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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="other" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Advances in Molecular Oncology</journal-id><journal-title-group><journal-title xml:lang="en">Advances in Molecular Oncology</journal-title><trans-title-group xml:lang="ru"><trans-title>Успехи молекулярной онкологии</trans-title></trans-title-group></journal-title-group><issn publication-format="print">2313-805X</issn><issn publication-format="electronic">2413-3787</issn><publisher><publisher-name xml:lang="en">Publishing House ABV Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">45</article-id><article-id pub-id-type="doi">10.17650/2313-805X.2015.2.3.51-59</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>REVIEW ARTICLES</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>ОБЗОРНЫЕ СТАТЬИ</subject></subj-group><subj-group subj-group-type="article-type"><subject></subject></subj-group></article-categories><title-group><article-title xml:lang="en">RANK/RANKL/OPG LIGAND-RECEPTOR SYSTEM AND ITS ROLE IN PRIMARY BONE NEOPLASMS (LITERATURE ANALYSIS AND OWN DATA)</article-title><trans-title-group xml:lang="ru"><trans-title>ЛИГАНД-РЕЦЕПТОРНАЯ СИСТЕМА RANK/RANKL/OPG И ЕЕ РОЛЬ ПРИ ПЕРВИЧНЫХ НОВООБРАЗОВАНИЯХ КОСТЕЙ (АНАЛИЗ ЛИТЕРАТУРЫ И СОБСТВЕННЫЕ РЕЗУЛЬТАТЫ)</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Gershtein</surname><given-names>E. S.</given-names></name><name xml:lang="ru"><surname>Герштейн</surname><given-names>Е. С.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="ru"><p>Герштейн  Елена Сергеевна</p></bio><email>esgershtein@gmail.com</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Timofeev</surname><given-names>Yu. S.</given-names></name><name xml:lang="ru"><surname>Тимофеев</surname><given-names>Ю. С.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>esgershtein@gmail.com</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Zuev</surname><given-names>A. A.</given-names></name><name xml:lang="ru"><surname>Зуев</surname><given-names>А. А.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>esgershtein@gmail.com</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Kushlinskii</surname><given-names>N. E.</given-names></name><name xml:lang="ru"><surname>Кушлинский</surname><given-names>Н. Е.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>esgershtein@gmail.com</email><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Laboratory of Clinical Biochemistry, N.N. Blokhin Russian Cancer Research Center, Ministry of Health of Russia, Moscow</institution></aff><aff><institution xml:lang="ru">Лаборатория клинической биохимии ФГБУ «Российский онкологический научный центр имени Н.Н. Блохина» Минздрава России, Москва</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2015-09-15" publication-format="electronic"><day>15</day><month>09</month><year>2015</year></pub-date><volume>2</volume><issue>3</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>51</fpage><lpage>59</lpage><history><date date-type="received" iso-8601-date="2015-12-18"><day>18</day><month>12</month><year>2015</year></date><date date-type="accepted" iso-8601-date="2015-12-18"><day>18</day><month>12</month><year>2015</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2015, Gershtein E.S., Timofeev Y.S., Zuev A.A., Kushlinskii N.E.</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2015, Герштейн Е.С., Тимофеев Ю.С., Зуев А.А., Кушлинский Н.Е.</copyright-statement><copyright-year>2015</copyright-year><copyright-holder xml:lang="en">Gershtein E.S., Timofeev Y.S., Zuev A.A., Kushlinskii N.E.</copyright-holder><copyright-holder xml:lang="ru">Герштейн Е.С., Тимофеев Ю.С., Зуев А.А., Кушлинский Н.Е.</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/"/><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://creativecommons.org/licenses/by/4.0</ali:license_ref></license></permissions><self-uri xlink:href="https://umo.abvpress.ru/jour/article/view/45">https://umo.abvpress.ru/jour/article/view/45</self-uri><abstract xml:lang="en"><p/></abstract><trans-abstract xml:lang="ru"><p/></trans-abstract><kwd-group xml:lang="en"><kwd>receptor activator of NF-κB (RANK)</kwd><kwd>RANK ligand (RANKL)</kwd><kwd>osteoprotegerin</kwd><kwd>bone sarcomas</kwd><kwd>giant-cell bone tumor</kwd><kwd>targeted therapy</kwd><kwd>denosumab</kwd><kwd>blood serum</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>рецептор-активатор NF-κB (RANK)</kwd><kwd>RANK-лиганд (RANKL)</kwd><kwd>остеопротегерин</kwd><kwd>костный гомеостаз</kwd><kwd>остеокластогенез</kwd><kwd>саркомы костей</kwd><kwd>гигантоклеточная опухоль кости</kwd><kwd>таргетная терапия</kwd><kwd>деносумаб</kwd><kwd>сыворотка крови</kwd></kwd-group><funding-group/></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><citation-alternatives><mixed-citation xml:lang="en">1. Dougall W.C. RANKL signaling in bone physiology and cancer. Curr Opin Support Palliat Care 2007;1(4):317–22.</mixed-citation><mixed-citation xml:lang="ru">Dougall W.C. RANKL signaling in bone physiology and cancer. Curr Opin Support Palliat Care 2007;1(4):317–22.</mixed-citation></citation-alternatives></ref><ref id="B2"><label>2.</label><citation-alternatives><mixed-citation xml:lang="en">2. Boyce B.F., Xing L. Functions of RANKL/ RANK/OPG in bone modeling and remodeling. Arch Biochem Biophys 2008;473(2):139–46.</mixed-citation><mixed-citation xml:lang="ru">Boyce B.F., Xing L. Functions of RANKL/ RANK/OPG in bone modeling and remodeling. Arch Biochem Biophys 2008;473(2):139–46.</mixed-citation></citation-alternatives></ref><ref id="B3"><label>3.</label><citation-alternatives><mixed-citation xml:lang="en">3. Hofbauer L.C., Kuhne C.A., Viereck V. The OPG/RANKL/RANK system in metabolic bone diseases. J Musculoskelet Neuronal Interact 2004;4(3):268–75.</mixed-citation><mixed-citation xml:lang="ru">Hofbauer L.C., Kuhne C.A., Viereck V. The OPG/RANKL/RANK system in metabolic bone diseases. J Musculoskelet Neuronal Interact 2004;4(3):268–75.</mixed-citation></citation-alternatives></ref><ref id="B4"><label>4.</label><citation-alternatives><mixed-citation xml:lang="en">4. Delmas P.D. Clinical potential of RANKL inhibition for the management of postmenopausal osteoporosis and other metabolic bone diseases. J Clin Densitom 2008;11(2):325–38.</mixed-citation><mixed-citation xml:lang="ru">Delmas P.D. Clinical potential of RANKL inhibition for the management of postmenopausal osteoporosis and other metabolic bone diseases. J Clin Densitom 2008;11(2):325–38.</mixed-citation></citation-alternatives></ref><ref id="B5"><label>5.</label><citation-alternatives><mixed-citation xml:lang="en">5. Kobayashi Y., Takahashi N. Genomic approaches to bone and joint diseases. Mutations of RANK, OPG and RANKL genes found in humans. Clin Calcium 2008;18(2):202–9.</mixed-citation><mixed-citation xml:lang="ru">Kobayashi Y., Takahashi N. Genomic approaches to bone and joint diseases. Mutations of RANK, OPG and RANKL genes found in humans. Clin Calcium 2008;18(2):202–9.</mixed-citation></citation-alternatives></ref><ref id="B6"><label>6.</label><citation-alternatives><mixed-citation xml:lang="en">6. Whyte M.P., Mumm S. Heritable disorders of the RANKL/OPG/RANK signaling pathway. J Musculoskelet Neuronal Interact 2004;4(3):254–67.</mixed-citation><mixed-citation xml:lang="ru">Whyte M.P., Mumm S. Heritable disorders of the RANKL/OPG/RANK signaling pathway. J Musculoskelet Neuronal Interact 2004;4(3):254–67.</mixed-citation></citation-alternatives></ref><ref id="B7"><label>7.</label><citation-alternatives><mixed-citation xml:lang="en">7. Crockett J.C., Mellis D.J., Scott D.I., Helfrich M.H. New knowledge on critical osteoclast formation and activation pathways from study of rare genetic diseases of osteoclasts: focus on the RANK/RANKL axis. Osteoporos Int 2010;22(1):1–20.</mixed-citation><mixed-citation xml:lang="ru">Crockett J.C., Mellis D.J., Scott D.I., Helfrich M.H. New knowledge on critical osteoclast formation and activation pathways from study of rare genetic diseases of osteoclasts: focus on the RANK/RANKL axis. Osteoporos Int 2010;22(1):1–20.</mixed-citation></citation-alternatives></ref><ref id="B8"><label>8.</label><citation-alternatives><mixed-citation xml:lang="en">8. Jorgensen H.L., Kusk P., Madsen B. et al. Serum osteoprotegerin (OPG) and the A163G polymorphism in the OPG promoter region are related to peripheral measures of bone mass and fracture odds ratios. J Bone Miner Metab 2004;22(2):132–8.</mixed-citation><mixed-citation xml:lang="ru">Jorgensen H.L., Kusk P., Madsen B. et al. Serum osteoprotegerin (OPG) and the A163G polymorphism in the OPG promoter region are related to peripheral measures of bone mass and fracture odds ratios. J Bone Miner Metab 2004;22(2):132–8.</mixed-citation></citation-alternatives></ref><ref id="B9"><label>9.</label><citation-alternatives><mixed-citation xml:lang="en">9. Whyte M.P. P ,s disease of bone and genetic disorders of RANKL/OPG/RANK/ NF-kappaB signaling. Ann NY Acad Sci 2006;1068:143–64.</mixed-citation><mixed-citation xml:lang="ru">Whyte M.P. P ,s disease of bone and genetic disorders of RANKL/OPG/RANK/ NF-kappaB signaling. Ann NY Acad Sci 2006;1068:143–64.</mixed-citation></citation-alternatives></ref><ref id="B10"><label>10.</label><citation-alternatives><mixed-citation xml:lang="en">10. Choi H.K., Kang H.R., Jung E. et al. Early estrogen-induced gene 1, a novel RANK signaling component, is essential for osteoclastogenesis. Cell Res 2013;23(4):524–36.</mixed-citation><mixed-citation xml:lang="ru">Choi H.K., Kang H.R., Jung E. et al. Early estrogen-induced gene 1, a novel RANK signaling component, is essential for osteoclastogenesis. Cell Res 2013;23(4):524–36.</mixed-citation></citation-alternatives></ref><ref id="B11"><label>11.</label><citation-alternatives><mixed-citation xml:lang="en">11. Santini D., Perrone G., Roato I. et al. Expression pattern of receptor activator of NFkappaB(RANK) in a series of primary solid tumors and related bone metastases. J Cell Physiol 2010;226(3):780–4.</mixed-citation><mixed-citation xml:lang="ru">Santini D., Perrone G., Roato I. et al. Expression pattern of receptor activator of NFkappaB(RANK) in a series of primary solid tumors and related bone metastases. J Cell Physiol 2010;226(3):780–4.</mixed-citation></citation-alternatives></ref><ref id="B12"><label>12.</label><citation-alternatives><mixed-citation xml:lang="en">12. Kwan Tat S., Padrines M., Theoleyre S. et al. IL-6, RANKL, TNF-alpha/IL-1: interrelations in bone resorption pathophysiology. Cytokine Growth Factor Rev 2004;15(1):49–60.</mixed-citation><mixed-citation xml:lang="ru">Kwan Tat S., Padrines M., Theoleyre S. et al. IL-6, RANKL, TNF-alpha/IL-1: interrelations in bone resorption pathophysiology. Cytokine Growth Factor Rev 2004;15(1):49–60.</mixed-citation></citation-alternatives></ref><ref id="B13"><label>13.</label><citation-alternatives><mixed-citation xml:lang="en">13. Jimi E., Shin M., Furuta H. et al. The RANKL/RANK system as a therapeutic target for bone invasion by oral squamous cell carcinoma (Review). Int J Oncol 2013;42(3):803–9.</mixed-citation><mixed-citation xml:lang="ru">Jimi E., Shin M., Furuta H. et al. The RANKL/RANK system as a therapeutic target for bone invasion by oral squamous cell carcinoma (Review). Int J Oncol 2013;42(3):803–9.</mixed-citation></citation-alternatives></ref><ref id="B14"><label>14.</label><citation-alternatives><mixed-citation xml:lang="en">14. Blake M.L., Tometsko M., Miller R. et al. RANK expression on breast cancer cells promotes skeletal metastasis. Clin Exp Metastasis 2013;31(2):233–45.</mixed-citation><mixed-citation xml:lang="ru">Blake M.L., Tometsko M., Miller R. et al. RANK expression on breast cancer cells promotes skeletal metastasis. Clin Exp Metastasis 2013;31(2):233–45.</mixed-citation></citation-alternatives></ref><ref id="B15"><label>15.</label><citation-alternatives><mixed-citation xml:lang="en">15. Casimiro S., Mohammad K.S., Pires R. et al. RANKL/RANK/MMP-1 molecular triad contributes to the metastatic phenotype of breast and prostate cancer cells in vitro. PLoS One 2013;8(5):e63153.</mixed-citation><mixed-citation xml:lang="ru">Casimiro S., Mohammad K.S., Pires R. et al. RANKL/RANK/MMP-1 molecular triad contributes to the metastatic phenotype of breast and prostate cancer cells in vitro. PLoS One 2013;8(5):e63153.</mixed-citation></citation-alternatives></ref><ref id="B16"><label>16.</label><citation-alternatives><mixed-citation xml:lang="en">16. Schramek D., Sigl V., Penninger J.M. RANKL and RANK in sex hormone-induced breast cancer and breast cancer metastasis. Trends Endocrinol Metab 2011;22(5):188–94.</mixed-citation><mixed-citation xml:lang="ru">Schramek D., Sigl V., Penninger J.M. RANKL and RANK in sex hormone-induced breast cancer and breast cancer metastasis. Trends Endocrinol Metab 2011;22(5):188–94.</mixed-citation></citation-alternatives></ref><ref id="B17"><label>17.</label><citation-alternatives><mixed-citation xml:lang="en">17. Gomez-Veiga F., Ponce-Reixa J., Martinez-Breijo S. et al. Advances in prevention and treatment of bone metastases in prostate cancer. Role of RANK/RANKL inhibition. Actas Urol Esp 2012;37(5):292–304.</mixed-citation><mixed-citation xml:lang="ru">Gomez-Veiga F., Ponce-Reixa J., Martinez-Breijo S. et al. Advances in prevention and treatment of bone metastases in prostate cancer. Role of RANK/RANKL inhibition. Actas Urol Esp 2012;37(5):292–304.</mixed-citation></citation-alternatives></ref><ref id="B18"><label>18.</label><citation-alternatives><mixed-citation xml:lang="en">18. Mikami S., Oya M., Mizuno R. et al. Invasion and metastasis of renal cell carcinoma. Med Mol Morphol 2013;47(2):63–7.</mixed-citation><mixed-citation xml:lang="ru">Mikami S., Oya M., Mizuno R. et al. Invasion and metastasis of renal cell carcinoma. Med Mol Morphol 2013;47(2):63–7.</mixed-citation></citation-alternatives></ref><ref id="B19"><label>19.</label><citation-alternatives><mixed-citation xml:lang="en">19. Peng X., Guo W., Ren T. et al. Differential expression of the RANKL/RANK/OPG system is associated with bone metastasis in human non-small cell lung cancer. PLoS One 2013;8(3):e58361.</mixed-citation><mixed-citation xml:lang="ru">Peng X., Guo W., Ren T. et al. Differential expression of the RANKL/RANK/OPG system is associated with bone metastasis in human non-small cell lung cancer. PLoS One 2013;8(3):e58361.</mixed-citation></citation-alternatives></ref><ref id="B20"><label>20.</label><citation-alternatives><mixed-citation xml:lang="en">20. Brown J.M., Zhang J., Keller E.T. Opg, RANKl, and RANK in cancer metastasis: expression and regulation. Cancer Treat Res 2004;118:149–72.</mixed-citation><mixed-citation xml:lang="ru">Brown J.M., Zhang J., Keller E.T. Opg, RANKl, and RANK in cancer metastasis: expression and regulation. Cancer Treat Res 2004;118:149–72.</mixed-citation></citation-alternatives></ref><ref id="B21"><label>21.</label><citation-alternatives><mixed-citation xml:lang="en">21. Zheng Y., Zhou H., Brennan K. et al. Inhibition of bone resorption, rather than direct cytotoxicity, mediates the anti-tumour actions of ibandronate and osteoprotegerin in a murine model of breast cancer bone metastasis. Bone 2007;40(2):471–8.</mixed-citation><mixed-citation xml:lang="ru">Zheng Y., Zhou H., Brennan K. et al. Inhibition of bone resorption, rather than direct cytotoxicity, mediates the anti-tumour actions of ibandronate and osteoprotegerin in a murine model of breast cancer bone metastasis. Bone 2007;40(2):471–8.</mixed-citation></citation-alternatives></ref><ref id="B22"><label>22.</label><citation-alternatives><mixed-citation xml:lang="en">22. Rucci N., Millimaggi D., Mari M. et al. Receptor activator of NF-kappaB ligand enhances breast cancer-induced osteolytic lesions through upregulation of extracellular matrix metalloproteinase inducer/CD147. Cancer Res 2010;70(15):6150–60.</mixed-citation><mixed-citation xml:lang="ru">Rucci N., Millimaggi D., Mari M. et al. Receptor activator of NF-kappaB ligand enhances breast cancer-induced osteolytic lesions through upregulation of extracellular matrix metalloproteinase inducer/CD147. Cancer Res 2010;70(15):6150–60.</mixed-citation></citation-alternatives></ref><ref id="B23"><label>23.</label><citation-alternatives><mixed-citation xml:lang="en">23. Kukita A., Kukita T. Multifunctional properties of RANKL/RANK in cell differentiation, proliferation and metastasis. Future Oncol 2013;9(11):1609–22.</mixed-citation><mixed-citation xml:lang="ru">Kukita A., Kukita T. Multifunctional properties of RANKL/RANK in cell differentiation, proliferation and metastasis. Future Oncol 2013;9(11):1609–22.</mixed-citation></citation-alternatives></ref><ref id="B24"><label>24.</label><citation-alternatives><mixed-citation xml:lang="en">24. Costa-Rodrigues J., Teixeira C.A., Fernandes M.H. Paracrine-mediated osteoclastogenesis by the osteosarcoma MG63 cell line: is RANKL/RANK signalling really important? Clin Exp Metastasis 2011;28(6):505–14.</mixed-citation><mixed-citation xml:lang="ru">Costa-Rodrigues J., Teixeira C.A., Fernandes M.H. Paracrine-mediated osteoclastogenesis by the osteosarcoma MG63 cell line: is RANKL/RANK signalling really important? Clin Exp Metastasis 2011;28(6):505–14.</mixed-citation></citation-alternatives></ref><ref id="B25"><label>25.</label><citation-alternatives><mixed-citation xml:lang="en">25. Mori K., Le Goff B., Berreur M. et al. Human osteosarcoma cells express functional receptor activator of nuclear factor-kappa B. J Pathol 2007;211(5):555–62.</mixed-citation><mixed-citation xml:lang="ru">Mori K., Le Goff B., Berreur M. et al. Human osteosarcoma cells express functional receptor activator of nuclear factor-kappa B. J Pathol 2007;211(5):555–62.</mixed-citation></citation-alternatives></ref><ref id="B26"><label>26.</label><citation-alternatives><mixed-citation xml:lang="en">26. Mori K., Berreur M., Blanchard F. et al. Receptor activator of nuclear factor-kappaB ligand (RANKL) directly modulates the gene expression profile of RANK-positive Saos-2 human osteosarcoma cells. Oncol Rep 2007;18(6):1365–71.</mixed-citation><mixed-citation xml:lang="ru">Mori K., Berreur M., Blanchard F. et al. Receptor activator of nuclear factor-kappaB ligand (RANKL) directly modulates the gene expression profile of RANK-positive Saos-2 human osteosarcoma cells. Oncol Rep 2007;18(6):1365–71.</mixed-citation></citation-alternatives></ref><ref id="B27"><label>27.</label><citation-alternatives><mixed-citation xml:lang="en">27. Lee J.A., Jung J.S., Kim D.H. et al. RANKL expression is related to treatment outcome of patients with localized, highgrade osteosarcoma. Pediatr Blood Cancer 2011;56(5):738–43.</mixed-citation><mixed-citation xml:lang="ru">Lee J.A., Jung J.S., Kim D.H. et al. RANKL expression is related to treatment outcome of patients with localized, highgrade osteosarcoma. Pediatr Blood Cancer 2011;56(5):738–43.</mixed-citation></citation-alternatives></ref><ref id="B28"><label>28.</label><citation-alternatives><mixed-citation xml:lang="en">28. Mori K., Ando K., Heymann D., Redini F. Receptor activator of nuclear factor-kappa B ligand (RANKL) stimulates bone-associated tumors through functional RANK expressed on bone-associated cancer cells? Histol Histopathol 2009;24(2):235–42.</mixed-citation><mixed-citation xml:lang="ru">Mori K., Ando K., Heymann D., Redini F. Receptor activator of nuclear factor-kappa B ligand (RANKL) stimulates bone-associated tumors through functional RANK expressed on bone-associated cancer cells? Histol Histopathol 2009;24(2):235–42.</mixed-citation></citation-alternatives></ref><ref id="B29"><label>29.</label><citation-alternatives><mixed-citation xml:lang="en">29. Rousseau J., Escriou V., Lamoureux F. et al. Formulated siRNAs targeting Rankl prevent osteolysis and enhance chemotherapeutic response in osteosarcoma models. J Bone Miner Res 2011;26(10):2452–62.</mixed-citation><mixed-citation xml:lang="ru">Rousseau J., Escriou V., Lamoureux F. et al. Formulated siRNAs targeting Rankl prevent osteolysis and enhance chemotherapeutic response in osteosarcoma models. J Bone Miner Res 2011;26(10):2452–62.</mixed-citation></citation-alternatives></ref><ref id="B30"><label>30.</label><citation-alternatives><mixed-citation xml:lang="en">30. Hsu C.J., Lin T.Y., Kuo C.C. et al. Involvement of integrin up-regulation in RANKL/RANK pathway of chondrosarcomas migration. J Cell Biochem 2010;111(1):138–47.</mixed-citation><mixed-citation xml:lang="ru">Hsu C.J., Lin T.Y., Kuo C.C. et al. Involvement of integrin up-regulation in RANKL/RANK pathway of chondrosarcomas migration. J Cell Biochem 2010;111(1):138–47.</mixed-citation></citation-alternatives></ref><ref id="B31"><label>31.</label><citation-alternatives><mixed-citation xml:lang="en">31. Wang Z., Ding L., Zhang S. et al. Effects of icariin on the regulation of the OPG- RANKL-RANK system are mediated through the MAPK pathways in IL-1betastimulated human SW1353 chondrosarcoma cells. Int J Mol Med 2014;34(6):1720–6.</mixed-citation><mixed-citation xml:lang="ru">Wang Z., Ding L., Zhang S. et al. Effects of icariin on the regulation of the OPG- RANKL-RANK system are mediated through the MAPK pathways in IL-1betastimulated human SW1353 chondrosarcoma cells. Int J Mol Med 2014;34(6):1720–6.</mixed-citation></citation-alternatives></ref><ref id="B32"><label>32.</label><citation-alternatives><mixed-citation xml:lang="en">32. Taylor R., Knowles H.J., Athanasou N.A. Ewing sarcoma cells express RANKL and support osteoclastogenesis. J Pathol 2011;225(2):195–202.</mixed-citation><mixed-citation xml:lang="ru">Taylor R., Knowles H.J., Athanasou N.A. Ewing sarcoma cells express RANKL and support osteoclastogenesis. J Pathol 2011;225(2):195–202.</mixed-citation></citation-alternatives></ref><ref id="B33"><label>33.</label><citation-alternatives><mixed-citation xml:lang="en">33. Pelle D.W., Ringler J.W., Peacock J.D. et al. Targeting receptor-activator of nuclear kappaB ligand in aneurysmal bone cysts: verification of target and therapeutic response. Transl Res 2014;164(2):139–48.</mixed-citation><mixed-citation xml:lang="ru">Pelle D.W., Ringler J.W., Peacock J.D. et al. Targeting receptor-activator of nuclear kappaB ligand in aneurysmal bone cysts: verification of target and therapeutic response. Transl Res 2014;164(2):139–48.</mixed-citation></citation-alternatives></ref><ref id="B34"><label>34.</label><citation-alternatives><mixed-citation xml:lang="en">34. Lopez-Pousa A., Broto J.M., Garrido T., Vazquez J. Giant cell tumour of bone: new treatments in development. Clin Transl Oncol 2015;17(6):419–30.</mixed-citation><mixed-citation xml:lang="ru">Lopez-Pousa A., Broto J.M., Garrido T., Vazquez J. Giant cell tumour of bone: new treatments in development. Clin Transl Oncol 2015;17(6):419–30.</mixed-citation></citation-alternatives></ref><ref id="B35"><label>35.</label><citation-alternatives><mixed-citation xml:lang="en">35. Mak I.W., Evaniew N., Popovic S. et al. A translational study of the neoplastic cells of giant cell tumor of bone following neoadjuvant denosumab. J Bone Joint Surg Am 2014;96(15):e127.</mixed-citation><mixed-citation xml:lang="ru">Mak I.W., Evaniew N., Popovic S. et al. A translational study of the neoplastic cells of giant cell tumor of bone following neoadjuvant denosumab. J Bone Joint Surg Am 2014;96(15):e127.</mixed-citation></citation-alternatives></ref><ref id="B36"><label>36.</label><citation-alternatives><mixed-citation xml:lang="en">36. Singh A.S., Chawla N.S., Chawla S.P. Giant-cell tumor of bone: treatment options and role of denosumab. Biologics 2015;9:69–74.</mixed-citation><mixed-citation xml:lang="ru">Singh A.S., Chawla N.S., Chawla S.P. Giant-cell tumor of bone: treatment options and role of denosumab. Biologics 2015;9:69–74.</mixed-citation></citation-alternatives></ref><ref id="B37"><label>37.</label><citation-alternatives><mixed-citation xml:lang="en">37. Ulas A., Bulent Akinci M., Silay K. et al. Denosumab: Excellent response of metastatic giant cell tumor of the bone. J BUON 2015;20(2):666–7.</mixed-citation><mixed-citation xml:lang="ru">Ulas A., Bulent Akinci M., Silay K. et al. Denosumab: Excellent response of metastatic giant cell tumor of the bone. J BUON 2015;20(2):666–7.</mixed-citation></citation-alternatives></ref><ref id="B38"><label>38.</label><citation-alternatives><mixed-citation xml:lang="en">38. Anastasilakis A.D., Toulis K.A., Polyzos S.A., Terpos E. RANKL inhibition for the management of patients with benign metabolic bone disorders. Expert Opin Investig Drugs 2009;18(8):1085–102.</mixed-citation><mixed-citation xml:lang="ru">Anastasilakis A.D., Toulis K.A., Polyzos S.A., Terpos E. RANKL inhibition for the management of patients with benign metabolic bone disorders. Expert Opin Investig Drugs 2009;18(8):1085–102.</mixed-citation></citation-alternatives></ref><ref id="B39"><label>39.</label><citation-alternatives><mixed-citation xml:lang="en">39. Burkiewicz J.S., Scarpace S.L., Bruce S.P. Denosumab in osteoporosis and oncology. Ann Pharmacother 2009;43(9):1445–55.</mixed-citation><mixed-citation xml:lang="ru">Burkiewicz J.S., Scarpace S.L., Bruce S.P. Denosumab in osteoporosis and oncology. Ann Pharmacother 2009;43(9):1445–55.</mixed-citation></citation-alternatives></ref><ref id="B40"><label>40.</label><citation-alternatives><mixed-citation xml:lang="en">40. Body J.J., Greipp P., Coleman R.E. et al. A phase I study of AMGN-0007, a recombinant osteoprotegerin construct, in patients with multiple myeloma or breast carcinoma related bone metastases. Cancer 2003;97(3 Suppl):887–92.</mixed-citation><mixed-citation xml:lang="ru">Body J.J., Greipp P., Coleman R.E. et al. A phase I study of AMGN-0007, a recombinant osteoprotegerin construct, in patients with multiple myeloma or breast carcinoma related bone metastases. Cancer 2003;97(3 Suppl):887–92.</mixed-citation></citation-alternatives></ref><ref id="B41"><label>41.</label><citation-alternatives><mixed-citation xml:lang="en">41. Branstetter D.G., Nelson S.D., Manivel J.C. et al. Denosumab induces tumor reduction and bone formation in patients with giant-cell tumor of bone. Clin Cancer Res 2012;18(16):4415–24.</mixed-citation><mixed-citation xml:lang="ru">Branstetter D.G., Nelson S.D., Manivel J.C. et al. Denosumab induces tumor reduction and bone formation in patients with giant-cell tumor of bone. Clin Cancer Res 2012;18(16):4415–24.</mixed-citation></citation-alternatives></ref><ref id="B42"><label>42.</label><citation-alternatives><mixed-citation xml:lang="en">42. Lam F.C., Arle J.E., Glazer P.A., Kasper E.M. Primary extradural tumors of the spine – case review with evidenceguided management. Surg Neurol Int 2014;5(Suppl 7):S373–5.</mixed-citation><mixed-citation xml:lang="ru">Lam F.C., Arle J.E., Glazer P.A., Kasper E.M. Primary extradural tumors of the spine – case review with evidenceguided management. Surg Neurol Int 2014;5(Suppl 7):S373–5.</mixed-citation></citation-alternatives></ref><ref id="B43"><label>43.</label><citation-alternatives><mixed-citation xml:lang="en">43. Cathomas R., Rothermundt C., Bode B. et al. RANK ligand blockade with denosumab in combination with sorafenib in chemorefractory osteosarcoma: a possible step forward? Oncology 2014;88(4):257–60.</mixed-citation><mixed-citation xml:lang="ru">Cathomas R., Rothermundt C., Bode B. et al. RANK ligand blockade with denosumab in combination with sorafenib in chemorefractory osteosarcoma: a possible step forward? Oncology 2014;88(4):257–60.</mixed-citation></citation-alternatives></ref><ref id="B44"><label>44.</label><citation-alternatives><mixed-citation xml:lang="en">44. Hannon R., Eastell R. Preanalytical variability of biochemical markers of bone turnover. Osteoporos Int 2000;11 Suppl 6: S30–44.</mixed-citation><mixed-citation xml:lang="ru">Hannon R., Eastell R. Preanalytical variability of biochemical markers of bone turnover. Osteoporos Int 2000;11 Suppl 6: S30–44.</mixed-citation></citation-alternatives></ref><ref id="B45"><label>45.</label><citation-alternatives><mixed-citation xml:lang="en">45. Findlay D.M., Atkins G.J. Relationship between serum RANKL and RANKL in bone. Osteoporos Int 2011;22(10):2597–602.</mixed-citation><mixed-citation xml:lang="ru">Findlay D.M., Atkins G.J. Relationship between serum RANKL and RANKL in bone. Osteoporos Int 2011;22(10):2597–602.</mixed-citation></citation-alternatives></ref><ref id="B46"><label>46.</label><citation-alternatives><mixed-citation xml:lang="en">46. Hawa G., Brinskelle-Schmal N., Glatz K. et al. Immunoassay for soluble RANKL (receptor activator of NF-kappaB ligand) in serum. Clin Lab 2003;49(9–10):461–3.</mixed-citation><mixed-citation xml:lang="ru">Hawa G., Brinskelle-Schmal N., Glatz K. et al. Immunoassay for soluble RANKL (receptor activator of NF-kappaB ligand) in serum. Clin Lab 2003;49(9–10):461–3.</mixed-citation></citation-alternatives></ref><ref id="B47"><label>47.</label><citation-alternatives><mixed-citation xml:lang="en">47. Furuya D., Kaneko R., Yagihashi A. et al. Immuno-PCR assay for homodimeric osteoprotegerin. Clin Chem 2001; 47(8):1475–7.</mixed-citation><mixed-citation xml:lang="ru">Furuya D., Kaneko R., Yagihashi A. et al. Immuno-PCR assay for homodimeric osteoprotegerin. Clin Chem 2001; 47(8):1475–7.</mixed-citation></citation-alternatives></ref><ref id="B48"><label>48.</label><citation-alternatives><mixed-citation xml:lang="en">48. Mercatali L., Ricci M., Scarpi E. et al. RANK/RANK-L/OPG in patients with bone metastases treated with anticancer agents and zoledronic acid: a prospective study. Int J Mol Sci 2013;14(6):10683–93.</mixed-citation><mixed-citation xml:lang="ru">Mercatali L., Ricci M., Scarpi E. et al. RANK/RANK-L/OPG in patients with bone metastases treated with anticancer agents and zoledronic acid: a prospective study. Int J Mol Sci 2013;14(6):10683–93.</mixed-citation></citation-alternatives></ref><ref id="B49"><label>49.</label><citation-alternatives><mixed-citation xml:lang="en">49. De Leenheer E., Mueller G.S., Vanderkerken K., Croucher P.I. Evidence of a role for RANKL in the development of myeloma bone disease. Curr Opin Pharmacol 2004;4(4):340–6.</mixed-citation><mixed-citation xml:lang="ru">De Leenheer E., Mueller G.S., Vanderkerken K., Croucher P.I. Evidence of a role for RANKL in the development of myeloma bone disease. Curr Opin Pharmacol 2004;4(4):340–6.</mixed-citation></citation-alternatives></ref><ref id="B50"><label>50.</label><citation-alternatives><mixed-citation xml:lang="en">50. Kushlinskii N.E., Timofeev Y.S., Solov,ev Y.N. et al. Components of the RANK/RANKL/OPG system, IL-6, IL-8, IL-16, MMP-2, and calcitonin in the sera of patients with bone tumors. Bull Exp Biol Med 2014;157(4):520–3.</mixed-citation><mixed-citation xml:lang="ru">Kushlinskii N.E., Timofeev Y.S., Solov,ev Y.N. et al. Components of the RANK/RANKL/OPG system, IL-6, IL-8, IL-16, MMP-2, and calcitonin in the sera of patients with bone tumors. Bull Exp Biol Med 2014;157(4):520–3.</mixed-citation></citation-alternatives></ref><ref id="B51"><label>51.</label><citation-alternatives><mixed-citation xml:lang="en">51. Kushlinskii N.E., Gershtein E.S., Timofeev Y.S. et al. Osteoprotegerin (OPG) – receptor activator of NF-κB (RANK) – RANK ligand (RANKL) signaling system components and pro-inflammatory cytokines in blood serum of patients with primary bone neoplasms. Proceedings of 3rd International Conference on Predictive, Preventive and Personalized Medicine &amp; Molecular Diagnostics, Sept. 01–03, 2015, Valencia, Spain. J Pharmacogenomics Pharmacoproteomics 2015;(2):71.</mixed-citation><mixed-citation xml:lang="ru">Kushlinskii N.E., Gershtein E.S., Timofeev Y.S. et al. Osteoprotegerin (OPG) – receptor activator of NF-κB (RANK) – RANK ligand (RANKL) signaling system components and pro-inflammatory cytokines in blood serum of patients with primary bone neoplasms. Proceedings of 3rd International Conference on Predictive, Preventive and Personalized Medicine &amp; Molecular Diagnostics, Sept. 01–03, 2015, Valencia, Spain. J Pharmacogenomics Pharmacoproteomics 2015;(2):71.</mixed-citation></citation-alternatives></ref><ref id="B52"><label>52.</label><citation-alternatives><mixed-citation xml:lang="en">52. Wagner D., Fahrleitner-Pammer A. Levels of osteoprotegerin (OPG) and receptor activator for nuclear factor kappa B ligand (RANKL) in serum: are they of any help? Wien Med Wochenschr 2010;160(17–18): 452–7.</mixed-citation><mixed-citation xml:lang="ru">Wagner D., Fahrleitner-Pammer A. Levels of osteoprotegerin (OPG) and receptor activator for nuclear factor kappa B ligand (RANKL) in serum: are they of any help? Wien Med Wochenschr 2010;160(17–18): 452–7.</mixed-citation></citation-alternatives></ref></ref-list></back></article>
