In Vitro Study of the Effects of Denosumab on Giant Cell Tumor of Bone: Comparison with Zoledronic Acid

2017 ◽  
Vol 25 (1) ◽  
pp. 409-419 ◽  
Author(s):  
Isao Shibuya ◽  
Masamichi Takami ◽  
Arei Miyamoto ◽  
Akiko Karakawa ◽  
Akira Dezawa ◽  
...  
1989 ◽  
Vol 75 (4) ◽  
pp. 389-395 ◽  
Author(s):  
Mario Campanacci ◽  
Gian Paolo Bagnara ◽  
Massimo Serra ◽  
Marco Giovannini ◽  
Paolo Tornasi ◽  
...  

The in vitro growth pattern of cells obtained from bioptic material of ten patients with giant cell tumor of bone (GCT) was investigated. Cytochemical reactions and monoclonal antibodies raised against macrophage markers were tested on the two histologically identifiable GCT cell populations. Only monoclonal antibody EBM/11 stained both mononuclear and giant cells. EBM/11 positivity and resistance of acid phosphatase to high doses of tartrate strongly suggest that both mononuclear and giant cells belong to the same lineage.


2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Shalini Singh ◽  
Isabella W. Y. Mak ◽  
Divya Handa ◽  
Michelle Ghert

Giant cell tumor of bone (GCT) is a bone tumor consisting of numerous multinucleated osteoclastic giant cells involved in bone resorption and neoplastic osteoblast-like stromal cells responsible for tumor growth. The tumor occasionally metastasizes to the lung; however, factors leading to metastasis in this tumor are unknown. The TWIST-1 protein (also referred to as TWIST) has been suggested to be involved in epithelial-mesenchymal transition (EMT) and tumor progression in some cancers. In this study we investigated the functional role of TWIST in GCT cell angiogenesis and migration. Overexpression of TWIST in neoplastic GCT stromal cells significantly increased mRNA and protein expression of VEGF and VEGFR1 in vitro, whereas knockdown of TWIST resulted in decreased VEGF and VEGFR1 expression. A stable cell line with TWIST overexpression resulted in features of EMT including increased cell migration and downregulation of E-cadherin. The results of our study indicate that TWIST may play an important role in angiogenesis and cell migration in GCT.


Author(s):  
Xudong Wang ◽  
Peiqiang Su ◽  
Yan Kang ◽  
Caixia Xu ◽  
Jincheng Qiu ◽  
...  

Melatonin (Mlt) confers potential antitumor effects in various types of cancer. However, to the best of our knowledge, the role of Mlt in the giant cell tumor of bone (GCTB) remains unknown. Moreover, further research is required to assess whether Mlt can enhance the therapeutic effect of zoledronic acid (Zol), a commonly used anti-GCTB drug. In this research, we investigated the effects of Mlt, Zol, and the combination of these two drugs on GCTB cells’ characteristics, including cell proliferation, apoptosis, osteogenic differentiation, migration, and invasion. The cell counting kit-8 (CCK-8) assay, colony formation assay, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay (TUNEL), alkaline phosphatase (ALP) staining, alizarin red staining (ARS), scratch wound healing assay, and transwell experiment were performed, respectively. Our results showed that Mlt could effectively inhibit the proliferation, migration, and invasion of GCTB cells, as well as promote the apoptosis and osteogenic differentiation of tumor cells. Of note, a stronger antitumor effect was observed when Mlt was combined with Zol treatment. This therapeutic effect might be achieved by inhibiting the activation of both the Hippo and NF-κB pathways. In conclusion, our study suggests that Mlt can be a new treatment for GCTB, which could further enhance the antitumor effect of Zol.


2013 ◽  
Vol 54 (6) ◽  
pp. 439-449 ◽  
Author(s):  
Carol P. Y. Lau ◽  
Lin Huang ◽  
Kwok Chuen Wong ◽  
Shekhar Madhukar Kumta

2015 ◽  
Vol 5 (4) ◽  
pp. 1586-1590
Author(s):  
Mehri Naseri . ◽  
Azim Akbarzadeh . ◽  
Zahra Saffari . ◽  
Hasan Ebrahimi Shahmabadi .

2020 ◽  
Vol 12 (2) ◽  
pp. 668-678 ◽  
Author(s):  
Yuan‐han Jin ◽  
Jing Zhang ◽  
Hao Zhu ◽  
Gen‐tao Fan ◽  
Guang‐xin Zhou

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3543
Author(s):  
Michal Mahdal ◽  
Jakub Neradil ◽  
Peter Mudry ◽  
Silvia Paukovcekova ◽  
Iva Staniczkova Zambo ◽  
...  

Giant-cell tumor of bone (GCTB) is an intermediate type of primary bone tumor characterized by locally aggressive growth with metastatic potential. The aim of this study was to identify new druggable targets among the cell signaling molecules involved in GCTB tumorigenesis. Profiles of activated signaling proteins in fresh-frozen tumor samples and tumor-derived cell lines were determined using phosphoprotein arrays. Analysis of the obtained data revealed epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor beta (PDGFRβ) as potential targets, but only the PDGFR inhibitor sunitinib caused a considerable decrease in stromal cell viability in vitro. Furthermore, in the case of a 17-year-old patient suffering from GCTB, we showed that the addition of sunitinib to the standard treatment of GCTB with the monoclonal antibody denosumab resulted in the complete depletion of multinucleated giant cells and mononuclear stromal cells in the tumor tissue. To summarize, the obtained data showed that a specific receptor tyrosine kinase (RTK) signaling pattern is activated in GCTB cells and plays an important role in the regulation of cell proliferation. Thus, activated RTKs and their downstream signaling pathways represent useful targets for precision treatment with low-molecular-weight inhibitors or with other types of modern biological therapy.


2019 ◽  
Vol 24 (7) ◽  
pp. 889 ◽  
Author(s):  
Astrid Lipplaa ◽  
Judith R. Kroep ◽  
Lizz van der Heijden ◽  
Paul C. Jutte ◽  
Pancras C.W. Hogendoorn ◽  
...  

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