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

2007 Fiscal Year Annual Research Report

• Project/Area Number: 17109013
• Research Institution: Kyushu University
• Principal Investigator: 森 正樹 Kyushu University, 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, がん対策情報セヒター, 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 九州大学, 埼玉県立がんセンター, 副病院長 (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施設すべてにおいて各施設内倫理委員会の申請・承認を受け症例の確保に引き続き努めた。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)かちの16ページに友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た症例を集め、現在では800例以上のアンケートを回収し、その情報のデジタル化(解析用ソフトウエアに入力)が完了した。また同数の採血を実施し、対象患者の収集の目標は達成した。食道癌患者からは、6施設から合計834例のアンケートを収集し、その情報をデジタル化が完了した。また同数の採血を実施し現在遺伝子情報の抽出を行っている。手術を受けた患者からの標本採取は合計129例が得られた。目標の200例に向けて、全精力を傾けて収集を継続している。得られた標本から、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。これらの中間結果を日本癌学会学術集会で発表した。
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遺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。食道癌発現に関連する遺伝子多型領域候補を抽出した。

Research Products

• [Journal Article] Clinical significance of LAMB3 and COL7Al mRNA in esophageal squamous cell carcinoma. (2008)
  • Author(s): Kita Y, Mimori K, Tanaka F, Matsumoto T, Haraguchi N, I shikawa K, Matsuzaki S, Fukuyoshi Y, Inoue H, Natsugoe S, AikouT, Mori M.
  • Journal Title: Eur J Surg Oncol (Epub)
  • Peer Reviewed
• [Journal Article] Efficient identification of a novel cancer/testis antigen for immunotherapy using three-step microarray analysis. (2008)
  • Author(s): Yokoe T, Tanaka F, Mimori K, Inoue H, Ohmachi T, Kusunoki M, Mori M.
  • Journal Title: Cancer Res. 68 Pages: 1074-82
  • Peer Reviewed
• [Journal Article] Clinical Significance of BMP7 in Human Colorectal Cancer (2008)
  • Author(s): Motoyama K, Tanaka F, Kosaka Y, Mimori K, Uetake H, Inoue H, Sugihara K, Mori M.
  • Journal Title: Ann Surg Oncol Epub
  • Peer Reviewed
• [Journal Article] Clinical significance of the reduced expression of G protein gamma 7(GNG7)in oesophageal cancer (2008)
  • Author(s): Ohta M, Mimori K, Fukuyoshi Y, Kita Y, Motoyama K, Yamashita K, Ishii H, Inoue H, Mori M.
  • Journal Title: Br J Cancer 98 Pages: 410-7
  • Peer Reviewed
• [Journal Article] Biological and genetic characteristics of tumor-initiating cells in colon cancer (2008)
  • Author(s): Ieta K, Tanaka F, Haraguchi N, Kita Y, Sakashita H, Mimori K, Matsumoto T, Inoue H, Kuwano H, Mori M.
  • Journal Title: Ann Surg Oncol 15 Pages: 638-48
  • Peer Reviewed
• [Journal Article] Activin a causes cancer cell aggressiveness in esophageal squamous cell carcinoma cells (2008)
  • Author(s): Yoshinaga K, Yamashita K, Mimori K, Tanaka F, Inoue H, Mori M.
  • Journal Title: Ann Surg Oncol 15 Pages: 96-103
  • Peer Reviewed
• [Journal Article] Phase II trial of preoperative chemoradiotherapy followed by surgical resection in patients with superior sulcus non-small-cell lung cancers:report of Japan Clinical Oncology Group trial 9806 (2008)
  • Author(s): Kunitoh H, Kato H, Tsuboi M, Shibata T, Asamura H, Ichonose Y, Katakami N, Nagai K, Mitsudomi T, Matsumura A, Nakagawa K, Tada H, Saijo N, Japan Clinical Oncology Group
  • Journal Title: J CIin Oncol 26 Pages: 644-9
  • Peer Reviewed
• [Journal Article] Analysis of T-helper type 1 and 2 cells and T-cytotoxic type 1 and 2 cells of sentinel lymph nodes in breast cancer (2008)
  • Author(s): Ehi K, Ishigami S, Masamoto I, Uenosono Y, Natsugoe S, Arigami T, Arima H, Kijima Y, Yoshinaka H, Yanagita S, Kozono T, Funasako Y, Maruyama I, Aikou T.
  • Journal Title: Oncol Rep 19 Pages: 601-7
  • Peer Reviewed
• [Journal Article] Expression of CXCL12 and its receptor CXCR4 correlates with lymph node metastasis in submucosal esophageal cancer (2008)
  • Author(s): Sasaki K, Natsugoe S, Ishigami S, Matsumoto M, Okumura H, Setoyama T, Uchikado Y, Kita Y, Tamotsu K, Sakurai T, Owaki T, Aikou T.
  • Journal Title: J Surg Oncol 97 Pages: 433-8
  • Peer Reviewed
• [Journal Article] Cyclooxygenase-2 expression is related to prognosis in patients with esophageal squamous cell carcinoma (2008)
  • Author(s): Takatori H, Natsugoe S, Okumura H, Matsumoto M, Uchikado Y, Setoyama T, Sasaki K, Tamotsu K, Owaki T, Ishigami S, Aikou T.
  • Journal Title: Eur J Surg Oncol 34 Pages: 397-402
  • Peer Reviewed
• [Journal Article] Clinical significance of growth differentiation factor 11 in colorectal cancer (2007)
  • Author(s): Yokoe T, Ohmachi, T, Inoue H, Mimori K, Tanaka F, Kusunoki M, Mori M.
  • Journal Title: Int J Oncol 31 Pages: 1097-101
  • Peer Reviewed
• [Journal Article] Clinicopafliological and biological significlnce of mitotic centromere-associated kinesin overexpression in human gastric cancer (2007)
  • Author(s): Nakamura Y, Tanaka F, Haraguchi N, Mimori K, Matsumoto T, Inoue H, Yanaga K, Mori M.
  • Journal Title: Br J Cancel 97 Pages: 543-9
  • Peer Reviewed
• [Journal Article] Clinical significance of the loss of MATSl mRNA expression in colorectal cancer (2007)
  • Author(s): Kosaka Y, Mimori K, Tanaka F, Inoue H, Watanabe M, Mori M.
  • Journal Title: Int J Oncol 31 Pages: 333-8
  • Peer Reviewed
• [Journal Article] Tripartite motif-containing 29(TRIM29)is a novel marker for lymph node metastasis in gastric cancer (2007)
  • Author(s): Kosaka Y, Inoue H, Ohmachi T, Yokoe T, Matsumoto T, Mimori K, Tanaka F, Watanabe M, Mori M.
  • Journal Title: Ann Surg Oncol 14 Pages: 2543-9
  • Peer Reviewed
• [Journal Article] Identification of the high-risk group for metastasis of gastric cancer cases by vascular endothelial growth factor receptor-1 overexpression in peripheral blood (2007)
  • Author(s): Kosaka Y, Mimori K, Fukagawa T, Ishikawa K, Etoh T, Katai H, Sano T, Watanabe M, Sasako M, Mori M.
  • Journal Title: Br J Cancer 96 Pages: 1723-8
  • Peer Reviewed
• [Journal Article] BAC clones related to prognosis in patients with esophageal squamous carcinoma:an array comparative genomic hybridization study (2007)
  • Author(s): Hirasaki S, Noguchi T, Mimori K, Onuki J, Morita K, Inoue H, Sugihara K, Mori M, Hirano T.
  • Journal Title: Oncologist 12 Pages: 406-17
  • Peer Reviewed
• [Journal Article] Identification of overexpressed genes in hepatocellular carinoma, with special reference to ubiquitin-conjugating enzyme E2C gene expression. (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 121 Pages: 33-8
  • Peer Reviewed
• [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
  • Peer Reviewed
• [Journal Article] A specific gene-expression signature quantifies 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
  • Peer Reviewed
• [Journal Article] Loss of MAL expression in precancerous lesions of the esophagus (2007)
  • Author(s): Mimori K, Nishida K, Nakamura Y, Ieta K, Yoshikawa Y, Sasaki A, Ishii H, Alonso MA, Mori M.
  • Journal Title: Ann Surg Oncol 14 Pages: 1670-7
  • Peer Reviewed
• [Journal Article] Subepithelial extension of squamous cell carcinoma in the esophagus:hist opathological study using D2-40 immunostaining for 108 superficial carcinoma (2007)
  • Author(s): Amano T, Matsumoto T, Hayashi T, Arakawa A, Sonoue H, Kajiyama Y, Tsurumaru M.
  • Journal Title: Pathol Int 57 Pages: 759-64
  • Peer Reviewed
• [Journal Article] Value of postoperative surveillance of tumor recurrence after curative esophageactomy (2007)
  • Author(s): Udagawa H, Tsutsumi K, Kinoshita Y, Ueno M, Mine S, Ehara K, Kohno T, Tsurumuu M.
  • Journal Title: Nippon Geka Gakkai Zasshi 108 Pages: 116-9
  • Peer Reviewed
• [Journal Article] Second-line combination chemotherapy with docetaxel for cisplatin-pretreated refractory metastatic esophageal cancer:a preliminary report of initial expenenc (2007)
  • Author(s): Tanaka T, Fujita H, Sueyoslu S, Tanaka Y, Sasahara H, Mori N, Nagano T, Yamaha H, Shirouzu K.
  • Journal Title: Chemotherapy 53 Pages: 449-53
  • Peer Reviewed
• [Journal Article] Helicobacter pylori infection influences the acidity in the gastric tube as an esophageal substitute after esophagectomy (2007)
  • Author(s): Mori N, Fujita H, Sueyoshi S, Aoyama Y, Yanagawa T, ShirouzuK.
  • Journal Title: Dis Esophagus 20 Pages: 333-40
  • Peer Reviewed
• [Journal Article] An effective treatment by chemoradiation therapy after stent insertion for advanced esophageal cancer with esophago-pulmonary fistula-report of acase (2007)
  • Author(s): Hanazono K, Natsugoe S, Okumura H, Matsumoto M, Oowaki T, Setoyama T, Hiraki Y, Arimura K, Nakamura F, Nakajo M, Aikou T.
  • Journal Title: Gan To Kagaku Ryoho 34 Pages: 1275-8
  • Peer Reviewed
• [Journal Article] Improvement in radiosensitivity using small interfering RNA targeting p53R2 in esophageal squamous cell cazcinoma (2007)
  • Author(s): Yokomakura N, Natsugoe S, Okumura H, Ikeda R, Uchikado Y, Mataki Y, Takatori H, Matsumoto M, Owaki T, Ishigami S, Aikou T.
  • Journal Title: Oncol Rep. 18 Pages: 561-7
  • Peer Reviewed
• [Journal Article] Isolated tumour cells in blood and E-cadherin expression in oesophageal squamous cell cancer (2007)
  • Author(s): Setoyama T, Natsugoe S, Okumura H, Matsumoto M, Uchikado Y, Aikou T.
  • Journal Title: Br J Surg 94 Pages: 984-91
  • Peer Reviewed
• [Journal Article] Snail plays a key role in E-cadherin-preserved esophageal squaxnous cell carcinoma (2007)
  • Author(s): Natsugoe S, Uchikado Y, Okumura H, Matsumoto M, Setoyama T, Tamotsu K, Kita Y, Sakamoto A, Owaki T, Ishigami S, Aikou T.
  • Journal Title: Oncol Rep 17 Pages: 517-23
  • Peer Reviewed
• [Journal Article] alpha-catenin is a significant prognostic factor than E-cadherin in esophageal squamous cell carcinoma (2007)
  • Author(s): Setoyama T, Natsugoe S, Okumura H, Matsumoto M, Uchikado Y, Yokomakura N, Islugami S, Aikou T.
  • Journal Title: J Surg Oncol 95 Pages: 483-90
  • Peer Reviewed
• [Presentation] 食道癌の発生・進展に関わる因子の解析 (2007)
  • Author(s): 田中 文明、三森 功士、蒲原 行雄、井上 裕, 森 正樹
  • Organizer: 第66回日本癌学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-05