Denosumab in the Treatment of Giant Cell Tumor of Bone

2010 ◽  
Vol 06 ◽  
pp. 39
Author(s):  
David Thomas ◽  
Keyword(s):  
Giant Cell Tumor ◽  
Giant Cell ◽  
Cell Population ◽  
Osteoclast Differentiation ◽  
Bone Destruction ◽  
Osteoclast Formation ◽  
Cell Tumor ◽  
Rare Benign Tumor ◽  
And Function

Giant cell tumor of bone (GCT) is a rare, benign tumor characterized by localized bone destruction. GCT is thought to be biphenotypic, comprising a neoplastic stromal cell population and an osteoclast-like giant cell population. Recent studies have established that receptor activator of NF κβ ligand (RANKL) plays an important role in GCT. Although its actions are not fully understood, RANKL acts as an obligate signal for normal osteoclast formation and function. The development of an antagonist to RANKL, denosumab, has led to clinical trials in osteoporosis, bone metastases in cancer, and GCT. Generally well-tolerated, denosumab is an extremely effective inhibitor of osteoclast differentiation and function in humans. A preliminary study of the use of denosumab in patients with advanced or unresectable GCT has suggested considerable activity and clinical benefit. The eventual role of denosumab in GCT is currently the subject of an ongoing clinical trial.

scholarly journals Stromal Cell-Derived CCL20 Promotes Tumor Progression and Osteolysis in Giant Cell Tumor of Bone

2018 ◽  
Vol 51 (5) ◽  
pp. 2472-2483 ◽  
Author(s):  
Chenglong Zhao ◽  
Dongsheng Wang ◽  
Liang Tang ◽  
Zhichao Zhang ◽  
Song Li ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Giant Cell Tumor ◽  
Giant Cell ◽  
Mononuclear Cells ◽  
Bone Destruction ◽  
Cell Tumor ◽  
Migration Ability ◽  
And Migration ◽  
Proliferation And Migration

Background/Aims: Giant cell tumor of bone (GCTB), one of the most common primary bone tumors, leads to extensive bone destruction. However, the mechanisms underlying GCTB progression remain elusive and prognostic factors and treatment targets are required. In the current study, we explored the function of the chemokine family member CCL20 in GCTB progression. Methods: We explored the expression of CCL20 in stromal cells (GCTSCs) using microarray. Clinical analyses of the role of CCL20 in tumor progression were performed based on the patient cohort of our institution. The role of CCL20 in tumor proliferation was evaluated by MTS assay, migration ability was measured by a Transwell assay, and osteoclastogenesis was induced by CCL20 or GCTSC-conditioned medium. Quantitative PCR and western blot were used to measure the expression levels of mRNAs and proteins related to tumor progression. Results: CCL20 was upregulated in GCTSCs and correlated with tumor progression and prognosis. CCL20 induced GCTSC proliferation and migration in an autocrine manner. In addition, CCL20 recruited mononuclear cells and induced osteoclastogenesis by overactivating the AKT and NF-κB signaling pathways. Antibody blockade of CCL20 abolished the exacerbated osteoclastogenesis. Conclusion: Taken together, our data indicate that GCTSC secretion of CCL20 acts as a key modulator in the pathological progression of GCTB. It can promote GCTSC proliferation and migration in an autocrine manner and can recruit bone marrow monocytes to the tumor microenvironment and enhance osteoclastogenesis in a paracrine manner. These findings strongly indicate the potential prognostic and therapeutic value of CCL20 in GCTB.

scholarly journals MicroRNA-16-5p Inhibits Osteoclastogenesis in Giant Cell Tumor of Bone

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Shang Sang ◽  
Zhichang Zhang ◽  
Shu Qin ◽  
Changwei Li ◽  
Yang Dong
Keyword(s):  
Bone Resorption ◽  
Giant Cell Tumor ◽  
Giant Cell ◽  
Therapeutic Target ◽  
Bone Destruction ◽  
Osteoclast Formation ◽  
Cell Tumor ◽  
Nuclear Factor ◽  
Receptor Activator

Giant cell tumor (GCT) of bone is an aggressive skeletal tumor characterized by localized bone resorption. MicroRNA-16-5p (miR-16-5p) has been reported to be downregulated in lesions of patients with GCT, but little is known about its role in GCT. To explore the underlying function of miR-16-5p in GCT, we first detected its expression in patients with GCT. The results showed that osteoclast formation increased, whereas miR-16-5p expression considerably decreased with the severity of bone destruction. Furthermore, we found that miR-16-5p expression considerably decreased with the progression of receptor activator of nuclear factor-κB ligand- (RANKL-) induced osteoclastogenesis. Functionally, miR-16-5p mimics significantly reduced RANKL-induced osteoclast formation. However, treatment with an inhibitor of miR-16-5p significantly promoted osteoclastogenesis. These findings reveal that miR-16-5p inhibits osteoclastogenesis and that it may represent a therapeutic target for giant cell tumor of bone.

scholarly journals Serglycin induces osteoclastogenesis and promotes tumor growth in giant cell tumor of bone

2021 ◽  
Vol 12 (10) ◽  
Author(s):  
Yunfei He ◽  
Dongdong Cheng ◽  
Cheng Lian ◽  
Yingjie Liu ◽  
Wenqian Luo ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Giant Cell Tumor ◽  
Giant Cell ◽  
Stromal Cells ◽  
Osteoclast Differentiation ◽  
Xenograft Model ◽  
Bone Destruction ◽  
Underlying Mechanism ◽  
Cell Tumor

AbstractGiant cell tumor of bone (GCTB) is an aggressive osteolytic bone tumor characterized by the within-tumor presence of osteoclast-like multinucleated giant cells (MGCs), which are induced by the neoplastic stromal cells and lead to extensive bone destruction. However, the underlying mechanism of the pathological process of osteoclastogenesis in GCTB is poorly understood. Here we show that the proteoglycan Serglycin (SRGN) secreted by neoplastic stromal cells plays a crucial role in the formation of MGCs and tumorigenesis in GCTB. Upregulated SRGN expression and secretion are observed in GCTB tumor cells and patients. Stromal-derived SRGN promotes osteoclast differentiation from monocytes. SRGN knockdown in stromal cells inhibits tumor growth and bone destruction in a patient-derived orthotopic xenograft model of mice. Mechanistically SRGN interacts with CD44 on the cell surface of monocytes and thus activates focal adhesion kinase (FAK), leading to osteoclast differentiation. Importantly, blocking CD44 with a neutralizing antibody reduces the number of MGCs and suppresses tumorigenesis in vivo. Overall, our data reveal a mechanism of MGC induction in GCTB and support CD44-targeting approaches for GCTB treatment.

Role of radiologic imaging in management planning of giant cell tumor of bone

1984 ◽  
Vol 12 (2) ◽  
pp. 79-89 ◽  
Author(s):  
E. Levine ◽  
A. A. De Smet ◽  
J. R. Neff
Keyword(s):  
Giant Cell Tumor ◽  
Giant Cell ◽  
Cell Tumor ◽  
Management Planning ◽  
Radiologic Imaging

RECURRENCE OF GIANT CELL TUMOR OF BONE: THE ROLE OF MRI IN DIAGNOSIS

Orthopedics ◽  
1997 ◽  
Vol 20 (1) ◽  
pp. 67-69
Author(s):  
Barry J Waldman ◽  
Elias A Zerhouni ◽  
Frank J Frassica
Keyword(s):  
Giant Cell Tumor ◽  
Giant Cell ◽  
Cell Tumor

scholarly journals Role of Bisphosphonates as Adjuvants of Surgery in Giant Cell Tumor of Spine

10.14444/5087 ◽  
2018 ◽  
Vol 12 (6) ◽  
pp. 695-702
Author(s):  
CHAITANYA DEV PANNU ◽  
PANKAJ KANDHWAL ◽  
VIJAY RAGHAVAN ◽  
SHAH ALAM KHAN ◽  
SHISHIR RASTOGI ◽  
...  
Keyword(s):  
Giant Cell Tumor ◽  
Giant Cell ◽  
Cell Tumor

scholarly journals The Role of TWIST in Angiogenesis and Cell Migration in Giant Cell Tumor of Bone

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Shalini Singh ◽  
Isabella W. Y. Mak ◽  
Divya Handa ◽  
Michelle Ghert
Keyword(s):  
Cell Migration ◽  
Giant Cell Tumor ◽  
Giant Cell ◽  
Stromal Cells ◽  
Epithelial Mesenchymal Transition ◽  
Cell Tumor ◽  
Stable Cell Line ◽  
Mesenchymal Transition

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.

Giant cell tumor of the plantar tendon sheath: Role of MR imaging in diagnosis case report

1993 ◽  
Vol 17 (2) ◽  
pp. 153-155 ◽  
Author(s):  
Edward H. Demouy ◽  
Kuniyuki Kaneko ◽  
Howard M. Bear ◽  
Raoul P. Rodriguez
Keyword(s):  
Case Report ◽  
Mr Imaging ◽  
Giant Cell Tumor ◽  
Giant Cell ◽  
Tendon Sheath ◽  
Cell Tumor

scholarly journals Artificial finger joint replacement due to a giant cell tumor of the tendon sheath with bone destruction: A case report

2015 ◽  
Vol 10 (6) ◽  
pp. 3502-3504 ◽  
Author(s):  
HUI LU ◽  
HUI SHEN ◽  
QIANG CHEN ◽  
XIANG-QIAN SHEN ◽  
SHOU-CHENG WU
Keyword(s):  
Case Report ◽  
Giant Cell Tumor ◽  
Giant Cell ◽  
Joint Replacement ◽  
Bone Destruction ◽  
Tendon Sheath ◽  
Cell Tumor ◽  
Finger Joint
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