Serum endostatin levels are elevated in patients with soft tissue sarcoma

BACKGROUND: Solid tumors are angiogenesis dependent, and elevated levels of proangiogenic cytokines have been reported in a variety of histologies. Endostatin is an antiangiogenic fragment of the basement membrane protein, collagen XVIII. Because antiangiogenic protein fragments may be generated by tumor-derived proteases, the authors sought to determine whether circulating levels of endostatin were elevated in patients with localized soft tissue sarcoma. METHODS: The authors analyzed preoperative serum levels of endostatin, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) in 25 patients (14 males and 11 females; mean age, 44 years) with soft tissue sarcoma. For each serum sample, two aliquots were assayed in duplicate using a competitive enzyme immunoassay. Serum levels were compared with levels from 34 age-matched and gender-matched volunteer blood donors. RESULTS: Endostatin levels were significantly higher in sera from sarcoma patients than in sera from healthy controls (43.0 ng/mL vs. 25.8 ng/mL, respectively; P = 0.0002; Mann-Whitney U test). Significant elevations also were noted in VEGF and bFGF levels (P = 0.0002 and P = 0.0001, respectively). Furthermore, endostatin levels > 2 standard deviations above the control mean (55 ng/mL) were associated with an increased risk of tumor recurrence after resection (P = 0.047; log-rank test). CONCLUSIONS: Serum endostatin, VEGF, and bFGF levels are elevated in patients with soft tissue sarcoma. Elevated endostatin levels appear to be associated with tumor aggressiveness. The role of these cytokines in sarcoma angiogenesis and as potential targets for therapy warrants further study.     

Tamoxifen and aromatase inhibitors differentially affect vascular endothelial growth factor and endostatin levels in women with breast cancer.

PURPOSE: Circulating and cellular proangiogenic and antiangiogenic proteins such as vascular endothelial growth factor (VEGF) and endostatin contribute to the local angiogenic balance. We explored the effects of tamoxifen and aromatase inhibitors on concentrations of VEGF and endostatin in plasma, serum, and platelet releasate (induced by platelet activation). EXPERIMENTAL DESIGN: VEGF and endostatin concentrations were measured with a quantitative immunoassay before and after 1 to 5 weeks of treatment in 30 women with breast cancer treated with either tamoxifen (n = 14) or aromatase inhibitors (n = 16). Platelet activation was induced by a thrombin receptor agonist. RESULTS: Tamoxifen therapy resulted in an increase in platelet releasate concentrations of VEGF (P = 0.01) but no change in plasma VEGF. In contrast, aromatase inhibitor therapy did not affect serum, plasma, or platelet releasate VEGF. In univariate analysis, aspirin use attenuated the tamoxifen-associated increase in VEGF in the platelet releasate and decreased serum levels of VEGF (P = 0.03). Aromatase inhibitor therapy resulted in a decrease in serum endostatin concentrations (P = 0.04), whereas plasma concentrations of endostatin tended to be higher during treatment with aromatase inhibitors (P = 0.06). Tamoxifen therapy resulted in no change in serum or plasma endostatin concentrations. Platelet releasate concentrations of endostatin did not change with either treatment. Interindividual variability was noted among both aromatase inhibitor--and tamoxifen-treated patients. CONCLUSIONS: Tamoxifen and aromatase inhibitor therapy affect VEGF and endostatin levels and likely contribute to the angiogenic balance in breast cancer patients. Aspirin decreased the proangiogenic effects of tamoxifen, suggesting that antiplatelet and/or antiangiogenic therapy might improve the effectiveness of tamoxifen in women with breast cancer.     

Serum endostatin levels are elevated and correlate with serum vascular endothelial growth factor levels in patients with stage IV clear cell renal cancer.

Clear cell renal carcinoma (CCRC) is a highly angiogenic tumor known to secrete vascular endothelial cell growth factor (VEGF). Endostatin is an endogenous antiangiogenic agent with antitumor activity in mice. The purpose of this study was to evaluate serum levels of endostatin in normal subjects and in patients with CCRC and to examine the relationship of these levels to circulating VEGF levels. Fifteen patients (mean age, 48 years) on a clinical protocol for stage IV CCRC at the National Cancer Institute were included in the study. Archived prenephrectomy serum samples were analyzed for endostatin and VEGF concentrations. Endostatin and VEGF levels were compared with those of an age-matched group of volunteer blood donors (n = 18) using a competitive enzyme immunoassay. Data were analyzed using the Mann-Whitney U test and the Spearman rank correlation. Median serum endostatin levels were 24.6 ng/ml (range, 15.1-54.0 ng/ml) in CCRC patients versus 14.1 ng/ml (range, 1.0-19.3 ng/ml) in healthy controls (P < 0.0001). Median VEGF levels were 3.4 ng/ml (range, 0.1-11.2 ng/ml) and 2.5 ng/ml (range, 0.1-4.2 ng/ml), respectively (P = 0.065). A highly significant correlation was observed between endostatin and VEGF levels among the CCRC patients (r = 0.81, P = 0.0003) but not among controls (r = -0.22, P = 0.37). Endostatin levels are detectable in serum from healthy subjects as well as from CCRC patients. Levels are significantly elevated and correlate with VEGF levels in CCRC patients. Elucidating the nature of this correlation may lend insight into the regulation of tumor angiogenesis in patients with renal cancer.     

Circulating angiogenic factor levels correlate with extent of disease and risk of recurrence in patients with soft tissue sarcoma.

BACKGROUND: Tumor angiogenesis, or new blood vessel formation, is regulated by a balance between pro-angiogenic factors such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), and anti-angiogenic factors such as endostatin. PATIENTS AND METHODS: To investigate this angiogenic balance in soft tissue sarcomas (STS), blood samples were collected from 76 STS patients and 15 healthy controls, and analyzed for VEGF, bFGF and endostatin using quantitative enzyme-linked immunosorbent assays (ELISA). RESULTS: Forty-one patients (54%) had primary tumors, 20 (26%) had local recurrences and 15 (20%) had metastatic disease with or without local disease. Levels of all three angiogenic factors were highly variable in STS patients. Mean levels of VEGF and bFGF were 12 and 14 times higher, respectively, in patients compared with controls (P<0.0001). VEGF levels correlated with size of tumor, with the highest levels found in tumors >10 cm in size. Patients with metastases had endostatin levels 45% lower than patients without metastases (P=0.047). In 54 patients who underwent resection of primary disease or local recurrence, low pre-operative bFGF level was associated with a higher risk of subsequent recurrence (P=0.044). CONCLUSIONS: STS secrete widely variable levels of angiogenic factors, and levels of specific factors may correlate with extent of disease, predict risk of recurrence and possibly guide the use of anti-angiogenic agents.     

血清VEGF、bFGF与胃癌生物学行为的关系

目的:探讨VEGF、bFGF与胃癌的生物学行为的关系,复发转移患者血清VEGF、bFGF的表达水平与化疗疗效的关系。方法:应用ABC-ELISA方法检测胃癌患者血清VEGF、bFGF的表达情况。结果:(1)术前未作放化疗的胃癌组患者术前血清VEGF、bFGF表达水平明显高于健康体检者(P<0.05),也明显高于同组患者术后血清VEGF、bFGF表达水平(P<0.05)。(2)术前未作放化疗的胃癌组患者术前血清VEGF、bFGF的表达水平与原发肿瘤的浸润深度、TNM分期、淋巴结转移、远处转移有关。(3)术前未作放化疗的胃癌组患者术前血清VEGF与bFGF的表达水平呈正相关(r=0.439,P<0.01)。(4)胃癌患者复发转移组化疗前血清VEGF、bFGF的表达水平比健康体检者及无病生存组明显增高(P<0.05)。(5)胃癌患者复发转移组化疗后CR PR组血清VEGF、bFGF表达水平比化疗前明显减低(P<0.05),胃癌患者复发转移组化疗后NC PD组血清VEGF、bFGF表达水平比化疗前略高,但没有显著性差异(P>0.05),胃癌患者复发转移组化疗后CR PR组血清VEGF、bFGF表达水平比NC PD组明显低(P<0.05)。结论:胃癌患者血清VEGF、bFGF与胃癌生物学行为有关,而且与胃癌化疗疗效有关。血清VEGF、bFGF可能成为胃癌的诊断、术后随访、复发转移监测新的肿瘤标志物。     

Serum VEGF and bFGF adds prognostic information in patients with normal platelet counts when sampled before, during and after treatment for locally advanced non-small cell lung cancer

Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) have both been implicated to have roles in tumour angiogenesis. In the present retrospective study, serum VEGF and bFGF from patients with locally advanced non-small cell lung cancer (NSCLC) were analysed before, during and after treatment. Seventy-three patients and a total of 460 serum samples were analysed for VEGF and 443 serum samples were analysed for bFGF. Pre-treatment bFGF levels in patients with normal platelet counts, were correlated to poorer survival, P-value = 0.047. During chemotherapy, each rise of one unit bFGF corresponded to a hazard ratio of 4.06 (P=0.022). In patients with normal platelet counts, VEGF levels after radiotherapy significantly correlated to good prognosis (P=0.023), during radiotherapy VEGF levels indicated the same correlation (P=0.085). We conclude that serum VEGF and especially bFGF are of clinical interest as prognostic factors, especially in patients presenting with normal platelet counts.     

Plasma vascular endothelial growth factor levels have prognostic significance in patients with acute myeloid leukemia but not in patients with myelodysplastic syndromes

BACKGROUND: Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are positive regulators of angiogenesis. Increased levels in urine, serum, plasma, or malignant tissue have been associated with an adverse prognosis in patients with solid tumors. METHODS: The authors used an enzyme-linked immunosorbent assay to measure VEGF and bFGF levels in plasma samples from 99 patients with previously untreated myelodysplastic syndromes (MDS) (n = 41 patients; 42%) or acute myeloid leukemia (AML) (n = 58 patients; 58%) and compared the results with the results from a group of normal control participants. RESULTS: Increased expression levels of VEGF and bFGF were found in the plasma from patients with AML and MDS (P < 0.01) compared with the levels found in the control group. Plasma levels of VEGF in patients with AML or MDS were similar (median, 30.63 pg/mL and 34.41 pg/mL, respectively). There was no significant difference in bFGF levels between patients with AML and patients with MDS (median, 6.38 pg/mL and 6.98 pg/mL, respectively). Elevated levels of VEGF were associated with reduced survival (P = 0.02) in patients with AML as well as lower complete remission (CR) rates (P = 0.004). Elevated VEGF levels were not associated with reduced remission duration (CRD) in patients with AML. There was no correlation between VEGF levels and survival, CRD, or CR rates in patients with MDS. There was no correlation between bFGF levels and CR rates or survival in patients with either AML or MDS. CONCLUSIONS: Plasma VEGF levels have prognostic significance in patients with AML. The lack of clinical relevance of VEGF levels in patients with MDS suggests some biologic difference between AML and MDS.     

原发性肝癌围化疗栓塞期血液中 VEGF、bFGF 的表达及其临床意义

目的：观察化疗栓塞治疗前后原发性肝癌患者血液中血管生成调节因子（VEGF和bFGF）表达水平的变化，探讨术后肿瘤血管生成情况。方法：采用双抗体夹心EHSA法检测人血清VEGF、bFGF含量，比较化疗栓塞治疗前后的表达水平。结果：11例肝癌患者血液中VEGF和bFGF的表达水平介入后均较介入前明显升高，（P〈0．05）。两者表达呈正相关（P=0．012）。结论：化疗栓塞治疗促进了血液中VEGF和bFGF表达；VEGF和bFGF的表达在一定程度上反映了化疗栓塞术后肿瘤血管生成状况。     

Prospective analysis of circulating endostatin levels in patients with renal cell carcinoma

BACKGROUND: The aim of the current study was to assess circulating levels of endogenous endostatin in patients with renal carcinoma and to determine the relationship of these levels to circulating levels of vascular endothelial growth factor (VEGF) and prognosis. METHODS: The authors prospectively studied 66 patients (48 male, 18 female; mean age, 50 years) undergoing nephrectomy for renal carcinoma on clinical trials at the National Cancer Institute. Metastases were present in 51 of 66 patients (77%) at the time of nephrectomy. Preoperative and followup serum endostatin and VEGF levels were determined using competitive enzyme immunoassays and compared to a group of 32 age- and gender-matched healthy controls. Associations between circulating endostatin levels and clinicopathologic variables, including survival, were determined. RESULTS: Preoperative endostatin levels were higher in renal carcinoma patients than in healthy controls (P = 0.05). There was a weak to moderate correlation between pretreatment serum endostatin levels and serum VEGF levels (r = 0.47; P = 0.001), and levels of both proteins increased significantly following nephrectomy (P < 0.0001 and P < 0.0001, respectively; n = 41). In addition, patients whose endostatin levels increased more than twofold after nephrectomy had significantly poorer prognoses than patients without such an increase (P = 0.018). This association was more pronounced when patients without metastases were excluded (P = 0.0037). CONCLUSIONS: Circulating endostatin levels are elevated in patients with renal carcinoma and correlate with circulating VEGF levels. Endostatin levels increase after nephrectomy, and patients with the greatest increases experience shortened survival times. These findings suggest an association between tumor aggressiveness and the production of endogenous endostatin in patients with renal carcinoma.     

Increased serum concentration of angiogenic factors in malignant melanoma patients correlates with tumor progression and survival.

PURPOSE: To determine the predictive value of the angiogenic serum factors angiogenin, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and interleukin-8 (IL-8) for the prognosis of patients with malignant melanoma. PATIENTS AND METHODS: Angiogenin, VEGF, bFGF, and IL-8 were measured in sera of 125 melanoma patients with different stages of disease and with or without current therapy including interferon alfa and different cytostatics in comparison with 30 healthy controls using enzyme-linked immunosorbent assay. RESULTS: Serum levels of angiogenin, VEGF, bFGF, and IL-8 were significantly increased in melanoma patients compared with healthy controls. Elevated serum concentrations of VEGF, bFGF, and IL-8 were associated with advanced disease stages and tumor burden. Cytostatic therapy of patients was accompanied by increased serum levels of angiogenin, bFGF, and IL-8. As shown by univariate analysis, elevated serum levels of VEGF (P = .0001 and .0036), bFGF (P < .00005 and < .00005), and IL-8 (P < .00005 and < .00005) were strongly correlated with a poor overall and progression-free survival, respectively. Multivariate analysis revealed stage of disease (P = .0238), tumor burden (P = .0347), VEGF (P = .0036), bFGF (P = .0252), and IL-8 (P = .0447) as independent predictive factors of overall survival. Tumor burden (P = .0081), VEGF (P = .0245), and IL-8 (P = .0089) were found as independent predictive factors of progression-free survival. CONCLUSION: Our data suggest that the angiogenic serum factors VEGF, bFGF, and IL-8 are useful predictive markers for overall and progression-free survival in melanoma patients.     

Circulating angiogenic cytokines in patients with advanced non-small cell lung cancer: correlation with treatment response and survival

Tumor angiogenesis is stimulated by a pro-angiogenic shift in both inducers and inhibitors of endothelial growth. To study this shift, we measured serum and plasma levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), endostatin, and thrombospondin 1 (TSP1) in 21 advanced non-small cell lung cancer (NSCLC) patients and 46 healthy control subjects. In addition, we assessed the relevance of these levels to disease outcome. Cytokine levels were prospectively measured in plasma and serum by enzyme-linked immunosorbent assay at three times: before chemotherapy and at 1 and 12 weeks following initiation of chemotherapy. In NSCLC patients, serum VEGF levels (sVEGF) were elevated (p<0.001), whereas serum and plasma TSP1 levels were lower (p=0.012 and p=0.004, respectively) than in healthy control subjects. Pretreatment plasma endostatin and serum bFGF levels were higher in NSCLC patients than in healthy controls (p=0.05 and 0.01, respectively). Change in sVEGF at week 12 after initiation of chemotherapy correlated with response to therapy (p=0.002). Patients with pretreatment sVEGF levels <500 pg/mL had a median survival of 11 months, but those with sVEGF >500 pg/mL had only a 6 months' median survival (p < 0.03). In NSCLC patients, VEGF levels are increased, whereas TSP1 levels are decreased, which may trigger and sustain tumor angiogenesis. High levels of serum VEGF at the time of presentation with NSCLC may predict worse survival.     

Vascular endothelial growth factor levels in ovarian cyst fluid correlate with malignancy.

Ovarian cancer is a richly vascularized neoplasm with solid and cystic components. The purpose of this study was to determine whether cyst fluid could be used to quantitatively evaluate production of angiogenic factors in ovarian lesions. ELISA was used to measure vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in the cyst fluid of patients with ovarian cancer (n = 13), benign cysts and cystadenomas (n = 23), borderline tumors (n = 5), and functional cysts (n = 8). VEGF levels were markedly elevated in the fluid of malignant cysts (38.5+/-8.2 ng/ml) as compared with benign (1.6+/-0.4 ng/ml; P < 0.001), borderline (5.7+/-1.5 ng/ml; P < 0.001), or functional cysts (3.8+/-2.0 ng/ml; P < 0.001). The presence of VEGF in cancer cells was confirmed by immunohistochemistry. Follow-up of patients with malignant and borderline lesions demonstrated a correlation between VEGF levels in cyst fluid and tumor recurrence (P = 0.03). bFGF in malignant cysts was either undetectable or very low (0.3+/-0.2 ng/ml), and no significant differences were found in bFGF levels among malignant, benign, borderline, and functional cysts. This study demonstrates that ovarian malignancy is associated with dramatic elevation of VEGF levels in ovarian cyst fluid. Conversely, there is no correlation between cyst fluid bFGF levels and malignant transformation. The high levels of VEGF in malignant cysts are consistent with the hypothesis that this growth factor plays an important role in ovarian cancer related-angiogenesis and tumor progression and represents a potentially important target of antiangiogenic therapy.     

Are basic fibroblast growth factor and vascular endothelial growth factor prognostic indicators in pediatric patients with malignant solid tumors?

Angiogenesis plays an important role in the growth, progression, and metastasis of solid tumors. Among angiogenic factors, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) appear to be useful markers in adults with cancer. The aim of this pilot study was to determine the levels of VEGF in serum and bFGF in serum and urine of children with solid tumor at diagnosis (as measured by ELISA), and to investigate whether these parameters provide prognostic information. Forty consecutive patients with different types of cancer were prospectively included in this study. Median values of all studied angiogenic factors were higher in patients than in controls (n = 40), and the differences were statistically significant for bFGF in serum and urine: 10 versus 3 pg/ml (P = 0.0004) and 6406 versus 0 pg/g of creatinine (P < 0.0001), respectively. Among patients, median serum values of bFGF and VEGF were higher in children with metastatic disease (n = 14) than in those with localized disease (n = 26). The difference was statistically significant for serum bFGF: 17.5 versus 6 pg/ml (P = 0.02). Serum angiogenic factor levels correlated with outcome. The estimated event-free survival at 3 years was 79% for patients with normal bFGF values (n = 13) versus 42% (n = 26; P = 0.02) for those with high levels, and 71% in case of normal VEGF values (n = 20) versus 38% (n = 19; P = 0.04) for those with high levels. No benefit of normal urinary bFGF values was observed. Our results provide a rationale for exploring the clinical interest of bFGF and VEGF measurements in body fluids of a larger group of children with cancer.     

Pet birds and risk of lung cancer in North-Western Germany

The relationship between non-small cell lung cancer and platelet counts, serum levels of vascular endothelial growth factor (VEGF) and endostatin, is unclear. Platelet counts and serum VEGF and endostatin levels were measured preoperatively in 99 patients with non-small cell lung cancer, and the relationship between these factors and clinicopathological features, including prognosis, was examined. Mean serum VEGF level was slightly higher in patients than in healthy subjects (P=0.23). Mean serum endostatin level was 42.4+/-40.4 ng/ml in patients compared to 16.3+/-10.3 ng/ml in healthy subjects (P=0.0003). Serum endostatin levels were significantly higher in patients with involvement greater than T2 or stage IB, compared to other patients. Platelet count and serum endostatin level greater than the median were associated with poor prognosis. Our results suggested that platelet count and serum endostatin level may be useful markers for non-small cell lung cancer.     

血清VEGF、bFGF与乳腺癌生物学行为的关系

目的：探讨VEGF、bFGF与乳腺癌的生物学行为的关系,复发转移患者血清VEGF、bFGF的表达水平与化疗疗效的关系。方法：应用ABC—ELISA方法检测乳腺癌患者血清VEGF、bFGF的表达情况。结果：术前未作放化疗的乳腺癌患者术前血清VEGF、bFGF表达水平明显高于健康体检者、乳腺腺瘤患者（P〈0．05）,也明显高于同组患者术后血清VEGF、bFGF表达水平（P〈0．05）。术前未作放化疗的乳腺癌患者术前血清VEGF、bFGF的表达水平与原发肿瘤的大小、TNM分期、淋巴结转移有关。术前未作放化疗的乳腺癌患者术前血清VEGF与bFGF的表达水平呈正相关（r=0．210,P〈0．05）。乳腺癌复发转移组化疗前血清VEGF、bF—GF的表达水平比健康体检者及无病生存组明显增高（P〈0．05）。乳腺癌复发转移组化疗后CR＋PR组血清VEGF、bFGF表达水平比化疗前明显减低（P〈0．05）;化疗后NC＋PD组血清VEGF、bFGF表达水平比化疗前略高,但没有显著性差异（P〉0．05）。乳腺癌复发转移组化疗后CR＋PR组血清VEGF、bFGF表达水平比NC＋PD组明显降低（P〈0．05）。结论：乳腺癌患者血清VEGF、bFGF的表达水平与乳腺癌生物学行为有关,而且与化疗疗效有关,提示通过检测乳腺癌患者血清VEGF、bFGF的表达水平可能对乳腺癌的诊断、客观预测肿瘤的复发转移、选择合理有效的治疗方案有一定的参考价值。     

Pretreatment serum endostatin as a prognostic indicator in metastatic gastric carcinoma

Endostatin is the C-terminal antiangiogenic fragment of the extracellular matrix protein collagen XVIII, and is generated by tumor-derived proteases. The presence of serum endostatin in patients with gastric cancer has not been reported. The authors assessed the serum levels of endostatin in patients with gastric carcinoma and evaluated their association with the levels of vascular endothelial growth factor (VEGF) and the clinical outcome. A total of 107 patients with gastric cancer were included in the study. Pretherapeutic serum levels of endostatin and VEGF were measured using an ELISA, and compared with those in 23 healthy controls. The serum levels of endostatin and VEGF were higher in gastric cancer patients than in healthy controls (endostatin, 70.1 +/- 16.6 vs. 52.2 +/- 6.2 ng/mL [p < 0.001]; VEGF, 55.1 +/- 7.6 vs. 32.1 +/- 2.4 ng/mL [p < 0.001]; mean +/- SD). Serum endostatin levels were significantly associated with the presence of distant metastases (r = 0.556, p < 0.001) and VEGF levels (r = 0.335, p < 0.001), but not with the depth of tumor invasion, differentiation, or regional lymph node status. A serum endostatin level above the 75th percentile of the distribution for the patients (79.2 ng/mL) was associated with a poor outcome (last follow-up at 42 months; median survival time, 9 vs. 20 months [log-rank, p = 0.017]; median time to progression, 5 vs. 10 months [log-rank, p = 0.022]) in the patients with metastatic gastric cancer. The results suggest for the first time that an elevated serum level of endostatin at the diagnosis of metastatic gastric cancer could be predictive of a poor outcome.     

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.     

Elevated perioperative serum vascular endothelial growth factor levels in patients with colon carcinoma

BACKGROUND: To the authors' knowledge, little is known to date regarding the prognostic relevance of measuring serum levels of vascular endothelial growth factor (VEGF), a potent stimulator of angiogenesis, in patients with colon carcinoma who undergo surgery. METHODS: Preoperative and postoperative VEGF serum levels were determined by enzyme-linked immunoadsorbent assay in 81 patients with colon carcinoma who were undergoing surgery. Fifty healthy individuals served to define normal VEGF serum levels. RESULTS: Preoperative VEGF serum levels were significantly higher in the group of patients with colon carcinoma (mean, 504.1 pg/mL +/- 223 pg/mL; range, 285-1390 pg/mL; 95% confidence interval [95%CI], 49 pg/mL) compared with the control group (mean, 78.1 pg/mL +/- 22 pg/mL; range, 40-110 pg/mL; 95%CI, 4.3 pg/mL; P < 0.001). Multiple regression analysis demonstrated a significant correlation (r) between preoperative VEGF serum levels and age (r = - 0.275; P = 0.013), Dukes stage (r = 0.488; P < 0.001), and carcinoembryonic antigen (CEA) levels (r = 0.285; P < 0.018). No significant correlation was found between preoperative VEGF serum levels and disease site, patient gender, tumor size, tumor grade, or performance status. Moreover, preoperative VEGF serum levels were significantly lower in patients who underwent curative surgery compared with patients who underwent noncurative surgery (443 pg/mL +/- 117 pg/mL vs. 821 +/- 353 pg/mL, respectively; P < 0.0001). Logistic regression analysis selected preoperative VEGF and CEA serum levels as the only good prognostic indicators of curative and noncurative surgery (P < 0.001; relative risk, 2.98 and 2.03, respectively). Furthermore, VEGF serum levels dropped significantly after surgery, with a further downward trend until the 30th postoperative day (P < 0.001). Stepwise regression analysis selected preoperative VEGF serum level as the only variable associated significantly with the prediction of both disease-specific survival and disease-free survival (P = 0.001). CONCLUSIONS: Preoperative serum VEGF levels may be useful for predicting outcome in patients with colon carcinoma who undergo surgery.     

Serum semicarbazide-sensitive amine oxidase (SSAO) activity correlates with VEGF in non-small-cell lung cancer patients

Semicarbazide-sensitive amine oxidase (SSAO) is an enzyme associated with vascular systems in mammals. SSAO catalyzes the deamination of primary monoamines and has been suggested to be a risk factor in vascular disorders, e.g., diabetic vascular complications. The primary aim of the present study was to investigate if serum SSAO activity is associated with clinical parameters in non-small cell lung cancer (NSCLC) patients. Secondary aims were to investigate if there is a correlation between SSAO activity and the angiogenic factors vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF).Thirty-three patients donated 231 serum samples. Detectable levels of bFGF, VEGF, and SSAO were observed in all patients. Serum SSAO activity was not statistically associated with survival (p = 0.35). A highly significant statistical correlation was found between SSAO activity and VEGF (p < 0.0001). No significant correlation between SSAO and bFGF was observed.We conclude that SSAO was not associated with survival in patients with NSCLC. However, a strong correlation between serum SSAO activity and the angiogenic factor VEGF was found that might implicate new aspects of the mechanisms controlling angiogenesis.     

Prognostic Values of VEGF and Endostatin with Malignant Pleural Effusions in Patients with Lung Cancer

Aims: Angiogenesis is important in malignant pleural effusion (MPE) formation and it is regulated by anumber of pro- and anti-angiogenic cytokines. The purpose of this study was to evaluate the prognostic valueof angiogenic factor vascular endothelial growth factor (VEGF) and angiogenesis inhibitor endostatin in lungcancer patients with MPE, and investigate the relationship between these two kinds of agent. Methods: Usingenzyme-linked immunoadsorbent assay, the concentrations of VEGF and endostatin were measured in pleuraleffusions (PE) and serum from a total of 70 lung cancer patients with MPE and 20 patients with tuberculosis.Results: Compared to patients with tuberculosis, the levels of VEGF and endostatin in both PE and serum weresignificantly higher in patients with lung cancer. There were statistically significant correlations between VEGFlevels in PE and serum (r=0.696, p<0.001), endostatin levels in PE and serum (r=0.310, p=0.022), and VEGF andendostatin levels in PE (r=0.287, p=0.019). Cox multivariate analysis revealed that elevated pleural VEGF andendostatin levels and serum endostatin level were independent predictors of shorter overall survival. Conclusion:Both pro- and anti-angiogenic factors are likely contributors to PE formation. Our results suggest that the levelsof VEGF and endostatin in PE, together with endostatin in serum, may be potential prognostic parameters forlung cancer patients with MPE.