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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Effect of glutamine on methotrexate efficacy and toxicity.</title><author><name sortKey="Rubio, I T" sort="Rubio, I T" uniqKey="Rubio I" first="I T" last="Rubio">I T Rubio</name></author><author><name sortKey="Cao, Y" sort="Cao, Y" uniqKey="Cao Y" first="Y" last="Cao">Y. Cao</name></author><author><name sortKey="Hutchins, L F" sort="Hutchins, L F" uniqKey="Hutchins L" first="L F" last="Hutchins">L F Hutchins</name></author><author><name sortKey="Westbrook, K C" sort="Westbrook, K C" uniqKey="Westbrook K" first="K C" last="Westbrook">K C Westbrook</name></author><author><name sortKey="Klimberg, V S" sort="Klimberg, V S" uniqKey="Klimberg V" first="V S" last="Klimberg">V S Klimberg</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">9605669</idno><idno type="pmc">1191365</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1191365</idno><idno type="RBID">PMC:1191365</idno><date when="1998">1998</date><idno type="wicri:Area/Pmc/Corpus">001470</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001470</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Effect of glutamine on methotrexate efficacy and toxicity.</title><author><name sortKey="Rubio, I T" sort="Rubio, I T" uniqKey="Rubio I" first="I T" last="Rubio">I T Rubio</name></author><author><name sortKey="Cao, Y" sort="Cao, Y" uniqKey="Cao Y" first="Y" last="Cao">Y. Cao</name></author><author><name sortKey="Hutchins, L F" sort="Hutchins, L F" uniqKey="Hutchins L" first="L F" last="Hutchins">L F Hutchins</name></author><author><name sortKey="Westbrook, K C" sort="Westbrook, K C" uniqKey="Westbrook K" first="K C" last="Westbrook">K C Westbrook</name></author><author><name sortKey="Klimberg, V S" sort="Klimberg, V S" uniqKey="Klimberg V" first="V S" last="Klimberg">V S Klimberg</name></author></analytic><series><title level="j">Annals of Surgery</title><idno type="ISSN">0003-4932</idno><idno type="eISSN">1528-1140</idno><imprint><date when="1998">1998</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>OBJECTIVE: To examine the effect of oral glutamine (GLN) on the efficacy and toxicity of methotrexate (MTX). SUMMARY BACKGROUND DATA: The use of high-dose chemotherapy regimens is limited by the severity of their toxicities. Oral GLN has been shown to decrease the gut toxicity seen with MTX treatment while enhancing its tumoricidal effect. METHODS AND RESULTS: Studies were done in laboratory rats and in breast cancer outpatients. Fischer 344 rats were randomized to 48 hours of prefeeding with GLN (1 g/kg/day) or an isonitrogenous amount of glycine. Rats were killed 24 hours after receiving a 20-mg/kg intraperitoneal dose of MTX. In the GLN group, there was a threefold increase in total MTX in the tumor as compared with the control group, and this increase was in both the diglutamated and pentaglutamated MTX. Inversely, there was a significant decrease in the total polyglutamated MTX in the gut in the GLN group. Given the results of this preclinical study, the authors performed a phase I trial. Nine patients diagnosed with inflammatory breast cancer received GLN (0.5 g/kg/day) during MTX neoadjuvant therapy, escalating from doses of 40 mg/m2 to 100 mg/m2 weekly for 3 weeks, followed by a doxorubicin-based regimen. No toxicity of oral GLN was detected. No patient showed any sign of chemotherapy-related toxicity. One patient had a grade I mucositis. Except for one, all patients responded to the chemotherapy regimen. Median survival was 35 months. CONCLUSIONS: These studies suggest that GLN supplementation is safe in its administration to the tumor-bearing host receiving MTX. By preferentially increasing tumor retention of MTX over that of normal host tissue, GLN may serve to increase the therapeutic window of this chemotherapeutic age.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Ann Surg</journal-id><journal-title>Annals of Surgery</journal-title><issn pub-type="ppub">0003-4932</issn><issn pub-type="epub">1528-1140</issn></journal-meta><article-meta><article-id pub-id-type="pmid">9605669</article-id><article-id pub-id-type="pmc">1191365</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title>Effect of glutamine on methotrexate efficacy and toxicity.</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Rubio</surname><given-names>I T</given-names></name></contrib><contrib contrib-type="author"><name><surname>Cao</surname><given-names>Y</given-names></name></contrib><contrib contrib-type="author"><name><surname>Hutchins</surname><given-names>L F</given-names></name></contrib><contrib contrib-type="author"><name><surname>Westbrook</surname><given-names>K C</given-names></name></contrib><contrib contrib-type="author"><name><surname>Klimberg</surname><given-names>V S</given-names></name></contrib></contrib-group><aff>Department of Surgery, University of Arkansas for Medical Sciences, Little Rock 72205, USA.</aff><pub-date pub-type="ppub"><month>5</month><year>1998</year></pub-date><volume>227</volume><issue>5</issue><fpage>772</fpage><lpage>780</lpage><abstract><p>OBJECTIVE: To examine the effect of oral glutamine (GLN) on the efficacy and toxicity of methotrexate (MTX). SUMMARY BACKGROUND DATA: The use of high-dose chemotherapy regimens is limited by the severity of their toxicities. Oral GLN has been shown to decrease the gut toxicity seen with MTX treatment while enhancing its tumoricidal effect. METHODS AND RESULTS: Studies were done in laboratory rats and in breast cancer outpatients. Fischer 344 rats were randomized to 48 hours of prefeeding with GLN (1 g/kg/day) or an isonitrogenous amount of glycine. Rats were killed 24 hours after receiving a 20-mg/kg intraperitoneal dose of MTX. In the GLN group, there was a threefold increase in total MTX in the tumor as compared with the control group, and this increase was in both the diglutamated and pentaglutamated MTX. Inversely, there was a significant decrease in the total polyglutamated MTX in the gut in the GLN group. Given the results of this preclinical study, the authors performed a phase I trial. Nine patients diagnosed with inflammatory breast cancer received GLN (0.5 g/kg/day) during MTX neoadjuvant therapy, escalating from doses of 40 mg/m2 to 100 mg/m2 weekly for 3 weeks, followed by a doxorubicin-based regimen. No toxicity of oral GLN was detected. No patient showed any sign of chemotherapy-related toxicity. One patient had a grade I mucositis. Except for one, all patients responded to the chemotherapy regimen. Median survival was 35 months. CONCLUSIONS: These studies suggest that GLN supplementation is safe in its administration to the tumor-bearing host receiving MTX. By preferentially increasing tumor retention of MTX over that of normal host tissue, GLN may serve to increase the therapeutic window of this chemotherapeutic age.</p></abstract></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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