The expression and significance of HIF-1α and GLUT-3 in glioma

Yang, Liu; Li, Y.; Tian, Ruifeng; Liu, Weiping; Fei, Zhou; Long, Qianfa; Wang, Xiaoan; Zhang, Xiang

doi:10.1016/j.brainres.2009.09.083

Cited by 68 publications

(48 citation statements)

References 20 publications

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“…Based on the evidence that HIF-1α was highly expressed in human astrocytoma U251 and human hepatoma Hep3B (14,15), and our findings that cell viability of both cell lines could be significantly inhibited by F2 under normoxic conditions (9), we selected the U251 and Hep3B cell lines to investigate the antitumor effect of F2 targeting HIF-1α to further explain its antitumor mechanism, which will help define the characteristics of F2 and may contribute to the discovery of novel antitumor or prevention agents.…”

Section: Introductionmentioning

confidence: 99%

Oligomer procyanidins (F2) isolated from grape seeds inhibits tumor angiogenesis and cell invasion by targeting HIF-1α in vitro

Zheng

Yang

Hou

et al. 2014

International Journal of Oncology

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Abstract. Overexpression of hypoxia-inducible factor-1 (HIF-1) α, a transcription factor which immortalizes tumors by inducing expression of the genes involved in cell survival, migration and angiogenesis, is closely associated with poor prognosis, increased risk of metastasis and increased mortality. Oligomer procyanidins (F2), a natural fraction from grape seeds, has been demonstrated to have antioxidant and antitumor activities, however the antitumor effect of F2 targeting HIF-1α remains unknown. The present study showed that F2 markedly decreased HIF-1α and the expression of its target genes in cancer cells through inactivating the EGFR-PI3K-AKT-mTOR and MAPK-ERK1/2 pathways. Moreover, F2 suppressed vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMP)-2 expressions, followed by the inhibition of tumor angiogenesis and cell invasion in a HIF-1α-dependent manner. Collectively, these findings indicate that the antitumor effect of F2 is, at least in part, mediated by suppressing HIF-1α-dependent pathway, and suggest that F2 may be a potentially useful agent for treatment of human cancer.

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Section: Introductionmentioning

confidence: 99%

Oligomer procyanidins (F2) isolated from grape seeds inhibits tumor angiogenesis and cell invasion by targeting HIF-1α in vitro

Zheng

Yang

Hou

et al. 2014

International Journal of Oncology

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“…F 145/01). On day 0 of the experiment, 10 5 human U87MG glioma cells were stereotactically implanted into the right striatum. On day 7, animals were randomly assigned to either an unrestricted standard diet rich in carbohydrates or an unrestricted ketogenic diet.…”

Section: Ethicsmentioning

confidence: 99%

“…Second, hypoxia typically present in malignant glioma is expected to stimulate accumulation of HIF-1α and subsequent expression of genes involved in glucose metabolism and in the suppression of oxidative phosphorylation (8,9). Indeed, there is evidence of HIF-1α and glucose transporter 3 (GLUT3) expression (10) and of increased lactate accumulation in malignant gliomas (11). Further, FDG-PET and 18 F-fluoromisonidazole (FMISO)-PET showed increased glucose uptake and hypoxia in malignant gliomas (12,13).…”

Section: Introductionmentioning

confidence: 99%

ERGO: A pilot study of ketogenic diet in recurrent glioblastoma

Rieger

Bähr

Maurer

et al. 2014

International Journal of Oncology

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Abstract. Limiting dietary carbohydrates inhibits glioma growth in preclinical models. Therefore, the ERGO trial (NCT00575146) examined feasibility of a ketogenic diet in 20 patients with recurrent glioblastoma. Patients were put on a low-carbohydrate, ketogenic diet containing plant oils. Feasibility was the primary endpoint, secondary endpoints included the percentage of patients reaching urinary ketosis, progression-free survival (PFS) and overall survival. The effects of a ketogenic diet alone or in combination with bevacizumab was also explored in an orthotopic U87MG glioblastoma model in nude mice. Three patients (15%) discontinued the diet for poor tolerability. No serious adverse events attributed to the diet were observed. Urine ketosis was achieved at least once in 12 of 13 (92%) evaluable patients. One patient achieved a minor response and two patients had stable disease after 6 weeks. Median PFS of all patients was 5 (range, 3-13) weeks, median survival from enrollment was 32 weeks. The trial allowed to continue the diet beyond progression. Six of 7 (86%) patients treated with bevacizumab and diet experienced an objective response, and median PFS on bevacizumab was 20.1 (range, 12-124) weeks, for a PFS at 6 months of 43%. In the mouse glioma model, ketogenic diet alone had no effect on median survival, but increased that of bevacizumab-treated mice from 52 to 58 days (p<0.05).In conclusion, a ketogenic diet is feasible and safe but probably has no significant clinical activity when used as single agent in recurrent glioma. Further clinical trials are necessary to clarify whether calorie restriction or the combination with other therapeutic modalities, such as radiotherapy or anti-angiogenic treatments, could enhance the efficacy of the ketogenic diet.

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“…Deacetylation of HIF1α at the N-terminus by HDAC4 increases its stability, transcriptional activity and thus the expression of a subset of Hif-1α target genes, including VEGF-α, lactate dehydrogenase A (LDHA), and Glut1 (Geng et al 2011); this, in turn, directs the cells towards transformation. Other HIF-1α targets generally upregulated in cancer cells include glycolytic genes such as 6-phosphofructo-2-kinase (pfkfb3) (Obach et al 2004), phosphoglycerate kinase 1 (PGK 1) and pyruvate kinase M2 (PKM2) (Kress et al 1998), and glucose transporters GLUT1 and GLUT3 (Liu et al 2009). In this context, it is probable that HDACs play a role in the metabolic changes seen in cancer cells and the deacetylation machinery help meet the demand of extra energy requirement of cancer cells by enhancing the expression of the aforementioned HIF-1α target genes to favor growth and proliferation.…”

Section: Disconcerted Acetylation Of Transcription Factors Bymentioning

confidence: 99%

Histone Deacetylases

Parbin

Kar

Shilpi

et al. 2013

J Histochem Cytochem.

127

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SummaryIn the current era of genomic medicine, diseases are identified as manifestations of anomalous patterns of gene expression. Cancer is the principal example among such maladies. Although remarkable progress has been achieved in the understanding of the molecular mechanisms involved in the genesis and progression of cancer, its epigenetic regulation, particularly histone deacetylation, demands further studies. Histone deacetylases (HDACs) are one of the key players in the gene expression regulation network in cancer because of their repressive role on tumor suppressor genes. Higher expression and function of deacetylases disrupt the finely tuned acetylation homeostasis in both histone and non-histone target proteins. This brings about alterations in the genes implicated in the regulation of cell proliferation, differentiation, apoptosis and other cellular processes. Moreover, the reversible nature of epigenetic modulation by HDACs makes them attractive targets for cancer remedy. This review summarizes the current knowledge of HDACs in tumorigenesis and tumor progression as well as their contribution to the hallmarks of cancer. The present report also describes briefly various assays to detect histone deacetylase activity and discusses the potential role of histone deacetylase inhibitors as emerging epigenetic drugs to cure cancer. (J Histochem Cytochem 62:11-33, 2014)

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The expression and significance of HIF-1α and GLUT-3 in glioma

Cited by 68 publications

References 20 publications

Oligomer procyanidins (F2) isolated from grape seeds inhibits tumor angiogenesis and cell invasion by targeting HIF-1α in vitro

Oligomer procyanidins (F2) isolated from grape seeds inhibits tumor angiogenesis and cell invasion by targeting HIF-1α in vitro

ERGO: A pilot study of ketogenic diet in recurrent glioblastoma

Histone Deacetylases

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