Aim: Alterations in circadian rhythms caused by tumor growth are thought to be clinically relevant as they affect the prognosis and treatment response. We aimed to evaluate the chronotherapeutic approach in rats with ovarian cancer receiving cisplatin intravenously (IV) or with hyperthermic intraperitoneal chemoperfusion (HIPEC) and to assess daily variations in tumor and intestinal epithelium proliferation. Methods: In the pilot study, we used 12 intact rats and 12 rats with transplantable ovarian cancer, which were euthanized at ZT0 (08:00, lights on), ZT6, ZT12 and ZT18. In the main study, we used 45 rats with transplantable ovarian cancer. Animals were randomized into five groups: control, HIPEC with cisplatin at ZT0 (08:00), HIPEC with cisplatin at ZT12 (20:00), IV cisplatin at ZT0 and IV cisplatin at ZT12. We assessed the proliferation rate of tumor and small intestinal epithelium, apoptosis in small intestinal epithelium, and levels of γ-H2AX (DNA damage/repair marker) in kidneys and liver. Survival was calculated in each group. Results: Ascitic ovarian cancer disrupted daily variations in intestinal epithelium proliferation and DNA damage/repair in rats. Ovarian carcinoma exhibited no daily variation in mitotic activity. In animals receiving IV cisplatin, massive cell damage in the renal medulla and cystic changes within renal tubules were observed, unlike in rats receiving HIPEC. Tumor mitotic activity was lower in morning-treated groups. The median survival of rats in the control group was 8.5 days (95% CI 6.0-22.0), in HIPEC at ZT0 40.5 days (95% CI 28.0-47.0, p<0.001) and in HIPEC at ZT12 32.0 days (95% CI 28.0-37.0, p<0.001). Conclusion:In a rat model, ovarian tumor growth disrupted daily variations in intestinal epithelium proliferation and caused genotoxic stress in tumor-free tissues. HIPEC with cisplatin at ZT0 had a better efficacy/toxicity profile than HIPEC with cisplatin at ZT12 and IV administration at both time points.
Purpose of the study: to review in vivo studies on the relationship and role of various molecular genetic components of the circadian rhythm system in the initiation and development of malignant neoplasms. in contrast to clinical and epidemiological studies, animal models, including transgenic animal models, can model various changes and disturbances in the activity of clock genes and track the results of these changes.Material and Methods. the review includes data from studies carried out over the past 10 years in animal models, studying the mechanisms and effects of disturbances in the system of circadian rhythms related to the formation and development of tumors. the data sources for the review were the Medline, embase and scopus databases.Results. analysis of the literature has shown that interference with the work of the «biological clock» by changing the light cycle, disrupting the expression of clock genes and other manipulations is a factor predisposing to the development of tumors. in tumors of various types, the expression of clock genes is often mismatched, and it is unclear at what stage of their formation this occurs. in addition, the development of tumors disrupts the circadian homeostasis of the body. there are three key areas of research aimed at studying the role of circadian rhythms in tumor development: disturbance of circadian rhythms as a carcinogenic factor, disturbances in the clock gene system in a tumor, disturbances in the clock gene system of the whole organism, provoked by tumor development.Conclusion. the results of studies on animal models demonstrate that the relationship between the disturbance of circadian rhythms and the tumor process is complex since the causal relationship has not yet been studied. in this regard, the prospect of targeted pharmacological correction of circadian rhythms in clinical practice in cancer patients does not seem to be the nearest one.
This article discusses the main approaches to performing laparoscopic partial nephrectomy. For the method using warm ischemia, the main studies related to the time of warm ischemia and its effect on renal function have been analyzed. The basic techniques for operations united by the general name zero ischemia kidney resection are also considered. The main positive and negative aspects of induced hypotension are described. The article presents the authors’ own experience in performing normotonic laparoscopic partial nephrectomy.
The purpose of rehabilitation for prostate cancer patients is to recover psychological, physical, cognitive, social, and vocational functions. Prostate cancer treatment options have the risk of several side effects including loss of muscle strength, fatigue, pain, urinary incontinence, erectile dysfunction, cognitive problems, decrease in bone density, weight loss, gynecomastia, and hot flushes with stress-related psychosocial problems. This paper describes briefly cancer rehabilitation of patients with prostate cancer for minimizing the morbidity rate associated with prostate cancer treatment and to improve QOL.
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