Molecular machinery underlying tissue-specific development of adverse drug reactions induced by anticancer drugs

抗癌药物引起的药物不良反应组织特异性发展的分子机制

• 批准号: 22590143
• 负责人: NUMAZAWA Satoshi
• 金额: $ 2.75万
• 依托单位: Showa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22590143/
• 关键词: 臨床薬学; 化学療法; 副作用発現機構; 5-フルオロウラシル; p53; 骨髄毒性; 医薬品副作用; 酸化ストレス; Nrf2

The purpose of this study was to clarify whether 5-fluorouracil (5-FU)-induced myelotoxicity is a cause of oxidative stress and to demonstrate machineryinvolved in tissue-specific development of adverse-drug reactions. 5-FU-inducedmyelotoxicity in mice was directly linked to intracellular glutathione and activity of Nrf2,indicating that oxidative stress is involved in the process. In addition, 5-FU induced different responses of p53 in the bone marrow and tumor xenografts, which could be participated in the tissue selectivity of the 5-FU-mediated toxicity.

本研究的目的是阐明5-氟尿嘧啶（5-FU）诱导的骨髓毒性是否是氧化应激的原因，并证明参与组织特异性药物不良反应发展的机制。5-FU诱导的小鼠骨髓毒性与细胞内谷胱甘肽和Nrf 2活性直接相关，表明氧化应激参与了该过程。此外，5-FU在骨髓和移植瘤中诱导不同的p53反应，这可能参与了5-FU毒性的组织选择性。

项目成果

フェノバルビタールによるmiR-122ダウンレギュレーションを介したCYP2B誘導機構

苯巴比妥下调 miR-122 的 CYP2B 诱导机制

• 发表时间: 2011
• 作者: 志津怜太;沼澤聡、吉田武美
• 通讯作者: 沼澤聡、吉田武美

Neurotoxicity in the LPS dosage in the mouse substantia nigra

LPS 剂量对小鼠黑质的神经毒性

• 发表时间: 2011
• 作者: Ishii A;Tanaka S;Ohtaki H;Nakamachi T;Shioda S;Numazawa S;Yoshida T
• 通讯作者: Yoshida T

Possible involvement of p53 mediated patways in the myelosuppression induced by 5-FU

p53 介导的途径可能参与 5-FU 诱导的骨髓抑制

• 发表时间: 2010
• 作者: Miyake S;Sugihara K;Numazawa S;Yoshida T
• 通讯作者: Yoshida T

Involvement of Interleukin-1 in Lipopolysaccaride-Induced Microglial Activation and Learning and Memory Deficits

• DOI: 10.1002/jnr.22582
• 发表时间: 2011-04-01
• 期刊: JOURNAL OF NEUROSCIENCE RESEARCH
• 影响因子: 4.2
• 作者: Tanaka, S.;Kondo, H.;Yoshida, T.
• 通讯作者: Yoshida, T.

Cross-talk between constitutive androstane receptor and hypoxia-inducible factor in the regulation of gene expression

组成型雄甾烷受体与缺氧诱导因子在基因表达调控中的串扰

• DOI: 10.1016/j.toxlet.2013.03.014
• 发表时间: 2013
• 期刊: Toxicol Lett
• 影响因子: 3.5
• 作者: Shizu R;Shindo S;Yoshida T and Numazawaa S
• 通讯作者: Yoshida T and Numazawaa S