High expressions of vascular endothelial growth factor and platelet-derived endothelial cell growth factor predict poor prognosis in alpha-fetoprotein-negative hepatocellular carcinoma patients after curative resection

Purpose  To evaluate the prognosis value of vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) in alpha-fetoprotein (AFP)-negative hepatocellular carcinoma (HCC) patients after curative resection. Methods  Tumor tissue microarrays (TMAs) were used to detect the expressions of VEGF and PD-ECGF in consecutive 162 AFP-negative HCC patients undergoing curative resection between 1997 and 2000 in our institute. Clinicopathologic data for these patients were evaluated. The prognostic significance was assessed using Kaplan–Meier survival estimates and log-rank tests. Multivariate study with Cox’s proportional hazard model was used to evaluate the prognosis-related aspects. Results  The positive rates of VEGF and PD-ECGF in tumor tissues were 59.9% (97/162) and 62.3% (101/162), respectively. Univariate analysis showed that VEGF and PD-ECGF were prognostic factors for relapse-free survival (P = 0.034 and P = 0.033, respectively). Multivariate analyses demonstrated that the co-index (VEGF/PD-ECGF) was an independent prognostic factor for overall survival and relapse-free survival (P = 0.002 and P = 0.000, respectively). Conclusion  The co-index of VEGF and PD-ECGF is a promising independent predictor for recurrence and survival of AFP-negative HCC patients after curative resection. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. J. Hu, Y. Xu and Z.-Z. Shen have contributed equally to this work.     

大肠癌血管内皮生长因子的表达及其意义

目的：探讨血管内皮生长因子（VEGF）mRNA在大肠癌和癌周组织中的表达及其与临床特征之间的关系,为在分子水平干预肿瘤血管形成,预防大肠癌复发和转移打下基础。方法：采用逆转录－聚合酶链反应（RT－PCR）检测方法,对68例大肠癌手术标本癌和癌周组织中VEGF mRNA的表达水平进行了相对定量研究。结果：肿瘤组织中VEGF mRNA的表达率为67．6％（46／68）,癌周组织表达率为32．4％（22／68）;肿瘤组织中VEGF mRNA表达水平在浆膜浸润组,淋巴结转移,远处转移和Dukes D期组分别显著高于未侵及浆膜组,无淋巴结转移组,无远处转移和Dukes A,B,C期组;肿瘤组织中VEGF mRNA表达水平在肿瘤直径大的大肠癌组（＞5cm)与大小肠癌组（≤5cm)以及不同组织学分组组之间相比差异无显著性。结论：VEGF在大肠癌浸润和转移过程中发挥重要作用,肿瘤血管形成与大肠癌浸润和转移关系密切。     

Serum vascular endothelial growth factor is a potential biomarker of metastatic recurrence after curative resection of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common malignancies in China. To date, surgery is still the best solution to it. However, metastatic recurrences after curative hepatic resections are very common. Tang et al have reported that recurrence rate within 5 years of curative hepatic resection is 61.5% [1]. As curative hepatic resection has a high tendency for metastatic recurrence, therapeutic interventions such as transarterial embolization and antiangiogenesis have been tried to further improve prognosis of HCC patients. Therefore, establishing a dependable, sensitive, easy, and economical method to predict metastatic recurrence following curative hepatic resection is of clinical urgency.     

Vascular endothelial growth factor in colorectal cancer

Background Angiogenesis plays an important role in colorectal cancer progression. Evidence from preclinical and clinical studies indicates that vascular endothelial growth factor (VEGF) is the predominant angiogenic factor in human colorectal cancer and is associated with formation of metastases and poor prognosis. Based on these results it was hypothesized that attacking one or more of the VEGF-mediated mechanisms may be promising in the treatment of colorectal cancer.Aims This article reviews the role of VEGF in colon cancer and summarizes recent advances in the treatment of colorectal cancer by anti-VEGF strategies.M. Guba and H. Seeliger contributed equally to this paper     

Intensive or not surveillance of patients with colorectal cancer after curative resection

It is common practice to follow patients with colorectal cancer for some years after resection and/or adjuvant treatment.Data are lacking about how often patients should be seen,what tests should be performed,and what surveillance strategy has a signifi cant impact on patient outcome.Seven randomized trials have addressed this issue,but none had sufficient statistical power.Four published meta-analyses have established that overall survival is significantly improved for patients in the more intensive progra...     

Expression of tissue factor and vascular endothelial growth factor is associated with angiogenesis in colorectal cancer

We examined the expression of tissue factor (TF) and vascular endothelial growth factor (VEGF) and the microvessel density (MVD) in 100 patients with colorectal cancer, and we investigated the relationship of the expression of TF or VEGF with angiogenesis. TF antigen was positive in 57.0% of all specimens. Incidence of TF expression was 41.2%, 45.5%, 52.6%, 84.6%, and 81.3% in tumors from patients in clinical stages I, II, IIIA, IIIB, and IV, respectively. TF expression was correlated with the Dukes' classification (P = 0.01) and the clinical stage of colorectal cancer (P = 0.02). VEGF antigen was positive in 64.0% of all specimens. Incidence of VEGF expression was 41.2%, 57.6%, 73.7%, 84.6%, and 75.0% in tumors from patients in clinical stages I, II, IIIA, IIIB, and IV, respectively. VEGF expression was correlated with the Dukes' classification (P = 0.01) but showed a weak association with the clinical stage (P = 0.08). MVD was significantly associated with the depth of invasion (P = 0.01), lymph node metastasis (P = 0.001), and liver metastasis (P = 0.02). The mean values of MVD were 7.5 +/- 2.8, 10.1 +/- 5.7, 14.6 +/- 5.8, 13.5 +/- 3.9, and 15.9 +/- 4.2 in tumors from patients in clinical stages I, II, IIIA, IIIB, and IV, respectively. A close relationship between VEGF and MVD (P < 0.001) and a significant correlation between TF expression and MVD were observed (P = 0.02). TF-positive carcinomas presented high MVD and VEGF expression (P < 0.001) more frequently than did TF-negative tumors. These results suggest that involvement of TF in the process of metastasis and progression of colorectal cancer may depend on increased angiogenesis.     

Hypoxia-inducible factor 1 alpha and vascular endothelial growth factor overexpression in ischemic colitis

AIM: To examine the etiology and pathophysiology in human ischemic colitis from the viewpoint of ischemic factors such as hypoxia-inducible factor 1 alpha (HIF-1 alpha and vascular endothelial growth factor (VEGF). METHODS: Thirteen patients with ischemic colitis and 21 normal controls underwent colonoscopy. The follow-up colonoscopy was performed in 8 patients at 7 to 10 d after the occurrence of ischemic colitis. Biopsy samples were subjected to real-time RT-PCR and immunohistochemistry to detect the expression of HIF-1 alpha and VEGF. RESULTS: HIF-1 alpha and VEGF expression were found in the normal colon tissues by RT-PCR and immunohistochemistry. HIF-1 alpha and VEGF were overexpressed in the lesions of ischemic colitis. Overexpressed HIF-1 alpha and VEGF RNA quickly decreased to the normal level in the scar regions at 7 to 10 d after the occurrence of ischemic colitis. CONCLUSION: Constant expression of HIF-1 alpha and VEGF in normal human colon tissue suggested that HIF-1 alpha and VEGF play an important role in maintaining tissue integrity. We confirmed the ischemic crisis in ischemic colitis at the molecular level, demonstrating overexpression of HIF-1 alpha and VEGF in ischemic lesions. These ischemic factors may play an important role in the pathophysiology of ischemic colitis.     

大肠癌组织中血管内皮生长因子的表达及意义

目的 探讨血管内皮生长因子（ＶＥＧＦ）在大肠癌组织中的表达及其与大砀癌发展的关系。方法 应用名单组织化学ＬＳＡＢ法检测５２你人大肠癌组织的ＶＥＧＦ表达,分析ＶＥＧＦ与大肠癌组织类类型、分化程度、Ｄｕｋｅｓ分期及淋巴结转移毕率随关大肠癌Ｋｕｋｅｓ分期的进展而增加,且Ｄｕｋｅｓ Ｃ期的ＶＥＧＦ表达率与ＤｕｋｅｓＡ期相比有显著性差异（Ｐ〈０．０５）,ＶＥＧＦ在有淋巴结转移组的４０．００％（Ｐ〈０．０１）     

Correlation of vascular endothelial growth factor (VEGF) and CEA with clinicopathological variables in colorectal cancer patients

The aim of the presented study is to analyze VEGF levels and its correlation with the clinicopathological characteristics of patients with colorectal carcinoma. Thirty-three patients with colorectal adenocarcinoma and 10 healthy controls were evaluated by estimation of VEGF and CEA levels and correlation with clinicopathological features. The serum VEGF and CEA concentrations of colorectal patients were higher than the healthy controls (p<0.05). Patients in advanced stage had high levels of both markers but these differences were not statistically significant. There was a positive correlation between both markers and, tumor size and peritumoral vascular invasion (PVI) but when compared VEGF with CEA, VEGF had a stronger correlation. Diagnostic sensitivity of VEGF for colorectal carcinoma was higher than the sensitivity of CEA and combining both markers the sensitivity to predict colorectal carcinoma was higher than of each marker alone. Our study indicated that VEGF compared to CEA had a higher diagnostic sensitivity for colorectal carcinoma and might provide even additional information about tumor features.     

Cyclooxygenase-2 overexpression correlates with vascular endothelial growth factor expression and tumor angiogenesis in gastric cancer

Angiogenesis is a key prerequisite for the successful establishment, growth, and dissemination of tumors. Vascular endothelial growth factor (VEGF) has a potent angiogenic activity and cyclooxygenase-2 (COX-2) promotes angiogenesis by modulated production of angiogenic factors including VEGF. The current study was designed to investigate the possible roles of COX-2 and VEGF in gastric cancer angiogenesis. In this study, we conducted an immunohistochemical investigation of COX-2 and VEGF expression in 97 patients with gastric cancer. To assess tumor angiogenesis, microvessel density (MVD) was determined by CD34 immunohistochemical staining. Expression of COX-2 and VEGF in gastric cancer tissues, was demonstrated in 63.9% and 75.3% of cases, respectively. The expression of COX-2 correlated significantly with VEGF expression. High MVD was significantly associated with depth of tumor invasion and poor survival. The mean MVD value of VEGF positive tumors was 79.8 +/- 32.0 and significantly higher than that of VEGF negative tumors. The mean MVD value of COX-2 positive tumors was 77.9 +/- 29.9 and not significantly higher than that of COX-2 negative tumor. The mean value of MVD in tumors positive for both COX-2 and VEGF was significantly higher than that in tumors negative for both. However, there was no correlation between COX-2 or VEGF expression and various clinicopathological features including patient survival. These results suggest that COX-2 may play an important role in carcinogenesis by stimulating tumor angiogenesis in concert with VEGF in human gastric cancer.     

血管内皮生长因子对腹水性质的诊断价值

目的　探讨腹水中血管内皮生长因子 (VEGF)测定在良恶性腹水鉴别诊断中的价值 ,以及联合检测癌胚抗原 (CEA)的临床意义。方法　于 2 0 0 2 - 0 5～ 2 0 0 3- 0 2采用酶联免疫吸附法检测苏州大学附属第一医院住院患者 5 8例腹水中的VEGF、CEA质量浓度。结果　恶性腹水VEGF含量明显高于良性腹水 ,差异有显著性 (P <0 0 1)。联合测定腹水VEGF和CEA质量浓度 ,其诊断恶性腹水的敏感性较单独腹水CEA检测有明显提高 ,差异有显著性 (P <0 0 5 )。结论　腹水VEGF测定有助于良恶性腹水的鉴别诊断 ,联合检测腹水VEGF和CEA对于腹水的鉴别诊断更有临床实用价值。     

术前循环肿瘤DNA含量对结直肠癌根治性切除术后3年生存率的预测价值

[目的]探究术前循环肿瘤DNA(ctDNA)含量对结直肠癌根治性切除术后3年生存率的预测价值。[方法]选择2014年3月~2016年3月行结直肠癌根治性切除术的78例患者,采用磁珠分离法提取受试者血浆ctDNA,荧光定量仪检测ctDNA的含量;随访至2019年3月31日,记录患者生存情况,比较存活患者和死亡患者血浆ctDNA含量,采用受试者工作曲线(ROC)分析血浆ctDNA含量对结直肠癌患者术后3年生存情况的预测价值,并采用Kaplan-Meier法进行生存分析。[结果]78例患者血浆ctDNA含量为(85.37±9.31)ng/mL,不同性别、年龄、肿瘤部位、TNM分期、分化程度及淋巴结转移情况患者血浆ctDNA含量差异无统计学意义;随访至2019年3月31日,存活患者56例,死亡22例,存活组患者血浆ctDNA含量明显低于死亡组(P<0.05);当血浆ctDNA≥85.91 ng/mL时,AUC为0.788,灵敏度为76.80%,特异度为72.70%,95%CI为0.674~0.901;低表达组患者3年总生存率为83.72%,显著高于高表达者(57.14%)(P<0.05)。[结论]术前血浆ctDNA含量的检测对结直肠癌根治性切除术后3年生存率有一定的预测价值,ctDNA含量越高的患者3年总生存率越低。     

结直肠癌患者血清中血管内皮生长因子和一氧化氮表达水平及其临床意义

目的:探讨结直肠癌患者血清中血管内皮生长因子(VEGF)和一氧化氮(NO)表达水平及其临床意义.方法:分别采用酶联免疫吸附测定(ELISA)法和分光光度法检测74例结直肠癌患者术前和45例结直肠腺瘤患者以及40例健康人血清中VEGF和NO的含量.结果:结直肠腺瘤患者血清VEGF和NO含量与健康人无明显差异(P＞0.05);结直肠癌患者血清VEGF和NO表达水平分别较结直肠腺瘤组以及健康人明显增高(P＜0.01),且结直肠癌浸润深度、有无淋巴结转移以及Dukes分期与血清VEGF和NO含量呈明显正相关(r=0.834,P＜0.01).结论:VEGF和NO与结直肠癌的发生发展密切相关,术前检测血清VEGF和NO含量可作为判断结直肠癌浸润转移以及Dukes分期的有效生物学指标.     

Peritoneal fluid contains high concentration of hepatocyte growth factor and vascular endothelial growth factor after resection for hepatocellular carcinoma

BACKGROUND/AIMS: Surges in blood growth factor levels is a typical response to surgical stress. However, growth factor profiles in peritoneal fluid after hepatectomy for hepatocellular carcinoma (HCC) have not been clarified. We evaluated hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) in blood and peritoneal fluid preoperatively and postoperatively. METHODOLOGY: Serial blood and peritoneal fluid samples were collected from 47 patients who underwent curative hepatectomy for primary HCC at a university hospital. Blood samples were collected postoperative days 0, 1, 3, 5, and 7; peritoneal fluid was collected at the same time except day 0. VEGF and HGF concentrations were determined, and correlations between concentrations and clinical parameters of HCC were analyzed. RESULTS: HGF surges appeared postoperatively in blood and peritoneal fluid; concentrations paralleled each other. There was no postoperative surge of VEGF in blood, but peritoneal fluid VEGF concentration was remarkably high after hepatectomy. Both HGF and VEGF levels in blood and peritoneal fluid correlated with some clinical parameters. The difference in HGF and VEGF patterns in blood and peritoneal fluid imply that the origins of these two growth factors differ. CONCLUSIONS: Post-hepatectomy, VEGF and HGF levels surged in peritoneal fluid, whereas only HGF surged in blood, suggesting independent origins for the two growth factors. Both VEGF and HGF concentrations correlated with some clinical parameters.