Journal ArticleDOI
Synergistic action of two polyamine antimetabolites leads to a rapid therapeutic response in childhood leukemia.
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TLDR
The synergism between the action of the two compounds was based upon a unique drug interaction; a preceding treatment with difluoromethyl ornithine greatly increased the uptake of subsequently administered methylglyoxal bis‐(guanylhydrazone) as verified by the actual determinations of the latter drug in the circulating leukemia cells.Abstract:
Sequential administration of alpha-difluoromethyl ornithine and methylglyoxal bis(guanylhydrazone), two differently acting inhibitors of the biosynthesis of natural polyamines, produced a rapid and distinct therapeutic response in four children with advanced lymphoblastic and in one with myeloblastic leukemia. The synergism between the action of the two compounds was based upon a unique drug interaction; a preceding treatment with difluoromethyl ornithine greatly increased the uptake of subsequently administered methylglyoxal bis(guanylhydrazone) as verified by the actual determinations of the latter drug in the circulating leukemia cells. The side-effects associated with the combined drug regiment were either absent or mild.read more
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Polyamines: from Molecular Biology to Clinical Applications
TL;DR: The development and introduction of specific inhibitors to the biosynthetic enzymes of the polyamines have revealed that an undisturbed synthesis of thePolyamines is a prerequisite for animal cell proliferation to occur, and thus offers a meaningful target for the treatment of certain hyperproliferative diseases, most notably cancer.
Journal ArticleDOI
Ornithine decarboxylase: a key regulatory enzyme in normal and neoplastic growth.
Journal ArticleDOI
Inhibitors of polyamine metabolism: review article.
TL;DR: Evidence of induction of both PAO and PAO-h1/SMO in response to polyamine analogue treatment, suggests the analogues may become an important part of future chemotherapeutic and/or chemopreventative regimens.
Journal ArticleDOI
In vivo effects of α-dl-Difluoromethylornithine on the metabolism and morphology of Trypanosoma brucei brucei
Cyrus J. Bacchi,Joanne Garofalo,Dianne Mockenhaupt,Peter P. McCann,Keith A. Diekema,Anthony E. Pegg,H C Nathan,Elizabeth A. Mullaney,Laura Chunosoff,Albert Sjoerdsma,S. H. Hutner +10 more
TL;DR: Treatment with α- dl -Difluoromethylornithine treatment progressively limits the parasites' ability to synthesize nucleic acids and blocks cytokinesis while inducing morphological changes resembling long slender → short stumpy transformation.
Journal ArticleDOI
Polyamines in colorectal cancer.
TL;DR: Polyamine content of colorectal cancers was independent of tumour site, Dukes' stage, histological grade and the presence of palpable liver metastases at laparotomy, suggesting that polyamines may play an essential role in the regulation of their growth.
References
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Journal ArticleDOI
Catalytic irreversible inhibition of mammalian ornithine decarboxylase (E.C.4.1.1.17) by substrate and product analogs
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Intracellular putrescine and spermidine deprivation induces increased uptake of the natural polyamines and methylglyoxal bis(guanylhydrazone)
TL;DR: Inhibition of polyamine synthesis by alpha-difluoromethylornithine in cultured Ehrlich ascites-carcinoma cells rapidly enhanced the uptake of exogenous putrescine, spermidine and spermine from the culture medium.
Journal Article
Effect of α-Difluoromethylornithine, an Enzyme-activated Irreversible Inhibitor of Ornithine Decarboxylase, on L1210 Leukemia in Mice
TL;DR: In the spleens of L1210-inoculated mice, α-DFMO prevented 75% of the maximal elevation in ornithine decarboxylase activity, and did not affect spermidine-activated S -adenosyl-l-methioninedecarboxyase activity.
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Treatment of acute leukemia with methylglyoxal-bis-guanylhydrazone (methyl gag).
TL;DR: Methyl GAG has antileukemic activity which, although associated with substantial toxicity, is unique in the treatment of acute myelohlastic leukemia.