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学科主题: 公共卫生
题名:
Integrin alpha(v)beta(3)-Targeted Radioimmunotherapy of Glioblastoma Multiforme
作者: Veeravagu, Anand2,3,4; Liu, Zhaofei1; Niu, Gang2,3; Chen, Kai2,3; Jia, Bing1; Cai, Weibo2,3; Jin, Cunjing1; Hsu, Andrew R.2,3; Connolly, Andrew J.5; Tse, Victor4; Wang, Fan1; Chen, Xiaoyuan2,3
刊名: CLINICAL CANCER RESEARCH
发表日期: 2008-11-15
DOI: 10.1158/1078-0432.CCR-08-0797
卷: 14, 期:22, 页:7330-7339
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: HUMANIZED MONOCLONAL-ANTIBODY ; Y-90 IBRITUMOMAB TIUXETAN ; NON-HODGKINS-LYMPHOMA ; BRAIN-TUMORS ; IN-VIVO ; ANGIOGENESIS ; THERAPY ; GROWTH ; CANCER ; GLIOMA
英文摘要:

Purpose: Abegrin is a monoclonal antibody to human integrin (alpha(v)beta(3), a cell adhesion molecule highly expressed on actively angiogenic endothelium and glioblastoma multiforme tumor cells. The purpose of this study was to evaluate the efficacy of a novel Y-90-Abegrin radioimmunotherapeutic agent in murine xenograft glioblastoma models with noninvasive in vivo molecular imaging modalities.

Experimental Design: A s.c. U87MG human glioblastoma xenograft model was used to determine maximum tolerated dose (MTD), biodistribution, dose response, and efficacy of Y-90-Abegrin. Antitumor efficacy was also characterized in an orthotopic U87MG and in a HT-29 colorectal cancer model, a low integrin-expressing carcinoma. Small-animal positron emission tomography imaging was used to correlate histologic findings of treatment efficacy.

Results: MTD and dose response analysis revealed 200 mu Ci per mouse as appropriate treatment dose with hepatic clearance and no organ toxicity. Y-90-Abegrin-treated U87 MG tumor mice showed partial regression of tumor volume, with increased tumor volumes in Y-90-IgG, Abegrin, and saline groups. F-18-FDG imaging revealed a reduction of cell proliferation and metabolic activity whereas F-18-FLT reflected decreased DNA synthesis in the Y-90-Abegrin group. Ki67 analysis showed reduced proliferative index and quantitative terminal deoxynucleotidyl transferase dUTP nick-end labeling - positive analysis revealed increased DNA fragmentation and apoptosis in Y-90-Abegrin animals. CD31 and 4′,6-diamidino-2-phenylindole staining showed increased vascular fragmentation and dysmorphic vessel structure in Y-90-Abegrin animals only. Orthotopic U87MG tumors treated with Y-90-Abegrin displayed reduced tumor volume. HT-29 tumors showed no significant difference among the various groups.

Conclusion: Radioimmunotherapy with Y-90-labeled Abegrin may prove promising in the treatment of highly vascular, invasive, and heterogeneous malignant brain tumors.

语种: 英语
所属项目编号: R01 CA119053 ; R21 CA121842 ; R21 CA102123 ; P50 CA114747 ; U54 CA119367 ; Z00004105040311 ; D0206001041991 ; 30640067
项目资助者: MedImmune Inc. (X. Chen) ; National Cancer Institute ; Beijing Science and Technology Program ; National Science Foundation of China
WOS记录号: WOS:000261014500021
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/60895
Appears in Collections:北京大学医药卫生分析中心_期刊论文

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作者单位: 1.Peking Univ, Med Isotopes Res Ctr, Beijing 100083, Peoples R China
2.Stanford Univ, Sch Med, Dept Radiol, Stanford, CA USA
3.Stanford Univ, Sch Med, BioX Program, Stanford, CA USA
4.Stanford Univ, Sch Med, Dept Neurosurg, Stanford, CA USA
5.Stanford Univ, Sch Med, Dept Pathol, Stanford, CA USA

Recommended Citation:
Veeravagu, Anand,Liu, Zhaofei,Niu, Gang,et al. Integrin alpha(v)beta(3)-Targeted Radioimmunotherapy of Glioblastoma Multiforme[J]. CLINICAL CANCER RESEARCH,2008,14(22):7330-7339.
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