Simultaneous stimulation of growth of malignant tumors with epithelioid and sarcomatous nature in experiment.

e23517 Background: The relevance of studying multiple primary malignant tumors (MPMTs) is determined by poor understanding of their pathogenesis. Our purpose was to create an experimental model of synchronous MPMTs with the stimulation of malignant growth of tumors with different histostructure. Methods: The study included 20 male BALB/c Nude mice. The main group included mice with simultaneous subcutaneous inoculation of tumors: murine B16/F10 melanoma (0.5 ml of suspension diluted 1:20 in saline solution) below the left scapula and rat sarcoma 45 (0.5 million tumor cells in 0.5 ml of saline solution) below the right scapula. Control groups included males with melanoma or sarcoma inoculated at the same dosage and volume as in the main group. Results: In the model of synchronous MPMTs, tumors appeared faster than in controls: melanoma–by 3 times, sarcoma–by 2 times; their volume was larger: melanoma–by 2.2 times, sarcoma–by 3.2 times. Melanoma metastasized, in addition to typical sites (the lungs, spleen, liver), into sarcoma 45 to the side adjacent to the chest, under the tumor node. The survival of mice with MPMTs was lower. The morphological structure of melanoma metastasis into sarcoma 45 was represented by large lamellar-rounded epithelium-like cells of melanosarcoma type with transparent cytoplasm and nuclei with a high frequency of pathological mitosis figures. Bundles of elongated spindle-shaped melanocytes with processes of the cytoplasm were determined in some melanoma areas, as well as alveolar and concentric structures. Conclusions: Synchronous subcutaneous inoculation of murine B16/F10 melanoma and rat sarcoma 45 to male BALB/c Nude mice increases their malignant potential due to an exchange of “structural information"; as a result, sarcoma acquires impulses of proliferative activity of melanoma, which, in turn, adapts and “mimics” a tumor into which it is going to metastasize.

Levels of the IGF system components in malignant lesions of the lungs with preventive effect of 1,3-diethylbenzimidazolium triiodide in the experiment.

e15095 Background: The system of insulin-like growth factors (IGF) is involved in carcinogenesis, since it promotes proliferation and survival of tumor cells. The purpose of the study was an analysis of the dynamics of the IGF system components in the lungs of rats with antitumor effect of 1,3-diethylbenzimidazolium triiodide. Methods: The main group included male (n=27) and female (n=27) white outbred rats with sarcoma 45 inoculated into the subclavian vein (2×106 cells in 0.5 mL saline) but not developed in the lungs due to administration of 1,3-diethylbenzimidazolium triiodide (intragastrically, 0.4 mg/kg once a day according to the regimen: administration for 5 days with a 2-day interval). Control group included males (n=14) and females (n=14) with sarcoma 45 growing in the lungs without treatment. Intact groups included 5 males and 5 females. After 4, 5 and 8 weeks of the experiment animals were decapitated, and levels of IGFI, IGFII, IGFBP1, IGFBP2 and IGFBP3 were measured by ELISA in 10% lung homogenates (CUSABIO BIOTECH Co., Ltd., China). Results: The sarcoma development in the lung was accompanied by the IGFI increase by 2.4-3.0 times in males and by 4.3 times in females, and the opposite IGFII dynamics: an increase in males (by 4.6 times) and decrease in females (by 4.3 times), together with the IGFBP decline. 1,3-diethylbenzimidazolium triiodide upregulated IGFI levels in the lungs of all rats on average by 1.3 times (p<0.05) and normalized IGFII in males, while increasing it in females by 1.6 times (p<0.05), together with higher (compared to controls) IGFBP levels. Conclusions: Preventive antitumor effect of 1.3-diethylbenzimidazolium triiodide is based on the stabilization of the IGF system grossly altered during the malignant process development in the lung.

Study of the antitumor activity of the drug Dekoglitz on two tumors and some aspects of its mechanism of action

Aim: Evaluation of the antitumor activity of the new drug Dekoglitz in animals with tumor strains of Sarcoma 45 in comparison with the drug dekocin, from which it was obtained, as well as with 5-fluorouracil and etoposide, and on ovarian tumors (OT) in comparison with the drug dekocin and identification of the effect of Dekoglitz on NA synthesis and internucleosomal DNA degradation. Methods: The study of preparations was carried out on 68 outbred rats with transplanted C-45 and OT tumors. The alkylating effect of the drugs was studied on cells tumor of Sarcoma 180. Results: The antitumor activity of dekoglitz on Sarcoma 45 was high, about 98/96%, with a remission rate of 80%. Its effect was 28-24% higher than that of dekocin. On OT, the effect of decoglitz with intraperitoneal administration reached 89/76% with a remission rate of 40%, with oral administration 96/86% with a remission rate of 60%. Conclusion: The study of the new drug Dekoglitz on animals with a tumor of Sarcoma 45 revealed its higher activity (by 20-27%) in comparison with the original Dekocin, 5-fluorouracil and etoposide with a lower level of side effects. On OT, the effect of Dekoglitz was 35-40% higher, especially after oral administration. Apparently, the great ability to suppress the synthesis of NA and carry out internucleosomal degradation and fragmentation of tumor DNA by the new drugs dekoglitz explains its antitumor efficacy, which is greater than that of Dekocin (K-18) in experiments on tumors.

Levels of growth factors in the lungs affected by cancer with preventive effect of 1,3-diethylbenzimidazolium triiodide in the experiment

Purpose of the study. Analyzing the dynamics of VEGF-А, TGF-β and their receptors in the lung tissues in rats with antitumor effect of 1,3-diethylbenzimidazolium triiodide (Stellanin).Material and methods. The study included white outbred rats weighing 180–220 g. The main group included males (n=27) and females (n=27) with sarcoma 45 (s45) inoculated into the subclavian vein but not developed in the lungs (2×106 cells in 0.5 ml of saline) due to the subsequent intragastric administration of Stellanin (0.4 mg/kg once a day) according to an intermittent scheme: administration for 5 days and a break for 2 days. The control group included males (n=14) and females (n=14) without treatment with growing s45 in the lungs. Intact groups included 5 males and 5 females. After 4, 5 and 8 weeks of the experiment animals were decapitated, and levels of VEGF-A, sVEGF-R1, sVEGF-R2, TGF-β and sTGFβR2 were measured in 10% lung homogenates by ELISA (CUSABIO BIOTECH Co., Ltd., China).Results. Lung tissues of intact females showed 1.4 times (p<0.05) lower VEGF-А and 3.3 times higher sVEGF-R1, compared to males. The development of tumors in all control rats was accompanied by the VEGF-А increase (by 1.6–3.0 times) and the TGF-β reduction (by 3 times). The dynamics of both VEGF receptors differed in males and females. The levels of sVEGF-R1 in males increased by 1.5 times (p<0.05), while in females it decreased by 1.8 times (p<0.05), and as a result, the levels became similar in all animals. The levels of sVEGF-R2 in males decreased by 2 times, and in females it increased by 1.4 times (p<0.05), so the sVEGF-R2 content in females became 2.4 times higher than in males. In two-thirds of rats, Stellanin prevented s45 development in the lungs due to inhibition of VEGF-A growth by more than 2.0 times and an increase in concentrations of sVEGF-R1 by 10.0 times and TGF-β by 6.0 times, together with normalization of sVEGF-R2 and sTGFβR2.Conclusions. Stellanin prevents the development of malignant process in the lungs by inhibiting neoangiogenesis (deficiency of VEGF-A and excess of sVEGF-R1) and suppressing the proliferation of malignant cells (TGF-β growth).

Study of Antioxidant and Membrane Resistant Peculiarities of a New Cyan Containing Lactone in Membranes of Hepatocytes with Sarcoma-45

The antioxidant and membrane resistant peculiarities of a new derivative (2-cyan-3,4,4-trymethil-2-buten-4-olyd - CTBO) of cyan containing unsaturated lactones have been studied in membranes of hepatocytes with Sarcoma-45 1. The results of our previous research 1, 2, 3 showed significant changes of phospholipid (PL) exchange in hepatocytes of microsomal membranes at experimental animals vaccinated with Sarcoma-45 tumor strain. It is manifested in significant changes of quantitative and qualitative contents of membrane phospholipids separate fractions, increase of cytotoxic lysophospholipids (LPCs), phosphatidylinositol (PI) and phosphatidic acid (PA) levels, significant decrease of phosphatitylcholines (PC) and sphingomyeline (SP) contents, statistically significant changes of PL/PL ratio, peroxidation ratio intensity, dramatic increase of phospholipase A2 (PLA2)activity, quantitative and qualitative changes of adenyl nucleotides, as well as disorders of adenosine triphosphatase (ATPase) system activity 3, 4, 5, 6, 7.

Stabilities of Irradiated DNA Complexes from Sarcoma 45 Tumors with Mitoxantrone at Small Fillings

In the present work, the thermostabilities of mitoxantrone (MTX) complexes with DNA from sarcoma 45 and healthy rat liver were studied. DNAs from both sources were irradiated by resonant (64.5 GHz and 50.3 GHz) and nonresonant (48.3 GHz) frequencies of water. The obtained data showed that DNA solution irradiation by resonant frequencies of water induces a dehydration of nucleotides and Na[Formula: see text] ions in the solution. It is shown that at relatively low concentrations of MTX, when one MTX molecule binds to almost 100 pairs of bases of DNA, the thermostabilities of complexes decrease. Moreover, this change is more pronounced ([Formula: see text]C) at the complex formation with DNA released from sarcoma 45 tumor.