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.
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.
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.
Objective To explore the clinical significance of estrogen receptor α( ERα) , estrogen receptor β( ERβ) in non-small cell lung cancer( NSCLC) .Methods EnVision method was used to detect the expressions of ERα, ERβ, vascular endothelial growth factor( VEGF) , and microvessel density( MVD) in 54 NSCLC patients, 10 patients with lung benign lesions, and 10 normal controls. The interrelation between ERα, ERβ, VEGF, and MVD was analyzed. Results No obvious expressions of ERα and ERβwere observed in the normal lung tissues and lung benign lesions. The positive expression rates of ERα, ERβ, and VEGF in NSCLC were 20. 4% ( 11/54) , 64. 8% ( 35/54) , and 64. 8% ( 35/54) , respectively. There were no significant differences between ERαin regard to clinical parameters of NSCLC. But the expression of ERβwas dependent on pathological classification and differentiation of NSCLC. The expression of ERβ was significantly higher in adenocarcinoma than in squamous cell carcinoma( P lt; 0. 05) . The expression rate of ERβin well differentiated group was significantly higher than that in low, moderately differentiated group( P lt;0. 05) . There were significant differences between VEGF in regard to lymph node metastasis and TNM stage. The expression of ERαinterrelated with VEGF and MVD with r value of 0. 4 and 0. 685 respectively ( P lt;0. 05) . There was little correlation between ERβ and VEGF, MVD( P gt; 0. 05) . Conclusion Theexpression of ERβ correlates with pathological classification and differentiation of NSCLC, suggesting its significance in evaluating the pathological classification and malignant degree of NSCLC. The expression of ERαcorrelates with VEGF and MVD, suggesting that ERαpossibly promote micro-angiogenesis of NSCLC by VEGF pathway.
ObjectiveTo study the effects of the expressions of endostatin, basic fibroblast growth factor (bFGF) and CD34 on oncogenesis and progression of gallbladder cancer, and to explore some valuable criterias for its biotherapy. Methods The expressions of endostatin, bFGF and CD34 were studied by means of immunohistochemistry (SP) in 61 cases of gallbladder cancer and 10 cases of normal cholecystic tissue, and microvessel density (MVD) was calculated by the expression of CD34. Their relationships with clinical pathological features were also investigated. Results The expression rates of endostatin in normal cholecystic tissue and in gallbladder cancer tissue were 40.00% (4/10) and 77.05% (47/61) respectively, which had statistical difference (P＜0.05). The expression of endostatin in 61 cases of caner was relational to clinical stage and metastasis of lymph nodes (P＜0.05), while no significant correlation was detected with sex and age of patient, location of tumor, size of tumor and histologic grade (P＞0.05). The expression rates of bFGF in normal cholecystic tissue and in gallbladder cancer tissue were 20.00%（2/10） and 67.21% （41/61） respectively, which had statistical difference (P＜0.05). The expression of bFGF in 61 cases of caner was relational to clinical stage and metastasis of lymph nodes (P＜0.05), while no significant correlation was detected with sex and age of patient, location of tumor, size of tumor and histologic grade (P＞0.05). MVD in gallbladder cancer tissue and in normal cholecystic tissue was （76.66±20.15） piece/HP and (29.53±5.03) piece/HP respectively, showing significant difference (P＜0.01). In 61 cases of cancer, MVD in clinical stage Ⅲ～Ⅴ 〔(80.53±17.98) piece/HP〕 was much higher than that in stage Ⅰ+Ⅱ 〔(46.79±5.38) piece/HP〕, P＜0.01; MVD was higher in those with lymph nodes metastasis 〔(94.60±7.28) piece/HP〕 than those without metastasis 〔(58.12±9.24) piece/HP〕, P＜0.01; and MVD was (60.59±14.71) piece/HP in histologic grade G1， (83.08±15.30) piece/HP in G2， and (96.53±6.92) piece/HP in G3, the difference was significant among them （P＜0.01）. There was no significant correlation between MVD and sex and age of patient, location of tumor and size of tumor (P＞0.05). There were statistically significant correlations between expressions of endostatin and MVD （P＜0.01）, expressions of bFGF and MVD （P＜0.01）. Conclusions The result suggests that endostatin, bFGF and CD34 play roles in oncogenesis and progression of gallbladder cancer. Detection of these proteins has positive effects on diagnosis, malignant degree determination and treatment of gallbladder cancer.
Microvascular dysfunction is a key pathological mechanism of diabetic retinopathy (DR). In recent years, it has been found that the phenomenon of "metabolic memory" is prevalent in diabetic patients, and diabetic microangiopaplasia cannot be avoided even if patients’ blood glucose is well controlled. Therefore, it is necessary to explore DR from a genetic perspective. miR-126 is the unique microRNA specifically expressed in vascular endothelial cells, which is closely related to the formation of neovascularization and can affect the stability of DR microvessels as well as the germination and migration of endothelial cells, and its gene level is significantly negatively correlated with the expression of vascular endothelial cell growth factor. The potential value of intracellular and circulating miR-126 in the regulation of DR microvascular homeostasis, early diagnosis and treatment, and monitoring of disease course has attracted great attention. However, studies in this area are mostly hypothesis-driven and still have some limitations. It is believed that with the rapid development of genomics, the miRNA spectrum and its molecular mechanism in eye development and eye diseases will gradually become clear, which may lead to a breakthrough in the intervention of individual refractory retinal diseases and establish a new miRNA diagnosis and treatment method in the future.
【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 observe the expression levels of nuclear factor kappa B （NF-κB）， vascular endothelial growth factor （VEGF）， and CD31 in portal vein and surrounding tissues of rats during the formation process of cavernoustransformation of portal vein （CTPV）， and try to search the relationship between NF-κB， VEGF， and the angiogenesisof portal areas， as well as the significance and the role of NF-κB and VEGF in the formation process of CTPV. Methods One hundred and ten Sprague-Dawley （SD） rats were randomly （random number method） divided into sham operation group and model group. The partial constriction operations on portal vein were performed in model rats with a blunt 21Gcaliber to establish CTPV animal models （model group）， while the exploratory operations on portal vein， not constriction，were performed in rats of sham operation group. All specimens （portal vein and surrounding tissues） were fixed in formalinand made into paraffin blocks. Each specimen was tested by immunohistochemistry for the expressions of NF-κB， VEGF， and CD31， then optical density （OD） of NF-κB expression and the mean integral optical density （IOD） of VEGF expressionwere measured by using Image Pro Plus 6.0 software， and microvessel density （MVD） was calculated under microscope. Results Nucleoplasm ratio of OD value of NF-κB， mean IOD value of VEGF， and MVD value in 1， 2， 3， 4， and 6 weeks after operation didn’t significantly differed from that of before operation in sham operation group （P＞0.05）， but higher at all time points after operation in model group （P＜0.01）. Compared with sham operation group， nucleoplasm ratio of OD value of NF-κB， mean IOD value of VEGF， and MVD value were significantly higher in 1， 2， 3， 4， and 6 weeks after operation in model group （P＜0.01）. NF-κB and VEGF， NF-κB and MVD， VEGF and MVD were positively correlated with each other （r=0.654 6，P＜0.01；r=0.620 7， P＜0.01；r=0.636 9， P＜0.01） in model group. Conclusion NF-κB and VEGF may relate to the formation of CTPV， and may involve in the angiogenesis.
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.
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.