Effects of XXXX ( @entity12841 ) kinase inhibitors on genetically reconstituted @entity19 mammary glands.

@entity1 @entity12841 @entity5 @entity19 @entity1722
The aim of the study was to determine the effects of a specific @entity12841 kinase inhibitor ( @entity12841 -KI) and Taxol on @entity5 growth in a novel @entity5 model. MATERIAL _ METHODS: A genetically engineered @entity5 model which uses "transgenic" organs in immune competent @entity19 was used. NeuT-transfected immortalized HC11 epithelial cells and primary @entity19 mammary epithelial cells have been transplanted into the gland-free mammary fat pad of female BALB/c @entity19 . @entity5 developed after a latency period of three to four weeks. The @entity19 were thereafter daily orally treated over a 19 or 22-day period with 0, 38, 75, 2 x 75 mg/kg body weight (b.w.) @entity12841 -KI (n: 7-9 per group) or intravenously with 10 mg/kg b.w. Taxol. After necropsy the histopathological evaluation of the @entity5 was performed in a coded manner. The proliferation activity of @entity5 cells was analyzed by laser scanning cytometry (LSC) using anti-Ki67-antibodies. RESULTS: Oral Treatment with @entity12841 -KI in this transgenic organ model showed clear antitumor efficacy in a dose-dependent manner in the range between 38 and 75 mg/kg b.w. This antiproliferative effect appears to be minimally increased at 75 mg/kg/day twice per day. For all treatments a strong correlation between the biological behavior of the @entity5 , histopathology and cell proliferation could be established. In contrast, treatment with Taxol showed no significant @entity5 growth or cell proliferation in this model. This new transgenic organ model comprising histopathological evaluation and cell proliferation analysis appears to be a suitable test system for drug candidates that affect specific biochemical pathways. It may have greater predictive nature for clinical effects in @entity1 as compared to conventional @entity5 models because of its @entity1722 gene overexpression.
