Efficacy of Combination Therapy with MET and VEGF Inhibitors for MET-overexpressing Glioblastoma

Okuda, Takeshi; Tasaki, Takayuki; Nakata, Susumu; Yamashita, Kimihiro; Yoshioka, Hirosuke; Izumoto, Shuichi; Fujita, Mitsugu

doi:10.21873/anticanres.11767

Cited by 11 publications

(6 citation statements)

References 14 publications

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“…Studies have demonstrated that VEGF is overexpressed in gastric, lung, colorectal, breast, prostate, liver cancer and other solid tumors (27,28). Recent studies have reported that the expression of VEGF in esophageal cancer is associated with lymph node metastasis, distant metastasis and clinical stage (P<0.05), but there is no significant correlation with pathological grading and depth of invasion (29,30). Additionally, overexpression of VEGF suggested poor prognosis of esophageal cancer, a meta-analysis reported that the risk of late stage (III and IV) increased in esophageal cancer patients with VEGF overexpression (HR=1.55), and the odds ratio (OR) was 2.14 (31).…”

Section: Discussionmentioning

confidence: 95%

DW‑MRI for esophageal squamous cell carcinoma, correlations between ADC values with histologic differentiation and VEGF expression: A retrospective study

Qing-xue

Wang

et al. 2019

Oncol Lett

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The aim of the present study was to assess the correlations between diffusion-weighted magnetic resonance imaging (DW-MRI) features with the histologic differentiation and the expression of vascular endothelial growth factor (VEGF) in esophageal squamous cell carcinoma (ESCC). A total of 52 patients with ESCC included in the present study received radiotherapy, and all patients underwent contrast enhanced MRI and DW-MRI prior to and following radiotherapy. The diffusion sensitivity coefficient ( b value) was set as 800 s/mm 2 . Apparent diffusion coefficient (ADC) values were automatically computed. VEGF expression was evaluated by immunohistochemical staining. The results demonstrated that the pathological grading of ESCC was positively correlated with ADC values ( r =0.635, P=0.0007), and the VEGF expression was inversely correlated with ADC values ( r =−0.321, P=0.008). However, no correlation was identified between the pathological grading and the VEGF expression ( r =0.178, P=0.284). All patients were categorized as complete response (CR) or partial response (PR) and the ADC values were increased significantly following radiotherapy. The mean ADC values in the CR group were higher than the PR group prior to radiotherapy ( t =5.156, P=0.0004). Therefore, we concluded that the DWI with ADC value measurement may represent the grade of tumor histologic differentiation and the degree of VEGF expression, and may also serve as a useful marker to predict radiotherapy and anti-VEGF response in ESCC. ADC value may be a substitution for assessing tumor angiogenesis and novel prognostic factor and contribute to the treatment of ESCC.

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Section: Discussionmentioning

confidence: 95%

DW‑MRI for esophageal squamous cell carcinoma, correlations between ADC values with histologic differentiation and VEGF expression: A retrospective study

Qing-xue

Wang

et al. 2019

Oncol Lett

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Section: Results: Nivolumab a Human Anti-pd-1 Effectively Inhibited T...mentioning

confidence: 99%

“…Bevacizumab is a humanized anti-VEGF monoclonal antibody that was approved by the FDA in 2009 for the treatment of recurrent glioblastoma. By targeting the VEGF pathway, it does not only inhibit angiogenesis but also alleviates BBB permeability and peritumoral edema (4,7,8).The synergy between the innate and adaptive immune systems is crucial for achieving antitumor immunity, which involves the combined action of both immune responses to effectively suppress tumors (9). CD8 + T cells, also known as cytotoxic T lymphocytes (CTLs), play a vital role in the immune response against tumors by eliminating tumor cells 1991…”

mentioning

confidence: 99%

Humanized PD-1 Knock-in Mice Reveal Nivolumab’s Inhibitory Effects on Glioblastoma Tumor ProgressionIn Vivo

CHIANG,

HUANG,

TSAI

et al. 2023

In Vivo

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Background/Aim: Immunotherapy has been considered a promising approach for brain tumor treatment since the discovery of the brain lymphatic system. Glioblastoma (GBM), the most aggressive type of brain tumor, is associated with poor prognosis and a lack of effective treatment options. Materials and Methods: To test the efficacy of human anti-PD-1, we used a humanized PD-1 knock-in mouse to establish an orthotopic GBM-bearing model. Results: Nivolumab, a human anti-PD-1, effectively inhibited tumor growth, increased the survival rate of mice, enhanced the accumulation and function of cytotoxic T cells, reduced the accumulation and function of immunosuppressive cells and their related factors, and did not induce tissue damage or biochemical changes. The treatment also induced the accumulation and activation of CD8 + cytotoxic T cells, while reducing the accumulation and activation of myeloid-derived suppressor cells, regulatory T cells, and tumor-associated macrophages in the immune microenvironment. Conclusion:Nivolumab has the potential to be a treatment for GBM.Glioblastoma (GBM) is a prevalent malignant tumor of the central nervous system that frequently occurs in both adults and children. Despite the benefits of resection, radiotherapy, and temozolomide chemotherapy in improving the prognosis, glioblastoma patients continue to face a significant mortality risk. The improvement of prognosis in glioblastoma is a critical area of research that necessitates the development of effective innovative approaches (1-3).Vascular endothelial growth factor (VEGF) is an angiogenic protein required for tumor progression. Glioblastoma employs the expression of VEGF to induce angiogenesis and increase blood-brain barrier (BBB) permeability. Consequently, this process results in the development of peritumoral edema (4, 5). Tumor-associated edema is frequently treated with corticosteroid therapy (6). Bevacizumab is a humanized anti-VEGF monoclonal antibody that was approved by the FDA in 2009 for the treatment of recurrent glioblastoma. By targeting the VEGF pathway, it does not only inhibit angiogenesis but also alleviates BBB permeability and peritumoral edema (4,7,8).The synergy between the innate and adaptive immune systems is crucial for achieving antitumor immunity, which involves the combined action of both immune responses to effectively suppress tumors (9). CD8 + T cells, also known as cytotoxic T lymphocytes (CTLs), play a vital role in the immune response against tumors by eliminating tumor cells 1991

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“…Though anti-VEGF therapy has been widely used and has shown benefits in the reduction of vasogenic edema associated with this disease, the overall survival benefit and resistance to therapy are yet to be improved. However, several approaches using combination therapy with radiotherapy, immunotherapy, cytotoxic drugs etc., in addition to anti-VEGF therapy showed improved results [45,46]. A recent study on combination therapy with platelet-derived growth factor (PDGF) inhibitors showed more promising results when combined with anti-VEGF therapy in terms of survival benefit and sensitization to therapy [47].…”

Section: Ceramide Signalingmentioning

confidence: 99%

Glioblastoma: Pathogenesis and Current Status of Chemotherapy and Other Novel Treatments

Rajaratnam

Islam

Yang

et al. 2020

Cancers

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Glioblastoma is one of the most common and detrimental forms of solid brain tumor, with over 10,000 new cases reported every year in the United States. Despite aggressive multimodal treatment approaches, the overall survival period is reported to be less than 15 months after diagnosis. A widely used approach for the treatment of glioblastoma is surgical removal of the tumor, followed by radiotherapy and chemotherapy. While there are several drugs available that are approved by the Food and Drug Administration (FDA), significant efforts have been made in recent years to develop new chemotherapeutic agents for the treatment of glioblastoma. This review describes the molecular targets and pathogenesis as well as the current progress in chemotherapeutic development and other novel therapies in the clinical setting for the treatment of glioblastoma.

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Efficacy of Combination Therapy with MET and VEGF Inhibitors for MET-overexpressing Glioblastoma

Abstract: The current data indicate that the inhibition of both MET and VEGF exhibits efficient therapeutic effects of GBM-bearing hosts.

Cited by 11 publications

References 14 publications

DW‑MRI for esophageal squamous cell carcinoma, correlations between ADC values with histologic differentiation and VEGF expression: A retrospective study

DW‑MRI for esophageal squamous cell carcinoma, correlations between ADC values with histologic differentiation and VEGF expression: A retrospective study

Humanized PD-1 Knock-in Mice Reveal Nivolumab’s Inhibitory Effects on Glioblastoma Tumor ProgressionIn Vivo

Glioblastoma: Pathogenesis and Current Status of Chemotherapy and Other Novel Treatments

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