Identification of biomarkers to predict anticancer drug sensitivities by means of transgene experiments

通过转基因实验鉴定生物标志物以预测抗癌药物敏感性

基本信息

项目摘要

All of the classical antineplastic agents, with the exception of vinca alkaloids and taxanes, work on DNA metabolism in cells and can therefore be categorised as 'DNA metabolism inhibitor'. Cellular sensitivity against these drugs largely depends on various activities in DNA metabolism. Thymidylate synthase (TS), which regulate the limiting step of thymidylate synthesis, has long received attention as a determinant of cellular sensitivity against the most widely used anticancer agent, 5-fluorouracil (5-FU). However, this possibility has thus far been studied by retrospective, i.e. inductive, approaches, with few exceptions, and has not been concluded yet. In order to approach this problem a priori, a TS-expression plasmid vector has been introduced into a human colorectal cancer cell line, DLD-1. In this system, the expression of the TS transgene is under the control of tetracycline-dependent promoter and inducible by depletion of the antibiotics in the culture media. Ten TS-expressing transformants were isolated and established as a cellline. In one, the dynamic range of TS expression was over ten-fold. Using this transformant cell line, the 5-FU sensitivity at diverse levels of TS expression are now being approached from various angles.
除了长春花碱和紫杉烷外,所有经典的抗肿瘤药物都对细胞中的DNA新陈代谢起作用,因此可以被归类为DNA新陈代谢抑制剂。细胞对这些药物的敏感性在很大程度上取决于DNA新陈代谢的各种活动。胸苷酸合酶(TS)调节胸苷合成的限制步骤,长期以来一直作为细胞对最广泛使用的抗癌药物5-氟尿嘧啶(5-FU)敏感性的决定因素而受到关注。然而,到目前为止,这种可能性已经通过回溯性、归纳性方法进行了研究,几乎没有例外,而且尚未得出结论。为了解决这个问题,我们将TS表达载体导入人结直肠癌细胞系DLD-1。在该系统中,TS基因的表达受四环素依赖启动子的控制,并可通过耗尽培养基中的抗生素来诱导表达。分离并建立了10个TS表达转化子的细胞系。其中,TS的表达动态范围超过10倍。利用这个转化细胞系,现在可以从不同的角度研究TS表达不同水平的5-FU的敏感性。

项目成果

期刊论文数量(18)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Human T-cell leukemia Virus type-I (HTLV-1)-specific T-cell responses detected using three-divided glutathione-S-transferase (GST)-Tax fusion proteins.
使用三分割谷胱甘肽-S-转移酶 (GST)-Tax 融合蛋白检测人类 T 细胞白血病病毒 I 型 (HTLV-1) 特异性 T 细胞反应。
  • DOI:
  • 发表时间:
    2006
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Ohira M;Oba S;Nakamura Y;Hirata T;Ishii S;Nakagawara A.;Nagano S;Kurihara K et al.
  • 通讯作者:
    Kurihara K et al.
Potential immunogenicity of adult T cell leukemia cells in vivo
  • DOI:
    10.1002/ijc.20737
  • 发表时间:
    2005-03-20
  • 期刊:
  • 影响因子:
    6.4
  • 作者:
    Kurihara, K;Harashima, N;Kannagi, M
  • 通讯作者:
    Kannagi, M
Human T-cell leukemia virus type-I (HTLV-I)-specific T-cell responses detected using three-divided glutathione-S-transferase (GST)-Tax fusion proteins.
使用三分割谷胱甘肽-S-转移酶 (GST)-Tax 融合蛋白检测人类 T 细胞白血病病毒 I 型 (HTLV-I) 特异性 T 细胞反应。
  • DOI:
  • 发表时间:
    2006
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Satoshi Funaki;Shori Takahashi;Naohiro Wada;Hitohiko Murakami;Kensuke Harada;Kurihara K et al.
  • 通讯作者:
    Kurihara K et al.
Prognostic factors for relapsed childhood acute lymphoblastic leukemia: Impact of allogeneic stem cell transplantation-a report from the Kyushu-Yamaguchi Children's Cancer Study Group.
复发性儿童急性淋巴细胞白血病的预后因素:同种异体干细胞移植的影响——九州山口儿童癌症研究组的报告。
  • DOI:
  • 发表时间:
    2005
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Matsuzaki;A. et al.
  • 通讯作者:
    A. et al.
Human T-cell leukemia virus type-l (HTLV-I)-specific T-cell responses detected using three-divided glutathione-S-transferase (GST)-Tax fusion proteins.
使用三分割谷胱甘肽-S-转移酶 (GST)-Tax 融合蛋白检测人类 T 细胞白血病病毒 I 型 (HTLV-I) 特异性 T 细胞反应。
  • DOI:
  • 发表时间:
    2006
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Kai;N.;Iwase;K.;Imai;K.;Nakahira;E.;Soma;M.;他5名;Yuasa;S.;Murofushi Y;Kurihara K et al.
  • 通讯作者:
    Kurihara K et al.
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OKAMURA Jun其他文献

OKAMURA Jun的其他文献

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{{ truncateString('OKAMURA Jun', 18)}}的其他基金

DNA mismatch repair deficiency in paediatric haematological malignancies: research and application for chemotherapeutic strategies
儿科血液恶性肿瘤DNA错配修复缺陷:化疗策略的研究与应用
  • 批准号:
    22591173
  • 财政年份:
    2010
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Molecular mechanisms of the antineoplastic agents inhibiting DNA replication and their applications to cancer patient treatmen
抗肿瘤药物抑制DNA复制的分子机制及其在癌症患者治疗中的应用
  • 批准号:
    19591274
  • 财政年份:
    2007
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
A comprehensive study of the regulatory mechanisms for prognosis-related leukaemia cell surface antigen expression
预后相关白血病细胞表面抗原表达调控机制的综合研究
  • 批准号:
    15591040
  • 财政年份:
    2003
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)

相似海外基金

Delays in Acquisition of Oral Antineoplastic Agents
口服抗肿瘤药物的获取延迟
  • 批准号:
    9975367
  • 财政年份:
    2020
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Eliminate the difficulty of venous puncture in patients receiving antineoplastic agents - Development of a new strategy for the prevention of induration-
消除接受抗肿瘤药物的患者静脉穿刺的困难 - 制定预防硬结的新策略 -
  • 批准号:
    16K11932
  • 财政年份:
    2016
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    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Molecular mechanisms of the antineoplastic agents inhibiting DNA replication and their applications to cancer patient treatmen
抗肿瘤药物抑制DNA复制的分子机制及其在癌症患者治疗中的应用
  • 批准号:
    19591274
  • 财政年份:
    2007
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
PNET EXPERIMENTAL THERAPEUTICS--ANTINEOPLASTIC AGENTS AND TREATMENT DELIVERY
PNET 实验治疗——抗肿瘤药物和治疗实施
  • 批准号:
    6346309
  • 财政年份:
    2000
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    $ 2.18万
  • 项目类别:
TRAINING IN PHARMACOLOGY OF ANTINEOPLASTIC AGENTS
抗肿瘤药物药理学培训
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    2720213
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    1999
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    $ 2.18万
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TRAINING IN PHARMACOLOGY OF ANTINEOPLASTIC AGENTS
抗肿瘤药物药理学培训
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    6513197
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    1999
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    $ 2.18万
  • 项目类别:
Training in Pharmacology of Antineoplastic Agents
抗肿瘤药物药理学培训
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    7101017
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    1999
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抗肿瘤药物药理学培训
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TYROSINE KINASE INHIBITORS AS ANTINEOPLASTIC AGENTS
酪氨酸激酶抑制剂作为抗肿瘤剂
  • 批准号:
    2885074
  • 财政年份:
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    $ 2.18万
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TYROSINE KINASE INHIBITORS AS ANTINEOPLASTIC AGENTS
酪氨酸激酶抑制剂作为抗肿瘤剂
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    6174221
  • 财政年份:
    1999
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    $ 2.18万
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