Bisphosphonates May Reduce Recurrence in Giant Cell Tumor by Inducing Apoptosis

Chang, Seong Sil; Suratwala, Sanjeev J; Jung, Kwang-Mook; Doppelt, Jason D.; Zhang, Hui Zhu; Blaine, Theodore A.; Kim, Tae Wan; Winchester, Robert; Lee, Francis Young‐In

doi:10.1097/01.blo.0000141372.54456.80

Cited by 98 publications

(67 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Systemically administered bisphosphonate has been shown to reduce skeletal-related event (SRE), including pathological fractures (non-vertebral, vertebral, combined), radiotherapy, spinal cord compression, orthopaedic surgery, and hypercalcaemia, in association with malignancy (eg. myeloma and breast carcinoma) (Chang et al, 2004). Local administrated bisphosphonate with eluted bone cement is also demonstrated effective in growth inhibition on cell lines from giant cell tumor of bone, myeloma and renal cell carcinoma (Zwolak et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Bisphosphonates (BPs) can block the bone resorption activity and promote osteoblast activity. In vitro studies also reveal the mechanism that bisphosphonates exert direct anti-tumor effects by inducing apoptosis of the stromal cells (Chang et al, 2004). However, there are still not many studies investigating the anti-GCT mechanism of bisphosphonates.…”

Section: Stimulation Of Osteogenic Differentiation In Stromal Cells Omentioning

confidence: 99%

See 1 more Smart Citation

Stimulation of Osteogenic Differentiation in Stromal Cells of Giant Cell Tumour of Bone by Zoledronic Acid

Yang¹,

Zheng²,

Li³

et al. 2013

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Therapeutic effects of zoledronic acid (ZOL) on giant cell tumour of bone (GCT) have been proven. Apoptosis induction was considered to be one of the mechanisms of ZOL tumour inhibition. In this study, we presented the possibility of an osteogenic differentiation stimulation mechanism of ZOL and further investigated dosage and time effects. We treated stromal cells of GCT (GCTSC) with ZOL for 48 hours at different concentrations (0 μM, 0.01 μM, 0.1 μM, 1 μM, 5 μM, 30 μM) and assessed apoptotic and osteogenic differentiation markers with immunohistochemical techniques and real-time quantitative RT-PCR. Our results suggested that ZOL enhanced mRNA expression of Cbfa-1, osterix and osteocalcin genes with a maximum effect at 1μM in GCTSC. Time course experiments indicated a time dependent osteogenic differentiation effect. In conclusion, ZOL may be considered as an adjuvant in the treatment of GCT not only by inducing apoptosis but also by stimulating osteogenic differentiation of remaining tumor stromal cells after surgery.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Stimulation Of Osteogenic Differentiation In Stromal Cells Omentioning

confidence: 99%

Stimulation of Osteogenic Differentiation in Stromal Cells of Giant Cell Tumour of Bone by Zoledronic Acid

Yang¹,

Zheng²,

Li³

et al. 2013

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

show abstract

“…The osteoclastic character of MNGC in GCT is the basis for the therapeutic use of bisphosphonates to inhibit tumour-induced osteolysis. Bisphosphonate-induced apoptosis of MNGC has already been shown under cell culture conditions [11,12] in which the dose-dependent effects of treatment with zolendronate were far greater than those with pamidronate [9]. There are currently no reports available on the clinical application of bisphosphonates in GCT as carried out under conditions of a clinical study.…”

Section: Therapeutic Approachesmentioning

confidence: 99%

Giant cell tumour of bone: morphological, biological and histogenetical aspects

Werner

2006

International Orthopaedics (SICOT)

212

156

View full text Add to dashboard Cite

The giant cell tumour of bone (GCT) is a locally aggressive intraosseous neoplasm of obscure biological behaviour. Although well defined in clinical, radiological and histological terms, detailed information on its biological development is still relatively incomplete. The tumoral tissue consists of three cell types -the neoplastic giant cell tumour stromal cells (GCTSC), representing the proliferative fraction, secondarily recruited mononuclear histiocytic cells (MNHC) and multinuclear giant cells (MNGC). These cellular components interact together with factors that have a role in regulating osteoclast function in normal bone tissue (e.g. RANK, RANKL, OPG, M-CSF). Recent publications suggest that the neoplastic stromal cells express differentiation features of mesenchymal stem cells. Further research of the pathogenesis of GCT as well as the complex interactions of its cellular populations may provide the knowledge necessary for developing approaches for a biological-based therapy of this neoplasm.Résumé Les tumeurs à cellules géantes (GCT) sont des tumeurs localement agressives de type néoplasme intra osseux don't les mécanismes biologiques restent relativement obscurs. Cependant si ces tumeurs sont bien définies sur le plan clinique, radiologique et histologique, les détails marquants de leur développement biologique restent inconnus. Le tissu tumoral consiste en un stroma de tumeurs à cellules géantes (GCTSC) qui représente la partie prolifér-ative de la tumeur avec adjonction secondaire de cellules de type histogitaire mononuclées (MNHC) et de cellules géantes (MNGC). Ces composants cellulaires interagissent avec un certain nombre de facteurs régulant l'action ostéoclastique du tissu osseux normal (e.g. RANK, RANKL, OPG, M-CSF). De récentes publications permettent de penser que ce stroma cellulaire de type néoplasique exprime une différenciation de cellules mésenchymateuses. De prochaines recherches sur la pathogénèse des tumeurs à cellules géantes ainsi que sur les interactions complexes des différentes populations cellulaires devraient permettre d'approcher un traitement médical pour ce type de néoplasme.

show abstract

“…Drugs that target the osteolytic process lower recurrence rates associated with morbidity and mortality and are considered useful for new clinical treatments. 5,6 …”

mentioning

confidence: 99%

Identification of Potential Biomarkers for Giant Cell Tumor of Bone Using Comparative Proteomics Analysis

Conti

Rodriguez

Chiechi

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

Giant cell tumor of bone can be locally aggressive and occasionally can metastasize in the lungs. To identify new markers predictive of aggressive behavior, we analyzed five patients who developed lung metastasis and five who remained disease free for a minimum of 5 years. Using two-dimensional electrophoresis, we detected 28 differentially expressed spots. Fourteen spots were identified using mass spectrometry, including seven up-regulated and seven down-regulated in metastatic samples and classified according to functional categories. We then selected five proteins involved in cell cycle or apoptosis. Thioredoxin peroxidase, allograft inflammatory factor 1, and ubiquitin E2N had more than threefold up-regulation; glutathione peroxidase 1 had 1.9-fold up-regulation; and heat shock protein 27 showed down-regulation in metastatic samples with a very low P value. After validation and analysis of protein levels, evaluation of clinical impact was assessed in a much wider cohort of primary archival specimens. Immunodetection showed a higher frequency of thioredoxin peroxidase, allograft inflammatory factor 1, ubiquitin E2N, and glutathione peroxidase 1 overexpression in primary tumors that developed into lung metastases or that locally relapsed than in the disease-free group, with variable stain intensity and distribution. KaplanMeier analysis showed that high expression of glutathi- Giant cell tumor (GCT) is a benign bone tumor with fairly high local aggressiveness, and development of lung metastases is rare, occurring in 2% to 5% of cases.1 Histologically, the tumor pattern is formed by a network of spindle-shaped mononuclear stroma cells, round mononuclear histiocytic cells, and multinuclear giant cells similar to osteoclasts.2 Cellular components interact with various factors playing a role in osteoclast function regulation. In fact, precursors of osteoclasts express receptor activator of NF-B that in the presence of macrophage colonystimulating factor and its ligand, receptor activator of NF-B ligand, mediates osteoclast formation by increasing the expression of enzymes that dissolve organic and inorganic components of bone.3,4 At the same time, the endogenous osteoprotegerin counteracts these effects by competing for receptor activator of NF-B ligand and neutralizing it. These interactions may provide information to help develop new approaches to biological therapy of this tumor. Drugs that target the osteolytic process lower recurrence rates associated with morbidity and mortality and are considered useful for new clinical treatments. 5,6

show abstract

Bisphosphonates May Reduce Recurrence in Giant Cell Tumor by Inducing Apoptosis

Cited by 98 publications

References 35 publications

Stimulation of Osteogenic Differentiation in Stromal Cells of Giant Cell Tumour of Bone by Zoledronic Acid

Stimulation of Osteogenic Differentiation in Stromal Cells of Giant Cell Tumour of Bone by Zoledronic Acid

Giant cell tumour of bone: morphological, biological and histogenetical aspects

Identification of Potential Biomarkers for Giant Cell Tumor of Bone Using Comparative Proteomics Analysis

Contact Info

Product

Resources

About