Risk evaluation of environmental carcinogenesis

• Project/Area Number: 22240093
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cancer epidemiology and prevention
• Research Institution: Juntendo University
• Principal Investigator: HINO Okio 順天堂大学, 医学部, 教授 (90127910)
• Co-Investigator(Kenkyū-buntansha): ADACHI Shuichi 相模女子大学, 栄養科学部, 教授 (90129148)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥43,550,000 (Direct Cost: ¥33,500,000、Indirect Cost: ¥10,050,000); Fiscal Year 2012: ¥13,390,000 (Direct Cost: ¥10,300,000、Indirect Cost: ¥3,090,000); Fiscal Year 2011: ¥14,170,000 (Direct Cost: ¥10,900,000、Indirect Cost: ¥3,270,000); Fiscal Year 2010: ¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000)
• Keywords: がん研究と社会の接点 / アスベスト / ナノマテリアル / 環境発がん / 中皮腫 / 発症前診断

Research Abstract

We reported N-ERC/mesothelin might be a useful blood tumor marker for mesothelioma. In order to investigate whether this tumor marker is useful for an early diagnosis in a mass examination, we started a large-scale pilot research screening in Japan for construction workers with the risk of asbestos exposure. In conclusion, it is indicated that the blood tumor marker is useful for an early diagnosis in a mass examination and may lead to the prolongation of their survival. We havedemonstrated that plasma N-ERC levels of rats administered multi-wall carbon nanotube, man-made mineral fibers or chrysotile were continuously higher even at 10 weeks after intraperitoneal (i.p.) injection than the other non-carcinogenic materials.

Research Products

• [Journal Article] The N-ERC index is a novel monitoring and prognostic marker for advanced malignant pleural mesothelioma. (2013)
  • Author(s): Mori T
  • Journal Title: J. Thoracic Disease Volume: in press
  • Peer Reviewed
• [Journal Article] Fenton reaction induced cancer in wild type rats recapitulates genomic alterations observed in human cancer. (2013)
  • Author(s): Akatsuka S
  • Journal Title: PloSONE Volume: in press
  • Peer Reviewed
• [Journal Article] C-ERC/mesothelin provokes lymphatic invasion of colorectal adenocarcinoma. (2013)
  • Author(s): Kawamata F
  • Journal Title: J. Gastroenterology Volume: in press
  • Peer Reviewed
• [Journal Article] The utility of serum N-ERC/mesothelin as biomarker of ovarian carcinoma (2012)
  • Author(s): Saeki H., Hashizume A., Izumi H., Suzuki F., Ishi K., Nojima M., Maeda M. and Hino O.
  • Journal Title: Oncology Letters Volume: 4 Pages: 637-641
• [Journal Article] The utility of serum N-ERC/mesothelin as biomarker of ovarian carcinoma. (2012)
  • Author(s): Saeki H
  • Journal Title: Oncology Letters Volume: 4 Pages: 637-641
  • Peer Reviewed
• [Journal Article] Deficiency of the Erc/mesothelingene ameliorates renal carcinogenesis in Tsc2 knockout mice (2011)
  • Author(s): Zhang D., Kobayashi T., Kojima T., Kanenishi K., Hagiwara Y., Abe M., Okura H., Hamano Y., Sun G., Maeda M., Jishage K., Noda T. and Hino O.
  • Journal Title: Cancer Science Volume: 102 Pages: 720-727
• [Journal Article] Feasibility of large-scale screening using N-ERC/mesothelin levels in the blood for the early diagnosis of malignant mesothelioma (2011)
  • Author(s): Imashimizu K., Shiomi K., Maeda M., Aoki N., Igarashi K., Suzuki F., Koizumi M., Suzuki K. and Hino O.
  • Journal Title: Experimental and Therapeutic Medicine Volume: 2 Pages: 409-411
• [Journal Article] Impact of renal failure on the tumor markers of mesothelioma, N-ERC/mesothelin and Osteopontin (2011)
  • Author(s): Shiomi K., Shiomi S., Ishinaga Y., Sakuraba M., Hagiwara Y., Miyashita K., Maeda M., Suzuki K., Takahashi K. and Hino O.
  • Journal Title: Anticancer Research Volume: 31 Pages: 1427-1430
• [Journal Article] LRR4 and UPK3B are markers of primary mesothelial cells (2011)
  • Author(s): Kanamori-Katayama M., Kaiho A., Ishizu Y., Okamura-Oho Y., Hino O., Abe M., Kishimoto T., Sekihara H., Nakamura Y., Suzuki H., Forrest A.R.R. and Hayashizaki Y.
  • Journal Title: PLoS One Volume: 6
• [Journal Article] Deficiency of the Erc/mesothelin gene ameliorates renal carcino genesis in Tsc2 knockout mice (2011)
  • Author(s): Zhang D., Kobayashi T., et.al.
  • Journal Title: Cancer Science Volume: 102 Pages: 720-727
  • Peer Reviewed
• [Journal Article] Feasibility of large-scale screening using N-ERG/mesothelin levels in the blood for the early diagnosis of malignant mesothelioma (2011)
  • Author(s): Imashimizu K., Shiomi K., et.al.
  • Journal Title: Experimental and Therapeutic Medicine Volume: 2 Pages: 409-411
  • Peer Reviewed
• [Journal Article] LRR4 and UPK3B are markers of primary mesothelial cells (2011)
  • Author(s): Kanamori-Katayama M., Kaiho A., et.al.
  • Journal Title: PLoS One Volume: 6
  • Peer Reviewed
• [Journal Article] Exposure to Polycyclic Aromatic Hydrocarbons, Arsenic and Environmental Tobacco Smoke, Nutrient Intake, and Oxidative Stress in Japanese Preschool Children (2011)
  • Author(s): Mori T., Yoshinaga J., et al
  • Journal Title: Science of the Total Environment Volume: 409 Pages: 2881-2887
  • Peer Reviewed
• [Journal Article] Histological Effect of Nitrous Acid with Secondary Products of Nitrogen Dioxide and Nitric Oxide Exposure on Pulmonary Tissue in Mice (2011)
  • Author(s): Ohyama M., Oka K., et al
  • Journal Title: Journal of Clinical Toxicology Volume: 1 Pages: 103-103
  • Peer Reviewed
• [Journal Article] Serum level of expressed in renal carcinoma (ERC)/mesothelin in rats with mesothelial proliferative lesions induced by multi-wall carbon nanotube (MWCNT) (2010)
  • Author(s): Sakamoto Y., Nakae D., Hagiwara Y., Satoh K., Ohashi N., Fukamachi K., Tsuda H., Hirose A., Nishimura T., Hino O. and Ogata A.
  • Journal Title: The Jounal of Toxicological Sciences Volume: 35 Pages: 265-270
  • NAID: 10026193564
• [Journal Article] Antitumor activity of anti-C-ERC/mesothelin monoclonal antibody in vivo (2010)
  • Author(s): Inami K., Abe M., Takeda K., Hagiwara Y., Maeda M., Segawa T., Suyama M., Watanabe S. and Hino O.
  • Journal Title: Cancer Sci Volume: 101 Pages: 969-974
  • NAID: 10026591120
• [Journal Article] Development of positron emission tomography imaging by 64Cu-labeled Fab for detecting ERC/mesothelin in mesothelioma mouse model (2010)
  • Author(s): Yoshida C., Sogawa C., Tsuji A., Sudo H., Sugyo A., Uehara T., Hino O., Yoshii Y., Fujibayashi Y., Fukumura T., Koizumi M., Arano Y. and Saga T.
  • Journal Title: Nuclear Medicine Communications Volume: 31 Pages: 380-388
• [Journal Article] Knockdown of COPA, identified by loss-of-functiuon screen, induces apoptosis and suppresses tumor growth in mesothelioma mouse mode (2010)
  • Author(s): Sudo H., Tuji A., Sugyo A., Kohda M., Sogawa C., Yoshida C., Harada Y., Hino O. and Saga T.
  • Journal Title: Genomics Volume: 95 Pages: 210-216
• [Journal Article] Mesothelin (MSLN) promoter is hypomethylated in malignant mesothelioma, but its expression is not associated with methylation status of the promoter (2010)
  • Author(s): Tan K., Kajino K., Momose S., Masaoka A., Sasahara K., Shiomi K., Izumi H., Abe M., Ohtsuji N., Wang T., Hino O. and Fujii H.
  • Journal Title: Human Pathol Volume: 41 Pages: 1330-1338
• [Journal Article] Suppression of cell death by the secretory form of N-terminal ERC/mesothelin (2010)
  • Author(s): Wang T., Kajino K., Abe M., Tan K., Maruo M., Sun G., Hagiwara Y., Maeda M. and Hino O.
  • Journal Title: Int. J. Molecular Med Volume: 26 Pages: 185-191
• [Journal Article] Mesothelin gene expression and promoter methylation/hypomethylation in gynecological tumors (2010)
  • Author(s): Obulhasim G., Fujii H., Matsumoto T., Yasen M., Abe M., Matsuoka S., Ohtsuji N. and Hino O.
  • Journal Title: Eur. J. Gynaec. Oncol. Volume: 31 Pages: 63-71
• [Journal Article] ntitumor activity of anti-C-ERC/mesothelin monoclonal antibody in vivo. (2010)
  • Author(s): Inami K., et al.
  • Journal Title: Cancer Sci. Volume: 101 Pages: 969-974
  • Peer Reviewed
• [Journal Article] The N-ERC index is a novel monitoring and prognostic marker for advanced malignant pleural mesothelioma
  • Author(s): Mori T., Tajima K., Hirama M., Sato T., Kido K., Iwakami S., Sasaki S., Iwase A., Shiomi K., Maeda M., Hino O. and Takahashi K.
  • Journal Title: J. Thoracic Disease Volume: (in press)
• [Journal Article] Fenton reaction induced cancer in wild type rats recapitulates genomic alterations observed in human cancer
  • Author(s): Akatsuka S., Yamashita Y., Ohara H., Liu Y-T., Izumiya M., Abe K., Ochiai M., Jiang L., Nagai H., Okazaki Y., Murakami H., Sekido Y., Arai E., Kanai Y., Hino O., Takahashi T., Nakagama H. and Toyokuni S.
  • Journal Title: PloSONE Volume: (in press)
• [Journal Article] C-ERC/mesothelin provokes lymphatic invasion of colorectal adenocarcinoma
  • Author(s): Kawamata F., Homma S., Kamachi H., Einama T., Kato Y., Tsuda M., Tanaka S., Maeda M., Kajino K., Hino O., Takahashi N., Kamiyama T., Nishihara H., Taketomi A. and Todo S.
  • Journal Title: J. Gastroenterology Volume: (in press)
  • NAID: 120005537455
• [Journal Article] Development of positron emission tomography imaging by 64Cu-labeled Fab for detecting ERC/mesothelin in mesothelioma mouse model.
  • Author(s): Yoshida C., et al.
  • Journal Title: Nuclear Medicine Communications Volume: (in press)
  • Peer Reviewed
• [Journal Article] Deficiency of the Erc/mesothelin gene ameliorates renal carcinogenesis in Tsc2 knockout mice.
  • Author(s): Zhang D., et al.
  • Journal Title: Cancer Science Volume: (in press)
  • Peer Reviewed
• [Journal Article] Persistent activation of Nrf2 p62 in hepatocellular carcinoma cells.
  • Author(s): Imashimizu K., et al.
  • Journal Title: J.Cell Biology Volume: (in press)
  • Peer Reviewed
• [Presentation] Early lesions in rats after an intraperitoneal administration of nanomaterials including multi-wall carbon nanotube (2011)
  • Author(s): Mizoi M., Nakatani E., et al
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋・名古屋国際会議場
  • Year and Date: 2011-10-04
• [Presentation] Rat ERC/mesothelin and early lesions of tumorigenic and non-tumorigenic fibrous materials including multi-wall carbon nanotube. (2010)
  • Author(s): 安達修一
  • Organizer: 10^<th> International Conference of Mesothelioma Interest Group
  • Place of Presentation: 京都・国立京都国際会館
  • Year and Date: 2010-09-02