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1.
目的:探讨缺氧诱导因子-1α(HIF-1α)和血管内皮细胞生长因子(VEGF)在前列腺癌中的表达及其与病理分级、临床分期的关系。方法:采用免疫组化方法检测前列腺癌和良性前列腺增生(BPH)组织中HIF-1α和VEGF的表达。结果:前列腺癌中HIF-1α和VEGF的表达均明显高于BPH;HIF-1α和VEGF在前列腺癌中的表达水平与其病理分级和临床分期均呈正相关;前列腺癌中的HIF-1α表达水平和VEGF的表达水平呈正相关。结论:HIF-1α和VEGF是检测前列腺癌的较好分子标志物,可望用于前列腺癌的辅助诊断和预后判断,HIF-1α是VEGF表达的调控因子之一。  相似文献   

2.
缺氧诱导因子-1α与血管内皮生长因子在胶质瘤中的表达   总被引:2,自引:0,他引:2  
目的 探讨缺氧诱导因子(HIF)-1α与血管内皮生长因子(VEGF)在不同级别胶质瘤中的表达特点及其生物学特性。方法 采用逆转录-聚合酶链反应(RT-PCR)法和免疫组织化学法分别检测20例新鲜冷冻标本及117例多聚甲醛固定的不同级别胶质瘤标本中HIF-1α与VEGF的表达情况,并对实验结果进行半定量计算和统计学分析。结果 RT-PCR结果示正常脑组织和Ⅰ-Ⅳ级胶质瘤中HIF-1αmRNA平均吸光度值分别为11.99、12.18、48.31、80.96、112.77,正常脑组织和Ⅰ级胶质瘤间差异元统计学意义,其余各组间差异均有统计学意义(F=969.45,P〈0.01);而VEGF mRNA平均吸光度值分别为29.50、37.97、60.33、84.61、112.97,各组间差异均有统计学意义(F=312.91,P〈0.01)。免疫组织化学结果示HIF-1α在正常脑组织和Ⅰ-Ⅳ级胶质瘤中的阳性表达率分别为10%、13.3%、53.5%、80.6%、100%,正常脑组织和Ⅰ级胶质瘤间差异无统计学意义,其余各组间差异均有统计学意义(χ^2=38.19,P〈0.05);同样,VEGF在各组中的阳性表达率分别为0%、33.3%、62.8%、83.3%、100%,各组问差异均有统计学意义(χ^2=45.78,P〈0.05)。结论 HIF-1α与VEGF在胶质瘤中的表达与胶质瘤的病理分级密切相关,随着病理级别的升高,HIF-1α与VEGF无论是在mRNA水平还是在蛋白水平的表达均上调,并且两者间的表达也具有相关性。  相似文献   

3.
近年来发现的转录因子缺氧诱导因子-1(hypoxia inducible factor-1,HIF-1)在氧平衡及肿瘤微血管形成中起着重要作用,HIF-1由α和β两个亚单位组成.其中HIF-1α是决定HIF-1活性的缺氧调节亚基.为此,我们采用原位分子杂交方法检测胃癌组织中的HIF-1α mRNA表达并分析其与血管内皮细胞生长因子(VEGF)蛋白,微血管密度(MVD)及生存期的关系,旨在探讨HIF-1α和VEGF在胃癌侵袭转移中的作用及对胃癌患者预后的影响.  相似文献   

4.
血管瘤中缺氧诱导因子-1α的表达和血管生成的研究   总被引:8,自引:3,他引:8  
目的 探讨缺氧诱导因子- 1α(HIF-1α)在血管瘤中的表达以及其和血管内皮细胞生长因子 (VEGF)、新生微血管密度 (MVD)的关系。方法 采用免疫组化SP法检测 2 8例婴幼儿血管瘤中HIF 1α、VEGF的蛋白表达和MVD。结果  2 8例血管瘤中HIF-1α、VEGF的蛋白表达阳性率分别是6 4 % ,71.4 %。其中增生期和消退期HIF 1α阳性率分别为 87.5 %、33.3% (P <0.0 1) ,VEGF阳性率分别为 93.7%、4 1.7% (P <0.0 1) ;MVD分别为 73 4± 14 6 3、30 2± 9 1(P <0.0 1)。HIF 1α蛋白表达与VEGF成正相关 (P <0.0 1) ,HIF 1α和VEGF与MVD都成正相关 (P <0.0 1)。结论 血管瘤增生期血管内皮细胞存在着特殊的缺氧微环境 ,并通过HIF-1α表达水平提高调节VEGF等血管生成相关因子表达水平升高 ,促进了新生微血管生成  相似文献   

5.
目的 观察缺氧诱导因子-1α(HIF-1α)和血管内皮生长因子(VEGF)在断流术前后肝前性门静脉高压症(PHPH)大鼠胃黏膜的表达,探讨HIF-1α和VEGF在门静脉高压胃病(PHG)的发生发展的作用。方法 取Wistar大鼠制备PHPH模型80只,设假手术组(SO)60只,在术后3周施断流术。检测HIF-1α、VEGF和CD34在大鼠胃壁组织中的表达。结果 断流术前PHPH组大鼠胃壁中HIF-1α(5.8±1.3)和VEGF(12.0±3.0)的表达均明显高于SO组[HIF-1α(0.03750±0.05175),VEGF(0.7±0.1),P〈0.01]。术后HIF-1α、VEGF和MVD均有升高趋势。结论 HIF-1α和VEGF可能参与了PHG的发生发展,断流术本身能通过某种机制影响HIF-1α和VEGF的表达,加重PHG。  相似文献   

6.
目的:探讨胰岛素样生长因子-Ⅱ(IGF-Ⅱ)与胃癌的关系。方法:采用放射免疫法对31例胃癌患者血清IGF-Ⅱ水平进行检测,并与10例正常组、10例慢性萎缩性胃炎伴肠腺化生(CAGGM)组及10例慢性萎缩性胃炎伴重度不典型增生(CAGD)组作对照。比较20例胃癌患者手术前后血清IGF-Ⅱ水平的变化,分析其与胃癌病理分期、恶性程度、肝转移及与幽门螺旋杆菌(Hp)感染的关系。结果:血清IGF-Ⅱ水平胃癌组和CAGD组较正常组均明显升高(P〈0.001,P〈0.01),且胃癌组较CAGGM组、CAGD组血清升高(P〈0.001,P〈0.001),CAGD组与CAGGM组比较亦有显著性差异(P〈0.01);术后2周血清IGF-Ⅱ水平较术前显著下降(P〈0.001)。中、晚期胃癌患者血清IGF-Ⅱ水平较早期患者显著升高(P〈0.01);差分化型胃癌患者血清IGF-Ⅱ水平较分化型明显升高(P〈0.05);胃癌有无肝转移、是否伴Hp感染其血清IGF-Ⅱ水平均无明显差异。结论:血清IGF-Ⅱ水平升高是胃癌发生、发展的重要因素之一;检测血清IGF-Ⅱ水平的变化,对胃癌的诊断、手术切除是否彻底、判断病情变化有一定临床价值。Hp感染与血清IGF-Ⅱ水平升高可能分别作为独立因素,共同参与胃癌的发生、发展。  相似文献   

7.
目的观察缺氧诱导因子(HIF)-1α在胃癌组织中的表达及其与化疗疗效和临床预后的关系。方法对52例未接受过任何放化疗的中晚期胃癌患者予以四氢叶酸(CF)、氟尿嘧啶(5-FU)、草酸铂(L-OHP)为基础的联合化疗方案(CF200mg/m^2静脉滴注2h。5-FU1500mg/m^2静脉持续滴注46h,L-OHP85mg/m^2静脉滴注2h),分别于第1天和第14天给药.4周为1个周期.至少需完成4个周期的化疗。化疗结束后进行疗效评价。并对患者加以随访以作生存分析。同时对该52例患者的胃癌组织标本进行免疫组织化学染色,检测HIF-1α、P糖蛋白(P—gP)和多药耐药相关蛋白(MRP4)在胃癌组织中的表达,另取27例正常胃黏膜作对照。结果HIF—1α、P—gP和MRP4在胃癌组织中的阳性表达率分别为53.9%、51.9%和57.7%,在正常胃黏膜组织中分别为0、18.5%和14.8%。两组间的差异均有统计学意义(均P〈0.05)。HIF-1α阳性表达者化疗有效率14.3%,显著低于HIF—1α阴性表达者(50.0%,P〈0.05)。HIF-1α阳性表达组中位无进展生存期(PFS)为4.9个月,中位总生存期(OS)为8.8个月,1年和2年生存率分别为37.5%和21.5%;而HIF-1α阴性表达组中位PFS为8.4个月.中位OS为12.6个月.1年和2年生存率分别为51.2%和33.5%:两组生存期的差异具有统计学意义(P〈0.05)。结论HIF-1α表达可作为临床上预测胃癌化疗疗效及临床预后的的指标之一。  相似文献   

8.
缺氧诱导因子-1α表达与膀胱癌分级与复发相关性研究   总被引:2,自引:0,他引:2  
目的 :探讨缺氧诱导因子 1α(HIF 1α)在膀胱癌中的表达与肿瘤微血管计数 (MVC)、分级、复发的关系。方法 :用免疫组织化学方法染色显示膀胱癌中HIF 1α表达 ,并用计数定量血管形成 ,回顾性分析HIF 1α表达与MVC、肿瘤分级、肿瘤复发的关系。结果 :HIF 1α表达 19例正常膀胱黏膜均为阴性 ,在Ⅰ、Ⅱ、Ⅲ级膀胱肿瘤中HIF 1α阳性率分别为 2 4 %、4 1%和 73% ,Ⅰ级与Ⅲ级阳性率差异有统计学意义 (P <0 .0 5 )。 19例正常膀胱黏膜MVC为 0 ,在Ⅰ、Ⅱ、Ⅲ级膀胱肿瘤中MVC分别为 (39.71± 11.6 2 )、(44 .70± 11.5 2 )和 (5 2 .36± 16 .83)。其中Ⅰ级与Ⅲ级差异有统计学意义 (P <0 .0 5 )。根据肿瘤属于初发或复发分组 ,初发组 5 1例 ,复发组 19例 ,HIF 1α阳性率分别为 35 %和 74 % ,差异有统计学意义 (P <0 .0 5 )。MVC初发组和复发组分别为 (42 .6 8± 13.73)和(5 3.4 7± 12 .5 0 ) ,差异有统计学意义 (P <0 .0 5 )。结论 :HIF 1α的表达与膀胱肿瘤MVC、分级以及复发呈正相关关系 ,提示HIF 1α表达与膀胱癌的生物学行为有关 ,可作为膀胱癌生物学行为的标志  相似文献   

9.
缺氧诱导因子-1α在结肠肿瘤中的表达及意义   总被引:1,自引:0,他引:1  
目的探讨缺氧诱导因子-1α(HIF-1α)在结肠肿瘤中的表达及其意义。方法采用免疫组织化学方法,对30例结肠癌患者癌组织及癌旁组织、10例结肠腺瘤患者腺瘤组织中H1F-1α的表达情况进行检测,并分析HIF-1α表达与结肠癌临床病理特征之间的关系。结果HIF-1α阳性率在结肠癌和结肠腺瘤组织中分别为73.3%(22/30)和10.0%(1/10),而在癌旁组织中无表达(P〈0.05)。结肠癌组织中HIF.1et的表达水平与患者性别、年龄、病理组织学类型及分化程度无关(P〉0.05),而与区域淋巴结转移状况及Dukes分期密切相关(P〈0.05)。结论HIF-1α过度表达与结肠癌的浸润、转移密切相关,可能作为判断预后的重要指标。  相似文献   

10.
缺氧诱导因子1α(hypoxia inducible factorld.HIF-1α)在目前肿瘤血管生成方面的研究中,作为调节血管生长因子的转录因子受到关注。我们检测膀胱移行细胞癌中HIF-1α和血管内皮生长因子(vascular endothelial growth factor,VEGF)的表达,以研究HIF-1α在膀胱癌中的作用及与血管生长调节的关系。  相似文献   

11.
12.
目的 探讨结直肠癌侵袭转移过程中缺氧诱导因子1-α(alpha,HIF-1α)与FasL表达的相关性.方法 采用分子克隆方法,将我室已构建的FasL-pcD-NA3.1(+)质粒与pcDNA3.1(一)质粒进行重组,得到新的FasL-pcDNA3.1(一)质粒并加以鉴定;通过脂质体转染法将空质粒、FasL-pcDNA3.1(+)与FasL-pcDNA3.1(一)质粒分别转染人直肠癌HR-8348细胞,构建侵袭力不同的结直肠癌细胞HR-8348L、HR一8348F和HR一8348As,未转染细胞HR一8348B为空白对照,应用Tran-swell,小室检测各组细胞的侵袭能力;采用化学缺氧法构建四组细胞的缺氧模型,Western blot方法定量检测缺氧0h、6h、12h及24h各组细胞内HIF-1α的表达.结果 FasL-pcDNA3.1(一)质粒符合要求,FasL片段大小约900bp,测序结果正确率99.2%;单层细胞体外侵袭实验见HR一8348F细胞穿透Transwell滤膜的细胞数目为(12.930±2.434),显著多于HR-8348B(8.133±1.959)、HR-8348L(7.670±2.093)和HR-8348As(7.870±1.685)细胞(P<0.05);Western blot检测示HIF-1α蛋白于120kD处显色,缺氧0h与6h,各组样品中HIF-α仅表达微量,HIF-1α水平无显著性差异(P>0.05);缺氧12h与24h,HR一8348F细胞内HIF-1α水平较0h和6h时明显增高(P<0.05),而HR-8348B、HR-8348L及HR-8348As细胞内HIF-1α表达与6h时无明显变化(P>0.05),HR-8348F细胞HIF-1α水平显著高于HR-8348B、HR-8348L及HR-8348As细胞(P<0.01).结论 缺氧环境中结直肠癌细胞FasL表达增强是除低氧分压外另一个诱导HIF-1α表达增高的因素,FasL与 HIF-1α水平呈正相关,高侵袭能力的结直肠癌细胞对缺氧的适应能力加强,促进肿瘤的远处转移.  相似文献   

13.
OBJECT: Vascular endothelial growth factor (VEGF) has been implicated in meningioma tumorigenesis and growth. The production of VEGF is regulated by hypoxia inducible factor-1alpha (HIF-1alpha), especially under conditions of hypoxia. In this study, the authors examine the expression of HIF-1alpha and VEGF in meningiomas, with a special emphasis on conditions of hypoxia, such as preoperative embolization, and on in vitro studies in cultured cells. METHODS: Meningiomas obtained in 142 patients were studied using immunohistochemical methods to detect HIF-1alpha and the results were correlated with the extent or lack of preoperative embolization and expression of VEGF. Primary meningioma cell cultures were established and cell culture experiments were performed using a hypoxia chamber to stimulate HIF-1alpha and VEGF production. Expression of HIF-1alpha in primary meningioma cell cultures was measured using immunoblot assays. The VEGF secretion was measured using enzyme-linked immunosorbent assay. Half of the meningiomas studied were positive for HIF-1alpha, with a strong correlation between complete embolization and HIF-1alpha expression. Most of the meningiomas studied expressed VEGF protein, and VEGF expression did not correlate with the degree of embolization. A strong correlation was found between VEGF and HIF-1alpha expression in immunohistochemical studies. Secretion of VEGF is increased by hypoxia and growth factor stimulation. In meningiomas, growth factors stimulate HIF-1alpha expression. The role of hypoxia is less clear. CONCLUSIONS: The expression of HIF-1alpha is increased by complete preoperative embolization of meningiomas. The expression of HIF-1alpha also correlates with VEGF secretion in meningiomas. Growth factor and hypoxic stimulation both contribute to VEGF control, but which is most important (or whether both are equally important) will require further studies.  相似文献   

14.
PURPOSE: In this study we investigated hypoxia inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) expression, and angiogenesis in an experimental model of varicocele in the rat testis. MATERIALS AND METHODS: A total of 30 adult male Sprague-Dawley rats were investigated in 3 groups, namely varicocele group 1 (13), sham operated group 2 (9) and control group 3 (8). At 30 days after surgery was completed in groups 1 and 2 orchiectomy was performed in all rats. Histological findings in the left testicles of rats from each group were compared. HIF-1alpha and VEGF expression was immunohistochemically studied and CD31 panendothelial antigen was used to identify the number of microvessels, that is microvessel density (MVD), in paraffin embedded sections of testis tissue. Data were analyzed using the chi-square test, Fisher's exact test, 1-way ANOVA and the Tukey HSD test for post hoc comparison. RESULTS: HIF-1alpha expression was detected in 12 specimens (92.3%) in group 1, 4 (44.4%) in group 2 and 2 (25%) in group 3. The frequency of HIF-1alpha positivity in group 1 was significantly higher than the rates in groups 2 (p = 0.023) and 3 (p = 0.003). VEGF expression was detected in 8 specimens (61.5%) in group 1 but none of the group 2 or 3 specimens were VEGF positive. The frequency of VEGF positivity in group 1 was significantly higher than that in groups 2 (p = 0.006) and 3 (p = 0.007). Mean MVD +/- SD in group 1 was 7.53 +/- 1.50 (range 6 to 12), and findings in groups 2 and 3 were 5.88+/-1.45 (range 4 to 8) and 5.12 +/-1.12 (range 4 to 7), respectively. Mean MVD in group 2 was higher than in group 3 but this difference was not significant (p = 0.509). Mean MVD in group 1 was significantly higher than the mean values in groups 2 (p = 0.030) and 3 (p = 0.002). CONCLUSIONS: Previous study of experimental varicocele models in rats documented HIF-1alpha and VEGF expression combined with angiogenesis in the testis. The results of this study show that varicocele can lead to tissue hypoxia and related pathophysiological events, such as angiogenesis.  相似文献   

15.
Ang2,HIF-1α及VEGF对肝癌血管形成的影响   总被引:2,自引:0,他引:2       下载免费PDF全文
摘要:目的:探讨促血管生成素2(Ang2)、缺氧诱导因子1α(HIF-1α)及血管内皮生长因子(VEGF)与肝细胞癌血管形成的关系。方法:检测52例肝癌组织中Ang2,HIF-1α及VEGF mRNA及蛋白的表达,对共表达的肝癌组织进行微血管计数。结果:RT-PCR 显示,52例肝癌组织中有38例共表达Ang2mRNA,HIF-1αmRNA 和VEGF mRNA,且两两之间呈明显正相关(分别为r=0.783,P<0.01;r=0.427,P<0.05;r=0.433,P<0.05);免疫组化发现,52例肝癌组织36例共表达Ang2,HIF-1α和VEGF蛋白。共表达Ang2 mRNA,HIF-αmRNA 和VEGF蛋白的38例肝癌组织中,平均微血管数[(45.4±8.90) 个/HP],明显高于非共表达组[(13.6±3.30)个/HP](P<0.05)。结论:Ang2,HIF-1α和VEGF与肝癌的新生血管形成有关;肿瘤组织缺氧可能是其始动因素。  相似文献   

16.
目的研究缺氧诱导因子1(HIF-1)和缺氧诱导因子2(HIF-2)在人类着床前胚胎各个阶段的表达,探讨这两个氧调节基因在人类早期胚胎发育过程中的作用和意义。方法收集不育症患者捐赠的胚胎,采用巢式逆转录聚合酶链反应(RT-PCR)和实时荧光定量PCR分别定性和定量在5%和20%O2条件下体外培养的人胚胎的HIF-1α和HIF-2αmRNA。采用免疫荧光染色检测人胚胎的HIF-1α和HIF-2α蛋白。结果巢式RT-PCR分别检测了5%和20%O2体外培养的2、4、6、8细胞胚胎和囊胚发现,所有34个胚胎均表达HIF-1α和HIF-2αmRNA。实时荧光定量PCR5%O2培养的人囊胚HIF-1α与18SrRNA的Ct比值为(1.22±0.05);20%O2培养的人囊胚,这一比值是(1.02±0.07);两者比较差异显著(P<0.05)。人胚胎在体外常氧培养条件下的HIF-1αmRNA水平显著高于低氧培养。5%O2培养的人囊胚HIF-2α与18SrRNA的Ct的比值为(1.29±0.04);20%O2培养的人囊胚,这一比值是(1.19±0.11);两者比较无显著差异(P>0.05)。人胚胎在体外低氧培养条件下的HIF-2αmRNA水平与常氧培养无显著差异。5%和20%O2体外培养的2、4、6、8细胞,各个发育阶段人胚胎的HIF-1α和HIF-2α免疫荧光染色均阳性。结论研究结果显示人类着床前胚胎在体外常氧和低氧培养时均表达HIF-1α和HIF-2α。二者可能通过广泛的靶基因系统参与早期胚胎的生长发育和着床过程,在早期胚胎的调控可能不在转录水平,而在转录后水平。  相似文献   

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PURPOSE: Sarcomatoid renal cell carcinomas, highly aggressive variants of renal cell carcinoma subtypes, often present with or develop metastases soon after the primary diagnosis. Most metastatic cases do not respond to immunotherapy or aggressive chemotherapy. Recently targeted therapies, particularly those targeting hypoxia inducible pathway molecules, have been tested clinically on metastatic clear cell renal cell carcinoma with promising initial results. No such studies are available on sarcomatoid renal cell carcinoma. We investigated the hypoxia inducible pathway marker immunohistochemical expression profile, and any potential therapeutic implications that such expression may have, in these tumors. MATERIALS AND METHODS: Immunohistochemical staining for hypoxia inducible factor-1alpha, glucose transporter 1, carbonic anhydrase IX and vascular endothelial growth factor was performed in 22 clear cell and 12 nonclear cell sarcomatoid renal cell carcinomas. The immunoreactivity in the tumors was graded from 0 to 3+ (0-no staining, 1+-1% to 25% cells positive, 2+-26% to 50% cells positive and 3+-greater than 50% cells positive). The results were then compared with various clinical parameters to assess for associations. RESULTS: Most clear cell renal cell carcinomas over expressed (2+ or 3+) hypoxia inducible factor-1alpha (in 59%), carbonic anhydrase IX (95%), glucose transporter 1 (91%) and vascular endothelial growth factor (95%). None of the nonclear cell sarcomatoid renal cell carcinomas showed 2+ or 3+ expression of hypoxia inducible factor-1alpha, carbonic anhydrase IX or glucose transporter 1, but 92% showed diffuse positivity for vascular endothelial growth factor. Over expression of carbonic anhydrase IX showed no association with survival, unlike that reported in (nonsarcomatoid) clear cell renal cell carcinoma. There was significant discordance in the staining grades among hypoxia inducible factor-1alpha, carbonic anhydrase IX and glucose transporter 1 in clear cell renal cell carcinoma, suggesting that mechanisms other than hypoxia inducible pathway may be involved in some sarcomatoid clear cell renal cell carcinoma. CONCLUSIONS: Hypoxia inducible pathway markers continue to be over expressed in sarcomatoid clear cell renal cell carcinoma, and can be of diagnostic usefulness in such high grade tumors. Over expression of vascular endothelial growth factor in the clear and nonclear cell groups raises the possibility that vascular endothelial growth factor targeted therapies may have a role in the management of sarcomatoid renal cell carcinoma, and deserve further investigation.  相似文献   

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目的本研究旨在探讨缺氧诱导因子1α(HIF-1α)和P53蛋白在人肾透明细胞癌组织中的表达及其对患者预后的影响。方法应用免疫组化方法检测65例肾透明细胞癌组织中HIF-1α和P53蛋白的表达情况,通过生存曲线法比较阳性组和阴性组患者的预后情况。结果 HIF-1α和P53蛋白表达的阳性率分别为40.0%(26/65)和52.3%(34/65);HIF-1α表达与肾透明细胞癌的组织学分级、临床分期和淋巴结转移有关(P〈0.05);HIF-1α蛋白阳性组患者的生存期明显较阴性组短(P=0.004);P53蛋白表达与肾透明细胞癌患者性别、年龄、肿瘤大小、组织学分级、临床分期、淋巴结转移及生存期均无关(P〉0.05);HIF-1α蛋白P53蛋白的表达之间存在相关性(r=0.402,P=0.001)。结论 HIF-1α的表达与肾透明细胞癌患者的预后相关,其阳性表达提示患者预后不良;检测HIF-1α表达水平有助于肾细胞癌预后评估。  相似文献   

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