摘要:目的: 探討選擇性內皮素A受體拮抗劑BQ123對人喉癌Hep2細胞裸鼠種植瘤的生長及血管形成的影響。 方法 :將實驗動物裸鼠隨機分為3組:BQ123［n =8,2mg/(kg·day)］、氟尿嘧啶組［n =8,2mg/(kg·day)］、生理鹽水組(n =8),比較各組裸鼠成瘤體積、微血管密度(MVD)。 結果 :BQ123組腫瘤體積為(162±053)cm3,明顯小于生理鹽水組及氟尿嘧啶組,差異具有統計學意義;BQ123組的腫瘤組織中MVD高倍鏡下為232,明顯低于生理鹽水組(586)及氟尿嘧啶組(395),差異具有統計學意義。 結論 :BQ123對人喉癌Hep2細胞在裸鼠體內有明顯抑瘤作用,腫瘤的體積、腫瘤組織MVD顯著低于對照組,表明BQ123可通過抑制腫瘤血管生成而顯著抑制腫瘤生長。Abstract: Objective: To study the effects of endothelin A receptor blockade BQ123 on the implanted human laryngeal carcinoma angiogenesis of nude mouse. Methods : From March 2008 to July 2009, 24 Balb/c nude mice were randomly divided into three groups: BQ123 group ［〖WTBX〗n =8, BQ123 at 2mg/(kg·day)］, 5Fu group ［〖WTBX〗n =8, fluorouracil at 2mg/(kg·day)］ and the control group (〖WTBX〗n =8, normal saline). The carcinoma volume and microvascular density of each group were compared. Results : The tumor size of BQ123 group, which was (162±053)cm3 in average, was significant smaller than the tumor sizes of the other two group s. The average microvascular density score of the tumors in BQ123 group was 232 per hyper power len (HP), which was also significantly less than the average scores of control groups (586 and 395 respectively). Conclusion : Nude mouse experiments show that the carcinoma volume and microvascular density of BQ123 group are significantly lower than those of the control groups. BQ123 inhibits the growth of carcinoma by its inhibition of carcinoma angiogenesis.
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.
【Abstract】 Objective To investigate the effect of NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase, on the growth of colorectal cancer xenografts in vivo and on tumor-associated neovascularization. Methods Twenty BALB/c nude mice were randomly divided into control group and study group equally. Human colorectal cancer cell line SL174T was inoculated subcutaneously into nude mice to form transplantation tumors. Saline 0.2 ml was intragastric-administrated to mice in control group and L-NAME （4 mg toties guoties) was administrated orally to mice in study group three times per week for four weeks. The changes of tumors in both groups were recorded and the microvessel density (MVD) was also measured by immunohistochemistry assay. Results L-NAME significantly inhibited the growth of colorectal cancer xenografts in nude mice. The weight of transplantation tumor reduced with the inhibitory rate of 41.36%, and the inhibitory rate of tumor volume was 43.48% in study group. MVD in the study group and control group were 14.83±2.10 and 21.04±3.11, respectively, which showed that the former was significantly lower than that of the control group （P＜0.05）. Conclusion L-NAME may inhibit the growth of colorectal cancer via the suppression of tumor neovascularization.
Objective To study the effect of recombinant adeno-associated virus (rAAV) vector co-expressing human vascular endothel ial growth factor 165 (hVEGF165) and human bone morphogenetic protein 7 (hBMP-7) genes on bone regeneration and angiopoiesis in vivo so as to provide a theoretical basis for the gene therapy of avascular necrosis of thefemoral head (ANFH). Methods Twenty-four male adult New Zealand rabbits were made the ischemic hind l imb model and divided into 4 groups (n=6). The 3rd generation rabbit bone marrow mesenchymal stem cells (BMSCs) were transfected with the following 4 virus and were administered intramuscularly into the ischemic thigh muscle of 4 groups, respectively: rAAVhVEGF165- internal ribosome entry site (IRES)-hBMP-7 (group A), rAAV-hVEGF165-green fluorescent protein (GFP) (group B), rAAV-hBMP-7-GFP (group C), and rAAV-IRES-GFP (group D). At 8 weeks after injection, the blood flow of anterior tibial artery in the rabbit hind l imb was detected by ultrasonographic image. Immunohistochemical staining for CD34 was performed to identify the prol iferation of capillary. Another 24 male adult New Zealand rabbits were made the femur muscle pouch model and divided into 4 groups (n=6). The above 4 BMSCs transfected with rAAV were administered intramuscularly into the muscle pouch. At 8 weeks after injection, X-ray radiography was used to assess orthotopic bone formation, and von Kossa staining to show mineral ization. Results No symptoms of local or systemic toxicity were observed after rAAV injection. At 8 weeks after injection, the ratio of ischemic to normal blood flow and the number of capillaries in group A were the highest among 4 groups (P lt; 0.05). The ratio of ischemic to normal blood flow and the number of capillaries in group B were significantly higher than those in group C and group D (P lt; 0.05). However, there was no significant difference between group C and group D (P gt; 0.05). At 8 weeks after injection, orthotopic ossification and mineral ization were evidently detected in group A and group C, and group A was ber than group C. No obvious evidence of orthotopic ossification and mineral ization were observed in group B and group D. Conclusion rAAV-hVEGF165-IRES-hBMP-7 vector has the biological activities of inductive bone regeneration and angiopoiesis in vivo.
【Abstract】Objective To study the effects of exogenous hyaluronidase on invasive and angiogenic potential of human breast cancer cell line ZR-75-30.MethodsThere were two groups in the study: the study group (hyaluronidase group) and the control group. The invasive potential and the angiogenic potential of human breast cancer cell ZR-75-30 were detected by the invasive model in vitro and technique of double-chamber co-culture that human breast cancer cell line ZR-75-30 and human umbilicus vein endothelium cell ECV-304 were co-cultured. ResultsThe penetrating number of tumor cell in the study group (70.625±11.64) was significantly higher than that in the control group (22.125±6.09),P＜0.01. The tube number from ECV-304 cell induced by ZR-75-30 cell in the study group (34.5±2.4) was significantly higher than that in the control group (8.5±1.5)， P＜0.01. ConclusionExogenous hyaluronidase can reinforth the invasive and angiogenic ability of breast cancer cells.
Objective To determine whether tumor angiogenesis correlates with progression of colorectal carcinoma. Methods Microvessel counts (MVC) of 102 specimens resected from patients with colorectal carcinoma were investigated by immunohistological staining with a monocolonal antibody against FⅧ RAg, the mean number of microvessels in three areas of highest vascular density were counted under 200 times magnification microscope. Correlation of MVC with various clinicopathologic factors, and prognosis was studied. Results MVC was increased with Dukes stage, the MVC of patients with advanced stage disease was significantly higher than that of early stage patients (P＜0.01). MVC was significantly higher in tumors with lymph node metastasis and liver metastasis (P＜0.01) than in those without such metastasis. The recurrence rate after curative resection in hypervascular group (MVC≥14, 60.4%) was significantly higher (P＜0.01) than that in the hypovascular group (MVC＜14,26.5%).Moreover, the prognosis of patients with a high MVC was significantly poorer than that of those with a low MVC (P＜0.01). Conclusion Angiogenesis within colorectal cancer is an indicator of tumor behavior and may identify patients at higher risk for recurrence and poorer prognosis.
Objective To improve the operative effects of patients who had tetralogy of Fallot with aortopulmonary collateral arteries (TOF-APCAs) and evaluate the clinical effects of staging and onestop hybrid approach for TOFAPCAs. Methods From January 2003 to December 2007, thirty patients with TOF-APCAs had undergone combined therapy of APCAs embolization and complete surgical repair. Fifteen patients had APCAs embolization therapy before or after TOF radical operation(staging hybrid group ); Fifteen had onestop hybrid treatment(onestop hybrid group). Results Angiography revealed that there were 19 APCAs in staging hybrid group, and of which 15(78％) were embolized successfully. Five cases had complications and one died from respiratory circulating failure. The rest all recovered and discharged. And 22 APCAs were found in one-stop hybrid group, eighteen (82％) of them were embolized successfully. Only one case had pulmonary effusion. The time of hospitalization(median 37 d vs. 22 d, P=0.011),ICU staying（median 7.0 d vs. 4.7 d,P=0.029）and endotracheal intubation（median 131 h vs. 19 h,P=0.009） was obviously longer, and the hospitalization expenses（median 64 101 [CM(159mm]yuan vs. 48 021 yuan, P=0.033）were obviously higher in staging hybrid group than that in one-stop hybrid group.And there was no statistical significance in cardiopulmonary bypass time（P=0.126） and aortic clamping time（P=0.174） between two groups. Conclusion In comparison with traditional staging hybrid approach, one-stop hybrid approach can simplify the operative process for patients who have TOFAPCAs, improve the operative successful rate and cut down expenses.
Objective To summarize the research progress of controlled release of angiogenic factors and osteogenic factors in bone tissue engineering. Methods The domestic and abroad literature on the controlled release structure of growth factors during bone regeneration in recent years was extensively reviewed and summarized. Results The sustained-release structure includes direct binding, microsphere-three-dimensional scaffold structure, core-shell structure, layer self-assembly, hydrogel, and gene carrier. A sustained-release system composed of different sustained-release structures combined with different growth factors can promote bone regeneration and angiogenesis. Conclusion Due to its controllability and persistence, the growth factor sustained-release system has become a research hotspot in bone tissue engineering and has broad application prospects.
Objective To summarize the role of matrix metalloproteinases (MMPs) in occurrence and development of gastric cancer. Methods Domestic and international publications online involving MMPs of gastric cancer in recent years were collected and reviewed. Results The occurrence and development of gastric cancer was a multi-step and multi-factorial complicated progress, whose etiology and pathogenesis were still unclarified. MMPs were a class of proteolytic enzymes, which played an important role in the proliferation, metastasis, angiogenesis of gastric cancer and apoptosis of tumor cells and their surrounding normal cells by regulating the microenvironment of the growth of tumor. Conclusion MMPs promote the evolution of gastric cancer in variable ways, the mechanisms of which should be comprehended to provide a theoretical basis for the future treatment of gastric cancer.