tailieunhanh - Báo cáo hóa học: "Anti-viral state segregates two molecular phenotypes of pancreatic adenocarcinoma: potential relevance for adenoviral gene therapy"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành hóa học dành cho các bạn yêu hóa học tham khảo đề tài: Anti-viral state segregates two molecular phenotypes of pancreatic adenocarcinoma: potential relevance for adenoviral gene therapy | Monsurrò et al. Journal of Translational Medicine 2010 8 10 http content 8 1 10 RESEARCH JOURNAL OF TRANSLATIONAL MEDICINE Open Access Anti-viral state segregates two molecular phenotypes of pancreatic adenocarcinoma potential relevance for adenoviral gene therapy 1 3 1 1 4 Vladia Monsurrò Stefania Beghelli Richard Wang Stefano Barbi Silvia Coin Giovanni Di Pasquale Samantha Bersani1 Monica Castellucci1 Claudio Sorio1 Stefano Eleuteri1 Andrea Worschech3 Jay A Chiorini4 Paolo Pederzoli5 Harvey Alter3 Francesco M Marincola3 Aldo Scarpa1 2 Abstract Background Pancreatic ductal adenocarcinoma PDAC remains a leading cause of cancer mortality for which novel gene therapy approaches relying on tumor-tropic adenoviruses are being tested. Methods We obtained the global transcriptional profiling of primary PDAC using RNA from eight xenografted primary PDAC three primary PDAC bulk tissues three chronic pancreatitis and three normal pancreatic tissues. The Affymetrix GeneChip HG-U133A was used. The results of the expression profiles were validated applying immunohistochemical and western blot analysis on a set of 34 primary PDAC and 10 established PDAC cell lines. Permissivity to viral vectors used for gene therapy Adenovirus 5 and Adeno-Associated Viruses 5 and 6 was assessed on PDAC cell lines. Results The analysis of the expression profiles allowed the identification of two clearly distinguishable phenotypes according to the expression of interferon-stimulated genes. The two phenotypes could be readily recognized by immunohistochemical detection of the Myxovirus-resistance A protein whose expression reflects the activation of interferon dependent pathways. The two molecular phenotypes discovered in primary carcinomas were also observed among established pancreatic adenocarcinoma cell lines suggesting that these phenotypes are an intrinsic characteristic of cancer cells independent of their interaction with the host s microenvironment. The