Various approaches to increase efficiency of antitumor therapy by a combination of vaccinotherapy, chemotherapy and surgical excision of primary tumor nodes, and also the comparative analyses of therapeutic and preventive application of antitumoral vaccines were carried out in melanoma experimental model. It was postulated that preventive vaccination is able to prevent tumor incidence by 70 %. The combination of vaccinotherapy and surgical treatment of melanoma increases antimetastatic activity of vaccination by 43 %. We conclude the combined therapy would lead to more effective antitumor response.
Improvement of anti-tumor biotherapy effectiveness by modification of immune response with histamine H2 receptor Cimetidinum (CM) was studied using the experimental murine model of B16 F10 melanoma in vivo. It is shown that skin melanoma biotherapy by antitumor whole-cell GM-CSF-producing vaccine with the addition of CM (in dose of 25 mg/kg, daily for 5 days) increases preventive effects of vaccination. 33 % of mice did not have tumor growth within 60 days of observation. Average life span of animals exceeded those of the control group up to 68 %. Using CM-combined bio-chemotherapy doesn't improve therapeutic effect, however in the case of a monotherapeutic approach tendency for increased average life-time and decreased metastatic processes in mice with the developed tumors was noticed. Aquired data provides expediency to study the further application of CM as adjuvant for skin melanoma vaccinotherapy, and also the necessity to verify the immune status of an organism against the complex bio-chemotherapy.
Various approaches to increase efficiency of antitumour therapy by a combination of vaccinotherapy, chemotherapy and surgical excision of primary tumoral node, and also the comparative analysis of therapeutic and preventive application of antitumoral vaccines is carried out in melanoma experimental model. It was postulated that preventive vaccination is able to prevent tumour process by 70 %. The combination of vaccinotherapy and surgical treatment of a melanoma increases antimetastatic activity of vaccination by 43 %. We conclude the combine therapy would led to more effective antitumor response.
We have studied the influence of triterpenoid of the plant origin miliacin on the antitumor activity of metotrexate in the experiment on the 63 mice males of the hybrids of the 1st generation BDF1 (C57Bl/6×DBA/2) on the model of the transplanted carcinoma. It was obtained that miliacin decreases the toxic effect of metotrexate in mice with the tumor LLC and increases the therapeutic effectiveness of citostatic according to the criteria of inhibition of growth of epidermoid lung carcinoma and the increasing life span of experimental animals in comparison with control ones.
Lysomustine is an original antitumor preparation, chloroethylic derivative of nitrosourea on L-homocitrulline basis. BCNU is 1,3-bis (2-chloroethyl)-1 -nitrosourea, Carmustine (BiCNU) generic substance. PEGliposomes of Lysomustine and BCNU with PEG-5000 (LEF-5000) and PEG-2000 (LEF-2000) in lipid membranes have been obtained. The antitumor efficiency of new pharmaceutical formulations was investigated on experimental tumor model lymphoblastic leucosis L-1210. Lysomustine in LEF-5000 on lymphoblastic leucosis L-1210 had shown optimal therapeutic effect at doses from 125 to 250 mg/kg resulting in 100 % recovery of treated animals, while LEF-2000 showed 100 % antitumor effect only at a dose of 175 mg/kg. BCNU in LEF5000 had shown maximal therapeutic effect at doses 40 and 45 mg/kg (100 % recover of animals) Dose of 50 mg/kg caused 100 % animals death due to toxicity. No 100 % recovery was revealed using BCNU in LEF-2000.
Cycloplatam is a new complex compound of platinum with original structure was synthesized by P.A. Tchelcov et. al. in 1982 in N.C. Kurnakov Institute of general and inorganic chemistry of RAS. The purpose of this investigation was to create a new liposomal form of cycloplatam and to study its anticancer effect. Average size of liposomes with cycloplatam was 142 ± 3 nm. The in vivo study was made on a murine melanoma B-16. Received data demonstrates the advantage of liposomal form of cycloplatam than lyophilized form on inhibition of tumor growth and on duration of the effect.
The purpose of this investigation was to carry out the PEG liposome-encapsulated form of lysomustine (PLEL) as well as to characterize its pharmaceutical properties and antitumor efficiency. At the technological stage of the investigation we have tested liposomal formulations of lysomustine using different PEG lipid compositions. The antitumor efficiency of new pharmaceutical formulation was investigated on two experimental tumor models lymphoblastic leucosis L-1210 and Lewis lung carcinoma (LLC). On lymphoblastic leucosis L-1210 PEG 5000 LEL showed optimal therapeutic effect at doses from 125 to 225 mg/kg, resulting in 100% recovery of treated animals. In addition to PEG 2000 LEL 100% antitumor effect was in dose 175 mg/kg. On Lewis lung carcinoma antitumor effect of PEG 5000 LEL resulting in 71,4 % and 86 % recovery of treated animals, was maximally pronounced at doses 225 and 250 mg/kg. Comparative investigation of lysomustine different drug formulations has shown that theuse of PEGLEL 5000 allowed to widen the range of therapeutic doses from 100 to 250 mg/kg and to increase PEG LEL reparation antitumour efficiency on animals bearing leucosis or solid tumors, achieving up to 100% recovery of treated animals without LEL toxicity noticeable increase.
Lysomustine is an original antitumor preparation based on chloroethylic derivative of nitrosourea on Lhomocitrulline basis. Earlier lysomustine had been shown to be effective against both solid tumors (e.g. Lewis lung carcinoma (LLC), carcinoma Ca-755, melanoma B-16) and leucoses (L-1210, P 388 etc.). However, clinical use of lysomustine was limited due to significant common toxicity. The purpose of this investigation was to carry out the liposome-encapsulated form of lysomustine(LEL) as well as to characterize its pharmaceutical properties and antitumor efficiency. In technological stage of the investigation we have tested liposomal formulations of lysomustine using different lipid compositions. The choice of the optimal lipid composition was based on the criteria of the liposomal dispersion aggregative stability. The antitumor efficiency of new pharmaceutical formulation was investigated on two experimental tumor models lymphoblastic leucosis L-1210 and Lewis lung carcinoma (LLC). On lymphoblastic leucosis L-1210 LEL had shown optimal therapeutic effect at doses of 125 and 150 mg/kg, resulting in 100 % recovery of treated animals. On Lewis lung carcinoma antitumor effect of LEL was maximally pronounced at doses of 175 and 200 mg/kg. Comparative investigation of lysomustine different drug formulations has shown that allowed to widen the range of therapeutic doses from 100 to 200 mg/kg and to increase LEL reparation antitumour efficiency on animals bearing leucosis or solid tumors, achieving up to 100% recovery of treated animals without toxicity LEL noticeable increase.
We studied prophylactic, antitumor and antimetastatic effects of allergen-removed extract of Rhus verniciflua on the C57Bl/6mice transplantable model Lewis lung carcinoma. To investigate prophylactic effect of ACM909Q at oral and intraperitoneal administration it was used on 12th and 6lh days in 90; 225; 300; 600 mg/kg doses before tumor transplantation. Antitumor effect was estimated at some doses and routs administration but during 2nd-7lh days after tumor transplantation. To learn more about antimetastatic effect of ASM909G it was administrated to animals before, after or before and after surgical removal of primary tumor. The primary tumors have been surgically removed on 7th day after neoplastic cells transplantation. Our experiments have demonstrated that ACM909Q possessed moderate prophylactic and antitumor activity. Preliminary administration of ACM909Q decreased the growth of primary Lewys lung carcinoma in different experiments for 30-55%, therapeutic administration by 40-60%. ACM909Q have demonstrated modulate activity against process metastasis of Lewis lung carcinoma. Administration of ACM909Q before the removal of primary node was not effective or has stimulated metastasis of Lewis lung carcinoma, but it administration after surgery decreased process of metastasis for about 45%. The results showed above are preliminary. Now the ACM909Q is on detailed investigation.