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Folates as adjuvant...
Folates as adjuvants to anticancer agents: Chemical rationale and mechanism of action
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Danenberg, P. V. (författare)
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- Gustavsson, Bengt, 1947 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för kirurgi,Institute of Clinical Sciences, Department of Surgery
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Johnston, P. (författare)
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Lindberg, P. (författare)
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Moser, R. (författare)
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- Odin, Elisabeth, 1955 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för kirurgi,Institute of Clinical Sciences, Department of Surgery
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Peters, G. J. (författare)
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Petrelli, N. (författare)
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(creator_code:org_t)
- Elsevier BV, 2016
- 2016
- Engelska.
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Ingår i: Critical Reviews in Oncology Hematology. - : Elsevier BV. - 1040-8428. ; 106, s. 118-131
- Relaterad länk:
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https://doi.org/10.1...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Folates have been used with cytotoxic agents for decades and today they are used in hundreds of thousands of patients annually. Folate metabolism is complex. In the treatment of cancer with 5-fluorouracil, the administration of folates mechanistically leads to the formation of [6R]-5,10-methylene-tetrahydrofolate, and the increased concentration of this molecule leads to stabilization of the ternary complex comprising thymidylate synthase, 2'-deoxy-uridine-5'-monophosphate, and [6R]-5,10-methylene-tetrahydrofolate.The latter is the only natural folate that can bind directly in the ternary complex, with other folates requiring metabolic activation. Modulation of thymidylate synthase activity became central in the study of folate/cytotoxic combinations and, despite wide use, research into the folate component was neglected, leaving important questions unanswered. This article revisits the mechanisms of action of folates and evaluates commercially available folate derivatives in the light of current research. Better genomic insight and availability of new analytical techniques and stable folate compounds may open new avenues of research and therapy, ultimately bringing increased clinical benefit to patients. (C) 2016 The Authors. Published by Elsevier Ireland Ltd.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- Folate metabolism
- Leucovorin
- Mechanism of action
- 5-Fluorouracil
- [6R]-5
- 10-methylene-tetrahydrofolate
- gamma-glutamate synthetase
- one-carbon metabolism
- ternary
- complex-formation
- thymidylate synthase
- folic-acid
- colorectal-cancer
- folylpolyglutamate synthetase
- intracellular metabolism
- substrate-analogs
- mammalian-cells
- Oncology
- Hematology
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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