Цель исследования -оценить эффективность предоперационной таргетной терапии, спектр и частоту побочных явлений, а также качество жизни на фоне ее проведения у пациентов с костными метастазами почечно-клеточного рака. Материалы и методы. Исследование проведено на базе НИИ онкологии Томского НИМЦ с 2014 по 2018 г. В работу включены 34 пациента с костными метастазами почечно-клеточного рака, которые получали предоперационную таргетную терапию пазопанибом в течение 8 нед. Всем пациентам выполняли хирургическое лечение как первичной опухоли, так и костных метастазов. Результаты и заключение. Показано, что проведение предоперационной таргетной терапии характеризуется высокой частотой достижения клинического ответа при удовлетворительной переносимости. В ряде случаев предоперационная таргетная терапия улучшает условия для выполнения хирургического этапа на костных метастатических очагах, снижает интраоперационную кровопотерю, уменьшает объем и продолжительность оперативного вмешательства, что, в свою очередь, позволяет сохранить бόльший объем движений в пораженном костном сегменте, а также улучшить качество жизни таких пациентов. Ключевые слова: почечно-клеточный рак, костные метастазы, таргетная терапия, пазопаниб, качество жизни Для цитирования: Юрмазов З.А., Лушникова Н.А., Спирина Л.В. и др. Возможности предоперационной таргетной терапии в лечении костных метастазов рака почки. Онкоурология 2019;15(2):35-41.The study objective is to evaluate the effectiveness of preoperative targeted therapy, spectrum and rate of adverse events, as well as quality of life in patients with bone metastases of renal cell carcinoma. Materials and methods. The study was conducted at the Research Institute of Oncology, Tomsk Medical Research Center between 2014 and 2018. The study included 34 patients with bone metastases of renal cell carcinoma who received preoperative targeted therapy with pazopanib for 8 weeks. All patients underwent surgical treatment of both the primary tumor and bone metastases.Results and conclusion. It was shown that preoperative targeted therapy is characterized by a high rate of clinical response and satisfactory tolerability. In some cases, preoperative targeted therapy improves the conditions for surgical treatment of metastatic bone lesions, decreases intraoperative blood loss, decreases the volume and duration of surgical intervention, which, in turn, allows to preserve bigger range of motion in the affected bone segment and improve patients' quality of life. Key words: renal cell carcinoma, bone metastases, targeted therapy, pazopanib, quality of lifeFor citation: Yurmazov Z.A., Lushnikova N.A., Spirina L.V. et al. Capabilities of preoperative targeted therapy in treatment of bone metastases in renal cancer. Onkourologiya = Cancer Urology 2019;15(2):35-41. ВведениеПочечно-клеточный рак (ПКР) занимает одно из лидирующих мест по темпам прироста среди онкологических заболеваний (40,3 % за последние 10 лет).Ежегодно в мире выявляют около 400 тыс. новых случаев ПКР [1]. В России в 2017 г. были зарегистрированы...

Introduction.The efficacy of anticancer treatment depends on biological factors of tumor.The aimof the study was to determine the activity of proteasomes and calpains and to  reveal their association with VEGF, HIF-1α and NF-κΒ expressions in normal, primary and metastatic renal cell carcinoma (RCC) tissues.Methods.Ninety-three patients with renal cell carcinoma were included into the study. The expression levels of transcription factor and VEGF were measured using ELISA kits. The  levels of proteasome subunits were measured by Western Blotting. Proteasome and calpain  activities were determined using specific fluorogenic  substrates.Results.We revealed inactivation of proteolysis in patients with kidney cancer. Disease advance was associated with a significant depression of cellular proteolysis and increase in  transcription and growth factor levels in primary kidney cancer tissues. The proteolysis  activation was found in metastatic tissues.Conclusions.Our results suggest that NF-κΒ, HIF-1α and VEGF transcription factors and intracellular proteolytic systems are involved in kidney cancer progression.

Introduction. The molecular picture of the development of HIF overexpression against VHL deficiency background is a key event associated with the manifestation and progression of clear cell renal cell carcinoma. However, this indicator's significance for the development of the disease and the formation of a response to targeted therapy is not clear. The study aimed to study the relationship between the expression and content of VHL in kidney cancer tissue with clinical, morphological parameters, mRNA level NF-κB p65, NF-κB p50, HIF-1, HIF-2, VEGF, and CAIX. Material and methods. The study included 39 patients with renal cell carcinoma. The disease's localized form (T1-2N0M0) was diagnosed in 20 patients; 19 patients had a disseminated process (T1-3N0-1M1). The study's material was normal, and tumor tissue was obtained during the surgical stage of treatment. VHL expression was determined by real-time PCR. The pVHL protein content was estimated using the Western Blotting method. Results. As a result of the study, it was noted that an increase in the VHL expression, together with a decrease in its protein level, was associated with an increase in tumor size. The prevalence of the disease was accompanied by an increase in both mRNA and VHL content in cancers. There was a negative correlation between the level of VHL expression, the content of the corresponding protein, and a positive association with the expression of NF-κB p65. VHL content in cancers was associated with decreased expression of NF-κB p50, NF-κB p65, and VEGF. Discussion. An increase in VHL expression in tumor tissue promoted the growth of mRNA of transcription factors, in particular NF-κB, which is accompanied by tumor spread. An increase in the VHL protein content led to the suppression of the mRNA level of transcriptional and growth factors, which is probably associated with their inactivation, including through proteasome cleavage, and is an important stage in oncogenesis. Conclusion. The relationship between the expression and content of the VHL protein is of decisive importance in the development of the disease, the formation of distant metastases.