Background. The arsenal of antitumor drug therapy for melanoma brain metastases is limited. The search and study of new agents capable to penetrate the blood-brain barrier and provide a therapeutic effect against intracranial tumors remains an unmet clinical need. The aim is to evaluate the antitumor activity of the domestic derivative of nitrosoalkylureas, chlonisol, in mice with intracranially transplanted syngeneic B16 melanoma. Methods. The experiment was carried out in 18 female inbred C57BL/6 mice. After intracranial tumor transplantation, performed according to modified technique, the animals were randomized into two groups: I. Control (n = 10) – the animals were injected with normal saline 10 ml/kg intraperitoneally; II. Chlonisol (n = 8) – the animals were treated with the test compound at a dose of 15 mg/kg in normal saline intraperitoneally. The single administration of normal saline and chlonisol was performed 24 hours after tumor transplantation. The end point of the study was overall survival (OS) of the animals. Results. Compared with the control group, administration of chlonisol significantly increased the median OS of mice from 13 to 18 days (log rank test, p = 0.0005). Chlonisol significantly decreased the risk of death by 71 % compared with the control group (HR = 0.29; 95 %CI 0.10–0.82). By the 15th day after intracranial transplantation of B16 melanoma, all 10 mice in the control group died from intracerebral tumors (100 %), whereas in the chlonisol group only 2 out of 8 (25 %) mice died (Fisher's exact test, p = 0.0015). Conclusion. Despite the exploratory nature of the present study, it provides a good starting point for further research of chlonisol in brain tumors.

В статье освещены особенности диагностики, клиническая картина и различные подходы к лечению меланом вульвы, влагалища и шейки матки.

To construct a perfusion circuit for experimental open hyperthermic intraperitoneal perfusion (HIPEP) and to evaluate the antitumor effects of regional hyperthermia in a model of advanced syngeneic high-grade ovarian carcinoma in vivo. Method: 24 mature female Wistar rats underwent intraperitoneal transplantation of ascitic ovarian tumor 1×10 7 cells per rat. 48 hours after transplantation the animals were randomized into two groups: I. NIPEP group (12 rats)normothermic intraperitoneal perfusion (NIPEP) with normal saline at room temperature during 45 minutes; II. HIPEP group (12 rats)open hyperthermic intraperitoneal perfusion (HIPEP) with normal saline (40.5-41.5 ℃) during 45 minutes. Endpoints included overall survival (OS), the total peritoneal cancer index (PCI), ascites weight and the grade of ascites hemorrhage. Results: In both groups all animals survived the procedure, in the HIPEP group one rat died due to infectious complications on day 32. Compared with NIPEP group HIPEP with normal saline significantly increased the median OS from 19 to 39 days (log-rank test, P=0.0013), reducing the risk of death by 68% (HR=0.32; 95% CI 0.13-0.82). The open HIPEP without a cytostatic was associated with significantly lower total PCI (14 vs 5 points, P=0.0155). In the HIPEP group 3 of 12 animals had intrathoracic tumor spread with malignant pleural effusion without signs of peritoneal carcinomatosis and ascites. Conclusion:The transplanted syngeneic tumor is a valid model that allows to quantitatively assess antitumor activity of intraperitoneal perfusion therapy. Our preclinical data confirmed the role of regional hyperthermia in the treatment of peritoneal carcinomatosis in ovarian tumors.

The purpose of the study was to summarize the available data on etiology, diagnosis, clinical symptoms and signs as well as on various approaches to the treatment of neuroendocrine cervical tumors.Material and Methods. The relevant sources were searched in the PubMed and cochrane Library systems, and publications from 1980 to 2019 were analyzed, 53 of which were used to write this review. We also included 6 case reports from N.N. Petrov National Research Center of Oncology.Results. Neuroendocrine tumors (NETs) are extremely rare and aggressive malignancies of the female genital tract, among which NETs of the cervix are the most common. Due to the rarity of these tumors, there are currently no treatment standards based on prospective, well-planned clinical trials. For these reasons, NETs present a significant therapeutic challenge for clinicians. Case reports. Six patients ranged in age from 32 to 71 years, with a median age of 46 years, were diagnosed with large-cell neuroendocrine carcinoma (4 patients) and small-cell neuroendocrine carcinoma (2 patients). One patient with stage IIIA dropped out of the follow-up schedule. Out of 5 followed up patients, 2 patients with stage IIIA and IIB died of disease progression after 6 and 11 months, respectively. One patient with stage IB1 is in remission for 16 months. Two patients with stage IIB continue to receive primary treatment.Conclusion. Neuroendocrine carcinoma of the cervix is a rare variant of cervical cancer. The choice of treatment options is decided only by a multidisciplinary team of doctors, and further research is required.

Aim. To reveal the characteristic features of tumor growth after orthotopic (OT) and intraperitoneal transplantation (IT) of high-grade syngeneic ovarian carcinoma. Material and methods. Twenty mature female Wistar rats were randomized into two groups of ten each. The first group – animals underwent OT of ovarian carcinoma (4,3×106 cells) under the membrane of the bursa of the left and right ovaries; the second group – animals underwent IT of the tumor (4,3×107 cells). The endpoints of the study included an assessment of the overall survival (OS) of rats in two groups, determination of the peritoneal cancer index (PCI) on autopsy, and ascites weight. Autopsy material was histologically assessed analysis by light microscopy after standard staining. Cytological examination of ascitic fluid was carried out. Results. Median OS was 29 days and 21 days in the OT and IT groups, respectively (log-rank test, P = 0.0276). Autopsy did not reveal significant differences in total PCI (12.6 vs 13.6 in the OT and IT groups, respectively) and ascites weight (78.0 g in the OT vs 65.8 g in the IT group). The method of transplantation did not affect the tumor grafting, histological characteristics, the nature of intraperitoneal spread and the ascites volume. It should be noted that there was a greater volume of tumor lesions in the organs of the reproductive system of rats (ovaries, uterus with horns, paragonadal fat pad) in the OT group. Conclusion. Both methods of transplantation allow to reproduce the advanced stages (III-IV stages) of epithelial ovarian carcinoma in women. OT requires more time and operating conditions. OT and IT can be used to solve various problems in fundamental and routine preclinical cancer research.