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• W2150226032 abstract "[Introduction] Growth factor receptor signalings are aberrantly regulated in cancers and mammalian target of rapamycin (mTOR) plays a center role in this stimulated growth/survival signals. mTOR is often upregulated in many types of cancers including non small cell lung cancer (NSCLC). Temsirolimus, an analogue of rapamycin, was recently synthesized to specifically inhibit mTOR and has provided a better outcome to patients with renal cell carcinoma. It was also reported that temsirolimus showed a certain antitumor effect on other types of malignancies such as breast cancer and brain tumors. In this study, we aimed to obtain a potential application of temsirolimus to NSCLC, especially a therapeutic strategy for pleural dissemination of NSCLC, which is a severe state of clinical NSCLC without yet any effective treatments. [Methods] Cultured human NSCLC cell lines (A549, H1299, and H358) were used in this study. The cells were treated with temsirolimus for 48 hours and its effect on cell proliferation was determined by calculating a concentration of 50% growth inhibition (IC 50 ) and cell cycle analysis was done by flowcytometry. Western blot was carried out to examine the protein expressions of mTOR and related molecules. Three million of cultured cancer cells were subcutaneously inoculated in nude mice and 10mg/kg of temsirolimus were weekly administered in an intraperitoneal cavity ( i.p. ) to assess its antitumor effect. To further assess the effect of temsirolimus on the survival periods of tumor-bearing animals, a pleural dissemination model was established by an intrapleural injection of cancer cells, followed by a weekly i.p .-administration of 10mg/kg-temsirolimus. Tumors were obtained from the animals for immunohistochemistry. [Results] Temsirolimus suppressed in vitro cell proliferation of A549, H1299, and H358 cells in a dose-dependent manner with accumulation of cell population at the G1 phase and their IC 50 s were 0.76nM, 0.75nM, and 0.64nM, respectively. 1nM of temsirolimus effectively inhibited the activations of mTOR and its downstream effectors. Next, when 10mg/kg of temsirolimus was weekly administered to the animals, a significant delay of A549 subcutaneous tumor growth was observed (tumor volume: vehicle vs temsirolimus = 698cm 3 vs 1239cm 3 ; p i.p. with 10mg/kg of temsirolimus) revealed a prolonged survival period of a pleural dissemination model (median survival: vehicle vs temsirolimus = 53.5days vs 72.5days; p Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-215." @default.
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• W2150226032 date "2009-05-01" @default.
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• W2150226032 title "Abstract #LB-215: Antiproliferative effects of a novel mTOR inhibitor (Temsirolimus) provide the prolonged survival in a pleural dissemination model using non-small cell lung cancer cells" @default.
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