Clinicopatholigcai and molecula biological analysis of carcinogenesis induced by chemicals

• Project/Area Number: 26462048
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Osaka City University
• Principal Investigator: Kubo Shoji 大阪市立大学, 大学院医学研究科, 准教授 (80221224)
• Co-Investigator(Kenkyū-buntansha): 竹村 茂一 大阪市立大学, 大学院医学研究科, 講師 (00322363) ; 中沼 安二 金沢大学, 医学系, 協力研究員 (10115256) ; 西尾 和人 近畿大学, 医学部, 教授 (10208134)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 職業性胆管癌 / 1,2-ジクロロプロパン / ジクロロメタン / 肝内胆管癌 / 前癌病変 / 遺伝子異常 / 多段階発育 / 前癌病変DNA傷害 / 多段階発癌 / DNA傷害

Outline of Final Research Achievements

The analysis of occupational cholangiocarcinoma showed that young age, high gamma-GTP level, regional dilation of intrahepatic bile duct, the presence of biliary intraepithelial neoplasia（BilIN）and intraductal neoplasm of the bile duct（IPNB）as well as invasive cholangiocarcinoma are characteristics of the carcinoma. The molecular biological studies showed that such lesions had hypermutation of DNA. These results indicate that some chemicals induced DNA injury, inducing premalignant lesions such as BilIN and IPNB, eventually developing invasive cholangiocarcinoma in the occupational cholangiocarcinoma.

Research Products

• [Journal Article] MR imaging and MR cholangiopancreatography of cholangiocarcinoma developing in printing company workers. (2017)
  • Author(s): Koyama K, Kubo S, Ueki A, Shimono T, Takemura S, Tanaka S, Kinoshita M, Hamano G, Miki Y.
  • Journal Title: Jpn J Radiol. Volume: 印刷中 Issue: 5 Pages: 233-241
  • DOI: 10.1007/s11604-017-0626-y
  • NAID: 50012595356
  • Peer Reviewed / Open Access
• [Journal Article] Outcomes after resection of occupational cholangiocarcinoma (2016)
  • Author(s): Kubo S, Takemura S, Tanaka S, Shinkawa H, Kinoshita M, Hamano G, et al.
  • Journal Title: Journal of Hepato-Biliary Pancreatic Sciences Volume: 23 Issue: 9 Pages: 556-564
  • DOI: 10.1002/jhbp.373
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The PD-1/PD-L1 may be aberrantly activated in occupational cholangiocarcinoma (2016)
  • Author(s): Sato Y, Kinoshita M, Takemura S, Tanaka S, Hamano G, Nakamori S, Fujikawa M, Sugawara Y, Yamamoto T, Arimoto A, Yamamura M, Sasaki M, Harada K, Nakanuma Y, Kubo S
  • Journal Title: Pathology International Volume: 67 Issue: 3 Pages: 163-170
  • DOI: 10.1111/pin.12511
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 職業性胆管癌の臨床的特徴 (2016)
  • Author(s): 久保正二、竹村茂一、田中肖吾、新川寛二、西岡孝芳、木下正彦、濱野玄弥、伊藤得路、中沼安二、圓藤吟史
  • Journal Title: 日本職業・災害医学会会誌 Volume: 64 Pages: 1-5
  • Peer Reviewed
• [Journal Article] 肝内胆管癌の疫学的動向と危険因子 (2016)
  • Author(s): 久保正二、竹村茂一、田中肖吾、新川寛二、木下正彦、濱野玄弥、伊藤得路、青田尚哲、江田将樹、上西崇弘
  • Journal Title: 外科 Volume: 78 Pages: 115-121
• [Journal Article] Screening and surveillance for occupational cholangiocarcinoma in workers exposed to organic solvents (2016)
  • Author(s): Kubo S, Takemura S, Tanaka S, Nishioka T, Kinoshita M, Hamano G, Ito T, Yamamoto T, Abue M, Aoki M, Nakagawa K, Hijioka S, Miyamoto A, Osaki Y, Endo G, Kumagai S.
  • Journal Title: Surg Today Volume: 46 Issue: 6 Pages: 705-712
  • DOI: 10.1007/s00595-015-1229-9
  • NAID: 120006586208
  • URL: https://ocu-omu.repo.nii.ac.jp/records/2020497
  • Peer Reviewed / Open Access
• [Journal Article] Pathological spectrum of bile duct lesions from chronic bile duct injury to invasice cholangiocarcinoma corresponding to bile duct imaging findings of occupational cholangiocarcinoma. (2016)
  • Author(s): Kinoshita M, Kubo S, Nakanuma Y, Sato Y, Takemura S, Tanaka S, Hamano G, Ito T, Terajima H, Yamada T, Nakamori S, Arimoto A, Fujikawa M, Sugawara Y, Yamamoto T, Abue M, Nakagawa K, Unno M, Mizuguchi T, Takenaka K, Shirabe K, Shibata T.
  • Journal Title: J Hepatobiliary Pancreat Sci Volume: 23 Issue: 2 Pages: 92-101
  • DOI: 10.1002/jhbp.305
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Screening and surveillance for occupational cholangiocarcinoma in workers exposed to organic solvents. (2016)
  • Author(s): Kubo S, Takemura S, Tanaka S, Nishioka T, Kinoshita M, Hamano G, Ito T, Yamamoto T, Abue M, Aoki M, Nakagawa K, Hijioka S, Miyamoto A, Osaki Y, Endo G, Kumagai S
  • Journal Title: Surgery Today Volume: 印刷中
  • NAID: 120006586208
  • Peer Reviewed
• [Journal Article] Comparison of clinicopathological characteristics between patients with occupational and non-occupational intrahepatic cholangiocarcinoma. (2016)
  • Author(s): Hamano G, Kubo S, Takemura S, Tanaka S, Shinkawa H, Kinoshita M, Ito T, Yamamoto T, Wakasa K, Shibata T.
  • Journal Title: J Hepatobiliary Pancreat Sci Volume: 印刷中
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 肝内胆管癌の疫学的動向とリスク因子 (2016)
  • Author(s): 久保正二、竹村茂一、田中肖吾、新川寛二、木下正彦、濱野玄弥、伊藤得路、青田哲尚、江田将樹、上西崇弘.
  • Journal Title: 外科 Volume: 78 Pages: 115-121
• [Journal Article] Comparison of Clinical Characteristics between Occupational and Sporadic Young-Onset Cholangiocarcinoma. (2015)
  • Author(s): Kaneko R, Kubo S, Sato Y.
  • Journal Title: Asian Pac J Cancer Prev. Volume: 16 Issue: 16 Pages: 7195-7200
  • DOI: 10.7314/apjcp.2015.16.16.7195
  • Peer Reviewed
• [Journal Article] Severe acute hepatitis in a printing company worker: A case study (2015)
  • Author(s): Kubo S, Matsuzaki K, Seki T, Ohsawa M, Kumagai S, Endo G.
  • Journal Title: Journal of Occupational Health Volume: 57 Issue: 1 Pages: 87-90
  • DOI: 10.1539/joh.14-0122-CS
  • NAID: 130004713078
  • ISSN: 1341-9145, 1348-9585
  • Peer Reviewed
• [Journal Article] Chemical exposure levels in printing and coating workers with cholangiocarcinoma (third report) (2015)
  • Author(s): Yamada K, Kumagai S, Kubo S, Endo G.
  • Journal Title: Journal of Occupational Health Volume: 57 Issue: 6 Pages: 565-571
  • DOI: 10.1539/joh.15-0170-OA
  • NAID: 130005116263
  • ISSN: 1341-9145, 1348-9585
  • Peer Reviewed / Open Access
• [Journal Article] 職業性胆管癌症例の臨床的特徴 (2015)
  • Author(s): 久保正二、竹村茂一、田中肖吾、木下正彦、濱野玄弥、伊藤得路、青田哲尚、江田将樹、中沼安二.
  • Journal Title: 産業医学レビュー Volume: 28 Pages: 139-146
  • Peer Reviewed
• [Journal Article] 職業性胆管癌の病態とその特徴 (2015)
  • Author(s): 久保正二、竹村茂一、田中肖吾、新川寛二、木下正彦、濱野玄弥、伊藤得路、青田哲尚、江田将樹、佐藤保則、中沼安二.
  • Journal Title: 肝胆膵 Volume: 71 Pages: 877-885
• [Journal Article] 職業性胆管癌の臨床的特徴 (2015)
  • Author(s): 久保正二、竹村茂一、田中肖吾、新川寛二、西岡孝芳、木下正彦、濱野玄弥、伊藤得路、中沼安二、圓藤吟史.
  • Journal Title: 日本職業・災害医学会会誌 Volume: 64 Pages: 1-5
  • Peer Reviewed
• [Journal Article] 腫瘍性コランギオパチー（胆道腫瘍） 職業性胆管癌の病態とその特徴 (2015)
  • Author(s): 久保正二、竹村茂一、田中肖吾、新川寛二、木下正彦、濱野玄弥、伊藤得路、青田哲尚、江田将樹、佐藤保則、中沼 安二.
  • Journal Title: 肝胆膵 Volume: 71 Pages: 877-885
• [Journal Article] 印刷業職業性胆管癌に対する化学放射線療法と根治的肝切除の経験 (2015)
  • Author(s): 中川 圭、片寄 友、石田和之、林 洋毅、森川孝則、吉田 寛、元井冬彦、内藤 剛、久保正二、海野倫明.
  • Journal Title: 日本消化器病学会雑誌 Volume: 112 Pages: 1341-1347
  • NAID: 130005084740
  • Peer Reviewed
• [Journal Article] 印刷業勤務を背景に発症した肝内胆管癌の1例 (2015)
  • Author(s): 木村光一、調 憲、久保正二、伊藤心二、播本憲史、山下洋市、吉住朋晴、相島慎一、小田義直、前原喜彦.
  • Journal Title: 胆道 Volume: 29 Pages: 972-977
  • NAID: 130005119509
  • Peer Reviewed
• [Journal Article] Case series of 17 patients with cholangiocarcinoma among young adult workers of a printing company in Japan. (2014)
  • Author(s): Kubo S, Nakanuma Y, Takemura S, Sakata C, Urata Y, Nozawa A, Nishioka T, Kinoshita M, Hamano G, Terajima H, Tachiyama G, Matsumura Y, Yamada T, Tanaka H, Nakamori S, Arimoto A, Kawada N, Fujikawa M, Fujishima H, Sugawara Y, Tanaka S, Toyokawa H, Kuwae Y, Ohsawa M, Uehara S, Sato KK, Hayashi T, Endo G.
  • Journal Title: J Hepatobiliary Pancreat Sci. Volume: 21 Issue: 7 Pages: 479-488
  • DOI: 10.1002/jhbp.86
  • Peer Reviewed / Open Access
• [Journal Article] Characteristics of printing company workers newly diagnosed with occupational cholangiocarcinoma (2014)
  • Author(s): KuboS, et al
  • Journal Title: Journal of Hepato-Biliary-Pancreatic Sciences Volume: 21 Pages: 809-817
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Different carcinogenic process in cholangiocarcinoma cases epidemically developing among workers of a printing company in Japan (2014)
  • Author(s): Sato Y, Kubo S, et al.
  • Journal Title: International Journal of Clinical and Experimental Pathology Volume: 7 Pages: 4745-4754
  • Peer Reviewed / Open Access
• [Journal Article] Changes in laboratory test results and diagnostic imaging presentation before the detection of occupational cholangiocarcinoma (2014)
  • Author(s): Kubo S, et al.
  • Journal Title: Journal of Occupational Health Volume: 56 Pages: 317-322
  • NAID: 130004447660
  • Peer Reviewed / Open Access
• [Journal Article] Cholangiocarcinomain a middle-aged patient working at a printing company (2014)
  • Author(s): Tanaka S, Kubo S, et al.
  • Journal Title: Osaka City Medical Journal Volume: 60 Pages: 39-44
  • Peer Reviewed / Open Access
• [Journal Article] 印刷労働者における胆管癌多発事例：新たな職業癌 (2014)
  • Author(s): 久保正二, 他
  • Journal Title: 日本消化器病学会雑誌 Volume: １１１ Pages: 500-509
  • NAID: 130003392012
  • Peer Reviewed / Open Access
• [Journal Article] 印刷労働者に多発した胆管癌 (2014)
  • Author(s): 久保正二、他
  • Journal Title: 胆道 Volume: ２８ Pages: 763-771
  • NAID: 130004838926
  • Peer Reviewed / Open Access
• [Journal Article] 職業性暴露（印刷業）による胆管・胆道癌の特徴：病理所見および発癌メカニズムを中心に (2014)
  • Author(s): 中沼安二、久保正二、他
  • Journal Title: 肝胆膵 Volume: 69 Pages: 1079-1085
• [Journal Article] 印刷会社勤務歴を有する肝内胆管癌の1例 (2014)
  • Author(s): 虻江 誠、久保正二、他
  • Journal Title: 胆道 Volume: 28 Pages: 696-702
  • NAID: 130004838917
  • Peer Reviewed / Open Access
• [Presentation] 職業性胆管癌の手術成績 (2016)
  • Author(s): 木下正彦，竹村茂一，田中肖吾，新川寛二，濱野玄弥，伊藤得路，江田将樹，青田尚哲，久保正二
  • Organizer: 第14回日本消化器外科学会大会
  • Place of Presentation: 神戸交際展示場（兵庫県神戸市）
  • Year and Date: 2016-11-04
• [Presentation] 職業性肝内胆管癌と非職業性肝内胆管癌との臨床病理学的比較 (2016)
  • Author(s): 濱野玄弥，竹村茂一，田中肖吾，新川寛二，木下正彦，伊藤得路，青田尚哲，江田将樹，山本隆嗣，久保正二
  • Organizer: 第71回日本消化器外科学会総会
  • Place of Presentation: アスティ徳島（徳島県徳島市）
  • Year and Date: 2016-07-14
• [Presentation] Development of cholangiocarcinoma in a printing company employee: Occupational cholangiocarcinoma (2016)
  • Author(s): Kubo S, Takemura S, Tanaka S, Kinoshita M, Hamano G, Nakanuma Y, Sato Y, Mimaki S, Tsuchihara K
  • Organizer: The 7th Asia-Pacific Primary Liver Cancer Expert Meeting
  • Place of Presentation: Hong Kong (China)
  • Year and Date: 2016-07-09
  • Int'l Joint Research
• [Presentation] 職業性胆管癌の臨床と対策. (2016)
  • Author(s): 久保正二
  • Organizer: 第52回日本肝癌研究会
  • Place of Presentation: 虎の門ヒルズフォーラム（東京都港区）
  • Year and Date: 2016-07-02
  • Invited
• [Presentation] 当科における職業性胆管癌切除症例の病理学的検討 (2015)
  • Author(s): 木下正彦，中沼安二，竹村茂一，佐藤保則，田中肖吾，新川寛二，西岡孝芳，濱野玄弥，伊藤得路，青田尚哲，江田将樹，久保正二
  • Organizer: 第13回日本消化器外科学会大会
  • Place of Presentation: 高野輪プリンスホテル（東京都）
  • Year and Date: 2015-10-10
• [Presentation] 印刷業従業者胆管癌のゲノム変異より明らかとなった変異原物質の特徴 (2015)
  • Author(s): 三牧幸代，戸塚ゆ加里，落合淳志，久保正二，中森正二，中釜 斉，江角浩安，土原一哉
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-10-08
• [Presentation] 職業性胆管癌の病態と対策 (2015)
  • Author(s): 久保正二
  • Organizer: 第70回日本消化器外科学会総会
  • Place of Presentation: アクトシティー浜松（静岡県浜松市）
  • Year and Date: 2015-07-15
• [Presentation] 肝内胆管癌の治療成績と戦略 (2015)
  • Author(s): 久保正二，上西崇弘，竹村茂一
  • Organizer: 第51回日本肝臓学会総会
  • Place of Presentation: 熊本ホテルキャッスル（熊本県熊本市）
  • Year and Date: 2015-05-21
• [Presentation] これまでの職業性胆管癌症例の検討-大阪での17例と新規労災認定９例の比較- (2015)
  • Author(s): 木下正彦，中沼安二，竹村茂一，田中肖吾，新川寛二，西岡孝芳，濱野玄弥，伊藤得路，江田将樹，久保正二
  • Organizer: 第115回日本外科学会定期学術集会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-04-16
• [Presentation] Comparison of clinicopathological characteristics between in the patients with occupational and non-occupational intrahepatic cholangiocarcinoma (2015)
  • Author(s): Hamano G,Kubo S, et al.
  • Organizer: The 2nd Kansai-Yeungnam HBP Surgenos Joint Meeting 2015
  • Place of Presentation: Wakayama Medical College ［和歌山県、和歌山市）
  • Year and Date: 2015-03-27
• [Presentation] Radiological and pathological characteristics in occupational cholangiocarcinoma developing among young workers at a printing company in Japan (2015)
  • Author(s): Kinoshita M,Kubo S, et al.
  • Organizer: The 2nd Kansai-Yeungnam HBP Surgenos Joint Meeting 2015
  • Place of Presentation: Wakayama Medical Colledge
  • Year and Date: 2015-03-27
• [Presentation] 職業性胆管癌の臨床的特徴 (2014)
  • Author(s): 久保正二、他
  • Organizer: 第62回日本職業・災害医学会学術大会
  • Place of Presentation: 神戸国際会議場（兵庫県 神戸市）
  • Year and Date: 2014-11-16
  • Invited
• [Presentation] 印刷工胆管癌の全エクソンシークエンス解析 (2014)
  • Author(s): 三牧幸代、久保正二、他
  • Organizer: 第73回日本癌学会学術集会
  • Place of Presentation: パシフィコ横浜（神奈川県 横浜市）
  • Year and Date: 2014-09-26
• [Presentation] 印刷労働者関連胆管癌症例における病理学的特徴 (2014)
  • Author(s): 木下正彦、久保正二、他
  • Organizer: 第50回日本胆道学会学術集会
  • Place of Presentation: グランドプリンスホテル新高輪（東京都港区）
  • Year and Date: 2014-09-26
• [Presentation] Outcomes of treatment intrahepatic cholangiocarcinoma among young workers at a printing company (2014)
  • Author(s): Kinoshita M, Kubo S, et al.
  • Organizer: Daegu-Kansai HBP Surgeons Joint Meeting 2014
  • Place of Presentation: YongNang University (YongNang 韓国）
  • Year and Date: 2014-08-08
• [Presentation] 印刷労働者関連胆管癌と他の胆管癌の臨床病理学的比較 (2014)
  • Author(s): 濱野玄弥、久保正二、他
  • Organizer: 第69回日本消化器外科学会総会
  • Place of Presentation: 郡山市民文化センター（福島県 郡山市）
  • Year and Date: 2014-07-18
• [Presentation] 印刷労働者関連胆管癌症例における画像所見および病理組織像の検討 (2014)
  • Author(s): 木下正彦、久保正二、他
  • Organizer: 第69回日本消化器外科学会総会
  • Place of Presentation: 郡山市民文化センター（福島県 郡山市）
  • Year and Date: 2014-07-17
• [Presentation] 若年者胆道癌の発症要因に関する研究 (2014)
  • Author(s): 吉田 寛、久保正二、他
  • Organizer: 第26回日本肝胆膵外科学会・学術集会
  • Place of Presentation: 和歌山県民文化会館（和歌山県 和歌山市）
  • Year and Date: 2014-06-13
• [Presentation] 胆道癌とその前癌病変におけるDNA損傷に関する病理的検討 (2014)
  • Author(s): 佐藤保則、久保正二、他
  • Organizer: 第50回日本肝癌研究会
  • Place of Presentation: 京都国際会館（京都府 京都市）
  • Year and Date: 2014-06-06
• [Presentation] オフセット校正印刷会社関連胆管癌切除例の病理組織学的検討 (2014)
  • Author(s): 浦田順久、久保正二、他
  • Organizer: 第114回日本外科学会定期学術集会
  • Place of Presentation: 京都国際会館（京都府 京都市）
  • Year and Date: 2014-04-05
• [Presentation] 印刷労働者関連胆管癌症例におけるFDG-PET像 (2014)
  • Author(s): 木下正彦、久保正二、他
  • Organizer: 第114回日本外科学会定期学術集会
  • Place of Presentation: 京都国際会館（京都府 京都市）
  • Year and Date: 2014-04-04