MOL #43349 MLH1 Deficiency Enhances Radiosensitization with 5-Fluorodeoxyuridine by Increasing DNA Mismatches
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منابع مشابه
MLH1 deficiency enhances radiosensitization with 5-fluorodeoxyuridine by increasing DNA mismatches.
The antitumor drug 5-fluoro-2'-deoxyuridine (FdUrd) also sensitizes tumor cells to ionizing radiation in vitro and in vivo. Although radiosensitization with FdUrd requires dTTP depletion and S-phase arrest, the exact mechanism by which these events produce radiosensitization remains unknown. We hypothesized that the depletion of dTTP produces DNA mismatches that, if not repaired before irradiat...
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The amount of iododeoxyuridine (IdUrd) incorporated into DNA determines the degree of radiosensitization. Fluorodeoxyuridine (FdUrd) has been shown to biochemically modulate IdUrd incorporation into DNA in vitro and in vivo. In this Phase I study, these drugs were coadministered to patients during 14-day continuous i.v. infusion periods in order to investigate whether the incorporation of IdUrd...
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Mismatch repair (MMR) deficiency, which underlies hereditary nonpolyposis colorectal cancer, has recently been linked to a number of sporadic human cancers as well. Deficiency in this repair process renders cells resistant to many clinically active chemotherapy agents. As a result, it is of relevance to find an agent that selectively targets MMR-deficient cells. We have recently shown that the ...
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Background and Objectives: MutL homolog (MLH1) is a key component of heterodimeric complex MutLα, which recognizes and repairs base-base mismatches or insertion/deletion loops that arise from nucleotide misincorporation. In the absence of MLH1 protein, the number of unrepaired mismatches will increase and cause tumors in organs. The present study aimed at quantitative analysis of MLH1 gene expr...
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Radiation sensitization by 2',2'-difluoro-2'-deoxycytidine (dFdCyd) has correlated with dATP depletion [dFdCDP-mediated inhibition of ribonucleotide reductase (RR)] and S-phase accumulation. We hypothesized that radiosensitization by dFdCyd is due to nucleotide misincorporations in the presence of deoxynucleotide triphosphate pool imbalances, which, if not repaired, augments cell death followin...
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تاریخ انتشار 2008