Development of companion diagnostics and molecular target therapy in malignancy : a model of the purine metabolic enzyme deficiency
恶性肿瘤伴随诊断和分子靶向治疗的发展:嘌呤代谢酶缺乏的模型
基本信息
- 批准号:20390166
- 负责人:
- 金额:$ 10.32万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (B)
- 财政年份:2008
- 资助国家:日本
- 起止时间:2008 至 2010
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Methylthioadenosine phosphorylase (MTAP) is an enzyme involved in the metabolism of purine and methionine. Genetic analysis of the MTAP-negative cancer cell lines indicated that the all enzyme-negative cell lines but one had the partial or total deletion of MTAP gene. When this exceptional cell line was incubated with 5'-deazacytidine, the MTAP gene expression was confirmed by RT-PCR, indicating that the promoter hypermethylation is one of the mechanisms for MTAP deficiency in malignancy. In addition to IHC and Western blotting with anti-human MTAP monoclonal antibody, FACS analysis was found to be useful for the diagnosis of MTAP deficiency in leukemic cell lines.In conclusions, MTAP deficiency will be diagnosed more precisely with IHC and FACS analysis than with the genetic test alone. Since the frequency of MTAP deficiency in a variety of primary tumors is relatively high, one could exploit this metabolic difference between normal and cancer cells for the development of the selective chemotherapy. Furthermore, the combination of MTAP deficiency as a molecular target and the selective chemotherapy is a good example of companion diagnostics.
甲基硫腺苷磷酸化酶(MTAP)是一种参与嘌呤和蛋氨酸代谢的酶。对MTAP阴性癌细胞的遗传分析表明,除1株外,其余均有MTAP基因的部分或全部缺失。将该异常细胞系与5'-去氮胞苷孵育后,RT-PCR证实了MTAP基因的表达,表明启动子超甲基化是MTAP在恶性肿瘤中缺乏的机制之一。除了IHC和抗人MTAP单克隆抗体的Western blotting外,FACS分析可用于诊断白血病细胞系的MTAP缺乏症。综上所述,IHC和FACS分析将比单独的基因检测更准确地诊断MTAP缺乏症。由于多种原发肿瘤中MTAP缺乏的频率相对较高,因此可以利用正常细胞和癌细胞之间的这种代谢差异来开发选择性化疗。此外,结合MTAP缺乏作为分子靶点和选择性化疗是伴随诊断的一个很好的例子。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Personalized treatment in the eradication therapy for Helicobacter pylori.
幽门螺杆菌根除治疗中的个体化治疗。
- DOI:
- 发表时间:2010
- 期刊:
- 影响因子:0
- 作者:Jinda S;Nakatani K;Nishioka J;Yasuda K;Soya Y;Hayashi A;Wada H;Nobori T
- 通讯作者:Nobori T
Prospective evaluation of three different diagnostic criteria for disseminated intravascular coagulation
- DOI:10.1160/th10-05-0293
- 发表时间:2011-01-01
- 期刊:
- 影响因子:6.7
- 作者:Takemitsu, Tetsushi;Wada, Hideo;Nobori, Tsutomu
- 通讯作者:Nobori, Tsutomu
Prevention of venous thromboembolism according to the guidelines of a domestic manual.
按照国内手册的指导方针预防静脉血栓栓塞。
- DOI:
- 发表时间:2010
- 期刊:
- 影响因子:2.1
- 作者:Kaneko T;et al.
- 通讯作者:et al.
造血幹細胞移植レシピエントにおける日和見感染原因ウイルス定量システムの有用性
量化导致造血干细胞移植受者机会性感染的病毒系统的实用性
- DOI:
- 发表时间:2010
- 期刊:
- 影响因子:0
- 作者:安田和成;他
- 通讯作者:他
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NOBORI Tsutomu其他文献
NOBORI Tsutomu的其他文献
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{{ truncateString('NOBORI Tsutomu', 18)}}的其他基金
Basic evaluation of diagnosis of nucleic acid metabolizing enzyme deficiency by flow cytometry
流式细胞术诊断核酸代谢酶缺乏症的基本评价
- 批准号:
23590668 - 财政年份:2011
- 资助金额:
$ 10.32万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Study on selective cancer chemotherapy targeting the deficiency of a purine metabolic enzyme
针对嘌呤代谢酶缺乏的选择性癌症化疗研究
- 批准号:
11557205 - 财政年份:1999
- 资助金额:
$ 10.32万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
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