ANTITUMOR EFFECT OF HYDROGEL CISPLATIN ON ZEJDEL ASCITES HEPATOMA

Aims and objectives. During regional intraperitoneal chemotherapy cytostatics in prolonged dosage form, in particular, on the basis of various biodegradable hydrogels, such as dextran phosphate are applied. Aim of the study - a comparative evaluation of the antitumor activity ofcisplatin and cisplatin in prolonged dextran phosphate hydrogel form on Zajdel ascites hepatoma. Materials and methods. On 49 white no inbreed rats (n = 7) with implanted intraperitoneal Zajdel ascites hepatoma the antitumor activity of cisplatin in prolonged dextran phosphate hydrogel form with single intraperitoneal injection of the dosage from 3 to 8 mg/kg (≈ maximum tolerated dose, MTD) was evaluated in comparison with officinal cisplatin. The treatment efficacy was assessed by a statistically significant standard criteria: the absence of ascites by 32nd day of the experiment (complete remission) and an increase in life span of rats with ascites (T/C >_125 %, «treatment/control») in comparison with the rats without treatment (tumor growth control, where T/C = 100 %) or treated with officinal cisplatin. Macroscopic, pathomorphological and statistical analysis of the results were used. Results. It has been shown that hydrogel form of cisplatin compared to cisplatin was significantly more effective: complete remission 4/7-6/7 vs 0/7, T/C = 140-188 % vs 91-101 %, the volume of ascites 13,6 ± 6,6 ml vs 50,0 ± 7,9 ml (p = 0,004) because of a better tolerance. Regression analysis confirms that hydrogel form of cisplatin in used dose range significantly improves the rats survival with Zajdel ascites hepatoma, reducing the risk of death from tumor in 7-35 times and the relative risk with the dose of 5,5 mg/kg in 36 times (95 % CI3,86 + 327,60) (p = 0,002-0,005). Conclusions. The data obtained allow considering the hydrogel form of cisplatin as a promising prolonged this drug form of cisplatin by the intraperitoneal therapy and recommending it to preclinical study.

Effect of the autonomic nervous system on cancer progression depends on the type of tumor: solid are more affected then ascitic tumors

Objectives. A number of recently published studies have shown that the sympathetic nervous system may influence cancer progression. There are, however, some ambiguities about the role of the parasympathetic nerves in the modulation of growth of different tumor types. Moreover, tumor models used for investigation of the autonomic neurotransmission role in the processes related to the cancer growth and progression are mainly of the solid nature. The knowledge about the nervous system involvement in the modulation of the development and progression of malignant ascites is only fragmental. Therefore, the aim of the present article was to summarize the results of our experimental studies focused on the elucidation of the role of the autonomic nervous system in the modulation of tumor growth in animals. We are summarizing data from studies, in which not only different experimental approaches in order to influence the autonomic neurotransmission, but also different tumor models have been used.Methods. Three different types of tumor models, namely solid rat intra-abdominal fibrosarcoma, solid murine subcutaneous melanoma, and rat ascites hepatoma, and three types of interventions have been used in order to modulate the autonomic neurotransmission, specifically chemical sympathectomy, subdiaphragmatic vagotomy, or the electric stimulation of the vagus nerve.Results. We have proved a strong stimulatory effect of the sympathetic nerves on the development and growth in both solid tumors, rat fibrosarcoma as well as murine melanoma, and significant inhibitory impact on the survival time of tumor-bearing animals. The progression of ascites hepatoma in rats was not influenced by chemical sympathectomy. Modulation of parasympathetic signalization by vagotomy or vagal nerve stimulation does not affect fibrosarcoma and ascites hepatoma growth and survival of the tumor-bearing rats.Conclusions. Based on the obtained data, it seems that the solid types of tumors are suitable substrate for the direct action of neurotransmitters released especially from the sympathetic nerves. In contrast, it appears that the malignant ascites are not under the direct autonomic nerves control; however, an indirect action via the immune functions modulation cannot be excluded.