食管癌组织中p53和VEGF的表达及其与肿瘤血管生成的关系

目的探讨p53、血管内皮生长因子 (vascular endothelial growth factor,VEGF)的表达和肿瘤内微血管密度 (microvessel density,MVD)测定在食管癌中的意义.方法采用免疫组化方法,检测 45例食管癌患者手术切除标本p53、VEGF的表达,并用CD34抗体标记肿瘤组织血管内皮细胞,计算MVD.结果 p53、VEGF总阳性表达率分别为73.3%(33/45)和62.2%(28/45),MVD平均为48±20.p53的表达与临床TNM分期和淋巴结转移相关,MVD和VEGF表达与食管癌的细胞分化程度、浸润深度和临床TNM分期密切相关.p53/VEGF表达均阳性组MVD高于p53/VEGF其一阳性组和p53/VEGF均阴性组,p53、VEGF表达与MVD密切相关,并存在交互作用.p53和VEGF表达符合率为84.4%(38/45),VEGF与p53的表达有相关性(P<0.001).结论 (1)p53、VEGF的表达以及MVD的测定可作为判断食管癌恶性潜能的重要生物学指标.(2)p53、VEGF的表达对肿瘤血管形成可能起重要作用,联合检测p53、VEGF的表达对了解肿瘤血管形成的机制有一定意义.     

卵巢上皮癌组织微血管密度及血管形成相关分子的检测及预后价值

目的 探讨卵巢上皮癌组织微血管密度(MVD)、血管内皮生长因子(VEGF)、血小板反应素1(TSP1)和p53蛋白表达与患者预后的关系.方法 采用免疫组化法检测57例原发性卵巢上皮癌组织中VEGF、TSP1和p53蛋白的表达情况,用CD34免疫染色后计数MVD.对VEGF、TSP1、p53蛋白和MVD与患者复发及生存时间的关系进行回顾性分析.结果卵巢上皮癌组织中VEGF、TSP1和p53蛋白表达阳性率分别为70.2%(40/57)、47.4%(27/57)和61.4%(35/57),MVD为30.3±8.5,MVD、VEGF和TSP1与复发相关(P值分别为0.030、0.025和0.026).高MVD、VEGF和p53蛋白阳性患者的中位生存时间短于低MVD、VEGF和p53蛋白阴性者(P值分别为0.0187,0.010和0.005),MVD、VEGF和p53蛋白是影响预后的危险因素.TSP1是影响患者预后的保护因素,其阳性患者的中位生存时间长于阴性患者(P=0.042).多因素分析表明,MVD和p53蛋白是影响卵巢上皮癌预后的独立因素(P值分别为0.018和0.009).结论 VEGF、TSP1和p53蛋白可能参与了卵巢上皮癌的血管形成,MVD和p53是影响卵巢上皮癌预后的独立因素.     

p53和VEGF在食管鳞癌中的表达及其临床意义

背景与目的:实验研究证明p53和血管内皮生长因子(vascularendothelialgrowthfactor,VEGF)协同表达在肿瘤血管生成中有重要作用。本研究的目的是探讨p53如何参与血管生成,以及p53和血管内皮生长因子的表达与食管鳞癌(esophagealsquamouscellcarcinoma,ESCC)临床病理参数和预后的关系。方法:采用免疫组织化学方法,检测76例食管鳞癌患者手术切除标本p53和VEGF的表达,并用FⅧ因子抗体标记癌组织血管内皮细胞,计数肿瘤内微血管密度(microvesseldensity,MVD)。结果:p53和VEGF的阳性表达率分别为60.5%和56.6%,两者共同表达率为42.1%。p53和VEGF阳性表达率与食管鳞癌的远处转移和血管浸润具有显著相关性(P<0.05;P<0.01)。远处转移和血管浸润最常发生于突变型p53和VEGF均阳性表达的患者。p53(+)或VEGF(+)组MVD(31.7±11.5;33.8±11.7)均显著高于p53(-)或VEGF(-)组(22.4±10.6;21.2±9.3,P<0.05),p53和VEGF均阳性表达时MVD最大(35.2±11.9,P<0.05)。结论:突变型p53表达与食管鳞癌的血管生成和远处转移密切相关;p53和VEGF的表达可作为评估食管鳞癌恶性程度的重要生物学指标,联合检测p53和VEGF表达具有重要的临床应用价值。     

p53蛋白表达和肿瘤微血管生成与肝癌发展及预后的关系

目的探讨p53蛋白表达和肿瘤微血管生成与肝细胞癌(HCC)发展及预后的关系.方法采用免疫组化方法检测50例肝细胞癌组织中p53蛋白的表达,并用抗CD34抗体标记癌组织血管内皮细胞,计算肿瘤微血管密度(microvessl density,MVD).分析p53蛋白和MVD与HCC临床病理学特征之间的关系.结果 p53阳性表达为癌细胞核棕黄色着色,CD34染色定位在血管内皮细胞上,HCC的p53表达及MVD与肿瘤大小、病灶数目、病理分级、门静脉癌栓形成、包膜是否完整显著相关(P＜0.05).p53蛋白表达阳性者MVD值显著高于阴性者(P＜0.05);p53蛋白表达阳性或MVD≥148的肝癌患者术后生存时间比p53蛋白表达阴性或MVD＜148者短(P＜0.05).结论 p53与肿瘤血管生成密切相关,p53蛋白及MVD可作为肝癌预后判断的一个重要指标.     

卵巢上皮性癌中p53和VEGF表达的相互关系及其临床意义

目的研究p53及血管内皮生长因子(VEGF)在卵巢上皮性癌组织中的表达,探讨其相关性以及它们对卵巢上皮性癌预后的影响.方法应用免疫组化法检测60例上皮性卵巢癌p53蛋白和VEGF表达.结果在卵巢上皮性癌中,p53蛋白表达率为53.3%(32/60),p53蛋白表达与肿瘤的临床病理特征及患者预后无显著相关性.26例(43.3%)患者VEGF表达阴性或低度表达,34例(56.7%)患者VEGF蛋白高度表达.VEGF蛋白高度表达与肿瘤的临床分期、细胞分化程度及患者结局有显著相关性.VEGF蛋白高度表达者生存率比VEGF无或低度表达者低.多变量回归模型分析表明,肿瘤FIGO分期及VEGF表达是影响上皮性卵巢癌患者术后存活时间的独立预后因素.Spearman相关分析显示,VEGF与p53在卵巢上皮癌中的表达呈正相关(r=0.396,P=0.002).结论 p 53蛋白与VEGF表达呈正相关,VEGF可作为判断卵巢上皮癌预后有价值的指标.     

食管癌VEGF与p53蛋白表达的临床意义

目的探讨食管癌VEGF与p53蛋白表达在食管癌的病理学意义及其与血管新生的关系。方法选择40例手术切除的食管癌标本,确定其病理学特点,并对其VEGF与p53蛋白和微血管进行免疫组织化学染色,明确VEGF与p53蛋白表达和血管新生的强度。结果VEGF表达阳性率为67.5％,p53蛋白表达阳性率为50.0％。MVD值为29.00±24.56。有淋巴结转移者与无淋巴结转移者VEGF表达的阳性率有明显差异(P<0.05)。VEGF表达阴性、弱阳性及强阳性者间MVD值比较均有显著差异(P值均<0.05)。p53蛋白表达阴性、弱阳性及强阳性者间MVD值比较无显著差异(P值均>0.05),与VEGF表达阳性率也无显著差异(P值均>0.05)。结论食管癌VEGF表达与血管新生密度及与淋巴结转移均有显著相关。p53蛋白表达与VEGF表达及血管新生强度均可能无密切关系。     

p53、血管内皮生长因子在大肠癌组织中的表达与血管生成

目的　探讨p53、血管内皮生长因子 (VEGF)在大肠癌组织中的表达及其与血管生成的关系。方法　利用免疫组化SABC法 ,对 1 0 6例大肠癌组织及 2 0例正常大肠组织中的 p53、VEGF的表达及微血管密度 (MVD)进行研究。 结果　p53、VEGF的表达与肿瘤的分化程度及Dukes分期无明显相关性 (P >0 .0 5 )。p53表达阳性或VEGF表达阳性的大肠癌组织MVD明显高于p53表达阴性 (P <0 .0 1 )或VEGF表达阴性者 (P <0 .0 1 )。p53表达阳性的大肠癌组织中VEGF的表达阳性率显著高于 p53表达阴性者 (P <0 .0 1 )。结论　p53、VEGF在大肠癌的发生和发展中起着重要作用 ,可反映大肠癌的恶性程度和进展情况并作为预后的指标 ,p53作用的发挥是通过上调VEGF的表达水平来实现的     

乳腺癌组织p53和nm23及VEGF表达相关性的研究

目的:探讨p53、nm23基因和血管内皮生长因子(VEGF)在乳腺癌微血管生成及转移中的作用.方法:通过免疫组化SP法对64例乳腺癌标本中p53、nm23蛋白、VEGF及CD34抗体进行了检测.结果:乳腺癌组织中p53、nm23蛋白及VEGF的阳性表达率分别为65.63%、53.12%和68.75%.p53蛋白表达和VEGF有一致性,呈正相关,P<0.01.在有淋巴结转移的肿瘤中p53蛋白和VEGF阳性表达率及微血管密度(MVD)明显高于非转移组,P<0.05.nm23基因和VEGF在乳腺癌标本中无一致性和直接相关性,在nm23基因表达阴性和VEGF阳性标本中MVD较高,这种现象多见于有淋巴结转移的乳腺癌组织中.结论:p53基因可能通过调控VEGF的表达影响瘤内MVD,促使乳腺癌发生转移;而nm23基因可能不是通过调控VEGF的表达,而是通过其他途径影响乳腺癌转移.     

原发性肝癌组织中MMP-9、p53的表达

目的探讨原发性肝癌组织中基质金属蛋白酶-9(MMP_9)和p53蛋白的表达以及其与临床病理之间的关系。方法应用免疫组织化学法检测74例原发性肝癌组织中MMP_9、p53蛋白表达情况及微血管密度(MVD),并结合临床病理参数进行综合分析。结果MMP_9、p53的表达与原发性肝癌组织MVD、肿瘤大小、侵袭行为(血管侵犯情况和肿瘤包膜)等显著相关(P<0·05)。结论MMP_9、p53在原发性肝癌肿瘤血管形成、恶性进展和浸润、转移等方面起着重要作用。检测原发性肝癌组织中MMP_9、p53的表达对进一步了解原发性肝癌细胞的生物学行为、临床表现和判断预后具有重要价值。     

食管癌幽门螺杆菌L型感染与其血管形成的关系

目的探讨食管癌Hp-L型(即球形:Hp)感染与肿瘤血管形成的相关性及Hp-L型对食管癌生长、侵袭和转移等生物学行为的影响。方法应用革兰染色、电镜和免疫组化ABC法,检测98例食管癌和30例对照组(食管癌切缘正常组织)的Hp-L型;用免疫组化SP法检测上述组织的微血管密度(MVD)值和血管内皮生长因子(VEGF)、p53表达,分析Hp-L型与MVD、VEGF、p53表达以及临床病理因素的关系。结果 食管癌组的Hp-L型阳性率为60.2％。电镜下组织中的Hp-L型有两种类型,可位于癌细胞间或癌细胞胞浆。食管癌组的Hp-L型阳性率、MVD值以及VEGF、p53表达阳性率均高于对照组(P<0.005～0.001),食管癌组中Hp-L型阳性组的MVD值、VEGF和p53表达阳性率也高于其Hp-L型阴性组(P<0.005～0.001)。Hp-L型阳性与MVD呈正相关(r=0.46,P<0.01),与VEGF、p53表达呈正相关(r=0.31,P<0.01)。食管癌组的Hp-L型阳性数与癌细胞的血管侵袭、侵袭深度、食管旁淋巴结转移及远处淋巴结转移相关,而与肿瘤大小无关。结论 Hp-L型与食管癌的血管形成密切相关,是影响食管癌生长、侵袭和转移的重要因素之一。     

VEGF and bFGF expression and microvessel density of maxillary sinus squamous cell carcinoma in relation to p53 status, spontaneous apoptosis and prognosis

We have previously reported that p53 mutations, loss of bax expression or decreased spontaneous tumor apoptosis were associated with poorer prognoses in maxillary sinus squamous cell carcinoma (SCC)(Cancer 94: 1968-1980, 2002). In the present study, we analyzed tumor angiogenesis monitored by expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and tumor microvessel density, in correlation with p53 status, spontaneous apoptosis or disease prognosis in the same group of 70 maxillary sinus SCC patients. Tumor biopsy specimens obtained prior to initiation of treatment were examined for expression of VEGF and bFGF and tumor microvessel density using immunohistological methods. Average vessel density (AVD) (range: 3-75; median: 25) and maximum vessel density (MVD) (range: 4-125; median: 53) were assessed by the number of microvessels stained with anti-CD31 mAb in tumor lesions. VEGF was expressed in 35 (50%) of 70 patients and bFGF was in 43 (61%). Patients with VEGF expression showed significantly higher levels of MVD than those without VEGF expression (57 vs. 38; P=0.019). The VEGF expression was observed more frequently in patients with p53 overexpression and/or mutation than in those with normal p53 status (P=0.048). The MVD inversely correlated with the apoptotic index (AI) defined as the number of single stranded (ss)-DNA-positive cells per 1000 tumor cells (r= -0.23; P=0.022). Patients with neck lymph node and/or distant metastases after surgery showed significantly higher levels of MVD than patients without any metastasis (64 vs. 42; P=0.048). Low histological effectiveness of radiochemotherapy correlated with bFGF expression (P=0.0059). To clarify actual prognostic factors for maxillary sinus SCC, we selected 57 patients treated uniformly with preoperative radiochemotherapy followed by maxillectomy. Kaplan-Meier analysis showed that survival was significantly worse in patients with high MVD (> or =80) than in those with low MVD (<80) (P=0.042). These data suggest that the VEGF expression in association with the p53 overexpression and/or mutations may cause increased microvascularity, decreased spontaneous apoptosis or metastases, while the bFGF expression may be associated with resistance to radiochemotherapy, thereby resulting in poorer prognoses in maxillary sinus SCC. VEGF and bFGF expression and tumor microvessel density in tumor lesions were analyzed in 70 patients with maxillary sinus squamous cell carcinoma. The VEGF expression dependent of p53 overexpression and/or mutations was associated with angiogenesis, decreased spontaneous tumor apoptosis and metastases, while the bFGF expression was associated with resistance to radiochemotherapy, resulting in poor prognosis.     

乳腺癌VEGF的表达和微血管形成的关系及意义

目的 :探讨血管内皮生长因子 (VEGF)与肿瘤内微血管形成的关系 ,以及微血管密度 (MVD)与乳腺癌淋巴结转移和预后的关系。方法 :采用免疫组化 S- P法对 4 0例人乳腺浸润性导管癌组织中的 VEGF和 MVD进行检测。结果 :VEGF阳性者 MVD值显著高于阴性者 ,VEGF表达和MVD与乳腺癌淋巴结转移关系密切。结论 :VEGF与乳腺癌血管生成密切相关 ,VEGF和 MVD表达的增高对乳腺癌淋巴结转移有促进作用 ,MVD和 VEGF均可作为反映乳腺癌生物学行为的指标之一     

Inhibition of hypoxia-induced angiogenesis by trichostatin A via suppression of HIF-1a activity in human osteosarcoma

The purpose of this study is to determine whether trichostatin A (TSA), a HDAC specific inhibitor, inhibited the induction and functional activity of hypoxia-inducible factor-1 a(HIF-1a) and hypoxia-induced angiogenesis in vitro in human osteosarcoma. The relationship between expression of HIF-1a proteion and angiogenesis in tumor specimens was also studied. Hypoxic regulation of VEGF was studied by RT-PCR, western blotting analysis and enzyme linked immunosorbent assay. The expression of HIF-la and VEGF in human osteosarcoma specimens was studied by immunohistochemical analysis. Under hypoxia, no regulation of HIF-1a mRNA expression was found. However, HIF-1a protein levels increased dramatically in response to hypoxia. Hypoxia increased VEGF mRNA level, but it was significantly inhibited by trichostatin A in a time- and dose-dependent manner (p < 0.05). Strongly positive immunostaining for HIF-1a and VEGF were detectable in the nuclear and cytoplasm of osteosarcoma cells. HIF-1a expressing cells were prominent in areas with high MVD. Significant correlation were found between HIF-1a expression and MVD (p = 0.005, r = 0.767), as well as between VEGF and MVD (p < 0.002, r = 0.701) by Spearman's rank coefficient analysis. These results indicated that HIF-1a is a key factor responsible for angiogenesis by the induction of VEGF. TSA downregulates hypoxia-response genes and hypoxia-induced angiogenesis by the suppression of HIF-1a activity.     

Correlation of p53 and bcl-2 expression with vascular endothelial growth factor (VEGF), microvessel density (MVD) and clinico-pathological features in colon cancer

This study was designed to elucidate the possible relationship between tumour related genes and angiogenesis in colon cancer. The protein expression of p53, bcl-2, Von Willebrand factor and vascular endothelial growth factor (VEGF) were analysed by immunohistochemistry in 57 paraffin-embedded colon cancer. The results showed that microvessel density (MVD) was lower in VEGF negative tumours than in VEGF positive ones (P<0.0001). MVD and VEGF in p53 negative tumours were significantly lower than in p53 positive tumours (respectively, P=0.003 and P<0.0001). Moreover, positive correlations were recorded between VEGF expression and MVD, and bcl-2 expression (respectively, P<0.0001 and P=0.009). Our data confirm the central role of VEGF in angiogenesis and suggest direct correlations among p53, bcl-2 and VEGF expression in colon cancer.     

肝细胞癌p53和VEGF的表达及其与肿瘤血管形成的关系

目的 :研究p5 3和血管内皮生长因子 (vascularendothelialgrowthfactor ,VEGF)的表达和肿瘤微血管密度 (microvesseldensity ,MVD)测定在人肝细胞癌 (HCC)中的意义。方法 :采用免疫组织化学方法 ,检测 5 0例HCC患者手术切除标本p5 3和VEGF的表达 ,并用抗CD3 4 抗体标记癌组织血管内皮细胞 ,计算MVD。结果 :p5 3、VEGF总阳性表达率分别为 5 4 0 % (2 7 5 0 )和 76 0 % (38 5 0 ) ,p5 3、VEGF的表达和MVD均与HCC组织病理分级呈正相关 ,P <0 0 5。p5 3和VEGF的阳性表达符合率为 74 % (37 5 0 ) ,两者的表达呈相关性 ,P <0 0 5。p5 3阳性和VEGF阳性的癌组织MVD分别为 178± 6 2和 175±5 9 ,而相应的阴性组分别为 12 5± 5 1和 131± 6 1,两者差异有显著意义 ,P <0 0 5。p5 3、VEGF表达均为阳性者 ,MVD为 176± 6 3;p5 3、VEGF的表达均为阴性者 ,MVD为 12 3± 5 2 ;两者差异有显著意义 ,P <0 0 5。结论 :1)p5 3、VEGF的表达以及MVD的测定可作为判断HCC恶性潜能的重要生物学指标 ;2 )p5 3、VEGF的表达对肿瘤血管形成可能起重要作用 ,联合检测p5 3、VEGF的表达对了解肿瘤血管形成的机制有一定意义     

EXPRESSION OF BASIC FIBROBLAST GROWTH FACTOR,TRANSFORMING GROWTH FACTOR β_1 AND THEIRRECEPTORS IN OSTEOSARCOMA AND ITSRELATIONSHIP TO ANGIOGENESIS

Theangiogenesisisacriticalstepintumorgrowthandmetastasis.lljRecentstudieshaveindicatedthatintratumoralmicrovasculardensity(MVD)wasanimportantfactortoinfluencetheprognosisinmanytumors,includingosteosarcoma.{2'3]Theangiogenesisisregulatedbymanyangiogeneicfactors,inwhichthebasicfibroblastgrowthfactor(bFGF)andtransforminggrowthfactor-5,(TGF-0.)wereconfirmedplayinganimportantroleintheangiogenicprocess.[nthisstudy,weinvestigatedthecorrelationbetweenbFGF,TGF--6,expressionandprognosisinosteosarc…     

Expression of vascular endothelial growth factor in primary non-small cell lung carcinoma

TumorgrowthisdependentuponangiogenesisifitdevelopsfromminimalsizesuchasImm3toabiggersize.[]]Themechanismbywhichtumorsinduceangiogenesishavereceivedconsiderableattentioninrecentyears.Oneofthetumor-secretedangiogenesisfactors,vascularendothelialgrowthfactor(VEGF),appearstoplayanimportantroleintumorangiogenesis.["']VEGFexpressionhasbeendetectedinseveralhumantumors,includingglioblastoma,["']ovarian,[']breast,l']colorectal,[']kidney,[']bladderll()Iandgastriccarcinomas.lll]Blockingwithanti-VEG…