食道癌の診療向上のための分子遺伝学的および分子疫学的研究

2006 Fiscal Year Annual Research Report

• Project/Area Number: 17109013
• Research Institution: Kyushu University
• Principal Investigator: 森 正樹 九州大学, 生体防御医学研究所, 教授 (70190999)
• Co-Investigator(Kenkyū-buntansha): 鶴丸 昌彦 順天堂大学, 医学部, 教授 (70155448) ; 加藤 抱一 国立がんセンター, がん対策情報センター, センター長 (60111506) ; 藤田 博正 久留米大学, 医学部, 教授 (90156878) ; 田中 洋一 埼玉県立がんセンター, 消化器外科, 部長 (10143489) ; 徳留 信寛 名古屋市立大学, 大学院医学研究科, 教授 (00037441)
• Keywords: 食道癌 / 分子遺伝学 / 宿主 / 環境 / 腫瘍 / マイクロアレイ

Research Abstract

1.食道癌発癌要因解析および2.転移・再発因子の遺伝子多型解析と遺伝子発現解析
九州大学を含む6施設(平成18年度に新規に鹿児島大学が加入)すべてにおいて各施設内倫理委員会の申請・承認を受け研究が開始し症例の確保に努めた。本研究がこれまで世界的にも例のない、かつ最大の特徴である総数1600例(うち800例の食道癌患者、800例の対照者)からの16ページに及ぶアンケートによる生活習慣調査、また末梢血からの遺伝子多型を実施するために、各施設は症例数確保に全力を注いだ。
対照者は主に九州大学が中心に症例を集め、現在では500例以上のアンケート及び採血を実施した。食道癌患者からは、合計613例(国立がんセンター100例、順天堂大学171例、埼玉がんセンター76例、久留米大学207例、鹿児島大学43例、九大16例)のアンケート及び採血を実施した。手術を受けた患者からの標本採取は合計100例(国立がんセンター31例、順天堂大学15例、埼玉がんセンター13例、久留米大学30例、鹿児島大学8例、九大3例)が得られた。その癌部・非癌部からは凍結切片を作製しmicrodissectionを実施し、厳密に癌部だけの採取を実施した。採取した癌部よりmRNAを抽出し網羅的遺伝子発現を解析するためにマイクロアレイを実施した。また、DNAを抽出しCGHアレイを実施した。
2.抗癌剤感受性に関わる遺伝子多型解析(発現解析)
手術後の補助化学療法治療患者および再発食道癌患者からアンケートおよび採血を実施した。これらの症例サンプル(末梢血)からDNAを抽出しSNP解析を実施し抗癌剤感受性に関与する遣伝子多型の抽出を九州大学生体防御医学研究所人類遺伝学教室で開始した。

Research Products

• [Journal Article] Identification of overexpressed genes in hepatocellular carcinoma, with special reference to ubiquitin-conjugating (2007)
  • Author(s): Ieta K, Ojima E, Tanaka F, Nakamura Y, Haraguchi N, Mimori K, Inoue H, Kuwano H, Mori M
  • Journal Title: Int J Cancer Epub(WEB)
• [Journal Article] TIMP-3 and Phosphatidylinositol 3-kinase Genes Were Found to Be Related to the Progression of Colon Cancer in a Comparison of Pneumoperitoneum and Laparotomy in a Murine Model. (2007)
  • Author(s): Tanaka F, Sonoda H, Okamoto M, Mimori K, Utsunomiya T, Inoue H, Hanai T, Mori M
  • Journal Title: Surg Today 37 Pages: 220-5
• [Journal Article] A specific gene-expression signature quantiffies the degree of hepatic fibrosis in patients with chronic liver disease (2007)
  • Author(s): Utsunomiya T, Okamoto M, Wakiyama S, Hashimoto M, Fukuzawa K, Ezaki T, Aishima S, Yoshikawa Y, Hanai T, Inoue H, Barnard GF, Mori M
  • Journal Title: World J Gastroenterol 13 Pages: 383-90
• [Journal Article] Receptor Activator of Nuclear Factor-kappaB Ligand (RANKL) Expression in Hepatocellular Carcinoma (2007)
  • Author(s): Sasaki A, Ishikawa K, Haraguchi N, Inoue H, Ishio T, Shibata K, Ohta M, Kitano S, Mori M
  • Journal Title: Ann Surg Oncol 14 Pages: 1191-9
• [Journal Article] Opa Interacting Protein 5 (OIP5) Is a Novel Cancer-testis Specific Gene in Gastric Cancer. (2007)
  • Author(s): Nakamura Y, Tanaka F, Nagahara H, Ieta K, Haraguchi N, Mimori K, Sasaki A, Inoue H, Yanaga K, Mori M.
  • Journal Title: Ann Surg Oncol 14 Pages: 885-92
• [Journal Article] Identification of EGFR mutations in esophageal cencer. (2007)
  • Author(s): Sudo T, Mimori K, Nagahara H, Utsunomiya T, Fujita H, Tanaka Y, Shirouzu K, Inoue H, Mori M
  • Journal Title: Eur J Surg Oncol. 33 Pages: 44-8
• [Journal Article] Fhit modulates the DNA damage checkpoint response. (2006)
  • Author(s): Ishii H, Mimori K, Inoue H, Inageta T, Ishikawa K, Semba S, Druck T, Trapasso F, Tani K, Vecchione A, Croce CM, Mori M, Huebner K
  • Journal Title: Cancer Res 66 Pages: 11287-92
• [Journal Article] Gene expression profiling of lymph node metastasis by oligomicroarray analysis using laser microdissection in esophageal squamous cell carcinoma (2006)
  • Author(s): Uchikado Y, Inoue H, Haraguchi N, Mimori K, Natsugoe S, Okumura H, Aikou T, Mori M
  • Journal Title: Int J Oncol. 29 Pages: 1337-47
• [Journal Article] Efficient induction of specific cytotoxic T lymphocytes to tumor rejection peptide using functional matured 2 day-cultured dendritic cells derived from human monocytes. (2006)
  • Author(s): Tanaka F, Yamaguchi H, Haraguchi N, Mashino K, Ohta M, Inoue H, Mori M
  • Journal Title: Int J Oncol 29 Pages: 1263-8
• [Journal Article] Specific gene-expression profiles of noncancerous luver tissue predict the risk for multicentric occurrence of hepatocellular carcinoma in hepatitis C virus-positive patients. (2006)
  • Author(s): Ohmachi T, Inoue H, Mimori K, Tanaka F, Sasaki A, Kanda T, Fujii H, Yanaga K, Mori M
  • Journal Title: Ann Surg Oncol 13 Pages: 947-54
• [Journal Article] Reduced tau expression in gastric cancer can identify candidates for successful Paclitaxel treatment (2006)
  • Author(s): Mimori K, Sadanaga N, Yoshikawa Y, Ishikawa K, Hashimoto M, Tanaka F, Sasaki A, Inoue H, Sugimachi K, Mori M
  • Journal Title: Br J Cancer 94 Pages: 1894-7
• [Journal Article] Clinical significance of TROP2 expression in colorectal cancer. (2006)
  • Author(s): Ohmachi T, Tanaka F, Mimori K, Inoue H, Yanaga K, Mori M
  • Journal Title: Clin Cancer Res 15 Pages: 3057-63
• [Journal Article] Expression of the TRAG-3 gene in human esophageal cancer : the frequent synchronous expression of MAGE-3 gene. (2006)
  • Author(s): Ohta M, Tanaka F, Sadanaga N, Yamaguchi H, Inoue H, Mori M.
  • Journal Title: Oncol Rep 15 Pages: 1529-32
• [Journal Article] Cancer stem cells in human gastrointestinal cancers. (2006)
  • Author(s): Haraguchi N, Inoue H, Tanaka F, Mimori K, Utsunomiya T, Sasaki A, Mori M
  • Journal Title: Hum Cell 19 Pages: 24-9
• [Journal Article] PGP9.5 methylation in diffuse-type gastric cancer. (2006)
  • Author(s): Yamashita K, Park HL, Kim MS, Osada M, Tokumaru Y, Inoue H, Mori M, Sidransky D.
  • Journal Title: Cancer Res. 66 Pages: 3921-7
• [Journal Article] Angiopoietin 2 expression in invasive ductal carcinoma of the breast : its relationship to the VEGF expression and microvessel density. (2006)
  • Author(s): Tsutsui S, Inoue H, Yasuda K, Suzuki K, Takeuchi H, Nishizaki T, Higashi H, Era S, Mori M.
  • Journal Title: Breast Cancer Res Treat 98 Pages: 261-6
• [Journal Article] FHIT is up-regulated by inflammatory stimuli and inhibits prostaglandin E2-mediated cancer progression. (2006)
  • Author(s): Mimori K, Ishii H, Nagahara H, Sudo T, Yamashita K, Inoue H, Barnard GF, Mori M.
  • Journal Title: Cancer Res 66 Pages: 2683-90
• [Journal Article] Significance of skp2 expression inprimary breast cancer. (2006)
  • Author(s): Sonoda H, Inoue H, Ogawa K, Utsunomiya T, Masuda TA, Mori M
  • Journal Title: Clin Cancer Res 15 Pages: 1215-20
• [Journal Article] Characterization of a side population of cancer cells from human gastrointestinal system. (2006)
  • Author(s): Haraguchi N, Utsunomiya T, Inoue H, Tanaka F, Mimori K, Barnard GF, Mori M
  • Journal Title: Stem Cells 24 Pages: 506-13
• [Journal Article] Alvocidib(Flavopiridol) suppresses tumor growth in SCID mice with human esophageal cancer xenografts without inducing apoptosis (2006)
  • Author(s): Sato S, Kajiyama Y, Sugano M, Iwanuma Y, Sonoue H, Matsumoto T, Tsurumaru M
  • Journal Title: Surg Oncol. 15 Pages: 107-13
• [Journal Article] Birt-Hogg-Dube(BHD) gene mutations in human gastric cancer with high frequency microsatellite instability. (2006)
  • Author(s): Jiang W, Fujii H, Matsumoto T, Ohtsuji N, Tsurumaru M, Hino O.
  • Journal Title: Cancer Lett 248 Pages: 103-11
• [Journal Article] Clinical pathways in the treatment of cancers (2006)
  • Author(s): Tanaka T, Tousaka T, Fujita H.
  • Journal Title: Gan To Kagaku Ryoho. 33 Pages: 1568-70
• [Journal Article] Aortic valve replacement after esophagectomy with substernal gastric tube reconstruction. (2006)
  • Author(s): Tobinaga S, Tayama K, Kawano H, Teshima H, Fujita H, Takaseya T, Shoujima T, Takagi K, Akashi H, Aoyagi S.
  • Journal Title: Ann Thorac Cardiovasc Surg 12 Pages: 213-5
• [Journal Article] Stenosis of the bicuspid aortic valve with systemic lupus erythematosus. (2006)
  • Author(s): Yoshikai M, Muraya J, Fujita H.
  • Journal Title: Jpn J Thorac Cardiovasc Surg. 54 Pages: 16-8
• [Journal Article] Long-term survival after three-field lymph-adenectomy for an adenocarcinoma in Barrett's esophagus with metastasis to Virchow's node. (2006)
  • Author(s): Matono S, Fujita H, Sueyoshi S, Tanaka T, Yamana H, Shirouzu K.
  • Journal Title: Jpn J Thorac Cardiovasc Surg 54 Pages: 11-5