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Lowering of tumor interstitial fluid pressure specifically augments efficacy of chemotherapy
Author(s) -
Salnikov Alexei V.,
Iversen Vegard V.,
Koisti Markus,
Sundberg Christian,
Johansson Lars,
Stuhr Linda B.,
Sjöquist Mats,
Ahlström Håkan,
Reed Rolf K.,
Rubin Kristofer
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-1201fje
Subject(s) - chemotherapy , prostaglandin , cancer research , medicine , fluorouracil , pharmacology , chemotherapeutic drugs , prostaglandin e , chemistry
ABSTRACT 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 (PGE 1 ), 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 PGE 1 . 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 PGE 1 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.