Objective To detect the expression of thromhospondin-1 （TSP-1） in gastric cancer and metastaticlymph node tissues， and to study its relationship of TSP-1 to clinicopathologic parameters or tumor angiogenesis. Methods The TSP-1 and vascular endothelial growth factor （VEGF） expressions and microvessel density （MVD） were evaluated by immunohistochemistry in 72 specimens obtained by gastric resection from patients with gastric cancer， including corres-ponding adjacent normal gastric mucosa tissues （distant from cancer ≥5 cm） and lymph nodes surrounding cancer. A semiquantitative scoring system was used for evaluating the staining. The relationship of TSP-1 to VEGF expression， MVD， or clinicopathologic parameters was analyzed. Results ① TSP-1 positive expression rate was 45.8% （33/72） in the primary gastric cancer tissues， 90.3% （65/72） in the corresponding adjacent normal gastric mucosa tissues， and 50.8% （30/59） in the metastatic lymph nodes tissues. The expressions of TSP-1 in the primary gastric cancer tissues and metastatic lymph nodes tissues were significantly lower than those in the adjacent normal gastric mucosa tissues （χ2=32.710，P=0.000；χ2=25.298， P=0.000）. The expression of TSP-1 had no statistical significance in the primary gastric cancer tissues as compared with in the metastatic lymph nodes tissues （χ2=0.327， P=0.568）. ② The expression of TSP-1 in the metastatic lymph nodes tissues was significantly lower than that in the non-metastatic lymph nodes tissues （Z=-2.573， P=0.010）. ③The expression of TSP-1 in the primary gastric cancer tissues and metastatic lymph nodes tissues suggested a negative correlation with VEGF （rs=-0.309， P=0.008；rs=-0.269， P=0.040） and MVD （rs=-0.348， P=0.003；rs=-0.272， P=0.037）. Conclusions TSP-1 expression is down-regulated and has a negative correlation with VEGF and MVD in the primary gastric cancer and the metastatic lymph nodes tissues. According to the present results， it seems likely that TSP-1 is a tumor angiogenesis inhibitor.
ObjectiveTo investigate the expression of tumor necrosis factor-α (TNF-α) in prostate cancer tissue and explore its relations with tumor angiogenesis. MethodsThe expression of TNF-α and CD105 were detected with two-step immunohistochemical staining technique in 20 cases of benign prostatic hyperplasia and 50 cases of prostate cancer between January 2010 and January 2012, and microvessel density (MVD) marked with CD105 was also measured. ResultsThe expressions of TNF-α and CD105 were higher in prostate cancer (41.72±8.67, 20.15±2.67) than those in benign prostatic hyperplasia (21.01±3.85, 4.34±1.67) (t'=13.990, P<0.001; t'=29.771, P<0.001). TNF-α and MVD were not correlated with age and size of tumor, but were positively correlated with tumor differentiation degree (rs=0.847, P<0.001; rs=0.776, P<0.001) and negatively correlated with clinical grades (rs=-0.769, P<0.001; rs=-0.842, P<0.001). ConclusionThe result indicates that over expression of TNF-α exists in prostate cancer. It may play an important role in the anginogenesis and carcinogenesis of prostate cancer.
The present paper aims to investigate whether or not vasculogenic mimicry (VM) exists in laryngeal squamous cell carcinoma (LSCC), and to elucidate its relationship to microvessel density (MVD), galectin-3 (Gal-3) expressionb and clinicopathological factors of patients with LSCC. VM, score of MVD and expression of Gal-3 protein were detected by immunohistochemistry and histochemistry in 83 specimens of LSCC tissue and 20 specimens of normal laryngeal tissue. The positive rate of VM in normal laryngeal tissues was 0%, and was 33.7% in LSCC tissues. There was a significant difference between the two groups (P<0.01). VM or MVD was significantly related to differentiation, pTNM stages and lymph node metastasis of LSCC (P<0.05), but not to age, gender and tumor site (P>0.05). And there was a positive correlation between every two of VM, score of MVD, and Gal-3 protein (P<0.05). The results suggest that expression of Gal-3 protein may be related to the initiation, angiogenesis and VM formation in LSCC; And VM, angiogenesis and Gal-3 protein may be involved in the development, invasion and metastasis of LSCC.
ObjectiveTo study the effects of angiogenesis inhibitor SU5416 on the microvessel density(MVD) of pancreatic cancer and to evaluate its influence on the growth and metastasis of pancreatic cancer. Methods A rat model of pancreatic cancer was established with dimethylbenzanthracine(DMBA). 60 rats with pancreatic cancer were randomly divided into 4 groups: saline group, 5-Fu group, SU5416 group, 5-Fu and SU5416 group. Thirteen weeks after injection, the microvascular density (MVD) of pancreatic cancer was detected.Results The microvascular densities (MVD) were (12.3±3.2)%, (11.4±3.8)%, (2.1±1.5)% and (1.8±1.1)% in the saline group, 5-Fu group, SU5416 group and 5-Fu+SU5416 group respectively. The MVDs in the SU5416 group and 5Fu+SU5416 group were statistically lower than those in the saline group and 5-Fu group(P＜0.05). There was no significant difference between the 5-Fu group and saline group(Pgt;0.05). ConclusionSU5416 can inhibit the microvascular growth in pancreatic cancer. And the inhibition can be enhanced when combined with chemotheraputic drugs.
目的 通过复制人肝癌细胞株HepG2裸鼠皮下移植瘤模型，观察绿茶提取物表没食子儿茶素没食子酸酯（EGCG）干预对HepG2移植瘤新生血管生成的影响。 方法 瘤体接种复制HepG2移植瘤模型，荷瘤裸鼠20只随机分组，实验组给予EGCG溶液每日20 mg/（kg·只），腹腔注射3周，对照组给予等量灭菌注射用水3周，末次用药24 h，后处死裸鼠，剥离移植瘤。常规病理切片观察移植瘤组织结构；逆转录-聚合酶链式反应和免疫组织化学法检测移植瘤缺氧诱导因子-1α（HIF-1α）、血管内皮生长因子（VEGF）mRNA及蛋白表达，并通过检测CD34表达计数瘤组织微血管密度（MVD）。 结果 组织病理学观察实验组移植瘤见大量坏死区，瘤体内血管数量明显少于对照组；实验组HIF-1α、VEGF mRNA及蛋白表达水平比对照组均明显下调（P＜0.05），实验组MVD比对照组明显下降（P＜0.05）。 结论 EGCG可抑制荷瘤裸鼠HepG2移植瘤新生血管生成。
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.
【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 investigate the effects of sustained-release basic fibroblast growth factor (bFGF) on healing of bile duct defect. Methods A model of bile duct wall defect (2 cm in length and 1/3-2/3 of the bile duct circumference in width) was made in 24 pigs (male or female, weighing 15-30 kg), and then defect was repaired with sustained-release bFGF collagen membrane (2.0 cm × 1.0 cm × 0.5 cm in size) in the experimental group (n=12) or with collagen membrane (2.0 cm × 1.0 cm × 0.5 cm in size) alone in the blank control group (n=12). Another 4 healthy pigs were used to obtain normal bile duct as normal control group. The survival condition of pigs was observed after operation; at 1, 2, and 3 months after operation, the blood sampling was collected to test the changes of liver function, and the bile duct specimens were harvested to count the microvessel density (MVD) and submucosal gland by HE staining and immunohistochemistry staining; and at 3 months after operation, cholangiography examination was done. Results All the animals survived to completion of the experiment. Intra-abdominal adhesion was serious in the experimental and blank control groups at 1 week after operation, but the adhesion was markedly improved in the experimental group when compared with the blank control group with time passing. The liver function test showed that alkaline phosphatase in the experimental group was significantly lower than that in the blank control group at 2 and 3 months (P lt; 0.05), but no significant difference in aspartate aminortransferase, total bilirubin, and albumin was found among 3 groups (P gt; 0.05). The histology and immunohistochemistry staining observations showed that the regeneration rates of submucosal glands and epithelium in the experimental group were faster than those in the blank control group; defect was covered with the epithelium at 2 months, and the structure was similar to that of normal control group at 3 months; and the edema and inflammation infiltration were reduced when compared with the blank control group. The counts of MVD and submucosal gland were significantly higher than those in blank control group and normal control group at 1 month after operation (P lt; 0.05), and then decreased and remained at normal levels at 2 months after operation. There was a positive correlation between submucosal gland counting and MVD counting in 3 groups after operation (P lt; 0.01). The cholangiography examination showed no biliary dilatation or cholelithiasis after 3 months in experimental group and blank control group. Conclusion Sustained-release bFGF can promote healing of bile duct defect by accelerating the vascularization, gland regeneration, and epithelialization.
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 explore the expressions of galectin-3 protein and CD105 protein in colorectal cancer and the relationship with clinicopathologic features. MethodsThe expressions of galectin-3 protein and CD105 protein 〔microvessel density (MVD)〕 were detected in 60 cases of colorectal cancer tissues, 30 cases of adenoma tissues, and 30 cases of normal mucosa tissues (at least 4 cm far from carcinoma) by MicrowaveEliVisionTM immunohistochemistry, and the relationship with clinicopathologic features was analyzed. ResultsThe expressions of galectin3 protein and MVD in normal mucosa tissues, adenoma tissues, and cancer tissues gradually increased (Plt;0.05). The expression of galectin-3 protein and MVD in colorectal cancer tissues were correlated to TNM stage, invasive depth, and lymph node metastasis (Plt;0.05， Plt;0.01), and the expression of glectin-3 protein was also correlated to differentiated degree (Plt;0.05). The expression of galectin-3 protein in colorectal cancer tissues was positively correlated to MVD (r=0.420， Plt;0.01). ConclusionsThe high expressions of galectin-3 protein and CD105 protein are correlated to the high invasion ability and lymph node metastasis, which may be potential sensitive index to predict the invasion and metastasis of colorectal cancer.