OBJECTIVETo investigate the relationship between vascular endothelial growth factor C (VEGF-C) expression, VEGFR-3 expression, lymphangiogenesis and angiogenesis in human non-small cell lung cancer (NSCLC).

METHODSSeventy-six NSCLC samples were stained for VEGF-C, VEGFR-3 and CD34 with immunohistochemical methods. Assessment of lymphatic vessel density (LVD) and microvessel density (MVD) was performed. The expressions of VEGF-C in 24 fresh NSCLC samples were determined with Western blot assay.

RESULTSOf the 76 NSCLC cases, 55 were VEGF-C positive and 40 were VEGFR-3 positive in cancer cells. A significant positive correlation was found between VEGF-C expression and VEGFR-3 expression in cancer cells (P < 0.05). VEGF-C expression was negatively associated with differentiation of tumor cells (P < 0.05). VEGF-C expression and VEGFR-3 expression were positively associated with lymph node metastasis and lymphatic invasion (P < 0.05). LVD was positively related to VEGF-C expression, lymph node metastasis, lymphatic invasion and clinical stage (P < 0.05). There was a significant correlation between LVD and MVD (R = 0.732, P < 0.05). Patients with positive VEGF-C expression had worse outcomes than those with negative VEGF-C expression (P < 0.01).

CONCLUSIONSIn NSCLC, VEGF-C and VEGFR-3 are related to the lymphangiogenesis, angiogenesis, and occurrence and development of lung cancers. VEGF-C expression could be a useful predictor of poor prognosis in NSCLC.

Carcinoma, Non-Small-Cell Lung ; metabolism ; Endothelial Growth Factors ; biosynthesis ; Humans ; Immunohistochemistry ; Lung Neoplasms ; metabolism ; Vascular Endothelial Growth Factor C ; Vascular Endothelial Growth Factor Receptor-3 ; biosynthesis

OBJECTIVETo investigate intratumoral microvessel density (MVD) and expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (BFGF) in hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE) and to evaluate their significance.

METHODSMVD and expression of VEGF and BFGF in cancerous tissues were examined in forty specimens resected from patients with HCC using immunohistochemical methods. Among these patients, 20 patients received 1 to 7 treatments of TACE prior to II-phase surgical resection (TACE group), the other 20 patients were treated by operation without receiving any other treatment preoperatively (surgical group). There was no significant difference in clinical features between the two groups. MVD was assessed by counting immunostained endothelial cells within a certain area, and staining intensity of VEGF was assessed quantitatively with computer-assisted image analyzer. The expression of BFGF was determined by cell-positive or cell-negative.

RESULTSThe average MVD was 130.51 75.5 in TACE group and 152.35 58.80 in surgical group. There was no significant difference between the two groups (t=-1.021, P=0.341). Staining intensity of VEGF was 645.60 543.27 in TACE group, higher than in surgical group (158.28 188.48, t=281, P<0.001). BFGF-positive rate was 35% in TACE group and 40% in surgical group. There was no significant difference (x(2)=0.107, P=0.744).

CONCLUSIONSThe results indicate that survived cancerous tissue has rich vascularity and the expression of VEGF of the cancerous cells can be enhanced by TACE which may play an important role in reestablishment of blood supply to tumor after TACE.

Carcinoma, Hepatocellular ; metabolism ; pathology ; physiopathology ; therapy ; Catheterization ; Embolization, Therapeutic ; Endothelial Growth Factors ; biosynthesis ; Fibroblast Growth Factor 2 ; biosynthesis ; Humans ; Liver Neoplasms ; metabolism ; pathology ; physiopathology ; therapy ; Lymphokines ; biosynthesis ; Neovascularization, Pathologic ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors

To investigate the effect of vascular endothelial growth factor (VEGF) on beta1 integrin (VLA-4 and VLA-5) activation ability in K562 cells transfected with antisense VEGF121 cDNA, K562 cells were transfected with antisense (As), sense (S) and vector (V, pcDNA(3)). Flow cytometry was used to evaluate the expression rate of VLA-4 (CD49d/CD29) and VLA-5 (CD49e/CD29) and beta1 integrin activation ability in the transfected K562 cells. The results showed that the expression rates of VLA-4 and VLA-5 were more than 92% in the transfected K562 cells and there was no difference among the K562/V, K562/S and K562/As cells. However, beta1 integrin activated 9EG7 expression rate in K562/As cells was higher than that in K562/V cells [(75.6 +/- 10.5)% vs (41.2 +/- 2.1)%, P < 0.01)] after activation with beta1 integrin activator 8A2. It is concluded that function of beta1 integrin to be activated is restored in K562 cells transfected with antisense VEGF121 cDNA.
DNA ; genetics ; DNA, Antisense ; genetics ; Endothelial Growth Factors ; genetics ; metabolism ; Flow Cytometry ; Humans ; Integrin alpha4beta1 ; biosynthesis ; Integrin alpha5beta1 ; biosynthesis ; Intercellular Signaling Peptides and Proteins ; genetics ; metabolism ; K562 Cells ; Lymphokines ; genetics ; metabolism ; Transfection ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors

Tumor rapid growth depends on neovascularization. Vascular endothelial growth factor, the main mediator during the occurrence and formation of vascularization, has specific receptors whose expression rate shows difference of orders of magnitude between tumor and the normal tissue, so it can be used to transport toxin molecules to the proliferative tumor endothelial and kill cancer cells. In our experiment, we constructed fusion protein DT-VEGF by linking diphtheria toxin's forward 389 amino acids's gene and VEGF165 via a linker. DT-VEGF is expressed in E. coli and purified. Our experiment proves in can kill vascular endothelial cells specifically, and the inhibition of neovascularization of chicken chorionic membrane is also confirmed.
Angiogenesis Inhibitors ; biosynthesis ; Diphtheria Toxin ; biosynthesis ; genetics ; Escherichia coli ; genetics ; metabolism ; Genetic Vectors ; Humans ; Immunotoxins ; genetics ; Recombinant Fusion Proteins ; biosynthesis ; genetics ; Vascular Endothelial Growth Factors ; biosynthesis ; genetics

OBJECTIVETo study the relationship of TCM syndrome type of gastric mucosal epithelial growth factor (EGF), vascular endothelial growth factor (VEGF) and proliferative cell nuclear antigen (PCNA) in patients with chronic atrophic gastritis (CAG) for exploring the essence of TCM type and providing a theoretical basis of clinical treatment.

METHODSTCM syndrome type of 200 patients with diagnosis of CAG confirmed by fibro-gastroscope and pathological examination were differentially classified, and the expressions of EGF, VEGF and PCNA in different types were determined using immunohistochemistry.

RESULTSPatients were differentiated as Pi-Wei deficiency type (Type I ) in 72; Gan-Wei disharmony type (Type II ) in 43; Pi-deficiency with qi stagnation type (Type III) in 32; Wei-yin deficiency type (Type IV) in 24; Pi-Wei damp-heat type (Type V) in 14; and Wei-collateral stasis obstruction type (Type VI) in 5. The difference of PCNA expression level between Type II with Type I , III and IV was significant (P < 0.05). No significant difference in expression levels of EGF and VEGF was found among the 6 types (P > 0.05).

CONCLUSIONType I and II were the dominant TCM syndrome types in CAG patients; the high expression of PCNA might be a diagnostic evidence for Gan-Wei disharmony syndrome.

Adult ; Aged ; Aged, 80 and over ; Diagnosis, Differential ; Endothelial Growth Factors ; biosynthesis ; Female ; Gastric Mucosa ; metabolism ; pathology ; Gastritis, Atrophic ; diagnosis ; metabolism ; Humans ; Immunohistochemistry ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Proliferating Cell Nuclear Antigen ; biosynthesis ; Syndrome ; Vascular Endothelial Growth Factor A ; biosynthesis

To investigate the relationship of the expression of vascular endothelial factor (VEGF) and matrix metalloproteinase-2 (MMP-2) with the recurrence and metastasis of hepatocellular carcinoma (HCC), the expression of VEGF and MMP-2 in HCC tissue(n = 50) and in normal liver tissue(n = 30) were examined by immunochemistry. The results showed that the positive rates of VEGF and MMP-2 in HCC tissue were 86% and 60% respectively, and in normal liver tissue were 53.3% and 30% respectively. The positive rates of VEGF and MMP-2 in HCC were significantly higher than those in normal liver tissue. The positive rates of VEGF and MMP-2 in HCC with intra- or extra-hepatic metastasis were higher than those of HCC without metastasis. VEGF and MMP-2 play important roles in the invasion and metastasis of HCC.
Adult ; Aged ; Carcinoma, Hepatocellular ; metabolism ; pathology ; secondary ; Endothelial Growth Factors ; biosynthesis ; Female ; Humans ; Intercellular Signaling Peptides and Proteins ; biosynthesis ; Liver Neoplasms ; metabolism ; pathology ; Lymphokines ; biosynthesis ; Male ; Matrix Metalloproteinase 2 ; biosynthesis ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors

To investigate the relationship of the expression of vascular endothelial growth factor (VEGF) and C-myc with the occurrence, development and metastasis of gallbladder carcinoma, the expression levels of VEGF and C-myc in gallbladder carcinoma tissue (n = 30) and in normal gallbladder tissue (n = 20) were examined by immunochemistry. Results show that the positive rates of VEGF and C-myc in gallbladder carcinoma tissue were 80% and 63.3% respectively, and 45% and 25% respectively in normal gallbladder tissue. The positive rates of VEGF and C-myc were significantly higher in gallbladder carcinoma than in normal gallbladder tissue. The expression of VEGF and C-myc in gallbladder carcinoma related to the metastasis of gallbladder carcinoma. VEGF and C-myc play important roles in the occurrence, development and metastasis of gallbladder carcinoma.
Adult ; Aged ; Endothelial Growth Factors ; biosynthesis ; physiology ; Female ; Gallbladder Neoplasms ; metabolism ; pathology ; Humans ; Intercellular Signaling Peptides and Proteins ; biosynthesis ; physiology ; Lymphokines ; biosynthesis ; physiology ; Male ; Middle Aged ; Neoplasm Metastasis ; Proto-Oncogene Proteins c-myc ; biosynthesis ; physiology ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors

OBJECTIVETo investigate the the expression and hypoxic regulation of vascular endothelial growth factor(VEGF) and matrix metalloproteinase-9.

METHODSVEGF mRNA and MMP-9 mRNA were examined by reverse transcription-polymerase chain reaction (RT-PCR) in 43 esophageal carcinoma specimens including 18 para-tumorous esophageal tissues. The expression of VEGF protein and mean microvessel density (MVD) in 56 specimens were examined by immunohistochemical stain. The effect of hypoxia on VEGF and MMP-9 expression in esophageal cancer cell lines was quantitatively determined by enzyme linked immunosorbent assay (ELISA).

RESULTSThe VEGF expression in the tumorous tissue, being significantly correlated with MVD in the tumor, was remarkably higher than that in the para-tumorous tissue. VEGF and MVD expression in the tumor was significantly associated with stage and metastasis of esophageal carcinoma. The MMP-9 expression in the tumorous tissue, being uncorrelated with vessel count and clinicopathologic features in esophageal carcinoma, was significantly higher than that in the para-tumorous tissue. Hypoxia significantly increased the VEGF expression in esophageal cancer cell lines but did not affect the MMP-9 expression.

CONCLUSIONSThe expression of VEGF plays an important role in the angiogenesis and metastasis of esophageal cancer, which is regulated by hypoxia. VEGF may serve as a predictor of progression in esophageal carcinoma and a potential target for antiangiogenic therapy of esophageal carcinoma.

Endothelial Growth Factors ; biosynthesis ; genetics ; Esophageal Neoplasms ; metabolism ; Female ; Gene Expression Regulation ; Humans ; Hypoxia ; Lymphokines ; biosynthesis ; genetics ; Male ; Matrix Metalloproteinase 9 ; biosynthesis ; genetics ; Middle Aged ; Oxygen ; metabolism ; RNA, Messenger ; biosynthesis ; Reverse Transcriptase Polymerase Chain Reaction ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors

OBJECTIVETo compare the expressions of transforming growth factor alpha (TGFalpha), tumor necrosis factor alpha (TNFalpha), and vascular endothelial growth factor (VEGF) between pheochromocytoma (PHEO) tissues and normal adrenal medulla tissues.

METHODSThe mRNA expressions of TGFalpha, TNFalpha, and VEGF detected by RT-PCR, were compared between 22 PHEO tissues and 18 normal adrenal medulla tissues (according with the principle of medical ethnics). Immunohistochemistry staining was performed on 27 PHEO tissues and 14 normal adrenal medulla tissues. The comparisons of the protein expression of TGFalpha, TNFalpha, and VEGF were analyzed in both of PHEO tissues and normal adrenal medulla tissues.

RESULTSCompared with normal adrenal medulla tissues, the expressions of TGFalpha and TNFalpha mRNA and protein were higher in PHEO tissues, and VEGF145 mRNA expression was also higher in PHEO tissues, while there was no significant difference of the mRNA expression of VEGF121 and VEGF165 between these two tissues. Positive staining rates for VEGF of endothelial cells and tumor cells were higher in PHEO tissues than in normal adrenal medulla tissues. Expressions of the TGFalpha, TNFalpha, and VEGF protein were higher in extra-adrenal PHEO than in adrenal PHEO. The TNFalpha immunohistochemistry staining rate was higher in the malignant or multiple PHEO than in the benign or single PHEO.

CONCLUSIONSThe mRNA and protein expressions of TGFalpha, TNFalpha, and VEGF are higher in PHEO tissues than those in normal adrenal medulla tissues. Expressions of these cytokines vary in PHEO with different characteristic.

Adrenal Gland Neoplasms ; metabolism ; Adrenal Medulla ; metabolism ; Humans ; Pheochromocytoma ; metabolism ; RNA, Messenger ; biosynthesis ; genetics ; Transforming Growth Factor alpha ; biosynthesis ; genetics ; Tumor Necrosis Factor-alpha ; biosynthesis ; genetics ; Vascular Endothelial Growth Factors ; biosynthesis ; genetics

BACKGROUND: Angiogenesis is of crucial importance for tumor growth and development of metastases. Vascular endothelial growth factor (VEGF) has a potent angiogenic activity and mutations of the p53 gene has been thought to upregulate VEGF. The purpose of our study was to evaluate the prognostic significance of these tumor biomarkers for angiogenesis relative to the information derived from established clinicopathological parameters in gastric cancer. METHODS: In this study, we conducted an immunohistochemical investigation of VEGF and p53 expression in 145 tissue samples obtained from gastric cancer patients undergoing curative surgical treatment. To evaluate angiogenesis, microvessel density (MVD) was counted by staining endothelial cells immunohistochemically using anti-CD34 monoclonal antibody. RESULTS: High MVD was significantly associated with depth of tumor invasion and distant metastasis (p=0.004, 0.021, respectively). Moreover, overall survival for patients with high MVD were significantly lower than that of low MVD (p=0.048). Positive expression of VEGF correlated significantly with lymph node and distant metastasis (p=0.040, 0.048, respectively). However, no significant correlation was found between p53 expression and various clinicopathological parameters. VEGF positive tumors showed a higher MVD than VEGF negative tumors (p=0.028). The expression of p53 did not correlate with VEGF expression. Also, the relationship between the status of p53 expression and MVD had not statistically significant differences. In the multivariate analysis, status of VEGF, p53 expression and MVD were not an independent prognostic factor. CONCLUSION: VEGF seems to be an important, clinically relevant inducer of angiogenesis and angiogenesis assessed by the MVD may be a useful marker for predicting metastasis in gastric cancer. However, further studies are warranted to clarify the impact of p53 on the angiogenesis and the prognostic significance of angiogenesis in gastric cancer.
Adult ; Aged ; Endothelial Growth Factors/*biosynthesis ; Female ; Human ; Immunohistochemistry ; Male ; Middle Aged ; *Neovascularization, Pathologic ; Protein p53/*biosynthesis ; Stomach Neoplasms/*blood supply/metabolism/pathology ; Support, Non-U.S. Gov't