Increased expression of transcription factor XXXX correlates with chemosensitivity in advanced @entity150 .

@entity1 @entity5 @entity10226 @entity900 @entity876 @entity150 @entity3 @entity136 @entity18720
BACKGROUND: The standard treatment for @entity1 with advanced transitional cell @entity150 is platin based chemotherapy. Only approximately 50% of the @entity1 respond to chemotherapy. Therefore, molecular predictive markers for identification of chemotherapy sensitive subgroups of @entity1 are highly needed. We selected the transcription factor @entity18720 from a previously identified gene expression signature for chemotherapy response. METHODS: @entity18720 expression and localization was assessed by immunohistochemistry using a tissue microarray (TMA) containing 282 @entity150 tumors from @entity1 with locally advanced (pT2-T4(b) and N(1-3)) or metastatic (M(1)) disease. All @entity1 had received @entity900 containing chemotherapy. Furthermore, QPCR analysis of three @entity18720 isoforms was performed on @entity5 specimens of advanced muscle invasive @entity150 (T2-4). Using the bladder cell lines T24 and SW780 the relation of @entity18720 and @entity900 and @entity136 sensitivity as well as cell proliferation was examined using siRNA directed @entity18720 knockdown. RESULTS: @entity18720 protein expression was analyzed on a @entity10226 with cores from 282 advanced @entity150 tumors from @entity1 treated with @entity900 based combinational chemotherapy. @entity18720 was identified as a strong independent predictive marker for a good response and survival after @entity900 -containing chemotherapy in @entity1 with advanced @entity150 . Strong @entity18720 nuclear and cytoplasmic staining predicted good response to chemotherapy in @entity1 with lymph node @entity3 , whereas weak @entity18720 nuclear staining predicted good response in @entity1 without lymph node @entity3 . In vitro studies showed that siRNA mediated knockdown of @entity18720 increased the proliferation of @entity1 cells and rendered the cells less sensitive to @entity900 and @entity136 . In contrast to that @entity1 bladder cells with mutated @entity876 showed to be more drug sensitive upon @entity18720 depletion. CONCLUSIONS: High levels of nuclear and cytoplasmic @entity18720 protein were a predictor of increased overall survival and progression free survival in @entity1 with advanced @entity150 treated with @entity900 based chemotherapy. @entity18720 knockdown increased the proliferation of the @entity1 bladder cells and reduced @entity900 and @entity136 induced cell death. The inverse effect was observed in the @entity876 mutated @entity1 cell line where @entity18720 silencing augmented @entity900 and @entity136 sensitivity and did not stimulate proliferation.
