HIF-1 and tumour radiosensitivity

Moeller, Benjamin J.; Dewhirst, Mark W.

doi:10.1038/sj.bjc.6603201

Cited by 160 publications

(124 citation statements)

References 30 publications

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“…Hypoxia is a major cause of radioresistance [15,25] and HIF also has an important role in hypoxia-related resistance to radiation [14,26] However in this study, we did not detect direct binding between NICD3 and HIF-1α when cells were treated with radiation in immunoprecipitation assay (data not shown). HIF-1α activates genes related to angiogenic factors, glycolytic enzymes and glucose transporters [32][33][34].…”

Section: Discussioncontrasting

confidence: 46%

Inhibition of Notch and HIF enhances the antitumor effect of radiation in Notch expressing lung cancer

et al. 2016

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Section: Discussioncontrasting

confidence: 46%

Inhibition of Notch and HIF enhances the antitumor effect of radiation in Notch expressing lung cancer

et al. 2016

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“…All of these results strongly suggest that the synergistic therapeutic effect of Ad & 5-FC & IR treatment was dependent on the expression of BCD and was caused by the conversion of 5-FC to cytotoxic 5-FU. Hypoxia-inducible factor-1 plays important roles in regulating tumour radiosensitivity, and therefore, it has been recognised as a potentially promising target for tumour radiosensitisation (Moeller et al, 2004;Moeller and Dewhirst, 2006). Because transcription from 5HREp mainly depends on HIF-1 activity, BCD expression from Ad/5HREp-BCD should be induced in the cells with increased HIF-1 activity.…”

Section: Discussionmentioning

confidence: 99%

Adenovirus-mediated hypoxia-targeting cytosine deaminase gene therapy enhances radiotherapy in tumour xenografts

et al. 2007

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Hypoxia is closely associated with the radioresistance of tumours; therefore, targeting hypoxic areas is very important for cancer therapy. The aim of this study is to establish such a targeting strategy by applying a bacterial cytosine deaminase (BCD)/5-fluorocytosine (5-FC) gene therapy system and to examine whether the strategy enhances the efficacy of radiotherapy in a tumour xenograft. The hypoxiaresponsive promoter 5HREp, in which five copies of the hypoxia-response element (HRE) enhance transcription from a cytomegalovirus minimal promoter, was employed to induce the expression of BCD under hypoxic conditions. The adenoviral vector Ad/5HREp-BCD, encoding the gene 5HREp-BCD, robustly induced BCD expression under hypoxic conditions and this led to significant cytotoxicity in combination with 5-FC in vitro. Intratumoral Ad/5HREp-BCD administration resulted in the expression of BCD at the border between normoxic and necrotic regions. The BCD/5-FC gene therapy enhanced the therapeutic effects of both single (12.5 Gy) and fractionated (3 Gy Â 5 days) radiotherapy with few side effects and significantly increased tumour growth doubling time by up to 2.4-fold (Po0.01) and 2.5-fold (Po0.05), respectively. All of these results suggest that the present BCD/5-FC gene therapy has the ability to specifically target hypoxic tumour cells and significantly improves the control of tumour growth after radiotherapy.

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“…HIF-1 controls the expression of over 40 target genes by binding to hypoxia-responsive elements. HIF-1 plays a crucial role in many processes, including oxygen homeostasis, glucose metabolism, cell survival, invasion, homing and angiogenesis [47][48][49], which have been shown to influence radioresponsiveness (reviewed by [50]). …”

Section: Hypoxia Induced Factor-1 (Hif-1)mentioning

confidence: 99%

Hypoxia Helps Glioma to Fight Therapy

Amberger-Murphy

2009

CCDT

101

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Abstract:Despite major improvements in the surgical management the prognosis for patients bearing malignant gliomas is still dismal. Malignant gliomas are notoriously resistant to treatment and the survival time of patients is between 3-8 years for low-grade and anaplastic gliomas and 6 -12 month for glioblastoma. Increasing malignancy of gliomas correlates with an increase in cellularity and a poorly organized tumour vasculature leading to insufficient blood supply, hypoxic areas and ultimately to the formation of necrosis, a characteristic of glioblastoma. Hypoxic/necrotic tumours are more resistant to chemotherapy and radiation. Hypoxia induces either directly or indirectly (through the activation of transcription factors) changes in the biology of a tumour and its microenvironment leading to increased aggressiveness and tumour resistance to chemotherapy and radiation. This review is focused on hypoxia-induced molecular changes affecting glioma biology and therapy.3

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HIF-1 and tumour radiosensitivity

Cited by 160 publications

References 30 publications

Inhibition of Notch and HIF enhances the antitumor effect of radiation in Notch expressing lung cancer

Inhibition of Notch and HIF enhances the antitumor effect of radiation in Notch expressing lung cancer

Adenovirus-mediated hypoxia-targeting cytosine deaminase gene therapy enhances radiotherapy in tumour xenografts

Hypoxia Helps Glioma to Fight Therapy

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