Radiation-Enhanced Vascular Endothelial Growth Factor (VEGF) Secretion in Glioblastoma Multiforme Cell Lines – A Clue to Radioresistance?

Hovinga, Koos E.; Stalpers, Lukas J.A.; Bree, Chris van; Donker, Mila; Verhoeff, J.; Rodermond, Hans M.; Bosch, Dirk; Furth, Wouter R. van

doi:10.1007/s11060-004-4204-7

Cited by 76 publications

(61 citation statements)

References 15 publications

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“…It is also suggested that the expression of VEGF in tumors is up-regulated after radiotherapy, which is thought to be a defense mechanism against radiation (Hovinga et al 2005). Consistently, cancers with overexpressed VEGF are insensitive to radiotherapy.…”

Section: Discussionmentioning

confidence: 96%

The enhancement of radiosensitivity in human esophageal squamous cell carcinoma cells by zoledronic acid and its potential mechanism

et al. 2013

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Esophageal squamous cell carcinoma (ESCC) has a low 5-year patient survival rate. Radiotherapy, as a preoperative or postoperative treatment of surgery, has a crucial role in improving local control and survival of ESCC. Various chemotherapeutic and biologic agents have been used as radio-sensitizers in combination with radiotherapy. Here, we demonstrate that zoledronic acid (ZOL) has a radio-sensitizing effect on ESCC cells. Exposure of ESCC cancer cells to ZOL plus radiation resulted in increased cell death through arresting the cell cycle between S and G2/M phases. ZOL appeared to inhibit proliferation, tube formation and invasion of endothelial cells. These anti-angiogenetic effects were more marked concurrently with irradiation. In addition, synergistic suppressive effects on VEGF expression were observed after combined treatment. Our data suggest that the combination of ZOL and radiation is a promising therapeutic strategy to enhance radiation therapy for ESCC patients.

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Section: Discussionmentioning

confidence: 96%

The enhancement of radiosensitivity in human esophageal squamous cell carcinoma cells by zoledronic acid and its potential mechanism

et al. 2013

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“…Previous studies (3,4) have indicated that radiation therapy results in the elevated expression of vascular endothelial growth factor (VEGF), which may contribute to the resistance to radiation in tumors. Therefore, radiation therapy combined with antiangiogenic therapy may be effective in decreasing radiation resistance.…”

Section: Introductionmentioning

confidence: 99%

Antitumor activity of Endostar combined with radiation against human nasopharyngeal carcinoma in mouse xenograft models

Zhou¹,

Wang²,

Xu³

et al. 2012

Oncology Letters

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Abstract. Radiation treatment for nasopharyngeal carcinoma (NPC) is common and effective. However, local recurrence occurs frequently. Endostar, a novel recombinant human endostatin, is an antiangiogenic drug with a potent antitumor effect. The present study aimed to observe and explore the radiosensitization effects of Endostar on NPC and its underlying mechanism. The NPC subcutaneous transplantation tumor animal model was established to evaluate the antitumor activity of Endostar combined with radiation (Endostar + radiation) treatment compared with monotherapy (Endostar or radiation). Tumor growth and tumor weight were measured to evaluate the antitumor effect. The level of vascular endothelial growth factor (VEGF) and microvessel density (MVD) were measured using immunohistochemical staining of the tumor tissues. Significant antitumor activity was found in the Endostar + radiation group. The tumor inhibition rates of Endostar, radiation and Endostar + radiation were 27.12, 60.45 and 86.11%, respectively. The VEGF levels in the tumor tissue in the Endostar + radiation group were lower than those in the radiation and control groups. The MVD in the tumor tissues in the Endostar + radiation group was 12.2±2.5, lower than that in the Endostar (29.3±3.4), radiation (23.5±3.6) and control (44.7±5.1) groups. These results suggest that Endostar increases the radiation sensitivity of NPC-transplanted tumors in nude mice by lowering VEGF expression. In this study, the NPC animal model was established, which reflects the efficacy of clinical combination therapies and the combination of Endostar and radiation. The mechanisms of the combination therapies should be further investigated using this model. IntroductionNasopharyngeal carcinoma (NPC) is one of the most common malignant tumors in China. Presently, the main treatment for NPC is radiation therapy. Over the past 20 years, with the development of imaging, radiation techniques and equipment for NPC, the local control rate among patients in the early stage of the disease has risen to 70-90%. However, in patients in the late stages of the disease (stages III-IV), the local control rate is only 50%, with a five-year overall survival rate of 40-70% (1). The main causes of treatment failure are local recurrence and distant metastases, which are closely related to each other (2). The key factor that results in the local recurrence of tumors is the presence of tumor cells possessing a resistance to radiation. Therefore, decreasing radiation resistance and increasing radiation sensitivity of tumor cells are of significant clinical relevance.Previous studies (3,4) have indicated that radiation therapy results in the elevated expression of vascular endothelial growth factor (VEGF), which may contribute to the resistance to radiation in tumors. Therefore, radiation therapy combined with antiangiogenic therapy may be effective in decreasing radiation resistance.A number of studies have indicated that neovascularization is closely related to the progression and metastasis of tumo...

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“…To examine the biological impact of VEGF stimulation on human GBM cell models, we treated the cell lines A172 and U251MG with increasing concentrations of VEGF (10,20,40 and 80 ng/ ml) and measured MTT absorbance in time-course experiments, as an index of cell growth/proliferation, as employed in previous studies of VEGF-induced astrocytoma cell proliferation. [15][16][17][18] As early as 6-12 hours after addition of VEGF 121 to culture medium, MTT absorbance was significantly increased (by 19-35% for A172 and 14-79% for U251MG, p < 0.001 for any of the four VEGF concentrations used) compared with the mock-treated control cells. Despite some modestly higher increases of MTT absorbance at the higher versus lower concentrations of added VEGF, such concentration-dependence was not statistically significant.…”

Section: Introductionmentioning

confidence: 99%

Autocrine regulation of glioblastoma cell-cycle progression, viability and radioresistance through the VEGF-VEGFR2 (KDR) interplay

Knizetova¹,

Ehrmann²,

et al. 2008

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Radiation-Enhanced Vascular Endothelial Growth Factor (VEGF) Secretion in Glioblastoma Multiforme Cell Lines – A Clue to Radioresistance?

Abstract: Irradiation enhanced VEGF secretion in all three tested glioma cell lines (up to eight times basal levels). It is tempting to associate the radiation-enhanced VEGF secretion with an increased angiogenic potential of the tumor, which may be a factor in radioresistance.

Cited by 76 publications

References 15 publications

The enhancement of radiosensitivity in human esophageal squamous cell carcinoma cells by zoledronic acid and its potential mechanism

The enhancement of radiosensitivity in human esophageal squamous cell carcinoma cells by zoledronic acid and its potential mechanism

Antitumor activity of Endostar combined with radiation against human nasopharyngeal carcinoma in mouse xenograft models

Autocrine regulation of glioblastoma cell-cycle progression, viability and radioresistance through the VEGF-VEGFR2 (KDR) interplay

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