人脑瘤裸小鼠原位移植模型的亲本性探索
|
摘要
目的(1)通过改良肿瘤组织移植的方法以获得良好的人脑胶质瘤裸小鼠脑内移植模型。在此基础上,去建立人脑多形性胶质母细胞瘤(glioblastoma multiform,GBM)和人肺腺癌脑转移瘤的裸小鼠模型,并探知其生物学特性能否保持其亲本肿瘤的特性。(2)培育表达绿色荧光蛋白(green fluoresent protein,GFP)的裸小鼠,将其用于人胶质瘤干细胞(human glioma stem cells,HGSCs)移植实验研究,并阐明HGSCs在宿主脑组织中具有播散和融合其它细胞的特征,以用于肿瘤组织重构的研究。
方法(1)先用SHG-44胶质瘤细胞(1×107)注射于裸小鼠皮下,形成皮下移植瘤,再把皮下移植瘤组织通过自制的组织挤压装置放入24#无菌套管针,并调整肿瘤的体积为2.0mm3,然后把定量要移植的肿瘤组织块植入裸小鼠右尾状核,制作成裸小鼠脑内移植瘤模型。观察移植后裸小鼠生存状态。30d后解剖裸小鼠取脑并行病理切片,观察原位移植瘤的形态、病理学特征和成瘤率。(2)将体外培养高表达表皮生长因子受体(epidermal growth factor receptor,EGFR)的人脑GBM细胞,在立体定向仪辅助下行裸小鼠右尾状核接种;继而将致瘤的组织通过自制的组织挤压装置放入24#无菌套管针,然后将2.0mm3的肿瘤组织经徒手操作接种于裸小鼠右尾状核,致瘤后即用裸小鼠的瘤组织再进行原位传代接种。接种后观察移植瘤的生长特性,并分析EGFR在各代移植瘤中的表达。(3)取人肺腺癌脑转移瘤组织块,通过自制的组织挤压装置放入24#无菌套管针,然后将2.0mm3的肿瘤组织经徒手操作接种于裸小鼠右尾状核。致瘤后即用裸小鼠的瘤组织再进行原位传代接种,然后观察致瘤率及荷瘤鼠生存期;HE染色分析各代移植瘤的组织学形态;MRI观察移植瘤在鼠脑内的大体形态;免疫组化染色观察移植瘤中CEA的表达;Alcian blue/PAS特殊染色检测移植瘤中粘液的性质。(4)将C57BL/6J-GFP转基因小鼠与NC系裸小鼠进行交配,在继代时严格挑选都表达GFP的无毛雄鼠(♂)与有毛雌鼠(♀)交配,通过肉眼和荧光显微镜等方法观察GFP在裸小鼠皮肤和脏器中的表达情况,继将HGSCs原位移植于表达GFP的裸小鼠,以观察移植瘤的生长情况。
结果(1)通过改良的肿瘤组织块移植后,18只裸小鼠除3只接种当日死亡外,其余15只于移植后30d被处死取脑行冰冻切片,HE染色在光镜下见移植瘤侵袭性生长。致瘤率为93%(14/15)。(2)人GBM移植瘤组织在裸小鼠尾状核已连续传至13代,共130只鼠,荷瘤鼠生存期为19±1.33d。移植瘤病理学符合呈高度侵袭性生长、EGFR过表达的人脑GBM的特征。不同时间测得的肿瘤增殖曲线提示,致瘤的潜伏期短(<3d),持续快速增殖期长(>15d),进入晚期至死亡时间短(<3d)。(3)人肺腺癌脑转移瘤组织在裸小鼠右尾状核已连续传至6代,共65只鼠。荷瘤鼠生存期:原代为47.6±1.8d,2-3代有所缩短,4-6代稳定在38.0±0.9d;移植瘤病理为低分化腺癌,不向周围正常鼠脑组织侵袭;MRI示移植瘤类圆形,瘤周无水肿,与临床病例的MRI一致;移植瘤中癌胚抗原(carcinoembryonic antigen,CEA)表达阳性,并有酸性粘液存在。(4)GFP荧光裸小鼠已传至8代,包括脑在内的全身主要器官和细胞都发绿色荧光。对用于HGSCs原位移植的脑,能清晰辨认出不发光的瘤细胞和发光的宿主细胞。而瘤细胞经抗人类白细胞抗原(human leukocyte antigen,HLA)-Ⅰ抗体偶联红色荧光剂(PE)的免疫组织化学染色后,在共聚焦显微镜下可清晰显示HGSCs与宿主脑细胞的组织学关系是:多数播散,个别的发生细胞与细胞融合。
结论(1)通过改良的组织定量移植具有操作简便,对小鼠创伤小,速度快,成瘤率高,便于批量制作原位移植裸小鼠模型。(2)人GBM肿瘤组织于鼠尾状核接种比传统的肿瘤细胞悬液接种,非但接种的细胞量大,还能将支持肿瘤细胞增殖的间质等其它成分一并植入,能较好体现临床上呈侵袭生长和过表达EGFR的高度恶性胶质瘤的特征。(3)人肺腺癌脑转移瘤组织块接种于鼠脑内建立的原位移植模型能更好地模拟临床原发肿瘤呈现低分化的病理学特征,并且具有缺乏侵袭性及CEA高表达的生物学特性,说明本方法为研究人肺腺癌脑转移瘤的生物学特性及实验治疗提供了一个可靠的动物模型。(4)用免疫功能健全、表达GFP的转基因鼠与免疫功能缺陷的裸小鼠杂交,可获得脑等组织器官表达GFP的裸小鼠。对其进行HGSCs原位移植,因可清晰辨认移植瘤与宿主组织的关系而有望用于肿瘤组织重构的研究。
PartⅠEstablishment of Orthotopic Grafts of Human Gliomas into Nude Mice
Objective To improve the methods of human glioma xenotransplanted into the brain of nude mice by tumor tissue injected. Methods SHG-44 glioma cells(1×107) were injected subcutaneouly into nude mice, when the solid tumor formed ,it was sharply dissected.Then the xenografts quantified was passed into the brain of nude mice. 30 days later ,all the mice were sacrificed.Slices of intracerebral tumor transplants was stained with hematein-eosin(HE).We study it’s histologic characteristics under microscope. Results 3 of the 18 orthotopic grafted nude mice was died earlier .30 days after tumor tissue implanted, all the mice were sacrificed. The brian was cut in frozen section,stained with HE. Under microscope, we can see the orthotopic grafts with invasiveness to normal brain tissue.Take tate of the grafts was 93 %( 14/15 ) .Conclusion Tissue quantitative implantation is operation simple, small wound ,which can save time and easily product model in large quantities .
PartⅡEstablishment of Orthotopic Transplantation Model of Human Brain Glioma with High Invasiveness and Overexpression of EGFR in Nude Mice
Objective To establish orthotopic transplantation model of human brain glioma in nude mice with characteristics of high invasiveness and overexpression of EGFR .Methods Human glioblastoma multiforme cell line with overexpression of EGFR was cultured in vitro,then tumor cells were injected stereotaxically into the right caudate nucleus of nude mice.The newly formed solid tumor were sharply dissected and solid were passed in the right caudate nucleus of nude mice. Histological characteristics and EGFR protein in the xenografts were determinated by HE staining or immunohistochemical method,respectively.Results The xenografts have been passed continuously in 130 mice for 13 generations in caudate nucleus of nude mice, and the survival time were 19±1.33 day.Histological assay suggests the grafts were high invasiveness and overexpression of EGFR,which were in accordance with the characteristics of human glioblastoma multiforme. The tumor proliferation curve measured at different time points suggests that tumor latent period were shoter(<3 day), rapidly proliferative phase were longer(>15 day),and from the advanced stage to dead point were shorter(<3 day). Conclusion Compared with tumor cells suspension directly innoculated into the caudate nucleus of nude mice,the transplantion of solid tumor tissue take on the advantages of not only injection of plenty of tumor cells,but also with tumor matrix which are necessary for the rapid tumor growth,hence embody the features of high malignant glioma with high invasiveness and overexpression of EGFR.
PartⅢEstablishment of Orthotopic Transplantation model of Metastatic Carcinoma Masses of Human Brain in Nude Mice
Objective To establish an orthotopic transplantation model of brain metastasis of human lung adenocarcinoma in nude mice and analysize its biological features.Methods Human brain metastatic tumor masses were collected and orthotopicly transplanted into the right caudate nucleus of nude mice. The newly formed xenografts were sharply minced into pieces and re-transplanted. The efficiency of tumorigenicity and the survival time of tumor-bearing mice were observed. HE staining and MRI scanning were performed to investigate the histopathological and imaging features of this metastatic lesion. The expression of tumor marker (CEA) and mucin in xenografts was also investigated by immunohistochemical or Alcian blue/PAS assays.Results The brain xenografs were passed into 65 nude mice to the 6th generation in the right caudate nucleus of nude mice,with average survival time of tumor-bearing mice 47.6±1.8d for primary generation and 38.0±0.9d for 4-6 generation;Histopathologically, the cerebral xenografts were poorly differentiated andenocarcinoma without invasiveness to normal brain tissue. MRI revealed a well-delimitated mass without surrounding edema, which perfectly recapitulated the original tumor. Expression of CEA and acid mucin was positive in the cerebral xenografts.Conclusions The orthotopic xenografts of brain metastasis from human lung andenocarcinoma could faithfully recapitulate the original tumor clinically and pathologically, and provides a reliable animal model not only for studying the biological features but also for experimental treatment of brain metastasis from lung adenocarcinoma.
PartⅣPrimarily Investigation on the Human Glioma Stem Cells Transplanted in the Nude Mice with GFP Expression
Objective To incubate nude mice which could stably express green fluoresent protein(GFP), then human glioma stem cells(GSCs)were transplanted intracranially into NC nude mice with GFP expression. Methods Transgenic C57BL/6J mouse expressing GFP was crossed with NC nude mouse, then the male nude mouse expressing GFP was crossed with the female pubescence mouse to obtain nude mouse with GFP expression, expression of GFP in the skin and organs of nude mice were evaluated under direct observation, by immuno histochemiscal and immunofluorescence assay. Accordingly GSCs were transplanted orthotopically into the brains of nude mice expressing GFP to observe the biological characteristics of the intracranial growth of the transplaned tumor. Results The organs and cells were all obviously expressed GFP in the nude mice propagated to 8th generation. Nonluminous tumour cells were distinguished from the host cell distinctly in the brains bearing tumor- transplanted orthotopically. Microanatomy relationship was clearly showed between the brain cells of host and tumour cells with immunohistochemiscal assay, which stained the tumor cells with species-specific monoclonal antibody(HLA)coupled with red fluorescer(PE) through confocal microscopy. Conclusions The nude mice expressing GFP were obtained by crossing the trangenic mice bearing na?ve immunity with NC nude mice. Orthotopic transplantation of human brain glioma may be used in the investigation on the tumour tissue reconstitution for the identification between the transplantation tumor and host tissue .
方法(1)先用SHG-44胶质瘤细胞(1×107)注射于裸小鼠皮下,形成皮下移植瘤,再把皮下移植瘤组织通过自制的组织挤压装置放入24#无菌套管针,并调整肿瘤的体积为2.0mm3,然后把定量要移植的肿瘤组织块植入裸小鼠右尾状核,制作成裸小鼠脑内移植瘤模型。观察移植后裸小鼠生存状态。30d后解剖裸小鼠取脑并行病理切片,观察原位移植瘤的形态、病理学特征和成瘤率。(2)将体外培养高表达表皮生长因子受体(epidermal growth factor receptor,EGFR)的人脑GBM细胞,在立体定向仪辅助下行裸小鼠右尾状核接种;继而将致瘤的组织通过自制的组织挤压装置放入24#无菌套管针,然后将2.0mm3的肿瘤组织经徒手操作接种于裸小鼠右尾状核,致瘤后即用裸小鼠的瘤组织再进行原位传代接种。接种后观察移植瘤的生长特性,并分析EGFR在各代移植瘤中的表达。(3)取人肺腺癌脑转移瘤组织块,通过自制的组织挤压装置放入24#无菌套管针,然后将2.0mm3的肿瘤组织经徒手操作接种于裸小鼠右尾状核。致瘤后即用裸小鼠的瘤组织再进行原位传代接种,然后观察致瘤率及荷瘤鼠生存期;HE染色分析各代移植瘤的组织学形态;MRI观察移植瘤在鼠脑内的大体形态;免疫组化染色观察移植瘤中CEA的表达;Alcian blue/PAS特殊染色检测移植瘤中粘液的性质。(4)将C57BL/6J-GFP转基因小鼠与NC系裸小鼠进行交配,在继代时严格挑选都表达GFP的无毛雄鼠(♂)与有毛雌鼠(♀)交配,通过肉眼和荧光显微镜等方法观察GFP在裸小鼠皮肤和脏器中的表达情况,继将HGSCs原位移植于表达GFP的裸小鼠,以观察移植瘤的生长情况。
结果(1)通过改良的肿瘤组织块移植后,18只裸小鼠除3只接种当日死亡外,其余15只于移植后30d被处死取脑行冰冻切片,HE染色在光镜下见移植瘤侵袭性生长。致瘤率为93%(14/15)。(2)人GBM移植瘤组织在裸小鼠尾状核已连续传至13代,共130只鼠,荷瘤鼠生存期为19±1.33d。移植瘤病理学符合呈高度侵袭性生长、EGFR过表达的人脑GBM的特征。不同时间测得的肿瘤增殖曲线提示,致瘤的潜伏期短(<3d),持续快速增殖期长(>15d),进入晚期至死亡时间短(<3d)。(3)人肺腺癌脑转移瘤组织在裸小鼠右尾状核已连续传至6代,共65只鼠。荷瘤鼠生存期:原代为47.6±1.8d,2-3代有所缩短,4-6代稳定在38.0±0.9d;移植瘤病理为低分化腺癌,不向周围正常鼠脑组织侵袭;MRI示移植瘤类圆形,瘤周无水肿,与临床病例的MRI一致;移植瘤中癌胚抗原(carcinoembryonic antigen,CEA)表达阳性,并有酸性粘液存在。(4)GFP荧光裸小鼠已传至8代,包括脑在内的全身主要器官和细胞都发绿色荧光。对用于HGSCs原位移植的脑,能清晰辨认出不发光的瘤细胞和发光的宿主细胞。而瘤细胞经抗人类白细胞抗原(human leukocyte antigen,HLA)-Ⅰ抗体偶联红色荧光剂(PE)的免疫组织化学染色后,在共聚焦显微镜下可清晰显示HGSCs与宿主脑细胞的组织学关系是:多数播散,个别的发生细胞与细胞融合。
结论(1)通过改良的组织定量移植具有操作简便,对小鼠创伤小,速度快,成瘤率高,便于批量制作原位移植裸小鼠模型。(2)人GBM肿瘤组织于鼠尾状核接种比传统的肿瘤细胞悬液接种,非但接种的细胞量大,还能将支持肿瘤细胞增殖的间质等其它成分一并植入,能较好体现临床上呈侵袭生长和过表达EGFR的高度恶性胶质瘤的特征。(3)人肺腺癌脑转移瘤组织块接种于鼠脑内建立的原位移植模型能更好地模拟临床原发肿瘤呈现低分化的病理学特征,并且具有缺乏侵袭性及CEA高表达的生物学特性,说明本方法为研究人肺腺癌脑转移瘤的生物学特性及实验治疗提供了一个可靠的动物模型。(4)用免疫功能健全、表达GFP的转基因鼠与免疫功能缺陷的裸小鼠杂交,可获得脑等组织器官表达GFP的裸小鼠。对其进行HGSCs原位移植,因可清晰辨认移植瘤与宿主组织的关系而有望用于肿瘤组织重构的研究。
PartⅠEstablishment of Orthotopic Grafts of Human Gliomas into Nude Mice
Objective To improve the methods of human glioma xenotransplanted into the brain of nude mice by tumor tissue injected. Methods SHG-44 glioma cells(1×107) were injected subcutaneouly into nude mice, when the solid tumor formed ,it was sharply dissected.Then the xenografts quantified was passed into the brain of nude mice. 30 days later ,all the mice were sacrificed.Slices of intracerebral tumor transplants was stained with hematein-eosin(HE).We study it’s histologic characteristics under microscope. Results 3 of the 18 orthotopic grafted nude mice was died earlier .30 days after tumor tissue implanted, all the mice were sacrificed. The brian was cut in frozen section,stained with HE. Under microscope, we can see the orthotopic grafts with invasiveness to normal brain tissue.Take tate of the grafts was 93 %( 14/15 ) .Conclusion Tissue quantitative implantation is operation simple, small wound ,which can save time and easily product model in large quantities .
PartⅡEstablishment of Orthotopic Transplantation Model of Human Brain Glioma with High Invasiveness and Overexpression of EGFR in Nude Mice
Objective To establish orthotopic transplantation model of human brain glioma in nude mice with characteristics of high invasiveness and overexpression of EGFR .Methods Human glioblastoma multiforme cell line with overexpression of EGFR was cultured in vitro,then tumor cells were injected stereotaxically into the right caudate nucleus of nude mice.The newly formed solid tumor were sharply dissected and solid were passed in the right caudate nucleus of nude mice. Histological characteristics and EGFR protein in the xenografts were determinated by HE staining or immunohistochemical method,respectively.Results The xenografts have been passed continuously in 130 mice for 13 generations in caudate nucleus of nude mice, and the survival time were 19±1.33 day.Histological assay suggests the grafts were high invasiveness and overexpression of EGFR,which were in accordance with the characteristics of human glioblastoma multiforme. The tumor proliferation curve measured at different time points suggests that tumor latent period were shoter(<3 day), rapidly proliferative phase were longer(>15 day),and from the advanced stage to dead point were shorter(<3 day). Conclusion Compared with tumor cells suspension directly innoculated into the caudate nucleus of nude mice,the transplantion of solid tumor tissue take on the advantages of not only injection of plenty of tumor cells,but also with tumor matrix which are necessary for the rapid tumor growth,hence embody the features of high malignant glioma with high invasiveness and overexpression of EGFR.
PartⅢEstablishment of Orthotopic Transplantation model of Metastatic Carcinoma Masses of Human Brain in Nude Mice
Objective To establish an orthotopic transplantation model of brain metastasis of human lung adenocarcinoma in nude mice and analysize its biological features.Methods Human brain metastatic tumor masses were collected and orthotopicly transplanted into the right caudate nucleus of nude mice. The newly formed xenografts were sharply minced into pieces and re-transplanted. The efficiency of tumorigenicity and the survival time of tumor-bearing mice were observed. HE staining and MRI scanning were performed to investigate the histopathological and imaging features of this metastatic lesion. The expression of tumor marker (CEA) and mucin in xenografts was also investigated by immunohistochemical or Alcian blue/PAS assays.Results The brain xenografs were passed into 65 nude mice to the 6th generation in the right caudate nucleus of nude mice,with average survival time of tumor-bearing mice 47.6±1.8d for primary generation and 38.0±0.9d for 4-6 generation;Histopathologically, the cerebral xenografts were poorly differentiated andenocarcinoma without invasiveness to normal brain tissue. MRI revealed a well-delimitated mass without surrounding edema, which perfectly recapitulated the original tumor. Expression of CEA and acid mucin was positive in the cerebral xenografts.Conclusions The orthotopic xenografts of brain metastasis from human lung andenocarcinoma could faithfully recapitulate the original tumor clinically and pathologically, and provides a reliable animal model not only for studying the biological features but also for experimental treatment of brain metastasis from lung adenocarcinoma.
PartⅣPrimarily Investigation on the Human Glioma Stem Cells Transplanted in the Nude Mice with GFP Expression
Objective To incubate nude mice which could stably express green fluoresent protein(GFP), then human glioma stem cells(GSCs)were transplanted intracranially into NC nude mice with GFP expression. Methods Transgenic C57BL/6J mouse expressing GFP was crossed with NC nude mouse, then the male nude mouse expressing GFP was crossed with the female pubescence mouse to obtain nude mouse with GFP expression, expression of GFP in the skin and organs of nude mice were evaluated under direct observation, by immuno histochemiscal and immunofluorescence assay. Accordingly GSCs were transplanted orthotopically into the brains of nude mice expressing GFP to observe the biological characteristics of the intracranial growth of the transplaned tumor. Results The organs and cells were all obviously expressed GFP in the nude mice propagated to 8th generation. Nonluminous tumour cells were distinguished from the host cell distinctly in the brains bearing tumor- transplanted orthotopically. Microanatomy relationship was clearly showed between the brain cells of host and tumour cells with immunohistochemiscal assay, which stained the tumor cells with species-specific monoclonal antibody(HLA)coupled with red fluorescer(PE) through confocal microscopy. Conclusions The nude mice expressing GFP were obtained by crossing the trangenic mice bearing na?ve immunity with NC nude mice. Orthotopic transplantation of human brain glioma may be used in the investigation on the tumour tissue reconstitution for the identification between the transplantation tumor and host tissue .
引文
1 Rana MW, Pinkerton H, Thornton H,et al.Heterotransplantation of human glioblastoma multiforme and meningioma to nude mice. Proc Soc Exp Biol Med ,1977,155:85-88.
2 Bradley NJ, Bloom JG, Dawies AJS, et al.Growth of human gliomas in immune-deficient mice: a possible model for pre-clinical therapy studies. Br J Cancer,1978,38:263-272.
3 Horten BC, Basler GA, Shapiro WR,et al. Xenograft of human malignant glial tumors into brains of nude mice. J Neuropathol Exp Neurol1981,40:493-511.
4 De Armond SJ, Stowring L, Amar A,et al.Development of a non-selecting, non-perturbing method to study human brain tumor cell invasion in murine brain. J Neurooncol,1994,20:27-34.
5 Antunes L, Angioi-Duprez KS, Bracard SR, et al. Analysis of tissue chimerism in nude mouse brain and abdominal xenograft models of human glioblastoma multiforme: what does it tell us about the models and about glioblastoma biology and therapy? J Histochem Cytochem 2000,48:847-58.
6 Taillandier L,Antunes L,Angioi-Duprez ,et al. Models for neuro-oncological preclinical studies: solid orthotopic and heterotopic grafts of human gliomas into nude mice. J Neurosci Methods,2003,125 (1-2), 147-57.
7黄强,杜子威,徐庚达,等.人脑胶质瘤细胞系实体瘤模型NHG-1的建立及其特征的研究.中华肿瘤杂志,1987,9(4):269-272.
8黄强,杜子威,刘振延,等.人脑室管膜瘤组织-小鼠模型NHE-2的研究.中华神经外科杂志.1989,5(1):27-31.
9 Bu Xingyao, Zhang Xiang, Walter E.Laug.Experimental study on the establishment for orthopic implantation model of human glioma cells in nude mice.中华神经外科疾病研究杂志,2006,5(2):100-105.
10黄强,谈琪云,许期年,等.抗恶性胶质瘤药物筛选的方法学研究.中华神经外科杂志,1990,6(4):276-279.
11朱剑虹,杜子威,黄强,等.单克隆抗体携带阿霉素对人脑胶质瘤裸鼠皮下和脑内实体瘤模型的导向治疗作用.中华神经外科志,1991,7(3):184-186.
12黄强,施铭岗,董军,等.诱导分化、化疗和免疫治疗在荷人脑胶质瘤动物体内序贯组合研究.中华神经外科志,2003,19(1):10-14.
13 Yamada S, Khankaldyyan V ,Bu X,et a1.A method to accurately inject tumor cells into the caudate/putamen nuclei of the mouse brain .Tokai J Exp Clin Med,2004,29(4):167-173.
14杜子威,徐庚达,王尧,等.人脑恶性胶质瘤体外细胞系SHG-44的建立及其特征.中华肿瘤杂志,1984,6(4):241-243.
15 Pinkel D, Segraves R, Sudar D, et al.High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays. Nat Genet, 1998,20(2):207-211.
16 Man TK, Lu XY, Jaeweon K, et al.Genome-wide array comparative genomic hybridization analysis reveals distinct amplifications in osteosarcoma. BMC Cancer ,2004,4:45.
17 Cowell JK, Matsui S, Wang YD, et al. Application of bacterial artificial chromosome array-based comparative genomic hybridization and spectral karyotyping to the analysis of glioblastoma multiforme. Cancer Genet Cytogenet 2004,151(1):36-51.
18 Lim G, Karaskova J, Vukovic B, et al. Combined spectral karyotyping, multicolor banding, and microarray comparative genomic hybridization analysis provides a detailed characterization of complex structural chromosomal rearrangements associated with gene amplification in the osteosarcoma cell line MG-63. Cancer Genet Cytogenet 2004,153(2):158-164.
19魏子龙,黄强,董军,等.针对胶质瘤发生发展组织芯片中表皮生长因子受体基因表达分析.中华神经医学杂志,2007,6(5):455-459.
20 Pandita A, Aldape KD, Zadeh G, et al. Contrasting in vivo and in vitro fates of glioblastoma cell subpopulations with amplified EGFR. Genes Chromosomes Cancer 2004,39(1):29-36.
21 Giannini C, Sarkaria JN, Saito A,et al. Patient tumor EGFR and PDGFRA geneamplifications retained in an invasive intracranial xenograft model of glioblastoma multiforme. Neuro oncol, 2005,7(2):164-176.
22 Thomas C, Ely G, James CD, et al. Glioblastoma-related gene mutations and over-expression of functional epidermal growth factor receptors in SKMG-3 glioma cells. Acta Neuropathol (Berl) 2001,101(6):605-615.
23林志雄,黄强.神经胶质瘤微生态系统研究.中国肿瘤,2005,14(2):82-84.
24 Wiseman BS,Werb Z.Stromal effects on mammary gland development and breast cancer.Science,2002,296(5570):1046-1049.
25 Janssen-Heijnen ML, Coebergh JW . The changing epidemiology of lung cancer in Europe. Lung Cancer,2003,41(3):245-258.
26 tearman RS, Dwyer-Nield L , Zerbe L,et al. Analysis of orthologous gene expression between human pulmonary adenocarcinoma and a carcinogen-induced murine model. Am J Pathol,2005,167(6):1763-1775.
27李如军,刁艺,黄强,等.可移植性人脑胶质瘤组织裸小鼠脑内移植及其MR显像研究.癌症,2007,26(9):937-941.
28 Wang JH, Zhang SC, Liu ZD,et al. Correlation between the mRNA levels of carcinoembryonic antigen and cytokeratin 19 in peripheral blood with staging,treatment response and prognosis in patients with lung cancer. Zhonghua Jie He He Hu Xi Za Zhi, 2005,28(11):773-776.
29 Vince GH,Bendszus M,Schweitzer T,et a1.Spontaneous regression of experimental gliomas-an immunohistochemical and MRI study of the C6 glioma spheroid implantation mode1.Exp Neurol, 2004,190(2):478-485.
30 Gouyer V, Conti M, Devos P,et al.Tissue inhibitor of metalloproteinase-1 is an independent predictor of prognosis in patients with nonsmall cell lung carcinoma who undergo resection with curative intent. Cancer,2005,103(8):1676-1684.
31 Ray JM, Stetler-Stevenson WG. The role of matrix metalloproteases and their inhibitors in tumour invasion, metastasis and angiogenesis.Eur Respir J,1994,7(11):2062-2072.
32 Goldberg GI, Strongin A, Collier IE, et al. Interaction of 92-kDa Type IV collagenasewith the tissue inhibitor of metalloproteinases prevents dimerization, complex formation with interstitial collagenase, and activation of the proenzyme with stromelysin. J Biol Chem,1992,267(7):4583–4591.
33 Mareel M. When and why does cancer metastasize? An overview of current viewpoints of the molecular mechanism of invasiveness. Verhk Acad Geneeskd Belg, 1994,56:105-125.
34 Yang M,Li L,Jiang P,et al. Dual -color fluorescence imagin distinguishes tumor cells from induced host angiogenetic vessels and stromal cells. Proc Natl Acad Sci USA,2003,100:14259-14262.
35 Yang M,Reynoso J,Jiang P,et al.Transgenic nud mous with ubiquitous green fluoresent protein expression as a host for uman tumors. Camcer Res,2004,64:8651-8656.
36黄强,朱玉德,董军,等.人脑胶质瘤组织中分离与培养肿瘤干细胞.中华肿瘤杂志,2006,28(5):331-333.
37戴益民.双重或多重免疫组织化学标记.倪灿荣,马大列,戴益民,主编.免疫组织化学实验技术与应用.北京:化学工业出版社,2006,P49-64.
38马祥宇,李新钢,赵鹏,等.绿色荧光蛋白在胶质瘤相关研究中的应用进展.中华神经外科杂志,2007,23(2):153-155.
39季晓燕,黄强,董军,等.脑肿瘤干细胞体外分化的形态、标志物及细胞增殖动力学特征.中华医学杂志,2006, 86(23):1604-1609.
40 Quan Bin Zhang,Xiao Yan Ji,Huang Qiang et al. Differentiation profile of brain tumor stem cells:a comparative study with neural stem cells. Cell Research,2006,16(12):909-915 .
41魏子龙,朱玉德,黄强.肿瘤拟态血管的发现与研究进展.肿瘤.2006, 26(10):960-963.
42 Bjerkvig R,Tysnes BB,Aboody KS,et al. The origin of the cancer stem cell:current con ersies and new insights. Nat Cancer Rev,2005,5:899-904.
1 David H,Gutmann,Suzanne J,et al.Mouse Models of Human Cancer Consortium Symposium on Nervous System Tumors.Cancer Res,2003,63(1): 3001–3004.
2 Maher E. A., Furnari F. B., Bachoo R. M.,et al. Malignant glioma: genetics and biology of a grave matter.Genes Dev,2001,15: 1311–1333.
3 Peiper R.O. Defined human cellular systems in the study of glioma development.Front Biosci,2003,8: S19–S27.
4 Kathryn Maddison,Alan R Clarke.New approaches for modelling cancer mechanisms in the mouse.J Pathol, 2005,205: 181–193.
5黄强,杜子威.人脑胶质瘤细胞系裸小鼠实体瘤模型NHG-1的建立及其特征的研究.中华肿瘤杂志,1987,9(4):269-271.
6黄强,杜子威.人脑室管膜母细胞瘤组织-裸小鼠移植模型NHE-2的研究.中华神经外科杂志,1989,5(1):27-30.
7衣服新,黄强,董军等.人淋巴细胞转输SCID小鼠抗人脑胶质瘤特性分析.江苏医药,2001,27(5):338-340.
8 Rana MW, Pinkerton H, Thornton H,et al.Heterotransplantation of human glioblastoma multiforme and meningioma to nude mice. Proc Soc Exp Biol Med ,1977,155:85-88.
9 Bradley NJ, Bloom JG, Dawies AJS, et al.Growth of human gliomas in immune-deficient mice: a possible model for pre-clinical therapy studies. Br J Cancer,1978,38:263-272.
10 Orten BC, Basler GA, Shapiro WR,et al. Xenograft of human malignant glial tumors into brains of nude mice. J Neuropathol Exp Neurol1981,40:493-511.
11 De Armond SJ, Stowring L, Amar A,et al.Development of a non-selecting, non-perturbing method to study human brain tumor cell invasion in murine brain. J Neurooncol,1994,20:27-34.
12 Antunes L, Angioi-Duprez KS, Bracard SR, et al. Analysis of tissue chimerism in nude mouse brain and abdominal xenograft models of human glioblastoma multiforme:what does it tell us about the models and about glioblastoma biology and therapy? J Histochem Cytochem 2000;48:847-58.
13 Luc Taillandier,Laurent Antunes,K.S Angioi-Duprez.Models for neuro-oncological preclinical studies:solid orthotopic and heterotopic grafts of human gliomas into nude mice. Journal of Neuroscience Methods . 2003;125 :147-157.
14 Singh SK,Ian DC,Mizuhiko T,et al.Identification of a cancer stem cell in human brain tumors. Cancer Res,2003; 63(18):5821- 5828.
15 Singh SK,Hawkins C,Clare ID,et al.Identification of human brain tumor initiating cell.Nature,2004,432(18):396-401.
16 Bachoo R.M.,Maher,E. A.,Ligon,K.L.,et al.Epidermal growth factor receptor and Ink4a/Arf:convergent mechanisms governing terminal differentiation and transformation along the neural stem cell to astrocyte axis. Cancer Cell,2002,1: 269–277.
17 Xiao A., Wu H, Pandolfi P. P, et al. Astrocyte inactivation of the pRb pathway predisposes micetomalignant astrocytoma developmentthat is accelerated by PTEN mutation. Cancer Cell,2002;1,157–168.
18 Ho lland EC, Celest ino J , DaiC, et al. Combined activation of Ras and Akt inneural progenitors induces glioblastoma formation in m ice . Nat Genet,2000,25 (1) : 55- 57.
19 Reilly KM , Lo isel DA , B ronson RT , et al. Nf1,Trp53 mutant m ice develop glioblastoma with evidence of strain-specific effects . Nat Genet,2000,26 (1) : 109- 113.
20 Zuraw el RH, A llen C,Wechsler-Reya R,et al.Evidence that hap lo insufficiency of Ptch leads to medulloblastoma in m ice . Genes Chromosomes Cancer,2000,28 (1) : 77- 81.
21 Wetmore C,Eberhart DE,Curran T.Loss of p53 but not ARF accelerates medulloblastoma in mice heterozygous for patched .Cancer Res,2001,61(2) : 513- 516.
22 Weiner HL,Bakst R,HurlbertM S,etal.Induction of medulloblastomas in mice by sonichedgehog, independent of Glil.Cancer Res,2002,62 (22) :6385- 6389.
23 TongWM,CortesU,Wang ZQ. Poly (ADP-ribose)polymerase: A guardian angel protecting the genome and suppressing tumorigenesis .Bioch im Biophys Acta,2001,20 (57) : 8167- 8174.
24黄强,王强,许期年,等. 3H-TdR参入裸小鼠移植瘤作为抗癌药物筛选方法的初步研究.核技术,1991,14(5):282.
25黄强,谈琪云,许期年,等.抗恶性胶质瘤药物筛选的方法学研究.中华神经外科杂志,1990,6(4):276-278
26朱剑虹,杜子威,黄强,等.单克隆抗体-阿霉素免疫交联物在脑胶质瘤裸鼠模型体内导向治疗的初步研究.苏州医学院学报,1988,8(4):264-266.
27兰青,黄强,孙志方.S-35标记SZ-39导向治疗胶质瘤的实验研究.中华核医学杂志,1999,19(1):19-21.
28黄强,陈忠平,兰青主编.胶质瘤.第1版.北京:中国科学技术出版社, 2000.489-492.
29李伟生,黄强,董军,等.苯丁酸钠诱导分化治疗可移植性人脑胶质瘤实验研究.中华神经外科疾病研究杂志,2002,1(2):160-163.
30黄强,施铭岗,董军,等.诱导分化、化疗和免疫治疗在荷人脑胶质瘤动物体内序贯组合研究.中华神经外科杂志,2003,19(1):10-14 .
31罗其中.脑胶质瘤诱导分化治疗的研究进展.中华神经医学杂志,2003,2(4):241-243.
32 Xiao-Nan Li,Zi-Wei Du,Qiang Huang.Modulation effects of hexamethylene bisacetamide on growth and defferentiation of curtured human malignant glioma cells. J.Neurosurg. 1996;84: 831-838.
33 Xiao-Nan Li, Zi-Wei Du, Qiang Huang, Jian-Qiang Wu. Growthinhibitory and differentiation- inducing activity of dimethylf-ormamide in cultured human malignant glioma cells. Neuosurgery. 1997,40(6):1250-59.
34 Tang SJ,Ko LW,Lee YH,et al.Induction of fos and sis proto-oncogenesis and genes of the extracellular matrix proteins during butyrate induced glioma diferentiation.Biochem Biophys Acta,1990,1048(1):59-65.
35 Shiotsu Y.Current screening for molecular target therapy of cancer. Japanese Journal of Cancer&Chemotherapy,2003,30(12):1863-1872.
36 Goudar RK, Shi Q, Hjelmeland MD.Combination therapy of inhibitors of epidermal growth factor receptor/vascular endothelial growth factor receptor 2 (AEE788) and the mammalian target of rapamyein (RADO01) ofers improved glioblastoma tumor growth inhibition.Mol Cancer Ther,2005,4(1):101-112.
37 Terrance G,Johns, Rodney B,et al.Antitumor efficacy of cytotoxic drugs and the monoclonal antibody 806 is enhanced by the EGF receptor inhibitor AG1478. Proc Natl Acad Sci U S A, 2003 ,23,100(26):15871-15876.
38 Lal A, Glazer CA, Martinson HM, et al.Mutant epidermal growth factor receptor up-regulates molecular effectors of tumor invasion. Cancer Res,2002,15, 62(12): 3335-3339.
39 Schmidt NO, Ziu M, Carrabba G,et al. Antiangiogenic therapy by local intracerebral microinfusion improves treatment efficiency and survival in an orthotopic human glioblastoma Model.Clin Cancer Res,2004,10(4):1255-1262.
40王飞,黄强.神经干细胞应用的新思路:基因治疗胶质瘤.中国肿瘤,2005,14(2):96-98.
41 Mckay R.Stem cells in central nervous system .Science,1997,276(5309):66-71.
42 Weissman IL.Translating stem and progenitor cell biology to the clinic:barriers and opportunities.Science,2000,287(5457):1442-l452.
43 Benedetti S,Piola B,Pollo B,et a1.Gene therapy of experimental brain tumors using neural progenitor cells.Nat Med,2000,6:447-450.
44 Herrlinger U,Woiciechowski C,Sena EM,et a1.Neuralprecursor cells for delivery of replication-conditional HSV-l vector to intracerebral gliomas.Mol Ther,2000,l(4):347-357.
45 Aboody KS,Brown A,Rainov NG,et a1.From the cover neural stem cells display extensive tropism for pathology in adult brain : Evidence from intracranial gliomas.Proc Nat Acad Sci USA,2000,97(23):l2846-l2851.
46 Ehtesham M,Kabos P,Gutierrez MA,et a1.Induction of glioblastoma apoptosis using neural stem cell-mediated delivery of tumor necrosis factor-related apoptosis-inducing ligand.Cancer Res,2002,62(24):7170-7174.
47 Ehtesham M,Kabos P,Kabosova A,et a1.The use of interleukin l2-secreting neural stem cells for the treatment of intracranial glioma.Cancer Res, 2002,62(20):5657-5663.
48 Lan Qing,Huang Qiang,Bao Shi Rao,et al.Preclinical evaluation of SPECT imaging with 131I-labelled monoclonal antibody SZ39 in nude mice.Journal of Neuroimaging(U.S.A),1996,6(2):131-135.
49 Massoud TF, Gambhir SS. Molecular imaging in living subjects,seeing fundamental biological processes in a new light.Genes Dev ,2003,17(5): 545–580.
50 Haubner R, Wester HJ, Weber WA, et al. Non-invasive imaging of alpha(v)beta3 integrin expression using 18F-labeled RGD-containing glycopeptide and positron emission tomography. Cancer Res ,2001,61(5):1781–1785.
51 Herschman HR. Micro-PET imaging and small animal models of disease. Curr Opin Immunol,2003,15(4): 378–384.
52 Lewis J.S,Achilefu S,Garbow J. R,et al. Small animal imaging current technology andperspectives for oncological imaging. Eur. J. Cancer,2002,38,2173–2188.
53 Pirko I, Fricke ST, Johnson AJ, et al. Magnetic resonance imaging, microscopy, and spectroscopy of the central nervous system in experimental animals. NeuroRx ,2005,2: 250-264.
54 Beck B, Plant DH, Grant SC et al. Progress in high field MRI at the University of Florida. MAGMA,2002,13:152-157.
55 Maniotis AJ,Folbcrg R,Hess A,et a1.Am J Patho1,1999,155(3):739-752.
56 Wei-Ying Yue ,Zhong-Ping Chen. Does Vasculogenic Mimicry Exist in Astrocytoma?Journal of Histochemistry & Cytochemistry,2005,53(8): 997-1002.
57 Zhang S,Guo H,Zhang D,et al.Microcirculation patterns in different stages of melanoma.Oncol Rep,2006,15(1):15-20.
58 Galli R,Binda E,Orfaneli U.Isolation and characterization of tumorigenic stem-like neural precursors from human gliblastoma.Cancer Res,2004,64:7011.
59 Qin Shu,Kwong Kwok Wong,Jack M,et al.Direct Orthotopic transplantation of fresh surgical specimen preserves CD133+ tumor cells in clinically relevant mouse models of medulloblastoma and glioma. Stem Cells, 2008 ,10:1-24.
2 Bradley NJ, Bloom JG, Dawies AJS, et al.Growth of human gliomas in immune-deficient mice: a possible model for pre-clinical therapy studies. Br J Cancer,1978,38:263-272.
3 Horten BC, Basler GA, Shapiro WR,et al. Xenograft of human malignant glial tumors into brains of nude mice. J Neuropathol Exp Neurol1981,40:493-511.
4 De Armond SJ, Stowring L, Amar A,et al.Development of a non-selecting, non-perturbing method to study human brain tumor cell invasion in murine brain. J Neurooncol,1994,20:27-34.
5 Antunes L, Angioi-Duprez KS, Bracard SR, et al. Analysis of tissue chimerism in nude mouse brain and abdominal xenograft models of human glioblastoma multiforme: what does it tell us about the models and about glioblastoma biology and therapy? J Histochem Cytochem 2000,48:847-58.
6 Taillandier L,Antunes L,Angioi-Duprez ,et al. Models for neuro-oncological preclinical studies: solid orthotopic and heterotopic grafts of human gliomas into nude mice. J Neurosci Methods,2003,125 (1-2), 147-57.
7黄强,杜子威,徐庚达,等.人脑胶质瘤细胞系实体瘤模型NHG-1的建立及其特征的研究.中华肿瘤杂志,1987,9(4):269-272.
8黄强,杜子威,刘振延,等.人脑室管膜瘤组织-小鼠模型NHE-2的研究.中华神经外科杂志.1989,5(1):27-31.
9 Bu Xingyao, Zhang Xiang, Walter E.Laug.Experimental study on the establishment for orthopic implantation model of human glioma cells in nude mice.中华神经外科疾病研究杂志,2006,5(2):100-105.
10黄强,谈琪云,许期年,等.抗恶性胶质瘤药物筛选的方法学研究.中华神经外科杂志,1990,6(4):276-279.
11朱剑虹,杜子威,黄强,等.单克隆抗体携带阿霉素对人脑胶质瘤裸鼠皮下和脑内实体瘤模型的导向治疗作用.中华神经外科志,1991,7(3):184-186.
12黄强,施铭岗,董军,等.诱导分化、化疗和免疫治疗在荷人脑胶质瘤动物体内序贯组合研究.中华神经外科志,2003,19(1):10-14.
13 Yamada S, Khankaldyyan V ,Bu X,et a1.A method to accurately inject tumor cells into the caudate/putamen nuclei of the mouse brain .Tokai J Exp Clin Med,2004,29(4):167-173.
14杜子威,徐庚达,王尧,等.人脑恶性胶质瘤体外细胞系SHG-44的建立及其特征.中华肿瘤杂志,1984,6(4):241-243.
15 Pinkel D, Segraves R, Sudar D, et al.High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays. Nat Genet, 1998,20(2):207-211.
16 Man TK, Lu XY, Jaeweon K, et al.Genome-wide array comparative genomic hybridization analysis reveals distinct amplifications in osteosarcoma. BMC Cancer ,2004,4:45.
17 Cowell JK, Matsui S, Wang YD, et al. Application of bacterial artificial chromosome array-based comparative genomic hybridization and spectral karyotyping to the analysis of glioblastoma multiforme. Cancer Genet Cytogenet 2004,151(1):36-51.
18 Lim G, Karaskova J, Vukovic B, et al. Combined spectral karyotyping, multicolor banding, and microarray comparative genomic hybridization analysis provides a detailed characterization of complex structural chromosomal rearrangements associated with gene amplification in the osteosarcoma cell line MG-63. Cancer Genet Cytogenet 2004,153(2):158-164.
19魏子龙,黄强,董军,等.针对胶质瘤发生发展组织芯片中表皮生长因子受体基因表达分析.中华神经医学杂志,2007,6(5):455-459.
20 Pandita A, Aldape KD, Zadeh G, et al. Contrasting in vivo and in vitro fates of glioblastoma cell subpopulations with amplified EGFR. Genes Chromosomes Cancer 2004,39(1):29-36.
21 Giannini C, Sarkaria JN, Saito A,et al. Patient tumor EGFR and PDGFRA geneamplifications retained in an invasive intracranial xenograft model of glioblastoma multiforme. Neuro oncol, 2005,7(2):164-176.
22 Thomas C, Ely G, James CD, et al. Glioblastoma-related gene mutations and over-expression of functional epidermal growth factor receptors in SKMG-3 glioma cells. Acta Neuropathol (Berl) 2001,101(6):605-615.
23林志雄,黄强.神经胶质瘤微生态系统研究.中国肿瘤,2005,14(2):82-84.
24 Wiseman BS,Werb Z.Stromal effects on mammary gland development and breast cancer.Science,2002,296(5570):1046-1049.
25 Janssen-Heijnen ML, Coebergh JW . The changing epidemiology of lung cancer in Europe. Lung Cancer,2003,41(3):245-258.
26 tearman RS, Dwyer-Nield L , Zerbe L,et al. Analysis of orthologous gene expression between human pulmonary adenocarcinoma and a carcinogen-induced murine model. Am J Pathol,2005,167(6):1763-1775.
27李如军,刁艺,黄强,等.可移植性人脑胶质瘤组织裸小鼠脑内移植及其MR显像研究.癌症,2007,26(9):937-941.
28 Wang JH, Zhang SC, Liu ZD,et al. Correlation between the mRNA levels of carcinoembryonic antigen and cytokeratin 19 in peripheral blood with staging,treatment response and prognosis in patients with lung cancer. Zhonghua Jie He He Hu Xi Za Zhi, 2005,28(11):773-776.
29 Vince GH,Bendszus M,Schweitzer T,et a1.Spontaneous regression of experimental gliomas-an immunohistochemical and MRI study of the C6 glioma spheroid implantation mode1.Exp Neurol, 2004,190(2):478-485.
30 Gouyer V, Conti M, Devos P,et al.Tissue inhibitor of metalloproteinase-1 is an independent predictor of prognosis in patients with nonsmall cell lung carcinoma who undergo resection with curative intent. Cancer,2005,103(8):1676-1684.
31 Ray JM, Stetler-Stevenson WG. The role of matrix metalloproteases and their inhibitors in tumour invasion, metastasis and angiogenesis.Eur Respir J,1994,7(11):2062-2072.
32 Goldberg GI, Strongin A, Collier IE, et al. Interaction of 92-kDa Type IV collagenasewith the tissue inhibitor of metalloproteinases prevents dimerization, complex formation with interstitial collagenase, and activation of the proenzyme with stromelysin. J Biol Chem,1992,267(7):4583–4591.
33 Mareel M. When and why does cancer metastasize? An overview of current viewpoints of the molecular mechanism of invasiveness. Verhk Acad Geneeskd Belg, 1994,56:105-125.
34 Yang M,Li L,Jiang P,et al. Dual -color fluorescence imagin distinguishes tumor cells from induced host angiogenetic vessels and stromal cells. Proc Natl Acad Sci USA,2003,100:14259-14262.
35 Yang M,Reynoso J,Jiang P,et al.Transgenic nud mous with ubiquitous green fluoresent protein expression as a host for uman tumors. Camcer Res,2004,64:8651-8656.
36黄强,朱玉德,董军,等.人脑胶质瘤组织中分离与培养肿瘤干细胞.中华肿瘤杂志,2006,28(5):331-333.
37戴益民.双重或多重免疫组织化学标记.倪灿荣,马大列,戴益民,主编.免疫组织化学实验技术与应用.北京:化学工业出版社,2006,P49-64.
38马祥宇,李新钢,赵鹏,等.绿色荧光蛋白在胶质瘤相关研究中的应用进展.中华神经外科杂志,2007,23(2):153-155.
39季晓燕,黄强,董军,等.脑肿瘤干细胞体外分化的形态、标志物及细胞增殖动力学特征.中华医学杂志,2006, 86(23):1604-1609.
40 Quan Bin Zhang,Xiao Yan Ji,Huang Qiang et al. Differentiation profile of brain tumor stem cells:a comparative study with neural stem cells. Cell Research,2006,16(12):909-915 .
41魏子龙,朱玉德,黄强.肿瘤拟态血管的发现与研究进展.肿瘤.2006, 26(10):960-963.
42 Bjerkvig R,Tysnes BB,Aboody KS,et al. The origin of the cancer stem cell:current con ersies and new insights. Nat Cancer Rev,2005,5:899-904.
1 David H,Gutmann,Suzanne J,et al.Mouse Models of Human Cancer Consortium Symposium on Nervous System Tumors.Cancer Res,2003,63(1): 3001–3004.
2 Maher E. A., Furnari F. B., Bachoo R. M.,et al. Malignant glioma: genetics and biology of a grave matter.Genes Dev,2001,15: 1311–1333.
3 Peiper R.O. Defined human cellular systems in the study of glioma development.Front Biosci,2003,8: S19–S27.
4 Kathryn Maddison,Alan R Clarke.New approaches for modelling cancer mechanisms in the mouse.J Pathol, 2005,205: 181–193.
5黄强,杜子威.人脑胶质瘤细胞系裸小鼠实体瘤模型NHG-1的建立及其特征的研究.中华肿瘤杂志,1987,9(4):269-271.
6黄强,杜子威.人脑室管膜母细胞瘤组织-裸小鼠移植模型NHE-2的研究.中华神经外科杂志,1989,5(1):27-30.
7衣服新,黄强,董军等.人淋巴细胞转输SCID小鼠抗人脑胶质瘤特性分析.江苏医药,2001,27(5):338-340.
8 Rana MW, Pinkerton H, Thornton H,et al.Heterotransplantation of human glioblastoma multiforme and meningioma to nude mice. Proc Soc Exp Biol Med ,1977,155:85-88.
9 Bradley NJ, Bloom JG, Dawies AJS, et al.Growth of human gliomas in immune-deficient mice: a possible model for pre-clinical therapy studies. Br J Cancer,1978,38:263-272.
10 Orten BC, Basler GA, Shapiro WR,et al. Xenograft of human malignant glial tumors into brains of nude mice. J Neuropathol Exp Neurol1981,40:493-511.
11 De Armond SJ, Stowring L, Amar A,et al.Development of a non-selecting, non-perturbing method to study human brain tumor cell invasion in murine brain. J Neurooncol,1994,20:27-34.
12 Antunes L, Angioi-Duprez KS, Bracard SR, et al. Analysis of tissue chimerism in nude mouse brain and abdominal xenograft models of human glioblastoma multiforme:what does it tell us about the models and about glioblastoma biology and therapy? J Histochem Cytochem 2000;48:847-58.
13 Luc Taillandier,Laurent Antunes,K.S Angioi-Duprez.Models for neuro-oncological preclinical studies:solid orthotopic and heterotopic grafts of human gliomas into nude mice. Journal of Neuroscience Methods . 2003;125 :147-157.
14 Singh SK,Ian DC,Mizuhiko T,et al.Identification of a cancer stem cell in human brain tumors. Cancer Res,2003; 63(18):5821- 5828.
15 Singh SK,Hawkins C,Clare ID,et al.Identification of human brain tumor initiating cell.Nature,2004,432(18):396-401.
16 Bachoo R.M.,Maher,E. A.,Ligon,K.L.,et al.Epidermal growth factor receptor and Ink4a/Arf:convergent mechanisms governing terminal differentiation and transformation along the neural stem cell to astrocyte axis. Cancer Cell,2002,1: 269–277.
17 Xiao A., Wu H, Pandolfi P. P, et al. Astrocyte inactivation of the pRb pathway predisposes micetomalignant astrocytoma developmentthat is accelerated by PTEN mutation. Cancer Cell,2002;1,157–168.
18 Ho lland EC, Celest ino J , DaiC, et al. Combined activation of Ras and Akt inneural progenitors induces glioblastoma formation in m ice . Nat Genet,2000,25 (1) : 55- 57.
19 Reilly KM , Lo isel DA , B ronson RT , et al. Nf1,Trp53 mutant m ice develop glioblastoma with evidence of strain-specific effects . Nat Genet,2000,26 (1) : 109- 113.
20 Zuraw el RH, A llen C,Wechsler-Reya R,et al.Evidence that hap lo insufficiency of Ptch leads to medulloblastoma in m ice . Genes Chromosomes Cancer,2000,28 (1) : 77- 81.
21 Wetmore C,Eberhart DE,Curran T.Loss of p53 but not ARF accelerates medulloblastoma in mice heterozygous for patched .Cancer Res,2001,61(2) : 513- 516.
22 Weiner HL,Bakst R,HurlbertM S,etal.Induction of medulloblastomas in mice by sonichedgehog, independent of Glil.Cancer Res,2002,62 (22) :6385- 6389.
23 TongWM,CortesU,Wang ZQ. Poly (ADP-ribose)polymerase: A guardian angel protecting the genome and suppressing tumorigenesis .Bioch im Biophys Acta,2001,20 (57) : 8167- 8174.
24黄强,王强,许期年,等. 3H-TdR参入裸小鼠移植瘤作为抗癌药物筛选方法的初步研究.核技术,1991,14(5):282.
25黄强,谈琪云,许期年,等.抗恶性胶质瘤药物筛选的方法学研究.中华神经外科杂志,1990,6(4):276-278
26朱剑虹,杜子威,黄强,等.单克隆抗体-阿霉素免疫交联物在脑胶质瘤裸鼠模型体内导向治疗的初步研究.苏州医学院学报,1988,8(4):264-266.
27兰青,黄强,孙志方.S-35标记SZ-39导向治疗胶质瘤的实验研究.中华核医学杂志,1999,19(1):19-21.
28黄强,陈忠平,兰青主编.胶质瘤.第1版.北京:中国科学技术出版社, 2000.489-492.
29李伟生,黄强,董军,等.苯丁酸钠诱导分化治疗可移植性人脑胶质瘤实验研究.中华神经外科疾病研究杂志,2002,1(2):160-163.
30黄强,施铭岗,董军,等.诱导分化、化疗和免疫治疗在荷人脑胶质瘤动物体内序贯组合研究.中华神经外科杂志,2003,19(1):10-14 .
31罗其中.脑胶质瘤诱导分化治疗的研究进展.中华神经医学杂志,2003,2(4):241-243.
32 Xiao-Nan Li,Zi-Wei Du,Qiang Huang.Modulation effects of hexamethylene bisacetamide on growth and defferentiation of curtured human malignant glioma cells. J.Neurosurg. 1996;84: 831-838.
33 Xiao-Nan Li, Zi-Wei Du, Qiang Huang, Jian-Qiang Wu. Growthinhibitory and differentiation- inducing activity of dimethylf-ormamide in cultured human malignant glioma cells. Neuosurgery. 1997,40(6):1250-59.
34 Tang SJ,Ko LW,Lee YH,et al.Induction of fos and sis proto-oncogenesis and genes of the extracellular matrix proteins during butyrate induced glioma diferentiation.Biochem Biophys Acta,1990,1048(1):59-65.
35 Shiotsu Y.Current screening for molecular target therapy of cancer. Japanese Journal of Cancer&Chemotherapy,2003,30(12):1863-1872.
36 Goudar RK, Shi Q, Hjelmeland MD.Combination therapy of inhibitors of epidermal growth factor receptor/vascular endothelial growth factor receptor 2 (AEE788) and the mammalian target of rapamyein (RADO01) ofers improved glioblastoma tumor growth inhibition.Mol Cancer Ther,2005,4(1):101-112.
37 Terrance G,Johns, Rodney B,et al.Antitumor efficacy of cytotoxic drugs and the monoclonal antibody 806 is enhanced by the EGF receptor inhibitor AG1478. Proc Natl Acad Sci U S A, 2003 ,23,100(26):15871-15876.
38 Lal A, Glazer CA, Martinson HM, et al.Mutant epidermal growth factor receptor up-regulates molecular effectors of tumor invasion. Cancer Res,2002,15, 62(12): 3335-3339.
39 Schmidt NO, Ziu M, Carrabba G,et al. Antiangiogenic therapy by local intracerebral microinfusion improves treatment efficiency and survival in an orthotopic human glioblastoma Model.Clin Cancer Res,2004,10(4):1255-1262.
40王飞,黄强.神经干细胞应用的新思路:基因治疗胶质瘤.中国肿瘤,2005,14(2):96-98.
41 Mckay R.Stem cells in central nervous system .Science,1997,276(5309):66-71.
42 Weissman IL.Translating stem and progenitor cell biology to the clinic:barriers and opportunities.Science,2000,287(5457):1442-l452.
43 Benedetti S,Piola B,Pollo B,et a1.Gene therapy of experimental brain tumors using neural progenitor cells.Nat Med,2000,6:447-450.
44 Herrlinger U,Woiciechowski C,Sena EM,et a1.Neuralprecursor cells for delivery of replication-conditional HSV-l vector to intracerebral gliomas.Mol Ther,2000,l(4):347-357.
45 Aboody KS,Brown A,Rainov NG,et a1.From the cover neural stem cells display extensive tropism for pathology in adult brain : Evidence from intracranial gliomas.Proc Nat Acad Sci USA,2000,97(23):l2846-l2851.
46 Ehtesham M,Kabos P,Gutierrez MA,et a1.Induction of glioblastoma apoptosis using neural stem cell-mediated delivery of tumor necrosis factor-related apoptosis-inducing ligand.Cancer Res,2002,62(24):7170-7174.
47 Ehtesham M,Kabos P,Kabosova A,et a1.The use of interleukin l2-secreting neural stem cells for the treatment of intracranial glioma.Cancer Res, 2002,62(20):5657-5663.
48 Lan Qing,Huang Qiang,Bao Shi Rao,et al.Preclinical evaluation of SPECT imaging with 131I-labelled monoclonal antibody SZ39 in nude mice.Journal of Neuroimaging(U.S.A),1996,6(2):131-135.
49 Massoud TF, Gambhir SS. Molecular imaging in living subjects,seeing fundamental biological processes in a new light.Genes Dev ,2003,17(5): 545–580.
50 Haubner R, Wester HJ, Weber WA, et al. Non-invasive imaging of alpha(v)beta3 integrin expression using 18F-labeled RGD-containing glycopeptide and positron emission tomography. Cancer Res ,2001,61(5):1781–1785.
51 Herschman HR. Micro-PET imaging and small animal models of disease. Curr Opin Immunol,2003,15(4): 378–384.
52 Lewis J.S,Achilefu S,Garbow J. R,et al. Small animal imaging current technology andperspectives for oncological imaging. Eur. J. Cancer,2002,38,2173–2188.
53 Pirko I, Fricke ST, Johnson AJ, et al. Magnetic resonance imaging, microscopy, and spectroscopy of the central nervous system in experimental animals. NeuroRx ,2005,2: 250-264.
54 Beck B, Plant DH, Grant SC et al. Progress in high field MRI at the University of Florida. MAGMA,2002,13:152-157.
55 Maniotis AJ,Folbcrg R,Hess A,et a1.Am J Patho1,1999,155(3):739-752.
56 Wei-Ying Yue ,Zhong-Ping Chen. Does Vasculogenic Mimicry Exist in Astrocytoma?Journal of Histochemistry & Cytochemistry,2005,53(8): 997-1002.
57 Zhang S,Guo H,Zhang D,et al.Microcirculation patterns in different stages of melanoma.Oncol Rep,2006,15(1):15-20.
58 Galli R,Binda E,Orfaneli U.Isolation and characterization of tumorigenic stem-like neural precursors from human gliblastoma.Cancer Res,2004,64:7011.
59 Qin Shu,Kwong Kwok Wong,Jack M,et al.Direct Orthotopic transplantation of fresh surgical specimen preserves CD133+ tumor cells in clinically relevant mouse models of medulloblastoma and glioma. Stem Cells, 2008 ,10:1-24.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |