Prognostic Significance of Tumor Hypoxia Inducible Factor–1α Expression for Outcome After Radiotherapy in Oropharyngeal Cancer

Silva, Priyamal; Slevin, Nicholas J; Sloan, Philip; Valentine, Helen; Cresswell, Jo; Ryder, W. David J.; Price, Patricia M; Homer, Jarrod J; West, Catharine M L

doi:10.1016/j.ijrobp.2008.07.051

Cited by 50 publications

(35 citation statements)

References 31 publications

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“…We believe that other factors, such as neck tumor bulk, comorbidities, and genetic and clinical parameters, may be altogether more decisive for OS than mere perfusion values. [29][30][31] The present study has certain limitations. The patient population had only oropharynx and hypopharynx cancers; thus, we cannot estimate the predictive value of PCT studies in laryngeal and nasopharyngeal cancers.…”

Section: Resultsmentioning

confidence: 82%

Perfusion CT in Squamous Cell Carcinoma of the Upper Aerodigestive Tract: Long-Term Predictive Value of Baseline Perfusion CT Measurements

Bisdas¹,

Rumboldt²,

Surlan-Popovic³

et al. 2009

AJNR Am J Neuroradiol

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Section: Resultsmentioning

confidence: 82%

Perfusion CT in Squamous Cell Carcinoma of the Upper Aerodigestive Tract: Long-Term Predictive Value of Baseline Perfusion CT Measurements

Bisdas¹,

Rumboldt²,

Surlan-Popovic³

et al. 2009

AJNR Am J Neuroradiol

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“…It was found in our study that both HIF-1 and HIF-2 were over-expressed when PANC-1 and CFPAC-1 cells were subjected to hypoxia. It was reported [34–36] that increased levels of HIF-1 or HIF-2 were correlated with adverse prognosis in breast, cervical, endometrial, colorectal, NSCLC, ovarian, rectal, pancreatic and prostate cancers. We also found that both HIF-1α and HIF-2α were increased in PC specimens.…”

Section: Discussionmentioning

confidence: 99%

HIF1/2α mediates hypoxia-induced LDHA expression in human pancreatic cancer cells

et al. 2017

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Glycolysis is a typical conduit for energy metabolism in pancreatic cancer (PC) due to the hypoxic microenviroment. Lactate dehydrogenase A (LDHA) catalyzes the conversion of pyruvate to lactate and is considered to be a key checkpoint of anaerobic glycolysis. The aim of the present study was to explore the mechanism of interactions between hypoxia, HIF-1/2α and LDHA, and the function of LDHA on PC cells by analyzing 244 PC and paratumor specimens. It was found that LDHA was over-expressed and related to tumor stages. The result of in vitro study demonstrated that hypoxia induced LDHA expression. To explore the relationship between HIF and LDHA, chromatin immunoprecipitation assay and luciferase assay were performed. The result showed that HIF-1/2α bound to LDHA at 89bp under the hypoxic condition. Furthermore, knockdown of endogenous HIF-1α and HIF-2α decreased the LDHA expression even in the hypoxic condition, which was accompanied with a significant decrease in lactate production and glucose utilization (p < 0.01). Immunofluorescence in the 244 specimens showed that HIF-1/2α was over-expressed and associated with LDHA over-expression (p < 0.0001). Forced expression of LDHA promoted the growth and migration of PC cells, while knocking down the expression of LDHA inhibited the cell growth and migration markedly. In summary, the present study proved that HIF1/2α could activate LDHA expression in human PC cells, and high expression of LDHA promoted the growth and migration of PC cells.

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“…The scoring system was as follows: 0, no nuclear staining; 1, o10% nuclear staining; 2, 10 -29% nuclear staining and 3, 430% nuclear staining. The scoring system has been validated and used in other studies of HNSCC (Silva et al, 2008).…”

Section: Hif1a Immunohistochemistrymentioning

confidence: 99%

Cytoglobin is upregulated by tumour hypoxia and silenced by promoter hypermethylation in head and neck cancer

et al. 2009

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BACKGROUND: Cytoglobin (Cygb) was first described in 2002 as an intracellular globin of unknown function. We have previously shown the downregulation of cytoglobin as a key event in a familial cancer syndrome of the upper aerodigestive tract. METHOD: Cytoglobin expression and promoter methylation were investigated in sporadic head and neck squamous cell carcinoma (HNSCC) using a cross-section of clinical samples. Additionally, the putative mechanisms of Cygb expression in cancer were explored by subjecting HNSCC cell lines to hypoxic culture conditions and 5-aza-2-deoxycitidine treatment. RESULTS: In clinically derived HNSCC samples, CYGB mRNA expression showed a striking correlation with tumour hypoxia (measured by HIF1A mRNA expression P ¼ 0.013) and consistent associations with histopathological measures of tumour aggression. CYGB expression also showed a marked negative correlation with promoter methylation (P ¼ 0.018). In the HNSCC cell lines cultured under hypoxic conditions, a trend of increasing expression of both CYGB and HIF1A with progressive hypoxia was observed. Treatment with 5-aza-2-deoxycitidine dramatically increased CYGB expression in those cell lines with greater baseline promoter methylation. CONCLUSION: We conclude that the CYGB gene is regulated by both promoter methylation and tumour hypoxia in HNSCC and that increased expression of this gene correlates with clincopathological measures of a tumour's biological aggression.

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Prognostic Significance of Tumor Hypoxia Inducible Factor–1α Expression for Outcome After Radiotherapy in Oropharyngeal Cancer

Cited by 50 publications

References 31 publications

Perfusion CT in Squamous Cell Carcinoma of the Upper Aerodigestive Tract: Long-Term Predictive Value of Baseline Perfusion CT Measurements

Perfusion CT in Squamous Cell Carcinoma of the Upper Aerodigestive Tract: Long-Term Predictive Value of Baseline Perfusion CT Measurements

HIF1/2α mediates hypoxia-induced LDHA expression in human pancreatic cancer cells

Cytoglobin is upregulated by tumour hypoxia and silenced by promoter hypermethylation in head and neck cancer

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