Expression of ezrin, CD44, and VEGF in giant cell tumor of bone and its significance

Zhang, Jing; Dong, Jian; Yang, Zuozhang; Ma, Xiang; Zhang, Jinlei; Li, Mei; Chen, Yun; Ding, Yingying; Li, Kun; Zhang, Zhiping

doi:10.1186/s12957-015-0579-5

Cited by 13 publications

(10 citation statements)

References 21 publications

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“…Pathological angiogenesis has been demonstrated to be a key role in the progression, invasion, and metastasis of tumor cells. Vascular endothelial growth factor (VEGF), overexpressed in many solid tumors including GCTB, is one of the central triggers for angiogenesis [13,14]. VEGFR-2 presenting a strong tyrosine kinase activity towards pro-angiogenic signals is the key mediator of recognized VEGF induced phenotypes [15].…”

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Multiple Pulmonary Metastases of Giant Cell Tumor of Bone with expression of VEGFR-2 Successfully Treated by Denosumab and Apatinib: A Rare Case Report

Gong¹,

Luo²,

Wang³

et al. 2021

Preprint

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Background: Giant cell tumor of bone (GCTB) is a rare benign but locally aggressive bone tumor. It has a high tendency for local recurrence, which may increase the occurrence of lung metastasis. Currently, the treatment of pulmonary metastases of GCTB is controversial. Denosumab is the preferred regimen for unresectable metastatic lesions, but there are no alternative treatment options when denosumab is resistant. So far, no case reports of metastatic GCTB treated with denosumab and apatinib have been published. Case presentation: This is a case report of a 26-year-old female who experienced right knee pain for over 6 months. Radiography and computed tomography revealed osteolytic bony destruction in the proximal right tibia. Using histological, radiological, and clinical techniques, a diagnosis of GCTB was achieved. Meanwhile, the immunohistochemical stain-identified the tumor cells were positive for vascular endothelial growth factor receptor 2 (VEGFR-2). After intralesional curettage of the primary tumor and wide resection of local recurrence surgeries, she developed recurrent hemoptysis. Chest computed tomography (CT) images showed multiple pulmonary nodules. She was administrated denosumab therapy but disease progression was confirmed after four months of treatment. She then received denosumab and apatinib therapy for 24 months, after a partial response was achieved.Conclusions: We depict a case of multiple pulmonary metastases of GCTB successfully controlled by denosumab and apatinib therapy. VEGFR-2 may be an effective therapeutic target for GCTB with pulmonary metastasis when denosumab is ineffective.

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Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Multiple Pulmonary Metastases of Giant Cell Tumor of Bone with expression of VEGFR-2 Successfully Treated by Denosumab and Apatinib: A Rare Case Report

Gong¹,

Luo²,

Wang³

et al. 2021

Preprint

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“…VEGF, overexpressed in many solid tumors including GCTB, is one of the central triggers for angiogenesis. 22 , 23 VEGFR-2, which presents a strong tyrosine kinase activity towards pro-angiogenic signals, is the key mediator underlying VEGF-induced phenotypes. 24 Apatinib is a small-molecule TKI that selectively competes for the VEGFR-2 ATP binding site, blocking downstream signaling and inhibiting tumor angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

Multiple Pulmonary Metastases of Recurrent Giant Cell Tumor of Bone with Expression of VEGFR-2 Successfully Controlled by Denosumab and Apatinib: A Case Report and Literature Review

Gong¹,

Luo²,

Wang³

et al. 2021

CMAR

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Giant cell tumor of bone (GCTB) is a rare, benign, but locally aggressive bone tumor. It has a high tendency for local recurrence, which may increase the incidence of lung metastasis. Currently, an optimal treatment strategy has not been established because of the rarity of pulmonary metastatic GCTB. Denosumab is the preferred regimen for unresectable metastatic lesions; however, there are no alternative treatment options when patients are resistant to denosumab. Apatinib is a small-molecule tyrosine kinase inhibitor that selectively competes for the vascular endothelial growth factor receptor 2 (VEGFR-2) ATP binding site, and several studies have analyzed the effectiveness of apatinib in advanced or metastatic tumors. However, there is no report of apatinib as an anti-angiogenesis therapy for pulmonary metastatic GCTB to date. Here, we present a case of a 26-year-old female who was diagnosed with recurrent and pulmonary metastatic GCTB. Immunohistochemical (IHC) staining indicated that the tumor cells were positive for VEGFR-2. Denosumab was administered to control the metastases; nevertheless, disease progression was confirmed after four months of treatment. Given the IHC results and rapid disease progression, apatinib was added to the treatment strategy. After 42 months of treatment, the patient showed noticeable symptomatic improvement and considerable tumor shrinkage.

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“…In addition, WF pool enriched the expression of CD117 + /CD44 ++ antigens, which become 30% and 75% of cell population, respectively. A high level of CD44 ++ antigen was previously described expressed in MSCs [ 28 ] and was associated with degree of malignancy of GCTB [ 29 ]. Similar results were reported for antigen CD117 + , although detected at very low level (1% of cells) in human biopsies [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

Post-surgery fluids promote transition of cancer stem cell-to-endothelial and AKT/mTOR activity, contributing to relapse of giant cell tumors of bone

Fazioli

Colella²,

Miceli

et al. 2017

Oncotarget

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Giant cell tumors of bone (GCTB) are rare sarcomas with a high rate of unpredictable local relapse. Studies suggest that surgical methods affect recurrence, supporting the idea that local disease develops from re-growth of residual cancer cells. To identify early prognostic markers of individual risk of recurrence, we evaluated the effect of post-surgery fluids from a cohort of GCTB patients on growth of primary and established sarcoma cell lines, and mice xenograph. Post-surgery fluids increased cell growth and enhanced expression of CD44++, the principal receptor for the extracellular matrix component hyaluronan and the mesenchymal stem marker CD117+. Cancer cells became highly invasive and tumorigenic, acquiring stemness properties, and activated AKT/mTOR pathway. Prolonged stimulation with post-surgery fluids down-regulated the mesenchymal gene TWIST1 and Vimentin protein, and transdifferentiated cells into tubule-like structures positive to the endothelial markers VE-Cadherin and CD31+. In mice, post-surgery fluids gave rise to larger and more vascularized tumors than control, while in patients AKT/mTOR pathway activation was associated with recurrence by logistic regression (Kaplan-Meier; P<0.001). These findings indicate that post-surgery fluids are an adjuvant in mechanisms of tumor regrowth, increasing stem cell growth and AKT/mTOR activity.

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Expression of ezrin, CD44, and VEGF in giant cell tumor of bone and its significance

Cited by 13 publications

References 21 publications

WITHDRAWN: Multiple Pulmonary Metastases of Giant Cell Tumor of Bone with expression of VEGFR-2 Successfully Treated by Denosumab and Apatinib: A Rare Case Report

WITHDRAWN: Multiple Pulmonary Metastases of Giant Cell Tumor of Bone with expression of VEGFR-2 Successfully Treated by Denosumab and Apatinib: A Rare Case Report

Multiple Pulmonary Metastases of Recurrent Giant Cell Tumor of Bone with Expression of VEGFR-2 Successfully Controlled by Denosumab and Apatinib: A Case Report and Literature Review

Post-surgery fluids promote transition of cancer stem cell-to-endothelial and AKT/mTOR activity, contributing to relapse of giant cell tumors of bone

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