Development of dosing schedule based on molecular clock mechanisms
基于分子钟机制的给药方案的制定
基本信息
- 批准号:18390050
- 负责人:
- 金额:$ 10.16万
- 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:2006
- 资助国家:日本
- 起止时间:2006 至 2007
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Mammalians circadian pacemaker resides in the paired suprachiasmatic nuclei (SCN). Clock genes are the genes that control the circadian rhythms in physiology and behavior. The effectiveness and toxicity of many drugs vary depending on dosing time associated with 24-hr rhythms of biochemical, physiological and behavioral processes under the control of circadian clock. However, many drugs are still given without regard to the time of day. Identification of a rhythmic marker for selecting dosing time will lead to improved progress and diffusion of chronopharmacotherapy. To monitor the rhythmic marker was useful to choose the most appropriate time of day for administration of drugs that increase their therapeutic effects and/or reduce their side effects. On the other hand, several drugs can cause alterations to the 24-hr rhythms, which leads to illness and altered homeostatic regulation. We showed the disruptive effect of interferon on the rhythm of locomotor activity, body temperature and clock genes mRNA expression in the periphery and SCN. The alteration of the clock function, a new concept of adverse effects, was overcome by devising a dosing schedule that minimizes adverse drug effects on clock function. Furthermore, to produce new rhythmicity by manipulating the conditions of living organs by using rhythmic administration of altered feeding schedules or several drugs appears to lead to the new concept of chronopharmacotherapy. One approach to increasing the efficiency of pharmacotherapy is administering drugs at times during which they are best tolerated. Finally, we developed the vector showing rhythmic gene expression for the intelligent chrono-drug delivery system.
哺乳动物的昼夜节律起搏点位于成对的视交叉上核(SCN)。生物钟基因是控制生理和行为昼夜节律的基因。许多药物的有效性和毒性取决于与生物钟控制下的生化、生理和行为过程的24小时节律相关的给药时间。然而,许多药物仍然不考虑一天中的时间。识别用于选择给药时间的节律标记将导致改善时间药物疗法的进展和扩散。监测节律标记物有助于选择一天中最合适的给药时间,以增加其治疗效果和/或减少其副作用。另一方面,几种药物可以导致24小时节律的改变,从而导致疾病和稳态调节的改变。我们发现干扰素对运动活动的节律、体温和外周和SCN中的时钟基因mRNA表达具有破坏性作用。生物钟功能的改变是一种新的不良反应概念,通过设计一种最大限度地减少药物对生物钟功能的不良影响的给药方案来克服。此外,通过使用改变的喂养时间表或几种药物的节律性给药来操纵活体器官的条件来产生新的节律性,似乎导致了时辰药物治疗的新概念。提高药物治疗效率的一种方法是在药物耐受性最好的时候给药。最后,我们开发了用于智能定时给药系统的基因节律表达载体。
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)
The molecular mechanism regulating 24-hr rhythm of CYP2E1 expression in the mouse liver (in press)
调控小鼠肝脏CYP2E1表达24小时节律的分子机制(出版中)
- DOI:
- 发表时间:2008
- 期刊:
- 影响因子:13.5
- 作者:Matsunaga;N.;Ikeda;M.;Takiguchi;T.;Koyanagi;S.;Ohdo;S.
- 通讯作者:S.
Glucocorticoid regulation of 24-hour oscillation in interferon receptor gene expression in mouse liver
糖皮质激素对小鼠肝脏干扰素受体基因表达24小时振荡的调节
- DOI:
- 发表时间:2006
- 期刊:
- 影响因子:0
- 作者:Koyanagi S;et al.
- 通讯作者:et al.
Modulatory effects of 5-fluorouracil on the rhythmic expression of circadian clock genes: A possible mechanism of chemotherapy-induced circadian rhythm disturbances
- DOI:10.1016/j.bcp.2008.01.011
- 发表时间:2008-04-15
- 期刊:
- 影响因子:5.8
- 作者:Terazonoa, Hideyuki;Hamdan, Ahmed;Ohdo, Shigehiro
- 通讯作者:Ohdo, Shigehiro
Molecular basis for rhythmic expression of CYP3A4 in serum-shocked HepG2 cells
- DOI:10.1097/fpc.0b013e3282f12a61
- 发表时间:2007-12
- 期刊:
- 影响因子:2.6
- 作者:Takako Takiguchi;Miho Tomita;Naoya Matsunaga;Hiroo Nakagawa;S. Koyanagi;S. Ohdo
- 通讯作者:Takako Takiguchi;Miho Tomita;Naoya Matsunaga;Hiroo Nakagawa;S. Koyanagi;S. Ohdo
Basis for dosing time-dependent change in the anti-tumor effect of imatinib in mice.
- DOI:10.1016/j.bcp.2006.08.002
- 发表时间:2006-11
- 期刊:
- 影响因子:5.8
- 作者:Hiroo Nakagawa;Takako Takiguchi;Mariko Nakamura;A. Furuyama;S. Koyanagi;H. Aramaki;S. Higuchi;S. Ohdo
- 通讯作者:Hiroo Nakagawa;Takako Takiguchi;Mariko Nakamura;A. Furuyama;S. Koyanagi;H. Aramaki;S. Higuchi;S. Ohdo
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OHDO Shigehiro其他文献
OHDO Shigehiro的其他文献
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{{ truncateString('OHDO Shigehiro', 18)}}的其他基金
Clarification of the mechanism underlying inflammation-based pathology from viewpoints of chrono-chemical biology
从时间化学生物学的角度阐明基于炎症的病理学机制
- 批准号:
16H02636 - 财政年份:2016
- 资助金额:
$ 10.16万 - 项目类别:
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The molecular clock mechanism underlying the circadian rhythm of cellular metal level: interaction between molecular clock and cellular metal
细胞金属水平昼夜节律的分子钟机制:分子钟与细胞金属的相互作用
- 批准号:
25670079 - 财政年份:2013
- 资助金额:
$ 10.16万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Role of molecular clock on the communication between each organ in organ dysfunction
分子钟在器官功能障碍中各器官之间通讯的作用
- 批准号:
23659084 - 财政年份:2011
- 资助金额:
$ 10.16万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Discovery and development of antitumor drugs focused on the molecular clock of dedifferentiation and apoptosis during carcinogenesis
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- 批准号:
21390047 - 财政年份:2009
- 资助金额:
$ 10.16万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Molecular clock mechanism of cancer
癌症的分子钟机制
- 批准号:
16390042 - 财政年份:2004
- 资助金额:
$ 10.16万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Development of Chronotherapy Based on Clock Genes
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- 批准号:
13672391 - 财政年份:2001
- 资助金额:
$ 10.16万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Development of the mouse model with 24-hour rhythm disturbances
24小时节律紊乱小鼠模型的建立
- 批准号:
09672330 - 财政年份:1997
- 资助金额:
$ 10.16万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
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