Rank ligand as a target in musculoskeletal neoplasms

Coté, Gregory M.

doi:10.1007/s12178-015-9310-y

Cited by 5 publications

(3 citation statements)

References 47 publications

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“… 1 More recently, denosumab (Ranmark; Daiichi Sankyo Company, Ltd., Tokyo, Japan) has been approved to treat GCTB. 2 Denosumab is a human monoclonal antibody that targets the receptor activator of nuclear factor-κB ligand (RANKL) with high specificity and affinity. 3 Receptor activator of nuclear factor kappa-Β ligand is a signaling molecule that is required for the bone resorptive function of osteoclast-like cells and is highly expressed on the stromal cells of tumors.…”

Section: Introductionmentioning

confidence: 99%

Giant Cell Tumors of the Bone: Changes in Image Features after Denosumab Administration

Oguro

Okuda

Sugiura

et al. 2018

MRMS

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Purpose:To assess the clinical importance in the feature change in giant cell tumors of the bone (GCTB) after denosumab treatment, detected by MRI.Methods:In 12 patients, MRI and CT of GCTB obtained before and after the treatment retrospectively compared. The tumor size, the signal intensity (SI) ratio between the solid part of the GCTB and muscle, cystic part size, gadolinium enhancement and apparent diffusion coefficient (ADC) value were measured on MRI. The bone formation in the tumor was observed on CT and X-ray.Results:The mean number of denosumab injections was 19 ± 10. The follow-up period was up to 2 years. One case showed partial remission, while the other 11 cases were stable. A mean SI ratio on T2-weighted image statistically significantly decreased from 3.9 to 1.9 after the treatment. A cystic component in the tumor was observed in five cases before the treatment, and the diameter of the cystic part decreased after the treatment in 80% of cases (4/5). All the tumors showed contrast enhancement on T1-weighted image pre- and post-treatment (11/11). The averaged ADC values were 1.52 × 10−3 mm2/s before and 1.44 × 10−3 mm2/s after the treatment (P = 0.63). Bone formation in the tumor was observed in 58% of cases (7/12).Conclusion:The decrease of SI ratio on T2-weighted image, shrinkage of cystic part and bone formation should be regarded as the effectiveness of denosumab treatment despite of no substantial change in the tumor size.

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Section: Introductionmentioning

confidence: 99%

Giant Cell Tumors of the Bone: Changes in Image Features after Denosumab Administration

Oguro

Okuda

Sugiura

et al. 2018

MRMS

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“…Consequently, drugs that target osteoclast formation can prevent osteolytic diseases. The RANKL signaling pathway is crucial for osteoclast formation and is an important druggable target for developing therapeutics against pathological diseases of bone loss (Cote 2015, Tat et al, 2009, McGrath 2011. In this study, we found that geraniol significantly alleviated the RANKL-induced osteoclast differentiation of RAW264.7 macrophages and CD14+ monocytes.…”

Section: Discussionmentioning

confidence: 52%

Geraniol attenuates osteoclast differentiation by suppressingNF-kB activity and expression of osteoclastogenic genes

2016

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Osteoporotic patients have lower bone mass due to increased bone resorption by osteoclasts. The aim of this study was to investigate the cytotoxic and anti-osteoclastogenic effects of geraniol, a natural monoterpene on human CD14+ monocytes (ex vivo) and murine RAW264.7 macrophages (in vitro) using alamar blue and tartrate resistant acid phosphatase (TRAP) staining respectively.The anti-osteoclastogenic activity of geraniol was further explored by analyzing its effects on actin ring formation and bone resorptive function of osteoclasts. Geraniol significantly (p<0.001) inhibited osteoclast formation in CD14+ monocytes and RAW264.7 macrophages without cytotoxicity. Moreover, reduced osteoclastogenesis in these cells led to an arrest in actin ring formation and diminished bone resorption. Analysis of underlying molecular mechanisms revealed that geraniol alleviated NF-kB activity, an indispensable upstream modulator of osteoclast formation. Furthermore, expression of key osteoclastogenic genes such as dendritic cell-specific transmembrane protein (DC-STAMP) involved in cell-cell fusion and nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1), a master transcription factor essential for osteoclast differentiation was downregulated by geraniol. These observations indicate that inhibition of osteoclast differentiation is presumably one of the pharmacological properties of geraniol.

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“…Two key osteoclastic factors suggested to be responsible for the progression of tumor-induced osteolysis are: receptor activator of nuclear factor kappa-Β (RANKL) and monocyte chemoattractant protein-1 (MCP-1) [18,19]. A clinical study reported that elevated RANKL expression in biopsies taken from patients with localized, high-grade OS is correlated with poorer prognosis and lower chance of survival [20].…”

Section: Introductionmentioning

confidence: 99%

Effects of Alendronate and Interferon-γ on Bone Cancer Cells In Vitro

Barone¹,

Fernandes²,

Dziak³

2020

Prime Archives in Biosciences

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Bisphosphonates are used to reduce pathological osteolysis in bone cancer patients. In addition to direct effects on tumor cells, these drugs may also alter the production of immune cell factors within the tumor microenvironment. Interferon-γ (IFN-γ) represents one such factor whose production by T lymphocytes is increased following bisphosphonate treatment. This study characterized the effects of alendronate (ALN), an aminobisphosphonate, and IFN-γ on viability, maturation, and osteoclastic factor production in human G292 osteosarcoma cells. Viability was assessed with a colorimetric assay; maturation by alkaline phosphatase (ALP) and mineralization via alizarin red. Receptor activator of nuclear factor kappa-Β ligand (RANKL) and monocyte chemoattractant protein-1 (MCP-1) production were quantified with ELISAs. ALN (5 nM) had no effect on viability. IFN-γ (1,000 U/mL) decreased this parameter alone and in the presence of ALN. ALN had a transient inhibitory effect on ALP. While IFN-γ increased this parameter, ALN inhibited this effect. Whereas ALN and IFN-γ each decreased RANKL, cotreatment with IFN-γ lessened the inhibitory effect of ALN. ALN decreased MCP-1 and attenuated IFN-γ induced increases. These studies suggest that bisphosphonates have direct effects on bone tumor cells and on the actions of cytokines in the tumor microenvironment and provide a basis for optimization of bone cancer therapy.

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Rank ligand as a target in musculoskeletal neoplasms

Cited by 5 publications

References 47 publications

Giant Cell Tumors of the Bone: Changes in Image Features after Denosumab Administration

Giant Cell Tumors of the Bone: Changes in Image Features after Denosumab Administration

Geraniol attenuates osteoclast differentiation by suppressingNF-kB activity and expression of osteoclastogenic genes

Effects of Alendronate and Interferon-γ on Bone Cancer Cells In Vitro

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