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V A Filov

Publications and source records attributed to V A Filov.

86 records · Page 5Linked to original sources

Inhibition of mouse melanoma cell proliferation by corticotropin-releasing hormone and its analogs.

BACKGROUND: Observations that epidermal cells release both corticotropin-releasing hormone (CRH) and proopiome lanocortin (POMC) peptides has raised questions about the physiological relevance of this hypothalamo-pituitary-like system in mammalian skin. As CRH has shown anti-proliferative effects on cultured keratinocytes, we tested whether CRH can also regulate growth of melanoma cells. MATERIALS AND METHODS: CRH, [D-Glu20]-CRH, [D-Pro5]-CRH, acetyl-cyclo(30-33)[D-Phe12,D-Glu20,Nle21,D-His32,Lys33,D-Nle38]-CRH(4-41), acetyl-cyclo(30-33)[D-Phe12,Nle18,D-Glu20,Nle21,D-Ala32]-urotensin I(4-41), urocortin, and sauvagine were tested on Cloudman melanoma cell proliferation in culture and B16 melanoma tumor growth in C57B1/6 mice. Calcium-sensitive fluorescence measurements were used to examine the effect of CRH on intracellular Ca2+ signaling. The effects of CRH and [D-Glu20]-CRH on blood pressure were compared by measuring mean arterial pressure in anesthetized rats. RESULTS: CRH and six analogs were tested, and all demonstrated exceptional potency in inhibiting Cloudman cell proliferation in culture, with half-maximal effective concentrations ranging between 0.2 and 100 pM. The amplitude of ionomycin-induced Ca2+ influx into Cloudman cells grown in suspension was reduced by 50% after 48-hr exposure to CRH. Daily injections of CRH or [D-Glu20]-CRH, 100 micrograms/kg.day s.c., for 5 days, reduced net B16 tumor volume in mice by 30-60% compared to control animals. [D-Glu20]-CRH was less hypotensive compared to CRH, despite having similar anti-proliferative potency. CONCLUSION: CRH, and various analogs thereof, inhibit proliferation of Cloudman cells in culture, and inhibit B16 tumor growth rate in vivo, most likely by activation of endogenous CRH1 receptors and subsequent altered intracellular Ca2+ signaling. CRH analogs, such as [D-Glu20]-CRH, with less hypotensive activity may provide new directions of therapy for melanoma.

Amino Acid Substitution↗

[Experimental data on the toxic action of hydrazine sulfate on the body and on a tumor].

Toxic action of hydrozine sulfate in rats and mice along with its influence on the mitotic activity of Walker carcino-sarcoma cells were studied. Single injections of the agent in high doses resulted in destruction of the animals during the first 2 days with no "delayed death" observed. Multiple injections caused a considerable loss of body weight. When given in toxic doses the agent did not influence hemopoiesis, but did affect sensitivity, drastically increasing the toxic action of ethanol or barbiturates. Administration of hydrazine sulfate in therapeutic doses decreased markedly the mitotic activity and increased the appearance of atypical mitotic cells.

Animals↗

[Pharmacokinetics of hydrazine sulfate in intact and tumor-bearing rats].

The pharmacokinetics of hydrazine sulfate was studied in intact and tumor-bearing (sarcoma 45) random-bred rats after intraventricular administration of the drug. To determine hydrazine in biosubstrates, a method was devised, which is based on spectrophotometry of the coloured product formed as a result of interaction with p-dimethylaminobenzaldehyde. Analysis of the pharmacokinetic data with the use of a 4-compartmental model showed appreciable differences in some of the pharmacokinetic parameters of hydrazine sulfate as regards intact and tumor-bearing animals.

Animals↗

[The pharmacological properties of preparations from the aziridinyl triazine group].

The results of experimental studies of three drugs from aziridinyltriazine group, dioxadet, trisadet, and furizil, are presented. These drugs exhibit a pronounced therapeutic effect against a broaden spectrum of tumors grafted in mice and rats. Toxic effect of the drugs is exhibited mainly in suppression of blood formation. Other side-effects are slightly pronounced. One of the drugs, dioxadet passed the I and II stages of clinical trials and is recommended for application in chemotherapy of malignant tumors.

Animals↗