Материалы доступны только для специалистов сферы здравоохранения. Авторизуйтесь или зарегистрируйтесь.
Молекулярно-биологический маркер Bcl-2 при колоректальном раке: характеристика, роль в механизмах регуляции апоптоза, влияние на прогноз (обзор литературы)
Молекулярно-биологический маркер Bcl-2 при колоректальном раке: характеристика, роль в механизмах регуляции апоптоза, влияние на прогноз (обзор литературы)
Даренская А.Д., Доброва Н.В., Степанова Е.В. Молекулярно-биологический маркер Bcl-2 при колоректальном раке: характеристика, роль в механизмах регуляции апоптоза, влияние на прогноз (обзор литературы). Современная Онкология. 2019; 21 (1): 52–58. DOI: 10.26442/18151434.2019.1.190278
________________________________________________
Материалы доступны только для специалистов сферы здравоохранения. Авторизуйтесь или зарегистрируйтесь.
Аннотация
Обоснование. За последние десятилетия проведено большое количество исследований, посвященных изучению молекулярно-биологических маркеров (МБМ) при колоректальном раке (КРР). Белок Вcl-2 (B-cell lymphoma-2) – один из наиболее изучаемых МБМ и привлекает внимание исследователей многих специальностей как при изучении канцерогенеза, так и во взаимосвязи с прогнозом заболевания.
Цель. Привести детальную характеристику МБМ Bcl-2; рассмотреть его роль в механизмах регуляции апоптоза; представить современные данные относительно прогностической значимости этого белка при КРР.
Материалы и методы. Для написания данного обзора литературы осуществлен поиск отечественных и зарубежных публикаций в российских и международных системах поиска (PubMed, eLibrary и др.) за последние 2–30 лет.
Результаты. Определение экспрессии антиапоптотического белка Вcl-2 в опухоли может давать дополнительную информацию о клиническом течении злокачественного процесса независимо от лечебного воздействия, о биологическом поведении опухоли: быстроте роста, способности к инвазии и метастазированию (т.е. о прогнозе заболевания).
Заключение. В научной литературе накапливаются данные о влиянии аномальной экспрессии ингибитора апоптоза Вcl-2 на клиническое течение и прогноз КРР, однако имеются лишь единичные работы, анализирующие взаимосвязь Вcl-2 с метастазированием КРР и факторами, влияющими на инвазивный потенциал опухолевых клеток. На сегодняшний день нет единого мнения о прогностической значимости белка Вcl-2 для больных КРР. В ряде работ по КРР показана корреляция повышенной экспрессии Bcl-2 в опухолевых клетках с относительно благополучным течением заболевания и хорошей выживаемостью больных. Другими авторами показано, что опухоли, высокоэкспрессирующие Bcl-2, наоборот, являются более агрессивными по сравнению с таковыми без экспрессии маркера. Существует ряд исследований, в которых прогностическое значение белка Bcl-2 не подтверждается. Многие вопросы, касающиеся корреляции данного МБМ с клинико-морфологическими характеристиками опухоли, также нуждаются в уточнении. Все сказанное – предмет дальнейших исследований.
Ключевые слова: молекулярно-биологические маркеры, Bcl-2, гиперэкспрессия, апоптоз, колоректальный рак.
Aim. To study in details the characteristics of Bcl-2; to study Bcl-2 role in the mechanisms regulating apoptosis; to show update data concerning the prognostic significance of this protein in CRC.
Materials and methods. To write this literature review we have studied domestic and foreign publications from Russian and international systems of search (PubMed, eLibrary, etc.) over the past 2–30 years.
Results. The evaluation of the expression of antiapoptopic protein Вcl-2 in tumor can give additional information about the course of malignant process independently of therapeutic effects, the biological behaviour of the tumor: the rapidity of growth, the ability of invasion and metastasis (i.e. the prognosis of a disease).
Conclusion. The results concerning the impact of abnormal expression of apoptosis inhibitor Вcl-2 on the course and prognosis of CRC have been accumulated in the scientific literature, but there have been only several studies, analyzing the relationship between Вcl-2 and metastasis of CRC and factors influencing the invasive potential of tumor cells. Nowadays, there is no consensus about the prognostic significance of protein Вcl-2 in patients with CRC. In some studies, concerning CRC, have been shown the correlation between Bcl-2 overexpression in tumor cells and a favorable course of disease and good survival in patients. Other authors have been shown that tumors with Bcl-2 overexpression, by contrast, are more aggressive in comparison with tumors without Bcl-2 expression. There are a number of studies in which the prognostic significance of Bcl-2 protein is not proved. Many issues, concerning the correlation between this molecular-biological marker and clinico-morphological characteristics of tumor, might also need to be itemized. All shown in the article is a subject to further research.
Key words: molecular biological markers, Bcl-2, overexpression, apoptosis, colorectal cancer.
Цель. Привести детальную характеристику МБМ Bcl-2; рассмотреть его роль в механизмах регуляции апоптоза; представить современные данные относительно прогностической значимости этого белка при КРР.
Материалы и методы. Для написания данного обзора литературы осуществлен поиск отечественных и зарубежных публикаций в российских и международных системах поиска (PubMed, eLibrary и др.) за последние 2–30 лет.
Результаты. Определение экспрессии антиапоптотического белка Вcl-2 в опухоли может давать дополнительную информацию о клиническом течении злокачественного процесса независимо от лечебного воздействия, о биологическом поведении опухоли: быстроте роста, способности к инвазии и метастазированию (т.е. о прогнозе заболевания).
Заключение. В научной литературе накапливаются данные о влиянии аномальной экспрессии ингибитора апоптоза Вcl-2 на клиническое течение и прогноз КРР, однако имеются лишь единичные работы, анализирующие взаимосвязь Вcl-2 с метастазированием КРР и факторами, влияющими на инвазивный потенциал опухолевых клеток. На сегодняшний день нет единого мнения о прогностической значимости белка Вcl-2 для больных КРР. В ряде работ по КРР показана корреляция повышенной экспрессии Bcl-2 в опухолевых клетках с относительно благополучным течением заболевания и хорошей выживаемостью больных. Другими авторами показано, что опухоли, высокоэкспрессирующие Bcl-2, наоборот, являются более агрессивными по сравнению с таковыми без экспрессии маркера. Существует ряд исследований, в которых прогностическое значение белка Bcl-2 не подтверждается. Многие вопросы, касающиеся корреляции данного МБМ с клинико-морфологическими характеристиками опухоли, также нуждаются в уточнении. Все сказанное – предмет дальнейших исследований.
Ключевые слова: молекулярно-биологические маркеры, Bcl-2, гиперэкспрессия, апоптоз, колоректальный рак.
________________________________________________
Aim. To study in details the characteristics of Bcl-2; to study Bcl-2 role in the mechanisms regulating apoptosis; to show update data concerning the prognostic significance of this protein in CRC.
Materials and methods. To write this literature review we have studied domestic and foreign publications from Russian and international systems of search (PubMed, eLibrary, etc.) over the past 2–30 years.
Results. The evaluation of the expression of antiapoptopic protein Вcl-2 in tumor can give additional information about the course of malignant process independently of therapeutic effects, the biological behaviour of the tumor: the rapidity of growth, the ability of invasion and metastasis (i.e. the prognosis of a disease).
Conclusion. The results concerning the impact of abnormal expression of apoptosis inhibitor Вcl-2 on the course and prognosis of CRC have been accumulated in the scientific literature, but there have been only several studies, analyzing the relationship between Вcl-2 and metastasis of CRC and factors influencing the invasive potential of tumor cells. Nowadays, there is no consensus about the prognostic significance of protein Вcl-2 in patients with CRC. In some studies, concerning CRC, have been shown the correlation between Bcl-2 overexpression in tumor cells and a favorable course of disease and good survival in patients. Other authors have been shown that tumors with Bcl-2 overexpression, by contrast, are more aggressive in comparison with tumors without Bcl-2 expression. There are a number of studies in which the prognostic significance of Bcl-2 protein is not proved. Many issues, concerning the correlation between this molecular-biological marker and clinico-morphological characteristics of tumor, might also need to be itemized. All shown in the article is a subject to further research.
Key words: molecular biological markers, Bcl-2, overexpression, apoptosis, colorectal cancer.
Полный текст
Список литературы
1. Степанова Е.В. Клинические и экспериментальные аспекты изучения молекулярно-биологических маркеров при злокачественных новообразованиях. Автореф. дис. … д-ра мед. наук. М., 2008.
[Stepanova E.V. Klinicheskie i eksperimental'nye aspekty izucheniia molekuliarno-biologicheskikh markerov pri zlokachestvennykh novoobrazovaniiakh. Avtoref. dis. … d-ra med. nauk. Moscow, 2008 (in Russian).]
2. Копнин Б.П. Мишени действия онкогенов и опухолевых супрессоров: ключ к пониманию базовых механизмов канцерогенеза (обзор). Биохимия. 2000; 65: 5–33.
[Kopnin B.P. Misheni deistviia onkogenov i opukholevykh supressorov: kliuch k ponimaniiu bazovykh mekhanizmov kantserogeneza (obzor). Biokhimiia. 2000; 65: 5–33 (in Russian).]
3. Копнин Б.П. Молекулярно-генетические изменения в злокачественных клетках. Под ред. Д.Г.Заридзе. Канцерогенез. М., 2000; с. 79–90.
[Kopnin B.P. Molekuliarno-geneticheskie izmeneniia v zlokachestvennykh kletkakh. Pod red. D.G.Zaridze. Kantserogenez. Moscow, 2000; s. 79–90. (in Russian).]
4. Fearnhead NS, Wilding JL, Bodmer WF. Genetics of colorectal cancer: hereditary aspects and overview of colorectal tumorigenesis. Brit Med Bull 2002; 64: 27–43.
5. Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell 1990; 6: 759–67.
6. Vogelstein B, Fearon ER, Hamilton SR et al. Genetic alterations during colorectal tumor development. N Engl J Med 1988; 319 (9): 525–32.
7. Ahmed FE. Development of novel diagnostic and prognostic molecular markers for sporadic colon cancer. Exp Rev Mol Diagnos 2005; 5: 337–52.
8. Ahmed FE. Molecular markers that predict response to colon cancer therapy. Exp Rev Mol Diagnos 2005; 5 (3): 353–75.
9. Arnold CN, Blum HE. Colon cancer: molecular markers. Dtsch Med Wochenschr 2005; 130 (14): 880–2.
10. Bianco AR, Carlomagno C, De Laurentiis M et al. Prognostic factors in human colorectal cancer. Tumori 1997; 83 (1. Supp. 1): S15–18.
11. Houlston RS. What we could do now: molecular pathology of colorectal cancer. Mol Pathol 2001; 54: 206–14.
12. Bendardaf R, Lamlum H, Pyrhonen S. Prognostic and predictive molecular markers in colorectal carcinoma. Anticancer Res 2004; 24 (4): 2519–30.
13. Руководство по иммуногистохимической диагностике опухолей. Под ред. С.В.Петрова, Н.Т.Райхлина. Казань, 2004.
[Rukovodstvo po immunogistokhimicheskoi diagnostike opukholei. Pod red. S.V.Petrova, N.T.Raikhlina. Kazan, 2004 (in Russian).]
14. Имянитов Е.Н., Хансон К.П. Молекулярная онкология: клинические аспекты. СПб.: СПбМАПО, 2007.
[Imianitov E.N., Khanson K.P. Molekuliarnaia onkologiia: klinicheskie aspekty. Saint Petersburg: SPbMAPO, 2007. (in Russian).]
15. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000; 100: 57–70.
16. Gasparini G, Pozza F, Harris AL. Evaluating the potential usefulness of new prognostic and predictive indicators in node negative breast cancer patients. J Natl Cancer Inst 1993; 85: 1206–19.
17. Aldrighetti L, Castoldi R, Di Palo S et al. Prognostic factors for long-term outcome of hepatic resection for colorectal liver metastases. Chir Ital 2005; 57 (5): 555–70.
18. Ambiru S, Miyazaki M, Isono T et al. Hepatic resection for colorectal metastases: analysis of prognostic factors. Dis Colon Rectum 1999; 42 (5): 632–9.
19. Neal CP, Garcea G, Doucas H. Molecular prognostic markers in resectable colorectal liver metastases: a systematic review. Eur J Cancer 2006; 42 (12): 1728–43.
20. Yamada H, Kondo S, Okushiba S et al. Analysis of predictive factors for recurrence after hepatectomy for colorectal liver metastases. World J Surg 2001; 25 (9): 1129–33.
21. Пожарисский К.М., Леенман Е.Е. Значение иммуногистохимических методик для определения характера лечения и прогноза опухолевых заболеваний. Архив патологии. 2000; 62 (5): 3–11.
[Pozharisskii K.M., Leenman E.E. Znachenie immunogistokhimicheskikh metodik dlia opredeleniia kharaktera lecheniia i prognoza opukholevykh zabolevanii. Arkhiv patologii. 2000; 62 (5): 3–11 (in Russian).]
22. Bendardaf R, Lamlum H, Ristamaki R. CD44 variant 6 expression predicts response to treatment in advanced colorectal cancer. Oncol Rep 2004; 11 (1): 41–5.
23. Cascinu S, Georgoulias V, Kerr D et al. Colorectal cancer in the adjuvant setting: perspectives on treatment and the role of prognostic factors. Ann Oncol 2003; 14: 25–9.
24. Graziano F, Cascinu S. Prognostic molecular markers for planning adjuvant chemotherapy trials in Dukes" B colorectal cancer patients: how much evidence is enough? Ann Oncol 2003; 14: 1026–38.
25. Немцова М.В., Пальцева Е.М., Бабаян А.Ю. и др. Молекулярно-генетический анализ клональной внутриопухолевой гетерогенности в колоректальных карциномах. Молекулярная биология. 2008; 42 (6): 1040–7.
[Nemtsova M.V., Pal'tseva E.M., Babaian A.Iu. et al. Molekuliarno-geneticheskii analiz klonal'noi vnutriopukholevoi geterogennosti v kolorektal'nykh kartsinomakh. Molekuliarnaia biologiia. 2008; 42 (6): 1040–7 (in Russian).]
26. Chu E. A Multidisciplinary Approach to the Treatment of Early Colorectal Cancer. Ed. by E.Chu. International Cancer Management: A Multidisciplinary Approach. Yale Cancer Center Yale University School of Medicine 2007; 63: 70–1.
27. Perez RO. Predicting response to neoadjuvant treatment for rectal cancer: a step toward individualized medicine. Dis Colon Rectum 2011; 54 (9): 1057–8.
28. Sulzyc-Bielicka V, Domagala P, Majdanik E et al. Nuclear thymidylate synthase expression in sporadic colorectal cancer depends on the site of the tumor. Virchows Arch 2009; 454 (6): 695–702.
29. Даренская А.Д. Первая линия лекарственной терапии метастатического колоректального рака. Новый режим лечения. Прогностическая значимость молекулярно-биологических маркеров. Автореф. дис. ... канд. мед. наук. М., 2017.
[Darenskaia A.D. Pervaia liniia lekarstvennoi terapii metastaticheskogo kolorektal'nogo raka. Novyi rezhim lecheniia. Prognosticheskaia znachimost' molekuliarno-biologicheskikh markerov. Avtoref. dis. ... kand. med. nauk. Moscow, 2017 (in Russian).]
30. Делекторская В.В. Молекулярно-биологические маркеры метастазирования и прогноза при раке толстой кишки. Автореф. дис. … д-ра мед. наук. М., 2007.
[Delektorskaia V.V. Molekuliarno-biologicheskie markery metastazirovaniia i prognoza pri rake tolstoi kishki. Avtoref. dis. … d-ra med. nauk. Moscow, 2007 (in Russian).]
31. Лушников Е.Ф., Абросимов А.Ю. Гибель клетки (апоптоз). М.: Медицина, 2001.
[Lushnikov E.F., Abrosimov A.Iu. Gibel' kletki (apoptoz). Moscow: Meditsina, 2001 (in Russian).]
32. Клиническая биохимия: учебное пособие. Под ред. В.А.Ткачука. 3-е изд. М.: ГЭОТАР-Медиа, 2008.
[Klinicheskaia biokhimiia: uchebnoe posobie. Pod red. V.A.Tkachuka. 3-e izd. Moscow: GEOTAR-Media, 2008 (in Russian).]
33. Аббасова С.Г., Кушлинский Н.Е., Липкий В.М., Трапезников Н.Н. Факты и перспективы изучения Fas-FasL-системы в норме и при патологии. Успехи современной биологии. 2000; 3: 303–18.
[Abbasova S.G., Kushlinskii N.E., Lipkii V.M., Trapeznikov N.N. Fakty i perspektivy izucheniia Fas-FasL-sistemy v norme i pri patologii. Uspekhi sovremennoi biologii. 2000; 3: 303–18 (in Russian).]
34. Фильченков А.А., Стойка Р.С. Апоптоз и рак. Киев: Морион, 1999.
[Fil'chenkov A.A., Stoika R.S. Apoptoz i rak. Kiev: Morion, 1999 (in Russian).]
35. Коган Е.А., Швец С.И., Коваленко В.Л. и др. Соотношение процессов пролиферации, апоптоза, ангиогенеза и метастазирования в различных гистогенетических типах рака легкого (иммуногистохимическое исследование). Архив патологии. 2004; 66 (6): 33–9.
[Kogan E.A., Shvets S.I., Kovalenko V.L. et al. Sootnoshenie protsessov proliferatsii, apoptoza, angiogeneza i metastazirovaniia v razlichnykh gistogeneticheskikh tipakh raka legkogo (immunogistokhimicheskoe issledovanie). Arkhiv patologii. 2004; 66 (6): 33–9 (in Russian).]
36. Mori S, Ogata Y, Shirouzu K. Biological features of sporadic colorectal carcinoma with high-frequency microsatellite instability: special reference to tumor proliferation and apoptosis. Int J Clin Oncol 2004; 9 (4): 322–9.
37. Коган Е.А., Угpюмов Д.А. Соотношение процессов пролиферации и клеточной гибели в немелкоклеточном раке легкого с железистой дифференцировкой на разных стадиях опухолевой прогрессии. Архив патологии. 2002; 64 (1): 33–7.
[Kogan E.A., Ugpiumov D.A. Sootnoshenie protsessov proliferatsii i kletochnoi gibeli v nemelkokletochnom rake legkogo s zhelezistoi differentsirovkoi na raznykh stadiiakh opukholevoi progressii. Arkhiv patologii. 2002; 64 (1): 33–7 (in Russian).]
38. Noguchi T, Kikuchi R, Ono K et al. Prognostic significance of p27/kip1 and apoptosis in patients with colorectal carcinoma. Oncol Rep 2003; 10 (4): 827–31.
39. Zhao HF. Prognostic significance of bcl-2 and p53 expression in colorectal carcinoma. J Zhejiang Univ Sci B 2005; 6 (12): 1163–9.
40. Hajra KM, Liu JR. Apoptosome dysfunction in human cancer. Apoptosis 2006; 95 (12): 1611–25.
41. Wei MC, Zong WX, Cheng EH et al. Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science 2002; 38 (2): 169–76.
42. Cory S, Adams JM. The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer 2002; 2: 647–56.
43. Kuwana T, Mackey MR, Perkins G et al. Bid, Bax, and lipids cooperate to form supramolecular openings in the outer mitochondrial membrane. Cell 2002; 111: 331–42.
44. Oltvai ZN, Milliman CL, Korsmeyer SJ. Bcl-2 heterodimers in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 1993; 74: 609–19.
45. Rampino N, Yamamoto H, Ionov Y et al. Somatic frameshift mutations in the BAX gene in colon cancers of the microsatellite mutator phenotype. Science 1997; 275: 967–9.
46. Zhang L, Yu J, Park BH et al. Role of BAX in the apoptotic response to anticancer agents. Science 2000; 290: 989–92.
47. Green DR. Apoptotic pathways: paper wraps stone blunts scissors. Cell 2000; 102: 1–4.
48. Loeffler M, Kroemer G. The mitochondrion in cell death control: certainties and incognita. Exp Cell Res 2000; 256: 19–26.
49. Van Loo G, Schotte P, Van Gurp M et al. Endonuclease G: a mitochondrial protein released in apoptosis and involved in caspase independent DNA degradation. Cell Death Differ 2001; 8: 1136–42.
50. Li P, Nijhawan D, Budihardjo I et al. Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 1997; 91: 479–89.
51. Rodriguez J, Lazebnik Y. Caspase-9 and APAF-1 form an active holoenzyme. Genes Dev 1999; 13: 3179–84.
52. Skulachev VP. Cytochrome c in the apoptotic and antioxidant cascades. FEBS Lett 1998; 423: 275–80.
53. Green DR, Amarante-Mendes GP. The point of no return: mitochondria, caspases, and the commitment to cell death. Results Probl Cell Differ 1998; 24: 45–61.
54. Bouillet P, Straser A. BH3-only proteins – evolutionarily conserved pro-apoptotic Bcl-2 family members essential for initiating programmed cell death. J Cell Sci 2002; 115: 1567–74.
55. Leahy DT, Mulcahy HE, O'Donoghue DP et al. Bcl-2 protein expression is associated with better prognosis in colorectal cancer. Histopathology 1999; 35 (4): 360–7.
56. Заботина Т.Н., Казаков С.П., Кушлинский Н.Б. Роль тканевых маркеров апоптоза и пролиферации в дополнительной дифференциальной диагностике папиллярного и фолликулярного рака щитовидной железы. Воен.-мед. журн. 2010; 7: 48–50.
[Zabotina T.N., Kazakov S.P., Kushlinskii N.B. Rol' tkanevykh markerov apoptoza i proliferatsii v dopolnitel'noi differentsial'noi diagnostike papilliarnogo i follikuliarnogo raka shchitovidnoi zhelezy. Voen.-med. zhurn. 2010; 7: 48–50 (in Russian).]
57. Казаков С.П. Исследование основных тканевых маркеров апоптоза и пролиферации, их диагностической эффективности при заболеваниях щитовидной железы. Воен.-мед. журн. 2010; 9: 73–7.
[Kazakov S.P. Issledovanie osnovnykh tkanevykh markerov apoptoza i proliferatsii, ikh diagnosticheskoi effektivnosti pri zabolevaniiakh shchitovidnoi zhelezy. Voen.-med. zhurn. 2010; 9: 73–7 (in Russian).]
58. Петров С.Б., Антонеева И.И. Маркеры апоптоза и пролиферации опухолевых клеток в динамике прогрессирования рака яичника. Онкология. 2008; 2: 234–7.
[Petrov S.B., Antoneeva I.I. Markery apoptoza i proliferatsii opukholevykh kletok v dinamike progressirovaniia raka iaichnika. Onkologiia. 2008; 2: 234–7 (in Russian).]
59. Selzer E, Schlagbauer-Wadl H, Okamoto I et al. Expression of Bcl-2 family members in human melanocytes, in melanoma metastases and in melanoma cell lines. Melanoma Res 1998; 8: 197–203.
60. Авдалян А.М. Патоморфологический и иммуногистохимический анализ лейомиомы и лейомиосаркомы тела матки: дифференциальная диагностика и прогноз. Автореф. дис. ... д-ра мед. наук. Новосибирск, 2013.
[Avdalian A.M. Patomorfologicheskii i immunogistokhimicheskii analiz leiomiomy i leiomiosarkomy tela matki: differentsial'naia diagnostika i prognoz. Avtoref. dis. ... d-ra med. nauk. Novosibirsk, 2013. (in Russian).]
61. Авдалян А.М., Бобров И.П., Климачев В.В. и др. Связь экспрессии рецепторов к прогестерону и эстрогену a и активность аргирофильных белков области ядрышковых организаторов в гладкомышечных опухолях тела матки. Архив патологии. 2009; 4: 50–4.
[Avdalian A.M., Bobrov I.P., Klimachev V.V. et al. Sviaz' ekspressii retseptorov k progesteronu i estrogenu a i aktivnost' argirofil'nykh belkov oblasti iadryshkovykh organizatorov v gladkomyshechnykh opukholiakh tela matki. Arkhiv patologii. 2009; 4: 50–4 (in Russian).]
62. Аничков Н.М., Чупров И.Н. Морфологические маркеры прогноза базально-клеточного рака кожи. Мед. акад. журн. 2011; 1: 3–11.
[Anichkov N.M., Chuprov I.N. Morfologicheskie markery prognoza bazal'no-kletochnogo raka kozhi. Med. akad. zhurn. 2011; 1: 3–11 (in Russian).]
63. Барышников А.Ю., Кузнецов В.В., Степанова Е.В. и др. Экспрессия маркеров апоптоза (р53, bcl-2, вах) и их прогностическое значение при эпителиальных новообразованиях яичников ранних стадий. Рос. биотерапевтич. журн. 2011; 2: 45–9.
[Baryshnikov A.Iu., Kuznetsov V.V., Stepanova E.V. et al. Ekspressiia markerov apoptoza (r53, bcl-2, vakh) i ikh prognosticheskoe znachenie pri epitelial'nykh novoobrazovaniiakh iaichnikov rannikh stadii. Ros. bioterapevtich. zhurn. 2011; 2: 45–9 (in Russian).]
64. Buglioni S, D'Agnano I, Cosimelli M et al. Evaluation of multiple bio-pathological factors in colorectal adenocarcinomas: independent prognostic role of p53 and bcl-2. Int J Cancer 1999; 84 (6): 545–52.
65. Meterissian SH, Kontogiannea M, Al-Sowaidi M et al. Bcl-2 is a useful prognostic marker in dukes’ B colon cancer. Ann Surg Oncol 2001; 8 (6): 533–7.
66. Zavrides H, Zizi-Sermpetzoglou A, Elemenoglou I et al. Immunohistochemical expression of bcl-2 in Dukes' stage B and C colorectal carcinoma patients: correlation with p53 and ki-67 and in evaluating prognostic significance. Pol J Pathol 2005; 56 (4): 179–85.
67. Zavrides HN, Zizi-Sermpetzoglou A, Panousopoulos D et al. Prognostic evaluation of CD44 expression in correlation with bcl-2 and p53 in colorectal cancer. Folia Histochem Cytobiol 2005; 43 (1): 31–6.
68. Zavrides H, Zizi-Sermpetzoglou A, Elemenoglou I et al. Immunohistochemical expression of bcl-2 in UICC stage I and III colorectal carcinoma patients: correlation with c-erbB-2, p53, ki-67, CD44, laminin and collagen IV in evaluating prognostic significance. Pol J Pathol 2006; 57 (3): 149–59.
69. Ilyas M, Hao X-P, Wilkinson K et al. Loss of Bcl-2 expression correlates with tumor recurrence in colorectal cancer. Gut 1998; 43: 383–7.
70. Bukholm IK, Nesland JM. Protein expression of p53, p21 (WAF1/CIP1), bcl-2, Bax, cyclin D1 and pRb in human colon carcinomas. Virchows Arch 2000; 436 (3): 224–8.
71. Rosati G, Chiacchio R, Reggiardo G et al. Thymidylate synthase expression, p53, bcl-2, Ki-67 and p27 in colorectal cancer: relationships with tumor recurrence and survival. Tumour Biol 2004; 25 (5–6): 258–63.
72. Tollenaar RA, van Krieken JH, van Slooten HJ et al. Immunohistochemical detection of p53 and Bcl-2 in colorectal carcinoma: no evidence for prognostic significance. Br J Cancer 1998; 77 (11): 1842–7.
73. Watson NF et al. Evidence that the p53 negative/bcl-2 positive phenotype is an independent indicator of good prognosis in colorectal cancer: a tissue microarray study of 460 patients. World J Surg Oncol 2005; 3 (47): 635–43.
74. Kim NK, Park JK, Lee KY et al. P53, Bcl-2, and Ki 67 expression according to tumor response after concurrent chemoradiotherapy for advanced rectal cancer. Ann Surg Oncol 2001; 8 (5): 418–24.
75. Кушлинский Н.Е., Ориновский М.Б., Гуревич Л.Е. и др. Экспрессия молекулярно-биологических маркеров (Ki-67, PCNA, Вcl-2, BАХ, BclX, VEGF) в опухолях молочной железы. Бюл. экспериментальной биологии и медицины. 2004; 137 (2): 206–10.
[Kushlinskii N.E., Orinovskii M.B., Gurevich L.E. et al. Ekspressiia molekuliarno-biologicheskikh markerov (Ki-67, PCNA, Vcl-2, BAKh, BclX, VEGF) v opukholiakh molochnoi zhelezy. Biul. eksperimental'noi biologii i meditsiny. 2004; 137 (2): 206–10 (in Russian).]
76. Elzagheid A, Kuopio T, Pyrhonen S et al. Lymph node status as a guide to selection of available prognostic markers in breast cancer: the clinical practice of the future? Diagn Pathol 2006; 8 (1): 41.
77. Haitel A, Posch B, El-Baz M et al. Bilharzial related, organ confined, muscle invasive bladder cancer: prognostic value of apoptosis markers, proliferation markers, p53, E-cadherin, epidermal growth factor receptor and c-erbB-2. J Urol 2001; 165 (5): 1481–7.
78. Ioachim EE, Malamou-Mitsi V, Kamina SA et al. Immunohistochemical expression of Bcl-2 protein in breast lesions: correlation with Bax, p53, Rb, C-erbB-2, EGFR and proliferation indices. Anticancer Res 2000; 20 (6B): 4221–5.
79. Magistrelli P, Coppola R, Tonini G et al. Apoptotic index or a combination of Bax/Bcl-2 expression correlate with survival after resection of pancreatic adenocarcinoma. J Cell Biochem 2006; 97 (1): 98–108.
80. Paik KH, Park YH, Ryoo BY et al. Prognostic value of immunohistochemical staining of p53, bcl-2, and Ki-67 in small cell lung cancer. J Korean Med Sci 2006; 21 (1): 35–9.
81. Santini D, Tonini G, Vecchio FM et al. Prognostic value of Bax, Bcl-2, p53, and TUNEL staining in patients with radically resected ampullary carcinoma. J Clin Pathol 2005; 58 (2): 159–65.
82. Wolf HK, Stober C, Hohenfellner R, Leissner J. Prognostic value of p53, p21/WAF1, Bcl-2, Bax, Bak and Ki-67 immunoreactivity in pT1 G3 urothelial bladder carcinomas. Tumour Biol 2001; 22 (5): 328–33.
83. Berney CR, Downing SR, Yang JL et al. Evidence for post-transcriptional down-regulation of the apoptosis-related gene bcl-2 in human colorectal cancer. J Pathol 2000; 191: 15–20.
84. Hwang TS, Han HS, Choi HK et al. Differential, stagedependent expression of Hsp70, Hsp110 and Bcl-2 in colorectal cancer. J Gastroenterol Hepatol 2003; 18: 690–700.
85. Mao JD, Wu P, Xia XH et al. Correlation between expression of gastrin, somatostatin and cell apoptosis regulation gene bcl-2/bax in large intestine carcinoma. World J Gastroenterol 2005; 11 (5): 721–5.
86. Paul-Samojedny M, Kokocinska D, Samojedny A et al. Expression of cell survival/death genes: Bcl-2 and Bax at the rate of colon cancer prognosis. Biochim Biophys Acta 2005; 1741 (1–2): 25–9.
2. Kopnin B.P. Misheni deistviia onkogenov i opukholevykh supressorov: kliuch k ponimaniiu bazovykh mekhanizmov kantserogeneza (obzor). Biokhimiia. 2000; 65: 5–33 (in Russian).
3. Kopnin B.P. Molekuliarno-geneticheskie izmeneniia v zlokachestvennykh kletkakh. Pod red. D.G.Zaridze. Kantserogenez. Moscow, 2000; s. 79–90. (in Russian).
4. Fearnhead NS, Wilding JL, Bodmer WF. Genetics of colorectal cancer: hereditary aspects and overview of colorectal tumorigenesis. Brit Med Bull 2002; 64: 27–43.
5. Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell 1990; 6: 759–67.
6. Vogelstein B, Fearon ER, Hamilton SR et al. Genetic alterations during colorectal tumor development. N Engl J Med 1988; 319 (9): 525–32.
7. Ahmed FE. Development of novel diagnostic and prognostic molecular markers for sporadic colon cancer. Exp Rev Mol Diagnos 2005; 5: 337–52.
8. Ahmed FE. Molecular markers that predict response to colon cancer therapy. Exp Rev Mol Diagnos 2005; 5 (3): 353–75.
9. Arnold CN, Blum HE. Colon cancer: molecular markers. Dtsch Med Wochenschr 2005; 130 (14): 880–2.
10. Bianco AR, Carlomagno C, De Laurentiis M et al. Prognostic factors in human colorectal cancer. Tumori 1997; 83 (1. Supp. 1): S15–18.
11. Houlston RS. What we could do now: molecular pathology of colorectal cancer. Mol Pathol 2001; 54: 206–14.
12. Bendardaf R, Lamlum H, Pyrhonen S. Prognostic and predictive molecular markers in colorectal carcinoma. Anticancer Res 2004; 24 (4): 2519–30.
13. Rukovodstvo po immunogistokhimicheskoi diagnostike opukholei. Pod red. S.V.Petrova, N.T.Raikhlina. Kazan, 2004 (in Russian).
14. Imianitov E.N., Khanson K.P. Molekuliarnaia onkologiia: klinicheskie aspekty. Saint Petersburg: SPbMAPO, 2007. (in Russian).
15. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000; 100: 57–70.
16. Gasparini G, Pozza F, Harris AL. Evaluating the potential usefulness of new prognostic and predictive indicators in node negative breast cancer patients. J Natl Cancer Inst 1993; 85: 1206–19.
17. Aldrighetti L, Castoldi R, Di Palo S et al. Prognostic factors for long-term outcome of hepatic resection for colorectal liver metastases. Chir Ital 2005; 57 (5): 555–70.
18. Ambiru S, Miyazaki M, Isono T et al. Hepatic resection for colorectal metastases: analysis of prognostic factors. Dis Colon Rectum 1999; 42 (5): 632–9.
19. Neal CP, Garcea G, Doucas H. Molecular prognostic markers in resectable colorectal liver metastases: a systematic review. Eur J Cancer 2006; 42 (12): 1728–43.
20. Yamada H, Kondo S, Okushiba S et al. Analysis of predictive factors for recurrence after hepatectomy for colorectal liver metastases. World J Surg 2001; 25 (9): 1129–33.
21. Pozharisskii K.M., Leenman E.E. Znachenie immunogistokhimicheskikh metodik dlia opredeleniia kharaktera lecheniia i prognoza opukholevykh zabolevanii. Arkhiv patologii. 2000; 62 (5): 3–11 (in Russian).
22. Bendardaf R, Lamlum H, Ristamaki R. CD44 variant 6 expression predicts response to treatment in advanced colorectal cancer. Oncol Rep 2004; 11 (1): 41–5.
23. Cascinu S, Georgoulias V, Kerr D et al. Colorectal cancer in the adjuvant setting: perspectives on treatment and the role of prognostic factors. Ann Oncol 2003; 14: 25–9.
24. Graziano F, Cascinu S. Prognostic molecular markers for planning adjuvant chemotherapy trials in Dukes" B colorectal cancer patients: how much evidence is enough? Ann Oncol 2003; 14: 1026–38.
25. Nemtsova M.V., Pal'tseva E.M., Babaian A.Iu. et al. Molekuliarno-geneticheskii analiz klonal'noi vnutriopukholevoi geterogennosti v kolorektal'nykh kartsinomakh. Molekuliarnaia biologiia. 2008; 42 (6): 1040–7 (in Russian).
26. Chu E. A Multidisciplinary Approach to the Treatment of Early Colorectal Cancer. Ed. by E.Chu. International Cancer Management: A Multidisciplinary Approach. Yale Cancer Center Yale University School of Medicine 2007; 63: 70–1.
27. Perez RO. Predicting response to neoadjuvant treatment for rectal cancer: a step toward individualized medicine. Dis Colon Rectum 2011; 54 (9): 1057–8.
28. Sulzyc-Bielicka V, Domagala P, Majdanik E et al. Nuclear thymidylate synthase expression in sporadic colorectal cancer depends on the site of the tumor. Virchows Arch 2009; 454 (6): 695–702.
29. Darenskaia A.D. Pervaia liniia lekarstvennoi terapii metastaticheskogo kolorektal'nogo raka. Novyi rezhim lecheniia. Prognosticheskaia znachimost' molekuliarno-biologicheskikh markerov. Avtoref. dis. ... kand. med. nauk. Moscow, 2017 (in Russian).
30. Delektorskaia V.V. Molekuliarno-biologicheskie markery metastazirovaniia i prognoza pri rake tolstoi kishki. Avtoref. dis. … d-ra med. nauk. Moscow, 2007 (in Russian).
31. Lushnikov E.F., Abrosimov A.Iu. Gibel' kletki (apoptoz). Moscow: Meditsina, 2001 (in Russian).
32. Klinicheskaia biokhimiia: uchebnoe posobie. Pod red. V.A.Tkachuka. 3-e izd. Moscow: GEOTAR-Media, 2008 (in Russian).
33. Abbasova S.G., Kushlinskii N.E., Lipkii V.M., Trapeznikov N.N. Fakty i perspektivy izucheniia Fas-FasL-sistemy v norme i pri patologii. Uspekhi sovremennoi biologii. 2000; 3: 303–18 (in Russian).
34. Fil'chenkov A.A., Stoika R.S. Apoptoz i rak. Kiev: Morion, 1999 (in Russian).
35. Kogan E.A., Shvets S.I., Kovalenko V.L. et al. Sootnoshenie protsessov proliferatsii, apoptoza, angiogeneza i metastazirovaniia v razlichnykh gistogeneticheskikh tipakh raka legkogo (immunogistokhimicheskoe issledovanie). Arkhiv patologii. 2004; 66 (6): 33–9 (in Russian).
36. Mori S, Ogata Y, Shirouzu K. Biological features of sporadic colorectal carcinoma with high-frequency microsatellite instability: special reference to tumor proliferation and apoptosis. Int J Clin Oncol 2004; 9 (4): 322–9.
37. Kogan E.A., Ugpiumov D.A. Sootnoshenie protsessov proliferatsii i kletochnoi gibeli v nemelkokletochnom rake legkogo s zhelezistoi differentsirovkoi na raznykh stadiiakh opukholevoi progressii. Arkhiv patologii. 2002; 64 (1): 33–7 (in Russian).
38. Noguchi T, Kikuchi R, Ono K et al. Prognostic significance of p27/kip1 and apoptosis in patients with colorectal carcinoma. Oncol Rep 2003; 10 (4): 827–31.
39. Zhao HF. Prognostic significance of bcl-2 and p53 expression in colorectal carcinoma. J Zhejiang Univ Sci B 2005; 6 (12): 1163–9.
40. Hajra KM, Liu JR. Apoptosome dysfunction in human cancer. Apoptosis 2006; 95 (12): 1611–25.
41. Wei MC, Zong WX, Cheng EH et al. Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science 2002; 38 (2): 169–76.
42. Cory S, Adams JM. The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer 2002; 2: 647–56.
43. Kuwana T, Mackey MR, Perkins G et al. Bid, Bax, and lipids cooperate to form supramolecular openings in the outer mitochondrial membrane. Cell 2002; 111: 331–42.
44. Oltvai ZN, Milliman CL, Korsmeyer SJ. Bcl-2 heterodimers in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 1993; 74: 609–19.
45. Rampino N, Yamamoto H, Ionov Y et al. Somatic frameshift mutations in the BAX gene in colon cancers of the microsatellite mutator phenotype. Science 1997; 275: 967–9.
46. Zhang L, Yu J, Park BH et al. Role of BAX in the apoptotic response to anticancer agents. Science 2000; 290: 989–92.
47. Green DR. Apoptotic pathways: paper wraps stone blunts scissors. Cell 2000; 102: 1–4.
48. Loeffler M, Kroemer G. The mitochondrion in cell death control: certainties and incognita. Exp Cell Res 2000; 256: 19–26.
49. Van Loo G, Schotte P, Van Gurp M et al. Endonuclease G: a mitochondrial protein released in apoptosis and involved in caspase independent DNA degradation. Cell Death Differ 2001; 8: 1136–42.
50. Li P, Nijhawan D, Budihardjo I et al. Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 1997; 91: 479–89.
51. Rodriguez J, Lazebnik Y. Caspase-9 and APAF-1 form an active holoenzyme. Genes Dev 1999; 13: 3179–84.
52. Skulachev VP. Cytochrome c in the apoptotic and antioxidant cascades. FEBS Lett 1998; 423: 275–80.
53. Green DR, Amarante-Mendes GP. The point of no return: mitochondria, caspases, and the commitment to cell death. Results Probl Cell Differ 1998; 24: 45–61.
54. Bouillet P, Straser A. BH3-only proteins – evolutionarily conserved pro-apoptotic Bcl-2 family members essential for initiating programmed cell death. J Cell Sci 2002; 115: 1567–74.
55. Leahy DT, Mulcahy HE, O'Donoghue DP et al. Bcl-2 protein expression is associated with better prognosis in colorectal cancer. Histopathology 1999; 35 (4): 360–7.
56. Zabotina T.N., Kazakov S.P., Kushlinskii N.B. Rol' tkanevykh markerov apoptoza i proliferatsii v dopolnitel'noi differentsial'noi diagnostike papilliarnogo i follikuliarnogo raka shchitovidnoi zhelezy. Voen.-med. zhurn. 2010; 7: 48–50 (in Russian).
57. Kazakov S.P. Issledovanie osnovnykh tkanevykh markerov apoptoza i proliferatsii, ikh diagnosticheskoi effektivnosti pri zabolevaniiakh shchitovidnoi zhelezy. Voen.-med. zhurn. 2010; 9: 73–7 (in Russian).
58. Petrov S.B., Antoneeva I.I. Markery apoptoza i proliferatsii opukholevykh kletok v dinamike progressirovaniia raka iaichnika. Onkologiia. 2008; 2: 234–7 (in Russian).
59. Selzer E, Schlagbauer-Wadl H, Okamoto I et al. Expression of Bcl-2 family members in human melanocytes, in melanoma metastases and in melanoma cell lines. Melanoma Res 1998; 8: 197–203.
60. Avdalian A.M. Patomorfologicheskii i immunogistokhimicheskii analiz leiomiomy i leiomiosarkomy tela matki: differentsial'naia diagnostika i prognoz. Avtoref. dis. ... d-ra med. nauk. Novosibirsk, 2013. (in Russian).
61. Avdalian A.M., Bobrov I.P., Klimachev V.V. et al. Sviaz' ekspressii retseptorov k progesteronu i estrogenu a i aktivnost' argirofil'nykh belkov oblasti iadryshkovykh organizatorov v gladkomyshechnykh opukholiakh tela matki. Arkhiv patologii. 2009; 4: 50–4 (in Russian).
62. Anichkov N.M., Chuprov I.N. Morfologicheskie markery prognoza bazal'no-kletochnogo raka kozhi. Med. akad. zhurn. 2011; 1: 3–11 (in Russian).
63. Baryshnikov A.Iu., Kuznetsov V.V., Stepanova E.V. et al. Ekspressiia markerov apoptoza (r53, bcl-2, vakh) i ikh prognosticheskoe znachenie pri epitelial'nykh novoobrazovaniiakh iaichnikov rannikh stadii. Ros. bioterapevtich. zhurn. 2011; 2: 45–9 (in Russian).
64. Buglioni S, D'Agnano I, Cosimelli M et al. Evaluation of multiple bio-pathological factors in colorectal adenocarcinomas: independent prognostic role of p53 and bcl-2. Int J Cancer 1999; 84 (6): 545–52.
65. Meterissian SH, Kontogiannea M, Al-Sowaidi M et al. Bcl-2 is a useful prognostic marker in dukes’ B colon cancer. Ann Surg Oncol 2001; 8 (6): 533–7.
66. Zavrides H, Zizi-Sermpetzoglou A, Elemenoglou I et al. Immunohistochemical expression of bcl-2 in Dukes' stage B and C colorectal carcinoma patients: correlation with p53 and ki-67 and in evaluating prognostic significance. Pol J Pathol 2005; 56 (4): 179–85.
67. Zavrides HN, Zizi-Sermpetzoglou A, Panousopoulos D et al. Prognostic evaluation of CD44 expression in correlation with bcl-2 and p53 in colorectal cancer. Folia Histochem Cytobiol 2005; 43 (1): 31–6.
68. Zavrides H, Zizi-Sermpetzoglou A, Elemenoglou I et al. Immunohistochemical expression of bcl-2 in UICC stage I and III colorectal carcinoma patients: correlation with c-erbB-2, p53, ki-67, CD44, laminin and collagen IV in evaluating prognostic significance. Pol J Pathol 2006; 57 (3): 149–59.
69. Ilyas M, Hao X-P, Wilkinson K et al. Loss of Bcl-2 expression correlates with tumor recurrence in colorectal cancer. Gut 1998; 43: 383–7.
70. Bukholm IK, Nesland JM. Protein expression of p53, p21 (WAF1/CIP1), bcl-2, Bax, cyclin D1 and pRb in human colon carcinomas. Virchows Arch 2000; 436 (3): 224–8.
71. Rosati G, Chiacchio R, Reggiardo G et al. Thymidylate synthase expression, p53, bcl-2, Ki-67 and p27 in colorectal cancer: relationships with tumor recurrence and survival. Tumour Biol 2004; 25 (5–6): 258–63.
72. Tollenaar RA, van Krieken JH, van Slooten HJ et al. Immunohistochemical detection of p53 and Bcl-2 in colorectal carcinoma: no evidence for prognostic significance. Br J Cancer 1998; 77 (11): 1842–7.
73. Watson NF et al. Evidence that the p53 negative/bcl-2 positive phenotype is an independent indicator of good prognosis in colorectal cancer: a tissue microarray study of 460 patients. World J Surg Oncol 2005; 3 (47): 635–43.
74. Kim NK, Park JK, Lee KY et al. P53, Bcl-2, and Ki 67 expression according to tumor response after concurrent chemoradiotherapy for advanced rectal cancer. Ann Surg Oncol 2001; 8 (5): 418–24.
75. Kushlinskii N.E., Orinovskii M.B., Gurevich L.E. et al. Ekspressiia molekuliarno-biologicheskikh markerov (Ki-67, PCNA, Vcl-2, BAKh, BclX, VEGF) v opukholiakh molochnoi zhelezy. Biul. eksperimental'noi biologii i meditsiny. 2004; 137 (2): 206–10 (in Russian).
76. Elzagheid A, Kuopio T, Pyrhonen S et al. Lymph node status as a guide to selection of available prognostic markers in breast cancer: the clinical practice of the future? Diagn Pathol 2006; 8 (1): 41.
77. Haitel A, Posch B, El-Baz M et al. Bilharzial related, organ confined, muscle invasive bladder cancer: prognostic value of apoptosis markers, proliferation markers, p53, E-cadherin, epidermal growth factor receptor and c-erbB-2. J Urol 2001; 165 (5): 1481–7.
78. Ioachim EE, Malamou-Mitsi V, Kamina SA et al. Immunohistochemical expression of Bcl-2 protein in breast lesions: correlation with Bax, p53, Rb, C-erbB-2, EGFR and proliferation indices. Anticancer Res 2000; 20 (6B): 4221–5.
79. Magistrelli P, Coppola R, Tonini G et al. Apoptotic index or a combination of Bax/Bcl-2 expression correlate with survival after resection of pancreatic adenocarcinoma. J Cell Biochem 2006; 97 (1): 98–108.
80. Paik KH, Park YH, Ryoo BY et al. Prognostic value of immunohistochemical staining of p53, bcl-2, and Ki-67 in small cell lung cancer. J Korean Med Sci 2006; 21 (1): 35–9.
81. Santini D, Tonini G, Vecchio FM et al. Prognostic value of Bax, Bcl-2, p53, and TUNEL staining in patients with radically resected ampullary carcinoma. J Clin Pathol 2005; 58 (2): 159–65.
82. Wolf HK, Stober C, Hohenfellner R, Leissner J. Prognostic value of p53, p21/WAF1, Bcl-2, Bax, Bak and Ki-67 immunoreactivity in pT1 G3 urothelial bladder carcinomas. Tumour Biol 2001; 22 (5): 328–33.
83. Berney CR, Downing SR, Yang JL et al. Evidence for post-transcriptional down-regulation of the apoptosis-related gene bcl-2 in human colorectal cancer. J Pathol 2000; 191: 15–20.
84. Hwang TS, Han HS, Choi HK et al. Differential, stagedependent expression of Hsp70, Hsp110 and Bcl-2 in colorectal cancer. J Gastroenterol Hepatol 2003; 18: 690–700.
85. Mao JD, Wu P, Xia XH et al. Correlation between expression of gastrin, somatostatin and cell apoptosis regulation gene bcl-2/bax in large intestine carcinoma. World J Gastroenterol 2005; 11 (5): 721–5.
86. Paul-Samojedny M, Kokocinska D, Samojedny A et al. Expression of cell survival/death genes: Bcl-2 and Bax at the rate of colon cancer prognosis. Biochim Biophys Acta 2005; 1741 (1–2): 25–9.
[Stepanova E.V. Klinicheskie i eksperimental'nye aspekty izucheniia molekuliarno-biologicheskikh markerov pri zlokachestvennykh novoobrazovaniiakh. Avtoref. dis. … d-ra med. nauk. Moscow, 2008 (in Russian).]
2. Копнин Б.П. Мишени действия онкогенов и опухолевых супрессоров: ключ к пониманию базовых механизмов канцерогенеза (обзор). Биохимия. 2000; 65: 5–33.
[Kopnin B.P. Misheni deistviia onkogenov i opukholevykh supressorov: kliuch k ponimaniiu bazovykh mekhanizmov kantserogeneza (obzor). Biokhimiia. 2000; 65: 5–33 (in Russian).]
3. Копнин Б.П. Молекулярно-генетические изменения в злокачественных клетках. Под ред. Д.Г.Заридзе. Канцерогенез. М., 2000; с. 79–90.
[Kopnin B.P. Molekuliarno-geneticheskie izmeneniia v zlokachestvennykh kletkakh. Pod red. D.G.Zaridze. Kantserogenez. Moscow, 2000; s. 79–90. (in Russian).]
4. Fearnhead NS, Wilding JL, Bodmer WF. Genetics of colorectal cancer: hereditary aspects and overview of colorectal tumorigenesis. Brit Med Bull 2002; 64: 27–43.
5. Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell 1990; 6: 759–67.
6. Vogelstein B, Fearon ER, Hamilton SR et al. Genetic alterations during colorectal tumor development. N Engl J Med 1988; 319 (9): 525–32.
7. Ahmed FE. Development of novel diagnostic and prognostic molecular markers for sporadic colon cancer. Exp Rev Mol Diagnos 2005; 5: 337–52.
8. Ahmed FE. Molecular markers that predict response to colon cancer therapy. Exp Rev Mol Diagnos 2005; 5 (3): 353–75.
9. Arnold CN, Blum HE. Colon cancer: molecular markers. Dtsch Med Wochenschr 2005; 130 (14): 880–2.
10. Bianco AR, Carlomagno C, De Laurentiis M et al. Prognostic factors in human colorectal cancer. Tumori 1997; 83 (1. Supp. 1): S15–18.
11. Houlston RS. What we could do now: molecular pathology of colorectal cancer. Mol Pathol 2001; 54: 206–14.
12. Bendardaf R, Lamlum H, Pyrhonen S. Prognostic and predictive molecular markers in colorectal carcinoma. Anticancer Res 2004; 24 (4): 2519–30.
13. Руководство по иммуногистохимической диагностике опухолей. Под ред. С.В.Петрова, Н.Т.Райхлина. Казань, 2004.
[Rukovodstvo po immunogistokhimicheskoi diagnostike opukholei. Pod red. S.V.Petrova, N.T.Raikhlina. Kazan, 2004 (in Russian).]
14. Имянитов Е.Н., Хансон К.П. Молекулярная онкология: клинические аспекты. СПб.: СПбМАПО, 2007.
[Imianitov E.N., Khanson K.P. Molekuliarnaia onkologiia: klinicheskie aspekty. Saint Petersburg: SPbMAPO, 2007. (in Russian).]
15. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000; 100: 57–70.
16. Gasparini G, Pozza F, Harris AL. Evaluating the potential usefulness of new prognostic and predictive indicators in node negative breast cancer patients. J Natl Cancer Inst 1993; 85: 1206–19.
17. Aldrighetti L, Castoldi R, Di Palo S et al. Prognostic factors for long-term outcome of hepatic resection for colorectal liver metastases. Chir Ital 2005; 57 (5): 555–70.
18. Ambiru S, Miyazaki M, Isono T et al. Hepatic resection for colorectal metastases: analysis of prognostic factors. Dis Colon Rectum 1999; 42 (5): 632–9.
19. Neal CP, Garcea G, Doucas H. Molecular prognostic markers in resectable colorectal liver metastases: a systematic review. Eur J Cancer 2006; 42 (12): 1728–43.
20. Yamada H, Kondo S, Okushiba S et al. Analysis of predictive factors for recurrence after hepatectomy for colorectal liver metastases. World J Surg 2001; 25 (9): 1129–33.
21. Пожарисский К.М., Леенман Е.Е. Значение иммуногистохимических методик для определения характера лечения и прогноза опухолевых заболеваний. Архив патологии. 2000; 62 (5): 3–11.
[Pozharisskii K.M., Leenman E.E. Znachenie immunogistokhimicheskikh metodik dlia opredeleniia kharaktera lecheniia i prognoza opukholevykh zabolevanii. Arkhiv patologii. 2000; 62 (5): 3–11 (in Russian).]
22. Bendardaf R, Lamlum H, Ristamaki R. CD44 variant 6 expression predicts response to treatment in advanced colorectal cancer. Oncol Rep 2004; 11 (1): 41–5.
23. Cascinu S, Georgoulias V, Kerr D et al. Colorectal cancer in the adjuvant setting: perspectives on treatment and the role of prognostic factors. Ann Oncol 2003; 14: 25–9.
24. Graziano F, Cascinu S. Prognostic molecular markers for planning adjuvant chemotherapy trials in Dukes" B colorectal cancer patients: how much evidence is enough? Ann Oncol 2003; 14: 1026–38.
25. Немцова М.В., Пальцева Е.М., Бабаян А.Ю. и др. Молекулярно-генетический анализ клональной внутриопухолевой гетерогенности в колоректальных карциномах. Молекулярная биология. 2008; 42 (6): 1040–7.
[Nemtsova M.V., Pal'tseva E.M., Babaian A.Iu. et al. Molekuliarno-geneticheskii analiz klonal'noi vnutriopukholevoi geterogennosti v kolorektal'nykh kartsinomakh. Molekuliarnaia biologiia. 2008; 42 (6): 1040–7 (in Russian).]
26. Chu E. A Multidisciplinary Approach to the Treatment of Early Colorectal Cancer. Ed. by E.Chu. International Cancer Management: A Multidisciplinary Approach. Yale Cancer Center Yale University School of Medicine 2007; 63: 70–1.
27. Perez RO. Predicting response to neoadjuvant treatment for rectal cancer: a step toward individualized medicine. Dis Colon Rectum 2011; 54 (9): 1057–8.
28. Sulzyc-Bielicka V, Domagala P, Majdanik E et al. Nuclear thymidylate synthase expression in sporadic colorectal cancer depends on the site of the tumor. Virchows Arch 2009; 454 (6): 695–702.
29. Даренская А.Д. Первая линия лекарственной терапии метастатического колоректального рака. Новый режим лечения. Прогностическая значимость молекулярно-биологических маркеров. Автореф. дис. ... канд. мед. наук. М., 2017.
[Darenskaia A.D. Pervaia liniia lekarstvennoi terapii metastaticheskogo kolorektal'nogo raka. Novyi rezhim lecheniia. Prognosticheskaia znachimost' molekuliarno-biologicheskikh markerov. Avtoref. dis. ... kand. med. nauk. Moscow, 2017 (in Russian).]
30. Делекторская В.В. Молекулярно-биологические маркеры метастазирования и прогноза при раке толстой кишки. Автореф. дис. … д-ра мед. наук. М., 2007.
[Delektorskaia V.V. Molekuliarno-biologicheskie markery metastazirovaniia i prognoza pri rake tolstoi kishki. Avtoref. dis. … d-ra med. nauk. Moscow, 2007 (in Russian).]
31. Лушников Е.Ф., Абросимов А.Ю. Гибель клетки (апоптоз). М.: Медицина, 2001.
[Lushnikov E.F., Abrosimov A.Iu. Gibel' kletki (apoptoz). Moscow: Meditsina, 2001 (in Russian).]
32. Клиническая биохимия: учебное пособие. Под ред. В.А.Ткачука. 3-е изд. М.: ГЭОТАР-Медиа, 2008.
[Klinicheskaia biokhimiia: uchebnoe posobie. Pod red. V.A.Tkachuka. 3-e izd. Moscow: GEOTAR-Media, 2008 (in Russian).]
33. Аббасова С.Г., Кушлинский Н.Е., Липкий В.М., Трапезников Н.Н. Факты и перспективы изучения Fas-FasL-системы в норме и при патологии. Успехи современной биологии. 2000; 3: 303–18.
[Abbasova S.G., Kushlinskii N.E., Lipkii V.M., Trapeznikov N.N. Fakty i perspektivy izucheniia Fas-FasL-sistemy v norme i pri patologii. Uspekhi sovremennoi biologii. 2000; 3: 303–18 (in Russian).]
34. Фильченков А.А., Стойка Р.С. Апоптоз и рак. Киев: Морион, 1999.
[Fil'chenkov A.A., Stoika R.S. Apoptoz i rak. Kiev: Morion, 1999 (in Russian).]
35. Коган Е.А., Швец С.И., Коваленко В.Л. и др. Соотношение процессов пролиферации, апоптоза, ангиогенеза и метастазирования в различных гистогенетических типах рака легкого (иммуногистохимическое исследование). Архив патологии. 2004; 66 (6): 33–9.
[Kogan E.A., Shvets S.I., Kovalenko V.L. et al. Sootnoshenie protsessov proliferatsii, apoptoza, angiogeneza i metastazirovaniia v razlichnykh gistogeneticheskikh tipakh raka legkogo (immunogistokhimicheskoe issledovanie). Arkhiv patologii. 2004; 66 (6): 33–9 (in Russian).]
36. Mori S, Ogata Y, Shirouzu K. Biological features of sporadic colorectal carcinoma with high-frequency microsatellite instability: special reference to tumor proliferation and apoptosis. Int J Clin Oncol 2004; 9 (4): 322–9.
37. Коган Е.А., Угpюмов Д.А. Соотношение процессов пролиферации и клеточной гибели в немелкоклеточном раке легкого с железистой дифференцировкой на разных стадиях опухолевой прогрессии. Архив патологии. 2002; 64 (1): 33–7.
[Kogan E.A., Ugpiumov D.A. Sootnoshenie protsessov proliferatsii i kletochnoi gibeli v nemelkokletochnom rake legkogo s zhelezistoi differentsirovkoi na raznykh stadiiakh opukholevoi progressii. Arkhiv patologii. 2002; 64 (1): 33–7 (in Russian).]
38. Noguchi T, Kikuchi R, Ono K et al. Prognostic significance of p27/kip1 and apoptosis in patients with colorectal carcinoma. Oncol Rep 2003; 10 (4): 827–31.
39. Zhao HF. Prognostic significance of bcl-2 and p53 expression in colorectal carcinoma. J Zhejiang Univ Sci B 2005; 6 (12): 1163–9.
40. Hajra KM, Liu JR. Apoptosome dysfunction in human cancer. Apoptosis 2006; 95 (12): 1611–25.
41. Wei MC, Zong WX, Cheng EH et al. Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science 2002; 38 (2): 169–76.
42. Cory S, Adams JM. The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer 2002; 2: 647–56.
43. Kuwana T, Mackey MR, Perkins G et al. Bid, Bax, and lipids cooperate to form supramolecular openings in the outer mitochondrial membrane. Cell 2002; 111: 331–42.
44. Oltvai ZN, Milliman CL, Korsmeyer SJ. Bcl-2 heterodimers in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 1993; 74: 609–19.
45. Rampino N, Yamamoto H, Ionov Y et al. Somatic frameshift mutations in the BAX gene in colon cancers of the microsatellite mutator phenotype. Science 1997; 275: 967–9.
46. Zhang L, Yu J, Park BH et al. Role of BAX in the apoptotic response to anticancer agents. Science 2000; 290: 989–92.
47. Green DR. Apoptotic pathways: paper wraps stone blunts scissors. Cell 2000; 102: 1–4.
48. Loeffler M, Kroemer G. The mitochondrion in cell death control: certainties and incognita. Exp Cell Res 2000; 256: 19–26.
49. Van Loo G, Schotte P, Van Gurp M et al. Endonuclease G: a mitochondrial protein released in apoptosis and involved in caspase independent DNA degradation. Cell Death Differ 2001; 8: 1136–42.
50. Li P, Nijhawan D, Budihardjo I et al. Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 1997; 91: 479–89.
51. Rodriguez J, Lazebnik Y. Caspase-9 and APAF-1 form an active holoenzyme. Genes Dev 1999; 13: 3179–84.
52. Skulachev VP. Cytochrome c in the apoptotic and antioxidant cascades. FEBS Lett 1998; 423: 275–80.
53. Green DR, Amarante-Mendes GP. The point of no return: mitochondria, caspases, and the commitment to cell death. Results Probl Cell Differ 1998; 24: 45–61.
54. Bouillet P, Straser A. BH3-only proteins – evolutionarily conserved pro-apoptotic Bcl-2 family members essential for initiating programmed cell death. J Cell Sci 2002; 115: 1567–74.
55. Leahy DT, Mulcahy HE, O'Donoghue DP et al. Bcl-2 protein expression is associated with better prognosis in colorectal cancer. Histopathology 1999; 35 (4): 360–7.
56. Заботина Т.Н., Казаков С.П., Кушлинский Н.Б. Роль тканевых маркеров апоптоза и пролиферации в дополнительной дифференциальной диагностике папиллярного и фолликулярного рака щитовидной железы. Воен.-мед. журн. 2010; 7: 48–50.
[Zabotina T.N., Kazakov S.P., Kushlinskii N.B. Rol' tkanevykh markerov apoptoza i proliferatsii v dopolnitel'noi differentsial'noi diagnostike papilliarnogo i follikuliarnogo raka shchitovidnoi zhelezy. Voen.-med. zhurn. 2010; 7: 48–50 (in Russian).]
57. Казаков С.П. Исследование основных тканевых маркеров апоптоза и пролиферации, их диагностической эффективности при заболеваниях щитовидной железы. Воен.-мед. журн. 2010; 9: 73–7.
[Kazakov S.P. Issledovanie osnovnykh tkanevykh markerov apoptoza i proliferatsii, ikh diagnosticheskoi effektivnosti pri zabolevaniiakh shchitovidnoi zhelezy. Voen.-med. zhurn. 2010; 9: 73–7 (in Russian).]
58. Петров С.Б., Антонеева И.И. Маркеры апоптоза и пролиферации опухолевых клеток в динамике прогрессирования рака яичника. Онкология. 2008; 2: 234–7.
[Petrov S.B., Antoneeva I.I. Markery apoptoza i proliferatsii opukholevykh kletok v dinamike progressirovaniia raka iaichnika. Onkologiia. 2008; 2: 234–7 (in Russian).]
59. Selzer E, Schlagbauer-Wadl H, Okamoto I et al. Expression of Bcl-2 family members in human melanocytes, in melanoma metastases and in melanoma cell lines. Melanoma Res 1998; 8: 197–203.
60. Авдалян А.М. Патоморфологический и иммуногистохимический анализ лейомиомы и лейомиосаркомы тела матки: дифференциальная диагностика и прогноз. Автореф. дис. ... д-ра мед. наук. Новосибирск, 2013.
[Avdalian A.M. Patomorfologicheskii i immunogistokhimicheskii analiz leiomiomy i leiomiosarkomy tela matki: differentsial'naia diagnostika i prognoz. Avtoref. dis. ... d-ra med. nauk. Novosibirsk, 2013. (in Russian).]
61. Авдалян А.М., Бобров И.П., Климачев В.В. и др. Связь экспрессии рецепторов к прогестерону и эстрогену a и активность аргирофильных белков области ядрышковых организаторов в гладкомышечных опухолях тела матки. Архив патологии. 2009; 4: 50–4.
[Avdalian A.M., Bobrov I.P., Klimachev V.V. et al. Sviaz' ekspressii retseptorov k progesteronu i estrogenu a i aktivnost' argirofil'nykh belkov oblasti iadryshkovykh organizatorov v gladkomyshechnykh opukholiakh tela matki. Arkhiv patologii. 2009; 4: 50–4 (in Russian).]
62. Аничков Н.М., Чупров И.Н. Морфологические маркеры прогноза базально-клеточного рака кожи. Мед. акад. журн. 2011; 1: 3–11.
[Anichkov N.M., Chuprov I.N. Morfologicheskie markery prognoza bazal'no-kletochnogo raka kozhi. Med. akad. zhurn. 2011; 1: 3–11 (in Russian).]
63. Барышников А.Ю., Кузнецов В.В., Степанова Е.В. и др. Экспрессия маркеров апоптоза (р53, bcl-2, вах) и их прогностическое значение при эпителиальных новообразованиях яичников ранних стадий. Рос. биотерапевтич. журн. 2011; 2: 45–9.
[Baryshnikov A.Iu., Kuznetsov V.V., Stepanova E.V. et al. Ekspressiia markerov apoptoza (r53, bcl-2, vakh) i ikh prognosticheskoe znachenie pri epitelial'nykh novoobrazovaniiakh iaichnikov rannikh stadii. Ros. bioterapevtich. zhurn. 2011; 2: 45–9 (in Russian).]
64. Buglioni S, D'Agnano I, Cosimelli M et al. Evaluation of multiple bio-pathological factors in colorectal adenocarcinomas: independent prognostic role of p53 and bcl-2. Int J Cancer 1999; 84 (6): 545–52.
65. Meterissian SH, Kontogiannea M, Al-Sowaidi M et al. Bcl-2 is a useful prognostic marker in dukes’ B colon cancer. Ann Surg Oncol 2001; 8 (6): 533–7.
66. Zavrides H, Zizi-Sermpetzoglou A, Elemenoglou I et al. Immunohistochemical expression of bcl-2 in Dukes' stage B and C colorectal carcinoma patients: correlation with p53 and ki-67 and in evaluating prognostic significance. Pol J Pathol 2005; 56 (4): 179–85.
67. Zavrides HN, Zizi-Sermpetzoglou A, Panousopoulos D et al. Prognostic evaluation of CD44 expression in correlation with bcl-2 and p53 in colorectal cancer. Folia Histochem Cytobiol 2005; 43 (1): 31–6.
68. Zavrides H, Zizi-Sermpetzoglou A, Elemenoglou I et al. Immunohistochemical expression of bcl-2 in UICC stage I and III colorectal carcinoma patients: correlation with c-erbB-2, p53, ki-67, CD44, laminin and collagen IV in evaluating prognostic significance. Pol J Pathol 2006; 57 (3): 149–59.
69. Ilyas M, Hao X-P, Wilkinson K et al. Loss of Bcl-2 expression correlates with tumor recurrence in colorectal cancer. Gut 1998; 43: 383–7.
70. Bukholm IK, Nesland JM. Protein expression of p53, p21 (WAF1/CIP1), bcl-2, Bax, cyclin D1 and pRb in human colon carcinomas. Virchows Arch 2000; 436 (3): 224–8.
71. Rosati G, Chiacchio R, Reggiardo G et al. Thymidylate synthase expression, p53, bcl-2, Ki-67 and p27 in colorectal cancer: relationships with tumor recurrence and survival. Tumour Biol 2004; 25 (5–6): 258–63.
72. Tollenaar RA, van Krieken JH, van Slooten HJ et al. Immunohistochemical detection of p53 and Bcl-2 in colorectal carcinoma: no evidence for prognostic significance. Br J Cancer 1998; 77 (11): 1842–7.
73. Watson NF et al. Evidence that the p53 negative/bcl-2 positive phenotype is an independent indicator of good prognosis in colorectal cancer: a tissue microarray study of 460 patients. World J Surg Oncol 2005; 3 (47): 635–43.
74. Kim NK, Park JK, Lee KY et al. P53, Bcl-2, and Ki 67 expression according to tumor response after concurrent chemoradiotherapy for advanced rectal cancer. Ann Surg Oncol 2001; 8 (5): 418–24.
75. Кушлинский Н.Е., Ориновский М.Б., Гуревич Л.Е. и др. Экспрессия молекулярно-биологических маркеров (Ki-67, PCNA, Вcl-2, BАХ, BclX, VEGF) в опухолях молочной железы. Бюл. экспериментальной биологии и медицины. 2004; 137 (2): 206–10.
[Kushlinskii N.E., Orinovskii M.B., Gurevich L.E. et al. Ekspressiia molekuliarno-biologicheskikh markerov (Ki-67, PCNA, Vcl-2, BAKh, BclX, VEGF) v opukholiakh molochnoi zhelezy. Biul. eksperimental'noi biologii i meditsiny. 2004; 137 (2): 206–10 (in Russian).]
76. Elzagheid A, Kuopio T, Pyrhonen S et al. Lymph node status as a guide to selection of available prognostic markers in breast cancer: the clinical practice of the future? Diagn Pathol 2006; 8 (1): 41.
77. Haitel A, Posch B, El-Baz M et al. Bilharzial related, organ confined, muscle invasive bladder cancer: prognostic value of apoptosis markers, proliferation markers, p53, E-cadherin, epidermal growth factor receptor and c-erbB-2. J Urol 2001; 165 (5): 1481–7.
78. Ioachim EE, Malamou-Mitsi V, Kamina SA et al. Immunohistochemical expression of Bcl-2 protein in breast lesions: correlation with Bax, p53, Rb, C-erbB-2, EGFR and proliferation indices. Anticancer Res 2000; 20 (6B): 4221–5.
79. Magistrelli P, Coppola R, Tonini G et al. Apoptotic index or a combination of Bax/Bcl-2 expression correlate with survival after resection of pancreatic adenocarcinoma. J Cell Biochem 2006; 97 (1): 98–108.
80. Paik KH, Park YH, Ryoo BY et al. Prognostic value of immunohistochemical staining of p53, bcl-2, and Ki-67 in small cell lung cancer. J Korean Med Sci 2006; 21 (1): 35–9.
81. Santini D, Tonini G, Vecchio FM et al. Prognostic value of Bax, Bcl-2, p53, and TUNEL staining in patients with radically resected ampullary carcinoma. J Clin Pathol 2005; 58 (2): 159–65.
82. Wolf HK, Stober C, Hohenfellner R, Leissner J. Prognostic value of p53, p21/WAF1, Bcl-2, Bax, Bak and Ki-67 immunoreactivity in pT1 G3 urothelial bladder carcinomas. Tumour Biol 2001; 22 (5): 328–33.
83. Berney CR, Downing SR, Yang JL et al. Evidence for post-transcriptional down-regulation of the apoptosis-related gene bcl-2 in human colorectal cancer. J Pathol 2000; 191: 15–20.
84. Hwang TS, Han HS, Choi HK et al. Differential, stagedependent expression of Hsp70, Hsp110 and Bcl-2 in colorectal cancer. J Gastroenterol Hepatol 2003; 18: 690–700.
85. Mao JD, Wu P, Xia XH et al. Correlation between expression of gastrin, somatostatin and cell apoptosis regulation gene bcl-2/bax in large intestine carcinoma. World J Gastroenterol 2005; 11 (5): 721–5.
86. Paul-Samojedny M, Kokocinska D, Samojedny A et al. Expression of cell survival/death genes: Bcl-2 and Bax at the rate of colon cancer prognosis. Biochim Biophys Acta 2005; 1741 (1–2): 25–9.
________________________________________________
2. Kopnin B.P. Misheni deistviia onkogenov i opukholevykh supressorov: kliuch k ponimaniiu bazovykh mekhanizmov kantserogeneza (obzor). Biokhimiia. 2000; 65: 5–33 (in Russian).
3. Kopnin B.P. Molekuliarno-geneticheskie izmeneniia v zlokachestvennykh kletkakh. Pod red. D.G.Zaridze. Kantserogenez. Moscow, 2000; s. 79–90. (in Russian).
4. Fearnhead NS, Wilding JL, Bodmer WF. Genetics of colorectal cancer: hereditary aspects and overview of colorectal tumorigenesis. Brit Med Bull 2002; 64: 27–43.
5. Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell 1990; 6: 759–67.
6. Vogelstein B, Fearon ER, Hamilton SR et al. Genetic alterations during colorectal tumor development. N Engl J Med 1988; 319 (9): 525–32.
7. Ahmed FE. Development of novel diagnostic and prognostic molecular markers for sporadic colon cancer. Exp Rev Mol Diagnos 2005; 5: 337–52.
8. Ahmed FE. Molecular markers that predict response to colon cancer therapy. Exp Rev Mol Diagnos 2005; 5 (3): 353–75.
9. Arnold CN, Blum HE. Colon cancer: molecular markers. Dtsch Med Wochenschr 2005; 130 (14): 880–2.
10. Bianco AR, Carlomagno C, De Laurentiis M et al. Prognostic factors in human colorectal cancer. Tumori 1997; 83 (1. Supp. 1): S15–18.
11. Houlston RS. What we could do now: molecular pathology of colorectal cancer. Mol Pathol 2001; 54: 206–14.
12. Bendardaf R, Lamlum H, Pyrhonen S. Prognostic and predictive molecular markers in colorectal carcinoma. Anticancer Res 2004; 24 (4): 2519–30.
13. Rukovodstvo po immunogistokhimicheskoi diagnostike opukholei. Pod red. S.V.Petrova, N.T.Raikhlina. Kazan, 2004 (in Russian).
14. Imianitov E.N., Khanson K.P. Molekuliarnaia onkologiia: klinicheskie aspekty. Saint Petersburg: SPbMAPO, 2007. (in Russian).
15. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000; 100: 57–70.
16. Gasparini G, Pozza F, Harris AL. Evaluating the potential usefulness of new prognostic and predictive indicators in node negative breast cancer patients. J Natl Cancer Inst 1993; 85: 1206–19.
17. Aldrighetti L, Castoldi R, Di Palo S et al. Prognostic factors for long-term outcome of hepatic resection for colorectal liver metastases. Chir Ital 2005; 57 (5): 555–70.
18. Ambiru S, Miyazaki M, Isono T et al. Hepatic resection for colorectal metastases: analysis of prognostic factors. Dis Colon Rectum 1999; 42 (5): 632–9.
19. Neal CP, Garcea G, Doucas H. Molecular prognostic markers in resectable colorectal liver metastases: a systematic review. Eur J Cancer 2006; 42 (12): 1728–43.
20. Yamada H, Kondo S, Okushiba S et al. Analysis of predictive factors for recurrence after hepatectomy for colorectal liver metastases. World J Surg 2001; 25 (9): 1129–33.
21. Pozharisskii K.M., Leenman E.E. Znachenie immunogistokhimicheskikh metodik dlia opredeleniia kharaktera lecheniia i prognoza opukholevykh zabolevanii. Arkhiv patologii. 2000; 62 (5): 3–11 (in Russian).
22. Bendardaf R, Lamlum H, Ristamaki R. CD44 variant 6 expression predicts response to treatment in advanced colorectal cancer. Oncol Rep 2004; 11 (1): 41–5.
23. Cascinu S, Georgoulias V, Kerr D et al. Colorectal cancer in the adjuvant setting: perspectives on treatment and the role of prognostic factors. Ann Oncol 2003; 14: 25–9.
24. Graziano F, Cascinu S. Prognostic molecular markers for planning adjuvant chemotherapy trials in Dukes" B colorectal cancer patients: how much evidence is enough? Ann Oncol 2003; 14: 1026–38.
25. Nemtsova M.V., Pal'tseva E.M., Babaian A.Iu. et al. Molekuliarno-geneticheskii analiz klonal'noi vnutriopukholevoi geterogennosti v kolorektal'nykh kartsinomakh. Molekuliarnaia biologiia. 2008; 42 (6): 1040–7 (in Russian).
26. Chu E. A Multidisciplinary Approach to the Treatment of Early Colorectal Cancer. Ed. by E.Chu. International Cancer Management: A Multidisciplinary Approach. Yale Cancer Center Yale University School of Medicine 2007; 63: 70–1.
27. Perez RO. Predicting response to neoadjuvant treatment for rectal cancer: a step toward individualized medicine. Dis Colon Rectum 2011; 54 (9): 1057–8.
28. Sulzyc-Bielicka V, Domagala P, Majdanik E et al. Nuclear thymidylate synthase expression in sporadic colorectal cancer depends on the site of the tumor. Virchows Arch 2009; 454 (6): 695–702.
29. Darenskaia A.D. Pervaia liniia lekarstvennoi terapii metastaticheskogo kolorektal'nogo raka. Novyi rezhim lecheniia. Prognosticheskaia znachimost' molekuliarno-biologicheskikh markerov. Avtoref. dis. ... kand. med. nauk. Moscow, 2017 (in Russian).
30. Delektorskaia V.V. Molekuliarno-biologicheskie markery metastazirovaniia i prognoza pri rake tolstoi kishki. Avtoref. dis. … d-ra med. nauk. Moscow, 2007 (in Russian).
31. Lushnikov E.F., Abrosimov A.Iu. Gibel' kletki (apoptoz). Moscow: Meditsina, 2001 (in Russian).
32. Klinicheskaia biokhimiia: uchebnoe posobie. Pod red. V.A.Tkachuka. 3-e izd. Moscow: GEOTAR-Media, 2008 (in Russian).
33. Abbasova S.G., Kushlinskii N.E., Lipkii V.M., Trapeznikov N.N. Fakty i perspektivy izucheniia Fas-FasL-sistemy v norme i pri patologii. Uspekhi sovremennoi biologii. 2000; 3: 303–18 (in Russian).
34. Fil'chenkov A.A., Stoika R.S. Apoptoz i rak. Kiev: Morion, 1999 (in Russian).
35. Kogan E.A., Shvets S.I., Kovalenko V.L. et al. Sootnoshenie protsessov proliferatsii, apoptoza, angiogeneza i metastazirovaniia v razlichnykh gistogeneticheskikh tipakh raka legkogo (immunogistokhimicheskoe issledovanie). Arkhiv patologii. 2004; 66 (6): 33–9 (in Russian).
36. Mori S, Ogata Y, Shirouzu K. Biological features of sporadic colorectal carcinoma with high-frequency microsatellite instability: special reference to tumor proliferation and apoptosis. Int J Clin Oncol 2004; 9 (4): 322–9.
37. Kogan E.A., Ugpiumov D.A. Sootnoshenie protsessov proliferatsii i kletochnoi gibeli v nemelkokletochnom rake legkogo s zhelezistoi differentsirovkoi na raznykh stadiiakh opukholevoi progressii. Arkhiv patologii. 2002; 64 (1): 33–7 (in Russian).
38. Noguchi T, Kikuchi R, Ono K et al. Prognostic significance of p27/kip1 and apoptosis in patients with colorectal carcinoma. Oncol Rep 2003; 10 (4): 827–31.
39. Zhao HF. Prognostic significance of bcl-2 and p53 expression in colorectal carcinoma. J Zhejiang Univ Sci B 2005; 6 (12): 1163–9.
40. Hajra KM, Liu JR. Apoptosome dysfunction in human cancer. Apoptosis 2006; 95 (12): 1611–25.
41. Wei MC, Zong WX, Cheng EH et al. Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science 2002; 38 (2): 169–76.
42. Cory S, Adams JM. The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer 2002; 2: 647–56.
43. Kuwana T, Mackey MR, Perkins G et al. Bid, Bax, and lipids cooperate to form supramolecular openings in the outer mitochondrial membrane. Cell 2002; 111: 331–42.
44. Oltvai ZN, Milliman CL, Korsmeyer SJ. Bcl-2 heterodimers in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 1993; 74: 609–19.
45. Rampino N, Yamamoto H, Ionov Y et al. Somatic frameshift mutations in the BAX gene in colon cancers of the microsatellite mutator phenotype. Science 1997; 275: 967–9.
46. Zhang L, Yu J, Park BH et al. Role of BAX in the apoptotic response to anticancer agents. Science 2000; 290: 989–92.
47. Green DR. Apoptotic pathways: paper wraps stone blunts scissors. Cell 2000; 102: 1–4.
48. Loeffler M, Kroemer G. The mitochondrion in cell death control: certainties and incognita. Exp Cell Res 2000; 256: 19–26.
49. Van Loo G, Schotte P, Van Gurp M et al. Endonuclease G: a mitochondrial protein released in apoptosis and involved in caspase independent DNA degradation. Cell Death Differ 2001; 8: 1136–42.
50. Li P, Nijhawan D, Budihardjo I et al. Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 1997; 91: 479–89.
51. Rodriguez J, Lazebnik Y. Caspase-9 and APAF-1 form an active holoenzyme. Genes Dev 1999; 13: 3179–84.
52. Skulachev VP. Cytochrome c in the apoptotic and antioxidant cascades. FEBS Lett 1998; 423: 275–80.
53. Green DR, Amarante-Mendes GP. The point of no return: mitochondria, caspases, and the commitment to cell death. Results Probl Cell Differ 1998; 24: 45–61.
54. Bouillet P, Straser A. BH3-only proteins – evolutionarily conserved pro-apoptotic Bcl-2 family members essential for initiating programmed cell death. J Cell Sci 2002; 115: 1567–74.
55. Leahy DT, Mulcahy HE, O'Donoghue DP et al. Bcl-2 protein expression is associated with better prognosis in colorectal cancer. Histopathology 1999; 35 (4): 360–7.
56. Zabotina T.N., Kazakov S.P., Kushlinskii N.B. Rol' tkanevykh markerov apoptoza i proliferatsii v dopolnitel'noi differentsial'noi diagnostike papilliarnogo i follikuliarnogo raka shchitovidnoi zhelezy. Voen.-med. zhurn. 2010; 7: 48–50 (in Russian).
57. Kazakov S.P. Issledovanie osnovnykh tkanevykh markerov apoptoza i proliferatsii, ikh diagnosticheskoi effektivnosti pri zabolevaniiakh shchitovidnoi zhelezy. Voen.-med. zhurn. 2010; 9: 73–7 (in Russian).
58. Petrov S.B., Antoneeva I.I. Markery apoptoza i proliferatsii opukholevykh kletok v dinamike progressirovaniia raka iaichnika. Onkologiia. 2008; 2: 234–7 (in Russian).
59. Selzer E, Schlagbauer-Wadl H, Okamoto I et al. Expression of Bcl-2 family members in human melanocytes, in melanoma metastases and in melanoma cell lines. Melanoma Res 1998; 8: 197–203.
60. Avdalian A.M. Patomorfologicheskii i immunogistokhimicheskii analiz leiomiomy i leiomiosarkomy tela matki: differentsial'naia diagnostika i prognoz. Avtoref. dis. ... d-ra med. nauk. Novosibirsk, 2013. (in Russian).
61. Avdalian A.M., Bobrov I.P., Klimachev V.V. et al. Sviaz' ekspressii retseptorov k progesteronu i estrogenu a i aktivnost' argirofil'nykh belkov oblasti iadryshkovykh organizatorov v gladkomyshechnykh opukholiakh tela matki. Arkhiv patologii. 2009; 4: 50–4 (in Russian).
62. Anichkov N.M., Chuprov I.N. Morfologicheskie markery prognoza bazal'no-kletochnogo raka kozhi. Med. akad. zhurn. 2011; 1: 3–11 (in Russian).
63. Baryshnikov A.Iu., Kuznetsov V.V., Stepanova E.V. et al. Ekspressiia markerov apoptoza (r53, bcl-2, vakh) i ikh prognosticheskoe znachenie pri epitelial'nykh novoobrazovaniiakh iaichnikov rannikh stadii. Ros. bioterapevtich. zhurn. 2011; 2: 45–9 (in Russian).
64. Buglioni S, D'Agnano I, Cosimelli M et al. Evaluation of multiple bio-pathological factors in colorectal adenocarcinomas: independent prognostic role of p53 and bcl-2. Int J Cancer 1999; 84 (6): 545–52.
65. Meterissian SH, Kontogiannea M, Al-Sowaidi M et al. Bcl-2 is a useful prognostic marker in dukes’ B colon cancer. Ann Surg Oncol 2001; 8 (6): 533–7.
66. Zavrides H, Zizi-Sermpetzoglou A, Elemenoglou I et al. Immunohistochemical expression of bcl-2 in Dukes' stage B and C colorectal carcinoma patients: correlation with p53 and ki-67 and in evaluating prognostic significance. Pol J Pathol 2005; 56 (4): 179–85.
67. Zavrides HN, Zizi-Sermpetzoglou A, Panousopoulos D et al. Prognostic evaluation of CD44 expression in correlation with bcl-2 and p53 in colorectal cancer. Folia Histochem Cytobiol 2005; 43 (1): 31–6.
68. Zavrides H, Zizi-Sermpetzoglou A, Elemenoglou I et al. Immunohistochemical expression of bcl-2 in UICC stage I and III colorectal carcinoma patients: correlation with c-erbB-2, p53, ki-67, CD44, laminin and collagen IV in evaluating prognostic significance. Pol J Pathol 2006; 57 (3): 149–59.
69. Ilyas M, Hao X-P, Wilkinson K et al. Loss of Bcl-2 expression correlates with tumor recurrence in colorectal cancer. Gut 1998; 43: 383–7.
70. Bukholm IK, Nesland JM. Protein expression of p53, p21 (WAF1/CIP1), bcl-2, Bax, cyclin D1 and pRb in human colon carcinomas. Virchows Arch 2000; 436 (3): 224–8.
71. Rosati G, Chiacchio R, Reggiardo G et al. Thymidylate synthase expression, p53, bcl-2, Ki-67 and p27 in colorectal cancer: relationships with tumor recurrence and survival. Tumour Biol 2004; 25 (5–6): 258–63.
72. Tollenaar RA, van Krieken JH, van Slooten HJ et al. Immunohistochemical detection of p53 and Bcl-2 in colorectal carcinoma: no evidence for prognostic significance. Br J Cancer 1998; 77 (11): 1842–7.
73. Watson NF et al. Evidence that the p53 negative/bcl-2 positive phenotype is an independent indicator of good prognosis in colorectal cancer: a tissue microarray study of 460 patients. World J Surg Oncol 2005; 3 (47): 635–43.
74. Kim NK, Park JK, Lee KY et al. P53, Bcl-2, and Ki 67 expression according to tumor response after concurrent chemoradiotherapy for advanced rectal cancer. Ann Surg Oncol 2001; 8 (5): 418–24.
75. Kushlinskii N.E., Orinovskii M.B., Gurevich L.E. et al. Ekspressiia molekuliarno-biologicheskikh markerov (Ki-67, PCNA, Vcl-2, BAKh, BclX, VEGF) v opukholiakh molochnoi zhelezy. Biul. eksperimental'noi biologii i meditsiny. 2004; 137 (2): 206–10 (in Russian).
76. Elzagheid A, Kuopio T, Pyrhonen S et al. Lymph node status as a guide to selection of available prognostic markers in breast cancer: the clinical practice of the future? Diagn Pathol 2006; 8 (1): 41.
77. Haitel A, Posch B, El-Baz M et al. Bilharzial related, organ confined, muscle invasive bladder cancer: prognostic value of apoptosis markers, proliferation markers, p53, E-cadherin, epidermal growth factor receptor and c-erbB-2. J Urol 2001; 165 (5): 1481–7.
78. Ioachim EE, Malamou-Mitsi V, Kamina SA et al. Immunohistochemical expression of Bcl-2 protein in breast lesions: correlation with Bax, p53, Rb, C-erbB-2, EGFR and proliferation indices. Anticancer Res 2000; 20 (6B): 4221–5.
79. Magistrelli P, Coppola R, Tonini G et al. Apoptotic index or a combination of Bax/Bcl-2 expression correlate with survival after resection of pancreatic adenocarcinoma. J Cell Biochem 2006; 97 (1): 98–108.
80. Paik KH, Park YH, Ryoo BY et al. Prognostic value of immunohistochemical staining of p53, bcl-2, and Ki-67 in small cell lung cancer. J Korean Med Sci 2006; 21 (1): 35–9.
81. Santini D, Tonini G, Vecchio FM et al. Prognostic value of Bax, Bcl-2, p53, and TUNEL staining in patients with radically resected ampullary carcinoma. J Clin Pathol 2005; 58 (2): 159–65.
82. Wolf HK, Stober C, Hohenfellner R, Leissner J. Prognostic value of p53, p21/WAF1, Bcl-2, Bax, Bak and Ki-67 immunoreactivity in pT1 G3 urothelial bladder carcinomas. Tumour Biol 2001; 22 (5): 328–33.
83. Berney CR, Downing SR, Yang JL et al. Evidence for post-transcriptional down-regulation of the apoptosis-related gene bcl-2 in human colorectal cancer. J Pathol 2000; 191: 15–20.
84. Hwang TS, Han HS, Choi HK et al. Differential, stagedependent expression of Hsp70, Hsp110 and Bcl-2 in colorectal cancer. J Gastroenterol Hepatol 2003; 18: 690–700.
85. Mao JD, Wu P, Xia XH et al. Correlation between expression of gastrin, somatostatin and cell apoptosis regulation gene bcl-2/bax in large intestine carcinoma. World J Gastroenterol 2005; 11 (5): 721–5.
86. Paul-Samojedny M, Kokocinska D, Samojedny A et al. Expression of cell survival/death genes: Bcl-2 and Bax at the rate of colon cancer prognosis. Biochim Biophys Acta 2005; 1741 (1–2): 25–9.
Авторы
А.Д.Даренская*, Н.В.Доброва, Е.В.Степанова
ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н.Блохина» Минздрава России. 115478, Россия, Москва, Каширское ш., д. 23
*darenskaya@bk.ru
N.N.Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation. 23, Kashirskoe h., Moscow, 115478, Russian Federation
*darenskaya@bk.ru
ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н.Блохина» Минздрава России. 115478, Россия, Москва, Каширское ш., д. 23
*darenskaya@bk.ru
________________________________________________
N.N.Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation. 23, Kashirskoe h., Moscow, 115478, Russian Federation
*darenskaya@bk.ru
Цель портала OmniDoctor – предоставление профессиональной информации врачам, провизорам и фармацевтам.