ОПЫТ ПРИМЕНЕНИЯ ОКТРЕОТИДА У ПАЦИЕНТОВ С КАСТРАЦИОННО-РЕФРАКТЕРНЫМ РАКОМ ПРЕДСТАТЕЛЬНОЙ ЖЕЛЕЗЫ

Fifteen patients with castration refractory prostate cancer have been treated with sustained-release octreotide in combination with dexamethasone at the Altai Territory Oncology Dispensary since 2008. Control PSA test revealed that 9 (60 %) patients had positive changes; tumor process stabilization was noted in 4 (26.7 %) and only 2 (13.3 %) were found to have disease progression. Thus, more than 86 % of patients responded to combination treatment with sustained-release octreotide + dexamethasone. Octreotide treatment caused no serious specific adverse toxic reactions.С 2008 г. в Алтайском краевом онкологическом диспансере 15 пациентов с кастрационно-рефрактерным раком предстательной железы получали лечение пролонгированной формой октреотида в комбинации с дексаметазоном. При контроле уровня простатспецифического антигена выявили, что у 9 (60 %) больных отмечена положительная динамика, у 4 (26,7 %) — стабилизация опухолевого процесса и только у 2 (13,3 %) пациентов выявлено прогрессирование заболевания. Таким образом, более 86 % больных положительно ответили на комбинированное лечение по схеме «пролонгированная форма октреотида + дексаметазон». Лечение больных октреотидом не сопровождалось какими-либо серьезными специфическими побочными токсическими реакциями

ПЕРВИЧНО-МНОЖЕСТВЕННЫЙ РАК ПРЕДСТАТЕЛЬНОЙ ЖЕЛЕЗЫ В АЛТАЙСКОМ КРАЕ

The proportion of men with multiple primary malignancies (MPM), by involving the prostate, is 9.3% of all the patients with prostate cancer in the Altai Territory. When prostate cancer is found, the lung, skin, oral cavity, and digestive tract should be examined to reveal secondary tumors. When primary malignancy is detected in these organs, the prostate should be more meticulously examined. In patients with double metachronic nonsystemic MPM with the involvement of the prostate, the disease is more frequently detectable in the 60-69 year age group.The proportion of men with multiple primary malignancies (MPM), by involving the prostate, is 9.3% of all the patients with prostate cancer in the Altai Territory. When prostate cancer is found, the lung, skin, oral cavity, and digestive tract should be examined to reveal secondary tumors. When primary malignancy is detected in these organs, the prostate should be more meticulously examined. In patients with double metachronic nonsystemic MPM with the involvement of the prostate, the disease is more frequently detectable in the 60-69 year age group

КЛИНИЧЕСКОЕ ЗНАЧЕНИЕ МАРКЕРОВ ПРОЛИФЕРАЦИИ И АПОПТОЗА У БОЛЬНЫХ СВЕТЛОКЛЕТОЧНЫМ ПОЧЕЧНО-КЛЕТОЧНЫМ РАКОМ

Renal cell carcinoma (RCC) is a heterogeneous disease in which the patients survive for months to years. At the present time the prognostic models have no sufficient information or exact prognostic value. Cell proliferation and apoptosis play a key role in cell cycle regulation; and impairment in these processes is commonly detected in different human tumors. The investigation enrolled 76 patients (49 men, 27 women) aged 32 to 73 years (mean age 56 ± 7.6 years) diagnosed with RCC. The follow-up was 8 to 116 months (mean 36.5 months). All the patients underwent nephrectomy; antibodies against р53, Bcl-2, and Ki-67 were investigated by immunohistochemistry. The expression of p53 and none or reduced expression of Bcl-2 are poor prognostic factors and associated with the metastatic potential of a tumor and with low relapse-free survival. High Ki-67 levels are a risk factor for metastases. A combination of p53 expression and high proliferative activity reflects the aggressive potential of a tumor and suggests the high risk of metastases just at the disease diagnosis and early tumor dissemination. Почечно-клеточный рак (ПКР) – гетерогенное заболевание, при котором пациенты живут от нескольких месяцев до нескольких лет. В настоящее время прогностические модели не обладают достаточной информативностью и точной прогностической ценностью. Клеточная пролиферация и апоптоз играют ключевую роль в регуляции клеточного цикла, и нарушение этих процессов часто выявляется при различных опухолях человека. В исследование были включены 76 пациентов (49 мужчин и 27 женщин) в возрасте от 32 до 73 лет, средний возраст 56 ± 7,6 года с диагнозом ПКР. Срок наблюдения составил от 8 до 116 мес (средний срок – 36,5 мес). Всем больным была выполнена нефрэктомия, проведено иммуногистохимическое исследование с антителами к р53, Bcl-2 и Ki-67. Экспрессия р53 и отсутствие экспрессии или редуцированная экспрессия Bcl-2 являются факторами небла-гоприятного прогноза, связаны с метастатическим потенциалом опухоли и низкой безрецидивной выживаемостью. Высокий уровень Ki-67 – фактор риска развития метастазов. А сочетание экспрессии р53 и высокой пролиферативной активности отражает агрессивный потенциал опухоли и свидетельствует о высоком риске метастазов уже на момент диагностики заболевания или ранней диссеминации опухоли.

ПРОГНОСТИЧЕСКОЕ ЗНАЧЕНИЕ ИССЛЕДОВАНИЯ МАТРИКСНОЙ МЕТАЛЛОПРОТЕИНАЗЫ 9 ПРИ ПОЧЕЧНО-КЛЕТОЧНОМ РАКЕ

Objective: to assess matrix metalloproteinase 9 (MMP-9)  expression in renal cell carcinoma cells and cells of intratumoral inflammatory infiltrates depending on clinical and morphological characteristics and postoperative survival.Materials and methods. We evaluated MMP-expression in 108 renal cancer tissue specimens. The intensity of immunohistochemical staining was estimated by measuring integral optical density in cytoplasm.Results. We found that the integral optical density of MMP-9 immunostaining in tumor cells and cells of intratumoral inflammatory infiltrates correlates with important prognostic factors for renal cancer, including histological type of cancer, TNM stage, tumor size, Fuhrman nuclear grade, metastasis, and 5-year postoperative survival.Conclusion. Integral optical density of MMP-9 immunostaining is an additional prognostic factor for renal cell carcinoma.Цель исследования – изучение экспрессии матриксной металлопротеиназы 9 (ММП-9) в клетках почечно-клеточного рака и клетках интратуморального воспалительного инфильтрата в зависимости от клинико-морфологических параметров и послеоперационной выживаемости пациентов.Материалы и методы. Исследованы 108 препаратов рака почки. Экспрессию ММП-9  выявляли иммуногистохимически, ее выраженность оценивали путем вычисления интегральной оптической плотности в цитоплазмах клеток.Результаты. Показано, что интегральная оптическая плотность ММП-9  в клетках  опухоли и клетках  интратуморального воспалительного инфильтрата взаимосвязана с важными прогностическими факторами рака почки: гистологическим вариантом рака, стадией заболевания по TNM,  размером опухолевого узла, градацией по Фурману, наличием метастазов и 5-летней послеоперационной выживаемостью больных.Заключение. Исследование интегральной оптической плотности ММП-9 может служить дополнительным фактором прогноза почечно-клеточного рака

Изучение ассоциации однонуклеотидных полиморфных замен в генах ферментов антиоксидантной системы с риском развития рака предстательной железы в Сибирском регионе России

The influence of polymorphic substitutions in antioxidant system genes (SNPsrs1050450 in the GPX1 gene, rs1695 and rs1138272 in the GSTP1gene and rs4880 in the MnSOD gene) on the risk of prostate cancer development in men living in the Siberian region of Russia was studied. The relationship between the studied genotypes and clinical parameters (disease stage and PSA level) was analyzed. For this purpose, the incidence of the studied allelic variants was compared between 399 with prostate cancer patients and 344 men with no history of prostate cancer. Genotyping was performed using real-time PCR. No statistically significant association with the risk of developing prostate cancer was found in the studied SNPs (p>0,05). For the GSTP1SNPrs1695, the correlation with disease stage was obtained: The GG genotype occurred more frequently in patients with stage III-IV prostate cancer (OR [C.I.]=2,66 [1,15–6,18], p=0,02). Both studied SNPs of the GSTP1 gene were associated with the level of prostate-specific antigen (PSA) in blood: the GG rs1695 genotype and TT rs1138272 genotype were associated with higher PSA levels (p=1,5×10-3)Изучено влияние ряда полиморфных замен в генах антиоксидантной системы (SNPsrs1050450 гена GPX1, rs1695 и rs1138272 гена GSTP1 и rs4880 гена MnSOD) на риск развития рака предстательной железы у мужчин, проживающих в Сибирском регионе России. Проведен анализ взаимосвязи исследуемых генотипов с клиническими параметрами (стадией заболевания и уровнем ПСА). С этой целью сравнили частоту встречаемости исследуемых аллельных вариантов у 392 пациентов с раком простаты и у 344 мужчин без онкологических заболеваний в анамнезе. Генотипирование выполнялось при помощи ПЦР в режиме реального времени. Ни для одного из исследуемых SNPs не было получено статистически значимой ассоциации с риском развития рака пред- стательной железы (p>0,05). Для SNPrs1695 гена GSTP1 получена корреляция со стадией заболевания: генотип GG статистически значимо чаще встречается у больных раком простаты III–IV стадий (OR[C.I.]=2,66 [1,15–6,18], p=0,02). Оба исследуемых SNPs гена GSTP1 ассоциированы с уровнем простат-специфического антигена (ПСА) в крови: генотип GG rs1695 и генотип TT rs1138272 ассоциированы с более высокими показателями ПСА (p=1,5×10-3)

EXPERIENCE WITH OCTREOTIDE IN PATIENTS WITH CASTRATION REFRACTORY PROSTATE CANCER

Fifteen patients with castration refractory prostate cancer have been treated with sustained-release octreotide in combination with dexamethasone at the Altai Territory Oncology Dispensary since 2008. Control PSA test revealed that 9 (60 %) patients had positive changes; tumor process stabilization was noted in 4 (26.7 %) and only 2 (13.3 %) were found to have disease progression. Thus, more than 86 % of patients responded to combination treatment with sustained-release octreotide + dexamethasone. Octreotide treatment caused no serious specific adverse toxic reactions

ПЕРВИЧНО-МНОЖЕСТВЕННЫЙ РАК ПРЕДСТАТЕЛЬНОЙ ЖЕЛЕЗЫ В АЛТАЙСКОМ КРАЕ

<span>The proportion of men with multiple primary malignancies (MPM), by involving the prostate, is 9.3% of all the patients with prostate cancer in the Altai Territory. When prostate cancer is found, the lung, skin, oral cavity, and digestive tract should be examined to reveal secondary tumors. When primary malignancy is detected in these organs, the prostate should be more meticulously examined. In patients with double metachronic nonsystemic MPM with the involvement of the prostate, the disease is more frequently detectable in the 60-69 year age group.</span

CLINICAL VALUE OF THE MARKERS OF PROLIFERATION AND APOPTOSIS IN PATIENTS WITH CLEAR CELL RENAL CELL CARCINOMA

Renal cell carcinoma (RCC) is a heterogeneous disease in which the patients survive for months to years. At the present time the prognostic models have no sufficient information or exact prognostic value. Cell proliferation and apoptosis play a key role in cell cycle regulation; and impairment in these processes is commonly detected in different human tumors. The investigation enrolled 76 patients (49 men, 27 women) aged 32 to 73 years (mean age 56 ± 7.6 years) diagnosed with RCC. The follow-up was 8 to 116 months (mean 36.5 months). All the patients underwent nephrectomy; antibodies against р53, Bcl-2, and Ki-67 were investigated by immunohistochemistry. The expression of p53 and none or reduced expression of Bcl-2 are poor prognostic factors and associated with the metastatic potential of a tumor and with low relapse-free survival. High Ki-67 levels are a risk factor for metastases. A combination of p53 expression and high proliferative activity reflects the aggressive potential of a tumor and suggests the high risk of metastases just at the disease diagnosis and early tumor dissemination.<p> </p

PROGNOSTIC VALUE OF MATRIX METALLOPROTEINASE 9 IN RENAL CELL CARCINOMA

Objective: to assess matrix metalloproteinase 9 (MMP-9)  expression in renal cell carcinoma cells and cells of intratumoral inflammatory infiltrates depending on clinical and morphological characteristics and postoperative survival.Materials and methods. We evaluated MMP-expression in 108 renal cancer tissue specimens. The intensity of immunohistochemical staining was estimated by measuring integral optical density in cytoplasm.Results. We found that the integral optical density of MMP-9 immunostaining in tumor cells and cells of intratumoral inflammatory infiltrates correlates with important prognostic factors for renal cancer, including histological type of cancer, TNM stage, tumor size, Fuhrman nuclear grade, metastasis, and 5-year postoperative survival.Conclusion. Integral optical density of MMP-9 immunostaining is an additional prognostic factor for renal cell carcinoma

STUDY OF ASSOCIATION OF SINGLE NUCLEOTIDE POLYMORHISMS IN GENES OF ANTIOXIDANT DEFENCE ENZYMES WITH RISK OF DEVELOPING PROSTATE CANCER IN SIBERIA

The influence of polymorphic substitutions in antioxidant system genes (SNPsrs1050450 in the GPX1 gene, rs1695 and rs1138272 in the GSTP1gene and rs4880 in the MnSOD gene) on the risk of prostate cancer development in men living in the Siberian region of Russia was studied. The relationship between the studied genotypes and clinical parameters (disease stage and PSA level) was analyzed. For this purpose, the incidence of the studied allelic variants was compared between 399 with prostate cancer patients and 344 men with no history of prostate cancer. Genotyping was performed using real-time PCR. No statistically significant association with the risk of developing prostate cancer was found in the studied SNPs (p&gt;0,05). For the GSTP1SNPrs1695, the correlation with disease stage was obtained: The GG genotype occurred more frequently in patients with stage III-IV prostate cancer (OR [C.I.]=2,66 [1,15–6,18], p=0,02). Both studied SNPs of the GSTP1 gene were associated with the level of prostate-specific antigen (PSA) in blood: the GG rs1695 genotype and TT rs1138272 genotype were associated with higher PSA levels (p=1,5×10-3