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...

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,...

3'-Deoxy-3'-fluorothymidine (FLT) is a positron emission tomography (PET) tracer used to identify proliferating tumor cells. The purpose of this study was to characterize FLT transport by human nucleoside transporters (hNTs) and to determine the role of hNTs for FLT uptake in various human cancer cell lines. FLT binding to hNTs was monitored by the inhibitory effects of FLT on [(3)H]uridine upt...

Brain neoplasms constitute a group of tumors with discrete differentiation grades, and therefore, course of disease and prognosis. Magnetic resonance imaging (MRI) remains the gold standard method for the investigation of central nervous system tumors. However, MRI suffers certain limitations, especially if radiation therapy or chemotherapy has been previously applied. On the other hand, given ...

BACKGROUND 3'-Deoxy-3'-[18F]-fluorothymidine ([18F]FLT) is being investigated as a Positron Emission Tomography (PET) proliferation biomarker. The mechanism of cellular [18F]FLT retention has been assigned primarily to alteration of the strict transcriptionally regulated S-phase expression of thymidine kinase 1 (TK1). This, however, does not explain how anticancer agents acting primarily throug...

Biomarkers that predict response to targeted therapy in oncology are an essential component of personalized medicine. In preclinical treatment response studies that featured models of wild-type KRAS or mutant BRAF colorectal cancer treated with either cetuximab or vemurafenib, respectively, we illustrate that [(18)F]-FLT PET, a non-invasive molecular imaging readout of thymidine salvage, closel...

The assessment of tissue-specific pharmacodynamics is desirable in the development of tumor-targeted therapies. Plasma deoxyuridine (dUrd) levels, a measure of systemic thymidylate synthase (TS) inhibition, has limited application for studying the pharmacodynamics of novel TS inhibitors targeted to the high affinity A-folate receptor (FR). Here, we have evaluated the utility of [F]fluorothymidi...

UNLABELLED For a PET agent to be successful as a biomarker in early clinical trials of new anticancer agents, some conditions need to be fulfilled: the selected tracer should show a response that is related to the antitumoral effects, the quantitative value of this response should be interpretable to the antitumoral action, and the timing of the PET scan should be optimized to action of the dru...

PURPOSE The primary objective of this study was to investigate whether changes in 3'-deoxy-3'-[¹⁸F]fluorothymidine (¹⁸F-FLT) kinetic parameters, taken early after the start of therapy, could predict overall survival (OS) and progression-free survival (PFS) in patients with recurrent malignant glioma undergoing treatment with bevacizumab and irinotecan. EXPERIMENTAL DESIGN High-grade recurrent...