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

2008 Fiscal Year Annual Research Report

• Project/Area Number: 17109013
• Research Institution: Osaka University
• Principal Investigator: 森 正樹 Osaka University, 医学系研究科, 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, 医学部, 教授 (00037441)
• Keywords: 食道癌 / 分子遺伝学 / 宿主 / 環境 / 腫瘍

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1000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1000例以上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完了した。SNPs解析を開始し、食道癌発生に関与する有力な候補領域として4カ所(2、11、20、22番染色体)を選択した。現在詳細な解析を進めている。手術を受けた患者からの標本採取は合計160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。
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] Health Risk Appraisal Models for Mass Screening for Esophageal and Pharyngeal Cancer : An Endoscopic Follow-up Study of Cancer-Free Japanese Men. (2009)
  • Author(s): Yokoyama A, Kumagai Y, Yokoyama T, Omori T, Kato H, Igaki H, Tsujinaka T, Muto M, Yokoyama M, Watanabe H
  • Journal Title: Cancer Epidemiol Biomarkers Prev. 18(2) Pages: 651-5
  • Peer Reviewed
• [Journal Article] Salvage esophagectomy after high-dose chemoradiotherapy for esophageal squamous cell carcinoma. (2009)
  • Author(s): Tachimori Y, Kanamori N, Uemura N, Hokamura N, Igaki H, Kato H
  • Journal Title: J Thorac Cardiovasc Surg. 137(1) Pages: 49-54
  • Peer Reviewed
• [Journal Article] Expression of CXCL12 and its receptor CXCR4 in esophageal squamous cell carcinoma. (2009)
  • Author(s): Sasaki K, Natsugoe S, Ishigami S, Matsumoto M, Okumura H, Setoyama T, Uchikado Y, Kita Y, Tamotsu K, Hanazono K, Owaki T, Aikou T
  • Journal Title: Oncol Rep 21(1) Pages: 65-71
  • Peer Reviewed
• [Journal Article] A history of esophageal surgery in the twentieth century. (2009)
  • Author(s): Kakegawa T, Fujita H
  • Journal Title: Gen Thorac Cardiovasc Surg 57(2) Pages: 55-63
  • Peer Reviewed
• [Journal Article] Clinical significance of ApoE expression in human gastric cancer. (2008)
  • Author(s): Sakashita K, Tanaka F, Zhang X, Mimori K, Kamohara Y, Inoue H, Sawada T, Hirakawa K, Mori M
  • Journal Title: Oncol Rep 20 Pages: 1313-9
  • Peer Reviewed
• [Journal Article] Potential role of dendritic cell vaccination with MAGE peptides in gastrointestinal carcinomas. (2008)
  • Author(s): Tanaka F, Haraguchi N, Isikawa K, Inoue H, Mori M
  • Journal Title: Oncol Rep 20 Pages: 1111-1116
  • Peer Reviewed
• [Journal Article] Clinical significance of low expression of Prostasin mRNA in human gastric cancer. (2008)
  • Author(s): Sakashita K, Mimori K, Tanaka F, Tahara K, Inoue H, Sawada T, Ohira M, Hirakawa K, Mori M
  • Journal Title: J Surg Oncol 98(7) Pages: 559-64
  • Peer Reviewed
• [Journal Article] Activin A enhances MMP-7 activity via the transcription factor AP-1 in an esophageal squamous cell carcinoma cell line. (2008)
  • Author(s): Yoshinaga K, Mimori K, Inoue H, Kamohara Y, Yamashita K, Tanaka F, Mori M
  • Journal Title: Int J Oncol 33 Pages: 453-9
  • Peer Reviewed
• [Journal Article] CD133+CD44+ population efficiently enriches colon cancer initiating cells. (2008)
  • Author(s): Haraguchi N, Ohkuma M, Sakashita H, Matsuzaki S, Tanaka F, Mimori K, Kamohara Y, Inoue H, Mori M
  • Journal Title: Ann Surg Oncol 15 Pages: 2927-33
  • Peer Reviewed
• [Journal Article] The search for cancer stem cells in hepatocellular carcinoma. (2008)
  • Author(s): Kamohara Y, Haraguchi N, Mimori K, Tanaka F, Inoue H, Mori M, Kanematsu T
  • Journal Title: Surgery 144 Pages: 119-24
  • Peer Reviewed
• [Journal Article] Prognostic relevance of Tensin4 expression in human gastric cancer. (2008)
  • Author(s): Sakashita K, Mimori K, Tanaka F, Kamohara Y, Inoue H, Sawada T, Hirakawa K, Mori M
  • Journal Title: Ann Surg Oncol 15 Pages: 2606-13
  • Peer Reviewed
• [Journal Article] Mitotic centromere-associated kinesin is a novel marker for prognosis and lymph node metastasis in colorectal cancer. (2008)
  • Author(s): Ishikawa K, Kamohara Y, Tanaka F, Haraguchi N, Mimori K, Inoue H, Mori M
  • Journal Title: Br J Cancer 98 Pages: 1824-9
  • Peer Reviewed
• [Journal Article] PDGF-BB is a novel prognostic factor in colorectal cancer. (2008)
  • Author(s): Nakamura Y, Tanaka F, Yoshikawa Y, Mimori K, Inoue H, Yanaga K, Mori M
  • Journal Title: Ann Surg Oncol 15 Pages: 2129-36
  • Peer Reviewed
• [Journal Article] Clinical significance of loss of Fhll expression in human gastric caneer. (2008)
  • Author(s): Sakashita K, Mimori K, Tanaka F, Kamohara Y, Inoue H, Sawada T, Hirakawa K, Mori M
  • Journal Title: Ann Surg Oncol 15 Pages: 2293-300
  • Peer Reviewed
• [Journal Article] Clinical significance of LAMB3 and COL7A1 mRNA in esophageal squamous cell carcinoma. (2008)
  • Author(s): Kita Y, Mimori K, Tanaka F, Matsumoto T, Haraguchi N, Ishikawa K, Matsuzaki S, Fukuyoshi Y, Inoue H, Natsugoe S, Aikou T, Mori M
  • Journal Title: Eur J Surg Oncol 35(1) Pages: 52-8
  • 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 15 Pages: 1530-7
  • 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] Prognostic value of tumor-infiltrating FOXP3(+) regulatory T cells inpatients with hepatocellular carcinoma. (2008)
  • Author(s): Sasaki A, Tanaka F, Mimori K, Inoue H, Kai S, Shibata K, Ohta M, Kitano S, Mori M
  • Journal Title: Eur J Sure Oncol 34 Pages: 173-9
  • Peer Reviewed
• [Journal Article] Correlation between loss of Bcl-XL cxpression and improved prognosis in advanced esophageal cancer treated by preoperative chemoradioth erapy. (2008)
  • Author(s): Okumura M, Kajiyama Y, Takeda K, Okumura K, Tsurumaru M
  • Journal Title: Eur Surg Res 41(3) Pages: 260-6
  • Peer Reviewed
• [Journal Article] Circulating micrometastases of esophageal cancer detected by carcinoembryonic antigen mRNA reverse transcriptase-polymerase chain reaction : clinical implications. (2008)
  • Author(s): Hashimoto T, Kajiyama Y, Tsutsumi-Ishii Y, Nagaoka I, Tsurumaru M
  • Journal Title: Dis Esophagus 21(8) Pages: 690-6
  • Peer Reviewed
• [Journal Article] Lymphatic invasion according to D2-40 immunostaining is a strong predictor of nodal metastasis in superficial squamous cell carcinoma of the esophagus : algorithm for risk of nodal metastasis based on lymphatic invasion. (2008)
  • Author(s): Tomita N, Matsumoto T, Hayashi T, Arakawa A, Sonoue H, Kajiyama Y, Tsurumaru M
  • Journal Title: Pathol Int 58(5) Pages: 282-7
  • Peer Reviewed
• [Journal Article] Histological diversity in basaloid squamous cell carcinoma of the esophagus. (2008)
  • Author(s): Kobayashi Y, Nakanishi Y, Taniguchi H, Sekine S, Igaki H, Tachimori Y, Kato H, Matsubara H, Okazumi S, Shimoda T
  • Journal Title: Dis Esophagus In Press
  • Peer Reviewed
• [Journal Article] Health risk appraisal models for mass screening of esophageal cancer in Japanese men. (2008)
  • Author(s): Yokoyama T, Yokoyama A, Kumagai Y, Omori T, Kato H, Igaki H, Tsujinaka T, Muto M, Yokoyama M, Watanabe H
  • Journal Title: Cancer Epidemiol Biomarkers Prev 17(10) Pages: 2846-54
  • Peer Reviewed
• [Journal Article] Two cases of early-stage esophageal malignant melanoma with long-term survival. (2008)
  • Author(s): Suzuki H, Nakanishi Y, Taniguchi H, Shimoda T, Yamaguchi H, Igaki H, Tachimori Y, Kato H
  • Journal Title: Pathol Int 58(7) Pages: 432-5
  • Peer Reviewed
• [Journal Article] Salvage gastrectomy following a combination of biweekly paclitaxel and S-1 for stage IV gastric cancer. (2008)
  • Author(s): Ishigami S, Natsugoe S, Nakajo A, Matsumoto M, Uenosono Y, Arigami T, Setoyama T, Arima H, Uchikado Y, Kita Y, Sasaki K, Aikou T
  • Journal Title: J Gastrointest Surg 12(8) Pages: 1370-5
  • Peer Reviewed
• [Journal Article] HLA-class I expression in gastric cancer. (2008)
  • Author(s): Ishigami S, Natsugoe S, Nakajo A, Arigami T, Kitazono M, Okumura H, Matsumoto M, Uchikado Y, Setoyama T, Sasaki K, Aikou T
  • Journal Title: J Surg Oncol 97(7) Pages: 605-8
  • Peer Reviewed
• [Journal Article] Sueyoshi S. Objective assessment of the efficacy of supermicrosurgical lymphaticovenous anastomosis and microsurgical lymphaticovenous implantation in a case of axillary lymphorrhea. (2008)
  • Author(s): Morihisa Y, Inoue Y, Kiyokawa K, Nishi Y, Fujita H
  • Journal Title: J Reconstr Microsurg 24(1) Pages: 29-32
  • Peer Reviewed