Study on 99 Tcm-3P4-RGD2 microSPECT/CT imaging to anti-angiogensis therapeutic effect / 中华放射医学与防护杂志

Objective To investigate the value of integrin αvβ3 targeted microSPECT/CT imaging with 99 Tcm-3P4-RGD2 as a radiotracer in tumor anti-angiogenesis therapy .Methods Animal models bearing glioma and prostate cancer xenografts were established by subcutaneously injecting tumor cells U87MG and PC-3 in nude mice.Anti-angiogensis therapy with Avastin was administered via intraperitoneal injection when the tumor diameter reached 6 to 7 mm while saline was served as control group . MicroSPECT/CT imaging was performed with 99 Tcm-3P4-RGD2 as radiotracer one day before and 3, 5, 10, 15 days after Avastin administration .Tumor volume and tumor uptake of 99 Tcm-3P4-RGD2 , expressed as percentage of injected dose (%ID) or %ID per gram (%ID/g) were measured and calculated based on microSPECT/CT.Mice basic condition was monitored and tumor xenograft was harvested in one tumor bearing nude mouse after its sacrifice at each imaging time point .Results Tumor volume of U87MG glioma in the administration group was significantly smaller than that of non-administration control group at 10 d after Avastin adminstration ( t=5.81, P0.05).The uptake of 99Tcm-3P4-RGD2 (%ID/g) in U87MG group was higher than that in PC-3 group before Avastin administration ( t=10.48, P<0.05), and it decreased to a value less than control ( t =3.26, P <0.05) at 3 d after Avastin administration and continually reduced at longer time after administration .PC-3 tumor had less uptake of 99 Tcm-3P4-RGD2 in both Avastin administration group and its control group .The pathologic results revealed on that the decrease of tumor integrin β3 expression in U87MG treatment group was mainly on the endothelial cells of the neovessel .Linear relationship was verified between tumor uptake (%ID/g ) and integrin β3 expression (y=0.499 1x-0.243 8, R2 =0.811 7).Conclusions Complete inhibition of integrin is demonstrated early after Avastin administration .99 Tcm-3P4-RGD2 microSPECT/CT imaging, assessing the expression level of integrin αvβ3 level by quantification of tumor uptake of 99 Tcm-3P4-RGD2 , is probably an important method to reflect the early therapeutic effect of tumor anti -angiogensis .

Angiogenesis and cell therapy / 대한내과학회지

All cells in human body receive oxygen and nutrients and remove metabolic wastes through the vascular network. New vessel formation in a human body is significantly decreased in adults compared with fetus. New vessel formation is a critical process in pathogenesis, thus, it is a therapeutic target in several diseases, such as cancer, diabetic retinopathy, myocardial infarction and cerebral ischemia. Angiogenesis initiates through the interaction of several factors. For the increment of angiogenesis, new vessel promoting factors, such as vascular endothelial growth factor, or their genes have been directly injected to patients in the past. However, in recent studies, direct injection of cells promoting blood flow to patients has been attempted. In this paper, I will focus on cell therapy and its application in promoting blood flow in patients with impaired vessel such as myocardial infarction, cerebral ischemia and limb ischemia.

COMP-angiopoietin 1 Gene Transfer Enhances Cutaneous Wound Healing by Promoting Angiogenesis

BACKGROUND: Angiogenesis is crucial for wound healing and exogenous supplements of the angiogenic growth factors have been known to promote cutaneous wound healing. Angiopoietin (Ang) 1 is a recently discovered angiogenic factor and there have been few studies of its effect on cutaneous wound healing. OBJECTIVE: We examined the effect of Ang 1 on cutaneous wound healing. METHODS: Cartilage oligomeric matrix protein (COMP)-Ang 1 (Ade-COMP-Ang 1)- was intravenously injected to rats two days before surgery creating full-thickness wounds. The clinical wound healing rate and the number of vessels in the skin samples were evaluated on days 3, 7 and 14 post operation. RESULTS: At post-operation day 3, 7 and 14, the clinical wound healing rate was 38.3%, 59.4% and 92.1%, respectively, in the Ade-COMP-Ang 1-treated group, compared with 20.5%, 47.5% and 87.3%, respectively, in the Ade-LacZ-treated group. There were significant differences in the results of day 3 and day 7 between two groups (p<0.05). Histopathologically, the number of the vessels of the Ade-COMP-Ang 1-treated group was 73.7, 94.1 and 62.7 at day 3, 7 and 14, compared with that of the Ade-LacZ-treated group, 53.5, 83.9, and 56.9. The differences in the results of the two groups were statistically significant (p<0.05). CONCLUSION: These results indicate that Ade-COMP-Ang 1 therapy significantly accelerats wound healing by promoting angiogenesis. However, further study using Ade-COMP-Ang 1 gene therapy for chronic wounds in which the formation of new blood vessels is impaired is needed in the near future.

Study of angiogensis of ovarian serous neoplasms and ras p21 expression as well as their clinical prognosis / 中国综合临床

Objective To study the relationship between tumor angiogenesis and expression of ras p21 protein as well as the prognosis in serous ovarian neoplasms.Methods Microvessel density (MCD) and expression of ras p21 protein in issues of 10 adenomas and 50 serous ovarian cancers were observed by immunohistochemical staining methods with monoclonal antibody CD 34 to mark vascular endotheliocytes.Results Microvessel density in specimens from over expression of ras p21 protein and from grade Ⅱ and Ⅲ was significantly higher than that in specimens from low expression or negative expression of ras p21 protein as well as from grade I (P

Structure, function and signal transduction of vascular endothelial growth factor receptor-2 / 中国病理生理杂志

Angiogenesis, or the formation of new blood vessels out of pre-existing capillaries, is very important in many physiologic and pathologic processes, such as embryonic development, cancer, retinopathies, etc. Vascular endothelial growth factor receptor-2 (VEGFR-2) plays a key role in angiogenesis. In this review, we discussed the structure, function and signal transduction of vascular endothelial growth factor receptor-2. Understanding these should provide important insights into how new strategies can be devised to interfere in the physiologic and pathologic processes involved in angiogensis. [

The Relationship between Tumor Stage and the Expression of Multiple Drug Resistance, Neovascularization and Tumor Proliferative Activity in Breast Cancer / 한국유방암학회지

BACKGROUND: Breast cancer is supposed that its biological behavior should be changed in some relationship with the advancement of tumor. P-glycoprotein is the well-known nuclear protein which shows multiple drug resistance, and its expression means the resistance to various chemotherapeutic agents including anthracyclines. Angiogenesis was also suggested to have an important role in tumor progression and metastasis, which has been considered to be one of valuable independent prognostic factors. Tumor proliferative activity also has been thought to be very useful as a factor representing the biological behavior of tumor, but its role isn't fully understood yet. In this study we aimed to observe how these factors are expressed with any relationship according to the tumor stage and to find the feature of its expression in each stage and its clinicopathologic significances. MATERIALS AND METHOD: 62 cases of patients histologically proven into invasive ductal carcinoma, who were diagnosed and treated at the Department of Surgery, Chonnam National University Hospital, were selected. In order to estimate the staining results accurately, we classified the expression grades of Pgp into 5 classes according to the count of immunostained cells after immunohistochemical staining. Angiogensis was determined by the mean count of microvessels measured by image analyzer moving more than 40 fields with 200 folds magnification after immunohistochemical staining for CD34. Tumor proloferative activity were presented in percentage by counting the positively immunostained cells in more than 500 tumor cells after immunohistochemical staining with Ki67. Statistical evaluation was done by Mann-Whitney test and we determined that the result showing p-value less than 0.05 is statistically significant. RESULTS: The mean that age was 49 year(from 33years to 82years) and the stage distribution was stage I: 4 patients, stage II a : 25, stage II b : 18, stage III a : 7, stage III b : 3, and stage IV : 5 patients. In spite of Pgp expression tended to increase as the stage advanced, it did not show any ststistically significant difference(P=0.165). Although Ki67 score representing tumor proliferation activity was observed from 0% to 30.8%, any significant differences according advancement of stage were not found(P=0.850). Tumoric angiogenesis also did not show any statistical difference according to advancement of stage(p=0.189). CONCLUSIONS: We could not find any significant proportional correlationship between the tumor stage and Pgp expression, tumor proliferative activity, and angiogenesis. Therefore, the clinicopathologic significances of these factors are supposed to determined an individual biological feature of the tumor irrespective of stage.