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Polyamine biosynthesis inhibitors combined with systemic hyperthermia in cancer therapy.
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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.
Hyperthermia studies in polyamine-altered human lung carcinoma cells.
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The effect of polyamine depletion on the survival response of human lung carcinoma cells (A-549) to acute heating at 45 degrees C and its effect on the induction and decay of thermotolerance were investigated in exponential and plateau-phase cells. A 48-h exposure to 1 mM
Involvement of polyamines in the contragestational effect of hyperthermia.
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Although hyperthermia produces teratogenic effects in a great variety of animal species, the molecular mechanisms by which hyperthermia exerts its action remain unknown. We have studied the implications of polyamines in contragestational hyperthermia in rats. Our results show that the
Polyamines and polyamine biosynthesis in cells exposed to hyperthermia.
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The issue of how polyamines act to sensitize cultured cells to the lethal effects of hyperthermia was investigated using Chinese hamster cells which were induced to express thermotolerance. Intracellular levels of these naturally occurring polycations were manipulated in certain situations by
Evidence against putrescine and polyamines as endogenous mediators of fever.
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Endogenous concentrations of putrescine, spermidine, spermine and related biosynthetic enzymes were not affected by the administration of bacterial endotoxin and the subsequent development of fever in rabbits. In addition, the febrile response to endotoxin was unaffected either by the ornithine
Hyperthermia, polyamine depletion, and inhibition of X-ray-induced DNA strand break repair.
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We have recently demonstrated that HeLa cells that had been depleted of polyamines by treatment with inhibitors of polyamine biosynthesis were deficient in their ability to repair X-ray-induced DNA strand breaks. Since it had previously been demonstrated that hyperthermic shock also inhibited strand
Polyamine patterns in plasma of patients with systemic lupus erythematosus and fever.
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Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with various clinical manifestations and serologic markers. In this study, we analyzed nine polyamine (PA) profiles of plasma from patients with SLE and healthy controls (HCs), and the relationship between the PA profiles and
Effects of treatments with alpha-difluoromethylornithine and hyperthermia on the growth and polyamine metabolism of Harding-Passey murine melanoma.
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The oral administration of alpha-difluoromethylornithine (DFMO), an enzyme-activated inhibitor of ornithine decarboxylase (ODC), produced a marked decrease in the rate of growth of amelanotic Harding-Passey melanoma transplanted in mice. The half-life of this compound in Harding-Pasey melanoma was
Polyamines, and effects from reducing their synthesis during egg development in the yellow fever mosquito, Aedes aegypti.
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Development of eggs after a blood meal in the yellow fever mosquito Aedes aegypti involves hormonal changes, synthesis of nucleic acids, activation of the digestive enzyme trypsin, and production of the yolk protein vitellogenin. Polyamines have been implicated in growth processes and were here
Hyperthermia and polyamine biosynthesis: decreased ornithine decarboxylase induction in skin and kidney after heat shock.
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The effect of hyperthermia treatments on ornithine decarboxylase (ODC) induction in mouse tissue was determined both in vitro and in vivo. In vitro, the addition of 12-0-tetradecanoylphorbol-13-acetate (TPA) to adult mouse skin pieces incubated at 37 degrees C in serum-free MEM led to a dramatic
Anticancer drugs and hyperthermia enhance cytotoxicity induced by polyamine enzymatic oxidation products.
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A correlation between regulation of cell proliferation and polyamine metabolism is described. The latter can enter protein synthesis through the modification of eukaryotic initiation factor 5A (eIF5A) and the formation of the peculiar amino acid hypusine. Specific inhibitors of hypusine formation
Enhancement of hyperthermia-induced cytotoxicity by polyamines.
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Synergistic effect of irradiation and hyperthermia on established cell lines derived from maxillary carcinoma. Report I.
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Cultured tumor cells of an established cell line derived from cancer of the head and neck (maxillary and lingual cancer) were irradiated with X-rays (5 or 10 Gy). This treatment inhibited cell proliferation in a dose-dependent way. Cell cycle analysis showed that the ratio of cells in the S phase to
Whole body hyperthermia and heat-sensitizing drugs: a pilot study in canine lymphoproliferative disease.
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Thirteen dogs were entered into a pilot study to assess the toxicities associated with polyamine biosynthetic enzyme inhibitors as heat sensitizing drugs and whole body hyperthermia either alone or in combination. Disease-free and tumour-bearing animals were entered in an effort to assess the
[Polyamines in microorganisms sensitive and resistant to antibiotics].
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Intracellular contents of polyamine dancyl derivatives were determined by the method of thin-layer chromatography in Coli and typhoid fever bacteria sensitive to antibiotics and their variants resistant to streptomycin, levomycetin, chlortetracyline and neomycin. Increased levels of spermidine and
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