Relationship between microangiogenesis and astrocytes after cerebral infarct in SHR-SP rats / 西安交通大学学报(医学版)

Objective: To investigate the possible role of astrocytes after brain infarction in stroke-prone, spontaneously hypertensive (SHR-SP) rats and the association with angiogenesis and the architecture. Methods: We maintained SHR-SP rats on high sodium water starting to accelerate the stroke onset. The 3D quantification of microvasculatures (diameter, branch number) by cofocal microscope after FITC-dextran was injected into the rats via the left femoral vein. Glial fibrillary acidic protein (GFAP) expression and microvessel density (MVD) using counting the number of factor -positive endothelial cells were evaluated by immunofluorescence and immunohistochemistry, respectively. Results: Cerebral infarction occurred at week 7 after high sodium water intake (13 g/L NaCl) in SHR-SP group. When compared with the non-infarcted contralateral hemisphere and SHR-SP on normal sodium intake and WKY rats, GFAP expression and MVD were significantly increased, respectively, and the diameter and the branch number of vessels were decreased, respectively, in cerebral infarcts with boundary zones of SHR-SP rats (P<0.01). Linear correlation analysis showed that GFAP expression was positively correlated with MVD and the diameter and the branch number of vessels in cerebral infarcts in SHR-SP (P<0.01). Conclusion: Astrocytes hyperplasia may be associated with increased regional angiogenesis and the changes of architecture in SHR-SP rats with high sodium water (13 g/L NaCl) that induces focal cerebral infarcts.

Relationship between the expression ofCEACAM1, CD34 and the metastasis of gastric cancer / 基础医学与临床

Objective To investigate the prognostic impact of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and CD34 on invasion and metastasis of gastric cancer.Methods CEACAM1 and CD34 expressions were detected by immunhistochemistry in 90 cases of gastric cancer and 30 cases of normal gastric mucosa.Then the relationship among CEACAM1, MVD marked by CD34 antibody and gastric cancer patients` clinical pathological features and prognosis were analyzed.Results The positive rates of CEACAM1 and CD34 protein in gastric cancer were significantly higher than those in normal gastric mucosa (P<0.05).The positive rate of CEACAM1 was closely related to histological differentiation, tumor invasion, nodal metastasis and TNM stage.MVD marked by CD34 was related with tumor size, histological differentiation, tumor invasion, nodal metastasis and TNM stage(P<0.05).Conclusions In gastric cancer, CEACAM1 and CD34 promote its invasion and metastasis, and they are potential indicators of predicting development and prognosis.

Anti-angiogenic therapy for gallbladder carcinoma using contrast enhanced ultrasound / 中华肝胆外科杂志

Objective To evaluate the feasibility of contrast enhanced ultrasound (CEUS) in gallbladder carcinoma anti-angiogenesis treatment.Methods Subcutaneous gallbladder carcinoma model was consturcted.The mice were divided into intervention-drug group and control group randomly.The mice of intervention-drug group were treated with Endostar (10 mg · kg-1 · d-1) by intraperitoneal injection for two weeks.Two groups of mice were detected by CEUS,then the time of arrival (AT),peak time (TTP),peak intensity (PI),area under the curve (AUC) were measured via time-intensity curve.Expression of MVD and VEGF both in the intervention and control groups were studied through immunohistochemistry.and the correlations between MVD,VEGF and CEUS parameteres were further analyzed.Results The mean values of PI in drug intervention group and control group were 10.8 ± 5.5 and 16.8 ± 5.8,respectively.The values of PI in intervention-drug group were lower than that in control group significantly (P ＜ 0.05).There was no significant difference in AT,TTP,AUC between the two groups.The mean values of MVD on drug intervention group and control group were 8.5 ± 3.8 and 13.1 ± 3.5,respectively.The mean values of VEGF on drug intervention group and control group were 4.3 ± 0.5 and 4.7 ± 0.4,respectively.The values of MVD and VEGF in intervention-drug group were significant lower than that control group (P ＜ 0.05).MVD and VEGF values of intervention-drug group were correlated with PI (r =0.712,P ＜ 0.05;r =0.739,P ＜ 0.05).Conclusion Endostar can inhibit the growth of gallbladder carcinoma and PI can be used as an effective marker to evaluatethe effect of anti-angiogenic therapy in gallbladder carcinoma.

Effects of thin recipe of Buyang Huanwu Decoction on angiogenesis and signal pathway of Nrf2/HO-1 after cerebral ischemic injury in rat / 中国药理学通报

Aim To observe the effects of thin recipe of Buyang Huanwu Decoction on angiogenesis and the signal pathway of Nrf2 / HO-1 after cerebral ischemic injury in rats. Methods Totally 120 SD rats were randomly divided into four groups: sham operation group,model group,Buyang Huanwu Decoction group and thin recipe of Buyang Huanwu Decoction group. The focal cerebral ischemia rat model was established by middle cerebral arterial occlusion. Each group was treated with corresponding treatment. Each group was detected after cerebral ischemia for day 1,day 3 and day 7, respectively. Immunohistochemical method was used to detect the plasma levels of factor VIII related antigen( vWF), determination of microvessel density (MVD). The expression of Nrf2,HO-1 gene and pro-tein in brain tissues was detected by Real-Time PCR (RT-PCR) and Western blot. Results ① Compared with sham-operation group, the expression of vWF in the model group was significantly increased on day 3(P< 0. 05). Compared with model group, the expression levels increased differently in each drug group on day 7 (P < 0. 05). ② The expression of Nrf2, HO-1 gene and protein in sham operation group showed a small a-mount of gamma expression. Compared with sham op-eration group at the same time point, the expression of Nrf2 protein was significantly increased on day 3(P <0. 01). Compared with model group at the same time point, the Nrf2mRNA and protein expression was up-regulated in each drug group. The Nrf2mRNA on day 1,the Nrf2 protein on day 1 and day 7 were significant-ly increased( P < 0. 01). Compared with sham opera-tion group at the same time point, the expression of HO-1mRNA and protein in the model group was signif-icantly increased on day 7(P < 0. 05). Compared with model group at the same time point, the HO-1mRNA on day 3, the HO-1 protein on day 3 and day 7 in each drug group were significantly increased (P < 0. 05,P <0. 01). Conclusions The thin recipe of Buyang Hua-nwu Decoction promotes brain angiogenesis after ische-mia. The effect may be related wih the expression of Nrf2 / HO-1 signal pathway.

Mimic hypoxia of deferasirox in improving growth of micrangium in a narrow pedicle flap / 中华医学美学美容杂志

Objective To study the function of hypoxia mimics of different exposure time of deferasirox in improving the growth of micrangium in a narrow pedicle flap.Methods Fourty male SD rats were divided into 2 groups:experimental group was fed with deferasirox 100 mg/kg per day from 1d,3d,5d and 7d,respectively,before the surgery of transferring the narrow pedicle flap,while control group just fed with saline.After 7 days,the immunohistochemistry,Western blot and quantitative reverse transcription-PCR (qPCR) were performed to examine the expression of CD34.qPCR was used to examine the expression of HIF-1α,VEGF in order to investigate the regulatory effect of deferasirox in improving the growth of micrangium and the distinction among the different exposed time of deferasirox in the narrow pedicle flap.Results The deferasirox group exhibited a marked improvement in flap healing time,and with the increasing administration time of deferasirox,the expression of MVD,HIF-1α and VEGF was improved in each treated group (P＜0.05).Conclusions Deferasirox can induce HIF-1α secretion and increase CD34 expression,and so deferasirox can protect endothelial cells from hypoxic and ischaemic injury.

Effects of Three Different Types of Anti-adhesive Agents in a Rat Abdominal Wall Defect Model

PURPOSE: Postsurgical adhesion formation is a significant clinical problem within every surgical specialty. Several adhesion barriers have been developed in the form of solution, membrane or film in an attempt to solve these problems. The purpose of the present study is to compare the efficacy of antiadhesive agents in the prevention of postsurgical adhesion formation in a standardized rat adhesion model. METHODS: We examined forty Sprague-Dawley rats, which is a cecal abrasion with partial peritonectomy model. Three treatment groups (Group I: Film-type Surgiwrap(R), Group II: Solution-type Guardix-sol(R), Group III: Membrane-type Interceed(R)), each consists of 10 rats, and a control group of 10 rats were used by saline. Ten days after surgery, the rats were killed, and the levels of adhesion were graded. Immunohistochemical staining for microvessel density (CD34, MVD) and macrophage (ED1) were performed in adhesion tissue. RESULTS: The peritoneum adhesion mean scores are as follows: control group: 2.2+/-0.78, Group I: 1.0+/-1.06, Group II: 0.9+/-0.99, Group III: 0.6+/-0.84. All treatment groups showed significantly less peritoneum adhesion (P=0.006), while there was no significant difference in each group. The intraperitoneal organs adhesion mean scores are as follows: control group: 2.8+/-0.91, Group I: 2.6+/-1.06, Group II: 1.4+/-0.84, Group III: 1.0+/-0.81. Group I had no significant difference about intraperitoneal organs adhesion with control group, but Group II and Group III showed less intraperitoneal organs adhesion. The mean numbers of microvessel density are as follows: control group: 42.5+/-4.83, Group I: 40.8+/-6.53, Group II: 30.9+/-6.15, Group III: 15.60+/-4.37, from which there was a significant difference between Group II and Group III with control group (P<0.001). The mean numbers of macrophage are as follows: control group: 223.3+/-33.12, Group I: 211.25+/-10.96, Group II: 171.60+/-23.96, Group III: 147.0+/-12.22, from which there was a significant difference between Group II and Group III with control group (P<0.001). CONCLUSION: In our animal model, three different types of antiadhesive agents (Surgiwrap(R), Guardix-sol(R), Interceed(R)) were effective in adhesion prevention, but Surgiwrap(R) had less antiadhesive effect for intraperitoneal organs adhesion. Membrane-type Interceed(R) had a better effect for microvessel density (MVD) and macrophage than solution-type Guardix-sol(R).

Study of morphological characteristics of tumor microvasculature in primary hepatocellular carcinoma / 解放军医学杂志

Objective To study the morphological characteristics of tumor microvasculature in primary hepatic cell carcinoma (HCC). Methods From Jan. 1998 to Feb. 2002, 32 cases, consisting of 26 male and 6 female, with age ranging from 28 to 76 years [mean (50.56?10.52) years], underwent preoperative digital subtraction angiography (DSA) without theraputic embolization in General Hospital of PLA and 307 hospital of PLA. The diameters of the tumors measured 2～23 (8.05?6.17) cm. The tumor microvessel density (MVD), type and diameter of the tumor microvessels, width of tumor trabeculae, and the size of the malignancy were measured and statistically analyzed. The outcome of the each patient was also statistically analysed. Results The size of tumor tended to be positivly correlated with the pattern of microvasculature of the tumor. The size of the tumor was negatively correlated with MVD, white the tumor size and the diameter of tumor related vessels were positively correlated with the diarneter of tumor trabeculae. Hoverer, the size of the tumor was not correlated with the diameter of vascular trabeculae. Conclusions The density, configuration and the distribution of tumor microvessels were not even in HCC. The features of tumor microvasculature were distinctive at different phases of tumor growth, having definite rules in the development.

Prognostic Significance of Tumor Angiogenesis in Breast Cancer / 한국유방암학회지

The well-known prognostic factors for breast cancer, such as axillary lymph node status, do not always account for the exact outcome. The development of other accurate prognostic factors would help in assessing high risk for recurrence and death. Recently, much experimental evidence has accumulated showing that tumor growth and metastasis are dependent on tumor angiogenesis. To investigate the status of angiogenesis in breast cancer, we counted the microvessel density (MVD) of brest cancer tissues, which were stained with anti-CD34 antibody, as a measure of tumor angiogenesis. We classified 43 breast-cancer patients into 22 with low MVD ( or =47/200xPF). We estimated the correlations between the MVD and other established prognostic factors. We also calculated survivals based on MVD. The MVD was in the range between 10 and 93 (mean+/-SD=46.9+/-21.7). The positive rate of lymph-node metastasis in high MVD patients was 32.6%, which was higher than the 23.3% for low-MVD patients. We found a significant correlation between MVD and histologic grade (p=0.037), but could not fine any significant correlation between MVD and menopausal status, tumor size, nuclear grade, estrogen receptor, or progesterone receptor. Retrospectively, the receptor status of estrogen and of progesterone had significant impacts on survival (ER: p=0.0001, PR: p=0.0001). The 4-year disease-free survival rate of high-MVD patients was 56.6+/-12.5%, and that of low-MVD patients was 69.0+/-10.8% (p=0.449). The 4-years overall survival rate of high-MVD patients was 71.1+/-11.1%, and that of low-MVD patients was 74.1+/-12.2 (p=0.449). In conclusion, the determination of MVD in breast cancer tissue may be useful as a prognostic factor, but it is necessary to investigate the MVD in a large number of patients before this conclusion can be stated with certainty.

Correlation Between Tumor Microvessel Density and Prognosis in Breast Cancer

It has been recognized that angiogenesis has a profound effect on growth of tumors in various animal models. Recently, it was suggested that tumor microvessel density may be an independent prognostic factor in breast cancer and other human tumors. This study was designed to define the correlation between tumor microvessel density and survival in breast cancer. Pathological parameters of 60 patients with breast cancer were analyzed: stage, nodal status, histologic grade, vascular invasion, and p53 expression. Tumor microvessels were stained by the immunohistochemical method in formalin-fixed, paraffin-embedded tissues by using the anti-CD31 monoclonal antibody (JC/70A, DAKO) and were counted with in a 10 objective field (about 0.74 mm2) in the area of the most intense neovascularization. The microvessel density (MVD) of the tumor was compared with other prognostic factors and 5-year survival rate. The mean MVD of the 60 breast cancers was 36.5 15.3 (range: 17~112). The MVD did not correlate with the stage, the node metastasis, the histologic grade, the vascular invasion, or the p53 expression. The MVD was graded by the number of microvessels as grade 1 (MVD 17~32), grade 2 (MVD 33~48), and grade 3 (MVD>49). The 5-year survival rate of patients with MVD grade 1 was 69.0%, and those of grades 2 and 3 were 58.2% and 29.6%, respectively, which was statistically significant (p=0.004). By univariate analysis, the stage (p<0.001), the axillary nodal status (p<0.001), the MVD (p=0.004), and the p53 expression (p=0.041) had a significant correlation with survival. In 25 patients with node-negative breast cancer, the MVD was the single significant prognostic factor (p=0.047). These results suggest that tumor microvessel density is a significant prognostic factor in invasive breast cancer and that it may be a prognostic factor in node-negative breast cancer.

Prognostic Significance of Tumor Angiogenesis in Breast Cancer

The well-known prognostic factors for breast cancer, such as axillary lymph node status, do not always account for the exact outcome. The development of other accurate prognostic factors would help in assessing high risk for recurrence and death. Recently, much experimental evidence has accumulated showing that tumor growth and metastasis are dependent on tumor angiogenesis. To investigate the status of angiogenesis in breast cancer, we counted the microvessel density(MVD) of breast cancer tissues, which were stained with anti-CD34 antibody, as a measure of tumor angiogenesis. We classified 43 breast-cancer patients into 22 with low MVD ( or =47/200 PF). We estimated the correlations between the MVD and other established prognostic factors. We also calculated survivals based on MVD. The MVD was in the range between 10 and 93(mean SD=46.9 21.7). The positive rate of lymph-node metastasis in high-MVD patients was 32.6%, which was higher than the 23.3% for low- MVD patients. We found a significant correlation between MVD and histologic grade (p=0.037), but could not find any significant correlation between MVD and menopausal status, tumor size, nuclear grade, estrogen receptor, or progesterone receptor. Retrospectively, the receptor status of estrogen and of progesterone had significant impacts on survival (ER : p=0.0001, PR : p=0.0001). The 4-year disease-free survival rate of high-MVD patients was 56.6 12.5%, and that of low-MVD patients was 69.0 10.8% (p=0.449). The 4-year overall survival rate of high-MVD patients was 71.1 11.1%, and that of low-MVD patients was 74.1 12.2 (p=0.449). In conclusion, the determination of MVD in breast cancer tissue may be useful as a prognostic factor, but it is necessary to investigate the MVD in a large number of patients before this conclusion can be stated with certainty.

The expression of angiopoietin-2 and its correlation with tumor angiogenesis in oral squamous cell cacinoma / 实用口腔医学杂志

Objective:To study the role of angiopoietin-2(Ang-2) in angiogenesis in oral squamous cell cacinoma(OSCC). Methods:Expression of angiopoietin-2 and CD_34 in 41 cases of OSCC(13 cases with lymph node metastasis)and 10 cases of normal oral mucosa was detected by immunohistochemical SABC method. Microvessel density(MVD) in the samples was counted under microscope. Results:Ang-2 was detected in 28 out of 41(68.29%) cases of OSCC and 2 out of 10(20%) of normal oral mucosa(P

Relationship between effect of tetramethylpyrazine and Danshen on inhibiting Lewis lung carcinoma growth and tumor angiogenesis / 中草药

Object To investigate the effects of tetramethylpyrazine (TMP) and Danshen (DS) on the growth and metastasis of Lewis lung carcinoma and tumor angiogenesis. Methods C 57BL mice with Lewis lung carcinoma were used in this study, which were injected respectively with TMP injection 50, 100, and 200 mg/(kg?d) and DS injection 5, 10, and 20 g/(kg?d), ip, for 21 days. Then the volume, weight, and numbers of the metastatic foci on lungs, tumor microvessel density (MVD) were determined, the expression of vascular endothelial growth factor (VEGF) of Lewis lung carcinoma was observed. Results TMP could remarkably reduce the volume, weight, and numbers of the metastatic foci, MVD, and the expression of VEGF of Lewis lung carcinoma. But DS did not show remarkably effect on Lewis lung carcinoma. Conclusion TMP can remarkably inhibit the growth and metastasis of Lewis lung carcinoma on mice, and its mechanism might be relative to inhibiting the expression of VEGF and angiogenesis. DS injection has no remarkably effect on Lewis lung carcinoma.

Isolation, purification, and biological activities of ray cartilage glycosaminoglycans / 中草药

Objective To explore the methods of extraction, isolation, purification, and biological activities of ray cartilage glycosaminoglycans (RCG). Methods RCG was purified by guanidine hydrochlorid extraction, acetone fractional precipitation, ultrafiltration, and Sephadex column chromatography. The purity and molecular mass of RCG were measured by means of HPLC. The model of mouse with Lewis lung carcinoma was made, the experimental mice were randomly divided into normal saline group, RCG (500, 250, and 125 mg/kg) groups, and CTX (60 mg/kg) group. Tumor growth states of mice were observed, tumor growth curve was described, inhibitory rates of primary tumor and number of lung metastasis focus were measured; microvessel density (MVD) was quantitated by immunohistochemistry using monoclonal antibodies of CD31; the expression of vascular endothelial growth factor (VEGF) mRNA was determined with RT-PCR. Results Using HPLC, a single glycosaminoglycans with molecular mass 9.7?104 was collected and its purity exceeded ninty-nine percent. Tumor growth curves in RCG groups were smooth compared with saline group. There were significant differences of inhibitory rates of primary tumor, number of lung metastasis focus and MVD between RCG groups and saline group. VEGF mRNA expression levels in RCG groups were reduced significantly compared with saline group. Conclusion RCG could effectively inhibit the growth and metastasis of primary Lewis lung carcinoma in C57BL/6 mouse and angiogenesis.