Serum basic fibroblast growth factor and vascular endothelial growth factor and tumour growth kinetics in advanced colorectal cancer

BACKGROUND:: The development of new microvessels in the surrounding stromais a prerequisite for tumour progression. Basic fibroblast growthfactor (bFGF) and vascular endothelial growth factor (VEGF)are angiogenic factors expressed in a broad range of human tumours.We have measured the concentrations of both cytokines in theserum of patients with advanced colorectal cancer. We questionedwhether these levels are related to the number of tumour sites,the volume of liver and/or lung involvement and the growth kinetics. PATIENTS AND METHODS:: 44 untreated colorectal adenocarcinoma patients who had developedmetastatic and/or recurrent disease were evaluated. Serum levelsof bFGF and VEGF were repeatedly measured using ELISA. The extentof target organ involvement and the kinetics of tumour volumegrowth were determined on consecutive computer tomography (CT)images. RESULTS:: Patients with a tumour volume doubling time of less than 6 monthsshowed a higher bFGF and VEGF serum level than others, independentof the number of sites involved and the extent of the metastaticdisease. CONCLUSIONS:: The data suggest a predictive value of serum bFGF and VEGF levelsfor the progression of disease in patients with untreated metastaticcolorectal cancer. The results corroborate the importance ofangiogenesis in the process of tumour growth. The serum levelsmight prove a useful tool in the quantitication of angiogenesisand might be of valuable information in the decision processof initiating palliative chemotherapy. It will be of considerableimportance to investigate whether the serum bFGF and VEGF levelshave a predictive value on the probability of response to cytotoxictherapy. angiogenesis, colorectal carcinoma, tumour growth, serum bFGF, esrum VEGF     

Low levels of basic fibroblast growth factor (bFGF) are associated with a poor prognosis in human breast carcinoma.

It has been suggested that angiogenesis and angiogenic factors may be strong predictors of relapse in patients with breast carcinoma. We measured the levels of the angiogenic peptide basic fibroblast growth factor (bFGF) in 140 breast tumour cytosols using an immunoassay. There were no significant differences in bFGF levels between breast non-malignant lesions and primary carcinomas. In 124 cases with primary breast cancer, we observed an association of low bFGF levels (< 400 pg mg[-1]) with increasing tumour size (P = 0.023) and stage of disease (P = 0.002). bFGF levels did not correlate with other variables, including axillary nodes, hormone receptors, cathepsin D and the serum tumour markers CA15.3 and CEA. With a median follow-up of 44.0 months, breast cancer patients with low levels of bFGF had a significantly shorter disease-free survival (DFS) than patients with elevated bFGF (log-rank, P < 0.0001). In a multivariate analysis of DFS, only bFGF, T-stage and histological grade showed statistical significance. In a parallel evaluation of circulating bFGF, we did not observe a correlation between the serum and tissue bFGF levels in the 29 selected cases with matched determinations. Our results indicate that low bFGF levels in breast carcinoma are an independent prognostic indicator of poor prognosis and disease recurrence.     

Quantitative analysis of basic fibroblast growth factor and vascular endothelial growth factor in human colorectal cancer.

Tumour growth is angiogenesis dependent. Some authors suggest a prognostic role of microvessel count in colorectal cancer. We tested the role of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) in the switch to the angiogenic phenotype in 35 patients with colorectal cancer at different stages of disease. We evaluated the two angiogenic factors, by enzyme-linked immunosorbent assay (ELISA), in tumour, peritumoral mucosa, pathological mesenteric and peripheral blood. We used ten endoscopic intestinal biopsies and ten peripheral blood samples from healthy subjects as control. bFGF was significantly lower in tumour tissues and in peritumoral mucosas than in healthy mucosas, whereas VEGF was up-regulated in tumours but not in peritumoral mucosa. Both angiogenic factors were greatly increased in mesenteric blood. VEGF tumour and serum levels were significantly correlated with the stage of disease. bFGF tumour and serum concentration were not correlated with the stage of disease. The high levels of bFGF in mesenteric blood suggest that this growth factor might be abnormally released from tumour tissue and peritumoral mucosa and could function as an early effector in the switch to the angiogenic phenotype. In contrast, VEGF, whose levels show a significant correlation with the stage of disease, could act in a following step, supporting tumour progression.     

Plasma vascular endothelial but not fibroblast growth factor levels correlate with colorectal liver mestastasis vascularity and volume

The extent to which plasma levels of angiogenic factors in healthy individuals and tumour volume-related variations in colorectal cancer affect the accuracy of circulating angiogenic factors as predictors of colorectal cancer vascularity is unknown. We used enzyme-linked immunosorbant assay to measure plasma vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) levels in colorectal liver metastasis (CLM) patients, and 'no cancer' controls. CLM volume was determined from computerized tomography scans, and tumour vessel count and vessel volume from anti-endothelial antibody-stained biopsies. There was a significant (P= 0.03) increase in plasma VEGF level in 29 CLM patients (median 180.3 pg/ml(-1), iqr 132.5-284.8 pg/ml(-1) compared with 19 controls (median 125.8 pg/ml(-1), iqr 58.2-235.9 pg/ml(-1). There were significant correlations between plasma VEGF and tumour vessel count (r = 0.66, P = 0.03), tumour vessel volume (r= 0.59, P = 0.03), and CLM volume (r= 0.53, P = 0.03). A VEGF level in the upper quartile of the plasma VEGF distribution had a 70% sensitivity and 75% specificity in predicting an upper quartile liver metastasis tumour vessel count. No relation was identified between CLM and plasma bFGF levels. Plasma VEGF level predicted CLM vascularity, despite an overlap with normal levels and tumour volume-related variations.     

Impact of serum basic fibroblast growth factor on prognosis in human renal cell carcinoma

Renal cell carcinoma is often characterised by extensive vascularity and angiogenic factors may be of importance for disease progression. Using a sandwich enzyme immunoassay, basic fibroblast growth factor (bFGF) was analysed in the sera from 206 patients with renal cell carcinoma before the initiation of therapy. The median bFGF level was 3.0 pg/ml (range <1.0–70.9 pg/ml). The serum levels were significantly correlated to tumour stage and nuclear grade. Patients with tumour thrombus to the renal or the inferior caval vein had significantly higher serum bFGF levels compared with those with non-invading tumours (P=0.007). Patients with serum bFGF levels above 3.0 pg/ml had a worse prognosis, compared with those with lower levels (P=0.001). Furthermore, patients with tumours with vein invasion had a worse prognosis compared with those without invasion. After multivariate analysis, only tumour stage and grade remained as independent prognostic factors.     

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.     

Upregulation of basic fibroblast growth factor in breast carcinoma and its relationship to vascular density, oestrogen receptor, epidermal growth factor receptor and survival

Background: Angiogenesis, the process whereby endothelial cells divide and migrate to form new blood capillaries, has been assessed in tumours by measuring microvessel density. High microvessel density is a significant adverse prognostic factor in breast cancer. The angiogenic factor, basic fibroblast growth factor (bFGF), has been associated with tumourigenesis and metastasis in several human cancers. There are few quantitative studies of bFGF expression in normal tissues compared to cancer.Patients and methods: We have measured bFGF levels in 149 human primary breast carcinomas and assessed the findings in relation to microvessel density, oestrogen receptor (ER) and epidermal growth factor receptor (EGFR).Basic FGF levels were measured by ELISA. Western blotting and immunohistochemistry were carreid out to confirm the presence of bFGF.Results: Levels of bFGF were more than 10-fold higher in tumour cytosols compared to reduction mammoplasty tissue and 3-fold compared to non neoplastic cytosols from the same breast as the tumour (P < 0.0001). Immunohistochemistry showed bFGF protein was localised exclusively in the stroma whereas no bFGF staining was observed in the epithelial cells. High bFGF levels were significantly related to high ER (P = 0.01). Similarly, high bFGF levels were significantly related to low grade (P = 0.046) and to small tumour size (P = 0.04). No significant relationship was observed between bFGF and microvessel count, EGFR or age. In univariate analysis and in a Cox proportional hazard model bFGF did not reach significance for overall or relapse free survival.Conclusions: Our results show that although bFGF is elevated in breast carcinomas compared to normal breast tissue it is not related to microvessel density and it is not an independent predictor of survival in breast cancer patients. Basic FGF may be one of multiple factors that synergise with other growth factors such as VEGF to enhance angiogenesis.     

Elevated preoperative serum levels of angiogenic cytokines correlate to larger primary tumours and poorer survival in non-small cell lung cancer patients

We have analysed the predictive and prognostic information in preoperatively collected serum levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in patients clinically evaluated as operable non-small cell lung cancer (NSCLC). Fifty-eight patients with operable NSCLC were included. VEGF and bFGF levels in serum were analysed using enzyme linked immunosorbent assays (Quantikine human VEGF and Quantikine HS human FGF basic, R&D Systems). Univariate analysis demonstrated that tumour volume, platelet counts, VEGF and bFGF were significant prognostic factors. However, only bFGF remained significant in the multivariate analysis (P=0.014). Significant correlation's were demonstrated between VEGF levels and tumour volume (r=0.33; P=0.012) and platelet count (r=0.43; P=0.001). bFGF levels correlated significant with recurrent disease (r=0.34; P=0.01), platelet count (r=0.53, P<0.001) and performance status (r=0.29; P=0.029). Furthermore, bFGF levels and VEGF levels correlated significantly (r=0.44; P<0.001). We conclude that elevated circulating angiogenic cytokines correlate with tumour volume, higher relapse risk and poorer survival in patients with operable non-small cell lung cancer.     

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.     

Highly metastatic human prostate cancer growing within the prostate of athymic mice overexpresses vascular endothelial growth factor.

Angiogenesis is essential for tumor progression and metastasis. It is mediated by the release of angiogenic factors by the tumor or host. We analyzed the expression of angiogenic factors by the prostate cancer cell line LNCaP and two derived variants, in vitro and in vivo, to determine whether metastatic cell lines express higher levels of these factors. The production of three angiogenic factors, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and interleukin 8 (IL-8), by LNCaP and its variants, LNCaP-LN3 (highly metastatic) and LNCaP-Pro5 (slightly metastatic), was measured by ELISA. VEGF, bFGF, and IL-8 mRNA expression was determined in vitro by Northern blot analysis. VEGF mRNA expression was determined in vivo by in situ hybridization. VEGF and flk-1 protein expression and microvessel density of LNCaP cell tumors were quantified by immunohistochemistry. In vitro, VEGF production by LNCaP-LN3 (3.15+/-0.04 pg/ml/10(3) cells) was significantly higher than those of both LNCaP (2.38+/-0.34 pg/ml/10(3) cells) and LNCaP-Pro5 (1.67+/-0.37 pg/ml/10(3) cells; P = 0.049 and 0.001, respectively). None of the three cell lines produced detectable levels of bFGF or IL-8 in vitro. In vivo, LNCaP-LN3 tumors exhibited higher levels of VEGF mRNA and protein (152.2+/-28.5 and 200.5+/-28.3) and of flk-1 protein (156.5+/-20.6) and had higher microvessel density (16.4+/-4.2) than either LNCaP tumors (89+/-17.5, 173.3+/-23.0, 124.6+/-21.6, and 12.4+/-3.5, respectively) or LNCaP-Pro5 tumors (63+/-14.7, 141.2+/-38.1, 126.1+/-20, and 5.8+/-2.2, respectively). In conclusion, metastatic human prostate cancer cells exhibited enhanced VEGF production and tumor vascularity compared with prostate cancer cells of lower metastatic potential. Thus, VEGF may play an important role in prostate cancer metastasis.     

Decline in angiogenic factors, such as interleukin-8, indicates response to chemotherapy of metastatic melanoma

Serum concentrations of angiogenic factors have been reported to correlate with tumour burden and prognosis in metastatic melanoma. The present study was performed to assess the value of angiogenic factors in serum in indicating response or failure to chemotherapy and immunochemotherapy in stage IV melanoma. Thirty-five patients suffering from stage IV melanoma according to the American Joint Committee on Cancer (AJCC) criteria were included in this prospective study. Before and following chemotherapy or immunochemotherapy, serum levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF-AB), vascular cell adhesion molecule-1 (VCAM-1) and interleukin-8 (IL-8) were measured. Staging examinations following chemotherapy revealed 15 patients with response to therapy (complete response, partial response, stable disease), 14 patients with progressive disease and six patients with mixed response. Patients who responded to therapy showed a significant decrease in the serum level of IL-8 at the time of staging examinations, whereas patients with progressive disease did not. Following chemotherapy, serum concentrations of PDGF-AB had significantly decreased in both patients with response and patients with progressive disease. Comparing the VEGF and bFGF levels of responders and non-responders after a single administration of cytostatics showed significantly lower concentrations in patients with response to therapy. In all patients, a high intra- and inter-individual variability of serum values was observed during application of therapy. It can be concluded that low IL-8 serum levels after chemotherapy indicate response to chemotherapy in stage IV melanoma patients. The persistence of elevated serum levels of VEGF and bFGF following the initial cytostatic administration may help to identify patients resistant to chemotherapy. The distinct variability of serum levels indicates that processes other than tumour angiogenesis also influence the serum concentration of the examined angiogenic factors.     

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.     

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.     

High level of vascular endothelial growth factor in hemorrhagic pleural effusion of cancer

Angiogenic cytokines, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and angiogenin, are candidates for the induction of pleural effusions because they have been implicated in the induction of neovascularization, vascular permeability, and hemorrhage both in the inflammatory process and in tumor progression. Thus, we hypothesized that these angiogenic factors in effusion might be involved in the clinical manifestation of malignant pleural disease. We measured the levels of VEGF, bFGF, and angiogenin in pleural effusions and sera from 40 patients. Pleural effusions due to malignancy (1,350 pg/ml) contained significantly higher levels of VEGF than effusions due to inflammatory diseases (102 pg/ml; p = 0.034). Furthermore, hemorrhagic effusions showed significantly higher VEGF levels (1,942 pg/ml) than non-hemorrhagic effusions (202 pg/ml; p = 0.016) in malignant patients. In contrast, neither bFGF nor angiogenin were correlated with any clinical manifestation of pleural effusion. Immunohistochemical study revealed that malignant cells in the pleura were stained with anti-VEGF antibody. Our data suggest that VEGF secreted from tumor cells may be involved in the accumulation of pleural effusion in malignancy, and that increased levels of VEGF may induce hemorrhagic effusion.     

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。     

Vascular endothelial growth factor and basic fibroblast growth factor in primary lung carcinomas and the incidence of metastases

Paraffin-embedded tumor sections from 166 patients with squamous cell lung carcinomas (n=114) and lung adenocarcinomas (n=52) were analyzed for the expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) by immunohistochemistry. The results were compared with the incidence of metastatic spread. Sixty-five tumors were characterized as VEGF-negative and 101 tumors as VEGF-positive. Fifty-eight tumors were bFGF-negative and 108 tumors classified as bFGF-positive. Tumors with expression of VEGF or bFGF showed an increase in the formation of metastases. Combining the VEGF and bFGF expressions improved the prognostic value. Corresponding results were obtained when the analysis was restricted to squamous cell lung carcinomas or adenocarcinomas of the lung. These data provide evidence that VEGF and bFGF may be relevant factors associated with the metastatic potential of primary lung carcinomas.     

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.     

Elevated plasma levels of vascular endothelial growth factor is associated with marked splenomegaly in chronic myeloid leukemia

Recent investigations support the idea that angiogenesis is involved in the pathophysiology of hematologic malignancies, including chronic myeloid leukemia (CML). The aim of the present study was to evaluate plasma levels of VEGF and bFGF in a cohort of 51 chronic-phase CML patients at the time of diagnosis, as well as to investigate the effect of imatinib therapy on VEGF amounts in CML patients. Plasma VEGF levels were significantly higher in patients studied as compared with the 20 healthy subjects (p<0.001), the median plasma VEGF level detected in patients analysed and healthy controls was 433.4 pg mL(-1) (range 65.2-2,452.7 pg mL(-1)) and 81.6 pg mL(-1) (range 44.2-338.7 pg mL(-1)), respectively. On the other hand, no difference in bFGF plasma levels could be found between chronic-phase CML patients and the control group. There were significant associations between plasma VEGF levels and some characteristics of patients evaluated, with trends for higher VEGF values in patients with enlarged spleens (p = 0.02) and those with higher platelet count (p<0.001). Of the patients, 11 received imatinib treatment. The initial VEGF levels markedly decreased after 6 months of imatinib therapy in each patient (p<0.001). These data support the important pathophysiological role of VEGF in CML. Further studies aiming to explore the detailed angiogenic profile of CML may help in developing new therapeutic strategies for this myeloproliferative disorder.     

Soluble vascular endothelial growth factor levels in patients with primary colorectal carcinoma. The Danish RANX05 Colorectal Cancer Study Group.

INTRODUCTION: Angiogenesis is decisive in tumour progression and metastasis. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor, and increased VEGF levels in patients with carcinomas may facilitate growth of both primary and secondary tumours. METHODS: Soluble (s) VEGF levels were determined in serum from 91 volunteer healthy blood donors and from 614 patients scheduled to undergo resection for primary colorectal cancer. None of the patients received pre- and/or post-operative chemo- and/or radiotherapy. The results of sVEGF were analysed with respect to Dukes> stage, gender, age and topographical tumour localization. RESULTS: Patients with colorectal cancer had significantly (P<0.0001) higher levels of sVEGF, compared to healthy blood donors. Patients with Dukes> stage D disease had significantly (P=0.01) higher values than patients with Dukes> stage A, B and C disease, who had comparable values. Patients with the primary tumour localized in the colon had significantly (P<0.0001) higher levels of sVEGF than patients with the primary tumour localized in the rectum. By classifying the patients into two groups, based on the upper limit of the 95(th)percentile of sVEGF of healthy individuals (sVEGF=465 pg/ml), we found a significantly (P<0.0001) reduced overall survival in patients with sVEGF >465 pg/ml compared to patients with sVEGF values below this level. Moreover, in the subgroup of patients with the carcinoma localized in the colon and sVEGF levels above 465 pg/ml, we found a significantly (P<0.0001) reduced overall survival compared to colon cancer patients with lower sVEGF values. In conclusion, data from the present study suggest a biological significance of VEGF in patients with colorectal cancer, and indicate that a high pre-operative sVEGF value is associated with poor outcome, but further research is needed to validate sVEGF as a cancer marker.     

Do serum angiogenic growth factors provide additional information to that of conventional markers in monitoring the course of metastatic breast cancer?

OBJECTIVE: Our work evaluated the potential role of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) serum levels with respect to that of conventional serum tumour markers, CEA and CA 15-3, in monitoring the course of metastatic breast cancer in 56 female patients treated with cytotoxic chemotherapy. METHODS: VEGF and bFGF concentrations were determined using a quantitative sandwich enzyme immunoassay technique. The positive predictive value (PPV) of each marker and of marker combinations for different types of clinical response was calculated. RESULTS: The highest PPV for overall disease control was shown by bFGF (70%), which also showed the highest PPV for both partial response (36.4%) and stable disease (63.2%). CEA showed the highest predictive value for progression (69.2%). A combined increase in CEA and bFGF or VEGF was associated with disease progression in all patients. CONCLUSIONS: Information provided by angiogenic factor levels seems to be independent of and is possibly complementary to that provided by conventional serum markers. bFGF showed the maximum predictive value for disease control and provided additional information to that obtained from CEA or CA 15-3 evaluation. It could therefore be a promising candidate for monitoring response to chemotherapy in advanced breast cancer.