Serum VEGF levels in women with a benign breast tumor or breast cancer

Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis and vascular permeability. Many types of malignant human tumors have been shown to produce VEGF. Recently, increased serum concentrations of VEGF (S-VEGF) have been reported in patients with various types of cancer, and high S-VEGF levels have also been associated with unfavorable prognosis. We have now measured S-VEGF in sera taken from 105 patients with a benign breast tumor or breast cancer. None of the women with a benign breast tumor had S-VEGF higher than 328 pg/ml (median, 57 pg/ml) whereas S-VEGF levels in metastatic breast cancer ranged from 7 to 1347 pg/ml (median, 186 pg/ml P=0.0018), and in locoregional breast cancer from 11 to 539 pg/ml (median, 104 pg/ml P=0.13). S-VEGF was higher in patients with locoregional ductal cancer (median, 107 pg/ml) than in those with locoregional lobular cancer (median, 44 pg/ml; P=0.029) or in patients with benign breast tumor (median, 57 pg/ml; P=0.033). Patients with metastatic cancer undergoing therapy had lower S-VEGF than those who had symptomatic treatment only (P=0.021). The results indicate that dissemination of breast cancer may be accompanied by an elevation of circulating VEGF and that primary ductal cancers are associated with higher S-VEGF levels than lobular cancers or benign breast lesions.     

Prognostic and predictive value of vascular endothelial growth factor and its soluble receptors, VEGFR-1 and VEGFR-2 levels in the sera of small cell lung cancer patients

OBJECTIVES: Small cell lung cancer (SCLC) has a rapid growth rate and is characterized by early metastases. Tumor growth is dependent on angiogenesis. Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis. Whether surveillance of pre- and post-treatment serum VEGF and especially its receptors VEGF-1 and VEGF-2 levels in SCLC patients have impact on clinical outcome is unknown. METHODS: From February 2001 to January 2003, 39 consecutive patients with histological proven SCLC were enrolled into the study. Pre-treatment (n: 39) and post-treatment (n: 25) samples of the same patients were collected at the time of their response evaluation. The levels of VEGF and its receptors VEGFR-1 and VEGFR-2 were measured in the serum by quantitative sandwich enzyme immunoassay technique. RESULTS: The median pre-treatment serum VEGF, VEGFR-1, and VEGFR-2 levels which were significantly higher than the normal controls were 1,200 pg/ml (range, 1,414.3 +/- 956.2 pg/ml), 85 pg/ml (range, 97.8 +/- 70.7 pg/ml), and 11,550 pg/ml (range, 14,481 +/- 6,267 pg/ml), respectively. We detected a poor but positive correlation between VEGF and VEGFR-2 (r: 0.46, p: 0.003). Pre-treatment low serum VEGF (<728.5 pg/ml) value (p: 0.02) and good response to treatment (p: 0.008) were found as good prognostic factors by multivariate analysis. CONCLUSIONS: Low serum VEGF concentration is a significant and independent prognostic factor in SCLC patients. Surveillance of VEGF and its receptors to predict chemotherapy response is not useful. Whether the levels of serum VEGF and its receptors VEGFR-1 and VEGFR-2 have value in detecting treatment modalities of SCLC need further studies.     

血清血管内皮生长因子在孤立性肺结节鉴别诊断中的价值

目的　检测血清血管内皮生长因子 (S VEGF)水平 ,探讨肺部孤立性结节良恶性的鉴别诊断价值。方法　采用酶联免疫吸附法 (ELISA)对 6 8例孤立性肺结节患者和 2 0例健康人的S VEGF进行测定 ,观察恶性结节 (肺癌组 )、良性结节和健康人之间S VEGF水平的差异。 6 8名患者均于术后获得病理诊断。结果　健康人S VEGF水平的中位数为 4 2 .5 (10～ 170 )pg/ml,良性结节为 4 4 .0 (18～36 0 )pg/ml,肺癌为 75 .0 (18～ 890 )pg/ml。肺癌组与健康对照组的S VEGF水平差异有显著性 (P <0 .0 1) ;与良性结节组的差异亦有显著性 (P <0 .0 5 ) ;而良性结节组与健康对照组的S VEGF水平差异无显著性 (P >0 .0 5 )。腺癌和鳞癌患者的S VEGF水平差异无显著性 (P >0 .0 5 )。结论　在孤立性肺结节患者中 ,肺癌患者的S VEGF水平明显高于良性结节患者和健康人 ,高水平 (>10 0pg/ml)的S VEGF提示病灶为肺癌的可能性大 ,可考虑手术治疗。     

Clinical significance of serum vascular endothelial growth factor in esophageal squamous cell carcinoma

BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent inducer of angiogenesis in malignant tumors. An increased in the serum VEGF concentration (S-VEGF) has been found in patients with various solid tumors and appears to be correlated with tumor burden. The objective of the current study was to determine the correlation between pretreatment S-VEGF and clinicopathologic features in patients with esophageal squamous cell carcinoma. METHODS: Pretreatment S-VEGF was measured by enzyme-linked immunoadsorbent assay in 24 healthy controls and 96 patients with esophageal squamous cell carcinoma (82 patients with primary tumors and 14 with recurrent tumors). Chemoradiotherapy was performed in 35 patients followed by response evaluation. RESULTS: S-VEGF was found to be significantly elevated in patients with primary esophageal carcinoma (P = 0.0011). Significant differences were observed when S-VEGF was categorized by tumor size (P = 0.0002), tumor depth (P = 0.0082), lymph node metastasis (P = 0.0002), distant metastasis (P = 0.028), and International Union Against Cancer TNM stage (P < 0.0001). The patients who achieved a partial or complete response to chemoradiotherapy showed significantly less S-VEGF than those patients who were nonresponders (P = 0.018). A high (> 451 pg/mL) S-VEGF level was associated with poor survival (P < 0.001). Multivariate analysis found S-VEGF to be a significant and independent prognostic factor (P < 0.001). CONCLUSIONS: In the current study, a high S-VEGF was found to be associated with tumor progression, poor treatment response, and poor survival in patients with squamous cell carcinoma of the esophagus.     

High serum levels of vascular endothelial growth factor predict poor response to transarterial chemoembolization in hepatocellular carcinoma: a prospective study

Vascular endothelial growth factor (VEGF) is an important mediator of tumor angiogenesis. A high serum VEGF level has been shown to predict poor response to chemotherapy and poor survival in several cancers, but its prognostic value in hepatocellular carcinoma (HCC) remains unknown. We conducted a prospective study to evaluate the prognostic significance of pretreatment serum VEGF levels on tumor response to treatment and survival of patients with HCC undergoing transarterial chemoembolization (TACE). Pretreatment serum VEGF levels were measured by an enzyme-linked immunosorbent assay in 80 patients with inoperable HCC undergoing TACE. Serum VEGF levels were correlated with clinical data, tumor response to TACE and survival results. The median serum VEGF level was 240 pg/ml (range 9-1730). Serum VEGF levels were positively correlated with the presence of venous tumor thrombus (P=0.011). Pretreatment serum VEGF levels were significantly higher in patients with progressive disease (median 434 pg/ml) than those with stable (median 176 pg/ml, P=0.010) or responsive disease (median 142 pg/ml, P<0.001) after TACE. Patients with serum VEGF >240 pg/ml had significantly worse survival than those with serum VEGF <240 pg/ml (median survival 6.8 vs. 19.2 months, P=0.007). In a Cox multivariate analysis, serum VEGF >240 pg/ml was an independent prognostic factor of survival. In conclusion, the results of this study suggest that serum VEGF level may be useful as a novel prognostic predictor of tumor response and survival of patients with inoperable HCC undergoing TACE treatment.     

Serum VEGF and VEGF-C values before surgery and after postoperative treatment in gastric cancer

Introduction

Angiogenesis and lymphangiogenesis are essential processes for the formation of blood and lymphatic vessels that allow tumour growth and spread. The binding of VEGF and VEGF-C factors with their receptors (VEGFR2, VEGFR3) in endothelial cells triggers signals that regulate these processes. We compared preoperative serum VEGF and VEGF-C levels with samples obtained after completion of surgery and adjuvant treatment in patients with gastric cancer. In addition, we determined the prognostic value and relationship to survival of serum VEGF and VEGF-C levels.

Methods

We used a prospective cohort study of 59 gastric cancer patients who underwent surgery. Serum VEGF and VEGF-C were measured by enzyme-linked immunosorbent assay (ELISA) the day before surgery and 6 months later, after completion of adjuvant treatment.

Results

Serum VEGF values decreased after treatment in patients with resectable tumours (mean ± SD) (405.42 ± 298.38 vs. 306.38 ± 212.47 pg/ml; p < 0.01), poorly differentiated and undifferentiated tumours (G3, G4) (438 ± 339.71 vs. 322.47 ± 210.71 pg/ml; p = 0.01), locally advanced gastric tumours (T4 stage) (424.27 ± 323.08 vs. 333.62 ± 221.72 pg/ml; p = 0.03) and tumours with a greater number of involved regional lymph nodes (N3) (442.38 ± 311.52 vs. 337.4 ± 203.64 pg/ml; p = 0.04). Serum preoperative VEGF values over 761 pg/ml were associated with shorter patient survival. The mean overall survival time for patients with serum VEGF levels higher than 761 pg/ml was 7 ± 2.99 months (95 % CI 1.14–12.86) while for patients with serum VEGF levels of less than 761 pg/ml was 21.18 ± 2.88 (95 % CI 15.54–26.83) The mean disease-specific survival time for patients with serum VEGF levels higher than 761 pg/ml was 6.25 ± 2.53 months (95 % CI 1.29–11.21) while for patients with serum VEGF levels of less than 761 pg/ml was 27.57 ± 3.45 (95 % CI 20.80–34.35). Multivariate analysis identified preoperative serum VEGF levels as an independent prognostic factor (HR = 0.144; p = 0.03).

Conclusions

Serum VEGF levels decreased after the completion of treatment in patients with resected tumours, suggesting VEGF tracking may be useful in monitoring progression. Preoperative measurement of serum VEGF may help us identify patients with a poor prognosis.     

Neuropilin‐2 and its ligand VEGF‐C predict treatment response after transurethral resection and radiochemotherapy in bladder cancer patients

The standard treatment for invasive bladder cancer is radical cystectomy. In selected patients, bladder‐sparing therapy can be performed by transurethral resection (TURBT) and radio‐chemotherapy (RCT) or radiotherapy (RT). Our published in vitro data suggest that the Neuropilin‐2 (NRP2)/VEGF‐C axis plays a role in therapy resistance. Therefore, we studied the prognostic impact of NRP2 and VEGF‐C in 247 bladder cancer patients (cN0M0) treated with TURBT and RCT (n = 198) or RT (n = 49) and a follow‐up time up to 15 years. A tissue microarray was analyzed by immunohistochemistry. NRP2 expression emerged as a prognostic factor in overall survival (OS; HR: 3.42; 95% CI: 1.48 – 7.86; p = 0.004) and was associated with a 3.85‐fold increased risk of an early cancer specific death (95% CI: 0.91 – 16.24; p = 0.066) in multivariate analyses. Cancer specific survival (CSS) dropped from 166 months to 85 months when NRP2 was highly expressed (p = 0.037). Patients with high VEGF‐C expression have a 2.29‐fold increased risk of shorter CSS (95% CI: 1.03–5.35; p = 0.043) in univariate analysis. CSS dropped from 170 months to 88 months in the case of high VEGF‐C expression (p = 0.041). Additionally, NRP2 and VEGF‐C coexpression is a prognostic marker for OS in multivariate models (HR: 7.54; 95% CI: 1.57–36.23; p = 0.012). Stratification for muscle invasiveness (T1 vs. T2‐T4) confirmed the prognostic role of NRP2 and NRP2/VEGF‐C co‐expression in patients with T2‐T4 but also with high risk T1 disease. In conclusion, immunohistochemistry for NRP2 and VEGF‐C has been determined to predict therapy outcome in bladder cancer patients prior to TURBT and RCT.     

Circulating vascular endothelial growth factor six months after primary surgery as a prognostic marker in patients with colorectal cancer

High preoperative circulating vascular endothelial growth factor (VEGF) is predictive of poor prognosis in patients with colorectal cancer (CRC). However, postoperative circulating VEGF has not yet been evaluated as a prognostic marker in CRC patients. In 318 consecutive patients who had undergone curative resection of primary CRC, the prognostic value of VEGF concentrations in plasma and serum obtained 6 months postoperatively was analysed and the results compared with the prognostic value of postoperative carcinoembryonic antigen (CEA) concentrations in matched serum samples. In univariate analyses, high serum and plasma VEGF ( > 533 pg/ml and > 112 pg/ml, respectively) had no significant (p = 0.17 and p = 0.13, respectively) impact on overall survival. On the contrary, high serum CEA ( > 5 ng/ ml) was significantly (p < 0.0001) correlated to a poor prognosis. Finally, in multivariate analyses, the combination of high serum CEA and high serum VEGF was significantly (hazard ratio 3.0, p = 0.02) associated with poor survival compared to high serum CEA and low serum VEGF. It is concluded that 6 months postoperatively serum CEA is a better prognostic marker than corresponding serum and plasma VEGF. However, high serum VEGF within high serum CEA was an even better predictor of overall survival than high serum CEA alone.     

Serum vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) levels in small cell lung cancer

This study was conducted to determine the value of the angiogenic serum factors, vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8), in patients with small cell lung cancer (SCLC). These serum angiogenic factors were measured of 34 SCLC patients on the before and after chemotherapy in comparison with 20 healthy controls using ELISA method. Serum levels of VEGF and IL-8 were significantly increased in SCLC patients compared with healthy controls (p < 0.001). No statistically significant relationships was found between investigated elevated serum angiogenic parameters and various characteristics of patients and disease such as disease stage and tumor burden. Likewise, we also found no correlation between serum angiogenic factors. Cytotoxic therapy of patients was accompanied by unchanged serum levels of angiogenic factors. Contrary to serum IL-8, elevated serum levels of VEGF was determined as a prognostic factor for survival by univariate analysis (p = 0.05). Multivariate analysis revealed that independent prognostic factors of overall survival included only response to chemotherapy and weight loss (p < 0.001 for both). In conclusion, our data suggest that the angiogenic serum factors, VEGF and IL-8, are useful diagnostic factors, but not predictive and prognostic markers for overall survival in SCLC patients.     

Percutaneous microwave ablation (MWA) increased the serum levels of VEGF and MMP-9 in Stage I non-small cell lung cancer (NSCLC)

Background: Lung cancer is the leading cause of cancer death around the world. Percutaneous microwave ablation (MWA) is an emerging treatment strategy for medically inoperable early-stage non-small cell lung cancer (NSCLC). In this study, we investigated the association of MWA and serum angiogensis promoters VEGF and MMP-9 in these patients subgroup.

Methods: We enrolled 52 patients with Stage I NSCLC patients in this study. For each patient, blood samples were drawn by venous puncture, one immediately prior to MWA and the others on Post-Procedure Days (PPD) 1, 3, 5, 7, 10 and 14. Serum samples were analysed for VEGF and MMP-9 levels with use of commercially available enzyme-linked immunosorbent assay. Also, blood samples of 28 healthy volunteers were set as the healthy controls.

Results: We did not observe a significant difference of serum VEGF and MMP-9 between NSCLC patients and healthy controls. The VEGF levels increased on the first day (256.0?±?6.16?pg/ml, p?p?p?p?p?p?>?0.05). The highest MMP-9 level was observed on PPD5 (399.7?±?17.70?ng/ml, p?Conclusion: Our preliminary results indicated that percutaneous MWA resulted in increased serum levels of VEGF and MMP-9 in Stage I NSCLC patients. Antiangiogenesis approaches may be helpful for patients defending against metastases during the immediate post-ablation time window.     

Serum VEGF levels in patients undergoing primary radiotherapy for cervical cancer: impact on progression-free survival

Vascular endothelial growth factor (VEGF) plays an important role in the regulation of tumour growth and metastasis. It was the aim of this study to examine the impact of serum VEGF levels on the likelihood of response to radiotherapy and on the disease-free survival in patients with cervical cancer. Blood was taken before commencing treatment and serum VEGF was assessed by quantitative ELISA in 23 patients with cervical cancer stage IB-IVA undergoing primary radiotherapy. Serum VEGF levels were correlated with clinical and histopathologic factors as well as with response to radiotherapy and time to progression. Nineteen of the 23 patients had a complete response and four patients had persistent disease at 3 months. The median follow-up was 25 months (95% confidence interval: 23.5-26.5 months). At the time of analysis, eight patients were tumour-free and 15 patients had tumour progression; 12 of these 15 patients died of disease. Overall, the median serum VEGF level was 244 pg/ml (range 31.9-817.6 pg/ml). All four patients with local failure had VEGF levels >244 pg/ml, whereas 11 of the 19 patients with complete response had serum VEGF of < or =244 pg/ml (P=0.035). The median time to progression was 5 months in patients with VEGF of >244 pg/ml compared to 19 months in patients with VEGF of < or = 244 pg/ml (log rank, P=0.003). In multivariate analysis, serum VEGF, tumour size and histological type, but not the patient's age, stage and grade of histological differentiation influenced the progression-free survival. Elevated pre-therapeutic serum VEGF levels are associated with poor response and a shorter time to progression in patients with cervical cancer undergoing primary radiotherapy.     

Vascular endothelial growth factor and breast cancer risk

Vascular endothelial growth factor (VEGF) is a key factor in angiogenesis and is important to carcinogenesis. Previous studies relating circulating levels of VEGF to breast cancer have been limited by small numbers of participants and lack of adjustment for confounders. We studied the association between serum VEGF and breast cancer in an unmatched case–control study of 407 pre- and postmenopausal women (n = 203 cases, n = 204 controls). Logistic regression was used to model the breast cancer risk as a function of natural log transformed VEGF levels adjusted for age, Gail score, education, physical activity, history of breastfeeding, serum testosterone, and hormone therapy (HT) use. The majority of the population was postmenopausal (67.6%) and the average age was 56 years; age and menopausal status were similar among cases and controls. Geometric mean VEGF levels were non-significantly higher in cases (321.4 pg/ml) than controls (291.4 pg/ml; p = 0.21). In a multivariable model, the odds of breast cancer was 37% higher for women with VEGF levels ≥314.2 pg/ml compared to those with levels below 314.2 pg/ml, albeit not significantly (p = 0.16). There was no interaction between VEGF and menopausal status (p = 0.52). In this case–control study, VEGF was not significantly associated with breast cancer risk in pre- and postmenopausal women.     

VEGF, TNF-alpha and 8-isoprostane levels in exhaled breath condensate and serum of patients with lung cancer

The aim of the present study was to evaluate the levels of VEGF, 8-isoprostane and TNF-alpha in EBC and serum of patients with primary lung cancer prior to the initiation of any treatment, in order to evaluate their possible diagnostic role. Furthermore, associations between VEGF, 8-isoprostane and TNF-alpha levels in EBC and serum with clinicopathologic factors were investigated. We enrolled 30 patients with lung cancer (mean age 65.2+/-10.5 years) and 15 age and gender-matched healthy smokers as controls. Serum and EBC were collected before any treatment. TNF-alpha, VEGF and 8-isoprostane levels in EBC and serum were analyzed by an immunoenzymatic method (ELISA). A statistically significant difference was observed between lung cancer patients and the control group regarding the values of TNF-alpha, both in EBC (52.9+/-5.0 pg/ml vs. 19.4+/-3.9 pg/ml, p<0.0001) and serum (44.5+/-6.3 pg/ml vs. 22.2+/-4.3 pg/ml, p=0.035). Moreover, EBC VEGF levels were higher in patients with T3-T4 tumor stage compared to T1-T2 (9.3+/-2.8 pg/ml vs. 2.3+/-0.7pg/ml, p=0.047). A statistically significant correlation was also observed between serum and EBC values of VEGF (r=0.52, p=0.019). In addition, serum levels of VEGF were higher in lung cancer patients than in controls (369.3+/-55.1 pg/ml vs. 180.5+/-14.7 pg/ml, p=0.046). VEGF serum levels were also found higher in patients with advanced stage of disease (IIIB-IV) and distant nodal metastasis (N2-N3). No differences were observed in 8-isoprostane in EBC between lung cancer patients and controls. In contrast, serum 8-isoprostane levels were higher in lung cancer patients compared to controls (24.9+/-3.6 pg/ml vs. 12.9+/-1.6 pg/ml, p=0.027) and were higher in patients with advanced disease. All three biomarkers presented acceptable reproducibility in the EBC on two consecutive days. In conclusion, we have shown that TNF-alpha, VEGF and 8-isoprostane are elevated in the serum of lung cancer patients and increased serum VEGF and 8-isoprostane levels are related to advanced disease. In EBC, increased TNF-alpha levels were observed in lung cancer patients, whereas increased VEGF levels were observed in advanced T-stage. Further longitudinal studies are warranted for the evaluation of the prognostic role of these biomarkers in lung cancer.     

Maspin,VEGF and p53 Expression in Small Biopsies of Primary Advanced Lung Cancer and Relationship with Clinicopathologic Parameters

Maspin, one of the serine protease inhibitors, has been shown to inhibit tumor progression and metastasis. We aimed to investigate maspin, p53 and VEGF expression in patients with squamous cell carcinoma (SCC), adenocarcinoma (AC) and small cell lung carcinoma (SCLC). The study included 28 SCC, 18AC, 17 SCLC biopsy samples. We used the streptavidin biotin immunoperoxidase method to test for maspin, p53 and VEGF antibodies. Medical records of these patients were reviewed from archival files. Cytoplasmic maspin expression was detected in 89.3%, 77.8%, 52.9% of SCC, AC and SCLC, respectively. The rate was significantly higher in non-small cell lung cancer (NSCLC) and SCC than SCLC (p = 0.013, p = 0.021, respectively). The mean percentages of maspin expression were significantly higher in NSCLC, SCC and AC than in SCLC (p = 0.0001, p = 0.0001, p = 0.038, respectively). In ACs, maspin and p53 expressions were correlated, although this was not statistically significant (p = 0.053, r = 0.464), and maspin positive cases had a significantly higher T status compared to negative cases (p = 0.036). In SCC, the stage of disease was positively correlated with p53 (p = 0.007, r = 0.536) and negatively correlated with VEGF expression (p = 0.013, r = −0.498). Multivariate analysis demonstrated that stage of disease was a significant independent prognostic parameter in NSCLC (95% confidence interval: 1.067–3.969; p = 0.031). Although maspin expression is higher in SCC and AC, and is related with higher T status in AC, our data did not indicate its prognostic significance. Larger scale studies are needed to reveal the exact role of maspin in lung cancer pathogenesis.     

Preoperative serum vascular endothelial growth factor levels: significance in ovarian cancer.

PURPOSE: To assess the clinical relevance of serum vascular endothelial growth factor (VEGF) levels in distinguishing patients with ovarian cancer from those with benign adnexal masses. Experimental Design: Preoperative serum VEGF levels were assessed in 101 women with invasive epithelial ovarian cancer, 16 with low malignant potential (LMP) ovarian tumors, and 34 women with benign ovarian tumors. VEGF levels were determined using an ELISA (R&D Systems, Minneapolis, MN). RESULTS: Ovarian cancer patients had a mean preoperative VEGF level of 549 pg/ml (median 379 pg/ml), which was significantly higher than those with benign adnexal masses (mean 228 pg/ml, median 155 pg/ml; P < 0.001) and LMP tumors (mean 200 pg/ml, median 129 pg/ml; P < 0.001). There were no significant differences in VEGF levels between individuals with benign masses and LMP tumors. The ability of VEGF to differentiate malignancy from benign masses at a cutoff VEGF level of 246 pg/ml gave a sensitivity of 74%, a specificity of 71%, a positive predictive value of 88%, and a negative predictive value of 48%. VEGF levels were also significantly higher in patients with stage I ovarian cancer compared with those with benign disease or LMP tumors. Among patients with ovarian cancer, there were no significant differences in VEGF levels based on age, stage, grade, or level of cytoreduction. The presence of ascites was associated with a significantly higher VEGF level (mean 667 pg/ml, median 445 pg/ml versus mean 317 pg/ml, median 293 pg/ml; P < 0.001). Various preoperative VEGF levels were assessed as a predictor of survival, and a VEGF level >380 pg/ml was associated with a hazard ratio of 2.13 (P = 0.009) by univariate analysis. In multivariate analysis of age, stage, cytoreduction, preoperative CA-125, grade, ascites, and VEGF levels above 380 pg/ml, only VEGF levels >380 pg/ml (hazard ratio 2.33; P = 0.02) and advanced stage (hazard ratio 9.03; P = 0.004) were significant. CONCLUSIONS: Preoperative VEGF levels may be useful in differentiating benign adnexal masses from malignancy. Preoperative VEGF levels >380 pg/ml are an independent risk factor for death because of disease.     

结直肠癌患者术前检测血清血管内皮生长因子白细胞介素6及C反应蛋白的临床意义

目的 探讨结直肠癌患者术前血清血管内皮生长因子(VEGF)、白细胞介素6(IL-6)和C反应蛋白(CRP)水平与临床病理的关系及其对预后的临床意义.方法 采用酶联免疫吸附法检测79例结直肠癌患者血清VEGF和IL-6,采用免疫比浊法检测血清CRP,比较结直肠癌患者与健康对照者的血清VEGF、IL-6和CRP水平.采用Kaplan-Meier法分析结直肠癌患者5年生存率,采用Log rank 单因素分析预后不良因素.结果 结直肠癌组血清VEGF、IL-6和CRp分别为(591±312)pg/ml、(13.2±3.7)pg/ml和(1.14±0.87)mg/dl,健康对照组分别为(321±210)pg/ml、(5.4±2.0)pg/ml和(0.39±0.35)mg/dl,其中VEGF和CRP间差异有统计学意义(P＜0.001,P=0.002).男性患者和女性患者的VEGF水平分别为(638±387)pg/ml和(552±271)pg/ml,差异有统计学意义(P=0.042);肿瘤＜5 cm和肿瘤≥5 cm患者的VEGF表达分别为(538±275)pg/ml和(647±331)pg/ml,差异有统计学意义(P=0.009).男性患者和女性患者的IL-6表达分别为(11.7±3.2)pg/ml和(15.2±4.0)pg/ml,差异有统计学意义(P=0.011).VEGF＜591 pg/ml和≥591 pg/ml患者的5年生存率分别为86.8%(33/38)和73.2%(30/41),IL-6＜13.2 pg/ml和≥13.2 pg/ml患者的5年生存率分别为82.9%(34/41)和76.3%(29/38),CRP＜1.14 mg/dl和≥1.14 mg/dl的5年生存率分别为81.4%(35/43)和77.8%(28/36).Log rank单因素分析显示,VEGF水平是影响结直肠癌预后的相关因素(P＜0.05).Logistic回归分析显示,肿瘤大小和VEGF水平为结直肠癌患者预后的危险因素(P=0.032,OR=0.985;P=0.011,OR=0.976).结论 血清VEGF和IL-6表达具有性别差异,血清VEGF检测可作为结直肠癌患者的临床诊断标志之一,对患者的预后具有重要的临床意义.     

Elevation of serum vascular endothelial growth factor in male patients with metastatic nasopharyngeal carcinoma

BACKGROUND: Angiogenesis is essential for tumor growth and metastasis. Vascular endothelial growth factor (VEGF) is the most potent angiogenic factor identified to date. The authors investigated the correlation between the levels of serum VEGF (S-VEGF) in patients with nasopharyngeal carcinoma (NPC) and disease progression. METHODS: The sera from 65 male patients with nonmetastatic NPC, 22 male patients with metastatic NPC, and 27 healthy male volunteers were obtained. A quantitative enzyme-linked immunosorbent assay was performed to measure the concentrations of S-VEGF in the sera. RESULTS: The mean S-VEGF levels were 371.0 pg/mL(-1) (range, 128.5-691.1 pg/mL(-1)) for healthy controls, 375.6 pg/mL(-1) (range, 72.9-1202.5 pg/mL(-1)) for patients with nonmetastatic NPC, and 958.6 pg/mL(-1) (range, 264.4-3744.9 pg/mL(-1)) for patients with metastatic NPC. The mean S-VEGF level in patients with metastatic NPC was significantly higher than in either patients with nonmetastatic NPC (P < 0.001) or healthy controls (P < 0.001). However, there was no statistical difference between these results for healthy controls and patients with nonmetastatic NPC. At the level of 900 pg/mL(-1), S-VEGF indicated distant dissemination of NPC with a specificity of 95.4%, a sensitivity of 31.8%, a positive predictive value of 70.0%, and a negative predictive value of 80.5%. No significant differences in the levels of S-VEGF were found among various T classifications, N classifications, and clinical stages of nonmetastatic NPC. CONCLUSIONS: The levels of S-VEGF were significantly elevated in male patients with metastatic NPC. These levels did not correlate with locoregional progression of NPC. The usefulness of detecting S-VEGF in the early diagnosis of NPC appears to be limited.     

Vascular endothelial growth factor and basic fibroblast growth factor urine levels as predictors of outcome in hormone-refractory prostate cancer patients: a cancer and leukemia group B study

Better prognostic markers are needed for hormone-refractory prostate cancer (HRPC) patients. No single biochemical or clinical parameter can reliably predict patient response to therapy or rapidity of disease progression. Peptide factors involved in major cancer growth pathways, such as tumor angiogenesis, are attractive candidates as markers of low- and high-risk HRPC patients. We analyzed prospectively collected urine specimens from 100 of 390 HRPC patients undergoing therapy with the growth factor antagonist suramin as part of CALGB 9480. Levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were assessed from day 1 of therapy (D1) and day 29 (D29) urine samples from this subset of 100 randomly selected patients. Growth factor levels were determined by standardized ELISA microtiter plate assays from a commercial (bFGF) or proprietary (VEGF) source. Pretreatment urine VEGF levels were predictive of survival. In univariate analysis, patients whose baseline urine VEGF level was < or =28 pg/ml (the median level) had an average survival of 17 months; those with baseline VEGF >28 pg/ml had a significantly shorter survival of 10 months (P = 0.024). This difference corresponded to a 60% increased risk of dying for the higher urine VEGF patients (hazard ratio, 1.62; P = 0.03) and remained significant in multivariate analysis (hazard ratio, 1.72, P = 0.02). No significant correlations between urine bFGF level or change in bFGF levels and survival were found. These results support the notion that certain peptide growth factor-mediated, mitogenic pathways are important in HRPC and that their levels can predict outcome.     

Should extrapulmonary small cell cancer be managed like small cell lung cancer?

BACKGROUND:

The aim of this study was to determine if extrapulmonary small cell carcinomas (EPSCC) should be managed using protocols similar to those for small cell lung cancer (SCLC).

METHODS:

Treatment strategies, survival, patterns of failure, and prognostic factors for patients with EPSCC were analyzed retrospectively at a large cancer center. SCLC was excluded by thoracic computed tomography (75%) or chest radiography (25%).

RESULTS:

Of 120 eligible patients, 70% had limited disease (LD). Treatment modalities included chemotherapy (n = 82; 68%), radiotherapy (RT) (n = 80; 67%), and surgery (n = 41, 34%). The median survival for patients with LD and extensive disease was 1.4 years and 0.7 years, respectively. Gynecologic (n = 31) and gastrointestinal (n = 28) were the most common primary tumor sites. Gynecologic and head and neck primary tumor sites had better 1‐year survival than other sites (P = .019 and 0.005, respectively). Brain metastasis was the site of first distant failure in 4.1% of patients versus 35% for soft tissue metastases. The lifetime risk of brain metastasis was 13%. Definitive RT (P = .004), LD (P = .028), and prophylactic cranial irradiation (PCI) (P = .022) were found to be positive prognostic factors and weight loss (P < .001) was a negative prognostic factor on multivariate analysis.

CONCLUSIONS:

Patients with EPSCC usually experienced short survival, often with early distant metastasis. Although PCI was associated with improved overall survival, brain metastasis was less frequent than in patients with SCLC, and therefore the potential benefit of PCI was less than in patients with SCLC. Definitive chemoradiotherapy was associated with better outcomes and should be delivered whenever feasible. Cancer 2010. © 2010 American Cancer Society.     

Intracavitary VEGF,bFGF, IL-8, IL-12 levels in primary and recurrent malignant glioma

Intracavitary levels of VEGF, bFGF, IL-8 and IL-12 were evaluated by ELISA in 45 patients, 7 with recurrent anaplastic astrocytoma (rAA), 12 with glioblastoma (GBM) and 26 with recurrent glioblastoma (rGBM). In 25 patients plasma levels of the molecules were also quantitated. Twenty-three healthy controls were also studied for plasma concentrations of the same molecules.Plasma levels of VEGF (mean 33.89 ± 6.71pg/ml) and bFGF (mean 11.1 ± 3.24pg/ml) were higher in patients than in controls (mean 16.78 ± 3.7pg/ml for VEGF, mean 0.21 ± 0.09pg/ml for bFGF) (p = 0.04 and p = 0.001, respectively) while plasma IL-12 levels were lower (mean 45.6 ± 1.5pg/ml in patients, mean 79.7 ± 1.3pg/ml in controls) (p = 0.009).Intracavitary VEGF levels were 5–53.307 fold higher (mean 90,900 ± 24,789pg/ml) than in the corresponding plasma. Also IL-8 concentrations were higher in intracavitary fluid (mean 6,349.76 ± 1,460.93pg/ml) than in plasma (mean 43.44 ± 24.82pg/ml). Maximum VEGF levels were found in tumor fluid of recurrent glioblastoma patients (mean 147,678 ± 39,903pg/ml), intermediate levels in glioblastoma patients (mean 20,322 ± 11,892pg/ml) and lower levels in rAA patients (mean 9,111 ± 5,789pg/ml). The data also suggest that higher intracavitary levels of VEGF and IL-8, and lower IL-12 levels, may be correlated with shorter adjunctive survival times, but more data will need to be collected to establish this correlation clearly.