肝细胞肝癌中血管内皮生长因子与浸润树突状细胞表达的相关性研究

研究肝细胞癌(HCC)中血管内皮生长因子(VEGF)的表达与浸润性树突状细胞(DC)的相关性。用免疫 组织化学方法研究45例HCC组织标本VEGF的表达及s-100阳性标记的DC数量,并探讨两者的相关性。在HCC 中VEGF的阳性表达和s-100蛋白阳性表达率分别为62．2％(28／45)和46．7％(21／45),VEGF及DC均与肝癌的转 移有关(P均<0．05);VEGF的阳性表达与DC的浸润程度呈负相关(P<0．05)。HCC组织中VEGF的表达与DC的 浸润程度呈负相关,两者在肝癌发生发展中均起重要作用。     

三叶因子1与胃癌发生发展过程中血管生成的关系

目的:观察三叶因子1(TFF1)和血管内皮生长因子(VEGF)在正常胃黏膜组织、癌旁组织和胃癌组织中的表达,并探讨TFF1与胃癌发生发展过程中血管生成的关系.方法:采用SP免疫组化方法检测142例正常组织、66例癌旁组织和66例胃癌组织中TFF1和VEGF的表达,以CD34标记血管内皮,测定MVD.结果:TFF1表达在正常胃黏膜组织→癌旁组织→胃癌组织中呈逐渐减弱趋势(209.40±16.00,199.12±16.68,189.17±16.20),差异具有显著性(P<0.01),而VEGF的表达和MVD呈逐渐上升趋势(69.7%,40.9%,35.7%;38.90±6.74,28.68±5.08.25.13±4.46).MVD值与TFF1灰度值呈正相关(r=0.811,P<0.01),即MVD值与TFF1的表达呈负相关.结论:TFF1作为一种胃癌特异性抑制因子,在胃癌发生发展过程中并未促进新生血管的生成.     

TFF2在胃癌、癌旁及正常胃黏膜组织中的表达及其与血管生成的关系

目的:探讨三叶因子2(TFF2)、血管内皮生长因子(VEGF)和微血管密度(MVD)在胃癌发生、发展、浸润和转移中的作用.方法:选取广西医科大学第一附属医院2008-01/2009-06接受胃大部切除术的胃癌标本50例,采用SP免疫组织化学方法检测30例正常胃黏膜组织、50例癌旁组织和50例胃癌组织中TFF2、VEGF...     

胃癌组织中树突状细胞和VEGF的表达变化及意义

目的观察胃癌组织中树突状细胞（DC）和血管内皮生长因子（VEGF）的表达变化,探讨二者之间的关系及其在胃癌转移中的作用。方法采用免疫组化SP法检测20例胃炎组织及50例胃癌组织中的DC和VEGF。结果胃炎组织中的DC数明显高于胃癌组织（P〈0．05）,肠型胃癌中DC数高于弥漫型胃癌（P〈0．05）,且与胃癌淋巴结转移有关。VEGF的阳性表达率在胃炎组织低于胃癌组织（P〈0．01）,肠型胃癌中VEGF的阳性表达率低于弥漫型胃癌（P〈0．05）,有淋巴结转移的胃癌组织中VEGF的阳性表达率高于无淋巴结转移者（P〈0．05）。胃癌组织中DC与VEGF的表达呈负相关（r=-0．385,P〈0．05）。结论胃癌组织中DC数减少、VEGF表达增多,二者相互作用,促进胃癌的发生及转移。     

血管生成与非小细胞肺癌预后的相关性研究

目的 探讨微血管密度 (MVD) 和血管内皮生长因子 (VEGF) 在非小细胞肺癌(NSCLC)中的表达及在NSCLC预后中的价值.方法 运用免疫组织化学方法研究43例NSCLC石蜡切片中MVD和 VEGF 的表达.结果 43例NSCLC石蜡标本中,VEGF阳性率为53.5%(23/43),且与MVD计数具有相关性.MVD计数与NSCLC组织学分化程度、T NM临床分期、淋巴结转移具有明显相关性.单因素生存分析显示MVD、VEGF阳性表达的NSCLC患者术后生存期(OS)缩短(P＜0.01);多因素 COX回归分析显示:MVD是NSCLC患者预后的独立预测因子.MVD高表达患者手术后死亡的相对危险度是MVD低表达患者的34.247倍(似然比检验,P＜0.01).结论 VEGF 对NSCLC肿瘤的血管生成可能起重要作用;MVD与NSCLC的转移密切相关,可能是较强的独立预后因子,MVD高的NSCLC患者预后不良.     

胃癌血管生成和血小板源生长因子表达的临床意义

目的：探讨血管生成和血小板源生长因子（PDGF）在胃癌中的表达并评价其临床病理的重要性。方法：采用免疫组化S－P法对10例正常胃粘膜和46例胃癌患者胃粘膜进行PDGF及微血管密度（MVD）检测。结果：胃癌组PDGF阳性表达率为78．3％（36／46）。在正常胃粘膜中无PDGF表达。MVD在PDGF阳性表达组高于阴性表达组。MVD及PDGF表达在淋巴结转移组高于淋巴结无转移组。结论：PDGF是肿瘤生成的正性调节因子,血管生成在胃癌发生、发展中起重要作用。     

血管内皮生长因子在喉癌中的表达及其与血管生成和转移的相关性

目的 探讨喉癌患者血管内皮生长因子(VEGF)水平与喉癌血管生成和转移的关系.方法 2006～2009年50例喉癌患者为病例组,20例声带息肉患者为对照组.应用免疫组织化学SABC法检测黏膜VEGF及微血管密度(MVD)的表达情况,分析VEGF水平与MVD的关系.结果 喉癌组VEGF及MVD的表达均明显高于对照组(P＜0.01),VEGF表达在肿瘤不同TNM分期和淋巴结转移中有统计学意义.结论 VEGF参与并促进了喉癌患者持续的血管再生,与喉癌生长、浸润及淋巴结转移密切相关,VEGF及MVD可作为判断喉癌预后的重要参考指标.     

CD34和VEGF在肝癌组织中的表达及与肿瘤血管生成的相关性

目的探讨CD34和血管内皮生长因子（VEGF）在肝细胞肝癌（HCC）组织中的表达及微血管密度（MVD）的临床病理意义。方法应用链霉素扰生物素蛋白-过氧化物酶法（S—P法）对50例HCC患者进行肿瘤血管生成免疫组织化学检测。对CD34阳性血管进行MVD计数．对VEGF进行半定量计数，并分析与HCC的临床病理特征的关系及意义。结果CD34在HCC组织中呈广泛、窦隙状表达，MVD值在有汇管区癌栓和肝内转移者高于无汇管区癌栓和无肝内转移者（P〈0．05），VEGF表达的阳性率在有汇管区癌栓和肝内转移者明显高于元汇管区癌栓及无肝内转移者（P〈0．05）。MVD值在VEGF阳性组和阴性组之间差异有显著性（P〈0．05）。结论HCC中MVD值和VEGF阳性表达率明显增高，由自分泌和旁分泌产生的VEGF通过促进HCC肿瘤血管生成而促进HCC的生长和转移。     

胃癌血管内皮生长因子与微血管密度的关系

血管生成与肿瘤的生长密切相关。最近的一些研究报道指出，血管内皮生长因子（ＶＥＧＦ）是一种重要的促肿瘤血管生长因子［１］，ＦⅧ因子是血管内皮的特异标记物。我们用ＶＥＧＦ和ＦⅧ因子染色的免疫组化技术，观察了胃癌组织不同区域ＶＥＧＦ阳性表达和微血管密度（Ｍ...     

贲门癌组织环氧化酶-2和血管生成因子的表达及其与血管生成的关系

目的:探讨环氧化酶-2(COX-2)和血管生成因子(VEGF)在贲门癌组织中的表达及其与肿瘤血管生成的关系.方法:免疫组化法检测贲门癌手术切除标本46例和癌旁正常黏膜标本21例中COX-2,VEGF表达.采用抗CD34抗体标记微血管内皮细胞,计算微血管密度(MVD).分析COX-2,VEGF表达与MVD和贲门癌主要临床病理特征的相关性.结果:贲门癌组织COX-2,VEGF阳性表达率、MVD值显著高于癌旁正常黏膜的(80.4% vs 14.3%,x~2=26.22,P<0.01;76.1% vs 19.1%,x~2=19.28,P<0.01:31.95±3.87 vs 16.28±1.55,t=17.76,P<0.01).COX-2,VEGF表达、MVD值与肿瘤临床TNM分期和淋巴结转移密切相关,TNM分期中Ⅲ Ⅳ期的贲门癌组织中COX-2,VEGF表达率、MVD值显著高于Ⅰ Ⅱ期的(90.3% vs 60.0%,x~2=5.91,P<0.05;96.8% vs 46.7%,x~2=16.13,P<0.01;33.43±3.34 vs 28.90±3.08,t=4.42,P<0.01).伴有淋巴结转移的贲门癌组织中COX-2,VEGF表达率,MVD值显著高于无淋巴结转移的(94.1% vs 41.7%,x~2=15.51,P<0.01:91.2% vs 50.0%,x~2=9.56,P<0.01;33.53±3.21 vs 27.48±1.03,t=6.38,P<0.01).Spearman等级相关分析表明,COX-2,VEGF表达与MVD呈显著正相关(r= 0.823:r=0.892,P<0.01).结论:COX-2,VEGF异常表达及其诱导的血管生成在贲门癌的侵袭和淋巴结转移中起重要作用.     

Xiaotan Sanjie decoction attenuates tumor angiogenesis by manipulating Notch-1-regulated proliferation of gastric cancer stem-like cells

AIM: To determine the underlying mechanisms of action and influence of Xiaotan Sanjie (XTSJ) decoction on gastric cancer stem-like cells (GCSCs).METHODS: The gastric cancer cell line MKN-45 line was selected and sorted by FACS using the cancer stem cell marker CD44; the stemness of these cells was checked in our previous study. In an in vitro study, the expression of Notch-1, Hes1, Vascular endothelial growth factor (VEGF), and Ki-67 in both CD44-positive gastric cancer stem-like cells (GCSCs) and CD44-negative cells was measured by Western blot. The effect of XTSJ serum on cell viability and on the above markers was measured by MTT assay and Western blot, respectively. In an in vivo study, the ability to induce angiogenesis and maintenance of GCSCs in CD44-positive-MKN-45- and CD44-negative-engrafted mice were detected by immunohistochemical staining using markers for CD34 and CD44, respectively. The role of XTSJ decoction in regulating the expression of Notch-1, Hes1, VEGF and Ki-67 was measured by Western blot and real-time polymerase chain reaction.RESULTS: CD44⁺ GCSCs showed more cell proliferation and VEGF secretion than CD44-negative cells in vitro, which were accompanied by the high expression of Notch-1 and Hes1 and positively associated with tumor growth (GCSCs vs CD44-negative cells, 2.72 ± 0.25 vs 1.46 ± 0.16, P < 0.05) and microvessel density (MVD) (GCSCs vs CD44-negative cells, 8.15 ± 0.42 vs 3.83 ± 0.49, P < 0.001) in vivo. XTSJ decoction inhibited the viability of both cell types in a dose-dependent manner in vitro. Specifically, a significant difference in the medium- (82.87% ± 6.53%) and high-dose XTSJ groups (77.43% ± 7.34%) was detected at 24 h in the CD44⁺ GCSCs group compared with the saline group (95.42% ± 5.76%) and the low-dose XTSJ group (90.74% ± 6.57%) (P < 0.05). However, the efficacy of XTSJ decoction was reduced in the CD44^- groups; significant differences were only detected in the high-dose XTSJ group at 48 h (78.57% ± 6.94%) and 72 h (72.12% ± 7.68%) when compared with the other CD44- groups (P < 0.05). Notably, these differences were highly consistent with the Notch-1, Hes1, VEGF and Ki-67 expression in these cells. Similarly, in vivo, XTSJ decoction inhibited tumor growth in a dose-dependent manner. A significant difference was observed in the medium- (1.76 ± 0.15) and high-dose XTSJ (1.33 ± 0.081) groups compared with the GCSCs control group (2.72 ± 0.25) and the low-dose XTSJ group (2.51 ± 0.25) (P < 0.05). We also detected a remarkable decrease of MVD in the medium- (7.10 ± 0.60) and high-dose XTSJ (5.99 ± 0.47) groups compared with the GCSC control group (8.15 ± 0.42) and the low-dose XTSJ group (8.14 ± 0.46) (P < 0.05). Additionally, CD44 expression was decreased in these groups [medium- (4.43 ± 0.45) and high-dose XTSJ groups (3.56 ± 0.31) vs the GCSC control (5.96 ± 0.46) and low dose XTSJ groups (5.91 ± 0.38)] (P < 0.05). The significant differences in Notch-1, Hes1, VEGF and Ki-67 expression highly mirrored the results of XTSJ decoction in inhibiting tumor growth, MVD and CD44 expression.CONCLUSION: Notch-1 may play an important role in regulating the proliferation of GCSCs; XTSJ decoction could attenuate tumor angiogenesis, at least partially, by inhibiting Notch-1.     

Akt的活化对胃癌血管新生的促进作用

目的:研究Akt在胃癌及癌旁正常组织中的表达、活化状况及其与胃癌血管新生的关系.方法:收集手术切除的胃癌及相应的癌旁正常组织标本48例.采用Western blot法检测20例新鲜胃癌及癌旁组织Akt和磷酸化Akt(pAkt)蛋白的表达.以免疫组织化学法检测pAkt蛋白在48例胃癌和癌旁正常组织的表达以及血管内皮生长因...     

Increased expression of angiogenin in gastric carcinoma in correlation with tumor angiogenesis and proliferation

AIM: To investigate the implication of angiogenin (ANG) in the neovascularizaton and growth of human gastric carcinoma (HGC). METHODS: ANG mRNA expression in HGC specimens obtained by surgical resection from patients with HGC were examined by RT-PCR. ANG, Ki-67, VEGF protein expression and microvessel density (MVD) in HGC specimens were detected by immunohistochemistry. RESULTS: RT-PCR showed significantly higher ANG mRNA expression (0.482±0.094) in HGC tissues than in the surrounding nontumorous tissues (0.276±0.019, P=0.03). MVD within tumorous tissues increased significantly with ANG mRNA expression (r=0.380,P=0.001) and ANG protein expression (P<0.01). The ANG expression levels of cancer tissues were positively correlated with VEGF (P<0.01) and the proliferation index of cancer cells (P<0.01). CONCLUSION: ANG is one of the neovascularization factors of HGC. ANG may work in coordination with VEGF, and promote the proliferation of HGC cells.     

树突状细胞联合细胞因子诱导的杀伤细胞对胃癌细胞杀伤作用

目的探讨树突状细胞联合细胞因子诱导的杀伤细胞对胃癌细胞的杀伤作用。方法采用胃癌患者自身血液中单个核细胞(peripheral blood mononuclear cells,PBMC),经体外诱导分别扩增出DC和CIK细胞,二者共同培养后,利用MTT法检测DC细胞联合CIK细胞体外杀伤人胃癌细胞株(MNK-45、MNK-28、SG-7901)的活性。结果DC与CIK细胞共培养后得到的细胞群高表达CD3 CD56 ,平均值达到(56.74±7.63)%。通过彼此相互作用诱导出的细胞群体对胃癌细胞株MNK-45、MNK-28、SG-7901有杀伤作用,且杀伤活性随着效靶比的增加而增强。结论DC与CIK细胞共培养后有很强的增殖能力,对胃癌细胞具有杀伤活性,且其杀伤作用与胃癌细胞类型无相关性。     

Tumor angiogenesis and its clinical significance in pediatric malignant liver tumor

AIM: To investigate the expression of vascular endothelial growth factor (VEGF) and microvascular density (MVD) count in pediatric malignant liver tumor and their clinical significances. METHODS: Fourteen children with malignant liver tumors including seven hepatocellular carcinomas (HCCs), five hepatoblastomas, one malignant mesenchymoma and one rhabdomyosarcoma were studied. Twelve adult HCC samples served as control group. All samples were examined with streptavidin-biotin peroxidase (SP) immunohistochemical staining for VEGF expression and MVD count. RESULTS: VEGF positive expression in all pediatric malignant liver tumors was significantly higher than that in adult HCC (0.4971±0.14 vs0.4027±0.03, P<0.05). VEGF expression in pediatric HCC group was also markedly higher than that in adult HCC group (0.5665±0.10 vs0.4027±0.03, P<0.01) and pediatric non-HCC group (0.5665±0.10 vs 0.4276±0.15, P<0.05). The mean value of MVD in pediatric malignant liver tumors was significantly higher than that in adult HCC (33.66±12.24 vs 26.52±4.38, P<0.05). Furthermore, MVD in pediatric HCC group was significantly higher compared to that in adult HCC group (36.94±9.28 vs 26.52±4.38, P<0.05), but there was no significant difference compared to the pediatric non-HCC group (36.94±9.28 vs 30.37±14.61, P>0.05). All 7 children in HCC group died within 2 years, whereas the prognosis in pediatric non-HCC group was better, in which two patients survived more than 5 years. CONCLUSION: Children with malignant liver tumors, especially with HCC, may have extensive angiogenesis that induces a rapid tumor growth and leads to a poor prognosis.     

胃癌血流灌注状态与血清血管新生指标的相关性

背景准确评估肿瘤组织的微循环血流灌注情况,对于临床治疗以及预后评估有着重要意义.超声造影(contrast-enhanced ultrasonography,CEUS)是一种敏感度极高的微循环血流监测手段,能客观反映肿瘤组织的微循环血流灌注状态,可为临床诊治提供可靠的血流动力学信息.目的运用CEUS评估胃癌(gastric cancer,GC)血流灌注状态,并探讨其与血管新生指标的相关性.方法选取在浙江医院行手术切除的66例GC患者作为研究对象(GC组).所有患者术前三天内行CEUS检查,运用时间-强度曲线测定GC组织、癌旁正常组织的增强强度、达峰时间,并采用酶联免疫吸附法(enzymelinked immunosorbent assay,ELISA)测定患者血清血管内皮生长因子(vascular endothelial growth factor,VEGF)、血管生成素-2(Angiopoietin-2,Ang-2)水平,术后测定组织标本微血管密度(microvessel density,MVD).同期选取72例健康志愿者作为对照组进行比较分析.结果GC组织的增强强度明显高于癌旁正常组织,差异有统计学意义(P<0.05);GC组织的达峰时间明显短于癌旁正常组织,差异有统计学意义(P<0.05);GC组织的MVD明显高于癌旁正常组织,差异有统计学意义(P<0.05);GC组的VEGF、Ang-2明显高于对照组,差异有统计学意义(P<0.05);GC组织的增强强度分别与VEGF、Ang-2、MVD呈正相关(r=0.85,r=0.81,r=0.88,P<0.05);GC组织的达峰时间分别与VEGF、Ang-2、MVD呈负相关(r=-0.72,r=-0.73,r=-0.86,P<0.05).结论CEUS能动态评估GC血流灌注状态,其血流参数与VEGF、Ang-2、MVD相关性良好,能为临床评估GC血管新生状态提供无创性影像学手段.     

阿司匹林对人胃癌细胞株的作用及机制探讨

目的 观察阿司匹林对人胃癌细胞株SGC7901生长及人胃癌裸鼠移植瘤生长的作用,并初步探讨其作用机制。方法 采用MTT法及流式细胞术检测不同浓度阿司匹林对胃癌细胞增殖及细胞周期的影响;Westem blot法检测阿司匹林对胃癌细胞COX-2、VEGF表达的影响;建立人胃癌裸鼠移植瘤模型,给予阿司匹林20天,观察肿瘤大小,免疫组化检测阿司匹林对肿瘤组织中COX-2、VEGF表达及MVD的影响。结果 阿司匹林对胃癌细胞的增殖具有抑制作用,且呈一定的时间、剂量依赖性;细胞周期分析表明阿司匹枳主要使细胞阻滞在G0/G1期;western blot检测表明阿司匹林能降低胃癌细胞COX-2、VEGF蛋白的表达;阿司匹林对裸鼠移植瘤的生长有抑制作用,免疫组化显示阿司匹林能降低移植瘤组织中(COX-2、VEGF的表达及MVD。结论 阿司匹林对胃癌细胞及裸鼠移植瘤均具有一定的抑制作用,其机制可能是通过对COX-2和VEGF等血管生成相关因子的抑制起作用。