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.     

Vascular endothelial growth factor (VEGF) in leptomeningeal metastasis: diagnostic and prognostic value

This study examined the diagnostic and prognostic value of vascular endothelial growth factor (VEGF) levels in the cerebrospinal fluid (CSF) of 39 patients with leptomeningeal metastasis (LM). Vascular endothelial growth factor levels at diagnosis were significantly higher in patients with LM (median 359 pg ml(-1)) than in patients with other neurological diseases (median <25 pg ml(-1)). The specificity of VEGF levels above 250 pg ml(-1) for LM was high (98.3%), while the sensitivity was low (51.4%; 73% for VEGF values above 100 pg ml(-1)). In 49% of the LM patients, particularly with lymphoma or medulloblastoma, VEGF levels were below 250 pg ml(-1) and thus in the range of VEGF levels in other neurological diseases. Vascular endothelial growth factor levels correlated significantly with CSF lactate and albumin. Vascular endothelial growth factor levels mirrored the clinical course with a marked reduction in response to therapy and an increase at relapse in some patients who had serial CSF samples available. Multivariate Cox regression analysis showed VEGF below 100 pg ml(-1) (relative risk (RR)=4.24, P=0.0002) and age below 60 years (RR=2.5, P=0.004) to be associated with longer survival in LM. In conclusion, CSF VEGF levels in LM vary considerably. High VEGF levels have a very high specificity for LM and may help to establish the diagnosis. The role of VEGF as a predictor of outcome should be substantiated in prospective studies.     

Serum endostatin and bFGF as predictive factors in advanced breast cancer patients treated with letrozole

Introduction To investigate the value of baseline serum levels of VEGF, bFGF, endostatin and their ratio as predictive factors of response to endocrine therapy in patients with metastatic breast cancer (MBC) and positive ER treated with letrozole after tamoxifen failure. Materials and method The serum levels of endostatin, VEGF and bFGF were determined in post-menopausal patients with progressing MBC from serum samples obtained before initiation of letrozole. The relation between serum angiogenic factor levels and TTP was investigated. Results Seventy-six patients (45.2%) presented a high endostatin level (>24.6 ng/ml), 40% low bFGF levels (0 pg/ml) and 50.4% low VEGF (≤187 ng/ml). With a median follow-up of 22 months, the median TTP was 12.3 months. Median TTP was worse in patients with high endostatin concentration as well as in the low bFGF group, but was not affected when VEGF was considered. When the two factors were combined, the median TTP of patients with endostatin >24.6 ng/ml and bFGF equal 0 pg/ml was 9.5 months versus 19.5 months in patients with endostatin ≤24.6 ng/ml and bFGF>0 pg/ml. Conclusions The baseline levels of bFGF and endostatin are predictive factors of efficacy in patients with MBC treated with letrozole and can select groups with different TTP.     

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.     

A common 936 C/T gene polymorphism of vascular endothelial growth factor is associated with decreased breast cancer risk

A common 936 C/T polymorphism in the gene for the vascular endothelial growth factor (VEGF) has been associated with VEGF plasma levels. In our case-control study, we investigated the role of this polymorphism for breast cancer risk. VEGF genotype was determined in 500 women with breast cancer and 500 sex- and age-matched healthy control subjects. Carriers of a 936T-allele were more frequent among controls (29.4%) than among patients (17.6%; p = 0.000014). The odds ratio for carriers of a 936T-allele for breast cancer was 0.51 (95% confidence interval 0.38-0.70). Additionally, VEGF plasma levels were determined in 21 nonsmoking post-menopausal controls; carriers of a 936T allele had significantly lower levels (median 23 pg/ml; range 6-50 pg/ml) than noncarriers (37; 21-387; p = 0.034). We conclude that carriers of a VEGF 936T-allele are at decreased risk for breast cancer, this, however, requiring further confirmation in a larger study.     

Surgery for gastric cancer increases plasma levels of vascular endothelial growth factor and von Willebrand factor

Background: Angiogenesis and hemostatic activation are important factors in tumor progression and metastasis. Because surgical intervention induces tissue hypoxia and hemostatic activation, we analyzed the effect of gastric surgery on the plasma concentrations of vascular endothelial growth factor (VEGF), soluble P-selectin (sP-selectin), and von Willebrand factor (vWf). Methods: Plasma VEGF, sP-selectin, and vWf concentrations were measured in 14 patients with gastric cancer before operation and on postoperative day 1 (POD 1). Correlations between disease stage and the effect of surgical intervention were analyzed. Results: The plasma concentrations of these three factors did not correlate with the disease stage. Plasma levels of sP-selectin did not change after operation (before surgery, 87.6 ± 34.1 ng/ml; on POD 1, 101.1 ± 48.1 ng/ml; P = 0.123). Plasma VEGF and vWf concentrations were significantly elevated on POD 1 (VEGF, 33.3 ± 20.5 pg/ml before surgery and 61.9 ± 35.6 pg/ml on POD 1; P = 0.0013; vWf, 164 ± 31.1% before surgery and 211.1 ± 66.1% on POD 1; P = 0.027). Conclusion: Because VEGF and vWf are involved in angiogenesis, tumor-platelet adhesion, and tumor-endothelial cell adhesion, surgical intervention could influence tumor growth and metastasis. Received: February 1, 2002 / Accepted: April 9, 2002 Offprint requests to: M. Ikeda     

早期乳腺癌血清VEGF水平与骨髓微转移的相关性及临床意义

目的 检测早期乳腺癌患者血清中VEGF及骨髓标本中CK19的表达水平,探讨二者的相互关系及临床意义.方法 应用ELISA法分别检测6例乳腺纤维腺瘤及64例乳腺癌患者血清中VEGF的水平,同时抽取相应的骨髓血标本,应用实时定量逆转录-聚合酶链反应(qRT-PCR)方法检测标本中CK-19的表达水平,并进行相关性分析.结果 VEGF在乳腺癌患者血清中的表达水平明显高于乳腺纤维腺瘤患者,二者差异显著(P=0.012);在HER2阳性患者中,血清VEGF水平明显高于HER2阴性患者(P=0.016).CK19在乳腺纤维腺瘤患者骨髓标本中未见表达,在乳腺癌患者骨髓血中,阳性表达24例(37.5%),而骨髓中CK19阳性的乳腺癌患者血清VEGF水平显著高于CK19阴性的患者(110.46±90.65 vs 70.88±77.13,P=0.038),且二者的表达呈正相关.结论 早期乳腺癌患者血清VEGF水平与骨髓微转移密切相关,提示VEGF可能参与了肿瘤细胞的侵袭和播散,可作为早期乳腺癌微转移的血清学指标.     

Serum vascular endothelial growth factor is related to systemic oxidative stress in patients with lung cancer

Vascular endothelial growth factor (VEGF) is known to play crucial role in tumour angiogenesis. It is demonstrated that VEGF can be up-regulated by oxidative stress. The aim of this study was to determine the serum VEGF levels and oxidative stress in patients with primary lung cancer and to investigate their association with clinicopathologic factors.

We measured serum VEGF levels and oxidative stress in 63 patients (age 63.02 ± 1.12 S.E.M.) with primary lung cancer before any treatment (39 NSCLC and 24 SCLC; 6 patients stage I, 3 stage II, 25 stage III and 29 stage IV) and 25 normal subjects. The serum VEGF levels were measured with enzyme linked immunosorbent assay. Serum oxidative stress levels were detected by a commercially available assay (D-ROMs test, Diacron, Grossetto, Italy).

The levels of oxidative stress in patients were higher than those in normal subjects (555.3 ± 30.35 UCarr vs. 360.1 ± 17.46 UCarr). Additionally, a significant difference was found in serum VEGF levels between lung cancer patients and healthy control subjects (428.1 ± 38.42 pg/ml vs. 298.8 ± 19.89 pg/ml, respectively, p = 0.040). Interestingly, serum oxidative stress presented a significant correlation with serum VEGF levels in patients with lung cancer (r = 0.542, p = 0.002). Serum VEGF levels were significantly associated with the clinical staging (N-stage) of the patients (p = 0.023), performance status (p = 0.004) and age (p = 0.004).

In conclusion, oxidative stress and VEGF are significantly increased in patients with primary lung cancer. The correlation between them might implicate new aspects of the mechanisms controlling tumour angiogenesis and may present clinical interest in the future. Further studies are warranted to evaluate the role of oxidative stress and VEGF as possible biomarkers for the diagnosis and follow-up of patients with lung cancer.     

CEA、VEGF标志物与小细胞肺癌预后相关性

目的:探讨不同评价标志物与小细胞肺癌预后相关性。方法:64例小细胞肺癌患者以及同期36例行肺叶切除术的正常患者,分为观察组与对照组。免疫组化SP法测定LRP,酶联免疫吸附法(ELISA)对血液中血清癌胚抗原（CEA）、血清血管内皮生长因子(VEGF)进行检测,同时测定观察组在化疗前后LRP阳性率、以及CEA与VEGF的水平变化情况。结果:小细胞肺癌患者与肺部良性病变的VEGF检测值分别为:(290.7±48.52)pg/ml、(123.5±31.48)pg/ml,CEA检测值分别为:(9.78±2.58)ng/L、(4.06±0.84)ng/L,LRP阳性率分别为:53.1%、5.6%,两组比较有显著性差异（P<0.05)。观察组化疗前后的VEGF检测值分别为:(286.7±47.52)pg/ml、(167.5±34.48)pg/ml,CEA检测值分别为:(9.68±2.48)ng/L、(5.16±1.25)ng/L,LRP阳性率分别为:51.6%、15.6%,两组比较有显著性差异（P<0.05)。结论:LRP、VEGF以及CEA等标记物在肺癌组织的表达水平显著高于正常组织,可用于对肺癌疾病的诊断以及对小细胞肺癌预后预测。     

High pre-treatment serum level of vascular endothelial growth factor (VEGF) is associated with poor outcome in small-cell lung cancer

Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis and vascular permeability. Increased serum VEGF concentrations (S-VEGF) have been found in patients with various types of human cancer, including cancer of the lung. However, the clinical and prognostic significance of S-VEGF in cancer is unknown. We measured S-VEGF, using enzyme-linked immunosorbent assay, in sera taken from 68 untreated patients with small-cell lung cancer (SCLC) at the time of diagnosis. The patients were treated with 6 cycles of cisplatin and etoposide, and were randomly assigned to receive recombinant interferon, leukocyte interferon or neither. S-VEGF ranged from 70 to 1 738 pg/ml (mean, 527 pg/ml). The patients who achieved partial or complete response to treatment had lower pre-treatment S-VEGF than the non-responding patients (p = 0.0083, Mann-Whitney test). High (>527 pg/ml) S-VEGF was associated with poor survival (p = 0.012, Log Rank Test), and all 3-year survivors had lower than mean pre-treatment S-VEGF. In a multivariate analysis, S-VEGF and stage were the only independent prognostic factors, and the estimated 3-year survival of the patients with limited stage disease and low pre-treatment S-VEGF (n = 17, 25% of all patients) was 41% (p = 0.0055, log rank test). These data show that high pre-treatment S-VEGF is associated with poor response to treatment and unfavourable survival in patients with SCLC treated with combination chemotherapy with or without interferon. Int. J. Cancer (Pred. Oncol.) 79:144–146, 1998.© 1998 Wiley-Liss, Inc.     

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.     

早期乳腺癌血清VEGF水平与骨髓微转移的相关性及临床意义

目的：检测早期乳腺癌患者血清中VEGF及骨髓标本中CK19的表达水平,探讨二者的相互关系及临床意义。方法：应用ELISA法分别检测6例乳腺纤维腺瘤及64例乳腺癌患者血清中VEGF的水平,同时抽取相应的骨髓血标本,应用实时定量逆转录-聚合酶链反应（qRT-PCR）方法检测标本中CK-19的表达水平,并进行相关性分析。结果：VEGF在乳腺癌患者血清中的表达水平明显高于乳腺纤维腺瘤患者,二者差异显著（P=0.012）;在HER2阳性患者中,血清VEGF水平明显高于HER2阴性患者（P=0.016）。CK19在乳腺纤维腺瘤患者骨髓标本中未见表达,在乳腺癌患者骨髓血中,阳性表达24例（37.5%）,而骨髓中CK19阳性的乳腺癌患者血清VEGF水平显著高于CK19阴性的患者（110.46±90.65 vs 70.88±77.13,P=0.038）,且二者的表达呈正相关。结论：早期乳腺癌患者血清VEGF水平与骨髓微转移密切相关,提示VEGF可能参与了肿瘤细胞的侵袭和播散,可作为早期乳腺癌微转移的血清学指标。     

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.     

血浆基质细胞衍化因子-1与乳腺癌临床病理学特征及预后分析

目的:探讨血浆基质细胞衍化因子-1(SDF-1)与乳腺癌临床病理学特征及预后的关系。方法:2006年2月至2007年3月首都医科大学宣武医院普外科住院手术乳腺癌患者82例,手术前空腹状态抽取血液标本,分离血浆后-20℃冻存,应用酶联免疫吸附试验(ELISA)检测患者血浆中SDF-1水平。收集所有患者的临床资料及随访资料,SPSS17.0统计软件进行多因素Cox回归、生存曲线分析。结果:82例中乳腺癌患者中,失访2例,随诊率为97.6%。随访时间为12.5-71.2个月,平均55.6个月。有淋巴结转移组血浆SDF-1水平显著高于无淋巴结转移组,两者分别为(65.78±8.47)pg/ml和(56.02±3.70)pg/ml,P<0.05。多因素Cox回归分析显示只有淋巴结转移是影响无病生存、总生存的风险因素,HR=4.958,95%CI(1.314,18.709),P=0.018和HR=5.541,95%CI(1.117,27.491),P=0.036。以血浆SDF-1中位数54.589pg/ml将患者分为SDF-1高水平组和低水平组,尽管两组间患者无病生存率及总生存率无显著差异(P=0.527和P=0.678),但是SDF-1高水平组呈现出预后差于血浆SDF-1低水平组的趋势。结论:血浆SDF-1水平与乳腺癌淋巴结有无转移密切相关,高血浆SDF-1水平可能预示着预后不良。有必要就SDF-1与乳腺癌预后的关系扩大标本量进一步研究。     

Clinical significance of plasma vascular endothelial growth factor in gastrointestinal cancer

Circulating vascular endothelial growth factor (VEGF) was measured in gastric and colorectal cancer patients using an enzyme-linked immunosorbent assay (ELISA). Firstly, serum and plasma samples were collected from 20 normal controls to compare the values of VEGF and to determine which specimen type was most suitable for detecting circulating VEGF. Seventeen of 20 normal controls had plasma VEGF levels under the limit of detection (15 pg/ml) and the levels of the remaining three controls were 21, 22 and 38 pg/ml. In contrast, all serum samples indicated high levels of VEGF (mean 238 pg/ml), ranging from 44 to 450 pg/ml. In a time-course test of two normal controls serum VEGF values increased markedly between 30 and 60 min and remained high, whilst plasma VEGF values were low up to 480 min. Thus, plasma samples are more suitable for the measurement of circulating VEGF. Next, plasma VEGF levels were examined in 44 patients with gastric cancer (8 early, 7 advanced without remote metastasis and 29 metastatic), 13 with colorectal adenoma (2 with focal cancer) and 26 with colorectal carcinoma (8 advanced without metastasis and 18 metastatic) before treatment. An extremely high plasma concentration of VEGF was seen in some cancer patients with metastasis. To discriminate these patients, a cut-off level was determined, considering both the distribution of the sample concentration and the upper limit of 95% confidence area of VEGF in the cancer patients without metastasis. The cut-off value was 108 pg/ml and most cancer patients without metastases had VEGF levels below the cut-off value. In 11 of 29 metastatic gastric cancer patients (38%) and 9 of 18 metastatic colorectal cancer patients (50%), plasma VEGF levels were higher than the cut-off value. Survival was also analysed in the patients with metastasis. It was significantly longer in the patients with low VEGF levels (below the cut-off) than in those with high VEGF levels (logrank test, P = 0.042). 34 patients with metastasis (19 gastric cancer and 15 colorectal cancer) were treated with systemic chemotherapy, and their pretreatment levels of plasma VEGF and conventional tumour markers (CEA and CA19-9) were evaluated in relation to response. The response to chemotherapy was significantly higher in patients with low VEGF levels (< or = 108 pg/ml) than in those with high VEGF levels (P = 0.047). Such a difference was not observed with CEA/CA19-9. In conclusion, plasma VEGF is a useful marker for tumour metastasis and patient survival, and a possible predictive factor for the response of patients with gastrointestinal cancer to chemotherapy.     

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.     

开胸手术对非小细胞肺癌患者血清VEGF、MMP-9水平变化的影响分析

目的 分析开胸手术对非小细胞肺癌(non-small cell lung cancer)患者血清VEGF、MMP-9水平变化的影响.方法 将非小细胞肺癌患者79例作为观察组;良性肺部疾病患者56例和健康志愿者25例作为对照组.观察组患者和良性肺部疾病患者均进行了开胸肺切除手术,然后按照病理类型和TNM分期对观察组患者治疗前的VEGF、MMP-9水平进行检测统计,并与健康对照组比较分析,并对治疗前后观察组和良性对照组患者的VEGF、MMP-9水平进行统计分析.结果 按照患者病理类型检测VEGF水平为:腺癌(332.3±82.3)pg/ml,鳞癌(364.5±81.8)pg/ml,其他病理类型(375.8±88.6)pg/ml;所有患者的MMP-9水平分别为腺癌(199.4±82.2)ng/ml,鳞癌(183.2±102.6)ng/ml,其他病理类型(185.1±112.9)ng/ml,所有肺癌患者的VEGF水平和MMP-9水平均显著高于健康对照组(P<0.05).Ⅰ期患者的VEGF水平和MMP-9水平分别为(245.4±54.3)pg/ml和(141.2±58.2)ng/ml,明显低于其他分期患者VEGF水平和MMP-9水平(P<0.05).观察组患者治疗前后VEGF水平和MMP-9水平均显著高于良性对照组患者(P<0.05).结论开胸手术治疗非小细胞肺癌患者,术后患者的VEGF水平和MMP-9水平明显升高,但没有明显的相关性.患者术前VEGF水平和MMP-9水平也明显高于良性肺部疾病患者,且与患者的分化程度相关.     

血浆基质细胞衍化因子-1与乳腺癌临床病理学特征及预后分析

目的：探讨血浆基质细胞衍化因子-1（SDF-1）与乳腺癌临床病理学特征及预后的关系。方法：2006年2月至2007年3月首都医科大学宣武医院普外科住院手术乳腺癌患者82例,手术前空腹状态抽取血液标本,分离血浆后-20℃冻存,应用酶联免疫吸附试验（ELISA）检测患者血浆中SDF-1水平。收集所有患者的临床资料及随访资料,SPSS17.0统计软件进行多因素Cox回归、生存曲线分析。结果：82例中乳腺癌患者中,失访2例,随诊率为97.6%。随访时间为12.5-71.2个月,平均55.6个月。有淋巴结转移组血浆SDF-1水平显著高于无淋巴结转移组,两者分别为（65.78±8.47）pg/ml和（56.02±3.70）pg/ml,P〈0.05。多因素Cox回归分析显示只有淋巴结转移是影响无病生存、总生存的风险因素,HR=4.958,95%CI（1.314,18.709）,P=0.018和HR=5.541,95%CI（1.117,27.491）,P=0.036。以血浆SDF-1中位数54.589pg/ml将患者分为SDF-1高水平组和低水平组,尽管两组间患者无病生存率及总生存率无显著差异（P=0.527和P=0.678）,但是SDF-1高水平组呈现出预后差于血浆SDF-1低水平组的趋势。结论：血浆SDF-1水平与乳腺癌淋巴结有无转移密切相关,高血浆SDF-1水平可能预示着预后不良。有必要就SDF-1与乳腺癌预后的关系扩大标本量进一步研究。     

Serum levels of tissue factor in colorectal cancer patients

Background. The expression of tissue factor (TF), the cellular receptor of clotting factor VII/VIIa, is a feature of certain malignant tumors, but the clinical significance of TF in colorectal cancer has not yet been clarified. Methods. The serum levels of TF and tissue factor pathway inhibitor (TFPI) were determined in 20 healthy persons and 66 colorectal cancer patients. Results. TF levels in colorectal cancer patients (median, 185.7; range, 64.5–420pg/ml) were significantly higher (P = 0.03) than in controls (median, 180.8; range, 65.2290.9 pg/ml). There was a significant correlation between serum levels of TF and TFPI, both in healthy persons (Spearmanr = 0.509;P = 0.02) and colorectal cancer patients (Spearmanr = 0.425;P = 0.0004). There was no significant correlation between levels of TF and the largest diameter of colorectal cancer, and no correlation of TF with any cancer stage. However, serum levels of TF in patients with poorly differentiated adenocarcinoma (median, 315.7; range, 281.4–367.9pg/ml) were significantly higher (P = 0.002) than levels in patients with well differentiated adenocarcinoma (median, 176.0; range, 64.5–401.3 pg/ml). There was no significant difference between TFPI levels in colorectal cancer patients and those in healthy persons. Serum levels of TFPI did not correlate with any clinicopathologic features of colorectal cancer. Conclusions. These results suggest that TF in serum is related to the differentiation of colorectal carcinoma, but that neither TF nor TFPI in the serum has prognostic significance in colorectal cancer patients.     

化疗对乳腺癌患者血清血管生成调节因子水平的影响

目的探讨乳腺癌患者化疗期间血清血管内皮生长因子(VEGF)和内皮细胞抑制素(ES)水平的变化及其与疗效的关系。方法收集40例转移性乳腺癌患者化疗前、化疗1个周期和5—6个周期后的系列血清标本120份,采用酶联免疫吸附试验(EUSA)检测VEGF和ES水平;同时采用该方法检测血清可溶性血管细胞黏附因子-1(VCAM-1)水平。结果(1)化疗前,乳腺癌患者血清VEGF中位水平为496.6 pg/ml,是健康对照组的4.7倍(P<0.001);ES中位水平为95.5 ng/ml,比健康对照组低18.3%(P=0.183);VCAM-1中位水平为1077.1 ng/ml,较健康对照组明显增高(P< 0.001)。化疗前VEGF与血清VCAM-1水平、疾病分期和转移部位相关(P<0.05)。(2)化疗1个周期后,乳腺癌患者血清VEGF中位水平为524.8 pg/ml,较化疗前增高(P=0.047);ES中位水平为110.5 ng/ml,与化疗前差异无统计学意义(P=0.055);VCAM-1中位水平为975.6 ng/ml,与化疗前差异亦无统计学意义(P=0.27)。(3)化疗5—6个周期后,乳腺癌患者血清VEGF中位水平为306.5 pg/ml,较化疗前、化疗1个周期后明显下降(P值分别为0.009和0.005);ES中位水平为113.3 ng/ml,比化疗前明显增高(P=0.042),但与化疗1个周期差异无统计学意义(P>0.05)。血清VEGF水平的变化与疗效相关。病情稳定或缓解的27例乳腺癌患者,VEGF均出现不同程度下降, 13例病情进展者无VEGF下降;VCAM-1水平也出现了与VEGF类似的治疗相关反应;而ES水平与疗效无关(P>0.05),提示化疗对ES水平影响可能较小。结论乳腺癌全身化疗明显影响血清VEGF水平,VEGF下降可能是疾病得到控制的一个指标;随着治疗后病情的稳定或缓解,肿瘤血管生成具有向着抗血管生成活性状态发展的趋势。