Цель исследования. Оценить содержание сурвивина в моче как диагностического маркера рака мочевого пузыря (РМП); изучить прогностическое значение полиморфизма -31G>C (rs9904341) в промоторной области гена BIRC5 в отношении агрессивности течения РМП среди населения Красноярского края. Материалы и методы. Иммуноанализом определен сурвивин в 43 образцах мочи пациентов: с РМП — 27, другим вариантом злокачественного новообразования — 4, воспалительными заболеваниями мочеполовой системы и доброкачественной гиперплазией — 8, здоровых — 4. Разработанным авторами способом на основе биолюминесцентного анализа генотипированы образцы ДНК 285 пациентов с РМП и 183 здоровых доноров. Количественные данные сравнивали U-тестом Манна-Уитни, критерием χ2 Пирсона — частоты генотипов среди случаев РМП и контролей. Ассоциацию между полиморфизмом и РМП оценивали по отношению шансов с 95 % доверительным интервалом, p < 0,05 считали значимым. Результаты. Установлено, что определение сурвивина в моче позволяет разделять пациентов с РМП и здоровых с чувствительностью 66,7 % и специфичностью 100 %. Повышенное содержание сурвивина обнаружено в образцах пациентов с воспалительными заболеваниями и доброкачественными гиперплазиями мочевыводящих путей. Показано, что полиморфизм -31G>C (rs9904341) для пациентов Красноярского края при оценке риска возникновения РМП и развития рецидива заболевания не является значимым. Носительство аллеля GG является возможным предиктором агрессивного течения заболевания с быстрым прорастанием в мышечную стенку мочевого пузыря (48,7 % vs 35,7 %, p = 0,02). Заключение. Сурвивин является хорошим преддиагностическим маркером для выявления пациентов с заболеваниями мочевых путей: его повышенный уровень в моче может указывать на развитие злокачественных (в т. ч. РМП) и доброкачественных гиперплазий, а также воспалительных заболеваний уротелия. Разработка отечественной «аларм» тест-системы по определению сурвивина в моче для быстрой и неинвазивной диагностики перспективна. Полиморфизм -31G>C (rs9904341) можно рассматривать как предиктор агрессивного течения РМП.
Renal cell carcinoma (RCC) is one of the most common tumor types in urologic oncology practice. Despite the improvement of diagnostics methods, about 1/3 of patients with renal cell carcinoma have distant metastases at presentation resulting in an extremely high death rate. For many years, treatment of advanced forms of RCC was utterly ineffective. Standard chemotherapy regimens with fluoropyrimidines and antitumor antibiotics, cytokine therapy with interleukin-2, and interferon- only slightly prolonged the life of patients while causing severe toxic side effects and anemia. Attempts to treat the tumor with radiation therapy have also failed and have been used only for symptomatic treatment of distant metastases. The introduction of tyrosine kinase inhibitors (TKIs) in the treatment of metastatic RCC (mRCC) has enabled much more significant results. Thus, a landmark event was the approval of TKIs sunitinib and then sorafenib, pazopanib, axitinib, lenvatinib, cabozantinib, and mammalian target of rapamycin (mTOR) inhibitors: everolimus and temsirolimus. Subsequent combined therapy using bevacizumab with low-dose interferon- and lenvatinib with everolimus improved recurrence-free survival and objective response rates but contributed to increased toxicity of therapy. The next step in RCC therapy was the approval of the combination of the immuno-oncology agents ipilimumab and nivolumab for the treatment of mRCC by the U.S. Food and Drug Administration in April 2018. Later, combinations of immune checkpoint inhibitors with targeted agents were approved, which increased the life expectancy of patients and reduced the toxicity of antitumor therapy. One of the most effective regimens is the combination of a TKI axitinib or lenvatinib with the PD-1 inhibitor pembrolizumab. This article addresses the current progress in the treatment of patients with mRCC, reviewing the results of completed clinical trials on the use of combination therapy with targeted and immuno-oncology agents.
Purpose: To study the relationship between the -31G/C (rs9904341) polymorphism in the promoter region of the survivin protein gene and the predisposition to bladder cancer (BC) in patients of the Krasnoyarsk region. Material and methods. The allelic composition of the studied gene was determined in a group of 158 BC patients, consisting of 30 women and 128 men (mean age 65.6 ± 10.7, median: 66.5; C25–C75: 59–72). The control group included 117 healthy donors and consisted of 27 women and 90 men with an average age of 60.2 ± 5.1 (median: 60; C25–C75: 57–63.25). The allelic composition was determined using the bioluminescent method. A sample with the GC genotype confirmed by sanger sequencing (center for collective use “genomika”, Novosibirsk, Russia) was used as a control. The Mann–Whitney U test was used to compare quantitative data. the studied sample was in Hardy–Weinberg equilibrium (p>0.5). The pearson χ2 test was used to compare the frequencies of gene variants among BC cases and control samples. The association between variants rs9904341 and BC was assessed in terms of odds ratio (OR) with a 95 % confidence interval (CI); p values<0.05 were considered significant. Results. The allelic composition was determined for the genes of patients and control group participants: GG – 62 (39.2%) vs 43 (36.8%); GC – 82 (51.9%) vs 54 (46.2%); CC – 14 (8.9%) vs 20 (17.15%). The relationship between the presence of the C allele and BC was assessed using the recessive inheritance model, combining all carriers – heterozygotes and homozygotes. The frequency of occurrence of genotypes for patients and the control group was established: GG + GC – 144 (91.1%) vs 97 (82.9%); CC – 14 (8.9%) vs 20 (17.1%). Thus, carriers of the CС genotype were significantly less in patients: OR (95% CI) 0.47 (0.23–0.98), p=0.04. The relationship with tumor invasion was not significant (p=0.08). Conclusion. Based on the results of detecting the rs9904341 (G/C) polymorphism among BC patients of the Krasnoyarsk region, a protective effect of the carriage of the CC genotype was found. In order to study the allelic composition with the threat of recurrence of the disease, additional research is needed.
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