Estimation of the role of genomic instability on drug response and its application for cancer chemotherapy.

2011 Fiscal Year Final Research Report

• Project/Area Number: 21590402
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human pathology
• Research Institution: Iwate Medical University
• Principal Investigator: HABANO Wataru 岩手医科大学, 薬学部, 准教授 (50332979)
• Project Period (FY): 2009 – 2011
• Keywords: 癌 / ゲノム不安定化 / 薬剤感受性 / エピジェネティクス

Research Abstract

Inter-individual differences in drug efficacy and toxicity are often observed in cancer chemotherapy. Drug resistance is an especially difficult problem. Therefore, understanding the mechanism of such variability in drug response is the key to personalized drug therapy. This study found that DNA methylation plays a role in the regulation of drug-metabolizing enzymes and can be associated with the variability in drug response. DNA methylation is expected to provide useful information for cancer chemotherapy.

Research Products

• [Journal Article] Altered expression of GADD45 genes during the development of chemical-mediated liver hypertrophy and liver tumor promotion in rats (2011)
  • Author(s): Ozawa S, Gamou T, Habano W, Inoue K, Yoshida M, Nishikawa A, Nemoto K, Degawa M.
  • Journal Title: J Toxicol Sci Volume: 36(5) Pages: 613-23
• [Journal Article] Super-induced gene expression of the N-methyl-D-aspartate receptor 2C subunit in chemical-induced hypertrophic liver in rats (2011)
  • Author(s): Nemoto K, Tanaka T, Ikeda A, Ito S, Mizukami M, Hikida T, Gamou T, Habano W, Ozawa S, Inoue K, Yoshida M, Nishikawa A, Degawa M.
  • Journal Title: J Toxicol Sci Volume: 36(5) Pages: 507-14
• [Journal Article] Expression of connexins and the effect of retinoic acid in oral keratinocytes (2011)
  • Author(s): Hatakeyama S, Mikami T, Habano W, Takeda Y.
  • Journal Title: J Oral Sci Volume: 53(3) Pages: 327-32
• [Journal Article] A genetic association between s3-aderenoceptor and cholinergic receptor muscarinic 3 polymorphisms in irritable bowel syndrome (2011)
  • Author(s): Onodera S, Chiba T, Sugai T, Habano W.
  • Journal Title: Hepatogastroenterology Volume: 58(110-111) Pages: 1474-8
• [Journal Article] Induction of CYP1 family members under low-glucose conditions requires AhR expression and occurs through the nuclear translocation of AhR (2011)
  • Author(s): Terashima J, Habano W, Gamou T, Ozawa S.
  • Journal Title: Drug Metab Pharmacokinet Volume: 26(6) Pages: 577-83
• [Journal Article] Involvement of promoter methylation in the regulation of Pregnane X receptor in colon cancer cells (2011)
  • Author(s): Habano W, Gamo T, Terashima J, Sugai T, Otsuka K, Wakabayashi G, Ozawa S.
  • Journal Title: BMC Cancer Volume: 11 Pages: 81
• [Journal Article] Association between tumor necrosis factor-alpha and Fc-gamma receptor polymorphisms with infliximab in Crohn's disease. (2010)
  • Author(s): Tomita K, Chiba T, Sugai T, Habano W.
  • Journal Title: Hepatogastroenterology Volume: 57(99-100) Pages: 535-9
• [Journal Article] Human intestinal spirochaetosis in northern Japan (2010)
  • Author(s): Sato H, Nakamura S, Habano W, Wakabayashi G, Adachi Y.
  • Journal Title: J Med Microbiol Volume: 59(Pt 7) Pages: 791-6
• [Journal Article] Molecular analysis of gastric differentiated-type intramucosal and submucosal cancers (2010)
  • Author(s): Sugai T, Habano W, Endoh M, Konishi Y, Akasaka R, Toyota M, Yamano H, Koeda K, Wakabayashi G, Suzuki K.
  • Journal Title: Int J Cancer Volume: 127(11) Pages: 2500-9
• [Journal Article] Molecular analysis of single isolated glands in gastric cancers and their surrounding gastric intestinal metaplastic mucosa (2010)
  • Author(s): Sugai T, Habano W, Jiao YF, Toyota M, Suzuki H, Tsukahara M, Koizuka H, Akasaka R, Koeda K, Wakabayashi G, Suzuki K.
  • Journal Title: Oncol Rep Volume: 23(1) Pages: 25-33
• [Journal Article] Screening the single nucleotide polymorphisms in patients with internal carotid artery stenosis by oligonucleotide-based custom DNA array (2009)
  • Author(s): Nakai K, Oyanagi M, Hitomi J, Ogasawara K, Inoue T, Kobayashi M, Nakai K, Suwabe A, Habano W, Baba T, Yoshida H, Ogawa A.
  • Journal Title: Bioinform Biol Insights Volume: 1 Pages: 63-9
• [Journal Article] CYP1B1, but not CYP1A1, is downregulated by promoter methylation in colorectal cancers (2009)
  • Author(s): Habano W, Gamo T, Sugai T, Otsuka K, Wakabayashi G, Ozawa S.
  • Journal Title: Int J Oncol Volume: 34(4) Pages: 1085-1
• [Presentation] Global DNA methylation analysis in Caco-2 and LS180 colon cancer cells (2011)
  • Author(s): Habano W, Gamou T, Terashima J, Ozawa S.
  • Organizer: 日本薬物動態学会第26回年会
  • Place of Presentation: 広島
  • Year and Date: 2011-11-16
• [Presentation] Involvement of promoter methylation in the regulation of Pregnane X receptor in colon cancer cells (2010)
  • Author(s): Habano W, Gamou T, Terashima J, Sugai T, Ozawa
  • Organizer: 日本薬物動態学会第25回年会
  • Place of Presentation: さいたま
  • Year and Date: 2010-10-08
• [Presentation] Methylation of PXR, VDR, and PRMT1 genes and their roles in the regulation of CYP3A4 expression in colon cancer cells (2009)
  • Author(s): Habano W, Gamou T, Terashima J, Sugai T, Ozawa
  • Organizer: 日本薬物動態学会第24回年会
  • Place of Presentation: 京都
  • Year and Date: 2009-11-27