Molecular mechanisms of gefitinib-induced rash formation: Gefitinib augments lipogenesis and steroidgenesis in sebaceous glands
| Project/Area Number |
22590506
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied pharmacology
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| Research Institution | Tokyo University of Pharmacy and Life Science |
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Principal Investigator |
SATO Takashi 東京薬科大学, 薬学部, 准教授 (90266891)
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| Co-Investigator(Kenkyū-buntansha) |
HAYASHI Nobukazu 冲中記念成人病研究所, その他部局等, 研究員 (90272575)
OHTA Shin 東京薬科大学, 薬学部, 教授 (30233125)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 医薬品副作用 / 薬物相互作用 / ざ瘡 / 抗癌剤 / ゲフィチニブ / 皮脂腺 / 副作用 / 上皮成長因子受容体 / チロシンキナーゼ阻害剤 / 皮疹 / 〓瘡 |
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| Research Abstract |
A small-molecule tyrosine kinase inhibitor, gefitinib, which targets the ligand-binding domain of epidermal growth factor receptors, exhibits anti-tumorigenic activity in patients with advanced non-small cell lung cancer. Many patients treated with gefitinib develop an acne-like rash on the face and upper body. Although acne is characterized as a functional disorder in sebaceous glands and pilosebaceous units, there have been no reports to date that gefitinib may modulate sebum production in sebaceous glands. In the present study, a mass spectrometry analysis revealed that orally administrated gefitinib was detectable in a pustule from a patient treated with gefitinib but not ones from four acne patients. In addition, gefitinib augmented the production of triacylglycerols (TG), the major sebum component, and perilipin, a sebocytic differentiation marker, in human and hamster sebocytes. Furthermore, gefitinib facilitated steroidogenesis in both hamster and human sebocytes. Therefore, these results provide novel evidence that gefitinib exists in the hair follicle of the skin after its oral administration and directly facilitates sebum production by the augmentation of TG production. Moreover, the augmentation of sebum production is likely to due to the increases of androgen synthesisin sebocytes. These findings will help to increase the clinical understanding of the side effects of gefitinib, and improve the QOL of patients being treated with gefitinib
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Report
(4 results)
Research Products
(40 results)
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[Journal Article] Identification and characterization of ABCB1-mediated and non-apoptotic sebum secretion in differentiated hamster sebocytes2011
Author(s)
Kurihara, H., Sato, T., Akimoto, N., Ogura, T., Ito, A.
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Journal Title
BBA Molecular Biology of Lipids
Volume: 1,811
Pages: 1090-1096
Related Report
Peer Reviewed
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[Journal Article] Augmentation of gene expression and production of promatrix metalloproteinase 2 by Propionibacterium acnes-derived factors in hamster sebocytes and dermal fibroblasts : A possible mechanism for acne scarring.2011
Author(s)
Sato, T., Kurihara, H, Akimoto, N., Noguchi, N., Sasatsu, M., Ito, A.
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Journal Title
Biol.Pharm.Bull.
Volume: 34
Pages: 295-299
NAID
Related Report
Peer Reviewed
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