ABSTRACT
Antitumor activity of the novel for oncology compound, such as polysuccinimide, against some of experimental tumor models (Lewis lung carcinoma, Acatol adenocarcinoma, Ca-755 adenocarcinoma) has been established. This drug induced 60-80% tumor growth inhibition of these murine solid tumor strains. Polysuccinimide is also effective (60%) against development of metastatic process in lung (Lewis lung carcinoma). Polysuccinimide causes no changes in pH level in tumor tissue (P-388 leukemia, Acatol adenocarcinoma). This agent may be recommended for further profound preclinical study.
Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Agents/administration & dosage , Aspartic Acid/analogs & derivatives , Carcinoma, Lewis Lung/drug therapy , Peptides/administration & dosage , Adenocarcinoma/pathology , Animals , Aspartic Acid/administration & dosage , Aspartic Acid/chemical synthesis , Carcinoma, Lewis Lung/pathology , Humans , Mice , Peptides/chemical synthesisABSTRACT
The anti-tumor activity of the binuclear form of dinitrosyl iron complexes with glutathione against Lewis lung carcinoma, found earlier upon intraperitoneal administration of the complexes, was also observed when this preparation was injected subcutaneously. A 100 µM/kg subcutaneous dose of the complex being used daily (as calculated per one iron atom in binuclear dinitrosyl iron complexes) for 10 or 15 days, inhibited the tumor growth by 43%. The effect was observed during the first two weeks after tumor transplantation. After that, the tumors began to grow at the rate equal to or even higher than that one for control animals. The mean survival time for treated mice exceeded the control values by 30%. Binuclear dinitrosyl iron complexes administered intraperitoneally was also effective against Ca-755 adenocarcinoma. However, in this case the mean survival time for treated animals increased only by 7%. The anti-tumor activity of S-nitrosoglutathione against Lewis lung carcinoma growth inhibition by 70% and Ca-755 adenocarcinoma growth inhibition by 90% was also shown. However, unlike binuclear dinitrosyl iron complexes the anti-tumor effect of S-nitrosoglutathione decreased when a daily dose of the compound increased (from 200 to 400 µM/kg) The initial anti-tumor effect of binuclear dinitrosyl iron complexes and S-nitrosoglutathione is suggested to be due to NO released from both compounds. A subsequent suppression of the effect is determined by the development of anti-nitrosative and anti-oxidant defense systems in tumors.
Subject(s)
Carcinoma, Lewis Lung/drug therapy , Glutathione/administration & dosage , Iron/administration & dosage , Nitrogen Oxides/administration & dosage , S-Nitrosoglutathione/administration & dosage , Adenocarcinoma/drug therapy , Adenocarcinoma/metabolism , Animals , Carcinoma, Lewis Lung/pathology , Cysteine/chemistry , Cysteine/metabolism , Glutathione/chemistry , Humans , Iron/chemistry , Mice , Nitric Oxide/chemistry , Nitric Oxide/metabolism , Nitrogen Oxides/chemistry , S-Nitrosoglutathione/chemistryABSTRACT
Antitumor activity of ultralow doses of cytostatic doxorubicin was studied on BDF1 mice with Lewis lung carcinoma. The preparation was injected intraperitoneally in single doses of 10(-5), 10(-10), 10(-15), and 10(-20) M on the next day after tumor inoculation. The effect of ultralow doses was compared with that of a standard therapeutic dose of doxorubicin (8 mg/kg, 1.4 x 10(-3) M). Doxorubicin in ultralow doses produced an antitumor effect comparable with that induced by the preparation in standard doses. On day 12 after administration of doxorubicin in ultralow and standard doses, tumor size in mice did not exceed 20% of the control level.
Subject(s)
Antineoplastic Agents/therapeutic use , Doxorubicin/therapeutic use , Animals , Antineoplastic Agents/administration & dosage , Carcinoma, Lewis Lung/drug therapy , Dose-Response Relationship, Drug , Doxorubicin/administration & dosage , Mice , Neoplasms, Experimental/drug therapyABSTRACT
The action of a number of active anticancer agents belonging to the alkylnitrosoureas (MNU, DMNU, ADEKO, BCNU, CCMU, MeCCNU), as well as the effectiveness of a combined use of DMMU and ADEKO with cyclophosphamide was assessed on experimental tumors transplanted by inocula of different size. A mathematical model of the connection between survival of tumor-bearing animals with the kinetics of tumor growth was proposed to analyze the treatment effect. The contribution of lethal and cytostatic factors to the resultant effect of the drugs was evaluated. A combination of DMNU and cyclophosphamide was found to possess an additive effect. The synergism of the therapeutic action shown in a combined application of ADEKO and cyclophosphamide was stipulated by the potentiation of the lethal effect of these drugs on tumor cells.
Subject(s)
Antineoplastic Agents/pharmacology , Neoplasms, Experimental/pathology , Nitrosourea Compounds/pharmacology , Alkylation , Animals , Cyclophosphamide/pharmacology , Mathematics , Mice , Mice, Inbred C57BL , Models, BiologicalABSTRACT
The kinetics of tumor growth and cell proliferation of eleven generations of spontaneous mammary carcinoma in F1(CBA2 X C57B1/6) mice was studied. Factors responsible for different sensitivity of tumors to 1-methyl-1-nitrosourea were analyzed. The process of tumor transplantation was accompanied by the reduction in latent period and the increase in the mean specific rate of tumor growth. The rise in tumor growth rate in consequent generations was associated with the increase of the number of DNA synthesizing cells. The fall in the intensity of the DNA synthesis was observed along with the tumor growth within one passage. The sensitivity of tumors to 1-methyl-1-nitrosourea was correlated reciprocally only with the initial labeling index of tumors and the specific rate of tumor growth.
