Antiangiogenic potential of beta-blockers in the context of juvenile hemangioma treatment
- Authors: Dubensky V.V.1, Dubensky V.V.1
-
Affiliations:
- Tver State Medical University, Ministry of Health of the Russian Federation
- Issue: Vol 95, No 2 (2019)
- Pages: 29-41
- Section: ORIGINAL STUDIES
- Submitted: 17.07.2019
- Accepted: 17.07.2019
- Published: 17.04.2019
- URL: https://vestnikdv.ru/jour/article/view/481
- DOI: https://doi.org/10.25208/0042-4609-2019-95-2-29-41
- ID: 481
Cite item
Full Text
Abstract
Juvenile hemangiomas (JH) — the most common tumor of childhood, which is estimated by various investigators found in 3–10 % of newborns resulting from the local development of significant violations of neoangiogenesis regulation. Research objective: determination of comparative antiangiogenic effectiveness and influence of beta-blockers on the level of a vascular endothelial factor of growth in an experiment. Material and methods. For determination of antiangiogenic effect of beta blockers, comparative studying of their influence on the level of a vascular endothelial factor of growth in an experiment on 72 nonlinear laboratory rats, by average weight 180 ± 20 g which were conditionally divided into 6 groups is executed: 1 — control, 2 — negative control — experimental ischemia (EI, crossing of femoral vessels), 3 — positive control (EI with bevacizumab introduction), 4 — EI with introduction of a timolol, 5 — EI with introduction of a betaksolol, 6 — EI with introduction of interferon alpha 2b. Results. The VEGF levels were: in 1 group — 1.50 ± 0.3 pg/ml, in 2 — 20.3 ± 3.2 pg/ml, 3 — 5.8 ± 0.9 pg/ml, 4 — 13.8 ± 1.4 pg/ml, 5 — 19.2 ± 2.3 pg/ml and 6 — 11.1 ± 2.2 pg/ml. Results of microscopy and immunohistochemical research demonstrate lack of activation of processes of neoangiogenesis in 1 group of animals. At animals of 2nd and 5th groups along with the expressed inflammatory processes the neoangiogenesis phenomena are established. Conclusion. Beta-blockers show the direct or mediated negative impact on synthesis of VEGF and oppression of neoangiogenesis. The activity of selective beta-blocker concerning neoangiogenesis suppression — was lower in comparison by activity non-selective that allows to consider the Timolol effective antiangiogenic remedy.
About the authors
Vl. V. Dubensky
Tver State Medical University, Ministry of Health of the Russian Federation
Author for correspondence.
Email: tgma.estet@yandex.ru
Vladislav V. Dubensky — Cand. Sci. (Med.), Assoc. Prof., Prof. of the Department of Dermatovenereology with a Course of Cosmetology
tel.: +7 (961) 016-00-00
РоссияV. V. Dubensky
Tver State Medical University, Ministry of Health of the Russian Federation
Email: fake@neicon.ru
Valery V. Dubensky — Dr. Sci. (Med.), Prof., Head of the Department of Dermatovenereology with a Course of Cosmetology Россия
References
- Frieden I. J. et al. Infantile hemangiomas: current knowledge, future directions, Proceedings of a research workshop on infantile hemangiomas. Pediatr Dermatol. 2005;22:383–406.
- Дубенский Вл. В. Этиопатогенез и морфология ювенильных гемангиом. Российский журнал кожных и венерических болезней. 2014;(4):8–12. [Dubensky V. V. Etiopathogenesis and morphology of juvenile hemangiomas. Russian Journal of Skin and Venereal diseases. 2014;(4):8–12. (In Russ.)]
- Дубенский Вл. В. Клинико-функциональные особенности ювенильных гемангиом. Современные проблемы дерматовенерологии, иммунологии, косметологии. 2013;(8):15–24. [Dubensky V. V. Clinical and functional features of juvenile hemangiomas. Modern Problems of Dermatovenerology, Immunology, Cosmetology. 2013;(8):15–24. (In Russ.)]
- Drolet B., Frieden I. J. Characteristics of infantile hemangiomas as clues to pathogenesis. Does hypoxia connect the dots? Arch Dermatol. 2010;146:1295–1299.
- Frieden I. J., Haggstrom A., Drolet B. A. et al. Infantile hemangiomas: current knowledge, future directions. Proceedings of a research workshop on infantile hemangiomas. Pediatr Dermatol Venereol. 2008;135:860–862.
- North P. E., Waner M., Mizeracki A. et al. A unique microvascular phenotype shared by juvenile heamangiomas and human placenta. Arch Dermatol. 2001;137:559–570.
- Barnes C. M., Christison-Lagay E. A., Folkman J. The placenta theory and the origin of infantile hemangioma. Lymphat Res Biol. 2007;5(4):245–255.
- Hoeger P. H. Infantile Hemangioma: new aspects on the pathogenesis of the most common skin tumour in children. Br J Dermatol. 2011 Feb;164(2):234–235.
- Razon M. J., Kraling B. M., Mulliken J. B., Bischoff J. Increase apoptosis coincides with onset of involution in infantile hemangioma. Microcirculation. 1998;5:189–195.
- Léauté-Labrèze C., Dumas de la Roque E., Hubiche T., Boralevi F., Thambo J. B., Taïeb A. Propranolol for severe hemangiomas of infancy. N Engl J Med. 2008;358:2649–2651 [PubMed].
- Drolet B. A., Frommelt P. C., Chamlin S. L., Haggstrom A., Bauman N. M., Chiu Y. E. et al. Initiation and use of propranolol for infantile hemangioma: report of a consensus conference. Pediatrics. 2013;131:128–140.
- D’Angelo G. et al. cAMP-dependant protein kinase inhibits the mitogenic action of vascular endothelial growth factor and fibroblast growth factor in capillary endothelial cells by blocking Raf activation. J. Cell Biochem. 1997;67:353–366.
- Laccarino G. et al. Ischemic neoangiogenesis enhanced by beta2-adrenergic receptors overexpression: a novel role for the endothelial adrenergic system. Circ Res. 2005;97:1182–1189.
- Тырсина Е. Г., Никулицкий С. И. Роль регуляторной VEGF/ VEGF-R1-системы в опухолевом ангиогенезе (обзор литературы). Онкогинекология. 2015. [Tyrsina E. G., Nikulitsky S. I. The role of the regulatory VEGF/VEGF-R1 system in tumour angiogenesis (literature review). Oncogynecology. 2015. (In Russ.)]
- Кукес В. Г., Сычев Д. А., Андреев Д. А. Клиническая фармакология β-адреноблокаторов. РМЖ. 2005;14:932. [Kukes V. G., Sychev D. A., Andreev D. A. Clinical pharmacology of b–adrenoblockers. Breast cancer. Russian Medical Journal. 2005;14:932. (In Russ.)]
- Миронов А. Н., Бунатян Н. Д. Руководство по проведению доклинических исследований лекарственных средств. М.: Гриф и К, 2012. 944 с. [Mironov A. N., Bunatyan N. D. Guidelines for conducting preclinical studies of drugs. Moscow: Grif i K, 2012. 944 p. (In Russ.)]
- Дубенский В. В., Аун Р. Ю. Эффективность и безопасность применения топического β-адреноблокатора для лечения ювенильных гемангиом. Фарматека. 2018;s1:32–39. [Dubensky V. V., Aun R. Yu. Efficacy and safety of topical β-blocker for the treatment of juvenile hemangiomas. Farmateka. 2018;s1:32–39. (In Russ.)]
- Дубенский В. В. Влияние неселективного бета-адреноблокатора на хемотаксис и активную миграцию клеток in vitro в аспекте лечения ювенильных гемангиом. Иммунопатология, аллергология, инфектология. 2016;4:50–59. [Dubensky V. V. Effect of non-selective beta-adrenergic blocker on chemotaxis and in vitro active cell migration in the context of treating juvenile hemangiomas. Immunopathology, Allergology, Infectology. 2016;4:50–59. (In Russ.)]