosinophilia (54%), thrombocytopenia (58,000/microl), together with an increased C-reactive protein of 247 mg/dl (reference range < 5 mg/dl). Initial computed tomography scans showed pulmonary embolism and a slightly enlarged left inguinal lymph node. Histological examination of the lymph node biopsy revealed in part an epitheloid and spindle cell-like tumorous lesion with slightly increased tissue eosinophilia consistent with an inflammatory myofibroblastic tumor (IMT). Resection of the left inguinal lymph node resulted in an immediate regression of the paraneoplastic eosinophilia and thrombocytopenia. Anti-inflammatory medication with ibuprofen was subsequently initiated. Imaging and clinical examination at 3 months after discharge revealed no relapse and no signs of a paraneoplastic syndrome. The IMT is a rare soft-tissue tumor of intermediate dignity with a low tendency to metastasize. It is consistently accompanied by paraneoplastic syndromes. Therapy of choice is complete resection of the tumor. In nonresectable cases, corticosteroids and nonsteroidal antirheumatics have been shown to be effective. Because of the variable clinical course ranging from spontaneous regression to metastasis, IMTs might be separated into different entities (autoimmune, inflammatory, neoplastic subtype) which thus far cannot be classified on a histopathologic basis. A clinical assessment of the dignity is therefore important until further subclassifications of this rare disease become available.

Optimization of spatiotemporally fractionated radiotherapy treatments with bounds on the achievable benefit

Science.gov (United States)

Gaddy, Melissa R.; Yıldız, Sercan; Unkelbach, Jan; Papp, Dávid

2018-01-01

Spatiotemporal fractionation schemes, that is, treatments delivering different dose distributions in different fractions, can potentially lower treatment side effects without compromising tumor control. This can be achieved by hypofractionating parts of the tumor while delivering approximately uniformly fractionated doses to the surrounding tissue. Plan optimization for such treatments is based on biologically effective dose (BED); however, this leads to computationally challenging nonconvex optimization problems. Optimization methods that are in current use yield only locally optimal solutions, and it has hitherto been unclear whether these plans are close to the global optimum. We present an optimization framework to compute rigorous bounds on the maximum achievable normal tissue BED reduction for spatiotemporal plans. The approach is demonstrated on liver tumors, where the primary goal is to reduce mean liver BED without compromising any other treatment objective. The BED-based treatment plan optimization problems are formulated as quadratically constrained quadratic programming (QCQP) problems. First, a conventional, uniformly fractionated reference plan is computed using convex optimization. Then, a second, nonconvex, QCQP model is solved to local optimality to compute a spatiotemporally fractionated plan that minimizes mean liver BED, subject to the constraints that the plan is no worse than the reference plan with respect to all other planning goals. Finally, we derive a convex relaxation of the second model in the form of a semidefinite programming problem, which provides a rigorous lower bound on the lowest achievable mean liver BED. The method is presented on five cases with distinct geometries. The computed spatiotemporal plans achieve 12-35% mean liver BED reduction over the optimal uniformly fractionated plans. This reduction corresponds to 79-97% of the gap between the mean liver BED of the uniform reference plans and our lower bounds on the lowest

Portal imaging to assess set-up errors, tumor motion and tumor shrinkage during conformal radiotherapy of non-small cell lung cancer

International Nuclear Information System (INIS)

Erridge, Sara C.; Seppenwoolde, Yvette; Muller, Sara H.; Herk, Marcel van; Jaeger, Katrien de; Belderbos, Jose S.A.; Boersma, Liesbeth J.; Lebesque, Joos V.

2003-01-01

Purpose: To investigate patient set-up, tumor movement and shrinkage during 3D conformal radiotherapy for non-small cell lung cancer. Materials and methods: In 97 patients, electronic portal images (EPIs) were acquired and corrected for set-up using an off-line correction protocol based on a shrinking action level. For 25 selected patients, the orthogonal EPIs (taken at random points in the breathing cycle) throughout the 6-7 week course of treatment were assessed to establish the tumor position in each image using both an overlay and a delineation technique. The range of movement in each direction was calculated. The position of the tumor in the digitally reconstructed radiograph (DRR) was compared to the average position of the lesion in the EPIs. In addition, tumor shrinkage was assessed. Results: The mean overall set-up errors after correction were 0, 0.6 and 0.2 mm in the x (left-right), y (cranial-caudal) and z (anterior-posterior) directions, respectively. After correction, the standard deviations (SDs) of systematic errors were 1.4, 1.5 and 1.3 mm and the SDs of random errors were 2.9, 3.1 and 2.0 mm in the x-, y- and z-directions, respectively. Without correction, 41% of patients had a set-up error of more than 5 mm vector length, but with the set-up correction protocol this percentage was reduced to 1%. The mean amplitude of tumor motion was 7.3 (SD 2.7), 12.5 (SD 7.3) and 9.4 mm (SD 5.2) in the x-, y- and z-directions, respectively. Tumor motion was greatest in the y-direction and in particular for lower lobe tumors. In 40% of the patients, the projected area of the tumor regressed by more than 20% during treatment in at least one projection. In 16 patients it was possible to define the position of the center of the tumor in the DRR. There was a mean difference of 6 mm vector length between the tumor position in the DRR and the average position in the portal images. Conclusions: The application of the correction protocol resulted in a significant

Intratumoral IL-12 and TNF-alpha-loaded microspheres lead to regression of breast cancer and systemic antitumor immunity.

Science.gov (United States)

Sabel, Michael S; Skitzki, Joseph; Stoolman, Lloyd; Egilmez, Nejat K; Mathiowitz, Edith; Bailey, Nicola; Chang, Wen-Jian; Chang, Alfred E

2004-02-01

Local, sustained delivery of cytokines at a tumor can enhance induction of antitumor immunity and may be a feasible neoadjuvant immunotherapy for breast cancer. We evaluated the ability of intratumoral poly-lactic-acid-encapsulated microspheres (PLAM) containing interleukin 12 (IL-12), tumor necrosis factor alpha (TNF-alpha), and granulocyte-macrophage colony stimulating factor (GM-CSF) in a murine model of breast cancer to generate a specific antitumor response. BALB/c mice with established MT-901 tumors underwent resection or treatment with a single intratumoral injection of PLAM containing IL-12, TNF-alpha, or GM-CSF, alone or in combination. Two weeks later, lymph nodes and spleens were harvested, activated with anti-CD3 monoclonal antibodies (mAb) and rhIL-2, and assessed for antitumor reactivity by an interferon gamma (IFNgamma) release assay. Tumor-infiltrating lymphocyte (TIL) analysis was performed on days 2 and 5 after treatment by mechanically processing the tumors to create a single cell suspension, followed by three-color fluorescence-activated cell sorter (FACS) analysis. Intratumoral injection of cytokine-loaded PLAM significantly suppressed tumor growth, with the combination of IL-12 and TNF-alpha leading to increased infiltration by polymorphonuclear cells and CD8+ T-cells in comparison with controls. The induction of tumor-specific reactive T-cells in the nodes and spleens, as measured by IFN-gamma production, was highest with IL-12 and TNF-alpha. This treatment resulted in resistance to tumor rechallenge. A single intratumoral injection of IL-12 and TNF-alpha-loaded PLAM into a breast tumor leads to infiltration by polymorphonuclear cells and CD8+ T-cells with subsequent tumor regression. In addition, this local therapy induces specific antitumor T-cells in the lymph nodes and spleens, resulting in memory immune response.

Floating tumor debris. A cause of intermittent biliary obstruction.

Science.gov (United States)

Roslyn, J J; Kuchenbecker, S; Longmire, W P; Tompkins, R K

1984-11-01

Tumor debris, free-floating in the major biliary ductal system, is a cause of intermittent biliary obstruction that has previously not been recognized. Six patients had hepatic neoplasms with episodic jaundice and/or cholangitis due to floating tumor debris. Diagnosis included metastatic adenocarcinoma of the colon (n = 3), cholangiocarcinoma (n = 1), hepatocellular carcinoma (n = 1), and cavernous hemangioma (n = 1). All patients underwent biliary exploration, with hepatic resection and transhepatic intubation in two and T-tube placement in four. One patient died in the early postoperative period, and the major complication rate in the five survivors was 0%. Four of the five survivors had no further episodes suggestive of major bile duct obstruction. Our experience emphasizes the importance of distinguishing extrahepatic obstruction secondary to tumor debris from the more common causes of jaundice in patients with tumors and suggests that safe and effective palliation can be achieved in these patients.

The novel Hsp90 inhibitor NXD30001 induces tumor regression in a genetically engineered mouse model of glioblastoma multiforme.

Science.gov (United States)

Zhu, Haihao; Woolfenden, Steve; Bronson, Roderick T; Jaffer, Zahara M; Barluenga, Sofia; Winssinger, Nicolas; Rubenstein, Allan E; Chen, Ruihong; Charest, Al

2010-09-01

Glioblastoma multiforme (GBM) has an abysmal prognosis. We now know that the epidermal growth factor receptor (EGFR) signaling pathway and the loss of function of the tumor suppressor genes p16Ink4a/p19ARF and PTEN play a crucial role in GBM pathogenesis: initiating the early stages of tumor development, sustaining tumor growth, promoting infiltration, and mediating resistance to therapy. We have recently shown that this genetic combination is sufficient to promote the development of GBM in adult mice. Therapeutic agents raised against single targets of the EGFR signaling pathway have proven rather inefficient in GBM therapy, showing the need for combinatorial therapeutic approaches. An effective strategy for concurrent disruption of multiple signaling pathways is via the inhibition of the molecular chaperone heat shock protein 90 (Hsp90). Hsp90 inhibition leads to the degradation of so-called client proteins, many of which are key effectors of GBM pathogenesis. NXD30001 is a novel second generation Hsp90 inhibitor that shows improved pharmacokinetic parameters. Here we show that NXD30001 is a potent inhibitor of GBM cell growth in vitro consistent with its capacity to inhibit several key targets and regulators of GBM biology. We also show the efficacy of NXD30001 in vivo in an EGFR-driven genetically engineered mouse model of GBM. Our findings establish that the Hsp90 inhibitor NXD30001 is a therapeutically multivalent molecule, whose actions strike GBM at the core of its drivers of tumorigenesis and represent a compelling rationale for its use in GBM treatment.

Technological progress in radiation therapy for brain tumors

LENUS (Irish Health Repository)

Vernimmen, Frederik Jozef

2014-01-01

To achieve a good therapeutic ratio the radiation dose to the tumor should be as high as possible with the lowest possible dose to the surrounding normal tissue. This is especially the case for brain tumors. Technological ad- vancements in diagnostic imaging, dose calculations, and radiation delivery systems, combined with a better un- derstanding of the pathophysiology of brain tumors have led to improvements in the therapeutic results. The widely used technology of delivering 3-D conformal therapy with photon beams (gamma rays) produced by Li-near Accelerators has progressed into the use of Intensity modulated radiation therapy (IMRT). Particle beams have been used for several decades for radiotherapy because of their favorable depth dose characteristics. The introduction of clinically dedicated proton beam therapy facilities has improved the access for cancer patients to this treatment. Proton therapy is of particular interest for pediatric malignancies. These technical improvements are further enhanced by the evolution in tumor physiology imaging which allows for improved delineation of the tumor. This in turn opens the potential to adjust the radiation dose to maximize the radiobiological effects. The advances in both imaging and radiation therapy delivery will be discussed.

Recombinant human endostatin improves tumor vasculature and alleviates hypoxia in Lewis lung carcinoma