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The Effect Of Angiogenesis On Human Fibrosarcoma Xenografts In Nude Mice Induced By 125I Seeds Brachytherapy

Posted on:2011-05-16Degree:MasterType:Thesis
Country:ChinaCandidate:Z H HuFull Text:PDF
GTID:2154360308974096Subject:Oncology
Abstract/Summary:PDF Full Text Request
The incidence of fibrosarcoma is relatively low, but does great harm to health of the people. At present,surgical operation is a main procedure which is often combined with radiotherapy and chemotherapy to improve therapeutic efficacy. As we know,there are a great many cases which cannot be treated with surgical resection or radical resection in practice,radiation doses is limitde by approaching important structure,and chemotherapy is deemed to poor sensitivity. Interstitial implantation of radioactive seeds,one kind of brachytherapy,is a good method which can greatly injury tumor by implanting radioactive microsources which can irradiate gammer rays with low capacity continousely wheres nomal tissue is not or slightly injuried.And compared to a high degree of external conformal radiotherapy, brachytherapy is characterlized by high dose in target area, small injury, and so on The brachytherapy of 125I is already used in the clinical applications of soft tissue sarcoma in a small range, But the treatment-related basic research is still absence. Tumor angiogenesis is not only a foundation for tumor growth, but also for creating the conditions for invasion and metastasis. At home and abroad have found that tumor cells promote angiogenesisthrough the secretion and activating vascular growth factors.However, fibrosarcoma in the expression of pro-angiogenic factors reported rare. In this study, through the establishment of human fibrosarcoma xenografts in nude mice, we detected the expression level of vascular endothelial growth factor (VEGF)and microvessel density (MVD) in the human fibrosarcoma, observed the early anti-tumor effect by 125I,found fibrosarcoma cells and microvascular pathological degree of injury,and the expression of VEGF and MVD.Then we would probe the early effects of angiogenesis in human fibrosarcoma by 125I seed implantation. Objective : To investigate the human fibrosarcoma of vascular endothelial growth factor expression , angiogenesis situation and find the causes of 125I brachytherapy particles fibrosarcoma inhibits subcutaneous tumor angiogenesis in nude mice . and to show the influence of fibrosarcoma capillary growth by different particle activity inhibited 125I.Methods: To establish the human fibrosarcoma cells (HT-1080) nude mice xenograft model,when the tumors` diameter were (10±1) mm, chose 24 survive tumor-bearing nude mice that the rule of shape standardized, by randomly divided into 4 groups, experimental group A, B, C were implanted in a single monolithic activity as 14.8MBq, 22.2MBq, 29.6MBq of 125I particles implanted in the control group D source of a single, empty. Particles after implantation, a complete resection 15d, using vernier caliper measurements xenografts in nude mice long diameter (a) and wide-diameter (b), according to V = ab2×0.52 formula tumor volume (mm3), according to the following formula tumor volume inhibition rate: (IR) = (mean tumor volume control group - experimental group, mean tumor volume) / control group mean tumor volume×100%, analysis of whether the statistically significant differences between the groups. In the largest tumor profiles drawn along the long axis view particle four groups each selected slices, observation of each group of tumor cells and microvascular histopathology by light microscopic. According to the 2002 Wheelerˋs rectal cancer regression grading standards [1] (Rectal Cancer Regression Grade, RCRG) evaluate the histopathologic response. Immunohistochemical detected the structural changes in tumor microvessels and vascular endothelial growth factor (vascular endothelial growth factor, VEGF) expression, comparing groups of markers CD105 microvessel density (microvessel density, MVD).Results:1. Establish of human fibrosarcoma xenografts in nude mice successfully. On the 15th day after the 125I seed implantation,the average tumor volume of A, B, C, D group,,respectively: (879.32±54.904),(186.91±32.70), (122.01±34.72) and (1302.71±62.39) mm3. There were significant differences between the groups (F = 844.21, P <0.0001), A, B, C group tumor volume inhibition rates by 125I particles were 32.50%, 85.65% and 90.63%.2. Compared with the control group, experimental group shown tumor cell necrosis, varying degrees of reduction in microvascular endothelial cells of anti-evident. There were different levels of histopathologic response in every group. In group A and B, F = 8.80 P = 0.036 <0.05, group A and C, F = 3.375 P = 0.012 <0.05, the differences were statistically significant,respectively. AD, between the two groups, F=3.37, P=0.066, the difference was not statistically significant. between B and C group, F =0.00, P=1.00 ,where were no statistically significant difference .3. Human fibrosarcoma xenografts in nude mice in the VEGF-positive rate was about 66.7%. The positive rate of VEGF expression in the four groups were 54.2%(13/24), 29.2%(7/24), 20.8%(5/24), 66.7%(16/24), between the group A, D there was no significant difference in VEGF expression (X2 = 0.784 P = 0.376). B, C group were significantly lower than VEGF expression in D group, X2, respectively 6.761,10.243, the difference was statistically significant (P = 0.001 <0.05).4. Expression of four groups of MVD were 27.49±3.10,10.27±3.57,9.14±2.49,30.15±4.26, between the group A, D there was no statistically significant difference in MVD expression (q=3.814 P = 0.259). group B, C MVD expression were significantly lower than D group, F respectively, 28.502,30.123, the difference was statistically significant (P = 0.0001 <0.05).Conclusions:VEGF, MVD in human fibrosarcoma have a higher expression.Interstitial implantation with 125I seed had significant effect on angiogenesis of the human fibrosarcoma xenografts in nude mice, and the initial activties of the 125I seed can effect treatment effectiveness。...
Keywords/Search Tags:Iodine-125 seed, Brachytherapy, Human fibrosarcoma, Nude mice, VEGF, MVD
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