Pathogenesis of Osteosclerotic Change Following Treatment with an Antibody Against RANKL for Giant Cell Tumour of the Bone
| Autor: | Akihiko Takeuchi, Hisaki Aiba, Hiroyuki Tsuchiya, Kensaku Abe, Yoshikazu Tanzawa, Mamer S. Rosario, Norio Yamamoto, Shinji Miwa, Katsuhiro Hayashi, Takashi Higuchi, Hideki Murakami, Yuta Taniguchi |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
Male musculoskeletal diseases Cancer Research Stromal cell Osteocalcin Bone Neoplasms Methylation Bone and Bones Histones 03 medical and health sciences 0302 clinical medicine Osteogenesis Biopsy medicine Humans Giant Cell Tumor of Bone 030222 orthopedics Bone Density Conservation Agents biology medicine.diagnostic_test business.industry Lysine RANK Ligand General Medicine Middle Aged Alkaline Phosphatase Immunohistochemistry Denosumab Microscopy Fluorescence Oncology Giant cell RANKL 030220 oncology & carcinogenesis Immunology biology.protein Cancer research Alkaline phosphatase Female business medicine.drug |
| Zdroj: | Anticancer Research. 37:748-754 |
| ISSN: | 1791-7530 0250-7005 |
| DOI: | 10.21873/anticanres.11373 |
| Popis: | Background Giant cell tumours (GCTs) of the bone are intermediate tumours that are locally aggressive. Denosumab, an antibody against receptor activator of nuclear factor kappa-B ligand (RANKL), was recently developed; however, it induces osteosclerotic change through an unknown mechanism. We determined whether osteosclerotic change could be induced by neoplastic stromal cells of giant cell tumours (GCTs). Patients and methods Participants included four patients with GCT of the bone who were treated with neoadjuvant denosumab. Expression of alkaline phosphatase (ALP), osteocalcin (OCN), RANKL and histone H3K36 trimethylation were assessed through immunohistochemistry of biopsy and surgical specimens. Results OCN expression was significantly elevated after denosumab treatment, whereas ALP and RANKL expressions were not significantly elevated. Immunofluorescence staining revealed OCN expression and H3K36 trimethylation while their co-localisation was confirmed in the surgical specimens. Conclusion Denosumab promoted OCN expression and might induce the osteogenic differentiation of GCT stromal cells. |
| Databáze: | OpenAIRE |
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