Establishment of the new therapy based on inflammatory mediator and DNA methylation in colorectal cancer

• Project/Area Number: 25462058
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kyushu University
• Principal Investigator: Oki Eiji 九州大学, 大学病院, 講師 (70380392)
• Co-Investigator(Kenkyū-buntansha): MORITA Masaru 独立行政法人国立病院機構(九州がんセンター), その他部局等, 消化器外科部長 (30294937) ; SAEKI Hiroshi 九州大学, 大学病院, 講師 (80325448) ; KITAO Hiroyuki 九州大学, 医学研究院, 准教授 (30368617) ; IKEDA Tetsuo 九州大学, 大学病院, 准教授 (60585701)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: DNAメチル化 / 炎症性メデイエーター / 大腸癌 / プロスタグランジン / 低侵襲手術 / MSI / BRAF / メチル化 / LINE1 / DNA修復 / 炎症

Outline of Final Research Achievements

Global DNA hypomethylation is associated with increased chromosomal instability and plays an important role in tumorigenesis. The methylation status of the long interspersed nuclear element-1 (LINE-1) element is a useful surrogate marker for global DNA methylation. Using resected tumor tissues and the corresponding normal colorectal cancer, bisulfite pyrosequencing analysis was performed to quantify the LINE-1 methylation levels. p53 mutations in exons two to ten were detected by polymerase chain reaction direct sequencing. Chromosomal instability was assessed by single nucleotide polymorphism array comparative genomic hybridization analysis. The LINE-1 methylation level of colorectal cancer was lower than matched normal mucosa. The LINE-1 methylation levels in colorectal cancer had a significant inverse association with the methylation in the MLH1.

Research Products

• [Journal Article] A Randomized Phase III Trial Comparing S-1 Versus UFT as Adjuvant Chemotherapy for Stage II/III Rectal Cancer (JFMC35-C1: ACTS-RC). (2016)
  • Author(s): Oki E
  • Journal Title: Annals of Oncology Volume: in press
  • Peer Reviewed / Open Access
• [Journal Article] Phase II Study of Docetaxel and S-1 (DS) as Neoadjuvant Chemotherapy for Clinical Stage III Resectable Gastric Cancer. (2014)
  • Author(s): Oki E, Emi Y, Kusumoto T, Sakaguchi Y, Yamamoto M, Sadanaga N, Shimokawa M, Yamanaka T, Saeki H, Morita M, Takahashi I, Hirabayashi N, Sakai K, Orita H, Aishima S, Kakeji Y, Yamaguchi K, Yoshida K, Baba H, Maehara Y.
  • Journal Title: Ann Surg Oncol Volume: 7 Pages: 2014-2014
  • Peer Reviewed
• [Journal Article] LINE-1 hypomethylation, DNA copy number alterations, and CDK6 amplification in esophageal squamous cell carcinoma. (2014)
  • Author(s): Baba Y, Watanabe M, Murata A, Shigaki H, Miyake K, Ishimoto T, Iwatsuki M, Iwagami S, Yoshida N, Oki E, Sakamaki K, Nakao M, Baba H.
  • Journal Title: Clin Cancer Res Volume: 1 Pages: 1114-1114
  • Peer Reviewed
• [Journal Article] Contribution of BubR1 to oxidative stress-induced aneuploidy in p53-deficient cells. (2013)
  • Author(s): Ikawa-Yoshida A., Ando K., Oki E., Saeki H., Kumashiro R., Taketani K., Ida S., Tokunaga E., Kitao H., Morita M., Maehara Y.
  • Journal Title: Cancer Med Volume: 2(4) Pages: 447-447
  • DOI: 10.1002/cam4.101
  • Peer Reviewed
• [Presentation] 大腸癌におけるバイオマーカーとしてのBRA遺伝子変異の意義 (2016)
  • Author(s): 中司 悠
  • Organizer: 第116回日本外科学会定期学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2016-04-14
• [Presentation] 散発性大腸癌 における抗BRAF(V600E)特異抗体を用いた免疫組織化学染色によるBRAF statusの. 解析 (2015)
  • Author(s): 中司 悠
  • Organizer: 第26回日本消化器癌発生学会
  • Place of Presentation: 鳥取
  • Year and Date: 2015-11-19