[Experimental evaluation of immunotoxicity of olipifat]. / Eksperimental'noe issledovanie immunotoksicheskikh svoistv olipifata.

The paper presents our data on the influence of Olipifat on the mass and cell patterns of the immune system organs, phagocytic activity of macrophages, number of antibody-producing B-lymphocytes and immune rosette-forming T-lymphocytes. Olipifat showed no immunotoxic characteristics; it stimulated T-system immunity as evidenced by a significant increase in the number of immune rosette-forming T-lymphocytes in mice after injection of 100 or 50 mg/kg.

[Effect of olipifate on the wound healing proces and relapse after resection of Pliss lymphosarcoma]. / O vliianoe olipifata na protsessy zazhivleniia ran i retsidivirovanie posle rezekstii limfosarkomy Plissa.

The investigation was concerned with the influence of preliminary injections of Olipiphat, irrigation of operative wound and combination of both procedures on healing and relapse processes, following resection of Pliss lymphosarcoma at different stages after transplantation into rats. The physical condition of the animals after tumor resection on days 12, 10 or 7 of tumor growth was better than in controls, as a result of irrigation of the operative wound with Olipiphat or in combination with preliminary injections of the drug: they came out from anesthesia quicker, tidied themselves up and moved about the cage. Irrigation of the wound with Olipiphat or in combination with preliminary injections followed by longer survival after surgery performed at all stages of tumor growth. Moreover, one animal out of 16 in each of the 4 Olipiphat-treated groups survived 60 days recurrence-free. The drug proved more effective in stimulating the healing of larger wounds but contributed to healing by first intention in all cases.

Analgesic effect of olipiphate on mouse model of chemical stimulation of peritoneum.

We studied the analgesic effect of olipiphate, a product of lignin, against writhing provoked by intraperitoneal injection of acetic acid. Paracetamol was used as the reference drug. Both agents dose-dependently decreased the number of motor reactions caused by the irritant. Olipiphate possessed analgesic activity and efficiency comparable with those of paracetamol, but produced a more long-lasting effect.

Effect of a novel antineoplastic drug olipifat on antitumor immunity in mice.

Olipifat is an antineoplastic drug containing pyrophosphate and a product of special lignin processing. Donor C57Bl/6J mice with syngeneic B16 melanoma received a single 5-day course of olipifat. Effect of olipifat on antitumor resistance was evaluated by local neutralization test [3]. In animals with rapid melanoma growth, splenic cells from intact donors stimulated tumor growth. Olipifat abolished this growth-stimulating effect of splenocytes. In animals with slow melanoma growth, splenocytes had no effect on the growth of melanoma or Lewis lung cancer. In this case, splenocytes from olipifat-treated donors completely arrested the growth of melanoma B16 and decelerated the growth of Lewis lung carcinoma.

[An experimental study of the antitumor properties of olipifat]. / Eksperimental'noe izuchenie protivoopukholevykh svoistv olipifata.

Olipiphat is an original lignin-based mix developed by special technology. It showed antitumor action against carcinoma of Ehrlich, breast adenocarcinoma Ca 755, melanoma B 16, lung carcinoma of Lewis, lymphosarcoma of Pliss, Walker's carcinoma, sarcoma 45 (tumor growth inhibition by 83-92%, increase in survival by 42-54%) and spontaneous murine tumors (the total of 9 pathologies). The drug was administered by 3-5 injections at 2-3 day intervals. No immediate cytotoxic or cytostatic effects were registered.

[Study of the toxicity of pyrophosphate (an ingredient of Olipiphat)]. / Izuchenie toksichnosti pirofosfata (ingredienta olipifata).

No signs of toxicity of pyrophosphate as an ingredient of olipiphat were found in acute and chronic experiments using mice, rats, guinea pigs, rabbits and dogs. Mild antitumor action was recorded.

[Chemobiokinetics of sarcolysin and its peptides with glutaminic acid]. / Khemobiokinetika sarkolizina i ego peptidnykh analogov s glutaminovoi kislotoi.

A 14C study of chemobiokinetics of sarcolysin and its peptides of glutaminic acid, dosage and routes of administration was conducted in intact rats and those bearing Walker's carcinoma. Similar in shape for peptides, kinetic curves differed from those found for sarcolysin. The rates of absorption and excretion of sarcolysin peptides in intraperitoneal and, particularly, oral administration were lower than those of sarcolysin. Tumor appeared to play a role in a higher rate of peptide excretion. While sarcolysin and its peptides distribution in organs and tissues was generally identical, time of peak radioactive concentration build-up was different. Time needed for accumulation and excretion of peptides from tumor was much longer than from other organs or tissues. Sarcolysin went chiefly to urine while peptides--to faeces.

[Alkyl nitrosoureidodioxans and alkyl nitrosoureidopropane diols -- new groups of antitumor compounds]. / Alkilnitrozoureidodioksany i alkilnitrozoureidopropandioly -- novye gruppy protivoopukholevykh soedinenii.

1,3-dioxan- and 1,3-propane diol derivatives of alkyl nitrosourea have been synthesized and studied. Like other 2/chloroethylnitrosoureas, they exerted pronounced influence on a wide range of transplantable tumors, including those transplanted intracranially. Antitumor effect was found to depend on C5 and C2 atom substituent in the 1,3-dioxan cycle and 1,3-propane diol, respectively. The therapeutic effect and toxicity of 1,3-propane diol derivatives were higher than those of 1,3-dioxan. The substances lost all antitumor properties if a methyl group was substituted for the 2-chloroethyl one, even though a nitroso group was retained in their structure.

[Antitumor activity and toxicity of combined doxorubicin and disodium salt of methylene-1,1-diphosphonic acid]. / O protivoopukholevoi aktivnosti i toksichnosti kompleksa doksorubitsina s dinatrievoi sol'iu metilen-1,1-difosfonovoi kisloty.

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.

[Basic and salvage pathways of NAD biosynthesis in organs of normal rats, tumor-bearing rats and in tumors]. / Osnovnoi i zapasnoi puti biosinteza NAD v organakh zdorovykh krys, krys-opukholenositelei i v opukholiakh.

The rates of quinolinic and nicotinic acids and nicotinamide utilization for NAD biosynthesis in organs of normal rats and those with lymphosarcoma of Pliss and Walker's carcinosarcoma were studied. All three compounds were shown to be NAD's precursors in the liver and kidneys of normal animals. Quinolinic acid failed to stimulate the increase in NAD concentration in the liver of Walker carcinosarcoma-bearing rats. An insignificant rise in NAD concentration was registered in the liver of rats with lymphosarcoma of Pliss following quinolinic acid treatment. The rates of nicotinic acid and nicotinamide utilization in the liver of tumor-bearing animals were lower than in healthy controls. Quinolinic acid utilization was the most intense in the kidney of rats with Walker's carcinosarcoma while nicotinic acid and nicotinamide were mostly utilized in the kidney of rats with lymphosarcoma of Pliss. None of the three precursors caused NAD concentration to rise in Walker's carcinosarcoma cells whereas nicotinamide injection was followed by an increase in NAD concentration in Pliss lymphosarcoma cells. To summarize, the neoplastic cells under study do not use the basic pathway of NAD biosynthesis and are characterized by different rates of nicotinic acid and nicotinamide utilization.

[An analysis of the connection between the inhibition of NAD biosynthesis and the antitumor activity of drugs]. / Analiz sviazi mezhdu ingibirovaniem biosinteza NAD i protivoopukholevoi aktivnost'iu preparatov.

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.

[Mechanism of various degrees of tumor sensitivity to olivomycin]. / O mekhanizme razlichnoi chuvstvitel'nosti opukholei k olivomitsinu.

Efficiency and duration of suppression of the synthesis of low-polymer (4S) and ribosomal (18S and 28S) fractions of total RNA due to exposure of the cells of Ehrlich's carcinoma and Zajdela's hepatoma to olivomycin were studied. The tumors differed in their sensitivity to the antibiotic. The efficiency of the rRNA synthesis inhibition by olivomycin on its addition to the cells of Ehrlich's carcinoma and Zajdela's hepatoma in vitro was of the same order. Study on the kinetics of rRNA synthesis after addition of olivomycin showed that the maximum inhibition of rRNA synthesis in the cells of Ehrlich's carcinoma was achieved 1 hour after the drug addition. After 2 hours the inhibition level returned to normal. The most efficient inhibition of rRNA synthesis in the cells of Zajdela's hepatoma was observed 2 hours after addition of the drug. The inhibition level in this case did not return to normal after 24 hours. It is concluded that tumor sensitivity to olivomycin is determined by the duration of the affection of the DNA template activity during the synthesis of RNA.

[Experimental study of the combined effect of 5-fluorouracil and cyclophosphane on growth of Zajdela hepatoma and nucleic acid metabolism]. / Eksperimental'noe izuchenie sochetannogo deistviia 5-ftoruratsila i tsiklofosfana na rost gepatomy Zaidela i metabolizm nukleinovykh kislot.

Zajdela's ascites hepatoma of rats was treated with diverse combinations of 5-fluorouracil (5-FU) and cyclophosphane to study antitumour effect and the intensity of inhibiting the synthesis of nucleic acids. It was established that administration of 5-FU during the first three days and CP during the next three days in doses producing no effect when the drugs are given alone leads to an abrupt inhibition of tumour growth with concurrent inhibition of the synthesis of DNA and all fractions of total RNA. Administration of the drugs in the same succession but in higher doses that produce an inhibition of tumour growth (when the drugs are given alone) results in an antitumour action without eliciting pronounced side effect on bone marrow hemopoiesis.