Search

Antitumor activity of a new cytostatic drug combination of gemcitabine and dioxadet have been studied in 86 female SHR mice transplanted with 5 x 10(6) of ascitic Ehrlich's tumor cells each. All mice received a single injection of gemcitabine, dioxadet on combination 48 hams after tumor cells introduction. In first series, experimental animals received maximal tolerable dose of gemcitabine (25 mg/kg) and one half of dioxadet maximal tolerable dose (2.5 mg/kg). In the second series of experiments, the animals received 5 mg/kg of dioxadet along with the same gemcitabine dose. Effect of drugs was compared using the time to ascites detection, body weight increase, and survival time. Gemcitabine and dioxadet administered separately and in combination inhibited the growth of ascitic Ehrlich's tumor in the mice. In both series of experiments antineoplastic activity of gemcitabine and dioxadet combination was significantly higher in comparison to the control groups receiving these drugs separately. The highest antineoplastic activity of the gemcitabine and dioxadet combination was observed when the maximal tolerable doses of both drugs was applied. However, the tumor cells growth was also significantly inhibited in mice receiving half of dioxadet dose. Synergism of antitumor activity of gemcitabine and dioxadet was not accompanied by appreciable increase in toxicity.

An experimental model of solid tumor of Ehrlich failed to reveal any influence of the hepatoprotector Metrop GP on tumor growth or affect antitumor action of doxorubicin.

Such biological parameters as tumor volume, Ki-67 and p53, which characterize the development of ascites and solid tumor of Ehrlich were evaluated. The kinetic curve of growth of ascites tumor was S-shaped (Gomperts) while that of the solid one--cubic (Speer-Retsky). Ki-67 expression level was found to be in cyclic correlation with duration (3 and 6 day intervals) which might be worth considering when working out therapeutic procedure. Moreover, no increase in cell death was observed when tumor growth slowed down.

Acoustic resonance induced by theta-rhythm modulation of bioelectric activity caused moderate inhibition of solid Ehrlich tumors to take place and extended murine life span. No untoward side-effects were registered.

Toxicity and antitumor action of two new complex compounds of rhenium (K2 [ReCl6] and [ReCl(4).2C6H4N2]) were investigated. LD50 of K2 [ReCl6], i.v., was 136 +/- 37 mg/kg; i.p.,--272 +/- 74 mg/kg. LD50 of [ReCl(4).2C6H4N2], i.v., was 543 +/- 148 mg/kg; i.p., 600 mg/kg was tolerable. Single maximum tolerable dose of 200 mg/kg K2 [ReCl6], i.p., did not influence the growth of ascitic tumor of Ehrlich, nor did daily intravenous dose of 50 mg/kg inhibit solid tumor of Ehrlich. No inhibition by [ReCl(4).2C6H4N2] was registered when 25 or 50 mg/kg were administered.

An additional criterion is suggested for description of effectiveness of therapy of experimental tumors--tumor growth index. It is a ratio of area covered by the kinetic curve of tumor growth in the study group and that in control. The index is intended to describe the efficacy of therapy in terms of degree and duration of the effect.

In experiments using mice and rats with transplantable Ehrlich ascites tumors, sarcoma-180 and adenocarcinoma of Walker, antitumor activity of doxorubicin in combination with disodium salt of 1,1-methylenediphosphonic acid proved higher than that of doxorubicin alone. Most advantage was gained with daily treatment. The toxic effect of said complex treatment seemed to differ slightly from that of doxorubicin as judged on the basis of survival, changes in body mass and peripheral blood count.

The study was concerned with a relationship between a decrease in NAD concentration and inhibition of precursor utilization for NAD biosynthesis, on the one hand, and inhibition of Ehrlich ascitic carcinoma growth in response to treatment with embichin, cyclophosphamide, thiophosphamide, adriablastin and methotrexate, on the other. The antitumor effect of drugs was found to be determined by degree of inhibition of precursor utilization for NAD biosynthesis but not by a decrease in NAD level. A relationship between alteration of synchronous induction of NAD and poly (ADP-ribose) biosynthesis rates and reversibility of the antitumor effect of drugs is discussed.

The paper discusses the biological properties of 2-(2-furyl)-5-oxymethyl-5-(2,4-diethyleneimino-1,3,5-triazine- 6-yl) amino-1,3-dioxane (furizil), synthesized by substituting ethyleneimine groups for chlorine atoms in individual stereoisomer of a dichlorotriazine derivative. Furizil was found to inhibit the growth of Ehrlich's tumor, Walker's carcinosarcoma, sarcoma 45 and rat ovarian tumors, the inhibition rate ranging 76-100%. Parenterally administered, LD50 appeared to be 6 mg/kg for rats and 15 mg/kg for mice. Studies of chronic toxicity established damaging effects of furizil on hematopoietic, gastrointestinal and reproductive organs. Toxic effects subsided 1-2 weeks after the drug withdrawal.

Based on characteristic features of the toxic effect of chemotherapeutic drugs, these were selected for chemotherapy of experimental tumors. The reliable results were obtained in three variants of combinations. 1) A combined administration of drugs active with respect to one and the same tumor but which toxic effect do not coincide. 2) Simultaneous administration of two drugs in doses tolerable for gaining a therapeutic effect, obtained in their separate use in massive doses, but with a less toxic damage to the body. 3) A combination of substances possessing a selective toxic action on the tissue bearing the tumor under treatment.