A study of the Distribution and Density of the VEGFR-2 Receptor on Glioma Microvascular Endothelial Cell Membranes

Zhan

Experimental and Therapeutic Medicine

et al. 2016

Self Cite

The aim of the current study was to demonstrate the distribution of VEGFR-2 on glioma microvascular endothelial cells on a nanoscale and investigate changes in VEGFR-2 activity following treatment with the VEGFR-2 inhibitor and agonist sorafenib and bradykinin, respectively. Three groups were evaluated in this study: Control glioma microvascular endothelial cells, sorafenib-treated glioma microvascular endothelial cells and bradykinin-treated glioma microvascular endothelial cells. Changes in the activity of VEGFR-2 on the glioma microvascular endothelial cell membranes following treatment with sorafenib and bradykinin were characterized by atomic force microscopy (AFM). Colloidal gold-labeled immune complexes and AFM were used to visualize the distribution of VEGFR-2 on the cell membranes. In the control group, VEGFR-2, which was observed as numerous globular structures, was evenly distributed on the cell surface membranes. The majority of the receptors were active. In the sorafenib group, only a few globular structures were observed on the cell membranes, with a density significantly lower than that in the control group (P<0.01). Furthermore, compared with the control group, fewer of the receptors were active. In the bradykinin group, numerous globular structures were densely distributed on the cell membranes, with a density significantly higher than that in the control group (P<0.01). The distribution and activity of VEGFR-2 on glioma microvascular endothelial cell membranes treated with sorafenib and bradykinin suggested that the activity of VEGFR-2 could be regulated by its inhibitor or agonist.

Section: Discussionmentioning

confidence: 96%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Characterizing nanoscale changes in the activity of VEGFR-2 on glioma microvascular endothelial cell membranes using atomic force microscopy

Zhan

Experimental and Therapeutic Medicine

et al. 2016

Self Cite

Anlotinib alone or in combination with bevacizumab in the treatment of recurrent high-grade glioma: a prospective single-arm, open-label phase II trial

Zhao,

Zhang,

Zhang

et al. 2024

BMC Cancer

Background Anlotinib is a multi-target tyrosine kinase inhibitor (TKI) targeting the vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), fibroblast growth factor receptor (FGFR), and c-Kit. This phase II study aimed to assess the efficacy and safety of anlotinib, either alone or in combination with bevacizumab (Bev) for recurrent high-grade glioma (rHGG) (NCT04822805, 30/03/2021). Methods Eligible patients had a histological diagnosis of rHGG with first or subsequent recurrences. All patients received oral anlotinib 12 mg or 10 mg on days 1–14 (repeated every 21 days). In cases where brain magnetic resonance imaging examination revealed an increase in peritumoral edema without worsening of symptoms, patients received a temporary treatment of intravenous bevacizumab 10 mg/kg to alleviate edema. The primary endpoint was the median progression-free survival (mPFS), and the secondary endpoints included median overall survival (mOS), objective response rate (ORR), disease control rate (DCR), and safety. Results Twenty-five patients with rHGG were included in the efficacy and safety assessments. Eighteen patients received anlotinib alone, and seven patients received anlotinib in combination with Bev. For all patients, the mPFS and mOS were 5.0 months and 13.6 months, respectively. The ORR was 32%, and the DCR was 96%. It is noteworthy that the survival and response data of recurrent glioblastoma (rGBM) exhibit similarities to those of rHGG. For rGBM patients, there were no significant differences in mPFS, mOS, ORR, or DCR between the anlotinib alone and anlotinib + Bev groups. However, the incidence of treatment-related adverse events of any grade was higher in the anlotinib + Bev group compared to the anlotinib alone group (100% vs. 78%, p = 0.041). Conclusions Both anlotinib alone and its combination with Bev demonstrated good efficacy and safety in the treatment of rHGG.

Combining apatinib and temozolomide for brainstem glioblastoma: a case report and review of literature

Zhu¹,

Zhao²,

Xu³

et al. 2022

Ann Palliat Med

Adult brainstem gliomas are characterized into subtypes depending on clinicopathologic and radiographic characteristics. Among them, brainstem glioblastoma is the most malignant and has the poorest prognosis, with surgical resection for this condition posing a great challenge and risk. Postoperative synchronous radiotherapy and temozolomide (TMZ) chemotherapy, or "Stupp's regimen", is the standard of care for glioblastomas. However, antiangiogenic therapy, which is widely used for different cancers, is now an alternative treatment for malignant tumors. Angiogenesis is one of the pathological features of glioblastoma and is involved in tumor progression and metastasis. Besides, previous studies suggested a better response to antiangiogenic therapy in some solid tumors with TP53 mutation than TP53 wide-type. Apatinib is a novel, oral, small-molecule tyrosine kinase inhibitor that mainly targets vascular endothelial growth factor receptor-2 (VEGFR-2) to inhibit angiogenesis. In addition, apatinib can cross the blood-brain barrier and improve encephaledema. This report describes the use of concurrent apatinib and dose-dense TMZ in a clinically inoperable patient who had a refractory brainstem glioblastoma with a TP53 germline mutation.He obtained an ongoing progression free survival (PFS) of nearly 16.0 months after resistance to TMZ maintenance. Due to the patient's circumstances, apatinib and TMZ was considered an effective and safe treatment method.