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      5-Fluorouracil: Mechanisms of Resistance and Reversal Strategies

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          Abstract

          The purpose of this work is to review the published studies on the mechanisms of action and resistance of 5-fluorouracil. The review is divided into three main sections: mechanisms of anti-tumor action, studies of the resistance to the drug, and procedures for the identification of new genes involved in resistance with microarray techniques. The details of the induction and reversal of the drug resistance are also described.

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          Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo.

          T Miyashita, S Krajewski, M. Krajewska … (1994)
          The p53 tumor suppressor gene product can induce apoptotic cell death through an unknown mechanism. Here we demonstrate that a temperature-sensitive p53 induces temperature-dependent decreases in the expression of the apoptosis-suppressing gene bcl-2 in the murine leukemia cell M1, while simultaneously stimulating increases in the expression of bax, a gene which encodes a dominant-inhibitor of the Bcl-2 protein. Mice deficient in p53 exhibit increases in Bcl-2 and decreases in Bax protein levels in several tissues as determined by immunohistochemical and immunoblot methods. The findings suggest a potential mechanism by which p53 regulates apoptosis, as well as responses to radiation and chemotherapeutic drugs in cancer.
          Article 0 comments Cited 210 times – based on 0 reviews     Review now
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            Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial

            G Gruia, P. Rougier, L Awad … (2000)
            Article 0 comments Cited 208 times – based on 0 reviews     Review now
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              Phase III multicenter randomized trial of oxaliplatin added to chronomodulated fluorouracil-leucovorin as first-line treatment of metastatic colorectal cancer.

              S Giacchetti, B Perpoint, R Zidani … (2000)
              To study how adding oxaliplatin (l-OHP) to chronomodulated fluorouracil (5-FU)-leucovorin (LV) affected the objective response rate, as first-line treatment of metastatic colorectal cancer. Two hundred patients from 15 institutions in four countries were randomly assigned to receive a 5-day course of chronomodulated 5-FU and LV (700 and 300 mg/m(2)/d, respectively; peak delivery rate at 0400 hours) with or without l-OHP on the first day of each course (125 mg/m(2), as a 6-hour infusion). Each course was repeated every 21 days. Response was assessed by extramural review of computed tomography scans. Grade 3 to 4 toxicity from 5-FU-LV occurred in
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                Author and article information

                Journal
                Journal ID (nlm-ta): Molecules
                Journal ID (iso-abbrev): Molecules
                Journal ID (publisher-id): molecules
                Title: Molecules
                Publisher: MDPI
                ISSN (Electronic): 1420-3049
                Publication date (Electronic): 05 August 2008
                Publication date Collection: August 2008
                Volume: 13
                Issue: 8
                Pages: 1551-1569
                Affiliations
                [1 ]Department of Orthopaedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, #88 Jiefang Road, Hangzhou, 310009, P.R. China; E-mail: zhangning98@ 123456gmail.com
                [2 ]Institute of Clinical Research, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, #3 East Qingchun Road, Hangzhou, 310016, P.R. China; E-mails: dy1225@ 123456gmail.com ; xusj@ 123456zju.edu.cn
                Author notes
                [* ] Author to whom correspondence should be addressed; E-Mail: zrspine@ 123456gmail.com .
                Article
                Publisher ID: molecules-13-01551
                DOI: 10.3390/molecules13081551
                PMC ID: 6244944
                PubMed ID: 18794772
                SO-VID: 0f862ba1-27a8-48a0-b714-e57a0abaa0ef
                Copyright © © 2008 by the authors.
                License:

                Licensee Molecular Diversity Preservation International, Basel, Switzerland. This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                Date received : 18 June 2008
                Date revision received : 01 July 2008
                Date accepted : 15 July 2008
                Categories
                Subject: Review

                Keywords: 5-fluorouracil,mechanism,resistance,microarray,therapeutic strategies
                Data availability:
                Keywords: 5-fluorouracil, mechanism, resistance, microarray, therapeutic strategies

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