Molecular mechanism of esophageal carcinogenesis induced by cigarette smoking and alcohol drinking and its clinical application
Project/Area Number |
24591966
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Digestive surgery
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Research Institution | National Hospital Organization, Kyushu Cancer Center (2014) Kyushu University (2012-2013) |
Principal Investigator |
MORITA Masaru 独立行政法人国立病院機構(九州がんセンター臨床研究センター), その他部局等, その他 (30294937)
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Co-Investigator(Kenkyū-buntansha) |
TOH Yasushi 国立病院機構九州がんセンター, 臨床研究センター, 副院長 (20217459)
SAKAGUCHI Yoshihisa 国立病院機構九州医療センター, 臨床研究センター, 消化器外科部長 (00215625)
OKI Eiji 九州大学, 医学(系)研究科(研究院), 准教授 (70380392)
SAEKI Hiroshi 九州大学, 大学病院, 講師 (80325448)
掛地 吉弘 神戸大学, 医学(系)研究科(研究院), 教授 (80284488)
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Project Period (FY) |
2012-04-01 – 2015-03-31
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Project Status |
Completed (Fiscal Year 2014)
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Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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Keywords | 食道癌 / 喫煙 / 飲酒 / 癌抑制遺伝子 / 染色体不安定性 / 酸化的DNAs損傷 / 酸化ストレス / メチル化 / がん抑制遺伝子 / 酸化的DNA損傷 / 多発癌 / 頭頸部癌 / 手術療法 / ポドプラニン / 上皮間葉移行 / p53 / LOH |
Outline of Final Research Achievements |
The purpose is to clarify mechanism of esophageal carcinogenesis induced by cigarette smoking and alcohol drinking. 1) The expression of 8-OHdG (a marker of oxidative stress) and that of its repair enzyme, OGG1 were immunohistochemically evaluated in esophageal specimens. The expression of 8-OHdG was related to smoking index. The expressions of OGG-1 were related to 8-OHdG in normal mucosa, while this correlation was not observed in the cancer. Oxidative DNA damage, which is attributable to smoking as well as disturbances in DNA repair systems, appears to be closely related to esophageal carcinogenesis. 2) LINE-1 methylation levels of normal esophageal mucosa had the inverse correlation with both cigarette smoking and alcohol consumption. LINE-1 methylation of esophageal cancer had the inverse association with the chromosomal instability. The whole genome hypomethylation caused by chronic inflammation could initiate the esophageal carcinogenesis through chromosomal instability.
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Report
(4 results)
Research Products
(82 results)
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[Journal Article] Clinical significance of surgical resection for the recurrence of esophageal cancer after radical esophagectomy.2015
Author(s)
Hiyoshi Y, Morita M, Kawano H, Otsu H, Ando K, Ito S, Miyamoto Y, Sakamoto Y, Saeki H, Oki E, Ikeda T, Baba H, Maehara Y
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Journal Title
Ann Surg Oncol
Volume: 22
Issue: 1
Pages: 206-240
DOI
Related Report
Peer Reviewed
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[Journal Article] Clinical Significance of SIP1 and E-cadherin in Patients with Esophageal Squamous Cell Carcinoma.2015
Author(s)
Yoshida R, Morita M, Shoji F, Nakashima Y, Miura N, Yoshinaga K, Koga T, Tokunaga E, Saeki H, Oki E, Oda Y, Maehara Y
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Journal Title
Ann Surg Oncol
Volume: [Epub ahead of print]
Pages: 0-0
Related Report
Peer Reviewed
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[Journal Article] SPINK1 Status in Colorectal Cancer, Impact on Proliferation, and Role in Colitis-associated Cancer.2015
Author(s)
Ida S, Ozaki N, Araki K, Hirashima K, Zaitsu Y, Taki K, Sakamoto Y, Miyamoto Y, Oki E, Morita M, Watanabe M, Maehara Y, Yamamura KI, Baba H Professor, Ohmuraya M
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Journal Title
Mol Cancer Res
Volume: [Epub ahead of print]
Pages: 0-0
Related Report
Peer Reviewed
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[Journal Article] Technical improvement of total pharyngo-laryngo-esophagectomy for esophageal cancer and head and neck cancer.2014
Author(s)
Morita M, Saeki H, Ito S, Ikeda K, Yamashita N, Ando K, Hiyoshi Y, Ida S, Tokunaga E, Uchiyama H, Oki E, Ikeda T, Yoshida S, Nakashima T, Maehara Y
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Journal Title
Ann Surg Oncol
Volume: 21
Issue: 5
Pages: 1671-1677
DOI
Related Report
Peer Reviewed
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[Journal Article] Mortalin is a prognostic factor of gastric cancer with normal p53 function.2014
Author(s)
Ando K., Oki E., Zhao Y., Yoshida A., Kitao H., Saeki H., Kimura Y., Ida S., Morita M., Kusumoto T., Maehara Y.
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Journal Title
Gastric Cancer
Volume: 17(2)
Issue: 2
Pages: 255-262
DOI
Related Report
Peer Reviewed / Open Access
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[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.
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Journal Title
Ann Surg Oncol.
Volume: -
Issue: 7
Pages: 2340-2346
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Chromosomal instability associated with global DNA hypomethylation is associated with the initiation and progression of esophageal squamous cell carcinoma2014
Author(s)
Kawano H, Saeki H, Kitao H, Tsuda Y, Otsu H, Ando K, Ito S, Egashira A, Oki E, Morita M, Oda Y, Maehara Y.
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Journal Title
Annals of Surgical Oncology
Volume: 4
Issue: S4
Pages: 696-702
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Gender differences in the prognosis after esophagectomy for esophageal cancer.2014
Author(s)
Morita M, Otsu H, Kawano H, Kasagi Y, Kimura Y, Saeki H, Ando K, Ida S, Oki E, Tokunaga E, Ikeda T, Kusumoto T, Maehara Y
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Journal Title
Surg Today
Volume: 44
Issue: 3
Pages: 502-512
DOI
Related Report
Peer Reviewed
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[Journal Article] Ann Surg Oncol2014
Author(s)
Ida S, Morita M, Hiyoshi Y, Ikeda K, Ando K, Kimura Y, Saeki H, Oki E, Kusumoto T, Yoshida S, Nakashima T, Watanabe M, Baba H, Maehara Y:
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Journal Title
Surgical resection of hypopharynx and cervical esophageal cancer with a history of esophagectomy for thoracic esophageal cancer.
Volume: 21
Issue: 4
Pages: 1175-1181
DOI
Related Report
Peer Reviewed
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[Journal Article] Multimodal treatment strategy for clinical T3 thoracic esophageal cancer.2014
Author(s)
Saeki H, Morita M, Tsuda Y, Hidaka G, Kasagi Y, Kawano H, Otsu H, Ando K, Kimura Y, Oki E, Kusumoto T, Maehara Y
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Journal Title
Ann Surg Oncol
Volume: 21
Issue: 13
Pages: 4267-4273
DOI
Related Report
Peer Reviewed
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[Journal Article] Impact of second-line and later cetuximab-containing therapy and KRAS genotypes in patients with metastatic colorectal cancer: a multicenter study in Japan.2014
Author(s)
Saeki H, Emi Y, Kumashiro R, Otsu H, Kawano H, Ando K, Ida S, Kimura Y, Tokunaga E, Oki E, Morita M, Shimokawa M, Maehara Y
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Journal Title
Surg Today.
Volume: 44
Issue: 8
Pages: 1457-1464
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Small molecule agonists of PPAR-γ exert therapeutic effects in esophageal cancer.2014
Author(s)
Sawayama H, Ishimoto T, Watanabe M, Yoshida N, Sugihara H, Kurashige J, Hirashima K, Iwatsuki M, Baba Y, Oki E, Morita M, Shiose Y, Baba H
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Journal Title
Cancer Res
Volume: 74
Issue: 2
Pages: 575-585
DOI
Related Report
Peer Reviewed
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[Journal Article] IGF2 DMR0 methylation, loss of imprinting, and patient prognosis inesophageal squamous cell carcinoma2014
Author(s)
A. Murata, Y. Baba, M. Watanabe, H. Shigaki, K. Miyake, T. Ishimoto, M. Iwatsuki, S. Iwagami, N. Yoshida, E. Oki, M. Morita, M. Nakao, and H. Baba.
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Journal Title
Ann. Surg. Oncol.
Volume: 21
Issue: 4
Pages: 1166-1174
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Advances in esophageal surgery in elderly patients with thoracic esophageal cancer.2013
Author(s)
Morita M, Otsu H, Kawano H, Kumashiro R, Taketani K, Kimura Y, Saeki H, Ando K, Ida S, Oki E, Tokunaga E, Ikeda T, Kusumoto T, Maehara Y
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Journal Title
Anticancer Res
Volume: 33
Pages: 1641-1647
Related Report
Peer Reviewed
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[Journal Article] Surgical resection for esophageal cancer synchronously or metachronously associated with head and neck cancer.2013
Author(s)
Morita M, Kawano H, Otsu H, Kimura K, Saeki H, Ando K, Ida S, Oki E, Ikeda T,Kusumoto T, Fukushima J, Nakashima T, Maehara Y
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Journal Title
Ann Surg Oncol
Volume: 20
Issue: 7
Pages: 2434-2439
DOI
Related Report
Peer Reviewed
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[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.
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Journal Title
Cancer Medicine
Volume: 2(4)
Issue: 4
Pages: 447-456
DOI
Related Report
Peer Reviewed
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[Journal Article] Podoplanin is expressed at the invasive front of esophageal squamous cell carcinomas and is involved in collective cell invasion.2013
Author(s)
Nakashima Y, Yoshinaga K, Kitao H, Ando K, Kimura Y, Saeki H, Oki E, Morita M, Kakeji Y, Hirahashi M, Oda Y, Maehara Y
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Journal Title
Cancer Sci
Volume: 104
Issue: 12
Pages: 1718-1725
DOI
Related Report
Peer Reviewed
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[Journal Article] Clinical Significance of Chemoradiotherapy and Surgical Resection for cT4 Esophageal Cancer.2012
Author(s)
Morita M., Toh Y., Saeki H., Sugiyama M., Ohgaki K., Maehara S., Minami K., Ikeda Y., Sakaguchi Y., Okamura T., Uehara S., Maehara Y.
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Journal Title
Anticancer Res
Volume: 32
Pages: 3275-3282
Related Report
Peer Reviewed
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[Journal Article] Staged operation for synchronous quintuple cancer in the oral cavity, hypopharynx, and esophagus.2012
Author(s)
Yoshida R., Morita M., Kumashiro R., Ikeda T., Egashira A., Saeki H., Ohga T., Shiratsuchi H., Fukushima J., Nakashima T., Kakeji Y., Maehara Y.
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Journal Title
Esophagus
Volume: 9
Issue: 4
Pages: 228-233
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] The treatment outcomes of synchronous and metachronous esophageal squamous cell carcinoma and head and neck squamous cell carcinoma.2012
Author(s)
Saeki H., Toh Y., Morita M., Sugiyama M., Morita K., Sakamoto Y., Soejima Y., Minami K., Sakaguchi Y., Higaki Y., Uehara S., Okamura T., Maehara Y.
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Journal Title
Esophagus
Volume: 9
Issue: 3
Pages: 158-164
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] Lymph node metastasis from cancer of the esophagogastric junction, and determination of the appropriate nodal dissection2012
Author(s)
Kakeji Y, Yamamoto M, Ito S, Sugiyama M, Egashira A, Saeki H, Morita M, Sakaguchi Y, Toh Y, Maehara Y
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Journal Title
Surg Today
Volume: 42
Issue: 4
Pages: 351-358
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] A Case of Recurrent Esophageal Cancer Treated with Chemoradiation Combined with Long-term Hyperthermia Treatment2012
Author(s)
Ohga S., Nakamura K., Yoshitake T., Shioyama Y., Ohga T., Sasaki T., Nonoshita T., Asai K., Morita M., Kakeji Y., Hirata H., Honda H.
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Journal Title
Thermal Medicine
Volume: 28
Issue: 1
Pages: 17-22
DOI
NAID
ISSN
1882-2576, 1882-3750
Related Report
Peer Reviewed
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[Journal Article] Biological mechanism and clinical effect of protein-bound polysaccharide K (KRESTIN([○!R])) : review of development and future perspectives2012
Author(s)
Maehara Y, Tsujitani S, Saeki H, Oki E, Yoshinaga K, Emi Y, Morita M, Kohnoe S, Kakeji Y, Yano T, Baba H
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Journal Title
Surg Today
Volume: 42
Issue: 1
Pages: 8-28
DOI
NAID
Related Report
Peer Reviewed
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[Presentation] Reliable procedure for total pharyngo-laryngo-esophagectomy2014
Author(s)
Morita M,Saeki H,Nakashima Y,Ando K,Ito S, Hiyoshi Y, Oki E, Ikeda T, Egashira A,Yamamoto M,Toh Y,Okamura T,Yoshida S,Nakashima T,Maehara Y,
Organizer
14th World Congress of the International Society for Diseases
Place of Presentation
Vancouver,Canada
Year and Date
2014-09-22 – 2014-09-24
Related Report
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[Presentation] Neoadjuvant chemoradiotherapy for potentially resectable esophageal squamous cell carcinoma and the significance of Rad51 expression as a factor predictive of the treatment response.2012
Author(s)
Saeki H., Nakanoko T., Ohtsu H., Kawano H., Ando K., Oki E., Ohga T., Morita M., Kakeji Y., Toh Y., Maehara Y.
Organizer
2012 ASCO Annual Meeting of American Society of Clinical Oncology
Place of Presentation
Chicago, IL, USA
Related Report
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