Офтальмохирургия. 2020; : 58-64
Трансформирующий фактор роста TGF-β при различном клиническом течении начальной меланомы хориоидеи до и после органосохранного лечения
https://doi.org/10.25276/0235-4160-2020-3-58-64Аннотация
Цель. Изучить роль трансформирующего фактора роста TGF-β при различном клиническом течении начальной меланомы хориоидеи до и после органосохранного лечения.
Материал и методы. Всего в исследовании участвовали 111 об- следуемых (средний возраст 53,7±12,2 года): с меланомой хориоидеи (n=78) и здоровых доноров (n=33). В 1-ю группу (n=32) вошли пациенты с начальной стадией меланомы хориоидеи, во 2-ю группу (n=25) – с опухолями средних размеров, в 3-ю группу (n=21) – с меланомами больших размеров. Всем больным с меланомой хориоидеи проводи- ли разрушающую лазерную коагуляцию, транспупиллярную термотерапию, брахитерапию. Наблюдение – через 7±1,2 мес. Исследование трансформирующего фактора роста (TGF-β1 и TGF-β2) осуществляли на проточном цитометре BD FACS Canto II. Статистическая обработ- ка: t-критерий Стьюдента, критерии Фишера и χ2, p<0,05.
Результаты. При анализе содержания TGF-β1 и TGF-β2 в сыворотке крови отмечены достоверно более высокие показатели при начальной меланоме хориоидеи с ретинальным экссудатом (19664,2±1708,7 и 4914,4±325,2 пкг/мл соответственно) по сравнению с таковыми без экссудата (18778,7±1609,6 и 3857,3±275,1 пкг/мл соответственно). При сравнении динамики содержания TGF-β1 и TGF-β2 в сыворотке крови при начальной стадии опухоли (19902,2±1406 и 4220,7±277,8 пкг/мл соответственно) и опухолях больших размеров (23143,1±1984,5 и 4591,7±334,1 пкг/мл соответственно) стадиями нами отмечено достоверное его увеличение с ростом новообразования. Количество TGF-β2 в сыворотке крови при неблагоприятном течении начальной меланомы хориоидеи (наличии остаточной опухоли или продолженного роста) после лечения оказалось достоверно выше (4864,1±1299,99 пкг/мл) по сравнению с благоприятным (3649,5±1216,5 пкг/мл).
Заключение. Полученные нами данные могут свидетельствовать о роли трансформирующего фактора роста TGF-β в неблагоприятном течении опухолевого процесса при начальной меланоме хориоидеи и послужить поводом для разработки таргетной анти-TGF-β-терапии в комбинации с лучевой.
Список литературы
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23. Kivela T, Eskelin S, Makitie T, Summanen P. Exudative retinal detachment from malignant uveal melanoma: predictors and prognostic significance. Invest Ophthalmol Vis Sci. 2001;42(9): 2085–2093.
24. Maniotis AJ, Folberg R, Hess A, Seftor EA, Gardner LMG, Pe’er J, Trent JM, Meltzer PS, Hendrix MJC. Vascular channel formation by human melanoma cells in vivo and in vitro: Vasculogenic mimicry. Am J Pathol. 1999;155: 739–752.
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Fyodorov Journal of Ophthalmic Surgery. 2020; : 58-64
Transforming growth factor TGF-β in various small choroid melanoma clinical characteristics before and after eye-preserving treatment
https://doi.org/10.25276/0235-4160-2020-3-58-64Abstract
Purpose. To study the role of transforming growth factor TGF-β in various small choroidal melanoma clinical characteristics before and after eye-preserving treatment.
Material and methods. In total, the study included 111 people with an average age of 53.7±12.2 years with choroidal melanoma (n=78) and healthy donors (n=33). Group 1 (n=32) included patients with small choroidal melanoma; group 2 (n=25) included patients with medium-sized tumors; group 3 (n=21) included patients with large melanomas. All patients with choroid melanoma were treated by laser coagulation, transpupillary thermotherapy, brachytherapy, observation after 7±1.2months. A study of transforming growth factor (TGF-β1 and TGF-β2) was performed on a BD FACS Canto II flow cytometer. Statistical processing: Student’s t-test, Fisher criteria and χ2, p<0.05.
Results. By analyzing the content of TGF-β1 and TGF-β2 in blood serum, significantly higher indices were noted in small choroidal melanoma with retinal exudate (19664.2±1708.7 and 4914.4±325.2 pkg/ml, respectively) compared with those without exudate (18778.7±1609.6 and 3857.3±275.1 pcg/ml, respectively). Comparing the dynamics of the content of TGF-β1 and TGF-β2 in blood serum in small stage of tumor (19902.2±1406 and 4220.7±277.8 pkg/ml, respectively) big tumor (23143.1±1984.5 and 4591.7±334.1 pcg/ml, respectively) we noted its significant increase with the growth of melanoma. The amount of TGF-β2 in the blood serum with bad course (presence of residual tumor or continued growth) of small choroidal melanoma after treatment was significantly higher (4864.1±1299.99 pcg / ml) compared with the good situation (3649.5±1216.5 pcg / ml).
Conclusion. Our data may indicate the role of transforming growth factor (TGF-β) in the bad course of small choroidal melanoma and serve as an occasion for the development of targeted anti-TGF–β therapy in combination with radiation therapy.
References
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2. Jouhi S, Jager MJ, De Geus SJR, Desjardins L, Eide NA, Grange J-D, Kilgaard JF, Seregard S, Midena E, Parrozzani R, Caujolle J-P, Rospond-Kubiak I, Kivela TT. The Small Fatal Choroidal Melanoma Study. A Survey by the European Ophthalmic Oncology Group. Am J Ophthalmol. 2019;202: 100–108. doi:10.1016/j.
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17. Bierie V, Moses HL. TGF-beta and cancer. Cytokine growth factor Rev. 2006;17: 29–40.
18. Siegel R, Massague J. Cytostatic and apoptotic actions of TGF-beta in homeostasis and cancer. Nat Rev Cancer. 2003;3: 807–821. doi:10.1038/nrc1208
19. Moustakas A, Pardali K, Gaal A, Heldin CH. Mechanisms of TGF-beta signaling in regulation of cell growth and differentiation. Immunol Lett. 2002;82: 85–91.
20. Graycar JL, Miller DA, Arrick BA, Lyons RM, Moses HL, Derynck R. Human transforming growth factor-beta-3: recombinant expression, purification and biological activities in comparison with transforming growth factors-beta-1 and beta-2. Molec Endocr. 1989;3: 1977–1986.
21. Streilein JW, Wilbanks GA, Taylor A, Cousins S. Eye-derived cytokines and the immunosuppressive intraocular microenvironment: a review. Current Eye Research. 1992;11: 41–47.
22. Diaz-Valdes N, Basagoiti M, Dotor J, Aranda F, Monreal I, Riezu-Boj JI, Borrás-Cuesta F, Sarobe P, Feijoó E. Induction of monocyte chemoattractant protein-1 and interleukin-10 by TGFbeta1 in melanoma enhances tumor infiltration and immunosuppression. Cancer Res. 2011;71: 812–821. doi:10.1158/0008-5472
23. Kivela T, Eskelin S, Makitie T, Summanen P. Exudative retinal detachment from malignant uveal melanoma: predictors and prognostic significance. Invest Ophthalmol Vis Sci. 2001;42(9): 2085–2093.
24. Maniotis AJ, Folberg R, Hess A, Seftor EA, Gardner LMG, Pe’er J, Trent JM, Meltzer PS, Hendrix MJC. Vascular channel formation by human melanoma cells in vivo and in vitro: Vasculogenic mimicry. Am J Pathol. 1999;155: 739–752.
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26. Esser P, Grisanti S, Bartz Schmidt KU. TGF β in uveal melanoma. Microscopy research and technique. 2001;52: 396–400. doi:10.1002/1097-0029(20010215)
27. Castet F, Garcia-Mulero S, Sanz-Pamplona R, Cuellar A, Casanovas O, Caminal JM, Piulats JM. Uveal Melanoma, Angiogenesis and Immunotherapy, Is There Any Hope? Cancers. 2019;11: 834. doi:10.3390/ cancers11060834
