EFFECT OF MAPK INHIBITION ON CELL CYCLE REGULATION OF THYMIDINE KINASE 1 AND [F]-FLT PET By
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Gastric cancer growth control by BEZ235 in vivo does not correlate with PI3K/mTOR target inhibition but with [18F]FLT uptake.
PURPOSE In this study, we tested the antitumor activity of the dual phosphoinositide 3-kinase (PI3K)/mTOR inhibitor BEZ235 against gastric cancer in vitro and in vivo. EXPERIMENTAL DESIGN Gastric cancer cell lines (N87, MKN45, and MKN28) were incubated with BEZ235 and assessed for cell viability, cell cycle, and PI3K/mTOR target inhibition. In vivo, athymic nude mice were inoculated with N87,...
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BACKGROUND Non-invasive imaging biomarkers of cellular proliferation hold great promise for quantifying response to personalized medicine in oncology. An emerging approach to assess tumor proliferation utilizes the positron emission tomography (PET) tracer 3'-deoxy-3'[(18)F]-fluorothymidine, [(18)F]-FLT. Though several studies have associated serial changes in [(18)F]-FLT-PET with elements of t...
متن کاملCancer Therapy: Preclinical Gastric Cancer Growth Control by BEZ235 In Vivo Does Not Correlate with PI3K/mTOR Target Inhibition but with [F]FLT Uptake
Purpose: In this study, we tested the antitumor activity of the dual phosphoinositide 3-kinase (PI3K)/ mTOR inhibitor BEZ235 against gastric cancer in vitro and in vivo. Experimental Design:Gastric cancer cell lines (N87, MKN45, and MKN28) were incubated with BEZ235 and assessed for cell viability, cell cycle, and PI3K/mTOR target inhibition. In vivo, athymic nude mice were inoculated with N87,...
متن کاملGastric cancer growth control by BEZ235 in vivo does not correlate with PI3K/mTOR target inhibition but with [F]FLT uptake Running Title [F]FLT uptake correlates with BEZ235 activity
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Activation of the PI3K/mTOR pathway is a common event in gastric cancer and correlates with poor prognosis. PI3K/mTOR inhibition by the dual kinase inhibitor BEZ235 provides a novel and promising strategy for more effective treatment of gastric cancer patients. BEZ235 was recently reported to b...
متن کاملEarly detection of pemetrexed-induced inhibition of thymidylate synthase in non-small cell lung cancer with FLT-PET imaging
Inhibition of thymidylate synthase (TS) results in a transient "flare" in DNA thymidine salvage pathway activity measurable with FLT ([18F]thymidine)-positron emission tomography (PET). Here we characterize this imaging strategy for potential clinical translation in non-small cell lung cancer (NSCLC). Since pemetrexed acts by inhibiting TS, we defined the kinetics of increases in thymidine salv...
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تاریخ انتشار 2009