Effects of endostatin on expression of vascular endothelial growth factor and its receptors and neovascularization in colonic carcinoma implanted in nude mice

AIM:To investigate the antiangiogenic effects of endostatin on colonic carcinoma cell line implanted in nude mice and its mechanism. METHODS:Nude mice underwent subcutaneous injection with LS-174t colonic carcinoma cell line to generate carcinoma and were randomly separated into two groups.Mice received injection of vehicle or endostatin every day for two weeks. After the tumor was harvested,the tumor volumes were determined,and the expressions of CD34,VEGF and FIk-1 were examined by immunohistochemical method. RESULTS:Tumor volume was significantly inhibited in the endostatin group(84.17%)and tumor weight was significantly inhibited in the endostatin group(0.197±0.049) compared to the control group(1.198±0.105)(F=22.56, P=0.001),microvessel density(MVD)was significantly decreased in the treated group(31.857±3.515)compared to the control group(100.143±4.290)(F=151.62,P<0.001). Furthermore,the expression of FIk-1 was significantly inhibited in the treated group(34.29%) ompared to the control group(8.57%)(X^2=13.745,P=0.001).However no significant decrease was observed in the expression of vascular endothelial growth factor(VEGF)between these two groups(X^2=0.119,P=0.730). CONCLUSION:Endostatin can inhibit tumor growth and angiogenesis by blocking Vegf/FIk-1 pathway.This experiment provides the theory basis for developing a new anti-carcinoma drug through studying the properties of anti-angiogenesis inhibitors.

聚焦超声治疗前后外阴白色病变组织中VEGF、bFGF和CD34表达的检测及其意义

目的:探讨VEGF、bFGF和CD34在聚焦超声治疗前后的外阴白色病变组织中表达率的变化情况,阐明聚焦超声治疗外阴白色病变的可能机制。方法:采取免疫组织化学SP法检测30例外阴白色病变组织、15例经聚焦超声治疗后1个月和8例治疗后3个月外阴白色病变患者病变组织中VEGF、bFGF和CD34的表达情况,比较三者在治疗前后的阳性细胞表达率。结果:聚焦超声治疗后VEGF和bFGF在外阴白色病变组织中的表达高于治疗前(P<0.05);聚焦超声治疗前后CD34在外阴白色病变组织中的表达差异无统计学意义(P>0.05)。结论:聚焦超声治疗可使外阴白色病变组织中VEGF和bFGF的表达升高,其机制可能是通过改善外阴白色病变局部组织神经微血管结构和功能使外阴白色病变组织恢复至正常。

肺癌组织bFGF和CD34的表达及bFGF的超微定位

目的 :研究 b FGF、CD34的表达与肺癌组织学类型、分化程度之间的关系 ,并对 b FGF进行超微定位。方法 :应用 b FGF、CD34单克隆抗体及免疫组织化学染色方法 ,观察 48例原发性肺癌组织中 b FGF及 CD34的表达情况。采用免疫电镜技术研究 b FGF在肺癌细胞中的定位。结果 :b FGF、CD34的阳性表达率与肺癌组织分化程度负相关 ,CD34在不同组织学类型的肺癌组织中表达差异性显著。b FGF主要定位于肺癌细胞近胞膜的胞浆中。结论 :b FGF、CD34可以作为评估肺癌组织分化程度的指标 。

造血细胞生长因子对脐血CD_(34)^+细胞短期体外扩增的作用

目的 探讨造血细胞生长因子 (HGF)的不同组合对脐血 CD34 + 细胞短期体外扩增的作用。 方法 用免疫磁珠法分离纯化脐血 CD34 +细胞 ,培养于无血清培养液中。加入不同的细胞因子 ,于第 4 ,7,10 ,14天检测 CD34 +细胞百分率和有核细胞 (NC)总数。 结果 和对照组相比 ,各组的 NC扩增倍数随着培养时间的延长呈不同程度的增加 ,干细胞在 FL、TPO、GM- CSF、SCF、IL - 6、G- CSF、EPO和 IL - 3等因子作用下 ,NC扩增倍数在培养第 14天达高峰 ,为32 8.96倍 ;而 CD34 +细胞扩增倍数在培养第 7天达最高峰 ,但在 FL、TPO、GM- CSF、SCF、IL- 6、G- CSF等因子作用下 ,CD34 + 细胞扩增倍数最大 ,7d后达 2 5 .2 3倍 ,而后随着培养时间的延长而逐渐下降。 结论 脐血 CD34 + 细胞在HGF作用下 ,扩增时间以 7～ 10

Buyanghuanwu decoction promotes angiogenesis after cerebral ischemia/reperfusion injury：mechanisms of brain tissue repair

Buyanghuanwu decoction has been shown to protect against cerebral ischemia/reperfusion injury,but the underlying mechanisms remain unclear.In this study,rats were intragastrically given Buyanghuanwu decoction,15 m L/kg,for 3 days.A rat model of cerebral ischemia/reperfusion injury was established by middle cerebral artery occlusion.In rats administered Buyanghuanwu decoction,infarct volume was reduced,serum vascular endothelial growth factor and integrin αvβ3 levels were increased,and brain tissue vascular endothelial growth factor and CD34 expression levels were increased compared with untreated animals.These effects of Buyanghuanwu decoction were partially suppressed by an angiogenesis inhibitor（administered through the lateral ventricle for 7 consecutive days）.These data suggest that Buyanghuanwu decoction promotes angiogenesis,improves cerebral circulation,and enhances brain tissue repair after cerebral ischemia/reperfusion injury.

Prognostic angiogenic markers(endoglin, VEGF, CD31) and tumor cell proliferation(Ki67) for gastrointestinal stromal tumors

AIM: To evaluate the correlation between the immunoexpression of angiogenic markers [CD31, CD105 and vascular endothelial growth factor(VEGF)], proliferative index(Ki67), and prognosis of patients with gastrointestinal stromal tumors(GIST).METHODS: This is a retrospective study of 54 GIST cases. Medical records were searched to obtain the GIST patients' demographic and clinical data, and paraffin-embedded blocks of tumor samples were retrieved from the hospital archives to conduct a new immunohistochemical evaluation. The tumor samples of GIST patients were subject to immunohistochemical evaluation for endoglin(CD105), CD31, VEGF, and Ki67 expression. The CD105 and CD31 intratumoral microvascular density(IMVD) was measured using automated analysis. We determined the correlation between the immunoexpression of CD105, CD31, VEGF,Ki67 and prognosis. In addition, we conducted a cutoff analysis using the receiver-operating characteristic curve. VEGF positivity was classified as either null/weak or strong. Ki67 was evaluated using a cutoff of 5%positive cells. The prognosis was classified as good(patient alive without recurrence) or poor(patient with recurrence/death).RESULTS: The distribution of tumor sites among the54 analyzed samples was as follows: 27(50%) in the stomach, 20(37.1%) in the small intestine, 6(11.1%)in the colon, and 1(1.8%) in the esophagus. The size of the tumors ranged from 2 to 33 cm(median: 8cm); in 12 cases(22.2%), the tumor was below 5 cm at the largest diameter, but in 42 cases(77.7%), the tumor was larger than 5 cm. The means of CD105 and CD31 were significantly higher in the group with poor prognosis(P < 0.001). The cut-off values of CD105(>1.2%) and CD31(> 2.5%) in the receiver-operating characteristic curve were related to a poorer prognosis.Cases with a better prognosis showed significantly null/weak staining for VEGF(P < 0.001). Ki-67 expression of≥ 5% was strongly correlated with a worse prognosis(P< 0.001). In the multivariate analysis, CD105 was the variable that most strongly correlated with prognosis.CONCLUSION: The IMVD cutoff values for the angiogenic markers CD105 and CD31, may be prognostic factors for GIST, in addition to VEGF and Ki67.

Protective effects of acupuncture and LGNHFD on expressions of vascular endothelial growth factor, basic fibroblast growth factor,and cluster of differentiation 34 in rats with cerebral ischemia-reperfusion injury

OBJECTIVE: To investigate the protective effects of electroacupuncture and LGNHFD on cerebral ischemia-reperfusion injury, and their effects on the expression of cluster of differentiation 34(CD 34), vascular endothelial growth factor(VEGF), and basic fibroblast growth factor(b FGF) in the peripheral tissue of the cerebral ischemic semi-dark zone in rats.The influence and mechanism of expression.METHODS: Healthy male Sprague-Dawley rats were randomly divided into the sham operation group, model group, Traditional Chinese Medicine (TCM) group, electroacupuncture group, and acupuncture group. The cerebral ischemia model was prepared by middle artery occlusion. The electroacupuncture and TCM groups received electroacupuncture at the "Neiguan(PC6)", "Baihui(GV20)", and "Renzhong(GV26)" acupoints from 4 h after modeling, once daily for 14 d. After modeling,the acupuncture and TCM groups were administered LGNHFD once daily for 14 d. After treatment,the infarct volume and regional cerebral blood flow(r CBF) were measured in each group, the expression of CD34 in the surrounding ischemic penumbra was determined using immunohistochemistry,and the expression of angiogenesis-related factors in the ischemic hemisphere was detected by western blot.RESULTS: Compared with the sham operation group, r CBF was significantly decreased(P < 0.01)and cerebral infarction volume was significantly increased(P < 0.01) in the model group at four time points(5 min and 3, 7, and 14 d after modeling). At three postoperative time points(3, 7, and 14 d), the number of CD34 + cells in the model group were significantly increased(P < 0.01), and the relative expression levels of VEGF, b FGF, and CD34+ in the ischemic hemisphere were significantly increased(P < 0.01, P < 0.05). Compared with the model group, the r CBF of the acupuncture group was significantly increased at 3, 7, and 14 d after intervention(P < 0.01), while the r CBF of the electroacupuncture and TCM groups was significantly increased at 7 and 14 d after intervention(P < 0.01).After 3, 7, and 14 d of intervention, infarct volume was significantly reduced(P < 0.01), the number of CD34 + cells was significantly increased(P < 0.01,P < 0.05), and the relative expression levels of VEGF,b FGF, and CD34 in the ischemic hemisphere were significantly increased(P < 0.01, P < 0.05). Compared with the electroacupuncture and TCM groups, the r CBF of the acupuncture group was significantly increased(P < 0.01), the infarct volume was significantly reduced(P < 0.01), and the relative expression levels of VEGF, b FGF, and CD34 were significantly increased(P < 0.05, P < 0.01) after 3, 7,and 14 d of intervention.CONCLUSION: Acupuncture therapy is superior to simple drug and electroacupuncture therapy for reducing infarct volume, increasing r CBF and CD34 expression in cells, and promoting capillary regeneration in rats with cerebral ischemia. This may be related to the increased expression of VEGF, b FGF,and CD34 — which are related to cerebrovascular neovascularization — in the ischemic hemispheres of such rats.

Primary multiple extragastrointestinal stromal tumors of the omentum with different mutations of c-kit gene

The author reports a very rare case of sporadic primary multiple extragastrointestinal stromal tumors (EGISTs) of the omentum associated with different mutations of the exon 11 of the c-kit gene in a 75-year-old man with gastric cancer. During an operation for the cancer, two solid tumors (10 mm and 8 mm) were found in the omentum. Both tumors consisted of cellular spindle cells. Mitotic figures were two and three per 50 high power fields. The tumor cells were positive for KIT, CD34 and vimentin, but negative for desmin, S100 protein, α-smooth muscle actin and p53 protein. Ki67 labeling was 2% and 3%. The larger EGIST showed a deletion of codons 552-558 of exon 11 of the c-kit gene, while the smaller EGIST had a point mutation at codon 559 (GTT←GAT) in exon 11 of the c-kit gene. Exons 9, 13, and 17 of the c-kit gene, and exons 12 and 18 of the platelet derived growth factor receptor α genes showed no mutations. The case shows that sporadic multiple EGISTs can occur in the omentum.

A Correlative Study between CT Perfusion Parameters and Angiogenesis in Rabbit VX2 Liver Tumors

Objective: The purpose of this study was to evaluate the correlation between CT perfusion parameters and the hypoxia-inducible factor-1 alpha (HIF-1α), vascular en-dothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2) and microvessel density (MVD) marked by CD34 molecular of rabbit VX2 liver tumors and to investigate the value of CT perfusion imaging in evaluating tumor angiogenesis. Material and methods: Twenty-four cases of rabbit VX2 liver tumor were performed by CT perfusion scanning. Hepatic artery perfusion (HAP), portal vein perfusion (PVP), total hepatic blood flow (THBF) and hepatic perfusion index (HPI) were measured by perfusion software. HIF-1α, VEGF and MMP-2 expression and MVD were detected in the 24 rabbit VX2 liver tumor tissue samples using immunohistochemical method. The correlation between the HIF-1α, VEGF, MMP-2 expression and MVD and CT perfusion parameters were analyzed. Results: Correlation analysis revealed that the expression of HIF-1α, MMP-2, MVD were positively related to the HAP, THBF, HPI (p < 0.01), but no relations with PVP (p > 0.05);and correlation analysis revealed that the expression of VEGF was positively related to the HAP, HPI (p 0.05). There was a positive relationship between the expression of HIF-1α, VEGF, MMP-2 and MVD (p < 0.01). Conclusions: CT perfusion imaging can reflect the blood perfusion of the rabbit VX2 liver tumors and evaluate the information of angiogenesis about tumors.