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.
【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.
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.
ObjectiveTo detect the expressions of microvessel density (MVD)-CD34 and vascular endothelial growth factor (VEGF) in hepatic alveolar hydatid tissue in gerbil model and explore their clinical significances. MethodsSixty health gerbils were randomly equally divided into two groups, an experimental group and a sham operation group, each gerbil was given liver vaccination by opening their abdominal. Each gerbil in the experimental group was injected with approximately 400 echinococcus protoscoleces (0.1 mL), and each gerbil in the sham operation group received a corresponding volume of physiological saline. Six gerbils were sacrificed on day 20, 40, 60, 80, and 100. The hepatic alveolar hydatid tissue (AE) and its surrounding liver tissue (HSAE) were collected from the experimental group and the normal liver tissue (NL) was collected from the sham operation group, and the expressions of MVD-CD34 and VEGF were detected by immunohistochemistry staining (EnVision method). ResultsEchioncoccus multilocularis hydatid tissues were observed over the liver and in the partly abdominal cavity in the experimental group each gerbil by general observation. The expressions of CD34 and VEGF were observed in the AE at each time point after infection and located in the cytoplasmic of endothelial cells. The number of MVD-CD34 of AE at each time point in the AE was (9.83±3.87)/HP, (25.33±6.71)/HP, (34.50±5.50)/HP, (37.67±5.71)/HP and (44.67±4.93)/HP, respectively, which were significantly higher than those in the HSAE〔0/HP, (1.17±0.98)/HP, (3.50±1.38)/HP, (5.83±2.71)/HP, and(8.83±2.48)/HP, respectively〕and NL (all were 0), P < 0.05. The point of VEGF at each time point in the AE was 2.95±0.46, 3.90±0.68, 4.27±1.05, 5.33±0.95, and 4.50±0.81 respectively, which were significantly higher than those in the HSAE(1.07±0.63, 1.38±0.75, 1.55±0.83, 1.67±0.47, 2.10±0.55, respectively) and NL (1.02±0.83, 1.12±0.63, 1.26±0.26, 1.20±0.74, 1.21±0.28), P < 0.05. ConclusionAngiogenesis might be involved in infiltrated growth of alveococcus, and VEGF might contribute to angiogenesis of alveolar hydatid tissue.
ObjectiveTo investigate the expression of keratinocyte growth factor (KGF) and cyclooxygen-ase-2 (COX-2) protein and microvessel density (MVD), and to explore their function and mechanism in the multistep process of gastric cancer. MethodsThe expressions of KGF and COX-2 protein in 64 samples of gastric cancer and 30 cases of normal gastric mucosa tissues were detected by immunohistochemistry. The MVD was detected by staining the endothelial cells in microvessles using anti-CD34 antibody. ResultsThe positive rate of KGF and COX-2 protein expression in gastric cancer were 65.6% (42/64) and 79.7% (51/64), respectively, which was significantly higher than that in normal gastric mucosa tissues 〔(23.3%, 7/30), P=0.046; (13.3%, 4/30), P=0.008〕. The MVD of gastric cancer was 31.8±8.0, which was significantly higher than that of normal gastric mucosa tissues (14.3±6.1), P=0.000. The MVD in gastric cancer with coexpressive KGF and COX-2 protein was 35.9±5.7, which was significant higher than that with non-coexpressive KGF and COX-2 protein (25.7±7.0), P=0.000. Both the expression of KGF and COX-2 protein were related to the invasion of serosa, lymph node metastasis and TNM staging (Plt;0.05, Plt;0.01). The MVD of gastric cancer tissues was related to lymph node metastasis and TNM staging (Plt;0.05), but unrelated to patient’s age, gender, and differentiation of tumor (Pgt;0.05). The co-expression of KGF and COX-2 protein was frequently found in patients with deeper invasion of serosa, lymph node metastasis, and higher TNM staging (Plt;0.05), but which was not associated withpatient’sage, gender, and differentiation of tumor (Pgt;0.05). The expression of KGF protein was positively correlated to the expression of COX-2 protein (r=0.610, P=0.000). There was positive correlation between MVD and the expression of KGF (r=0.675, P=0.000) and COX-2 protein (r=0.657, P=0.000) in gastric cancer, respectively. ConclusionKGF and COX-2 highly expressed by gastric cancer, which may be involved in the invasion and metastasis of gastric cancer by synergisticly promoting the angiogenesis.
Objective To explore the effect of toremifene on estrogen receptor （ER） expression and tumor micro-angiogenesis in rat Lewis lung carcinoma. Methods Cell suspension of rat Lewis lung carcinoma was implanted into 40 female Wistar rats subcutaneously. The rats were randomly divided into a control group，a estradiol group （0.006 mg/mL），a low dose toremifene group （0.25 mg/mL） and a high dose toremifene group （5 mg/mL）. Tumor size was measured every 3 days and the tumor growth curve was charted. On 15th day，the tumor weight and the growth inhibition rate were measured. Immunohistochemical method was used to detect the expressions of estrogen receptor α （ERα），estrogen receptor β （ERβ），vascular endothelial growth factor （VEGF），and platelet endothelial cell adhesion molecule-1 （PECAM-1）. Integral optical density （IOD） of ERα，ERβ and VEGF was calculated by image analysis software. Quantitative method of Weidner with PECAM-1 was employed for microvessel density （MVD） count. Results Tumor size of the four groups all presented a quadratic function growth trend with time （Plt;0.05）. Tumor growth speed was slower in toremifene groups of low and high doses than that in the control group and the estradiol group. The growth inhibition rate of the estradiol group，the low dose toremifene group and the high dose toremifene group was －15.1%，22.6%，and 45.1%，respectively. The expressions of ERα，VEGF，and MVD in the estradiol group were significantly higher than those in the control group，the low dose toremifene group and the high dose toremifene group （all Plt;0.05）. The expressions of ERα，VEGF，and MVD in the low dose toremifene group were significantly lower than those in control group，but higher than those in high dose toremifene group （all Plt;0.05）.The expression of ERα was positively related to VEGF （r=0.664，Plt;0.05） and MVD（r=0.593，Plt;0.05）. Conclusion Toremifene can inhibit tumor growth，which maybe involved in inhibiting ERα mediated VEGF expression.
ObjectiveTo observe the effects of hydroxysafflor yellow A (HSYA) on microvessel density (MVD) of mice transplanted Lewis lung cancer and mRNA expression of vascular endothelial growth factor (VEGF) so as to explore the tumor-inhibiting mechanism of HSYA. MethodsSixty tumor-bearing C57/BL mice were randomly divided into five groups, with 12 mice in each group, namely a control group, a cyclophosphamide (CTX) group (25mg/kg), a large dose HSYA group (112mg/L), a medium dose HSYA group (56mg/L), and a small dose HSYA group (28mg/L). These different drugs were administered by intraperitoneal injection. The mice were sacrificed 22 days after the treatment. Tumor tissues were sampled and examined by immunohistochemical method and quantitative real-time PCR to detect the expression of MVD and VEGF mRNA. ResultsThe MVD of the medium and small dose HSYA groups and CTX group were 30.01±3.12, 22.56±2.11 and 16.21±2.40, respectively, which were significantly lower than 41.10±2.93 of the control group and 37.66±3.04 of the large dose HSYA group (χ2=2.82, P=0.010;χ2=3.16, P=0.007;χ2=4.58, P=0.000) and (χ2=1.98, χ2=0.038;χ2=2.45, P=0.016;χ2=3.82, P=0.001). The difference in VEGF amplified fluorescence expression threshold between the HSYA groups and the control group was not significant. However, after amplification, the expression of VEGF mRNA in the small dose HSYA group was only 0.43±0.16, which was obviously lower than 0.82±0.06 in the control group (F=0.77, P=0.038). ConclusionHSYA can significantly reduce MVD in mice transplanted Lewis lung cancer and down-regulate expression of VEGF mRNA to achieve tumor-inhibiting effect.
ObjectiveTo assess the feasibility of intravoxel incoherent motion diffusion-weighted imaging (IVIM) in evaluating microvessel density (MVD) and microvascular invasion (MVI) of hepatocellular carcinoma (HCC).MethodsRat models were established to be scanned by IVIM. HCC lesions corresponding to IVIM image were examined pathologically to get data of MVD and MVI. Spearman correlation analysis was used to compare the apparent diffusion coefficient (ADC), D, D*, and f with MVD, independent samples t test was used to compare ADC, D, D*, and f between MVI (+) and MVI (–) groups.ResultsFifty HCC lesions were included finally. ADC and D values both showed a negative correlation with MVD (r=–0.406, P=0.003; r=–0.468, P=0.001), D* and f showed no statistical correlation with MVD (P=0.172, 0.074, respectively). The differences in ADC and all the IVIM parameters (D, D*, and f) between MVI (+) and MVI (–) HCCs were not statistically significant (P=0.393, 0.395, 0.221, 0.550).ConclusionADC and D can be used to evaluate MVD of HCC, but ADC and IVIM parameters were limited in evaluating MVI.
Objective To investigate the expression of hypoxia inducing factor 1 alpha (HIF-1α) in human breast cancer and its relationships with microvessel density （MVD）, proliferating cell nuclear antigen (PCNA) protein, other tumor biomarkers and clinicopathologic factors. Methods Immunohistochemical staining (SP) was used to measure the expressions of HIF-1α and PCNA in human breast fibroadenoma, usual hyperplasia and adenocarcinoma, and the MVD was determined by anti-CD34 immunostaining. Results No HIF-1α was observed in the lesions of breast fibroadenoma and hyperplasia. However, the positive expression rate of HIF-1α in the ductal carcinoma in situ （DCIS） was 55.0% (11/20) and the infiltrative breast cancer was 85.0%(51/60). The total high expression rate of PCNA in breast cancer was 75.0% (60/80), in which the rate of DCIS counted for 65.0% (13/20) and the rate of infiltrative adenocarcinoma counted for 78.3% (47/60). There were positive correlations between the expresson of HIF-1α and the expression of PCNA (r=0.693， P＜0.01) and MVD in DCIS (r=0.682, P＜0.05), respectively, but there was no relation between HIF-1α and MVD in infiltrative breast cancer. The expression of HIF-1α was associated with tumor cell proliferation, lymph node metastasis, estrogen receptor status (P＜0.01). Conclusion The expression of HIF-1α increased in breast cancer and it is associated with tumor cell proliferation, lymph node metastasis, estrogen receptor status. Thus, HIF-1α may play an important role in the tumor cell proliferation, vasiformation, progression and metastasis of breast cancer, and may become a new target for tumor treatment.