Dr. Lyuba Varticovski headed this initiative to adapt genetically engineered mouse tumors for preclinical testing using transplantation of cell suspension into syngeneic or immunodeficient hosts. Multiple mammary tumors have been investigated to date. A manuscript describing the model system was recently revised to include microarray analysis as requested by the reviewers. (Varticovski, L., Hollingshead, M.G., Robles, A.I., et al., Transplantation strategy for generation of genetically engineered mammary mouse models suitable for preclinical testing. Clin Cancer Res., in review). Recommendations from Dr. Bob Wiltrout and Dr. Glenn Merlino were addressed by performing microarray analysis of MMTV-PyMT and wnt1 mammary tumors, and to complete a repository for tissues on each model. Gene expression analysis of other mammary models used in the study is in progress. Additional validation of the MMTV-PyMT model using Cyclophosphamide and Paclitaxel was performed as recommended by breast cancer clinicians at CCR. Based on success in using transplantation to generate synchronous mammary tumors for preclinical testing, we began harvesting and validation of transplantation protocol for selected lung cancer tumors from genetically engineered mice. In collaboration with Dr. Charles Vinson, we examined tumor development in diabetic A ZIP/F 1 fatless transgenic mice bred with several genetically engineered mouse models. This work was a cover article in Cancer Research, 2006. The inflammatory mechanisms responsible for accelerated carcinogenesis observed in this mouse model are not known and a proposal to follow up on this work was submitted. In collaboration with the Preclinical Pharmacokinetics Section of MTP (Dr. W. Doug Figg) we are investigating differences in pharmacokinetics of Paclitaxel between man and mouse. These studies are critical for development of appropriate schedule of drug administration for preclinical testing.
