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Comparing pancreatic ductal adenocarciinoma and cholangiocarcinoma to elucidate the mechanism of carcinogenesis

Research Project

Project/Area Number 16H05410
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionTohoku University

Principal Investigator

UNNO MICHIAKI  東北大学, 医学系研究科, 教授 (70282043)

Co-Investigator(Kenkyū-buntansha) 古川 徹  東北大学, 医学系研究科, 教授 (30282122)
元井 冬彦  東北大学, 医学系研究科, 准教授 (30343057)
Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2018: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2017: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2016: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
Keywords膵管癌 / 胆管癌 / 膵管内乳頭状粘液腫瘍 / 胆管内乳頭状腫瘍 / 膵癌 / プロテオミクス / IPMN / IPNB / 癌 / 外科
Outline of Final Research Achievements

Pancreatic ductal adenocarcinoma(PDAC), cholangiocarcinoma(CC), intraductal papillary mucous neoplasm (IPMN), and intraductal papillary neoplasm of the bile duct (IPN-B) are considered to be similar tumors, but the differences in their molecular basis are not clear.
A comprehensive proteomic analysis of PDAC and CC shows that some protein expression patterns differ significantly. The results indicate that the differential diagnosis of PDAC and CC can be made by immunohistochemistry.
IPN-B was subclassified morphologically into types 1 and 2. Gene mutation analysis revealed that type 1 was more similar to IPMN and type 2 was more similar to PDAC than IIPMN. Moreover, the Japan-Korea joint study compared the prognosis of the patients of IPN-B type1 and type2, and found that this hypothesis was supported by the results of the study.

Academic Significance and Societal Importance of the Research Achievements

膵癌と胆管癌、特に膵頭部癌と遠位胆管癌は膵頭部を占拠する腫瘍であり、鑑別が困難であった。従来、外科切除のみが有効な治療法であり両者の鑑別は重要ではなかったが、現在は抗癌剤の選択が異なること、膵癌の術前治療の有効性が証明されたことなどから、両者間の鑑別における分子基盤の理解は必須である。今回の研究結果を受け、両者の鑑別は微量組織でも検討することが可能な免疫染色により鑑別可能であることが明らかになった。また、IPN-Bも形態学的にtype1, type2の2つに亜分類したところ、type1はより膵臓のIPMNに近く、type2はより膵管癌に近いということが明らかになり今後臨床治療に応用される。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (24 results)

All 2020 2019 2018 2017 2016

All Journal Article (16 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 16 results,  Open Access: 7 results) Presentation (8 results) (of which Invited: 1 results)

  • [Journal Article] Neoadjuvant chemotherapy for resectable pancreatic cancer2020

    • Author(s)
      海野 倫明
    • Journal Title

      Nippon Shokakibyo Gakkai Zasshi

      Volume: 117 Issue: 4 Pages: 297-301

    • DOI

      10.11405/nisshoshi.117.297

    • NAID

      130007830075

    • ISSN
      0446-6586, 1349-7693
    • Year and Date
      2020-04-10
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinicopathological characteristics of intraductal papillary neoplasm of the bile duct: a Japan‐Korea collaborative study2020

    • Author(s)
      Kubota Keiichi、Jang Jin‐Young、Nakanuma Yasuni、Unno Michiaki、et al.
    • Journal Title

      Journal of Hepato-Biliary-Pancreatic Sciences

      Volume: - Issue: 9 Pages: 581-597

    • DOI

      10.1002/jhbp.785

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Risk factors and characteristics of young patients with the biliary tract carcinoma: results of a project study for biliary surgery by the Japanese Society of Hepato‐Biliary‐Pancreatic Surgery2020

    • Author(s)
      Ariake Kyohei、Unno Michiaki、Yoshida Hiroshi、Kubo Shoji、Horiguchi Akihiko、Yamaue Hiroki、Yamamoto Masakazu
    • Journal Title

      Journal of Hepato-Biliary-Pancreatic Sciences

      Volume: - Issue: 9 Pages: 571-580

    • DOI

      10.1002/jhbp.776

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impact of a board certification system and implementation of clinical practice guidelines for pancreatic cancer on mortality of pancreaticoduodenectomy2020

    • Author(s)
      Mizuma Masamichi、Yamamoto Hiroyuki、Miyata Hiroaki、Gotoh Mitsukazu、Unno Michiaki、Shimosegawa Tooru、Toh Yasushi、Kakeji Yoshihiro、Seto Yasuyuki
    • Journal Title

      Surgery Today

      Volume: - Issue: 10 Pages: 1297-1307

    • DOI

      10.1007/s00595-020-02017-3

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] How does intestinal-type intraductal papillary mucinous neoplasm emerge? CDX2 plays a critical role in the process of intestinal differentiation and progression.2020

    • Author(s)
      Omori Y, Ono Y, Kobayashi T, Motoi F, Karasaki H, Mizukami Y, Makino N, Ueno Y, Unno M, Furukawa T.
    • Journal Title

      Virchows Archiv

      Volume: - Issue: 1 Pages: 1-11

    • DOI

      10.1007/s00428-020-02806-8

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] An integrated analysis of host- and tumor-derived markers for predicting high-grade dysplasia and associated invasive carcinoma of intraductal papillary mucinous neoplasms of the pancreas.2020

    • Author(s)
      Hata T, Nakagawa K, Hayashi H, Kanno A,et al.
    • Journal Title

      Surg Today.

      Volume: - Issue: 9 Pages: 1039-1048

    • DOI

      10.1007/s00595-020-01982-z

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intraductal papillary neoplasms of the bile duct consist of two distinct types specifically associated with clinicopathological features and molecular phenotypes2020

    • Author(s)
      Aoki Yasutaka、Mizuma Masamichi、Hata Tatsuo、Aoki Takeshi、Omori Yuko、Ono Yusuke、Mizukami Yusuke、Unno Michiaki、Furukawa Toru
    • Journal Title

      The Journal of Pathology

      Volume: 251 Issue: 1 Pages: 38-48

    • DOI

      10.1002/path.5398

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparison of pancreaticoduodenectomy and bile duct resection for middle bile duct cancer: A multi‐center collaborating study of Japan and Korea2020

    • Author(s)
      Hayashi Hiroki、Jang Jin‐Young、Kim Kyung Sik、Choi Jin Sub、Takahara Takeshi、Choi Sung Hoon、Hirano Satoshi、Yu Hee Chul、Uemura Syuichiro、Unno Michiaki
    • Journal Title

      Journal of Hepato-Biliary-Pancreatic Sciences

      Volume: - Issue: 6 Pages: 289-298

    • DOI

      10.1002/jhbp.724

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Prediction of the Probability of Malignancy in Mucinous Cystic Neoplasm of the Pancreas With Ovarian-Type Stroma: A Nationwide Multicenter Study in Japan.2020

    • Author(s)
      Ohtsuka T, Nakamura M, Hijioka S, Shimizu Y, Unno M, Tanabe M, Nagakawa Y, Takaori K, Hirono S, Gotohda N, Kimura W, Ito K, Katanuma A, Sano T, Urata T, Kita E, Hanada K, Tada M, Aoki T, Serikawa M, Okamoto K, Isayama H, Gotoh Y, Ishigami K, Yamaguchi H, Yamao K, Sugiyama M, Okazaki K.
    • Journal Title

      Pancreas

      Volume: 49 Issue: 2 Pages: 181-186

    • DOI

      10.1097/mpa.0000000000001475

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CD109 promotes the tumorigenic ability and metastatic motility of pancreatic ductal adenocarcinoma cells2020

    • Author(s)
      Hatsuzawa Yuuri、Yamaguchi Kazunori、Takanashi Tomoka、Sato Ikuro、Tamai Keiichi、Mochizuki Mai、Iwai Wataru、Wakui Yuta、Abue Makoto、Yamamoto Kuniharu、Yasuda Jun、Mizuma Masamichi、Unno Michiaki、Sugamura Kazuo
    • Journal Title

      Pancreatology

      Volume: 20 Issue: 3 Pages: 493-500

    • DOI

      10.1016/j.pan.2020.01.013

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Risk model for severe postoperative complications after total pancreatectomy based on a nationwide clinical database2020

    • Author(s)
      Hashimoto D.、Mizuma M.、Kumamaru H.、Miyata H.、Chikamoto A.、Igarashi H.、Itoi T.、Egawa S.、Kodama Y.、Satoi S.、Hamada S.、Mizumoto K.、Yamaue H.、Yamamoto M.、Kakeji Y.、Seto Y.、Baba H.、Unno M.、Shimosegawa T.、Okazaki K.
    • Journal Title

      British Journal of Surgery

      Volume: 107 Issue: 6 Pages: 734-742

    • DOI

      10.1002/bjs.11437

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] BACH1 Promotes Pancreatic Cancer Metastasis by Repressing Epithelial Genes and Enhancing Epithelial-Mesenchymal Transition2020

    • Author(s)
      Sato Masaki、Matsumoto Mitsuyo、Saiki Yuriko、Alam Mahabub、Nishizawa Hironari、Rokugo Masahiro、Brydun Andrey、Yamada Shinji、Kaneko Mika K.、Funayama Ryo、Ito Mamoru、Kato Yukinari、Nakayama Keiko、Unno Michiaki、Igarashi Kazuhiko
    • Journal Title

      Cancer Research

      Volume: 80 Issue: 6 Pages: 1279-1292

    • DOI

      10.1158/0008-5472.can-18-4099

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Induction of Metastasis by Low-dose Gemcitabine in a Pancreatic Cancer Orthotopic Mouse Model: An Opposite Effect of Chemotherapy2019

    • Author(s)
      SUGISAWA NORIHIKO、MIYAKE KENTARO、HIGUCHI TAKASHI、OSHIRO HIROMICHI、ZHANG ZHIYING、PARK JUN HO、KAWAGUCHI KEI、CHAWLA SANT P.、BOUVET MICHAEL、SINGH SHREE RAM、UNNO MICHIAKI、HOFFMAN ROBERT M.
    • Journal Title

      Anticancer Research

      Volume: 39 Issue: 10 Pages: 5339-5344

    • DOI

      10.21873/anticanres.13726

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Novel biomarkers distinguishing pancreatic head Cancer from distal cholangiocarcinoma based on proteomic analysis2019

    • Author(s)
      Takenami Tsutomu、Maeda Shimpei、Karasawa Hideaki、Suzuki Takashi、Furukawa Toru、Morikawa Takanori、Takadate Tatsuyuki、Hayashi Hiroki、Nakagawa Kei、Motoi Fuyuhiko、Naitoh Takeshi、Unno Michiaki
    • Journal Title

      BMC Cancer

      Volume: 19 Issue: 1 Pages: 318-318

    • DOI

      10.1186/s12885-019-5548-x

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sustained Elevation of Postoperative Serum Level of Carbohydrate Antigen 19-9 is High-Risk Stigmata for Primary Hepatic Recurrence in Patients with Curatively Resected Pancreatic Adenocarcinoma.2019

    • Author(s)
      Motoi F, Murakami Y, Okada KI, Matsumoto I, Uemura K, Satoi S, Sho M, Honda G, Fukumoto T, Yanagimoto H, Kinoshita S, Kurata M, Aoki S, Mizuma M, Yamaue H, Unno M; Multicenter Study Group of Pancreatobiliary Surgery (MSG-PBS).
    • Journal Title

      World J Surg.

      Volume: 43 Issue: 2 Pages: 634-641

    • DOI

      10.1007/s00268-018-4814-4

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] FBXW7 modulates malignant potential and cisplatin-induced apoptosis in cholangiocarcinoma through NOTCH1 and MCL12018

    • Author(s)
      Mori Akiko、Masuda Kunihiro、Ohtsuka Hideo、Shijo Masahiro、Ariake Kyohei、Fukase Koji、Sakata Naoaki、Mizuma Masamichi、Morikawa Takanori、Hayashi Hiroki、Nakagawa Kei、Motoi Fuyuhiko、Naitoh Takeshi、Fujishima Fumiyoshi、Unno Michiaki
    • Journal Title

      Cancer Science

      Volume: 109 Issue: 12 Pages: 3883-3895

    • DOI

      10.1111/cas.13829

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 膵癌に対する術前化学放射線療法後に遺残する腫瘍細胞の分子病理学的解析2019

    • Author(s)
      佐藤 稔久
    • Organizer
      日本病理学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 腸型IPMNはどのように発生するか? CDX2、MUC2、alcian blue三重染色による検討2019

    • Author(s)
      大森優子
    • Organizer
      日本膵臓学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] IPMNとIPNB-診断と治療のアップデート- 新分類(type1、type2)による胆管内乳頭状腫瘍(IPNB)切除例の検討2019

    • Author(s)
      水間正道
    • Organizer
      日本外科学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 膵臓腫瘍の発生進展機構の解明2019

    • Author(s)
      古川徹
    • Organizer
      日本病理学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 膵頭部癌・遠位胆管癌の鑑別診断を可能とするタンパク質バイオマーカーの同定2018

    • Author(s)
      竹浪 努, 前田 晋平, 唐澤 秀明, 鈴木 貴, 高舘 達之, 水間 正道, 大塚 英郎, 森川 孝則, 林 洋毅, 中川 圭, 元井 冬彦, 内藤 剛, 亀井 尚, 石田 孝宣, 海野 倫明
    • Organizer
      第118回日本外科学会定期学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 膵頭部癌・遠位胆管癌の鑑別診断を可能とするタンパク質バイオマーカーの同定2018

    • Author(s)
      竹浪努
    • Organizer
      第118回日本外科学会定期学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] プロテオーム解析を用いた膵癌・胆管癌の鑑別を可能にする新規バイオマーカーの同定2017

    • Author(s)
      竹浪努
    • Organizer
      第76回日本癌学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] BAP1発現変化による肝内胆管癌への影響2016

    • Author(s)
      石居健太郎
    • Organizer
      第75回日本癌学会
    • Place of Presentation
      横浜(パシフィコ横浜)
    • Year and Date
      2016-10-06
    • Related Report
      2016 Annual Research Report

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Published: 2016-04-21   Modified: 2021-02-19  

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