Induction of thymidylate synthase as a 5-fluorouracil resistance mechanism
نویسندگان
چکیده
منابع مشابه
Digital karyotyping identifies thymidylate synthase amplification as a mechanism of resistance to 5-fluorouracil in metastatic colorectal cancer patients.
Resistance to chemotherapy is a major cause of mortality in advanced cancer patients. In this study, digital karyotyping was used to search for genomic alterations in liver metastases that were clinically resistant to 5-fluorouracil (5-FU). In two of four patients, we identified amplification of an approximately 100-kb region on 18p11.32 that was of particular interest because it contained the ...
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Fifty-four patients with metastatic adenocarcinoma received i.v. bolus 5-fluorouracil, 500 mg/m2, prior to surgical biopsy of tumor at 20-400 min, for analysis of biochemical parameters of resistance to thymidylate synthase (TS) inhibition. The majority of patients, 37, had colon or rectal adenocarcinoma, five had breast cancer, five had gastric primary disease, four had pancreatic adenocarcino...
متن کاملThymidylate synthase expression in circulating tumor cells: a new tool to predict 5-fluorouracil resistance in metastatic colorectal cancer patients.
Thymidylate synthase (TYMS) is an important enzyme for 5-fluorouracil (5-FU) metabolism in metastatic colorectal cancer (mCRC) patients. The search for this enzyme in circulating tumor cells (CTCs) can be a powerful tool to follow-up cancer patients. mCRC patients were enrolled before the beginning of 5-FU-based chemotherapy. The blood was filtered on Isolation by Size of Epithelial Tumor Cells...
متن کاملp53-regulated Gene Expression in Response to 5-Fluorouracil The Role of Thymidylate Synthase Induction in Modulating
Thymidylate synthase (TS) is a critical target for chemotherapeutic agents such as 5-fluorouracil (5-FU) and antifolates such as tomudex (TDX), multitargeted antifolate, and ZD9331. Using the MCF-7 breast cancer line, we have developed p53 wild-type (M7TS90) and null (M7TS90-E6) isogenic lines with inducible TS expression ( 6-fold induction compared with control after 48 h). In the M7TS90 line,...
متن کاملThymidylate synthase and drug resistance.
Thymidylate synthase is an important target for both fluorinated pyrimidines and for new folate analogues. Resistance to 5-fluorouracil (5FU) can be related to insufficient inhibition of thymidylate synthase. The 5FU-nucleotide FdUMP induces inhibition of thymidylate synthase which is enhanced and retained for longer in the presence of increased folate pools, for which leucovorin is a precursor...
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ژورنال
عنوان ژورنال: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
سال: 2002
ISSN: 0925-4439
DOI: 10.1016/s0925-4439(02)00082-0