【Abstract】Objective To understand the features of lymphatic vessel, and to summarize the foundation and mechanism of the promotion and inhibition of tumor lymphangiogenesis recorded on the current studies of animal experiments and clinical researches. Methods The related literatures of the structural features of lymphatic vessel, lymphatic endothelial molecular markers, the origin of lymphatic tumors, the molecular mechanisms and regulatory factors were reviewed, and the relationship between tumor lymphangiogenesis and lymphatic metastasis, the treatment targeting at the formation of the anti-tumor lymphatic vessel and its existing problems were also analyzed. Results Hyperplasia of lymphatic vessels occurred during the process of tumor formation and progression. The structural features of the lymphatic vessels in the tumor were conducive to tumor lymphatic metastasis. In recent years, methods of anti-lymphangiogenesis and inhibition of tumor lymphatic metastasis had achieved considerable success in animal experiments. However, there were still a lot of problems need to be solved. Conclusion Tumor lymphangiogenesis has a significantly positive correlation between tumor lymphatic metastasis and patients’ prognosis, which may indicate that treatment against the formation of tumor lymphatic vessel maybe effective.
Objective To investigate whether the growth of the human experimental hepatocellular carcinoma (HCC) can be suppressed by the antibody against vascular endothelial growth factor (VEGF). MethodsThe monoclonal antiVEGF antibody was injected to nude mice nearby the xenograft tumour foculs of the human SMMC7721 HCC. The changes of the tumour size were measured at different times. The intratumoural microvessels were showed by immunohistochemical staining of CD31 antigen; the apoptotic cells in the tumour tissues were detected in situ by terminal deoxynucleotidyl transferasemediated dUTPbiotin nick end labeling (TUNEL) assay. ResultsIn the first and second week after finishing the injection procedure, the tumour sizes were compared as the length (mm) multiplying width (mm) between the two groups, the tumour sizes as the test group vs the control group were (26.46±19.81) mm2 vs (105.77±17.40) mm2 (P＜0.001) and (45.20±23.02) mm2 vs (150.77±77.41) mm2 (P＜0.05), respectively. After 2 weeks the intratumoural microvessel density (iMVD) and the apoptotic index (AI) were compared between two groups with iMVD being (2 311±120)/mm2 vs (3 900±328)/mm2(P＜0.001 ) and AI being (15.31% vs 6.83%), P＜0.005. Conclusion The antiVEGF antibody can suppress the xenograft tumour growth of the human SMMC7721 HCC by antiangiogenesis.In fact, its antitumour effect is produced by elevating the incidence of apoptosis in tumour tissues.
Objective To study the expression of thymidine phosporylase (TP) and the counts of lymph vessels in pancreatic cancer and chronic pancreatitis tissues, and to explore their clinicopathologic significances and correlation in the course of pancreatic cancer. Methods SP immunohistochemical method was used to detetct the expression of TP and the locations of lymph vessels on the routinely paraffin-embedded sections of the specimens from 51 cases pancreatic cancer and 10 cases of chronic pancreatitis. Results The positive rate of TP and the counts of lymph vessels were significantly higher (P＜0.05 and P＜0.01 respectively) in pancreatic cancer 〔54.9%, (12.5±4.3)/HP〕 than those in chronic pancreatitis 〔20.0%，(5.2±2.4)/HP〕. The positive rate of TP and the counts of lymph vessels were significantly lower （P＜0.05, P＜0.01） in well-differentiated adenocarcinoma cases and cases without metastasis compared with poor-differentiated adenocarcinoma cases and cases with metastasis. The counts of lymph vessels were significantly higher in the positive cases of TP than those in the negative ones in pancreatic cancer 〔(13.8±3.4)/HP vs (10.9±3.2)/HP〕, P＜0.01.Conclusion The expression of TP and counts of lymph vessels might be important markers reflecting the progression, biological behaviors, metastatic status and prognosis of pancreatic cancer. TP might promote lympoangiogenesis in pancreatic cancer tissues.
【Abstract】Objective To introduce the current studies of the role of vascular endothelial growth factorC (VEGFC) and VEGFD in lymphangiogenesis and lymph node metastasis of gastrointestinal neoplasma. Methods The related literatures in recent 5 years were reviewed. Results The growth factors VEGFC and VEGFD enhance lymphangiogenic metastasis of gastrointestinal neoplasma with the property of angiogenesis and lymphangiogenesis. In gastric adenocarcinoma, VEGFC mRNA and tissue protein expression correlate with lymphatic invasion, lymph node metastasis, venous invasion and reduced 5year survival rates. The role of VEGFC in esophageal squamous cancer and colorectal cancer and VEGFD in colorectal cancer is not certain, with conflicting reports in the published literatures.Conclusion The VEGFC, VEGFD/VEGFR3 signal pathway may become the ideal target for inhibition of tumor proliferation and metastases, antilymphangiogenesis therapy may be a novel potential strategy in tumor biological therapy.
This research is to explore the perfusion time-intensity curve parameters of a lung adenocarcinoma xenograft into nude mouse model with contrast enhanced ultrasonography (CEUS); and to investigate the angiogenesis features of tumor at different growth time. Twenty one lung adenocarcinoma xenografted nude mice were divided into three groups and inculcated with human lung adenocarcinoa. Time window for examining CEUS were respectively in 7-day, 14-day and 28-day. The perfusion parameters including rise time (RT), peak intensity (PI), area under the curve (AUC) of lung tumor were obtained on CEUS images by using off-line software Q lab. Immunohistochemically staining for CD34 was used to observe the microvessel density (MVD).The 7-day group had the highest AUC and PI; AUC and PI of 14-day and 28-day group decreased gradually (P < 0.05). RT was increased as tumor growth. In tumor with necrosis, AUC and PI of non-necrosis part were also larger than necrosis part (P < 0.05). Immunohistochemically staining for CD34 of all tumors reflected that the density of microvessels in necrosis tumor was significantly higher than those without necrosis (7.50±3.44 vs.12.44±5.74, P=0.034). Pearson correlation indicated that PI was positively related with MVD (r=0.668, P=0.008). Lung adenocarcinoma perfusion characteristic can be accessed from time-intensity curve parameters by using noninvasively and non-radiative contrast enhanced ultrasonography. Time-intensity curve parameters including AUC, PI and RT may reflect tumor angiogenesis.
This study aims to investigate the effect of substances secreted or metabolized by vascular endothelial cells on epithelial-mesenchymal transition (EMT) of hepatocellular carcinoma cells under indirect co-culture condition. Human hepatocellular carcinoma cell line QGY-7703 was cultured in vitro, and then was co-cultured with conditioned medium of human umbilical vein endothelial cells (HUVEC). The morphological changes of QGY-7703 cells were observed by inverted phase contrast microscopy. The migration ability of QGY-7703 cells was analyzed by scratch-wound assays. The effect of conditioned medium on the expression and distribution of EMT related proteins was detected by Western blot and immunofluorescence assays, respectively. The results showed that the QGY-7703 cells gradually changed from polygonal to spindle shape, the migration ability promoted significantly, and both the expression and distribution of EMT related marker changed in a time-dependent manner after co-culturing. The results confirm that vascular endothelial cells can induce EMT in hepatocellular carcinoma cells under indirect co-culture condition.
摘要:目的: 探讨选择性内皮素A受体拮抗剂BQ123对人喉癌Hep2细胞裸鼠种植瘤的生长及血管形成的影响。 方法 :将实验动物裸鼠随机分为3组:BQ123［n =8,2mg/(kg·day)］、氟尿嘧啶组［n =8,2mg/(kg·day)］、生理盐水组(n =8),比较各组裸鼠成瘤体积、微血管密度(MVD)。 结果 :BQ123组肿瘤体积为(162±053)cm3,明显小于生理盐水组及氟尿嘧啶组,差异具有统计学意义;BQ123组的肿瘤组织中MVD高倍镜下为232,明显低于生理盐水组(586)及氟尿嘧啶组(395),差异具有统计学意义。 结论 :BQ123对人喉癌Hep2细胞在裸鼠体内有明显抑瘤作用,肿瘤的体积、肿瘤组织MVD显著低于对照组,表明BQ123可通过抑制肿瘤血管生成而显著抑制肿瘤生长。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 find the role of oncogene cmet and suppressor gene p53 in the process of tumor angiogenesis and their clinical significance. MethodsBy immunohistochemical method and computer image analysis technique, microvessel count and cmet, p53 protein expression were quantitatively determined in 80 cases of breast carcinoma and 20 cases of breast fibroadenoma. ResultsThe high microvessel count and the positive expression of cmet, p53 were significantly correlated with histologic grade, lymph node metastasis and the stage of the tumor (P＜0.01). The high microvessel count was significantly correlated with the positive expression of cmet and p53 (P＜0.01).ConclusionBoth oncogene cmet and suppressor gene p53 modulate tumor angiogenesis of breast carcinoma.
ObjectiveTo review the research progress on the role and mechanism of matrix stiffness in regulating endothelial cell sprouting. MethodsThe related literature at home and abroad in recent years was extensively reviewed, and the behaviors of matrix stiffness related endothelial cell sprouting in different cell cultivation conditions were analyzed, and the specific molecular mechanism of matrix stiffness regulating related signal pathways in endothelial cell sprouting was elaborated. Results In two-dimensional cell cultivation condition, increase of matrix stiffness stimulates endothelial cell sprouting within a certain range. However, in three-dimensional cell cultivation condition, the detailed function of matrix stiffness in regulating endothelial cell sprouting and angiogenesis are still unclear. At present, the research of the related molecular mechanism mainly focuses on YAP/TAZ, and roles of its upstream and downstream signal molecules. Matrix stiffness can regulate endothelial cell sprouting by activating or inhibiting signal pathways to participate in vascularization. ConclusionMatrix stiffness plays a vital role in regulating endothelial cell sprouting, but its specific role and molecular mechanism in different environments remain ambiguous and need further study.
ObjectiveTo investigate the mechanism of early vascularization of the tissue engineered bone in the treatment of rabbit radial bone defect by local injection of angiopoietin 2 (Ang-2).MethodsForty-eight New Zealand white rabbits were established unilateral 1.5 cm long radius defect models. After implantation of hydroxyapatite/collagen scaffolds in bone defects, the rabbits were randomly divided into 2 groups: control group (group A) and Ang-2 group (group B) were daily injected with 1 mL normal saline and 1 mL saline-soluble 400 ng/mL Ang-2 at the bone defect within 2 weeks after operation, respectively. Western blot was used to detect the expressions of autophagy related protein [microtubule associated protein 1 light chain 3 (LC3), Beclin-1], angiogenesis related protein [vascular endothelial growth factor (VEGF)], and autophagy degradable substrate protein (SQSTMl/p62) in callus. X-ray films examination and Lane-Sandhu X-ray scoring were performed to evaluate the bone defect repair at 4, 8, and 12 weeks after operation. The rabbits were sacrificed at 12 weeks after operation for gross observation, and the angiogenesis of bone defect area was observed by HE staining.ResultsWestern blot assay showed that the relative expressions of LC3-Ⅱ/LC3-Ⅰ, Beclin-1, and VEGF in group B were significantly higher than those in group A, and the relative expression of SQSTMl/p62 was significantly lower than that in group A (P<0.05). Radiographic and gross observation of specimens showed that only a few callus were formed in group A, the bone defect was not repaired; more callus were formed and complete repair of bone defect was observed in group B. The Lane-Sandhu scores in group B were significantly higher than those in group A at 4, 8, and 12 weeks after operation (P<0.05). HE staining showed that the Harvard tubes in group B were well arranged and the number of new vessels was significantly higher than that in group A (t=–11.879, P=0.000).ConclusionLocal injection of appropriate concentration of Ang-2 may promote early vascularization and bone defect repair of tissue engineered bone in rabbits by enhancing autophagy.