VEGF表达与鼻咽癌血管生成、瘤细胞增殖及预后的关系

目的探讨血管内皮生长因子（VEGF）表达与鼻咽癌（NPC）血管生成、肿瘤细胞增殖及预后的关系。方法选取有明确病理诊断、临床资料完整并随访5a以上的86例NPC患者活检标本,采用免疫组织化学技术检测活检标本中VEGF、微血管密度（iMVD）和增殖细胞核抗原（PCNA）的表达,并分析其与临床病理及预后的关系。结果全组VEGF阳性表达率69．9％（60／86）,与iMVD、PCNA呈显著正相关,与组织学分级、原发灶范围、淋巴结转移、临床分期及生存期亦具相关性。结论NPC组织中VEGF过表达可能参与NPC发生发展,可作为判断NPC恶性程度、侵袭能力和预后的指标。     

人脑胶质瘤中血管内皮细胞生长因子表达及其与细胞增殖的关系

为探讨人脑胶质瘤组织中血管内皮细胞生长因子 (VEGF)表达及其与细胞增殖的关系 ,应用链霉菌抗生物素蛋白 -过氧化物酶连接法 (SABC)免疫组织化学技术检测了 6 7例人脑胶质瘤、8例正常脑组织中 VEGF表达及增殖细胞核抗原 (PCNA)标记指数 (PCNA L I)。结果 VEGF在人脑胶质瘤组织中的阳性表达率为 83.6 %,正常脑组织中无表达 (P<0 .0 0 5 ) ;肿瘤组织中 VEGF表达与 PCNA L I呈显著正相关 (P<0 .0 0 5 )。认为胶质瘤细胞能分泌 VEGF,VEGF表达在肿瘤细胞增殖中起重要作用。     

胰腺癌组织中VEGF、PCNA与血管生成的关系及预后相关性

目的 探讨胰腺癌组织中VEGF、PCNA和血管生成的关系。方法 用免疫组织化学方法检测48例胰腺癌及癌旁组织、6例正常胰腺组织中VEGF、PCNA的表达和微血管密度（MVD）。结果 胰腺癌组织中VEGF、PCNA的阳性表达率分别为54．17％和77．5％，显著高于癌旁组织和正常组织的表达率（P〈0．01），胰腺癌组织中MVD显著高于癌旁组织和正常组织。VEGF表达与肿瘤大小和TNM分期有关（P=0．020，P=0．045），并且与MVD有相关性（r=0．294，P=0．043）。PCNA与临床病理因素无关。多元回归分析显示VEGF、PCNA和MVD都不是影响胰腺癌预后的独立因素。结论 血管生成在胰腺癌的发生、发展过程中起重要作用，抗肿瘤血管生成可能会提高胰腺癌的治疗效果。     

老年鼻咽癌组织增殖细胞核抗原、血管内皮细胞表达与PET/CT显像FDG摄取的相关性

目的探讨老年鼻咽癌的PET/CT显像中肿瘤18F-FDG摄取与肿瘤组织增殖细胞核抗原(PCNA)及血管内皮细胞生长因子(VEGF)表达的关系。方法对2005年3月至2006年10月收治的40例老年鼻咽癌患者进行正电子发射体层显像(PET)检查,测定肿瘤最大标准摄取值和平均摄取值(SUVmax和SUVmean);应用标准链霉菌抗生物素蛋白-过氧化物酶亲和(SP)免疫组化法检测38例患者肿瘤组织PCNA和VEGF的表达。结果 38例老年鼻咽癌组织的SUV max为8.46±1.92;38例老年鼻咽癌组织PCNA阳性细胞率为36.18%,VEGF染色阳性细胞率为60.8%;鼻咽癌组织FDG摄取(SUV max)与PCNA表达阳性率无相关(r=0.135,P=0.407),与VEGF表达阳性率相关(r=0.460,P=0.03)。结论老年鼻咽癌组织FDG摄取与VEGF过度表达相关。     

子宫颈癌血管内皮生长因子表达与肿瘤微血管数及肿瘤细胞增殖活性的关系

探讨血管内皮生长因子（VEGF）表达与子宫颈癌微血管数、肿瘤细胞增殖活性及其与肿瘤恶性程度的关系。应用免疫组化方法检测60例子宫颈癌患者、8例正常宫颈组织中VEGF、血小板粘附分子（CD31）和增殖细胞核抗原（PCNA）的表达,测定其阳性细胞数和阳性血管数。结果显示,子宫颈癌中均有VEGF、CD31及PCNA的表达,VEGF表达水平与肿瘤恶性程度、CD31及PCNA呈正相关。提示VEGF、CD31和PCNA在子宫颈癌中的高表达是高颈癌恶性表型之一。可作为病理诊断的补充,对患者颈后判断及选择适当的治疗方案有重要参考价值。     

胰腺癌组织中VEGF、PCNA与血管生成的关系及预后相关性

目的探讨胰腺癌组织中VEGF、PCNA和血管生成的关系.方法用免疫组织化学方法检测48例胰腺癌及癌旁组织、6例正常胰腺组织中VEGF、PCNA的表达和微血管密度(MVD).结果胰腺癌组织中VEGF、PCNA的阳性表达率分别为54.17%和77.5%,显著高于癌旁组织和正常组织的表达率(P < 0.01),胰腺癌组织中MVD显著高于癌旁组织和正常组织.VEGF表达与肿瘤大小和TNM分期有关(P = 0.020, P = 0.045),并且与MVD有相关性(r = 0.294, P = 0.043).PCNA与临床病理因素无关.多元回归分析显示VEGF、PCNA和MVD都不是影响胰腺癌预后的独立因素.结论血管生成在胰腺癌的发生、发展过程中起重要作用,抗肿瘤血管生成可能会提高胰腺癌的治疗效果.     

血管内皮生长因子表达在胃癌浸润转移中的作用

目的探讨血管内皮生长因子（VEGF）在胃癌组织中表达及其与临床特征之间的关系。方法材料取自瑞金医院外科1988年～1991年间手术切除标本，共128例。研究方法按LSAB法免疫组织化学操作技术常规进行，抗人VEGF单克隆抗体及抗人因子Ⅷ相关抗原单克隆抗体分别用于检测肿瘤组织内的VEGF蛋白和微血管数（MVC）。结果128例胃癌组织中，VEGF表达阳性率为6O．9％（78／128）。VEGF表达阳性肿瘤的MVC明显高于阴性者（P＜0．005）.高水平的VEGF表达与肿瘤的浸润性生长、浆膜浸润、淋巴结转移和肝转移具有明显相关关系。此外，VEGF表达阳性者的复发率高于阴性者，阳性者的预后明显较阴性者差。多因素分析表明，VEGF表达是胃癌的一个独立预后因子。结论VEGF可能通过刺激新生血管形成，与胃癌的恶性进程和不良预后有密切关系。     

血管内皮生长因子及其受体与肺癌血管新生的研究

目的：研究血管内皮生长因子及其受体促进肺癌血管新生的机制，探讨肺癌治疗的新策略。方法：共收集49份原发性支气管肺癌标本，用免疫组织化学技术检测微血管密度（MVD），血管内皮生长因子（VEGF），受体1（Flt1)受体2（KDR）在肺癌组织不同细胞成份中的表达程度。用Kaplan-Meier方法比较不同血管密度患者的生存情况。结果：（1）VEGF，Flt1和KDR在肿瘤细胞，基质成纤维细胞和血管内皮细胞上均有表达。（2）肺癌组织MVD与肿瘤TNM分期，临床分期，病理类型和分化程度等关联不明显，但微血管高密度组患者生存时间短，预后差（P＜0．05）。而Flt1和KDR在血管高密度组的表达程度均明显高于低密度组（P＜0．01）。（4）肿瘤细胞与基质成纤维细胞VEGF的表达程度有密切关联并且具有良好的一到场生。（5）肿瘤细胞VEGF与肿瘤细胞和血管内皮细胞KDR的表达均具有一致性，而与Flt1的表达却不具有一致性。结论：（1）肺癌组织MVD不受或较少受其它临床因素干扰，是肺中层得评估疗效，推测预后的一个独立和良好的指标。（2）VEGF促进血管新生的作用不单取决于其自身，还必须通过受体Flt1和KDR的介导才能实现，VEGF及其受体是抗肿瘤治疗良好的新靶点。（3）肿瘤细胞和基质成纤维细胞可能都分泌VEGF。（4）VEGF通过受体介导的机制均包含旁分泌和自分泌，但两种受体的重要性不同，KDR可能起主要作用。     

I期非小细胞肺癌的分子预后

目的 联合检测I期非小细胞肺癌（NSCLC）的细胞增殖、凋亡和血管生成，探讨I期非小细胞肺癌预后分层。方法应用免疫组织化学方法检测118例I期非小细胞肺癌、30例肺良性组织和30例正常肺组织血管内皮生长因子（VEGF）的表达，应用比Ki67标记检测细胞增殖指数（PI）。TUNEL法检测70例I期非小细胞肺癌，30例正常肺组织凋亡指数（AI）。结果单因素分析结果表明，肿瘤血管浸润、VEGF高表达、高PI、低AI为I期非小细胞肺癌的不良预后因素。多因素分析结果显示，肿瘤血管浸润（BVI、VEGF及PI可以作为影响I期非小细胞肺癌预后的独立因素。根据免疫组化综合评分（IRS）IRS=VEGF＋PI＋AI，将患者分为低危组及高危组，5年总体生存率分别为82．22％、23．33％，有显著性差异（P=0．0056）。综合评分可作为独立预后因素（RR=4．878，95％CI：1．379～17．258，P=O．014）。结论联合检测肿瘤的细胞增殖、凋亡和血管生成，可能实现对I期非小细胞肺癌的预后分层，判断预后以及指导治疗。     

PCNA、VEGF、ER在甲状腺乳头状癌中的表达及临床意义

目的探讨增殖细胞核抗原（PCNA）、血管内皮生长因子（VEGF）、雌激素受体（ER）在甲状腺乳头状癌等组织中的表达及临床意义。方法采用免疫组织化学技术S-P法检测58例甲状腺乳头状癌、30例甲状腺滤泡状腺瘤和30例癌旁正常甲状腺组织的PCNA、VEGF、ER表达。结果 PCNA、VEGF、ER在甲状腺乳头状癌中的表达率显著高于甲状腺滤泡状腺瘤组织及癌旁正常甲状腺组织（P〈0.01）;PCNA与VEGF呈正相关关系（r=0.8,P〈0.01）,与ER呈负相关关系（r=-0.3,P〈0.05）。结论 PCNA、VEGF、ER表达可作为甲状腺乳头状癌的协助诊断指标,对临床治疗和预后判断具有重要的指导意义。     

Relationship between VEGF and p53 expression and tumor cell proliferation in human gastrointestinal carcinomas

Purpose The vascular endothelial growth factor (VEGF) and p53 play important roles in the growth of tumor. However, the relationship between the expression of VEGF and p53 and tumor cell proliferation in human gastrointestinal cancer remains unknown. In the present study, therefore, we have examined the relationship between VEGF and p53 expression and tumor cell proliferation in gastrointestinal carcinoma (GITC), as well as the association between these biomarkers and clinicopathological factors. Methods Surgical specimens from 30 patients with GITC were examined for VEGF, p53, and proliferating cell nuclear antigen (PCNA) expression by immunohistochemical staining. Results We found a predominant VEGF expression of moderate intensity in 16(54.84%) of 30 GITC cases, while p53 expression was mainly high in 13(45.16%) of 30 GITC cases. PCNA expression was high in 20(64.52%) of 30 GITC cases. Tumor size, infiltration, vascular invasion, and gastritis were significantly correlated with VEGF, p53, and PCNA expression. There was a significant correlation between VEGF and p53 expression (P = 0.0001), VEGF and PCNA expression (P = 0.00004), and between p53 expression and PCNA expression (P = 0.0016). When the VEGF and p53 expression, and PCNA expression were considered together, both VEGF and p53 expression were not significantly associated with PCNA. A significant correlation between the PCNA expression and the mitotic index (P = 0.0016) was also found. Conclusion These results demonstrate that VEGF and p53 expression are significantly correlated as independent prognostic factors with tumor cell proliferation, and might be associated with relevant events involved in gastrointestinal tumor biology.     

TNP-470对肺腺癌细胞增殖和凋亡的影响

目的 探讨TNP－470对肺腺癌细胞增殖和凋亡的影响及其作用机制。方法 以不同浓度的TNP－470信息处理地培养的肺腺癌AGZY－82A细胞株,以免疫组化S－P法检测肺腺癌细胞增殖核抗原（PCNA）、p53、bcl-2、血管内皮生长因子（VEGF）和VEGF受体Flk-1的表达。结果 随着TNP－470浓度的增加,肺腺癌细胞VEGF、Flk-1、PCNA的表达减少,p53、bcl-2的表达逐渐增加;当TNP－470为10^7μg/L时,细胞增殖几乎停止,随着TNP－470（10^4μg/L）作用时间的延长,肺腺癌细胞VEGF、Flk-1、PCNA的表达逐渐减少,而p53、bcl-2的表达逐渐增加。结论 TNP－470通过使肺腺癌细胞自分泌VEGF减少,Flk表达降低,从而抑制肺腺癌细胞增殖,促进其凋亡。     

VEGF trap abolishes shear stress- and overload-dependent angiogenesis in skeletal muscle

OBJECTIVE: To determine which elements of the angiogenic process are controlled by VEGF under physiological conditions. METHODS: VEGF Trap was administered at 10 mg x kg(-1) by subcutaneous injection twice weekly to mice, which were subject to one of two established angiogenic stimuli: (1) increasing blood flow by administration of prazosin (50 mg L(-1)); (2) muscle overload by extirpation of a synergist. Angiogenesis was determined by calculating capillary to fiber ratio (C:F), and proliferating cell nuclear antigen (PCNA) staining localized to capillaries or the interstitium used to measure cell proliferation. Characteristic ultrastructural changes were quantified using electron microscopy. RESULTS: Administration of VEGF Trap abolished the increases in C:F seen in both models, and prevented growth of luminal filopodia and large vacuole formation. Overload-induced proliferation associated with capillaries was reduced, along with endothelial cell number abluminal sprouts and basement membrane breakage. However, interstitial proliferation remained high, along with the increased capillary association of pericytes and fibroblasts. CONCLUSIONS: VEGF is required for both models of angiogenesis, although some morphological changes lie upstream, or are independent of, VEGF involvement. The abolition of angiogenesis in a model unaffected by NO inhibition shows that NO is not required for all VEGF-dependent angiogenesis in vivo.     

Expression of PTEN and its correlation with angiogenesis in gastric carcinoma]

BACKGROUND/AIMS: Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a recently clarified tumor suppressor gene located in 10q23.3. Alterations of this gene are associated with tumor progression and unfavorable outcome in various human cancers. Recently, PTEN has a possible role in angiogenesis by modulating angiogenic factor including vascular endothelial growth factor (VEGF). The aim of this study was to investigate the roles of PTEN and VEGF status for angiogenesis in human gastric cancer. METHODS: We conducted an immunohistochemical investigation of PTEN and VEGF expression in 90 cases of paraffin section obtained from gastric cancer patients undergone surgical treatment. RESULTS: Negative expression of PTEN and positive expression of VEGF in gastric cancer tissues, were demonstrated in 40.0% and 77.8% of cases, respectively. However, no significant correlation was found between PTEN, VEGF expression and various clinicopathological parameters. PTEN expression did not correlate significantly with VEGF expression (p=0.301). High microvessel density (MVD) was significantly associated with lymph node metastasis and poor survival (p=0.014, 0.011, respectively). The mean MVD value of PTEN negative tumors was 90.4+/-43.0 and significantly higher than that of PTEN positive tumors (p=0.028). The mean MVD value of VEGF positive tumors was 86.4+/-6.7 and significantly higher than that of VEGF negative tumors (p=0.002). The mean MVD value of PTEN negative and VEGF positive tumors was 98.0+/-42.2, and significantly higher than those of the others. CONCLUSIONS: These results suggest that loss of PTEN expression may play a critical role in tumor progression and metastasis by stimulating tumor angiogenesis in human gastric cancer.     

Effects of TNP-470 on proliferation and apoptosis in human colon cancer xenografts in nude mice

AIM: To study the effect of TNP-470 on cell growth, proliferation and apoptosis in human colon cancer xenografts in nude mice. METHODS: Human colon cancer xenografts were transplanted into 20 nude mice. Mice were randomly divided into two groups. TNP-470 treated group received TNP-470(30 mg/kg, s.c) every other day and the control group received a sham injection of same volume saline solution. They were sacrificed after 4 weeks and their tumors were processed for histological examination. The expression of proliferating cell nuclear antigen (PCNA) in tumors was detected using immunohistochemical method with image analysis, and apoptosis in tumor cells was measured by TdT-mediated biotinyated-dUTP nick end labeling (TUNEL) staining. RESULTS: Comparing with controls, tumor growth was significantly inhibited in TNP-470 treated group, the inhibitory rate being 54.4 %. Expression of PCNA in tumors of TNP-470 treated group (PI 54.32+/-11.47) was significantly lower than that of control group (PI 88.54+/-12.36), P<0.01. Apoptosis index (AI) of TNP-470 treated group (18.95+/-1.71) was significantly higher than that of control group (7.26+/-1.44), P<0.001, typical morphological change of apoptosis in tumor cells was observed in TNP-470 treated group. CONCLUSION: Besides the anti-angiogenic effects, TNP-470 can inhibit tumor growth by inhibiting the proliferation and inducing apoptosis of tumor cells.     

西罗莫司对人肝癌裸鼠肝脏移植瘤生长的影响

目的 探讨西罗萸司(SRL)对人肝癌裸鼠肝脏移植瘤生长的影响.方法 建立人肝癌裸鼠肝脏移植瘤模型,使用SRL、他克莫司(FK506)进行干预治疗,采用免疫组织化学方法和图像分析技术检测移植瘤血管内皮细胞生长因子、增殖细胞核抗原的表达和微血管密度,原位末端标记法检测肿瘤细胞凋亡情况.统计学处理采用方差分析或t检验.结果 (1)SRL、FK506组和对照组移植瘤质量分别为(352±38)mg、(683±53)mg、(675±45)mg;SRL组移植瘤质量较对照组明显减少(t=10.378,P<0.01);FK506组和对照组比较无明显差异(P>0.05).(2)SRL组移植瘤血管内皮细胞生长因子和增殖细胞核抗原的表达较对照组明显下凋亡(f值分别为5.753和5.296,P<0.05),FK506组和对照组比较无明显差异(P>0.05).(3)SRL组移植瘤微血管密度较对照组明显减少(t=8.637,P<0.01);FK506组和对照组相比无明显变化(P>0.05).(4)SRL组移植瘤凋亡指数明显高于对照组(t=11.518,P<0.05);FK506对移植瘤凋亡指数无明显影响(P>0.05). 结论 SRL可通过减少肿瘤血管形成、阻I卜肿瘤增殖、诱导肿瘤细胞凋亡抑制肝癌的生长.     

Expression of COX-2, PCNA, Ki-67 and p53 in gastrointestinal stromal tumors and its relationship with histopathological parameters

AIM： To investigate the expression of Cyclooxygenase-2 （COX-2）, proliferating cell nuclear antigen （PCNA）, Ki-67 and p53 in gastrointestinal stromal tumors （GISTs） and its relationship with histopathological parameters.
METHODS： Twenty-five GISTs were examined by light microscopy and immunohistochemistry, c-kit, CD34, SMA, S-100 protein, COX-2, PCNA, Ki-67 and p53 were detected immunohistochemically and the relationship was evaluated among histopathologic parameters such as mitotic index （MI）, tumor grade, tumor size, COX-2, PCNA, Ki-67 and p53.
RESULTS： COX-2 protein expression was found in 19 of 25 （76%） of the tumors, and expression was noted in the cytoplasm of the tumor cells, p53 was significantly related to MI and tumor grade but no relationship was found between COX-2, proliferation markers and MI, tumor grade and tumor size.
CONCLUSION： COX-2 is expressed in most GISTs and it may play an important role in the proliferation and progression of these tumors or a useful marker to identify GIST. Although immunohistochemical assessment of p53 can be used for distinguishing the risk groups of GISTs, tumor size and mitotic rate should be considered at the same time.     

Inhibition of angiogenesis and HCT-116 xenograft tumor growth in mice by kallistatin

AIM: To investigate the inhibitory effect of kallistatin (KAL) on angiogenesis and HCT-116 xenograft tumor growth. METHODS: Heterotopic tumors were induced by subcutaneous injection of 2 × 106 HCT-11 cells in mice. Seven days later, 2 × 1011 rAAV-GFP or rAAV-KAL was injected intratumorally (n = 5 for each group). The mice were sacrificed at d 28, by which time the tumors in the rAAV-GFP group had grown to beyond 5% of the total body weight. Tumor growth was measured by calipers in two dimensions. Tumor angiogenesis was determined with tumor microvessel density (MVD) by immunohistology. Tumor cell proliferation was assessed by Ki-67 staining. RESULTS: Intratumor injection of rAAV-KAL inhibited tumor growth in the treatment group by 78% (171 ± 52 mm3) at d 21 after virus infection compared to the control group (776 ± 241 mm3). Microvessel density was significantly inhibited in tumor tissues treated with rAAV-KAL. rAAV-KAL also decreased the proportion of proliferating cells (Ki-67 positive cells) in tumors compared with the control group.CONCLUSION: rAAV-mediated expression of KAL inhibits the growth of colon cancer by reducing angiogenesis and proliferation of tumor cells, and may provide a promising anti-angiogenesis-based approach to the treatment of metastatic colorectal cancer.     

Vascular endothelial growth factor expression in airways of patients with lung cancer: a possible diagnostic tool of responsive angiogenic status on the host side

STUDY OBJECTIVE: We evaluated the expression of vascular endothelial growth factor (VEGF) in airways in patients with lung cancer. METHODS: BAL fluid (BALF) and plasma samples were obtained from 41 patients with primary lung carcinomas and 7 patients with noncancerous diseases, and were analyzed for VEGF by an enzyme-linked immunosorbent assay. After standardization with the albumin protein levels, the relative intensity (VEGF index) was determined as the ratio of VEGF expression on the disease side to that on the healthy side. RESULTS: In all cases, VEGF concentrations in BALF were greater than those in plasma samples. On the healthy side, the mean value of VEGF in BALF was significantly greater in lung cancer patients than in patients with noncancerous diseases (p = 0.0470). While age, gender, location of cancer (right vs left), histology (adenocarcinoma vs squamous cell carcinoma), and T factor (T1/2 vs T3/4) did not affect the VEGF levels in BALF, the VEGF index was inversely associated with distant metastasis and nodal involvement. The VEGF index of patients in stage I was significantly greater than that of patients in stage IV (p = 0.0308). CONCLUSIONS: The VEGF expression in airways is likely to reflect the response to tumor angiogenesis on the host side. Of direct clinical relevance is that the assessment of VEGF concentrations in airways may provide information concerning the dependency of tumor angiogenesis on VEGF, which is variable according to tumor progression.