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Lowering of tumor interstitial fluid pressure specifically augments efficacy of chemotherapy
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
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2003 (English)In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 17, no 12, 1756-1758 p.Article in journal (Refereed) Published
Abstract [en]

Chemotherapy of solid tumors is presently largely ineffective at dosage levels that are compatible with survival of the patient. Here, it is argued that a condition of raised interstitial fluid pressure (IFP) that can be observed in many tumors is a major factor in preventing optimal access of systemically administered chemotherapeutic agents. Using prostaglandin E1-methyl ester (PGE1), which is known transiently to reduce IFP, it was shown that 5-fluorouracil (5-FU) caused significant growth inhibition on two experimental tumors in rats but only after administration of PGE1. Furthermore, timing experiments showed that only in the period in which IFP is reduced did 5-FU have an antitumor effect. These experiments uniquely demonstrate a clear and, according to the starting hypothesis, logical, synergistic effect of PGE1 and 5-FU that offers hope for better treatment of many tumors in which raised IFP is likely to be inhibiting optimal results with water-soluble cancer chemotherapeutic agents.

Place, publisher, year, edition, pages
2003. Vol. 17, no 12, 1756-1758 p.
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Medical and Health Sciences
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URN: urn:nbn:se:uu:diva-153066DOI: 10.1096/fj.02-1201fjePubMedID: 12958200OAI: oai:DiVA.org:uu-153066DiVA: diva2:415051
Available from: 2011-05-05 Created: 2011-05-05 Last updated: 2017-12-11Bibliographically approved

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Sundberg, Christian

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