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Biomedical subjects

G K Gerasimova

Publications and source records attributed to G K Gerasimova.

At least 19 recordsLinked to original sources
PubMed2001

[A novel immunoregulating hexapeptide with antineoplastic effect].

A synthesized analog of myelopeptide HP-2-->M[symbol: see text]-2 (Leu-Val-Val-Tyr-Pro-Trp) caused a significant (60-80%) and prolonged inhibition of s.c. grafted tumors P388, Ca-755, B-16 and sarcoma 180 in isogenic mice but did not affect the growth of tumor B-16 in nude mice. Nor did it influence proliferative activity or viability of cultured human tumor cells. The best results were obtained with s.c. injections of 0.5-2 mg/kg HP-2-->M[symbol: see text]-2, twice or trice a day, at 96 hr intervals. No symptoms of severe poisoning were registered at doses of HP-2-->M[symbol: see text]-2 100 times the therapeutic one. A pharmacokinetic study in mice revealed prolonged circulation of HP-2-->M[symbol: see text]-2 in blood and a high affinity for the bone marrow (t 1/2 (130.1 hr and 431.6 hr, respectively). HP-2-->M[symbol: see text]-2 restored in vitro the ascites P388-suppressed cytotoxicity of murine T-lymphocytes. HP-2-->M[symbol: see text]-2 is regarded as a candidate for clinical studies of its potential of immunocorrection in cancer patients suffering T-lymphocyte immunity disturbances.

Adjuvants, Immunologic↗
PubMed2001

[Results of cooperation of Experimental and Clinical Chemotherapy, N. N. Blokhin Center for Oncology Research, Russian Academy of Medical Sciences (1952-2000)].

Milestones of the Russian antitumor chemotherapy development inseparably associated with the names of N.N. Blokhin, L.F. Larionov and V.I. Astrakhan are reviewed. Since the early 50s of the last century, more than 7,000 generic and synthetic compounds have been studied by the three generations of chemotherapy researchers. 17 antitumor drugs have been developed and passed for clinical trials, 11 of them have been or still are being used in clinic.

Academies and Institutes↗
PubMed1998

[Synthesis and biological properties of 3,5-cyclophosphates- and -amidophosphates of 1,2-O-alkylydene-6-deoxy-6-halogeno-alpha -D-glucofuranoses].

3,5-Cyclic phosphates and phosphoramides of 6-halogenated glucofuranoses were synthesized via interaction of 3,5,6-bicyclophosphites of 1,2-O-alkylidene-alpha-D-glucofuranoses with halogens (followed by treatment with nucleophilic reagents) and N-chloroamines. 3,5-Cyclic trans-dibutylphosphoramides of 6-chloro-6-deoxy-1,2-O-isopropylidene- and 6-chloro-6-deoxy-(R)-(2,2,2)-trichloroethylidene)-alpha-D-glucofuranoses were shown to possess antiproliferative activity against CaOv human ovarian carcinoma cells in vitro (CE50 of approximately 10(-5) M). Cyclic trans-dibutylphosphoramide of 6-chloro-6-deoxy-1,2,-O-isopropylidene-alpha-D-glucofuranose also displayed marked antitumor effect on P-388 transplantable murine leukemia in vivo (the maximum increase in life span of 100% was reached at the quintuple injection of 100 mg/kg daily).

Animals↗
PubMed1997

Antitumor activity of conjugates of the oncofetal protein alpha-fetoprotein and phthalocyanines in vitro.

The several conjugates of aluminium and cobalt complexes of phthalocyanines with human alpha-fetoprotein have been synthesized. Their cytotoxic activity against tumor cells and human peripheral blood lymphocytes was studied. The experimental data demonstrate that the cytotoxic activity of alpha-fetoprotein-phthalocyanine conjugates against three types of tumor cells of various origin is much higher (for aluminium and cobalt complexes more than 1000 and 50 times, respectively) in comparison with phthalocyanines themselves. The application of phthalocyanines as conjugates with alpha-fetoprotein makes it possible to markedly enhance the selective toxicity of phthalocyanines against human tumor cells.

Aluminum↗
PubMed1997

Antitumor activity of conjugates of the oncofetal protein alpha-fetoprotein and phthalocyanines in vitro.

The several conjugates of aluminium and cobalt complexes of phthalocyanines with human alpha-fetoprotein have been synthesized. Their cytotoxic activity against tumor cells and human peripheral blood lymphocytes was studied. The experimental data demonstrate that the cytotoxic activity of alpha-fetoprotein-phthalocyanine conjugates against three types of tumor cells of various origin is much higher (for aluminium and cobalt complexes more than 1000 and 50 times, respectively) in comparison with phthalocyanines themselves. The application of phthalocyanines as conjugates with alpha-fetoprotein makes it possible to markedly enhance the selective toxicity of phthalocyanines against human tumor cells.

Aluminum↗
PubMed1996

[Effect of anti-tumor agents cisplatin and cycloplatam on membrane protein kinase C activity in murine T-lymphocytes].

The effect of cisplatin and the new drug cycloplatam (amine (cyclopentylamine)-S-(-)-malatoplatinum (II)) on protein kinase C (PKC) activity and Ca(2+)-dependent binding of PKC to T lymphocytes membranes was studied in vivo and in vitro. At first, the effect of the drugs on PKC activity of intact and activated lymphocytes was studied in vivo. In 48 hours after intraperitoneal injection of mice with therapeutic doses of the drugs, PKC activity of intact lymphocytes was differentially affected. Cisplatin did not practically alter the enzyme activity, whereas cycloplatam inhibited the PKC activity by 37% versus control. In lymphocytes activated by mouse P-388 leukemia cells in vivo, the drugs caused almost complete suppression of PKC activity and Ca(2+)-dependent binding of the enzyme to the membranes. The drugs were effective in intact cells. After incubation of intact lymphocytes in vitro for 24 hours with cisplatin or cycloplatam (10(-5)M), PKC activity was increased 1.62- and 1.35-fold, respectively, versus control. Ca(2+)-dependent binding of the enzyme to the membranes was also increased 1.61- and 1.36-fold by cisplatin and cycloplatam, respectively. On the contrary, at 10(-4) M concentration under similar conditions, the drugs did not affect the PKC activity of the lymphocytes. Furthermore, cycloplatam, unlike cisplatin, reduced the PKC binding to cellular membranes by 31%. The mechanisms of the drugs effects on PKC activity are suggested. The data indicate that increase or decrease of PKC activity induced by the drugs cause stimulation or depression of functional activity of T lymphocytes, respectively. Thus, the membrane-bound PKC can play the key role in initiation and development of immunomodulatory effects of cisplatin and cycloplatam.

Animals↗
PubMed1993

[The use of verapamil in tests for determining the drug resistance of leukemic blasts].

To determine prognostically unfavourable groups of acute leukemia patients, the authors studied the in vitro accumulation of 3H-vincristine (Vcr) and adriamycin (ADR) as well as inclusion of 3H-cytosar (Ara-C) into marrow blast DNA from patients showing different effects of treatment. It was found resistant to induction chemotherapy increases with verapamil addition to culture medium (Vrp+ cells). ADR inclusion into Vrp+ cells was the same as that into Vrp- cells. The inclusion of 3H-Ara-C into S-phase cell DNA in the cells Vrp+ was 3 time that in the cells Vrp-. All the responders to cytosar treatment had Vrp- blasts. It is evident that evaluation of Vrp effect on 3H-Vcr accumulation under short-term culturing is able to indicate groups of patients with low probability of achieving complete remissions in response to standard regimens of Vcr, Ara-C and anthracyclines treatment.

Adolescent↗
PubMed1992

Antiproliferative effect of complexes of platinum (II) with plasmanyl-(N-acyl)-ethanolamine, an inhibitor of protein kinase C.

Antiproliferative activities of combinations of semisynthetic plasmanyl-(N-acyl)-ethanolamine [PNAE(s)], an inhibitor of protein kinase C, with two antitumor complexes of platinum (II) [cisplatin and ammine(cyclopentylamine)-S-(-)-malatoplatinum (cycloplatam)] were investigated. The exposure of human melanoma BRO cells in culture simultaneously with cisplatin (1-10 microM) and PNAE(s) (100 microM-1 mM) in a molar ratio of 1/100 for 24 h induced a considerable decrease in the ability of these cells to incorporate [3H]thymidine into DNA. A considerable antiproliferative synergism of these agents was observed. The effect of cycloplatam/PNAE(s) combination in similar experiments was significantly different from cisplatin/PNAE(s), i.e. interaction of these agents was complex and synergism was not found.

Antineoplastic Agents↗
PubMed1992

[Biochemical indicators of anthracycline sensitivity of blast cells from patients with hemoblastoses].

It was shown that accumulation of adriamycin (ADR) and its impact on DNA synthesis in the blast cells of patients with hemoblastosis studied under conditions of short-term incubation correlated with the antileukemic activity of anthracyclines. The combination of the two biochemical and pharmacological indices, i.e. the high levels of ADR accumulation and inhibition of DNA synthesis, is may useful in solving the problem on inclusion of the antibiotics to the schemes of combined chemotherapy of patients with hemoblastosis.

Blast Crisis↗
PubMed1991

Synergistic antiproliferative effect of cis-diammine-dichloroplatinum (II) and a new anticancer agent, plasmanyl-(N-acyl)-ethanolamine, an inhibitor of protein kinase C.

The action of a new anticancer agent, the semisynthetic alkyl-phospholipid plasmanyl-(N-acyl)-ethanolamine (sPNAE), namely 1-O-octadecyl-2-oleoyl-sn-glycero-3-phospho-(N-palmitoyl)-ethanolamine, on protein kinase C (PKC) was investigated, and it was found to inhibit in a dose-dependent manner PKC isolated from mouse brain. The inhibition was competitive with respect to phosphatidylserine (K(i) = 20 microM). Lyso-PNAE, a possible cell metabolite of sPNAE, also inhibited PKC. A two-site model was used to calculate the binding affinity and the number of binding sites for phorbol ester in a culture of human melanoma BRO cells. The values of Kd, the dissociation constant, were K'd = 0.5 nM and K"d = 72 nM, whereas the values of Bmax, the number of binding sites, were B'max = 4.6 x 10(4) sites cell-1, and B"max = 2.9 x 10(5) sites cell-1. sPNAE was able to reduce the affinity of BRO cells for phorbol ester with almost no changes in the number of binding sites: K'd = 1.6 nM, K"d = 557 nM, and B'max = 4 x 10(4), B"max = 1.9 x 10(5). These data suggest that sPNAE may inhibit PKC in intact cells. Since various inhibitors of PKC may enhance the antiproliferative activity of cis-diamminedichloroplatinum(II) (cis-DDP), we investigated the effect of the combination of sPNAE and cis-DDP on the proliferation of BRO cells. sPNAE synergistically enhanced the antiproliferative activity of cis-DDP.

Animals↗
PubMed1991

Inhibition of protein kinase C by semisynthetic phospholipid plasmanyl-(N-acyl)-ethanolamine, a nontoxic antitumor preparation.

Protein kinase C was extracted from mouse brain and partially purified by ion-exchange chromatography on a DEAE-cellulose column. Its activity was determined by incorporation of phosphate from [gamma-32P]ATP into histone H2b. The semisynthetic alkyl-phospholipid plasmanyl-(N-acyl)-ethanolamine (PNAEs) with selective antitumor activity inhibited the activity of the protein kinase in a cell-free system in the presence of phosphatidylserine, a protein kinase C activator. The inhibition was competitive with respect to phosphatidylserine, the inhibition constant being 40 microM.

Animals↗
PubMed1985

[Effect of methylcobalamin on methotrexate transport in normal and tumorous tissues].

The effect of methylcobalamin on 3H-methotrexate uptake by tumor and normal tissues of mice with mammary adenocarcinoma (Ca-755) was studied. Methylcobalamin stimulated the rate of 3H-methotrexate influx into the tumor and small intestine but did not change its influx into the spleen. The effect was dependent on the dose of methylcobalamin. Comparative analysis of the kinetic differences in 3H-methotrexate influx and efflux in tumor and susceptible host tissues revealed the optimal dose of methylcobalamin 0.01 mg/kg to improve the antitumor drug action.

Adenocarcinoma↗
PubMed1981

[Methionine synthetase activity in tumor cells following administration of methylcobalamin and its analog].

Methylcobalamin (10 microgram/kg bw, intramuscularly, on the 3d and 5th days after tumor transplantation) or methylcobalamin chlorpalladat -- MeCbl.PdCl3 (250 mg/kg bw in 2% starch suspension per os on the 2d and 6th days) were given to C57BI mice bearing adenocarcinoma Ca--755. On the 8th day after transplantation the methionine synthetase activity and proliferative pool of tumor cells were estimated. It has been disclosed that under the effect of MeCbl the activity of methionine synthetase rises concurrently with an increase in pool of the proliferating cells. Inhibition of tumor growth (by 80--90%) after the treatment with MeCbl.PdCl3 correlated with a decrease in the holoenzyme level in tumor cells.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗