Histologically Intact Human Tumor Tissue in Nude Mice Cancer Constructed Using Orthotopic Transplantation of A Novel ''Patient-like'' Treatment Model of Human Pancreatic

Pancreatic cancer is a disease with essentially no effective treatment. To increase the potential for discovering effective treatment, we have devel oped a new treatment model whereby a human pancreatic cancer line, PANC-4, was orthotopically transplanted to the pancreas of nude mice as historically intact tumor tissue. The tumor grew with subsequent inva sive local tumor growth and liver and peritoneal métastases.The antitumor activity of 5-fluorouracil (5-FU) and mitomycin C (MMC) against PANC-4 was initially determined in the in vitro collagen-sponge-gel sup ported histoculture drug-response assay with the 3-(4.5-dimethylthiazol2-yl)-2.5-diphenyltetrazolium bromide end point. Inhibition rates were 5.6% for 5-FU and 39.4% for MMC indicating higher efficacy of MMC than 5-Kt' against PANC-4. When the antitumor activities of 5-FU and MMC against PANC-4 were determined in vivo using the nude mouse orthotopic transplant treatment model, slight local tumor growth inhibi tion with equivalent incidence of métastasesto the liver and the perito neum as the control were observed in the mice treated with 5-FU, while those treated with MMC had considerably reduced local tumor growth without liver and peritoneal métastases.Thus the histoculture drug-re sponse assay in combination with the orthotopic transplant metastatic models provides for the first time a paradigm for evaluation of agents which may he effective against not only locally growing human pancreatic cancer but resulting métastasesas well.