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Инсулиноподобные факторы роста у больных с опухолями яичника (результаты собственного исследования)
Инсулиноподобные факторы роста у больных с опухолями яичника (результаты собственного исследования)
Князев Р.И., Кузнецов В.В., Бокин И.И. и др. Инсулиноподобные факторы роста у больных с опухолями яичника (результаты собственного исследования). Современная Онкология. 2016; 18 (1): 67–74.
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Аннотация
В экспериментальных моделях показано, что семейство инсулиноподобных факторов роста (ИФР), основным представителем которого является ИФР 1-го типа, проявляет митогенную, антиапоптотическую и ангиогенную активность. Известно, что ИФР-сигнальный путь участвует в активации каскада митогенактивируемых протеинкиназ, приводящих к блокированию апоптоза. Клинические работы подтверждают необходимость участия ИФР-сигнального пути в развитии и прогрессировании рака яичника (РЯ).
Материалы и методы. В исследование включены 44 больных РЯ, 7 пациенток с пограничными и 14 – доброкачественными опухолями яичника. Иммуноферментным анализом определено содержание ИФР 1 и 2-го типа в опухолевой ткани и сыворотке крови у больных с новообразованиями яичника.
Результаты. В ткани РЯ содержание ИФР-1 достоверно ниже, чем в ткани доброкачественных опухолей. Сывороточные уровни ИФР-1 и ИФР-2 отрицательно коррелируют с распространенностью РЯ. Обнаружена прямая корреляционная зависимость между уровнями ИФР-1 и ИФР-2 в ткани РЯ, а также слабая достоверная прямая зависимость между сывороточными уровнями ИФР-1 и ИФР-2. Медиана срока наблюдения составила 14 мес, а медиана срока жизни без рецидива – 13,5 мес. Установлено снижение 2-летней безрецидивной выживаемости на 40% при низких уровнях ИФР-1 сыворотки крови и на 30% – при низких значениях ИФР-2. У больных с размером остаточной опухоли менее 1 см при высоких сывороточных уровнях ИФР-1 (более 87 нг/мл) 2-летняя безрецидивная выживаемость составила 66,2%, а при низких уровнях ИФР-1 – 25% (р=0,016).
Выводы. Уровни ИФР-1 и ИФР-2 в опухолевой ткани и сыворотке крови у больных РЯ уменьшались при распространенности опухолевого процесса. Повышенные уровни ИФР-1 могут рассматриваться в качестве фактора благоприятного прогноза у больных РЯ, которым была выполнена циторедуктивная операция с остаточной опухолью менее 1 см.
Ключевые слова: рак яичника, канцерогенез, метастазирование, апоптоз, инсулиноподобные факторы роста, диагностика, прогноз, выживаемость, циторедуктивная операция, опухолевые маркеры.
Subjects and methods. The study included 44 patients with ovarian cancer, 7 patients with borderline and 14 benign ovarian tumors. The ELISA analysis determined the content of insulin-like growth factors type 1 and 2 in tumor tissue and serum of patients with neoplasm of the ovary.
Results. In the tissue of ovarian cancer content of IGF-1 were significantly lower than in the tissue of benign tumors. Serum levels of IGF-1 and IGF-2 correlated negatively with the prevalence of OC. Found direct correlation between levels of IGF-1 and IGF-2 in ovarian cancer tissue, and poor direct correlation between serum levels of IGF-1 and IGF-2. The median follow-up period was 14 months and the median time without recurrence was 13.5 months. It is established that two-year disease-free survival is reduced by 40% when low serum levels of IGF-I, and 30% at low levels of IGF-2. In patients with residual tumor size less than 1 cm with high serum levels of IGF-1 (87 ng/ml) two-year disease-free survival was 66.2%, and at low levels of IGF-1 – 25% (p=0.016).
Conclusions. The levels of IGF-1 and IGF-2 in tumor tissue and serum in patients with ovarian cancer were decreased in the tumor process. Elevated levels of IGF-I can be considered as a factor of favorable prognosis in patients with ovarian cancer who underwent cytoreductive surgery with residual tumor of less than 1 cm.
Key words: ovarian cancer, carcinogenesis, metastasis, apoptosis, insulin-like growth factors, diagnosis, prognosis, survival, cytoreductive surgery, tumor markers.
Материалы и методы. В исследование включены 44 больных РЯ, 7 пациенток с пограничными и 14 – доброкачественными опухолями яичника. Иммуноферментным анализом определено содержание ИФР 1 и 2-го типа в опухолевой ткани и сыворотке крови у больных с новообразованиями яичника.
Результаты. В ткани РЯ содержание ИФР-1 достоверно ниже, чем в ткани доброкачественных опухолей. Сывороточные уровни ИФР-1 и ИФР-2 отрицательно коррелируют с распространенностью РЯ. Обнаружена прямая корреляционная зависимость между уровнями ИФР-1 и ИФР-2 в ткани РЯ, а также слабая достоверная прямая зависимость между сывороточными уровнями ИФР-1 и ИФР-2. Медиана срока наблюдения составила 14 мес, а медиана срока жизни без рецидива – 13,5 мес. Установлено снижение 2-летней безрецидивной выживаемости на 40% при низких уровнях ИФР-1 сыворотки крови и на 30% – при низких значениях ИФР-2. У больных с размером остаточной опухоли менее 1 см при высоких сывороточных уровнях ИФР-1 (более 87 нг/мл) 2-летняя безрецидивная выживаемость составила 66,2%, а при низких уровнях ИФР-1 – 25% (р=0,016).
Выводы. Уровни ИФР-1 и ИФР-2 в опухолевой ткани и сыворотке крови у больных РЯ уменьшались при распространенности опухолевого процесса. Повышенные уровни ИФР-1 могут рассматриваться в качестве фактора благоприятного прогноза у больных РЯ, которым была выполнена циторедуктивная операция с остаточной опухолью менее 1 см.
Ключевые слова: рак яичника, канцерогенез, метастазирование, апоптоз, инсулиноподобные факторы роста, диагностика, прогноз, выживаемость, циторедуктивная операция, опухолевые маркеры.
________________________________________________
Subjects and methods. The study included 44 patients with ovarian cancer, 7 patients with borderline and 14 benign ovarian tumors. The ELISA analysis determined the content of insulin-like growth factors type 1 and 2 in tumor tissue and serum of patients with neoplasm of the ovary.
Results. In the tissue of ovarian cancer content of IGF-1 were significantly lower than in the tissue of benign tumors. Serum levels of IGF-1 and IGF-2 correlated negatively with the prevalence of OC. Found direct correlation between levels of IGF-1 and IGF-2 in ovarian cancer tissue, and poor direct correlation between serum levels of IGF-1 and IGF-2. The median follow-up period was 14 months and the median time without recurrence was 13.5 months. It is established that two-year disease-free survival is reduced by 40% when low serum levels of IGF-I, and 30% at low levels of IGF-2. In patients with residual tumor size less than 1 cm with high serum levels of IGF-1 (87 ng/ml) two-year disease-free survival was 66.2%, and at low levels of IGF-1 – 25% (p=0.016).
Conclusions. The levels of IGF-1 and IGF-2 in tumor tissue and serum in patients with ovarian cancer were decreased in the tumor process. Elevated levels of IGF-I can be considered as a factor of favorable prognosis in patients with ovarian cancer who underwent cytoreductive surgery with residual tumor of less than 1 cm.
Key words: ovarian cancer, carcinogenesis, metastasis, apoptosis, insulin-like growth factors, diagnosis, prognosis, survival, cytoreductive surgery, tumor markers.
Полный текст
Список литературы
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2. Bruchim I, Sarfstein R, Werner H. The IGF hormonal network in endometrial cancer: functions, regulation, and targeting approaches. Front Endocrin 2014; 5.
3. Ma J et al. IGF-1 mediates PTEN suppression and enhances cell invasion and proliferation via activation of the IGF-1/PI3K/Akt signaling pathway in pancreatic cancer cells. J Surg Res 2010; 160 (1): 90–101.
4. Mairet-Coello G, Tury A, DiCicco-Bloom E. Insulin-like growth factor-1 promotes G1/S cell cycle progression through bidirectional regulation of cyclins and cyclin-dependent kinase inhibitors via the phosphatidylinositol 3-kinase/Akt pathway in developing rat cerebral cortex. J Neurosci 2009; 29 (3): 775–88.
5. Rinaldi S et al. Serum levels of IGF‐I, IGFBP‐3 and colorectal cancer risk: results from the EPIC cohort, plus a meta‐analysis of prospective studies. Int J Cancer 2010; 126 (7): 1702–15.
6. Cao Y et al. Prediagnostic plasma IGFBP‐1, IGF‐1 and risk of prostate cancer. Int J Cancer 2015; 136 (10): 2418–26.
7. Hormones TE, Group BCC. Insulin-like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), and breast cancer risk: pooled individual data analysis of 17 prospective studies. Lancet Oncol 2010; 11 (6): 530–42.
8. Бочкарева Н.В., Кондакова И.В., Коломиец Л.А. и др. Инсулиноподобные факторы роста и связывающие их белки в патогенезе рака эндометрия. Сиб. онкол. журн. 2008; 3: 27. / Bochkareva N.V., Kondakova I.V., Kolomiets L.A. i dr. Insulinopodobnye faktory rosta i sviazyvaiushchie ikh belki v patogeneze raka endometriia. Sib. onkol. zhurn. 2008; 3: 27. [in Russian]
9. Flannery CA et al. SAT-0017: Differential Expression of IR-a, IR-B and IGF-1R in Endometrium Reflects Physiology during the Menstrual Cycle and Demonstrates a Distinct Expression Signature in Endometrial Adenocarcinoma. 2014.
10. Дигаева М.А. Предикторы эпителиальных опухолей яичников, их роль в патогенезе, диагностике, тактике выбора объема оперативного лечения и прогнозе. Автореф. дис. … д-ра мед. наук. М., 2011. / Digaeva M.A. Prediktory epitelial'nykh opukholei iaichnikov, ikh rol' v patogeneze, diagnostike, taktike vybora ob"ema operativnogo lecheniia i prognoze. Avtoref. dis. … d-ra med. nauk. M., 2011. [in Russian]
11. An Y et al. Local expression of insulin-like growth factor-I, insulin-like growth factor-I receptor, and estrogen receptor alpha in ovarian cancer. Oncol Res Treat 2009; 32 (11): 638–44.
12. Brokaw J et al. IGF-I in epithelial ovarian cancer and its role in disease progression. Growth Factors 2007; 25 (5): 346–54.
13. Lu L et al. The relationship of insulin-like growth factor-II, insulin-like growth factor binding protein-3, and estrogen receptor-alpha expression to disease progression in epithelial ovarian cancer. Clin Cancer Res 2006; 12 (4): 1208–14.
14. Sayer RA et al. High insulin-like growth factor-2 (IGF-2) gene expression is an independent predictor of poor survival for patients with advanced stage serous epithelial ovarian cancer. Gynecol Oncol 2005; 96 (2): 355–61.
15. Spentzos D et al. IGF axis gene expression patterns are prognostic of survival in epithelial ovarian cancer. Endocrine-related Cancer 2007; 14 (3): 781–90.
16. Ose J et al. Insulin-like growth factor I and risk of epithelial invasive ovarian cancer by tumour characteristics: results from the EPIC cohort. Br J Cancer 2015; 112 (1): 162–6.
17. Pollak M. Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer 2008; 8 (12): 915–28.
18. Mikami K et al. Prostate cancer risk in relation to insulin-like growth factor (IGF)-I and IGF-binding protein-3: A nested case-control study in large scale cohort study in Japan. Asian Pac J Cancer Prevention: APJCP 2009; 10: 57–61.
19. Sakauchi F et al. Serum Insulin-like Growth Factors I and II, Insulin-like Growth Factor Binding Protein-3 and Risk of Breast Cancer in the JACC Study. Asian Pac J Cancer Prevent 2009; 10: 51–5.
20. Suzuki S et al. Insulin-like Growth Factor (IGF)-I, IGF-II, IGF Binding Protein-3, and Risk of Colorectal Cancer: a Nested Case-control Study in the JACC Study. Age 2009; 64 (8.1): 64.9–8.3.
21. Tas F et al. Clinical significance of serum insulin-like growth factor-1 (IGF-1) and insulinlike growth factor binding protein-3 (IGFBP-3) in patients with epithelial ovarian cancer. Tumor Biology 2014; 35 (4): 3125–32.
22. Huang YF et al. Circulating IGF system and treatment outcome in epithelial ovarian cancer. Endocrine-related Cancer 2014; 21 (2): 217–29.
2. Bruchim I, Sarfstein R, Werner H. The IGF hormonal network in endometrial cancer: functions, regulation, and targeting approaches. Front Endocrin 2014; 5.
3. Ma J et al. IGF-1 mediates PTEN suppression and enhances cell invasion and proliferation via activation of the IGF-1/PI3K/Akt signaling pathway in pancreatic cancer cells. J Surg Res 2010; 160 (1): 90–101.
4. Mairet-Coello G, Tury A, DiCicco-Bloom E. Insulin-like growth factor-1 promotes G1/S cell cycle progression through bidirectional regulation of cyclins and cyclin-dependent kinase inhibitors via the phosphatidylinositol 3-kinase/Akt pathway in developing rat cerebral cortex. J Neurosci 2009; 29 (3): 775–88.
5. Rinaldi S et al. Serum levels of IGF‐I, IGFBP‐3 and colorectal cancer risk: results from the EPIC cohort, plus a meta‐analysis of prospective studies. Int J Cancer 2010; 126 (7): 1702–15.
6. Cao Y et al. Prediagnostic plasma IGFBP‐1, IGF‐1 and risk of prostate cancer. Int J Cancer 2015; 136 (10): 2418–26.
7. Hormones TE, Group BCC. Insulin-like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), and breast cancer risk: pooled individual data analysis of 17 prospective studies. Lancet Oncol 2010; 11 (6): 530–42.
8. Bochkareva N.V., Kondakova I.V., Kolomiets L.A. i dr. Insulinopodobnye faktory rosta i sviazyvaiushchie ikh belki v patogeneze raka endometriia. Sib. onkol. zhurn. 2008; 3: 27. [in Russian]
9. Flannery CA et al. SAT-0017: Differential Expression of IR-a, IR-B and IGF-1R in Endometrium Reflects Physiology during the Menstrual Cycle and Demonstrates a Distinct Expression Signature in Endometrial Adenocarcinoma. 2014.
10. Digaeva M.A. Prediktory epitelial'nykh opukholei iaichnikov, ikh rol' v patogeneze, diagnostike, taktike vybora ob"ema operativnogo lecheniia i prognoze. Avtoref. dis. … d-ra med. nauk. M., 2011. [in Russian]
11. An Y et al. Local expression of insulin-like growth factor-I, insulin-like growth factor-I receptor, and estrogen receptor alpha in ovarian cancer. Oncol Res Treat 2009; 32 (11): 638–44.
12. Brokaw J et al. IGF-I in epithelial ovarian cancer and its role in disease progression. Growth Factors 2007; 25 (5): 346–54.
13. Lu L et al. The relationship of insulin-like growth factor-II, insulin-like growth factor binding protein-3, and estrogen receptor-alpha expression to disease progression in epithelial ovarian cancer. Clin Cancer Res 2006; 12 (4): 1208–14.
14. Sayer RA et al. High insulin-like growth factor-2 (IGF-2) gene expression is an independent predictor of poor survival for patients with advanced stage serous epithelial ovarian cancer. Gynecol Oncol 2005; 96 (2): 355–61.
15. Spentzos D et al. IGF axis gene expression patterns are prognostic of survival in epithelial ovarian cancer. Endocrine-related Cancer 2007; 14 (3): 781–90.
16. Ose J et al. Insulin-like growth factor I and risk of epithelial invasive ovarian cancer by tumour characteristics: results from the EPIC cohort. Br J Cancer 2015; 112 (1): 162–6.
17. Pollak M. Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer 2008; 8 (12): 915–28.
18. Mikami K et al. Prostate cancer risk in relation to insulin-like growth factor (IGF)-I and IGF-binding protein-3: A nested case-control study in large scale cohort study in Japan. Asian Pac J Cancer Prevention: APJCP 2009; 10: 57–61.
19. Sakauchi F et al. Serum Insulin-like Growth Factors I and II, Insulin-like Growth Factor Binding Protein-3 and Risk of Breast Cancer in the JACC Study. Asian Pac J Cancer Prevent 2009; 10: 51–5.
20. Suzuki S et al. Insulin-like Growth Factor (IGF)-I, IGF-II, IGF Binding Protein-3, and Risk of Colorectal Cancer: a Nested Case-control Study in the JACC Study. Age 2009; 64 (8.1): 64.9–8.3.
21. Tas F et al. Clinical significance of serum insulin-like growth factor-1 (IGF-1) and insulinlike growth factor binding protein-3 (IGFBP-3) in patients with epithelial ovarian cancer. Tumor Biology 2014; 35 (4): 3125–32.
22. Huang YF et al. Circulating IGF system and treatment outcome in epithelial ovarian cancer. Endocrine-related Cancer 2014; 21 (2): 217–29.
2. Bruchim I, Sarfstein R, Werner H. The IGF hormonal network in endometrial cancer: functions, regulation, and targeting approaches. Front Endocrin 2014; 5.
3. Ma J et al. IGF-1 mediates PTEN suppression and enhances cell invasion and proliferation via activation of the IGF-1/PI3K/Akt signaling pathway in pancreatic cancer cells. J Surg Res 2010; 160 (1): 90–101.
4. Mairet-Coello G, Tury A, DiCicco-Bloom E. Insulin-like growth factor-1 promotes G1/S cell cycle progression through bidirectional regulation of cyclins and cyclin-dependent kinase inhibitors via the phosphatidylinositol 3-kinase/Akt pathway in developing rat cerebral cortex. J Neurosci 2009; 29 (3): 775–88.
5. Rinaldi S et al. Serum levels of IGF‐I, IGFBP‐3 and colorectal cancer risk: results from the EPIC cohort, plus a meta‐analysis of prospective studies. Int J Cancer 2010; 126 (7): 1702–15.
6. Cao Y et al. Prediagnostic plasma IGFBP‐1, IGF‐1 and risk of prostate cancer. Int J Cancer 2015; 136 (10): 2418–26.
7. Hormones TE, Group BCC. Insulin-like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), and breast cancer risk: pooled individual data analysis of 17 prospective studies. Lancet Oncol 2010; 11 (6): 530–42.
8. Бочкарева Н.В., Кондакова И.В., Коломиец Л.А. и др. Инсулиноподобные факторы роста и связывающие их белки в патогенезе рака эндометрия. Сиб. онкол. журн. 2008; 3: 27. / Bochkareva N.V., Kondakova I.V., Kolomiets L.A. i dr. Insulinopodobnye faktory rosta i sviazyvaiushchie ikh belki v patogeneze raka endometriia. Sib. onkol. zhurn. 2008; 3: 27. [in Russian]
9. Flannery CA et al. SAT-0017: Differential Expression of IR-a, IR-B and IGF-1R in Endometrium Reflects Physiology during the Menstrual Cycle and Demonstrates a Distinct Expression Signature in Endometrial Adenocarcinoma. 2014.
10. Дигаева М.А. Предикторы эпителиальных опухолей яичников, их роль в патогенезе, диагностике, тактике выбора объема оперативного лечения и прогнозе. Автореф. дис. … д-ра мед. наук. М., 2011. / Digaeva M.A. Prediktory epitelial'nykh opukholei iaichnikov, ikh rol' v patogeneze, diagnostike, taktike vybora ob"ema operativnogo lecheniia i prognoze. Avtoref. dis. … d-ra med. nauk. M., 2011. [in Russian]
11. An Y et al. Local expression of insulin-like growth factor-I, insulin-like growth factor-I receptor, and estrogen receptor alpha in ovarian cancer. Oncol Res Treat 2009; 32 (11): 638–44.
12. Brokaw J et al. IGF-I in epithelial ovarian cancer and its role in disease progression. Growth Factors 2007; 25 (5): 346–54.
13. Lu L et al. The relationship of insulin-like growth factor-II, insulin-like growth factor binding protein-3, and estrogen receptor-alpha expression to disease progression in epithelial ovarian cancer. Clin Cancer Res 2006; 12 (4): 1208–14.
14. Sayer RA et al. High insulin-like growth factor-2 (IGF-2) gene expression is an independent predictor of poor survival for patients with advanced stage serous epithelial ovarian cancer. Gynecol Oncol 2005; 96 (2): 355–61.
15. Spentzos D et al. IGF axis gene expression patterns are prognostic of survival in epithelial ovarian cancer. Endocrine-related Cancer 2007; 14 (3): 781–90.
16. Ose J et al. Insulin-like growth factor I and risk of epithelial invasive ovarian cancer by tumour characteristics: results from the EPIC cohort. Br J Cancer 2015; 112 (1): 162–6.
17. Pollak M. Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer 2008; 8 (12): 915–28.
18. Mikami K et al. Prostate cancer risk in relation to insulin-like growth factor (IGF)-I and IGF-binding protein-3: A nested case-control study in large scale cohort study in Japan. Asian Pac J Cancer Prevention: APJCP 2009; 10: 57–61.
19. Sakauchi F et al. Serum Insulin-like Growth Factors I and II, Insulin-like Growth Factor Binding Protein-3 and Risk of Breast Cancer in the JACC Study. Asian Pac J Cancer Prevent 2009; 10: 51–5.
20. Suzuki S et al. Insulin-like Growth Factor (IGF)-I, IGF-II, IGF Binding Protein-3, and Risk of Colorectal Cancer: a Nested Case-control Study in the JACC Study. Age 2009; 64 (8.1): 64.9–8.3.
21. Tas F et al. Clinical significance of serum insulin-like growth factor-1 (IGF-1) and insulinlike growth factor binding protein-3 (IGFBP-3) in patients with epithelial ovarian cancer. Tumor Biology 2014; 35 (4): 3125–32.
22. Huang YF et al. Circulating IGF system and treatment outcome in epithelial ovarian cancer. Endocrine-related Cancer 2014; 21 (2): 217–29.
________________________________________________
2. Bruchim I, Sarfstein R, Werner H. The IGF hormonal network in endometrial cancer: functions, regulation, and targeting approaches. Front Endocrin 2014; 5.
3. Ma J et al. IGF-1 mediates PTEN suppression and enhances cell invasion and proliferation via activation of the IGF-1/PI3K/Akt signaling pathway in pancreatic cancer cells. J Surg Res 2010; 160 (1): 90–101.
4. Mairet-Coello G, Tury A, DiCicco-Bloom E. Insulin-like growth factor-1 promotes G1/S cell cycle progression through bidirectional regulation of cyclins and cyclin-dependent kinase inhibitors via the phosphatidylinositol 3-kinase/Akt pathway in developing rat cerebral cortex. J Neurosci 2009; 29 (3): 775–88.
5. Rinaldi S et al. Serum levels of IGF‐I, IGFBP‐3 and colorectal cancer risk: results from the EPIC cohort, plus a meta‐analysis of prospective studies. Int J Cancer 2010; 126 (7): 1702–15.
6. Cao Y et al. Prediagnostic plasma IGFBP‐1, IGF‐1 and risk of prostate cancer. Int J Cancer 2015; 136 (10): 2418–26.
7. Hormones TE, Group BCC. Insulin-like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), and breast cancer risk: pooled individual data analysis of 17 prospective studies. Lancet Oncol 2010; 11 (6): 530–42.
8. Bochkareva N.V., Kondakova I.V., Kolomiets L.A. i dr. Insulinopodobnye faktory rosta i sviazyvaiushchie ikh belki v patogeneze raka endometriia. Sib. onkol. zhurn. 2008; 3: 27. [in Russian]
9. Flannery CA et al. SAT-0017: Differential Expression of IR-a, IR-B and IGF-1R in Endometrium Reflects Physiology during the Menstrual Cycle and Demonstrates a Distinct Expression Signature in Endometrial Adenocarcinoma. 2014.
10. Digaeva M.A. Prediktory epitelial'nykh opukholei iaichnikov, ikh rol' v patogeneze, diagnostike, taktike vybora ob"ema operativnogo lecheniia i prognoze. Avtoref. dis. … d-ra med. nauk. M., 2011. [in Russian]
11. An Y et al. Local expression of insulin-like growth factor-I, insulin-like growth factor-I receptor, and estrogen receptor alpha in ovarian cancer. Oncol Res Treat 2009; 32 (11): 638–44.
12. Brokaw J et al. IGF-I in epithelial ovarian cancer and its role in disease progression. Growth Factors 2007; 25 (5): 346–54.
13. Lu L et al. The relationship of insulin-like growth factor-II, insulin-like growth factor binding protein-3, and estrogen receptor-alpha expression to disease progression in epithelial ovarian cancer. Clin Cancer Res 2006; 12 (4): 1208–14.
14. Sayer RA et al. High insulin-like growth factor-2 (IGF-2) gene expression is an independent predictor of poor survival for patients with advanced stage serous epithelial ovarian cancer. Gynecol Oncol 2005; 96 (2): 355–61.
15. Spentzos D et al. IGF axis gene expression patterns are prognostic of survival in epithelial ovarian cancer. Endocrine-related Cancer 2007; 14 (3): 781–90.
16. Ose J et al. Insulin-like growth factor I and risk of epithelial invasive ovarian cancer by tumour characteristics: results from the EPIC cohort. Br J Cancer 2015; 112 (1): 162–6.
17. Pollak M. Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer 2008; 8 (12): 915–28.
18. Mikami K et al. Prostate cancer risk in relation to insulin-like growth factor (IGF)-I and IGF-binding protein-3: A nested case-control study in large scale cohort study in Japan. Asian Pac J Cancer Prevention: APJCP 2009; 10: 57–61.
19. Sakauchi F et al. Serum Insulin-like Growth Factors I and II, Insulin-like Growth Factor Binding Protein-3 and Risk of Breast Cancer in the JACC Study. Asian Pac J Cancer Prevent 2009; 10: 51–5.
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Авторы
Р.И.Князев1, В.В.Кузнецов2, И.И.Бокин1, В.В.Баринов2, Н.Е.Кушлинский2, И.В.Поддубная1,2
1 ГБОУ ДПО Российская медицинская академия последипломного образования Минздрава России. 125993, Россия, Москва, ул. Баррикадная, д. 2/1;
2 ФГБУ Российский онкологический научный центр им. Н.Н.Блохина Минздрава России. 115478, Россия, Москва, Каширское ш., д. 23
*sluwba@mail.ru
1 Russian Medical Academy of Postgraduate Education of the Ministry of Health of the Russian Federation. 125993, Russian Federation, Moscow, ul. Barrikadnaia, d. 2/1;
2 N.N.Blokhin Russian Cancer Research Center of the Ministry of Health of the Russian Federation. 115478, Russian Federation, Moscow, Kashirskoe sh., d. 23
*sluwba@mail.ru
1 ГБОУ ДПО Российская медицинская академия последипломного образования Минздрава России. 125993, Россия, Москва, ул. Баррикадная, д. 2/1;
2 ФГБУ Российский онкологический научный центр им. Н.Н.Блохина Минздрава России. 115478, Россия, Москва, Каширское ш., д. 23
*sluwba@mail.ru
________________________________________________
1 Russian Medical Academy of Postgraduate Education of the Ministry of Health of the Russian Federation. 125993, Russian Federation, Moscow, ul. Barrikadnaia, d. 2/1;
2 N.N.Blokhin Russian Cancer Research Center of the Ministry of Health of the Russian Federation. 115478, Russian Federation, Moscow, Kashirskoe sh., d. 23
*sluwba@mail.ru
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