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Biomedical subjects

L M Volkova

Publications and source records attributed to L M Volkova.

At least 19 recordsLinked to original sources
PubMed2003

Nitric oxide donor increases the efficiency of cytostatic therapy and retards the development of drug resistance.

The potentiality to increase the chemotherapeutic effectiveness of some cytostatics in low, subtherapeutic doses in combination with nitric oxide (NO) donor has been shown. This type of combined therapy results in significant increase in life span and number of survivors among mice bearing leukemias P388 and L-1210. A similar effect was observed for intracerebral leukemia P388 transplantation. In this case the life span of mice treated with cyclophosphamide and NO donor increased by three times in comparison to therapy with cyclophosphamide alone. The coinjection of nitric oxide donor and cytostatics improved the antimetastatic activity of the cytostatics: the index of melanoma B16 metastasis inhibition at the cyclophosphamide monotherapy is 50%; on addition of NO donor the index is over 80%. Comparative studies of NO donor (organic nitrate) and a similar compound in which ONO(2) moieties were replaced by OH groups demonstrated that the presence of NO(2) is required for adjuvant activity of compounds and confirmed that nitric oxide modifies the antitumor effects of cytostatics. It is shown also that nitric oxide donor retards the development of drug resistance to cyclophosphamide.

Abdominal Neoplasms↗
PubMed2003

[Nitric oxide donor increases the effectiveness of cytostatic therapy and inhibits the development of drug resistance].

The investigation has established a potential of low-dosage chemotherapy with cytostatics when used in combination with nitric oxide (NO) donor. Such regimen resulted in more animals being cured of leukemias P388 and L1210 and longer survival. Similar effect was reported with transplantable intracerebral leukemia P388 in which case mean survival after cyclophosphamide plus NO-donor was three times as high as that after cyclophosphamide alone. Combination therapy also promoted animetastatic effect: melanoma B16 inhibition by cyclophosphamide alone was 50% vs. 80% after cyclophosphamide plus NO-donor. NO-donor inhibited development of drug resistance to cyclophosphamide.

Abdominal Neoplasms↗
PubMed2000

[Effect of Ruboxyl (nitroxyl derivative of daunorubicin) on hepatic metastases of colorectal carcinoma].

Inhibition by ruboxyl, a nitroxyl derivative of daunorubicin, source preparation and 5-fluorouracil was compared in metastases of experimental colorectal carcinoma to murine liver. The indices of metastasis inhibition were 84.43 and 70%, respectively. In rats receiving the drugs by continuous intravenous infusion for 7 days, the number of metastases was reduced (ruboxyl--1.0 +/- 1.4; 5-fluorouracil 3.2 +/- 1.3.

Animals↗
PubMed1997

[Inhibitory effect of the radiosensitizer AK-2123 on experimental liver metastasis and active transport of calcium ions].

Radiosensitizer AK-2123, a triazol, has been shown to significantly inhibit the development of hepatic metastases induced in syngeneic mice by intrasplenic injections with cels of bowel adenocarcinoma. The antimetastatic effect was produced by use of a very low dose of the drug. A therapeutic dose of AK-2123 has been shown to inhibit active transport of calcium ions across sarcoplasmic reticular cells effected by Ca(2+)-dependent Mg(2+)-activated ATPase. It is suggested that the antimetastatic effect of AK-2123 is determined by at least partial inhibition of active transport of calcium.

Adenocarcinoma↗
PubMed1997

Inhibitory effect of radiosensitizer AK-2123 on experimental hepatic metastases and Ca2+ active transport.

A triazole group radiosensitizer AK-2123 is shown to inhibit considerably the growth of hepatic metastases induced by the intrasplenic injection of colon adenocarcinoma cells in syngenic mice. Even an extremely low dose of the drug exhibits the antimetastatic effect. It is shown that AK-2123 injected at therapeutic dose inhibits active transport of calcium ions by the (Ca2+-Mg2+)-dependent ATP-ase. The antimetastatic effect of AK-2123 is suggested to be related, at least partially, to the inhibition of the active calcium transport.

Adenocarcinoma↗
PubMed1996

Synthesis and antitumor activity of platinum(II) complexes with trans-3,4-diamino-2,2,6,6-tetramethylpiperidine-1-oxyl.

Platinum complexes PtII(DAPO)X2 with diaminonitroxyl radical-trans-3,4-diamino-2,2,6,6-tetramethylpiperidine-1-oxyl (DAPO)-were synthesized by the direct reaction of DAPO with K2PtX4 (X = Cl, I) or by the replacement of chloro ligands in PtII(DAPO)Cl2 by bromo, nitrato, oxalato, malonato, and 1,1-cyclobutanedicarboxylato ligands. The complexes thus obtained were characterized by elemental analysis, infrared,electronic, electron paramagnetic resonance spectroscopic techniques, and high-performance liquid chromatography. The toxicity of compounds in terms of LD50 strongly depends on the nature of X-ligands, and varies between 11 mg/kg (X = NO3) and 400 mg/kg (X2 = 1,1-cyclobutanedicarboxylate). Up to 66% of mice bearing leukemia L1210 survive after the administration of these complexes. This effect is comparable to the effect of cisplatin (50% survive). An increase in the life span of the rest of the animals ranges from 158 to 383%. Complex PtII(DAPO)Cl2 appears to be more efficient than cisplatin against adenocarcinoma 755. Cisplatin, cis-diamminedichloroplatinum(II); CBDCA, 1,1-cyclobutanedicarboxylic acid; DAPO, trans-3,4-diamino-2,2,6,6-tetramethylpiperidine-1-oxyl; Mal, malonic acid; Ox, oxalic acid; IR, infrared; EPR, electron paramagnetic resonance; HPLC, high-performance liquid chromatography; Ca755, adenocarcinoma 755; LD50 and LD100, dose of compounds (mg/kg), causing a death of 50 or 100% or treated animals; ILS, increase in life span of mice.

Animals↗
PubMed1996

[Nitroxyl radical Tempol as a modulator of toxic and antineoplastic effect of 6-mercaptopurine].

Both intact mice and those with transplantable adenocarcinoma 755 were used in the investigation. The nitroxyl radical Tempol was shown to cut down the toxicity of 6-mercaptopurine and potentiate its antitumor effect to a certain degree. The study results suggest on the basis of an investigation of cytochrome P450 and some other evidence that said effect of Tempol might be due, at least, in part to antioxidant activity.

Adenocarcinoma↗
PubMed1996

Modulatory effect of tempol on toxicity and antitumor activity of 6-mercaptopurine and on P450 cytochrome level.

Low selectivity of contemporary antitumor drugs requires a search for its improvement. In this context, nitroxyl radicals are of interest as promising pharmacological agents. The introduction of nitroxyl radical into the structure of antitumor cytostatics was found to reduce considerably their general and specific toxicity. In this work, we demonstrate a detoxifying effect of tempol upon its combined injection with cytostatics at their absolute lethal dose in the intact mice as well as an improvement of sensitivity of tumor-bearing animals to 6-MP. Tempol is shown to normalize the level of oxidized form of P450 cytochrome in a liver, reduced as a result of the injection of 6-MP.

Animals↗
PubMed1995

Radiosensitizer AK-2123 as modulating agent in the chemotherapy of experimental metastases.

Therapeutic effect of Cyclophosphamide (CPA) and radiosensitizer AK-2123 (AK) combination versus CPA alone in the same doses was investigated on transplanted LL carcinoma and B 16 melanoma. Antimetastatic efficacy of different doses of CPA and combined therapy was evaluated. Our data demonstrate that the effect of combined treatment by CPA at low uneffective doses (60 mg/kg, 40 mg/kg, 20 mg/kg at the 3rd and the 7th day after transplantation) and AK at low daily doses (1 mg/kg and 0.1 mg/kg for 3-9 days after transplantation) is equal or superior to the effect of CPA alone at the therapeutic dose (120 mg/kg).

Animals↗
PubMed1991

Nitroxyl radicals decrease toxicity of cytostatic agents.

Nitroxyl radicals of a series of piperidineoxyles and pirrolinoxyles increase the tolerance of experimental animals to the injection of otherwise lethal doses of anti-tumor cytostatic agents. Simultaneous injection of nitroxyl radicals in different doses with 6-mercaptopurine, thiophosphamide, cyclophosphamide and the other cytostatic agents results in decreased toxicity and survival of animals. Nitroxyl radicals normalize the level of the oxidized form of P450 cytochrome that is decreased by the injection of lethal doses of cytostatic agents.

Animals↗
PubMed1991

Subrenal capsule assay of human tumor chemosensitivity.

Breast and colon tumor response to emoxyl, a nitroxyl derivative of daunomycin, was detected using human tumor heterotransplantation under the renal capsule of immunocompetent mice. The substitution of adriamycin by emoxyl in the combined therapy led to enhanced therapeutic efficacy. The evidence of enhanced response of breast tumors to emoxyl obtained during the histologic examination of xenografts is in good agreement with measurements of tumor fragment weight. It is suggested to use a quantitative kinetic index kappa calculated by the method of equivalent exponents for objective evaluation of tumor response to the drugs.

Aclarubicin↗
PubMed1988

Pharmacokinetics of a spin-labeled rubomycin analog.

Pharmacokinetics of a spin-labeled analog of rubomycin (ruboxyl) was studied. Differences were found in ruboxyl pharmacokinetics in normal and tumor-bearing animals. Most of the drug was excreted within 6 h. The differences in pharmacokinetics of ruboxyl and nitroxyl radical were established.

Animals↗
PubMed1988

[Sensitivity of human tumor heterografts to a spin-labelled rubomycin derivative].

A degree of emoksil activity has been determined by applying the subrenal capsule assay methodology to fresh surgical explants of the normal immunocompetent mice. The ability of emoksil to inhibit growth of breast and colon tumours xenografts was determined. Emoksil substitution for adriamycin in the combination therapy increases the therapeutic activity. The kinetic criterion kappa calculated by the method of equivalent exponents was suggested to determine the tumour susceptibility to the drugs.

Animals↗
PubMed1988

[Changes in biological properties of malignant melanoma B-16 after transplantation to (CBA x C57Bl/6)F1 mice].

The primary tumour properties are studied for their effect on the recurrent tumour growth and metastatic spreading after chemotherapy. Serial transplantation of the B16 melanoma to (CBA X C57Bl/6)F1 mice induced gradual changes in tumour malignancy. With an increase of the generation number the metastatic activity of hybrid mice rises and chemotherapeutic sensitivity lowers. The thirty-first and the fifty-fourth tumour generations after the chemotherapy metastasize earlier and the number of metastases increases more rapidly as compared with the recurrence of the primary tumour. The metastatic potential of recurrent tumours increases with the number of generations in hybrid mice.

Animals↗
PubMed1985

[Kinetics of the cell population in adenocarcinoma 755 after cyclophosphane administration and rate of tumor growth after an additional course of therapy with cyclophosphane and 6-mercaptopurine].

The two injections of cyclophosphane (100 mg/kg) to mice with adenocarcinoma 755 on the 6th and 11th days after tumour transplantation had no influence on the cell cycle but induced a decrease of its growth rate due to an increase in the level of cell losses. The third cyclophosphane injection (the same dose) on the 17th day after the tumour transplantation or an additional course of five 6-mercaptopurine injections (50 mg/kg each dose) did not change essentially the growth rate of tumours.

Adenocarcinoma↗
PubMed1979

[Factor analysis of the effectiveness of combined therapy in experimental leukemia].

The effectiveness of the combined therapy of leukemia P-388 with cyclophosphane and diazane was studied. The pattern of administering these substances was selected with due consideration of the cyclospecificity of their action. In a number of cases considerable synergism was observed, resulting in a cure of 100% of animals. Estimation of the effectiveness and the degree of synergism was made by the method of fractionation analysis, which allowed delineating some trends for providing the optimum combined therapy.

Animals↗
PubMed1979

[Joint therapy of experimental tumors with diazan in combination with antibiotics].

Antitumor efficiency of combined therapy of experimental tumors with diazan and antibiotics was studied. The experiments were performed with leukosis La and P-388 and Walker carcinosarcoma. The kinetic regularities of the tumor process were used in planning regimens of the combined therapy. It was found that the combined use of diazan with antitumor antibiotics of the anthracyclin series increased the therapy efficacy. Therapeutic synergism of the drugs was noted which was evident from a significant increase in the average life rate and recovery of a part of the animals.

Animals↗