Objective To evaluate the effect on microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression of combining radiofrequency ablation (RFA) with arsenious acid (AA) locally treating liver VX2 tumor in rabbits. Methods Twenty-eight New Zealand White rabbits with implanted liver VX2 tumors were randomly divided into four groups, control group (n=7), AA group (n=7), RFA group (n=7) and combination (RFA+AA) group (n=7). All rabbits were killed 14 days after treatment. MVD and VEGF expression were examined by immunohistochemistry. Results The MVD degraded one by one in control group,AA group,RFA group and RAF+AA group, which were (38.50±0.44), (23.07±0.47), (18.65±0.39) and (11.36±0.36)/HP respectively, compared while each two groups, P＜0.05. The VEGF expression also degraded one by one, the ratio of positive cases were 7/7, 5/7, 4/7 and 2/7 respectively, compared while each two groups, P＜0.05. There was positive correlation between VEGF expression and MVD (Person conefficient of product-moment correlation r=0.47, P＜0.01). Conclusion Combining RAF with AA therapy can greatly decrease MVD and VEGF expression of tumor tissue.
【Abstract】Objective To investigate the correlation between the expression of fibronectin (FN) in extracellular matrix (ECM) and angiogenesis of gastric carcinoma.Methods The expressions of FN and vascular endothelial growth factor (VEGF) in 20 specimens of normal gastric tissue (normal group) and 80 specimens of gastric carcinoma tissue(gastric carcinoma group) were detected by EnVisonTM immunohistochemical technique. Tumor microvessel densit y (MVD) was evaluated by using antiCD34 antibody as an endothelial marker by the same technique as well. Results The immune complex of FN stained in brown were distributed around glands and in connective tissue of gastric specimens. In normal group, the staining of FN formed intact linear structure at basement membrane and presented regular striae form in connective tissue. In gastric carcinoma group, the integrity of linear structure of FN staining at basement membrane were destroyed to different extent and the staining of FN in connective tissue were changed deeper and distributed irregularly. The expression of VEGF and the value of MVD in the gastric carcinoma group was higher than those in normal group’s(P＜0.01, P＜0.01, respectively).This study indicated, that in gastric carcinoma group, the degree of FN expression in connective tissue had statistically positive correlations with the degree of VEGF expression and MVD value(P＜0.01, P＜0.05, respectively). Whereas the destruction extent of linear structure of FN staining at basement membrane showed no correlation with VEGF expression and MVD value(Pgt;0.05, Pgt;0.05, respectively).Conclusion The higher expression of FN in connective tissue of gastric carcinoma may well play a critical role in its process of angiogenesis and vasculogenesis. There may be an cooperative interactions between FN and VEGF in the process of angiogenesis and vasculogenesis of gastric carcinoma.
Objective To study the expression of inducible nitric oxide synthase (iNOS)，endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) in human gastric cancer and their relationship with tumor angiogenesis and to investigate the interaction of NOS and VEGF in gastric cancer. Methods The expression and distribution of VEGF, iNOS and eNOS in 34 gastric cancer specimens were detected with immunohistochemistry. Microvessel density (MVD) was counted with FⅧRAg immune specific staining. Results The expression rates of iNOS, eNOS and VEGF in 34 gastric cancers were 73.5%, 82.4% and 91.2% respectively. The expression of VEGF had a significant positive relation with iNOS, but not with eNOS. The MVDs of VEGF or iNOS positive gastric cancers were obviously higher than those of VEGF or iNOS negative gastric cancers. There was no significant difference between the MVDs of eNOS positive gastric cancers and eNOS negative ones. Conclusion MVD increases with increase of expression of VEGF and iNOS in gastric cancer. It is indicated that VEGF and iNOS can promote gastric cancer angiogenesis. VEGF and iNOS have a significant positive correlation, which suggests that in human gastric cancer, iNOS plays an important role in the production and action of VEGF.
ObjectiveTo investigate the clinicopathological significance of integrin α5β1 expression and microvessel density(MVD) in gastric cancer(GC) and the correlation of MVD with integrin α5β1. MethodsThe expression of integrin α5β1 was detected by means of immunohistochemical staining (SP method) on paraffinembeded tissue specimens from 35 primary gastric carcinoma(PGC), 10 metastasic lymph node of gastric cancer and 8 chronic superficial gastritis (CSG). Vascular endothelial cells were stained immunohistochemically using antiCD34 monoclonal antibody to recognize microvessel(MV) in 35 cases of PGC and 8 CSG, MV was counted in 4 hot spot per slide under lightmicroscope (×400) and the average was defined as MVD. The results combined with clinicopathological parameters were analyzed statistically to characterize the role of integrin α5β1 and MVD in the progression of gastric cancer. ResultsIntegrin α5β1 expression and MVD in PGC were significantly higher than those in CSG respectively （t=3.32, P lt;0.01; t=2.30, Plt;0.05）; the expression of integrin α5β1 in PGC showed only a correlation with the invasion depth of tumor (t=2.29, Plt;0.05） while MVD showed all correlations with invasion depth,lymph node status and TNM stage （t=3.07, Plt;0.01; t=2.48, Plt;0.05; t=2.94,Plt;0.01）. Neither integrin α5β1expression nor MVD showed a relation with differential of PGC （t=0.15, Pgt;0.05; t=0.41, Pgt;0.05）. Integrin α5β1 was significantly overexpressed in lymph node metastatic cancer compared with that in corresponding PGC （t=2.45, Plt;0.05）; the difference of MVD showed no statistical significance among levels of integrin α5β1 expression in PGC （F =1.43,P＞0.05） and it showed no correlation with integrin α5β1 expression（r= 0.156, P=0.37）.Conclusion Overexpression of integrin α5β1 is present in GC and associates with the progression of tumor, implying that it may be viewed as the indicator of invasion and metastasis and the candidate target of gene therapy of gastric cancer. However, integrin α5β1 may not play an important role in the vascularization of GC.
ObjectiveTo study the mechanism of reducing the intratumoral microvessel density (MVD) by Ginsenoside Rg3 (Rg3) combined with cytotoxic agent in xenotransplanted human breast infiltrating duct carcinoma in nude mice. MethodsSixteen female nude mice were randomly divided into 4 groups to receive cyclophosphamid (16 mg/kg,qd) combined with Rg3 (10 mg/kg, qd),Rg3(10 mg/kg,qd) alone,cyclophosphamid (16 mg/kg,qd) alone and 0.5% sodium carboxymethyl cellulose (0.5 ml,qd) respectively for 55 days. Breast cancer mass were weighed and sampled for light microscopic observation. The intratumor MVD was examined by immunohistochemical staining. ResultsThe tumor weight of treated group was significantly lower than that of control group. The tumor weight of the Rg3 combined with CTX group was lower than that of Rg3 group. The MVD value of Rg3 group was significantly lower than that of CTX group and control group. The MVD was significantly reduced in the Rg3 combined with CTX group than that in the others.ConclusionRg3 combined with CTX can inhibit the growth of xenotransplanted human breast infiltrating duct carcinoma, and reduce the intratumoral MVD.
ObjectiveTo discuss the feasibility of treating noumenon tumor by antiangiogenesis.MethodsRelated literatures of recent 5 years was reviewed.ResultsTumor angiogenesis were related closely with growth, development, metastasis and prognosis of noumenon tumor. It was possible to inhibit the growth and metastasis of noumenon tumor with antiangiogenesis in vitro and vivo.ConclusionAntiangiogenesis will be a new therapy of treating noumenon tumor.
Objective To investigate the relationship of vascular endothelial growth factor (VEGF), microvessel density (MVD) and progression of gastric carcinoma (GC). Methods The expression of VEGF and MVD in archival waxembedded specimens of 80 cases of GC and 20 gastric benign disease (GBD) were examined by using immunohistochemical staining. ResultsThe positive expression rate (PER) of VEGF in GC was 75.0%, and in GBD 5.0% (P＜0.05). The PER of VEGF in GC with invasive serosa was 95.5%, in those without serosal invasion 50.0% (P＜0.05). 82.8% was the PER of VEGF in GC with lymph node metastasis, 54.5% without lymph node metastasis (P＜0.05).The PER of VEGF in GC accompanied by distant metastasis was 100%, higher than that without distant metastasis (71.0%, P＜0.05). PER of VEGF in pTNM Ⅰ+Ⅱ was 53.1%, in Ⅲ+Ⅳ 89.6% (P＜0.05). MVD correlated significantly with depth of invasion, lymph node metastasis,distant metastasis and pTNM stages (P＜0.05). There was correlationship between MVD and VEGF (P＜0.05).Conclusion VEGF expression upregulation and MVD contribute to the progression of gastric carcinoma.
ObjectiveTo explore the relation between vascular endothelial growth factor （VEGF） and the formation of tumor thrombosis in the main trunks of portal vein (PVTT). MethodsTumor specimens were collected from 36 patients (16 patients with PVTT, the other patients without PVTT and metastasis) undergoing resection of hepatocellular carcinoma (HCC) and portal thrombectemy, PVTT specimens of 16 patients named group A1, the same patients’ with HCC named group A2, tumor specimens of the other patients named group B. In situ hybridization and immunohistochemistry were used to investigate VEGF mRNA, protein and microvessel density (MVD) on surgical specimens. The intensity was evaluated using a computer image analyzercell analysis system.ResultsVEGF mRNA expression was detected in the tumor’ cell of the specimens. The expression rates of VEGF mRNA in the group B, A2, A1 were 30%, 100%, 100% respectively, and the expression rates of VEGF mRNA in group A2 and A1 were higher than that in group B （P＜0.01）. The intensity of VEGF mRNA in group A2 （0.078 5±0.019 6） were lower than in group A1 （0.194 4±0.059 0） （P＜0.01）. VEGF protein expression was often detected in the tumor cell, vascular endothelial cell and fibroblast cells. Invasion was detected in small vein in group A2, more tumor cell colony detected in group A1. The expression rates of VEGF protein in group B, A2, A1 were same as VEGF mRNA; the intensity of VEGF protein in A1 （0.165 6± 0.034 5） was higher than in group A2 （0.108 1±0.024 3） （P＜0.01）. MVD in group B, A2, A1 was 31.9±14.4, 63.3±15.1, 116±27.6/view of 200 microscopefield, MVD in group A1 was higher than group A2 （P＜0.01）, higher in group A2 than in group B. There was a statistically significant correlation between the intensity of VEGF expression and MVD in group B,A2 and A1. ConclusionVEGF could play an important role in the invasion, metastasis of HCC and the formation of PVTT. Angiogenesis in tumor is correlated well with the progression of HCC.
Objective To investigate the relationship between microvessel density(MVD) and lymph node metastasis and prognosis in gallbladder carcinoma. MethodsThe MVD in 42 gallbladder carcinoma by immunohistochemical SP method using a polyclonal antibody to FⅧ and the relationship between MVD and histologic types, depth of invasion, lymph node metastasis, distant metastasis and prognosis was studied. Results The value of MVD was correlated with the depth of invasion (P＜0.05), lymph node metastasis (P＜0.01) and distant metastasis (P＜0.05). It was not significantly related to the pathologic pattern and tumor differentiation. The significantly negtive correlation was found between MVD and 5-year survival in patients with gallbladder carcinoma. Conclusion MVD is bly related to the metastasis of gallbladder carcinoma. It may serve as a prognotic factor.
This study was designed to define the microvessel density (MVD) in breast carcinoma and benign breast disease and the relationship of microvessel density with the tumor size, histologic grade, and lymph node status. Under light microscopy, the microvessels by staining their endothelial cells immunocytochemically for factor Ⅷ were highlighted. Results: The mean level of MVD of breast carcinoma was significantly higher than that of benign disease (Ｐ＜0.01); the MVD of breast carcinoma was associated with tumor size (Ｐ＜0.05), histologic grade (Ｐ＜0.05), and axillary node status (Ｐ＜0.05), but no association with estrogen receptor. These show that MVD of breast carcinoma is significantly higher than that of benign breast disease, and MVD of breast carcinoma is one of significant prognostic indicators.