PMID: 2116388Jul 1, 1990Paper

Polyamine biosynthesis inhibitors combined with systemic hyperthermia in cancer therapy

International Journal of Radiation Oncology, Biology, Physics
P M HarariE W Gerner

Abstract

A Phase I clinical trial has been initiated at the University of Arizona Cancer Center which combines escalating oral doses of the polyamine biosynthesis inhibitor alpha-difluoromethylornithine (DFMO), with systemic hyperthermia (approximately 41.5 degrees C) in the treatment of metastatic melanoma. The rationale for the combination of hyperthermia and polyamine biosynthesis inhibitors in the treatment of human cancers includes studies which show that depletion of endogenous polyamines, as a result of treatment with DFMO, sensitizes both rodent and human tumor cells to the cytotoxic effects of hyperthermia. Heat shock induces the first enzyme in polyamine catabolism, spermidine/spermine N1-acetyltransferase (N1-SAT). The consequently acetylated forms of spermidine and spermine are then constitutively oxidized by the enzyme polyamine oxidase (PAO). Both CHO and human A549 lung cancer cells exhibit heat-inducible polyamine acetylation, display potent heat sensitization after polyamine depletion, and ultimately reveal prolonged expression of thermotolerance. Conversely, HeLa cells do not demonstrate heat-inducible polyamine catabolism, are not sensitized to heat with DFMO, and display more rapid kinetics of thermotolerance decay. ...Continue Reading

References

Jun 15, 1978·The New England Journal of Medicine·S E SalmonT E Moon
Apr 1, 1989·American Journal of Clinical Oncology·D S ShimmJ R Cassady
Feb 1, 1989·International Journal of Radiation Oncology, Biology, Physics·P M HarariE W Gerner
Jan 1, 1988·International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group·D S ShimmD A Sim
Jan 1, 1983·Annual Review of Biochemistry·A Meister, M E Anderson
Jan 1, 1984·Annual Review of Biochemistry·C W Tabor, H Tabor

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Citations

Sep 15, 1994·Biochemical Pharmacology·E AgostinelliD A Averill-Bates
Jan 1, 1992·Pharmacology & Therapeutics·P P McCann, A E Pegg
Nov 30, 2011·Best Practice & Research. Clinical Gastroenterology·Christina M Laukaitis, Eugene W Gerner

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