Interleukin (IL)-8 and vascular endothelial growth factor (VEGF) are important factors that induce the migration and proliferation of endothelial cells, increase the vascular permeability, and the modulate chemotaxis of monocytes. These molecules have been found in human atherosclerotic plaques. However, it is not clear whether the circulating levels of IL-8 and VEGF correlate with the extents of carotid stenosis. In this study, we investigated the relationship between circulating levels of IL-8 as well as VEGF and the extents of carotid stenosis. Sera from 41 patients with carotid stenosis were assessed for concentrations of IL-8 and VEGF by enzyme-linked immunosorbent assay. The degree of stenosis of extracranial carotid artery was calibrated by carotid B- mode ultrasonography. The serum concentration of IL-8 (r=-0.04733, p>0.05) was not correlated with the degree of stenosis. However, the serum concentration of VEGF (r=0.4974, p<0.01) was significantly correlated with the degree of carotid stenosis. These findings suggest that increased serum level of VEGF might be a marker for higher degree of stenosis of extracranial carotid artery.
Adult ; Aged ; Carotid Artery Diseases/blood ; Carotid Stenosis/*blood ; Disease Progression ; Endothelial Growth Factors/*blood ; Female ; Human ; Interleukin-8/*blood ; Lymphokines/*blood ; Male ; Middle Age

The purpose of this preliminary study is to elucidate that vascular endothelial growth factor (VEGF) influences contrast enhancement of hepatic tumors on computed tomography (CT). Fourteen patients with hepatic tumors (11 hepatocellular carcinomas; 3 metastatic cancers) underwent a dual-phase dynamic helical CT or computed tomographic hepatic arteriography. The attenuation of each mass was determined as hyperattenuation, isoattenuation or hypoattenuation with respect to the adjacent nontumorous parenchyma. Gun-needle biopsy was done for each tumor, and paraffin sections were immunostained with anti- VEGF antibody by the avidin-biotin-peroxidase complex method. The pathologic grade was made by intensity (1 +, 2+, 3+) and area (+/-, 1 +, 2+). The tumor ranged 2.0-14.0 cm in size (mean, 5.8 cm). In arterial phase, the intensity was not correlated with the degree of enhancement (p=0.086). However, the correlation between the attenuation value of hepatic arterial phase and the area of positive tumor cells was statistically significant (p=0.002). VEGF may be the factor that enhances the hepatic mass with water-soluble iodinated contrast agent in CT.
Adult ; Aged ; Capillary Permeability ; Endothelial Growth Factors/physiology* ; Endothelial Growth Factors/analysis ; Female ; Human ; Liver Neoplasms/radiography* ; Liver Neoplasms/blood supply ; Lymphokines/physiology* ; Lymphokines/analysis ; Male ; Middle Age ; Prospective Studies ; Radiographic Image Enhancement* ; Tomography, X-Ray Computed

OBJECTIVELooking for an objective biomedical index to distinguish types and phases of hemangioma in order to provide an objective basis for selecting clinical treatment to hemangioma.

METHODSELISA (enzyme-linked immunosorbent assay) was used to determine serum VEGF concentration of 15 patients with proliferative hemangioma, 6 with involuted hemangioma, 6 with vascular malformation and 8 infants of the control group.

RESULTSThe serum VEGF concentrations of 15 proliferative hemangioma patients were significantly higher than those of involuted hemangioma patients, vascular malformation patients and control group infants. The serum VEGF concentrations of involuted hemangioma patients were a little bit higher than those of vascular malformation patients and control group infants, but without statistic significance.

CONCLUSIONSELISA could easily and accurately determine the serum VEGF concentration of different types and different phases of hemangioma. The determination of serum VEGF concentration could provide guidance for selecting a protocol of systemic corticosteroid treatment for proliferative hemangioma. Combined with gene expression and distribution of VEGF and its receptors and some other cytokines, the determination of serum VEGF concentration could help elucidate the mechanism of proliferative hemangioma.

Endothelial Growth Factors ; blood ; Enzyme-Linked Immunosorbent Assay ; Hemangioma ; blood ; Humans ; Infant ; Lymphokines ; blood ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors

Angiogenesis is a series of processes that include endothelial proliferation, migration and tube formation. Vascular endothelial growth factor (VEGF) is regarded as a potent mediator of angiogenesis, vascular permeability and tumor cell growth in renal cell carcinoma. This study was designed to evaluate the expression of VEGF and the microvessel count (MVC) and to determine their prediction efficacies for prognosis in renal cell carcinoma. The relationship between the expression of VEGF and MVC were evaluated immunohistochemically in 50 patients with renal cell carcinoma who received a radical nephrectomy at Wonju Christian Hospital between 1989 and 1997. Microvessels were identified by immunostaining endothelial cells for CD-31 antigen. The mean follow-up was 96 months (3 - 133 months). Overall 5-year survival rate was 71.5%. VEGF was expressed in the tumor cell cytoplasm. Of the 50 tumors, 23 (46%) were weak to strongly positive for VEGF but 27 (54%) were unreactive. The respective 5-year survival rates for patients with positive and negative expressions of VEGF were 70% and 73% (p > 0.05). The overall mean MVC was 13.4 in a 400x field. Mean MVCs were significantly higher in VEGF-positive tumors (17.6 +/- 12.1) than in VEGF-negative tumors (9.9 +/- 5.4), and the MVCs of the high vascular density group and the low ascular density groups were significantly different. The 5-year survival rates of patients with high vascular density and low vascular density were 59% and 86%. The median survival period for patients with MVCs higher than or equal to 10 vessels/field was 85 months, whereas for those with MVCs lower than 10 vessels/field the median survival time was 102 months. These results suggest that MVC may be a better prognostic factor in renal cell carcinoma than the expression of VEGF.
Adult ; Aged ; Carcinoma, Renal Cell/*blood supply/*metabolism ; Endothelial Growth Factors/*metabolism ; Female ; Human ; Kidney Neoplasms/*blood supply/*metabolism ; Lymphokines/*metabolism ; Male ; Middle Age ; Neovascularization, Pathologic/*pathology ; Prognosis

OBJECTIVESTo determine the pre-therapeutic serum level of vascular endothelial growth factor (VEGF) in patients with hepatocellular carcinoma (HCC) and to elucidate the relation between the serum level and clinical characteristics and metastasis of HCC.

METHODSOne-hundred and fifteen HCC patients, 40 patients with benign liver lesions, and 30 healthy control subjects were included in this study. The serum VEGF level was measured with the quantitative sandwich enzyme linked immunosorbent assay (ELISA, R&D systems).

RESULTSThe serum VEGF levels in the HCC group (465.62 +/- 336.24 pg/ml) was significantly elevated as compared with those in patients with benign liver lesions (159.54 +/- 120.58 pg/ml) and those in normal controls (123.53 +/- 51.84 pg/ml). The VEGF levels were not significantly different between the patients with benign liver lesions and the normal controls. The serum VEGF levels showed a positive rate of 77.4%, 25%, and 3.3% in the HCC patients, benign liver lesion patients and normal controls, respectively. In the 115 HCC patients, the serum VEGF levels in patients with portal vein (PV) emboli (n = 26, 582.76 +/- 441.89 pg/ml), with metastasis (n = 43, 548.29 +/- 438.57 pg/ml) or with large HCC lesions (>/= 5 cm in diameter) (n = 69, 554.43 +/- 369.99 pg/ml) were significantly higher than those without PV-emboli (n = 89, 431.39 +/- 292.84 pg/ml), without metastasis (n = 72, 416.24 +/- 247.27 pg/ml) or with small HCC lesions (n = 42, 328.67 +/- 227.47 pg/ml). The serum VEGF levels in stage I, II, III, IVa and IVb HCC patients were 340.6 pg/ml, 451.55 +/- 307.84 pg/ml, 397.44 +/- 257.18 pg/ml, 486.10 +/- 397.73 pg/ml and 647.93 +/- 344.56 pg/ml, respectively.

CONCLUSIONThe pre-therapeutic serum VEGF levels in HCC patients appear to reflect the disease's potential activity of vascular invasion and metastasis.

Adult ; Aged ; Carcinoma, Hepatocellular ; blood ; pathology ; Endothelial Growth Factors ; blood ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Intercellular Signaling Peptides and Proteins ; blood ; Liver Neoplasms ; blood ; pathology ; Lymphokines ; blood ; Male ; Middle Aged ; Neoplasm Metastasis ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors

To investigate the role of angiogenesis in multiple myeloma (MM), bone marrow biopsy from 75 adults with newly diagnosed, untreated MM were evaluated. Microvessels were scored in at least 3 areas ( x 200 fields) of the highest microvessel density in representative sections of each bone marrow specimen using immunohistochemistry for CD34. Prognostic variables were also evaluated for the overall survival. Microvessel counts were significantly higher in patients with MM (n=69.42+/-9.67), compared with control (n=26.81+/-2.85). Microvessel density had a weak correlation with percentage of bone marrow plasma cells. By univariate analysis, age, beta2-microglobulin, serum albumin, serum creatinine, serum calcium, hemoglobin, platelet count, and bone marrow plasma cell percentage were correlated with survival. By multivariate analysis, age, serum albumin, serum creatinine, hemoglobin, platelet count and bone marrow plasma cell percentage were correlated with overall survival, whereas microvessel density was not. In summary, microvessel density in bone marrow of MM is significantly increased compared to control, but was not correlated with overall survival. Further studies regarding angiogeneic molecules are needed to determine the functional role of angiogenesis in MM.
Adult ; Aged ; Aged, 80 and over ; Bone Marrow/blood supply ; Endothelial Growth Factors/physiology ; Female ; Hematopoietic Stem Cell Transplantation ; Human ; Lymphokines/physiology ; Male ; Microcirculation ; Middle Age ; Multiple Myeloma/therapy ; Multiple Myeloma/mortality ; Multiple Myeloma/blood supply* ; Neovascularization, Pathologic/physiopathology* ; Survival Rate

Using immunohistochemical staining, we studied the relationship between the microvessel count (MC) and the expression of K-ras, mutant p53 protein, and vascular endothelial growth factor (VEGF) in 61 surgically resected non-small cell lung cancers (NSCLC) (42 squamous cell carcinoma, 14 adenocarcinoma, 2 large cell carcinoma, 2 adenosquamous carcinoma, and 1 mucoepidermoid carcinoma). MC of the tumors with lymph node (LN) metastasis was significantly higher than that of tumors without LN metastasis (66.1+/-23.1 vs. 33.8+/-13.1, p<0.05). VEGF was positive in 54 patients (88.5%). MC was 58.1+/-25.2 (mean+/-S.D.) in a x200 field, and it was significantly higher in VEGF(+) tumors than in VEGF(-) tumors (61.4+/-23.7 vs. 32.9+/-23.8, p<0.05). VEGF expression was higher in K-ras-positive or mutant p53-positive tumors than in negative tumors (p<0.05). MC was significantly higher in K-ras(+) tumors than in K-ras(-) tumors, although it did not differ according to the level of mutant p53 protein expression. Survival did not differ with VEGF, mutant p53, or K-ras expression, or the level of MC. In conclusion, there is a flow of molecular alterations from K-ras and p53, to VEGF expression, leading to angiogenesis and ultimately lymph node metastasis. Correlations between variables in close approximation and the lack of prognostic significance of individual molecular alterations suggest that tumorigenesis and metastasis are multifactorial processes.
Adult ; Aged ; Carcinoma, Non-Small-Cell Lung/*blood supply/chemistry/mortality ; Endothelial Growth Factors/*analysis ; Female ; Human ; Lung Neoplasms/*blood supply/chemistry/mortality ; Lymphokines/*analysis ; Male ; Middle Age ; Neovascularization, Pathologic/*metabolism ; Protein p53/*analysis ; Survival Rate ; ras Proteins/*analysis

OBJECTIVETo observe microvessel density(MVD), epithelial stromal vascular cuffing(VC) and expression of vascular endothelial growth factor(VEGF) in human cervical carcinomas and to clarify their significance in the invasion and metastasis of cervical carcinoma.

METHODSVEGF and CD34 were stained immunohistochemically (SP) in 57 cases of cervical carcinoma (30 cases of squamous cell carcinoma, 20 of adenocarcinoma 7 of glandular and squamous cell carcinoma), 29 cases of cervical intraepithelial neoplasia (CIN) and 16 cases of normal cervices, meanwhile, MVD and VC were also assayed.

RESULTSThere were significant differences among the above 5 groups for MVD P<0.01 . The VC pattern showed a significant difference between cervical carcinoma and CIN or control group P<0.01). The positive rates of VEGF in normal cervical epithelium, CIN, squamous cell carcinoma, adenocarcinoma, glandular and squamous cell carcinoma were 18.8% 3/16, 82.8% 24/29), 93.3% 28/30), 100% 20/20 and 7/7(100%), respectively. There were significant differences between these cervical lesion groups and the control group(P<0.001). The MVD showed significant differences between the positive pelvic node metastasis and negative pelvic node metastasis P<0.05). There was no significant correlation between the expression of VEGF and the tumor diameter, clinical stage, pathologic grade and pelvic node metastasis.

CONCLUSIONThe expression of VEGF may play an important role in the angiogenesis of cervical carcinoma. Degree of malignancy of cervical carcinoma has a close association with microvessel density.

Adult ; Aged ; Aged, 80 and over ; Endothelial Growth Factors ; analysis ; Female ; Humans ; Intercellular Signaling Peptides and Proteins ; analysis ; Lymphatic Metastasis ; Lymphokines ; analysis ; Microcirculation ; Middle Aged ; Uterine Cervical Neoplasms ; blood supply ; chemistry ; pathology ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors

Angiogenesis is a necessary step in tumor progression, and it correlates an unfavorable prognosis. In multiple myeloma, bone marrow microvessel density and angiogenesis grading correlated with plasma cell labeling index and are poor survival predictors, but the study of myeloma's angiogenesis is very rare. This article was to study the effect of multiple myeloma cell line conditioned media on the proliferation, migration and angiogenesis of human bone marrow endothelial cells (HBMEC). The multiple myeloma cell line conditioned media were obtained by using RPMI 1640 media containing 2% fetal bovine serum (FBS) to cultivate myeloma cell lines for 18 hours. Proliferation and migration of HBMEC were detected by using those media to cultivate HBMEC. Capillary tube formation was performed by using microcarriers cytodex-3 covered with HBMEC in three-dimensional fibrin matrices. The results showed that myeloma conditioned media induced HBMEC's proliferation and migration (P < 0.001), and those media induced capillary tube formation (length and width) of HBMEC (P < 0.001). It was concluded that myeloma cell lines induce HBMEC's proliferation, migration, and capillary tube formation by secreting several cytokines.
Bone Marrow Cells ; cytology ; Cell Division ; Cell Movement ; Endothelial Growth Factors ; analysis ; physiology ; Humans ; Intercellular Signaling Peptides and Proteins ; analysis ; physiology ; Lymphokines ; analysis ; physiology ; Multiple Myeloma ; blood supply ; chemistry ; pathology ; Neovascularization, Pathologic ; etiology ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors

Neovascularization is an important factor in the prognosis of brain tumor and many angiogenetic factors have been evaluated for prognostic significance. Among them, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) are known as potent angiogentic factors and mitogens. We evaluated seven cases of grade II brain astrocytoma. Four, group A, was diagnosed as anaplastic progression at their second operation, and three, group B, did not. Using monoclonal antibodies to bFGF and VEGF in paraffin embedded tissue from first operation, their immunoreactivity and differences between two groups were examined. The growth fractions of these tumor were also measured by Ki-67 monoclonal antibodies (MIB1). Immunostaining for bFGF in tumor cells were observed in both nuclei and cytoplasm, and for VEGF, mainly observed in the cytoplasm. Mean cell count number +/- standard deviation per high power field in each were as follows: 1) for bFGF, 20.08 +/- 6.38 in group A and 0.87 +/- 0.90 in group B (p< 0.01), 2) for VEGF, 43.75 +/- 17.09 in group A, and 0.8 +/- 1.06 in group B (p< 0.05) and 3) for the proliferation index with Ki-67 antibodies, 3.20 +/- 0.81 in group A and 0.77 +/- 1.03 in group B (p< 0.05). This data supports the assertion that angiogenetic factor such as bFGF and VEGF may contribute to progressive change of astrocytoma by tumor angiogenesis.
Adolescent ; Adult ; Astrocytoma/*pathology ; Brain/*blood supply ; Brain Neoplasms/*pathology ; Endothelial Growth Factors/*metabolism ; Female ; Fibroblast Growth Factor 2/*metabolism ; Human ; Lymphokines/*metabolism ; Male ; Middle Age ; Neovascularization, Pathologic/*genetics ; Prognosis ; Tumor Markers, Biological