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.
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.
Контакты: Эльдар Мухамедович Мамижев mamijev@mail.ru В представленном обзоре литературы рассмотрены исследования, основной целью которых было распределить опухоли мочевого пузыря по молекулярным подтипам. Схожая классификация давно активно используется при лечении рака молочной железы. К основополагающим работам в области молекулярных подтипов рака мочевого пузыря относятся исследования группы Lund, проект TCGA (The Cancer Genome Atlas), исследования MD Anderson. Также мы включили данные о попытках применения молекулярной таксономии рака мочевого пузыря в лечении. Ключевые слова: рак мочевого пузыря, молекулярный подтип, лечение рака мочевого пузыря, иммуногистохимия Для цитирования: Осетник В.К., Мамижев Э.М., Джалилов И.Б. и др. Молекулярные подтипы рака мочевого пузыря и первые успехи в персонализированном лечении. Онкоурология 2020;16(1):106-13.In the literature review we described studies, the main purpose of which was to distribute bladder tumors by molecular subtypes. A similar classification has long been actively used in the treatment of breast cancer. The pioneering work in the molecular subtypes of bladder cancer includes the work by Lund group, the TCGA (The Cancer Genome Atlas) project, the MD Anderson study. We have also included data on attempts to apply molecular taxonomy of bladder cancer in treatment.
Background: Hyperthermic intraperitoneal chemoperfusion (HIPEC) is thought to have less side effects than intravenous (i.v.) chemotherapy due to lower systemic absorption of drugs. The underlying mechanisms of this difference in toxicity remain unknown. We studied absorption and distribution of cisplatin after HIPEC and i.v. injection in a rat model. Methods: Female Wistar rats (N¼9) received either HIPEC with cisplatin, 20 mg/kg (N¼9), or cisplatin i.v., once, 4 mg/kg (N¼9). These were maximum tolerated doses. Six animals from each group were used for blood sampling at following time points: prior to administration, in 15,20,30,45,60,70 minutes, in 8,12 hours, and in 1,2,5 days after administration, with following euthanasia. Three animals from each group were euthanised in 24 hours after cisplatin administration. Samples of ovaries, liver and kidneys were used to study cisplatin content and level of platinum free of blood plasma proteins.Results: Cisplatin content in blood plasma at different time points as well as secretion kinetics didn't differ significantly between groups. Cisplatin content in kidneys of rats after i.v. administration went up from 5.9AE1.1 to 11.2AE1.4 mg/kg, and for HIPEC it changed from 1.2AE0.3 to 1.9AE0.3 mg/kg (p<0.001). IHC with gamma H2AX (DNA damage marker) also showed larger damage to kidneys after i.v. administration. Fraction of free platinum in blood filtrate samples after HIPEC (taken right after HIPEC, point of peak concentration) was 0.51AE0.02 versus 0.67AE0.02 after i.v. injection (taken in 15 min after injection, point of peak concentration) (p¼0.0014). Conclusion:Lower toxicity of HIPEC is due to lower content of free platinum in blood plasma rather than lower overall concentration of cisplatin in the blood as it was thought previously. Financial support by RSF grant 18-75-100-17.
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.
Patients who practice Islam often refuse the proposed type of treatment for malignant neoplasms, citing religious reasons. Most fear that complete or partial non-retention of urine, the presence of a urostoma (ileal conduit) will violate their ritual purity and, as a result, their religious duties. The consequence of such refusal of treatment may be a lower quality of life, compared with patients of other faiths. Unfortunately, a low awareness of religious responsibilities among surgeons performing pelvic exentesis, cystectomy, prostatectomy, may prevent a full-fledged discussion of these issues before surgery. The presented review of the literature examined studies, legal aspects, and religious arguments that assist doctors in choosing treatment tactics for patients.
Testicular tumors occur in 1–1.5 % of cases in the structure of the general oncological morbidity among men and constitute 5 % among tumors of the urogenital tract. In Western Europe, 3–6 new cases are recorded a year per 100 thousand male population. Nevertheless, in relation to young men, this particular type of neoplasm is not only the most common oncological pathology (up to 60 % of all neoplasms), but also the main cause of cancer mortality. Risk factors for developing ovarian cancer include a family history, previous development of a tumor in the contralateral testicle, and components of testicular dysgenesis syndrome (cryptorchidism, hypospadias, spermatogenesis disorders leading to infertility). Tumors of paratesticular tissues are much less common and most of them are benign. Squamous cell carcinoma rarely develops as a primary tumor of the testis and / or paratesticular tissue, isolated cases have been described in the English literature. Secondary damage to the scrotum organs is more frequent, but such situations are usually found in patients of an older age group. This article presents the clinical case and the final results of treatment of a patient with squamous cell carcinoma of paratesticular tissue.
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