Pharmacologically increased tumor hypoxia can be measured by 18F-Fluoroazomycin arabinoside positron emission tomography and enhances tumor response to hypoxic cytotoxin PR-104.

ABSTRACT:

Purpose

Solid tumors contain microenvironmental regions of hypoxia that present a barrier to traditional radiotherapy and chemotherapy, and this work describes a novel approach to circumvent hypoxia. We propose to overcome hypoxia by augmenting the effectiveness of drugs that are designed to specifically kill hypoxic tumor cells.

Experimental design

We have constructed RKO colorectal tumor cells that express a small RNA hairpin that specifically knocks down the hypoxia-inducible factor 1a (HIF1a) transcription factor. We have used these cells in vitro to determine the effect of HIF1 on cellular sensitivity to the hypoxic cytotoxin PR-104, and its role in cellular oxygen consumption in response to the pyruvate dehydrogenase kinase inhibitor dichloroacetate (DCA). We have furt

SUBMITTER: Cairns RA 

PROVIDER: S-EPMC2810128 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature