[Investigation of antitumor action of acoustic resonance induced by theta-rhythm modulation].

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.

[Anti-inflammatory and reparative effect of olipiphate].

The therapeutic effect of olipiphate was demonstrated for chronic inflammation of advanced arthritis and concanavalin A-related acute edema. The best systemic effect was obtained with 50 mg/kg, symptomatic--100 mg/kg. Skin wounds treated with 5% olipiphate (26 + 2) healed faster than those treated with 2% solcoseryl (30 + 0.8) or in control (33 + 0.6). It was shown histologically that the proliferative and antiphlogistic effect of olipiphate involved no scars.

Radiobiological effects of olipifat during radiation exposure.

Preventive injections of olipifat to rats (intramuscularly in a single dose of 250 mg/kg 24 h before gamma-exposure in a dose of 7.6 Gy) decrease animal mortality from 70 to 50%, the mean life span of dead rats remained unchanged. Injection of olipifat before exposure in a dose of 5.2 Gy did not change animal mortality in comparison with irradiated controls, but stimulated postradiation recovery of leukocyte count (mainly the granulocytic component and less so the increase in lymphocyte count). No appreciable effects of olipifat on the postradiation changes in individual fractions of blood leukocytes were observed in animals exposed in a dose of 7.6 Gy.

[Investigation of allergenic properties of olipiphat]. / Issledovanie allergicheskikh svoistv olipifata.

Olipiphat, which is experimentally capable of antitumor action, did not induce any immediate hypersensitivity, but lowered such response to horse serum; nor did it stimulate delayed hypersensitivity to full Freund adjuvant or sharp venous return after concavalin A. No skin or eye mucosa irritation was reported.

[Toxicity and antitumoral activity of two new complex compounds of rhenium]. / Izuchenie toksichnosti i protivoopukholevoi aktivnosti dvukh novykh kompleksnykh soedinenii reniia.

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.

[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.

Inhibition of mouse melanoma cell proliferation by corticotropin-releasing hormone and its analogs.

BACKGROUND: Observations that epidermal cells release both corticotropin-releasing hormone (CRH) and proopiome lanocortin (POMC) peptides has raised questions about the physiological relevance of this hypothalamo-pituitary-like system in mammalian skin. As CRH has shown anti-proliferative effects on cultured keratinocytes, we tested whether CRH can also regulate growth of melanoma cells. MATERIALS AND METHODS: CRH, [D-Glu20]-CRH, [D-Pro5]-CRH, acetyl-cyclo(30-33)[D-Phe12,D-Glu20,Nle21,D-His32,Lys33,D-Nle38]-CRH(4-41), acetyl-cyclo(30-33)[D-Phe12,Nle18,D-Glu20,Nle21,D-Ala32]-urotensin I(4-41), urocortin, and sauvagine were tested on Cloudman melanoma cell proliferation in culture and B16 melanoma tumor growth in C57B1/6 mice. Calcium-sensitive fluorescence measurements were used to examine the effect of CRH on intracellular Ca2+ signaling. The effects of CRH and [D-Glu20]-CRH on blood pressure were compared by measuring mean arterial pressure in anesthetized rats. RESULTS: CRH and six analogs were tested, and all demonstrated exceptional potency in inhibiting Cloudman cell proliferation in culture, with half-maximal effective concentrations ranging between 0.2 and 100 pM. The amplitude of ionomycin-induced Ca2+ influx into Cloudman cells grown in suspension was reduced by 50% after 48-hr exposure to CRH. Daily injections of CRH or [D-Glu20]-CRH, 100 micrograms/kg.day s.c., for 5 days, reduced net B16 tumor volume in mice by 30-60% compared to control animals. [D-Glu20]-CRH was less hypotensive compared to CRH, despite having similar anti-proliferative potency. CONCLUSION: CRH, and various analogs thereof, inhibit proliferation of Cloudman cells in culture, and inhibit B16 tumor growth rate in vivo, most likely by activation of endogenous CRH1 receptors and subsequent altered intracellular Ca2+ signaling. CRH analogs, such as [D-Glu20]-CRH, with less hypotensive activity may provide new directions of therapy for melanoma.

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.

[Multicenter clinical trial of the antitumor drug Dioxadet (phase II)]. / Rezul'taty kooperirovannogo klinicheskogo izucheniia protivoopukholevogo preparata dioksadèt po II faze.

A stage II of the joint clinical study of Dioxadet, an ethylene imine drug, was carried out to evaluate its therapeutic effect in 229 patients and side-effects in 239 patients with malignancies of various sites. Marked therapeutic effect was observed in ascitic malignancies of the ovary and a moderate one--in disseminated breast cancer. The most frequent side-effect was reversible myelodepression, often delayed.

[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.

[Results of endovascular interventions (embolization and chemoembolization) in the treatment of operable and extensive kidney cancer]. / Resul'taty primeneniia éndovaskuliarnykh vmeshatel'stv (émbolizatsii i khimioèmbolizatsii) v lechenii operabel'nogo i rasprostranennogo raka pochki.

The results of an all-round examination and complex treatment of 323 patients with renal cell carcinoma were evaluated. Locally advanced tumors were diagnosed in 143 (44.3%) and extended ones--in 180 (66.7%). In patients with locally advanced tumor who had undergone nephrectomy after embolization or chemoembolization, 12-, 24- and 36-month survival rates showed no significant difference. In patients with extended renal carcinoma, 2- and 3-year survival was significantly higher after chemoembolization than after standard embolization of the renal artery.

[The use of dioxadet in chemoembolization of the hepatic artery in primary and metastatic cancer of the liver]. / Ispol'zovanie dioksadéta dlia khimioémbolizatsii pechenochnoi arterii pri pervichnom i metastaticheskom rake pecheni.

An evaluation of the treatment of 42 patients with extended primary hepatic tumors and multiple intrahepatic metastases of colorectal carcinoma established the effectiveness of a newly-developed fat-soluble cytostatic drug--dioxadet, used for chemoembolization particularly, when foci fed from small arterial vessels were located along the periphery.