Pancreatic cancer is one of the most intractable and least understood of all human cancers. Pancreatic cancer is the fourth-leading cause ofcancer-related mortality in the United States with <2% of the patients surviving for 5 yr.In an effort to help develop more effective treatment moities for pancreatic cancer and improve detection, we report an animal model for individual human pancreatic-cancer patients. The model involves orthotopic transplantation of histologically intact pancreatic-cancer specimens -to the nude-mouse pancreas, which can result in models that resemble the clinical picture including (i) extensive local tumor growth, (it) extension of the locally growing human pancreatic cancer to the nudemouse stomach and duodenum, (Wi) metastases of the human pancreatic tumor to the nude-mouse liver and regional lymph nodes, and (iv) distant metastases of the human pancreatic tumor to the nude-mouse adrenal gland, diaphragm, and mediastinal lymph nodes. In a series of five patient cases, a 100% take rate has been demonstrated, and of 17 mice transplanted, 15 supported tumor growth. Immunohistochemical analysis of the antigenic phenotype of the transplanted human pancreatic tumors showed a similar pattern of expression of two different human tumor-associated antigens, such as tumor-associated glycoprotein 72 and carcinoembryonic antigen in the transplanted tumors when compared with the original surgical biopsy, suggesting similarity between the two. This model should, therefore, prove valuable for treatment evaluation of individual cancer patients, as well as for evaluation of experimental treatment modalities for this disease. Our approach is to avoid disruption of tumor integrity and to orthotopically implant histologically intact patient tumor tissue directly after surgery or biopsy. Such a model should better resemble the original properties of the human cancer and could be ofgreat value in developing additional drugs and treatment strategies for cancer. Guided by this overall strategy, we have used nude mice to construct human coloncancer models that directly use surgical specimens and can exhibit the variety of clinical behaviors seen in human subjects (31). These behaviors include (i) local growth, (ii) abdominal metastasis, (iii) general abdominal carcinomatosis with extensive peritoneal seeding, (iv) lymph-node metastasis, (v) liver metastasis, and (vi) colonic obstruction: a tumor-establishment rate of 13 cases in 20 attempts was found (31). We have constructed a similar set of models for human bladder cancer (32).We report here the use of the orthotopic-transplant strategy of histologically intact patient specimens to develop a human pancreatic-cancer model with a 100% take rate and subsequent growth and metastatic behavior while retaining human tumor-associated antigens (TAAs), thereby resembling the clinical picture. Cancer of the pancreas is one of the most intractable cancers and is the fourth-leading cause of cancer death in the United States (1-3). At surgery, most patients are foun...

Background: Management and traceability of biospecimen preanalytical variations are necessary to provide effective and efficient interconnectivity and interoperability between Biobanks.Methods: Therefore, the International Society for Biological and Environmental Repositories Biospecimen Science Working Group developed a "Standard PREanalytical Code" (SPREC) that identifies the main preanalytical factors of clinical fluid and solid biospecimens and their simple derivatives.Results: The SPREC is easy to implement and can be integrated into Biobank quality management systems and databases. It can also be extended to nonhuman biorepository areas. Its flexibility allows integration of new novel technological developments in future versions. SPREC version 01 is presented in this article.Conclusions and Impact: Implementation of the SPREC is expected to facilitate and consolidate international multicenter biomarker identification research and biospecimen research in the clinical Biobank environment. Cancer Epidemiol Biomarkers Prev; 19(4); 1004-11. ©2010 AACR.

Neutrophil/lymphocyte (NLR) and platelet/lymphocyte (PLR) ratios might represent a yet unrecognized risk factor for venous thromboembolism (VTE) in cancer out-patients receiving chemotherapy. Accordingly, this study was aimed at analyzing the significance of these novel markers in the risk prediction of a first VTE episode in a population representative of a general practice cohort. To this purpose, a mono-institutional cohort study was conducted to retrospectively analyze NLR and PLR in 810 consecutive cancer out-patients with primary or relapsing solid cancer at the start of a new chemotherapy regimen. Over a median follow-up of 9.2 months, VTE occurred in 6.7% of patients. Incidental VTE was diagnosed at time of restaging in 47% of cases. Median pre-chemotherapy NLR (p 5 0.015) and PLR (p 5 0.040) were significantly higher in patients with intermediate risk class who developed symptomatic VTE with a twofold increased VTE risk for both inflammation-based markers (NLR: p 5 0.022; PLR: p 5 0.037) and a worst 1-year VTE-free survival for patients with high NLR or PLR. However, only PLR (HR 5 2.4, p 5 0.027) confirmed to be an independent predictor of future VTE in patients in the intermediate risk class in multivariate analysis, together with ECOG performance status (HR 5 3.4, p 5 0.0002) and bevacizumab use (HR 5 4.7, p 5 0.012). We may, thus, conclude that PLR, but to a lesser extent NLR, could represent useful clinical predictors of VTE, especially in selected categories of patients such as those in the intermediate risk class in whom the assessment of PLR could allow a better risk stratification of VTE without additional costs to the national health systems.Cancer patients have a four to sixfold higher risk of venous thromboembolism (VTE) compared to the general population, the factors being patient-, cancer-or treatment-related and the pathophysiology classically dependent on the Virchow triad.

Purpose The epithelial-mesenchymal transition (EMT) is emerging as a critical factor for the progression and metastasis of carcinomas, as well as drug resistance. The T-box transcription factor Brachyury has been recently characterized as a driver of EMT in human carcinoma cells. The purpose of this study was to characterize Brachyury as a potential target for lung cancer therapy. Experimental Design The expression of Brachyury was evaluated by PCR and by immunohistochemistry in human lung tumors and adult normal tissues. Brachyury gene copy number and promoter methylation status were analyzed in tumor tissues with various levels of Brachyury expression. Lung carcinoma cells’ susceptibility to T-cell lysis and EGFR kinase inhibition were also evaluated relative to the levels of Brachyury. Results Our results demonstrated Brachyury protein expression in 41% of primary lung carcinomas, including 48% of adenocarcinomas and 25% of squamous cell carcinomas. With the exception of normal testis and some thyroid tissues, the majority of normal tissues evaluated in this study were negative for the expression of Brachyury protein. Brachyury-specific T cells could lyse Brachyury positive tumors and the level of Brachyury corresponded to resistance of tumor cells to EGFR kinase inhibition. Conclusion We hypothesize that the elimination of Brachyury-positive tumor cells may be able to prevent and/or diminish tumor dissemination and the establishment of metastases. The ability of Brachyury-specific T-cell lines to lyse Brachyury-positive tumor cells, in vitro, supports the development of Brachyury-based immunotherapeutic approaches for the treatment of lung cancer.