Association of hypoxia-inducible factor-1α (HIF1α) 1772C/T genepolymorphism with susceptibility to renal cell carcinoma/prostatecancer

In this study,we used a meta-analysis method to evaluate the relationship between hypoxia-inducible factor-1α(HIF1α)1772C/T gene polymorphism(rs 11549465)and renal cell carcinoma(RCC)/prostate cancer risk.We searched for relevant studies(before March 1,2019)on Cochrane Library,Embase,and PubMed.Studies meeting the inclusion criteria were recruited into this meta-analysis.The outcome of dichotomous data was showed in the way of odds ratios(OR),and 95%confidence intervals(CI)were also counted.In this investigation,there was no association between HIF1α1772C/T gene polymorphism and susceptibility to RCC in Caucasians,Asians as well as overall populations.In addition,HIF1α1772C/T gene polymorphism was not found to be relevant to the survival in RCC.Interestingly,the T allele was relevant to prostate cancer risk in all populations,but not in Caucasians and Asians.However,the TT genotype and the CC genotype were not related to prostate cancer susceptibility in Asian,Caucasian,and all populations.In conclusion,the T allele of the HIF1α1772C/T gene polymorphism was related to prostate cancer risk in the overall populations.

Phosphatase and tensin homology deleted in chromosome 10,hypoxia-inducible factor-1 alpha gene expression in colorectal adenoma and adenocarcinoma and their relation to vascular endothelial growth factor protein expression

To examine phosphatase and tensin homology deleted in chromosome 10 (PTEN),hypoxia-inducible factor-1 alpha (HIF-1 alpha) gene expressions and their relation to vascular endothelial growth factor(VEGF) protein expression in the patients with human colorectal adenomas and adenocarcinomas.Methods The expression of PTEN,HIF-1 alpha gene was detected by using in situ hybridization,and the VEGF expression levels by immunohistochemistry in colorectal adenomas and primary colorectal adenocarcinoma.Results Strong expression of HIF-1 alpha was detectable in the majority of colorectal dadenocarcinoma,particularly surrounding areas of necrosis in adenocarcinoma.PTEN,HIF-1 alpha mRNA and VEGF protein were positive in 51.6%,67.7% and 59.7% respectively in 62 cases of adenocarcinomas,and 77.8%,44.4% and 33.3% respectively in 18 cases of adenomas.The positive rate of VEGF was higher in the patients with colorectal adenocarcinomas than that in those with adenomas,whereas that of PTEN mRNA was contrary.HIF-1 mRNA expression was correlated significantly with lymph node metastasis,liver metastasis,Duke’s stage and recurrence.During colorectal tumor progression,the expression of HIF-1 alpha mRNA was positively correlated with the VEGF protein expression (χ2= 4.751 ,P<0.05),but negatively with the PTEN mRNA expression(χ2=21.84,P<0.01).Conclusion The absence or low expression of PTEN and the increased levels of HIF-1α and VEGF may paly an important role in carcinogenesis and progression of colorectal carcinoma.These results suggest that VEGF upregulated by HIF-1 alpha gene may be involved in angiogenesis of colorectal adenocarcinoma.4 refs,1 tab.

Expression of cyclooxyenase-2 protain and its relationship with HIF-1α in HCC

Objective： To investigate the clinical significance of COX-2 （Cyclooxygenase-2） expression in HCC （Primary hepatocellular carcinoma） and clarify whether COX-2 is correlated with hypoxia-inducible factor-1α （HIF-1α） in the development of HCC. Methods： Tumor tissues were obtained from 53 patients with HCC. COX-2 and HIF-1α were determined by immunohistochemistry. All 53 patients were regularly followed up and the data were collected prospectively. Results： Immunostaining showed the expression of COX-2 （ n = 33, 62.3 % ） and HIF-1α （ n = 36, 67.9% ） in most tumor cells. The level of COX-2 was correlated with HIF-1α levels（ r = 0.4413, P 〈0.01 ）. There were significant correlation between clinicopathological features and higher tumor cytosolic COX-2 level was in the presence of multiple tumors （ P = 0.01）, venous invasion （ P = 0.03）, advanced tumor stage （ P = 0.01）, and well-different tumor grade （P =0.03）. High-tumor cytosolic COX-2 level was correlated with patient＇s worse prognosis （P = 0.0085）. Conclusion： Elevated tumor COX-2 level is correlated with elevated HIF-1α levels and invasiveness in HCC, suggesting COX-2 plays an important role in the progression of HCC, and may be an important therapeutic target in HCC.

Ursolic acid sensitized colon cancer cells to chemotherapy under hypoxia by inhibiting MDR1 through HIF-1α

Objective： To explore the efficacy of ursolic acid in sensitizing colon cancer cells to chemotherapy under hypoxia and its underlying mechanisms. Methods： Three colon cancer cell lines （RKO, LoVo, and SW480） were used as in vitro models. 5-Fluorouracil （5-FU） and oxaliplatin were used as chemotherapeutic drugs. Cell viability and apoptosis were tested to evaluate the sensitivity of colon cancer cells to chemotherapy. The transcription and ex- pression levels of hypoxia-inducible factor-1α （HIF-1α）, multidrug resistance gene 1 （MDR1）, and vascular endothelial growth factors （VEGF） were assessed by quantitative real-time polymerase chain reaction （qRT-PCR） and im- munoblotting. Cycloheximide and MG132 were used to inhibit protein synthesis and degradation, respectively. In vitro tube formation assay was used to evaluate angiogenesis. Results： We demonstrated the chemosensitizing effects of ursolic acid with 5-FU and oxaliplatin in three colon cancer cell lines under hypoxia. This effect was correlated to its inhibition of MDR1 through HIF-la. Moreover, ursolic acid was capable of inhibiting HIF-1α accumulation with little effects on its constitutional expression in normoxia. In addition, ursolic acid also down-regulated VEGF and inhibited tumor angiogenesis. Conclusions： Ursolic acid exerted chemosensitizing effects in colon cancer cells under hypoxia by inhibiting HIF-la accumulation and the subsequent expression of the MDR1 and VEGF.