人食管癌EC9706细胞乏氧环境中放射敏感性变化及其机制

目的 观察乏氧干预对人食管癌细胞EC9706放射敏感性及乏氧诱导因子-1α(HIF-1α)、血管内皮生长因子-A (VEGF-A)和血管内皮生长因子-D (VEGF-D)表达的影响,以及乏氧诱导因子-1o和血管内皮生长因子表达的相关性.方法 将人食管癌细胞EC9706体外常氧及乏氧培养6、12、24 h,置于6MVX射线下照射0、1、2、4、6、8 Gy,细胞克隆法绘制生长曲线;Western blot法检测常氧及乏氧培养6、12、24 h后各组HIF-1α、VEGF-A、VEGF-D蛋白表达情况;RNA干扰沉默HIF-1α后乏氧培养6、12、24 h,再以Western blot法检测各组HIF-1α、VEGF-A、VEGF蛋白表达情况.结果 乏氧组细胞存活分数(SF2)为0.62,常氧组SF2为0.43,而且乏氧组HIF-1α、VEGF-A、VEGF-D蛋白表达量随乏氧时间的延长逐渐增加(F=205.24、227.88、130.55,P＜0.05).RNA干扰后,乏氧EC9706细胞中HIF-1α、VEGF-A、VEGF-D蛋白表达量均未见升高.结论 乏氧环境下食管癌细胞EC9706对放射敏感性下降,这可能与乏氧诱导的HIF-1α及其下游因子VEGF-A和VEGF-D的蛋白表达增加相关.     

VEGF-D及Ki-67在乳腺癌淋巴道转移中的作用

目的探讨VEGF-D及Ki-67在乳腺癌淋巴道转移中的作用和意义。方法采用免疫组化二步法检测90例乳腺癌组织中VEGF-D和Ki-67的表达。结果1）VEGF-D阳性率在淋巴结转移组为82％（41／50）显著高于未转移淋巴组37．5％（15／40）（P〈0．01）。Ki-67阳性率在淋巴道转移组为84％（42／50）显著高于未转移淋巴组42．5％（17／40）（P〈0．05），且VEGF-D与Ki-67的表达显著相关（P〈0．05）。2）VEGF-D的表达与年龄、肿瘤大小、病理分型、临床分级、ER、PR无关，与CerbB-2表达显著相关（P〈0．05）。Ki-67的表达与年龄、肿瘤大小无显著性相关（P〉0．05），而与肿瘤组织分级、淋巴结转移有显著相关性（P〈0．05）。结论VEGF-D和Ki-67的表达与乳腺癌淋巴道转移有关，可能促进了乳腺癌淋巴管的生成和增殖。     

VEGF-C和VEGF-D在胃癌及相关淋巴结组织中表达和临床意义的研究

目的：比较血管内皮生长因子C（vascular endothelial growth factor C,VEGF-C）和血管内皮生长因子D（vascular endothelial growth factor D,VEGF-D）在胃癌和相关淋巴结的表达,并评价其预后意义.方法：采用原位杂交技术检测45例胃癌患者原发病灶和转移淋巴结中VEGF-C和VEGF-D mRNA的表达水平;并检测转移及非转移淋巴结中VEGF-C和VEGF-D mRNA表达差异.结果：71%和62.2%的胃癌原发病灶可见VEGF-C和VEGF-D mRNA表达,原发病灶阳性者,相应的淋巴结转移病灶都可见VEGF-C和VEGF-D mRNA表达,55.6%和51.1%的胃癌患者淋巴结转移病灶VEGF-C和VEGF-D mRNA表达水平高于原发病灶,原发病灶和转移病灶淋巴管生成表达水平的差异与胃癌的预后密切相关（P＜0.05）.结论：胃癌癌细胞转移至淋巴结后淋巴管生成因子表达可能进一步提高,以进一步增强转移能力.     

Clinicopathological and prognostic significance of vascular endothelial growth factors (VEGF)-C and -D and VEGF receptor 3 in invasive breast carcinoma.

AIMS: Vascular endothelial growth factors C and D (VEGF-C and VEGF-D) play a major role in lymphangiogenesis and activate VEGF receptor 3 (VEGFR-3). Our purpose was to study the clinicopathologic and clinical value of VEGF-C, VEGF-D and VEGFR-3 in invasive breast carcinoma. MATERIAL AND METHODS: Immunohistochemistry was performed in paraffin-embedded tissue specimens from 177 invasive breast carcinomas to detect the proteins VEGF-C, VEGF-D, VEGFR-3, p53, Ki67, c-erbB-2, topoII alpha and ER/PR. The results were statistically processed. RESULTS: VEGF-C, VEGF-D and VEGFR-3 were found to be predominantly expressed in the cytoplasm of the malignant cells. VEGF-C occasionally showed a submembranous intensification. VEGF-D and VEGFR-3 were also immunodetected in the nuclei of the malignant cells. Nuclear VEGF-D was positively correlated to p53, Ki67 and topoII alpha proteins' expression (p=0.003, p=0.009 and p=0.017 respectively) and nuclear VEGFR-3 to topoII alpha (p=0.034). Cytoplasmic expression of VEGF-C and its submembranous intensification were found to be independent indicators of patients' overall and disease-free survival, respectively (p=0.003 and p=0.044 respectively). The group with high expression of both cytoplasmic VEGF-C and stromal VEGFR-3 showed poor overall survival (p=0.024) and the group with both submembranous VEGF-C and stromal VEGFR-3 immunostaining showed poor both disease-free and overall survival (p=0.012 and p=0.038 respectively). CONCLUSION: VEGF-D and VEGFR-3 seem to exert proliferative activity in invasive breast carcinomas. VEGF-C was found to be an independent indicator of patient's poor prognosis and the simultaneous expression of tumor VEGF-C and stromal VEGFR-3 yielded additional prognostic information.     

Advance on molecular mechanism of lymphangiogenesis

This article focused on lymphatic vessel＇s origin, structure, function, classified regulation and side effect aroused by anti-lymphaniogenesis （lymphangiogenesis means the development of new lymphatic vessels）.     

肾小球足突细胞黏蛋白，肿瘤内皮标记物-8，血管内皮生长因子D在结、直肠癌中的表达及意义

目的：分析肾小球足突细胞黏蛋白（Podoplanin），肿瘤内皮标记物-8（TEM-8），血管内皮生长因子D（VEGF-D）在结、直肠癌中的表达及其意义。方法：用实时定量PCR方法分析30结、肠癌标本中TEM-8，Podoplanin及VEGF-D的表达，并结合病理学分期，淋巴结转移等肿瘤特点进行分析。结果：Podoplanin在肿瘤组织中的表达较正常组织中高，并与淋巴结转移及肿瘤分期相关；VEGF-D在肿瘤组织中的表达较正常组织中高，并与淋巴结转移相关，而与肿瘤分期无明显相关性；TEM-8在正常组织中基本无阳性表达，而在结、直肠癌组织中阳性表达率为90％，与肿瘤分期，淋巴结转移相关。结论：TEM-8，Podoplanin，VEGF-D均可作为结、直肠癌的标记物，并可反映淋巴结转移状况，TEM-8更可作为肿瘤特异性标记物，在结、直肠癌的诊断、治疗、预后判断中可望发挥重要作用。     

大肠癌VEGF-C和VEGF-D的表达及其相关性的研究

目的探讨血管内皮生长因子-C和-D(VEGF-C和-D)在大肠癌组织中的表达特点及其临床意义.方法应用免疫组化S-P法检测96例大肠癌及正常大肠组织中VEGF-C和-D的表达,并分析其与大肠癌临床病理参数及预后的关系.结果大肠癌组织VEGF-C和-D阳性率明显高于正常大肠组织(P＜0.01),而且两项指标间表达率呈显著正相关(r=0.466,P＜0.01).大肠癌VEGF-C或-D表达率在大肠癌分化程度、Dukes分期、淋巴结转移及患者预后间差异显著.(P＜0.01,P＜0.05).大肠癌原发灶与淋巴结转移灶中VEGF-C和-D表达相一致(P＜0.01,r=0.429和P＜0.01,r=0.511).结论大肠癌VEGF-C和-D高表达可能在肿瘤发生中起一定作用,并且可以作为判断大肠癌淋巴结转移和评估患者预后的重要参考指标.