Adult ; Aged ; Endothelial Growth Factors ; analysis ; physiology ; Female ; Humans ; Intercellular Signaling Peptides and Proteins ; analysis ; physiology ; Lymphokines ; analysis ; physiology ; Male ; Middle Aged ; Nasal Polyps ; chemistry ; etiology ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factor Receptor-2 ; analysis ; Vascular Endothelial Growth Factors

OBJECTIVETo investigate the correlation between epidermal growth factor (EGF) and overexpression of vascular endothelial growth factor (VEGF) in hepatocellular carcinoma (HCC).

METHODSExpressions of EGF, VEGF and microvessel density were studied through immunohistochemical SABC method in 36 HCC specimens, their paraneoplastic liver tissues and 6 normal liver tissues with the correlation between these parameters analyzed. Recombinant human EGF was used to stimulate HepG(2) cells and semi-quantitative reverse transcription PCR was adopted to detect the expression of VEGF in HepG(2) cells.

RESULTSThe positive rates of EGF and VEGF expression in HCC tissue were 75.0% and 88.9%. There was positive correlation between EGF and VEGF expression (P < 0.01, r = 0.462). Recombinant human EGF could induce the expression of VEGF in HepG(2) cells in a dose and time dependent manner.

CONCLUSIONThe expression of EGF in HCC underlies the overexpression of VEGF in HCC.

Adult ; Aged ; Carcinoma, Hepatocellular ; metabolism ; Endothelial Growth Factors ; analysis ; Epidermal Growth Factor ; analysis ; Female ; Humans ; Intercellular Signaling Peptides and Proteins ; analysis ; Liver Neoplasms ; metabolism ; Lymphokines ; analysis ; Male ; Middle Aged ; Neovascularization, Pathologic ; Statistics as Topic ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors

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

OBJECTIVETo investigate the feasibility of endothelialization of bioprosthesis by transfer of vascular endothelial growth factor (VEGF) gene.

METHODSBovine pericardium treated with glutaraldehyde and L-glutamic acid was positioned into the pig right atrium. pcD(2)/hVEGF(121) gene (1 mg) was transferred into the right ventricular myocardium using surgical sutures Reverse transcri ption polymerase chain reaction (RT PCR) was employed to evaluate the expression of myocardial VEGF mRNA. The determination of concentrations of VEGF protein in blood from both the right atrium and peripheral vein, and histological and ultrastructural analysis of implanted bovine pericardium were completed simultaneously.

RESULTSThe concentration of VEGF derived from the right atrium in pcD(2)/hVEGF(121) group was significantly higher than that in the pcD(2) group 10 days after VEGF gene transfer (P < 0.01). The expression of myocardial VEGF mRNA in pcD(2)/hVEGF(121) group was much higher in comparison with that in the pcD(2) group. The morphological analysis demonstrated that the coverage rate of host endothelium in the pcD(2)/hVEGF(121) group was 2.6 times as fast as that in the pcD(2) group at 16 days after VEGF(121) gene transfer (P < 0.01). Entire endothelialization occurred at 30 days after VEGF gene transfer. In addition, higher expression of myocardial VEGF mRNA was still available.

CONCLUSIONSVEGF gene transfer by surgical suture can remarkably accelerate endothelialization of bioprosthesis, which may provide a new approach for inhibiting biological valve calcification and improve biocompatibility and long-term durability of the bioprosthesis.

Animals ; Bioprosthesis ; Endothelial Growth Factors ; analysis ; genetics ; Endothelium, Vascular ; physiology ; Female ; Gene Transfer Techniques ; Heart Valve Prosthesis ; Humans ; Lymphokines ; analysis ; genetics ; Male ; RNA, Messenger ; analysis ; Swine ; 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

BACKGROUNDThe mechanism of retinal neovascularization is not understood completely. Many growth factors are involved in the process of retinal neovascularization, such as vascular endothelial growth factor (VEGF) and pigment epithelium-deprived factor (PEDF), which are the representatives of angiogenic and antiangiogenic molecules respectively. Oxygen induced retinopathy (OIR) is a useful model to investigate retinal neovascularization. The present study was conducted to investigate the feasibility of small interference RNA (siRNA) targeting VEGF gene in attenuating oxygen induced retinopathy (OIR) by regulating VEGF to PEDF ratio (VEGF/PEDF).

METHODSIn vitro, cultured EOMA cells were transfected with VEGF-siRNA (psi-HI(TM)/EGFP/VEGF siRNA) and Lipofectamine(TM) 2000 for 24, 48, and 72 hours, respectively. Expression of VEGF mRNA was evaluated by real time polymerase chain reaction (PCR) and the level of VEGF protein was analyzed by Western blotting. In vivo, OIR model mice were established, the mice (C57BL/6J) received an intra-vitreal injection of 1 µl of mixture of psi-HI(TM)/EGFP/VEGF siRNA and Lipofectamine 2000. Expressions of retinal VEGF and PEDF protein were measured by Western blotting, retinal neovascularization was observed by fluorescein angiography, and quantified.

RESULTSIn vitro psi-HI(TM)/EGFP/VEGF siRNA treatment significantly reduced VEGF mRNA and protein expression. In vivo, with decreased VEGF and VEGF-PEDF ratio, significant attenuation of neovascular tufts, avascular regions, tortuous, and dilated blood vessels were observed in the interfered animals.

CONCLUSIONSVEGF plays an important role in OIR, and the transfection of VEGF-siRNA can effectively downregulate VEGF expression in vivo, accompanied by the downregulation of VEGF-PEDF ratio, and simultaneous attenuation of retinal neovascularization was also observed. These findings suggest that VEGF/PEDF may serve as a potential target in the treatment of retinal neovascularization and RNA interference targeting VEGF expression, which represents a possible therapeutic strategy.

Animals ; Eye Proteins ; analysis ; Mice ; Mice, Inbred C57BL ; Nerve Growth Factors ; analysis ; RNA, Small Interfering ; genetics ; Retinal Neovascularization ; therapy ; Serpins ; analysis ; Vascular Endothelial Growth Factor A ; analysis ; genetics ; physiology

PURPOSE: Lymphatic spread of tumor is an important prognostic factor for patients with non-small cell lung carcinoma (NSCLC). Vascular endothelial growth factor-C (VEGF-C) and VEGF-D play important roles in lymphangiogenesis via the VEGF receptor 3 (VEGFR-3). We sought to determine whether VEGF-C, VEGF-D and VEGFR-3 are involved in the clinical outcomes of patients with resected NSCLC. MATERIALS AND METHODS: Using immunohistochemical staining, we investigated the protein expressions of VEGF-C, VEGF-D and VEGFR-3 in the tissue array specimens from patients who underwent resection for NSCLC. The immunoreactivity for p53 was also examined. The clinicopathological implications of these molecules were statistically analyzed. RESULTS: Analysis of a total of 118 specimens showed that VEGF-C, VEGF-D and their co-expression were significantly associated with more advanced regional lymph node metastasis (p=0.019, p=0.044 and p=0.026, respectively, N2 versus N0 and N1). A VEGFR-3 expression had a strong correlation with peritumoral lymphatic invasion (p=0.047). On the multivariate analysis for survival and recurrence, pathologic N2 lymph node metastasis was the only independent prognostic factor, but none of the investigated molecules showed any statistical correlation with recurrence and survival. CONCLUSIONS: The present study revealed that high expressions of VEGF-C and VEGF-D were strongly associated with more advanced regional lymph node metastasis in patients with resected NSCLC.
Carcinoma, Non-Small-Cell Lung ; Humans ; Lung ; Lymph Nodes ; Lymphangiogenesis ; Multivariate Analysis ; Neoplasm Metastasis ; Receptors, Vascular Endothelial Growth Factor ; Recurrence ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factor C ; Vascular Endothelial Growth Factor D ; Vascular Endothelial Growth Factor Receptor-3 ; Vascular Endothelial Growth Factors

OBJECTIVETo detect the expression of vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), p16 protein in lip cancers and oral squamous cell carcinoma (OSCC) as well as their clinicopathological significance.

METHODSImmunohistochemisty for expression VEGF, EGFR, P16 were carried out in 69 cases of lip cancers and OSCC.

RESULTSExpression of VEGF, EGFR, p16 protein in OSCC and lip cancers was respectively 71.01%, 46.37%, 28.98% and there were no significance between their positive expressions (P > 0.05) as well as in different sites of them (P > 0.05). Expression of VEGF was respectively 71.01% in cancers and 10.00% in non-tumor tissues, there was statistic significance among those (P < 0.05).

CONCLUSIONSThe results show that there is no correlation to the expression of VEGF, EGFR and P16 protein in OSCC and lip cancers. It is suggests that the expression of VEGF might become one of the useful markers for OSCC.

Adult ; Aged ; Carcinoma, Squamous Cell ; chemistry ; pathology ; Cyclin-Dependent Kinase Inhibitor p16 ; analysis ; Endothelial Growth Factors ; analysis ; Female ; Humans ; Immunohistochemistry ; Intercellular Signaling Peptides and Proteins ; analysis ; Lip Neoplasms ; chemistry ; pathology ; Lymphokines ; analysis ; Male ; Middle Aged ; Mouth Neoplasms ; chemistry ; pathology ; Receptor, Epidermal Growth Factor ; analysis ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors

OBJECTIVETo detect the biological factor association with metastasis and recurrence of hepato cellular carcinoma (HCC).

METHODSLabeled streptavidin biotin method was performed to study VEGF, uPA and ICAM-1 protein, and antigen of PCNA expression in 123 patients with HCC. Venous invasion was observed under microscope at the same time.

RESULTSThe expression rate of VEGF was higher in HCC with intra-hepatic metastasis in group B than in HCC without PVTT/metastasis in group A (P < 0.01) and higher in HCC with PVTT in group C and PVTT in group D higher than in group B (P < 0.05). The expression rate of uPA protein was higher in group B than in group A (P < 0.01), but no significant difference in groups B and C. The expression rate of ICAM-1 showed no significant difference in the four groups. MVD and PCNA-LI increased gradually from group A to D. The rate of microscopic venous invasion in group B was higher than in group A (P < 0.05), in group D higher than in group B (P < 0.05), but no significant difference was observed between groups B and C, groups C and D (P = 0.16, 0.13 respectively). The rate of postoperative recurrence of HCC was higher in group B than in group A, and lower than in group C. Multivariate regression analysis: showed postoperative recurrence was correlated very well with microscopic venous invasion (r = 0.783, P < 0.01), and MVD (r = 0.143, P < 0.05). Metastasis of HCC were associated very well with PCNA-LI (r = 0.590, P < 0.01) and MVD (r = 0.179, P < 0.05), and negatively correlated with the rate of ICAM-1 expression (r = -0.183, P < 0.01).

CONCLUSIONSVEGF, uPA and ICAM-1 protein expression and proliferation of cancer cells could contribute to the formation of PVTT, metastasis and postoperative recurrence of HCC. Over-proliferated cancer cells in HCC could be the direct factor of intrahepatic metastasis and formation of PVTT, and microscopic venous invasion may be a significant factor to predict postoperative recurrence of HCC.

Carcinoma, Hepatocellular ; blood supply ; pathology ; secondary ; Endothelial Growth Factors ; analysis ; Humans ; Immunohistochemistry ; Intercellular Adhesion Molecule-1 ; analysis ; Intercellular Signaling Peptides and Proteins ; analysis ; Liver Neoplasms ; blood supply ; chemistry ; pathology ; Lymphokines ; analysis ; Neoplasm Recurrence, Local ; Proliferating Cell Nuclear Antigen ; analysis ; Urokinase-Type Plasminogen Activator ; analysis ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors

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