Accession Number : ADA556011


Title :   Development of Mouse Models of Ovarian Cancer for Studying Tumor Biology and Testing Novel Molecularly Targeted Therapeutic Strategies


Descriptive Note : Final rept. 1 Jun 2008-30 Jun 2011


Corporate Author : MICHIGAN UNIV ANN ARBOR


Personal Author(s) : Rehemtulla, Alnawaz


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a556011.pdf


Report Date : Sep 2011


Pagination or Media Count : 27


Abstract : The objective of this project was to create genetically engineered mouse (GEM) models that in addition to developing ovarian carcinomas similar to human endometrioid carcinomas, also express a reporter for Caspase-3 activity, a hallmark of cells undergoing apoptosis. During the three year funding period, we generated stable lines of transgenic mice carrying a Cre-inducible luciferase reporter or apoptosis reporter and verified function of the reporter transgenes in vivo. Using Apcflox/flox;Ptenflox/flox;ROSA26LSL-Luc/+ and Apcflox/flox;Ptenflox/flox; ApoptosisLSL-Luc mice generated as part of this project, we confirmed that BLI can be used to monitor ovarian tumor progression and drug response in vivo. In addition, we showed that Apcflox/flox;Ptenflox/flox;ApoptosisLSL-Luc mice can be used to image treatment-dependent induction of apoptosis. Efficacy of a targeted therapeutic agent (Akt inhibitor, Perifosine), alone and in combination with a standard chemotherapeutic agent (Cisplatin) was evaluated. Our studies revealed that combination therapy resulted in enhanced levels of apoptosis compared to either agent alone, and suggest this may be a promising approach for treating women with advanced stage ovarian endometrioid adenocarcinomas with PI3K/Akt/mTOR signaling pathway defects.


Descriptors :   *OVARIAN CANCER , APOPTOSIS , CHEMOTHERAPEUTIC AGENTS , NEOPLASMS , THERAPY


Subject Categories : Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE