Tumor cell proliferation, infiltration, migration, and neovascularization are known causes of treatment resistance in glioblastoma multiforme(GBM). The purpose of this study was to determine the effect of radiation on...Tumor cell proliferation, infiltration, migration, and neovascularization are known causes of treatment resistance in glioblastoma multiforme(GBM). The purpose of this study was to determine the effect of radiation on the growth characteristics of primary human GBM developed in a nude rat. Primary GBM cells grown from explanted GBM tissues were implanted orthotopically in nude rats. Tumor growth was confirmed by magnetic resonance imaging on day 77(baseline) after implantation. The rats underwent irradiation to a dose of 50 Gy delivered subcuratively on day 84 postimplantation(n = 8), or underwent no radiation(n = 8). Brain tissues were obtained on day 112(nonirradiated) or day 133(irradiated). Immunohistochemistry was performed to determine tumor cell proliferation(Ki-67) and to assess the expression of infiltration marker(matrix metalloproteinase-2, MMP-2) and cell migration marker(CD44). Tumor neovascularization was assessed by microvessel density using von-Willebrand factor(vWF) staining. Magnetic resonance imaging showed well-developed, infiltrative tumors in 11 weeks postimplantation. The proportion of Ki-67-positive cells in tumors undergoing radiation was(71 ± 15)% compared with(25 ± 12)% in the nonirradiated group(P = 0.02). The number of MMP-2-positive areas and proportion of CD44-positive cells were also high in tumors receiving radiation, indicating great invasion and infiltration. Microvessel density analysis did not show a significant difference between nonirradiated and irradiated tumors. Taken together, we found that subcurative radiation significantly increased proliferation, invasion, and migration of primary GBM. Our study provides insights into possible mechanisms of treatment resistance following radiation therapy for GBM.展开更多
病人教育是发生在医生与病人之间宣教与学习的过程,病人教育能够改善医患关系、提高病人满意度、降低病人费用、降低发病率和死亡率,提高生活质量,使病人能自觉规范自己的健康行为或增加他们促进健康的自主能力.研究表明,病人教育的战...病人教育是发生在医生与病人之间宣教与学习的过程,病人教育能够改善医患关系、提高病人满意度、降低病人费用、降低发病率和死亡率,提高生活质量,使病人能自觉规范自己的健康行为或增加他们促进健康的自主能力.研究表明,病人教育的战略可以给社会带来巨大效益(Mulen et al,1995),在病人教育方面投资1美元,可以节约3～4美元的医疗费用(Bartlett,1995).目前主要由美国全科医生学院(AAPF)和全科医学的师资团体(STFM)负责组织病人教育系列专题委员会,设立病人教育的分支机构.展开更多
基金supported by grants from the National Institutes of Health (NIH) [No. K25CA129173 (MMA), R01CA122031 (ASA), and 1R01CA160216 (ASA)]
文摘Tumor cell proliferation, infiltration, migration, and neovascularization are known causes of treatment resistance in glioblastoma multiforme(GBM). The purpose of this study was to determine the effect of radiation on the growth characteristics of primary human GBM developed in a nude rat. Primary GBM cells grown from explanted GBM tissues were implanted orthotopically in nude rats. Tumor growth was confirmed by magnetic resonance imaging on day 77(baseline) after implantation. The rats underwent irradiation to a dose of 50 Gy delivered subcuratively on day 84 postimplantation(n = 8), or underwent no radiation(n = 8). Brain tissues were obtained on day 112(nonirradiated) or day 133(irradiated). Immunohistochemistry was performed to determine tumor cell proliferation(Ki-67) and to assess the expression of infiltration marker(matrix metalloproteinase-2, MMP-2) and cell migration marker(CD44). Tumor neovascularization was assessed by microvessel density using von-Willebrand factor(vWF) staining. Magnetic resonance imaging showed well-developed, infiltrative tumors in 11 weeks postimplantation. The proportion of Ki-67-positive cells in tumors undergoing radiation was(71 ± 15)% compared with(25 ± 12)% in the nonirradiated group(P = 0.02). The number of MMP-2-positive areas and proportion of CD44-positive cells were also high in tumors receiving radiation, indicating great invasion and infiltration. Microvessel density analysis did not show a significant difference between nonirradiated and irradiated tumors. Taken together, we found that subcurative radiation significantly increased proliferation, invasion, and migration of primary GBM. Our study provides insights into possible mechanisms of treatment resistance following radiation therapy for GBM.
文摘病人教育是发生在医生与病人之间宣教与学习的过程,病人教育能够改善医患关系、提高病人满意度、降低病人费用、降低发病率和死亡率,提高生活质量,使病人能自觉规范自己的健康行为或增加他们促进健康的自主能力.研究表明,病人教育的战略可以给社会带来巨大效益(Mulen et al,1995),在病人教育方面投资1美元,可以节约3～4美元的医疗费用(Bartlett,1995).目前主要由美国全科医生学院(AAPF)和全科医学的师资团体(STFM)负责组织病人教育系列专题委员会,设立病人教育的分支机构.
