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BIOCELL 2020年第2期44卷 257-262页

作者： HONGYAN LI CHUNLING LIAO WENJUAN WENG HONGZHEN ZHONG TIANBIAO ZHOU Department of Nephrology Huadu District People’s Hospital of GuangzhouSouthern Medical UniversityGuangzhouChina Department of Nephrology The Second Affiliated Hospital of Shantou University Medical CollegeShantou515041China

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 *** searched for relevant studies(before March 1,2019)on Cochrane Library,Embase,and *** meeting the inclusion criteria were recruited into this *** outcome of dichotomous data was showed in the way of odds ratios(OR),and 95%confidence intervals(CI)were also *** this investigation,there was no association between HIF1α1772C/T gene polymorphism and susceptibility to RCC in Caucasians,Asians as well as overall *** addition,HIF1α1772C/T gene polymorphism was not found to be relevant to the survival in ***,the T allele was relevant to prostate cancer risk in all populations,but not in Caucasians and ***,the TT genotype and the CC genotype were not related to prostate cancer susceptibility in Asian,Caucasian,and all *** conclusion,the T allele of the HIF1α1772C/T gene polymorphism was related to prostate cancer risk in the overall populations.

关键词： Renal cell carcinoma (RCC) Prostate cancer Hypoxia-inducible factor-1α (HIF1α) 1772C/T gene polymorphism Meta-analysis

Expression and clinical significance of CD73 and hypoxia-inducible factor-1α in gastric carcinoma

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World Journal of Gastroenterology 2013年第12期19卷 1912-1918页

作者： Xiao-Xia Lu Yi-Tian Chen Bing Feng Xiao-Bei Mao Bo Yu Xiao-Yuan Chu Department of Medical Oncology Nanjing General Hospital of Nanjing Military Command Medical School of Nanjing University Department of Pathology Nanjing General Hospital of Nanjing Military Command

AIM: To investigate the expression of CD73 and hypoxia-inducible factor-1α (HIF-1α) in human gastric carcinoma, and explore their clinical significance and prognostic value. METHODS: CD73 and HIF-1α expressions were detected by immunohistochemistry in consecutive sections of tissue samples from 68 gastric carcinoma patients. The peritumor tissues 2 cm away from the tumor were obtained and served as controls. The presence of CD73 and HIF-1α was analyzed by immunohis-tochemistry using the Envision technique. RESULTS: CD73 and HIF-1α expressions in gastric carcinoma were significantly higher than those in gastric mucosal tissues as control (P 1) and showed a close correlation (Spearman r = 0.390, P = 0.001). Overexpression of CD73 was positively correlated with differentiation of tumor (P = 0.000), histopathology (P = 0.041), depth of invasion (P 1), nodal status (P = 0.003), metastasis (P = 0.013), and the American Joint Committee on Cancer (AJCC) stage (P 1). High expression of HIF-1α was positively correlated with tumor diameter (P = 0.031), depth of invasion (P = 0.022), and AJCC stage (P = 0.035). The overall survival rate was low in the patients with high expression of CD73 (P 1). Moreover, CD73+/HIF-1α+ patients had the worst prognosis (P 1). CD73 expression was proven to be an independent predictor for patients with gastric carcinoma by both multivariate Cox regression analysis (P = 0.021) and receiver operating characteristic curves (P = 0.001).CONCLUSION: CD73 expression correlates closely with HIF-1α expression in gastric carcinoma. CD73 could be an independent prognostic indicator for gastric carcinoma.

关键词： CD73 Hypoxia-inducible factor-1α Gastric carcinoma Immunohistochemistry Prognosis

Prognostic value of hypoxia-inducible factor-1 alpha and prolyl 4-hydroxylase beta polypeptide overexpression in gastric cancer

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World Journal of Gastroenterology 2018年第22期24卷 2381-2391页

作者： Jun Zhang Yue Wu Yu-Hang Lin Shuai Guo Pei-Fang Ning Zhi-chao Zheng Yue Wang Yan Zhao Department of Gastric Cancer Liaoning Cancer Hospital and Institute (Cancer Hospital of China Medical University) Department of Emergency Sheng Jing Hospital of China Medical University Department of Pancreatic and Thyroid Surgery Sheng Jing Hospital of China Medical University Department of Pathology Liaoning Cancer Hospital and Institute (Cancer Hospital of China Medical University)

AIM To investigate the relationship between hypoxia-inducible factor-1α(HIF-1α), prolyl 4-hydroxylase beta(P4 HB) expression, and clinicopathologic parameters, as well as the prognostic value of these genes for patients with gastric cancer(Gc).METHODS Hypoxia is a critical factor that shapes the Gc microenvironment. In previous reports, we have demonstrated that P4 HB is a potential target of HIF-1α. In the present study, gene expression profiling interactive analysis(GEPIA) was used to analyze the relationship between P4 HB and hypoxia-associated genes. To this end, 428 Gc tissue samples were used to analyze the expression of HIF-1α and P4 HB via immunohistochemical staining. Patient samples were classified as having weak-expression or over-expression both in terms of HIF-1α and P4 HB. Correlations between biomarkers and clinicopathological factors were analyzed to predict survival. RESULTS P4 HB demonstrated a positive correlation with hypoxiaassociated genes(P 0.05).CONCLUSION Overexpression of HIF-1α and P4 HB is associated with poor prognosis in patients with Gc. Thus, these genes may be potential pr

关键词： Gastric cancer Hypoxia inducible factor-1α Prolyl 4-hydroxylase beta polypeptide Overall survival Clinicopathological predictors Disease free survival

Forskolin Modulates the Inhibitory Effect of C-Type Natriuretic Peptide on Hypoxia-Induced Atrial Dynamics and Hypoxia Inducible factor 1 Alpha Activity

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Journal of Biosciences and Medicines 2017年第1期5卷 1-10页

作者： Chengming Guan Yanan Jia Chaochao Bian Bo Zhang Dazhi Ding Xun Cui Institue of Clinical Medicine Yanbian University Yanji China Department of Physiology School of Medicine Yanbian University Yanji China Key Laboratory of Organism Functional factors of the Changbai Mountain Ministry of Education Yanbian University Yanji China Cellular Function Research Center Yanbian University Yanji China

Our study investigated effects of C-type natriuretic peptide (CNP) on atrial dynamics and hypoxia inducible factor 1 alpha (HIF-1α) activity in perfused beating rat atria, under hypoxic conditions. Hypoxia significantly increased the levels of HIF-1α, concomitant with decreased trial dynamics. CNP (0.1 μmol/L) further decreased atrial dynamics under hypoxia and suppressed hypoxia-induced stimulation of HIF-1α expression. An adenylylcyclase (AC) activator, forskolin (0.1 μmol/L), significantly up-regulated atrial phosphodiesterase subtype 3A (PDE 3A) protein without affecting hypoxia-induced dynamics. In the presence of forskolin, the inhibitory effects of CNP on hypoxia-induced atrial dynamics and HIF-1α levels were significantly attenuated. Forskolin also prevented hypoxia-induced downregulation of PDE3A protein. These findings suggested that CNP inhibited atrial dynamics and HIF-1α activity in the isolated perfused beating rat atria under hypoxic conditions. Furthermore, both effects were modulated by the AC activator forskolin, through activation of CNP-PDE 3A signaling.

关键词： C-Type Natriuretic Peptide Hypoxia Inducible factor-1α Phosphodiesterase Adenylyl Cyclase Forskolin

基质细胞衍生因子-1α和白细胞介素-1β诱导淋巴管内皮表型的作用

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解剖学报 2014年第3期45卷 388-392页

作者：索宁王雪颖杨春林周辉李菲张宗璞万芳竹田铧山东大学医学院解剖学与组织学胚胎学研究所济南250012 山东省郯城县第一人民医院肿瘤科山东临沂276199 山东大学技术支持科济南250012

目的探讨基质细胞衍生因子-1α(SDF-1α)及白细胞介素-1β(IL-1β)诱导内皮细胞表达淋巴管表型的作用。方法 SDF-1α和IL-1β分别诱导内皮细胞株CRL-1730,用Real-time PCR、Western blotting及免疫细胞化学等方法检测其内皮及淋巴管标志... 详细信息

目的探讨基质细胞衍生因子-1α(SDF-1α)及白细胞介素-1β(IL-1β)诱导内皮细胞表达淋巴管表型的作用。方法 SDF-1α和IL-1β分别诱导内皮细胞株CRL-1730,用Real-time PCR、Western blotting及免疫细胞化学等方法检测其内皮及淋巴管标志物,的表达情况。结果 SDF-1α诱导培养之后,CRL-1730细胞株的内皮细胞标志物血管性血友病因子(vWF)、血管内皮钙黏蛋白(VE-cadherin)、血管内皮生长因子受体(VEGFR)2随其浓度增高而表达降低,淋巴管标志物平足蛋白(podoplanin)、同源异形盒蛋白-1(Prox-1)和淋巴管内皮透明质酸受体-1(LYVE-1)随其浓度增高而表达增高。IL-1β诱导之后,CRL-1730细胞株的vWF、VEGFR2和podoplanin、prox-1、LYVE-1的变化趋势同SDF-1α,而VE-cadherin的表达量基本不变。结论 SDF-1α和IL-1β都能够诱导血管内皮细胞表达淋巴管标志物。

关键词：基质细胞衍生因子-1α 白细胞介素-1β 同源异形盒蛋白-1 血管内皮细胞实时定量聚合酶链反应 Stromal cell-derived factor-1α Interleukin-1β Prospero ho-meobox protein-1

缺氧诱导因子-1α及促红细胞生成素在大鼠角膜新生血管中的表达

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国际眼科杂志 2014年第12期14卷 2139-2142页

作者：王济民石蕊魏会玲马勇高丹中国陕西省大荔县人民医院眼科 715100 陕西省人民医院眼科中国陕西省西安市710068

目的:探讨缺氧诱导因子-1α(hypoxia-inducible factor-1α,HIF-1α)及促红细胞生成素(erythropoietin,EPO)在碱烧伤大鼠角膜组织中的表达,评估其在角膜新生血管(corneal neovascularization,CNV)发生发展中的作用。方法:健康3月龄SD大鼠,随机分为实验组和对照组,碱烧伤法建立CNV模型,分别于造模成功后1,3,5,7,14d测量CNV的长度并计算面积,同时取角膜组织以免疫组织化学检测HIF-1α及EPO的表达部位,并以RT-PCR法检测其mRNA的表达情况,实验数据采用SPSS 20.0处理。结果:碱烧伤后1,3,5,7,14d,CNV的面积随时间逐渐增加,7d生长最为旺盛,14d后生长减慢。免疫组织化学提示:正常角膜各层未见HIF-1α的表达,可见微量EPO,碱烧伤后1d时HIF-1α及EPO免疫活性增强,主要表达于角膜上皮及内皮层。RT-PCR结果显示HIF-1α及EPO mRNA的表达在正常大鼠角膜组织中表达极少,在角膜碱烧伤后3d表达增强,7d达到高峰,14d后明显下降;不同时间点组间比较存在统计学差异(P1α和EPO与CNV的形成密切相关。

关键词：角膜新生血管碱烧伤缺氧诱导因子-1α 促红细胞生成素 hypoxia-inducible factor-1α

Inhibition of β-elemene on the expressions of HIF-lα, VEGF and i NOS in diabetic rats model

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International Journal of Ophthalmology(English edition) 2019年第11期12卷 1693-1698页

作者： Yun Zhou Yan Liu Jun Chen Yi-Zhou Sun Li-Hua Li Lei Chen Department of Ophthalmology the First Affiliated Hospital of China Medical University

AIM: To evaluate the effect of β-elemene on the expressions of hypoxia-inducible factor(HIF)-lα, vascular endothelial growth factor(VEGF) and inducible nitric oxide synthase(i NOS) in a streptozotocin(STZ) induced diabetic SpragueDawley(SD) rat ***: SD rats were administered an abdominal injection of STZ and induced to a diabetic model. After 6 wk course of diabetes, the treatment groups were given β-elemene through periocular and intravitreous injection separately and the control groups were given blank emulsion injection. HE staining was used to observe the morphology of retina. The m RNA expressions of HIF-1α, VEGF and i NOS was assayed by real-time polymerase chain reaction(PCR) and the protein expression was measured by Western blot and immunocytochemistry ***: The results indicated that the protein and m RNA expressions of HIF-1α, VEGF and i NOS after treated by β-elemene periocularly and intravitreally injections were all found to be reduced compared with the levels in the diabetic rats group(P1α, VEGF and iNOS.

关键词： β-elemene hypoxia-inducible factor-1α vascular endothelial growth factor inducible nitric oxide synthase diabetic rat

缺氧诱导因子1α和转化生长因子β1在子宫内膜癌中的表达及其临床意义

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中国综合临床 2016年第9期32卷 830-833页

作者：杨军文倪观太皖南医学院弋矶山医院妇产科安徽省芜湖市241001

目的：检测子宫内膜癌组织中缺氧诱导因子1α（ HIF-1α）和转化生长因子β1（ TGF-β1）的表达并探讨其临床意义。方法选取2012年2月至2015年2月手术治疗54例子宫内膜癌及20例正常子宫内膜，应用免疫组化法检测HIF-1α和TGF-β1的表达... 详细信息

目的：检测子宫内膜癌组织中缺氧诱导因子1α（ HIF-1α）和转化生长因子β1（ TGF-β1）的表达并探讨其临床意义。方法选取2012年2月至2015年2月手术治疗54例子宫内膜癌及20例正常子宫内膜，应用免疫组化法检测HIF-1α和TGF-β1的表达，并分析其与临床病理及预后的关系。结果子宫内膜癌组织中HIF-1α和TGF-β1表达分别为59．26％（32／54）、64．81％（35／54），二者显著高于正常子宫内膜癌组织（1／20、0）（χ2值分别为17．390、24．596，P均＜0．01）；HIF-1α表达与子宫内膜癌FIGO分期（χ2＝6．712，P＝0．010）、脉管浸润（χ2＝4．804，P＝0．036）、浸润深度（χ2＝6．484，P＝0．011）及腹膜后淋巴结转移（χ2＝5．732， P＝0．017）均相关；TGF-β1表达与子宫内膜癌 FIGO 分期（χ2＝4．878， P＝0．027）、浸润深度（χ2＝4．060，P＝0．044）及腹膜后淋巴结转移（χ2＝5．211，P＝0．022）；在子宫内膜癌组织HIF-1α和TGF-β1表达呈正相关（ r＝0．705，P＝0．000）。结论 HIF-1α和TGF-β1增高可能共同参与了宫内膜癌发生及浸润转移，并有可能成为其治疗的靶点。

关键词：子宫内膜癌缺氧诱导因子1α 转化生长因子β1 Hypoxia inducible factor-1α Transforming growth factor-β1

The timing and extent of intraosseous hypoxia in the oxidative stress-induced rat osteonecrosis model

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Advances in Bioscience and Biotechnology 2013年第8期4卷 814-817页

作者： Toru Ichiseki Ayumi Kaneuji Seiji Kaneko Syusuke Ueda Yoshimichi Ueda Hideto Yonekura Kiyokazu Fukui Tadami Matsumoto Department of Biochemistry Kanazawa Medical University Uchinada Ishikawa Japan Department of Orthopaedic Surgery Kanazawa Medical University Uchinada Ishikawa Japan Department of Pathophysiological and Experimental Pathology Kanazawa Medical University Uchinada Ishikawa Japan

Using a rat oxidative stress-induced femoral head osteonecrosis model, we determined the presence/ absence and timing of the generation of hypoxia in the femoral head. DL-Buthionine-(S,R)-sulfoximine (BSO) 500 mg/kg was administered intraperitoneally to male Wistar rats. The rats were killed at 1, 3, 6, 12 hours, and 1, 3, 5 days after BSO administration, and the bilateral femora were removed. A group not administered BSO (control group) was also studied (each group n = 5). In the femoral heads of each group, the expression of hypoxia-inducible factor-1 alpha (HIF-1α) as an index of hypoxia was confirmed by the Western blot method, and quantified using analytical software. In the femoral head increased HIF-1α expression was found in all groups from 1 hour after BSO administration (p 1α amounting to about 13-fold of that of control group was noted (p 1). The present results suggested that in the extremely short period of 3 hours after BSO administration hypoxia severe enough to cause osteonecrosis was induced by oxidative stress in the rat femoral head.

关键词： Osteonecrosis Oxidative Stress Buthionine Sulfoximine Hypoxia-Inducible factor-1α

HIF-1α-1790G>A polymorphism significantly increases the risk of digestive tract cancer:A meta-analysis

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World Journal of Gastroenterology 2015年第5期21卷 1641-1649页

作者： Xiao Sun Ying-Di Liu Wei Gao Shao-Hua Shen Meng Li Department of Gastroenterology of PLA General Hospital Department of Gastroenterology Hainan Branch of PLA General Hospital

AIM:To investigate the association between hypoxiainducible factor-1α(HIF-1α) polymorphisms(-1772C>T and-1790G>A) and the risk of digestive tract ***:A total of 13 eligible studies were retrieved from Pub Med,EMBASE,and the ChinaNational Knowledge Infrastructure *** odds ratios(ORs) and 95% confidence intervals(CIs) were calculated to estimate the strength of the ***:By pooling the eligible studies,we found that the HIF-1α-1772C>T polymorphism was not associated with the risk of developing digestive tract cancer(dominant comparison,OR:1.156; 95%CI:0.839-1.593; P heterogeneity = 0.007),and no significant association was found in the Asian population or the Caucasian ***,for the-1790G>A polymorphism,carriers of the variant-1790 A allele had a significantly increased risk of digestive tract cancer compared with those with the wildtype-1790 G allele(dominant comparison,OR:3.252; 95%CI:1.661-6.368; P heterogeneity 1).Additionally,this increased risk of digestive cancer was only detected in Asians; there was no significant association in ***:This meta-analysis demonstrates that the HIF-1α-1790G>A polymorphism is associated with a significantly increased risk of digestive tract cancer,while the-1772C>T polymorphism is not.

关键词： Hypoxia-inducible factor-1α Digestive tract cancer