Serum vascular endothelial growth factor (VEGF) and bcl-2 levels in advanced stage non-small cell lung cancer

The characteristic changes in cancer process are assumed to be genetic alterations about the imbalance of cell proliferation and apoptotic cell death. This study was conducted to determine the value of the circulating vascular endothelial growth factor (VEGF) and Bcl-2 in patients with advanced stage non-small cell lung cancer (NSCLC). These serum factors were measured of 52 NSCLC patients pathologically verified on before and after chemotherapy in comparison with 16 healthy controls by using ELISA method. Both of the serum levels of VEGF (p = 0.015) and Bcl-2 (p < 0.001) were increased significantly in NSCLC patients compared with the healthy controls. No statistically significant relationships between investigated elevated serum parameters and various characteristics of patients and disease such as stage and tumor burden were determined. Likewise, we also found no correlation between serum VEGF and Bcl-2. Cytotoxic therapy of patients was accompanied by unchanged serum levels of serum factors. The median survival of all patients was 27 weeks and one-year survival rate was 22.4 percent. With the median serum levels as the cut-off value, patients were divided into high- and low-serum parameter groups. While we found that patients' performance status (p < 0.0001), serum LDH level (p = 0.0002), response to chemotherapy (p = 0.0023), and stage of the disease (p = 0.0085) were prognostic factors for survival, serum VEGF (p = 0.48) and Bcl-2 (p = 0.91) levels were determined as ineffective on survival in patients with advanced NSCLC. In conclusion, our data suggest that these serum factors, VEGF and Bcl-2, are useful diagnostic factors, not predictive and prognostic markers for overall survival in advanced NSCLC patients.     

Serum vascular endothelial growth factor (VEGF) levels correlate with tumor VEGF and p53 overexpression in endocrine positive primary breast cancer

Vascular endothelial growth factor (VEGF) is a potent stimulator of angiogenesis, associated with unfavorable clinical characteristics in breast cancer. The aim of this study was to evaluate different angiogenic markers in endocrine-positive breast cancer patients. The authors analyzed serum and tumor samples from 71 patients with endocrine-positive operable primary breast cancer to determine the expression and the possible relationship between circulating serum VEGF levels, tumor VEGF expression, microvessel density (MVD), and other immunohistochemical parameters. Basal VEGF serum levels were significantly higher in breast cancer patients than in healthy controls. A significant correlation was observed between basal VEGF serum concentrations, microvessel density (p = 0.01) and p53 status (p = 0.004). Intratumoral VEGF expression was significantly associated with neoplastic embolization (p = 0.041) and circulating VEGF levels (p = 0.047). The results confirm that in primary endocrine-positive breast cancer serum VEGF levels are elevated and show a positive relationship with tumor VEGF and p53 overexpression.     

Ribozyme approach to downregulate vascular endothelial growth factor (VEGF) 189 expression in non-small cell lung cancer (NSCLC)

The aim of this study was to further clarify the role of the cell-associated isoform of vascular endothelial growth factor (VEGF189) on tumour growth and vascularity. Five isoforms of VEGF have been identified with different biological activities. VEGF121, VEGF145, VEGF165, VEGF189, VEGF206 are generated by alternative splicing. We used a hammerhead-type ribozyme (V189Rz) to suppress VEGF189 mRNA. The V189Rz specifically cleaved exon 6 of VEGF189 mRNA, but showed no activity against the VEGF121 or VEGF165 isoforms. The V189Rz was introduced into the human non-small cell lung cancer (NSCLC) cell line (OZ-6/VR). The expression level of VEGF189 mRNA was decreased in the OZ-6/VR cells, while VEGF121 and 165 expression was unaltered. The OZ-6/VR cells xenotransplanted into nude mice showed markedly reduced vascularisation and growth, whereas the cell line did not show any decreased growth under tissue culture conditions. The OZ-6/VR cells (1×10⁵ cells/mouse) formed no tumours, whereas the parental OZ-6 cells formed large tumours within 8 weeks. The specific suppression of VEGF189 by the ribozyme decreased vascularity and xenotransplantability of the lung cancer cell line. Thus, the cell-associated isoform of VEGF, VEGF189, might have a key role in stromal vascularisation and the growth of NSCLC xenografts in vivo.     

小细胞肺癌患者血清血管内皮生长因子含量水平的临床意义

目的探讨小细胞肺癌(SCLC)患者血清血管内皮生长因子(sVEGF)水平的临床意义。方法用酶联免疫吸附法(ELISA)测定45例SCLC患者、30例肺炎及50例健康人sVEGF的含量,并分析了sVEGF与患者临床分期、淋巴结及远处转移、化疗效果及化疗前后关系。结果SCLC组sVEGF水平(325.21±45.22μg/ml)明显高于对照组(175.18±60.56μg/ml,P<0.001)及肺炎组(182.29±45.22μg/ml,P<0.01),Ⅰ、Ⅱ期SCLC患者sVEGF水平(328.38±35.21μg/ml)低于Ⅲ、Ⅳ期(379.12±61.51μg/ml,P<0.005);与无转移者比较,淋巴结及远处转移者具较高的sVEGF水平(368.54±44.27μg/ml,P<0.001;376.21±21.52μg/ml,P<0.001)。29例患者治疗3个月后sVEGF水平下降(258.23±31.53μg/ml,P<0.001),但当肿瘤复发时sVEGF升高。结论SCLC者sVEGF变化与肿瘤转移、复发及预后等可能有关。     

Serum vascular endothelial growth factor (VEGF) and VEGF-C levels as tumor markers in patients with cervical carcinoma

BACKGROUND: Vascular endothelial growth factor (VEGF) and VEGF-C play a crucial role in the regulation of tumor growth and metastasis. The current study examined the significance of serum VEGF and VEGF-C levels in relation to conventional clinicopathologic parameters, response to treatment, and survival in patients with cervical carcinoma. METHODS: Between December 1999 and March 2004, serum VEGF and VEGF-C levels were analyzed in 78 patients with cervical carcinoma undergoing primary treatment (primary surgery [n=40] and radiotherapy [n=38]), as well as in 30 healthy controls. Serum VEGF and VEGF-C levels were assessed by enzyme-linked immunosorbent assay before and within 2 weeks after treatment. RESULTS: Serum VEGF and VEGF-C levels were higher in patients with cervical carcinoma than in the healthy control (P=0.0002 and P=0.0007, respectively). Both VEGF and VEGF-C concentrations increased significantly in patients with squamous cell carcinoma (SCC vs. normal control: P<0.0001 and P=0.0001, respectively), but not in adenocarcinoma (vs. normal control: P=0.2982 and P=0.7766, respectively). In an analysis of SCC, the pretherapeutic serum levels of VEGF and VEGF-C correlated significantly with advanced International Federation of Gynecology and Obstetrics stage and large tumor size, but not with lymph node metastasis. The pretherapeutic serum level of VEGF-C also correlated significantly with disease recurrence or persistence after treatment. Both serum VEGF and VEGF-C levels decreased significantly after treatment. CONCLUSIONS: The serum levels of both VEGF and VEGF-C have potential usefulness as biologic markers of SCC of the uterine cervix.     

血管内皮生长因子与小细胞肺癌

  回顾了近年来血管内皮生长因子在小细胞肺癌中的研究现状及其进展，从血管内皮生长因子的结构、功能及影响其表达的因素、血管内皮生长因子与小细胞肺癌的关系、血管内皮生长因子与小细胞肺癌治疗的关系研究情况等方面作一综述。     

Pretreatment vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) serum levels in patients with metastatic non-small cell lung cancer (NSCLC)

PURPOSE: In the present study, we investigated the prognostic value of vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-9 serum levels in patients with metastatic non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: From September 1999 to June 2001, pretreatment serum levels of VEGF and MMP-9 were analysed in 194 patients of a randomized phase III trial with enzyme-linked immunoassays. RESULTS: Patients with a VEGF serum level higher than the median serum level (10,995 pg/ml) had a significantly shorter overall survival than those with a lower serum level (P=0.04). The MMP-9 serum level did not correlate with survival. In a multivariate Cox regression analysis, only the pretreatment serum level of VEGF, the Karnofsky performance status, and the presence of bone metastases were identified as independent prognostic factors. CONCLUSIONS: The pretreatment VEGF serum level was identified as independent prognostic factor in this study and may help to assess individual risk and treatment profiles in patients with metastatic NSCLC.     

Elevated vascular endothelial growth factor (VEGF) serum levels in idiopathic myelofibrosis.

An increase of angiogenesis has been shown in idiopathic myelofibrosis with myeloid metaplasia (MMM) by microvessel density count method but evaluation of circulating angiogenic factors is still incomplete. In 31 patients affected by MMM and in 12 healthy subjects we evaluated the serum levels of VEGF (vascular endothelial growth factor) and correlated VEGF with clinical and laboratory features of disease. We found that MMM patients had circulating VEGF concentrations much higher than controls (Median 1208 ng/ml vs 138 ng/ml, P < 0.0001). No correlation was found between VEGF and Hb, WBC, PLT, LDH, creatinine, bone marrow cellularity, fibrosis, splenomegaly, hepatomegaly, and therapy. However, in the subgroup of patients with a normal or low VEGF concentration, a direct correlation between VEGF and platelet count (r = 0.90, P = 0.002) was detected. Moreover, patients with a platelet count < 300 x 10(9)/l had VEGF serum levels lower than patients with a higher PLT count (median VEGF 864 vs 1557 pg/ml, P = 0.001). In six patients and in eight controls we also had the opportunity to measure VEGF in the plasma and we calculated that VEGF concentration was much higher in platelet-rich than in platelet-poor plasma and that platetets of MMM patients contained four times more VEGF than those of healthy controls. These results indicate that VEGF is overproduced in MMM, thus confirming an increased angiogenic activity. Platelets are probably a major source of VEGF in MMM but not the only one.     

小细胞肺癌化疗前后血清VEGF的变化及临床意义

目的：探讨化疗前后小细胞肺癌（SCLC）患者血清血管内皮生长因子（sVEGF）水平及临床意义。方法：用酶联免疫吸附法（ELISA）测定48例SCLC患者化疗前后sVEGF的变化,并与健康志愿者做对照。结果：化疗前SCLC组sVEGF水平为（351.57±30.93）μg/ml,健康志愿者（128.83±13.90）μg/ml,差别有统计学意义（P〈0.01）。化疗后sVEGF为（274.99±38.20）μg/ml,明显低于化疗前（P〈0.01）,但仍然高于健康志愿者（P〈0.01）。结论：SCLC组sVEGF水平明显高于健康志愿者,化疗可以降低SCLC患者sVEGF水平,但仍高于健康志愿人,加用抗血管生成的分子靶向治疗是必要的。     

小细胞肺癌化疗前后血清VEGF的变化及临床意义

目的:探讨化疗前后小细胞肺癌(SCLC)患者血清血管内皮生长因子(sVEGF)水平及临床意义.方法:用酶联免疫吸附法(ELISA)测定48例SCLC患者化疗前后sVEGF的变化,并与健康志愿者做对照.结果:化疗前SCLC组sVEGF水平为(351.57±30.93)μg/ml,健康志愿者(128.83±13.90)μg/ml,差别有统计学意义(P＜0.01).化疗后sVEGF为(274.99.4±38.20)μg/ml,明显低于化疗前(P＜0.01),但仍然高于健康志愿者(P＜0.01).结论:SCLC组sVEGF水平明显高于健康志愿者,化疗可以降低SCLC患者sVEGF水平,但仍高于健康志愿人,加用抗血管生成的分子靶向治疗是必要的.     

血管内皮生长因子对小细胞肺癌诊治的应用价值研究

背景与目的血管内皮生长因子(VEGF)与肿瘤的发生、发展和转移关系密切,而小细胞肺癌(SCLC)患者预后差,转移早,生存期短。本研究拟探讨VEGF在SCLC中发生、发展的作用及其对SCLC患者诊治的临床意义和预后价值。方法酶联免疫吸附方法检测未经任何治疗的SCLC患者、良性肺部疾病患者及健康对照血清VEGF浓度和SCLC患者血清前胃泌素释放肽(ProGRP)的浓度,放射免疫分析方法检测血清神经元特异烯醇化酶(NSE)的浓度。结果SCLC患者血清VEGF浓度较健康对照及良性肺部疾病患者高,差异有统计学意义(P<0.05),而且SCLC患者血清VEGF的浓度与患者的临床分期有明显的相关性(P<0.05)。以血清VEGF的平均浓度489.1ng/L作为临界值,诊断SCLC的灵敏度和特异度分别是32.8%和95.7%。SCLC患者血清VEGF与血清NSE、ProGRP的水平无明显的相关性(r分别为0.221、0.217,P值均>0.05)。血清VEGF与血清NSE、ProGRP及三者的联合检测SCLC阳性率分别为54.1%、73.8%和78.7%。单变量生存分析和多变量生存分析SCLC患者血清VEGF水平与生存期的关系,结果显示低水平组的平均生存期比高水平组显著延长(P<0.05)。结论SCLC患者血清VEGF浓度与其生存期有明显的相关性,可以作为SCLC患者的一个预后因子。由于血清VEGF酶联免疫吸附试验方法学的特点,可以考虑作为SCLC肿瘤标志物的一辅助实验。     

Serum and plasma vascular endothelial growth factor levels in testicular cancer patients.

I read with interest Aigner and colleagues’ article [1]published recently in Annals of Oncology. Although the authorsshould be congratulated for their results on the study of pleiotrophinand fibroblast growth factor, I would like to report some methodologicalissues concerning     

血管内皮生长因子表达与非小细胞肺癌侵袭、淋巴结转移的关系

 目的 探讨血管内皮生长因子（VEGF）表达与非小细胞肺癌（NSCLC）侵袭、淋巴结转移的相关关系。方法 选取NSCLC组织58例及正常肺支气管黏膜组织25例，采用免疫组化染色法检测VEGF 在各组织中的表达。结果 58例肺癌组织VEGF阳性表达率为43.1 %，明显高于正常肺支气管黏膜组织（14.3 %）（P＜0.01）。VEGF表达与NSCLC组织的分化程度、肿瘤组织类型无关，与淋巴结转移及生存期密切相关（P＜0.05或P＜0.01）。结论 VEGF表达可能是NSCLC发生的一种生物学标志，VEGF的表达检测是判断NSCLC侵袭转移及预后的一个重要参考指标。     

Serum concentrations of interleukin-8, vascular endothelial growth factor, and epidermal growth factor receptor in patients with squamous cell cancer of the head and neck

Squamous cell cancer of the head and neck (SCCHN) is associated with production of pro-inflammatory and pro-angiogenic cytokines. We hypothesized that cytokine serum levels will correlate with tumor volume and aggressiveness. We investigated interleukin-8 (IL-8), vascular endothelial growth factor (VEGF), and epidermal growth factor receptor (EGFR) in SCCHN. The patient population consisted of normal and irradiated controls: patients with newly diagnosed SCCHN, and patients with recurrent or metastatic disease. Pretreatment sera were studied by ELISA. Serum IL-8 levels, as opposed to VEGF or EGFR, were consistently elevated in patients with recurrent or metastatic disease. The differences in mean serum IL-8, compared to controls, were significant (p=0.02). Serum levels of IL-8 are consistently elevated in patients with recurrent or metastatic SCCHN and elevated levels may correlate with advanced or aggressive disease. Further, more intensive, study of IL-8 as a biomarker in SCCHN is warranted.     

Effects of COX-2 inhibition on expression of vascular endothelial growth factor and interleukin-8 in lung cancer cells

Background  

Cyclooxygenase (COX)-2 has been implicated in tumour progression, angiogenesis and metastasis in non-small cell lung cancer (NSCLC). We speculated that inhibition of COX-2 activity might reduce expression of the pro-angiogenic factors vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) in lung cancer cells.     

The significance of circulating vascular endothelial growth factor (VEGF) protein in gastric cancer

We examined the vascular endothelial growth factor (VEGF) levels in peripheral blood and drainage vein (plasma and serum), and then these were compared with local VEGF expression from gastric cancer. Peripheral blood plasma VEGF levels was increased in the patients with venous invasion, and moderately correlated with the number and ratio of lymph nodes with metastasis. Local VEGF expression was correlated significantly with tumor size, advanced stage and lymph node metastasis, but not correlated with peripheral VEGF levels. The level of plasma VEGF in peripheral veins is one of the sensitive markers of the status of gastric cancer.