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胆管分化を示す肝癌の層別化

Research Project

Project/Area Number 22K06976
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49020:Human pathology-related
Research InstitutionThe University of Tokyo

Principal Investigator

田中 麻理子  東京大学, 医学部附属病院, 講師 (50645710)

Project Period (FY) 2022-04-01 – 2025-03-31
Project Status Granted (Fiscal Year 2023)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2024: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2023: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2022: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords胆管癌 / 肝癌 / KRAS / 混合型肝癌 / 病理組織学的形態 / 臨床的転帰
Outline of Research at the Start

胆管分化を示す肝癌は極めて予後不良であるが、肝細胞癌と比べて研究が進んでいない。本研究では胆管分化を示す肝癌の臨床的動態を反映した層別化を行うことを目的として、遠隔転移をきたしやすい肝内胆管癌の同定とその分子生物学的機序の解明、胆管分化を示す肝癌の亜分類を行う。外科的切除症例の大規模コホートを用い、臨床病理学的特徴、遺伝子異常、タンパク発現、腫瘍内微小環境を組み合わせ、予後不良群の抽出、臨床動態に結び付いた細分類を行う。本研究により得られる成果は、希少癌である胆管分化を示す肝癌において、術後早期治療介入を要する一群の同定や新規治療開発に資するものと期待される。

Outline of Annual Research Achievements

各種の癌病態において、遺伝子異常のもたらす臨床的動態と分子生物学的機序の同定や臨床的転帰と結び付いた亜分類は、疾病発生の理解や迅速かつ最適な治療介入を行う上で非常に重要である。しかしながら、胆管分化を示す肝癌は極めて予後不良であるにもかかわらず肝細胞癌に比して研究が進んでいない。本研究では、胆管分化を示す肝癌について、臨床的動態を反映した層別化を行うこと、またその発生起点を明らかにすることを目的とする。昨年度までに、本研究で収集・解析中の、胆管分化を示す肝癌の外科的切除症例の大規模なコホートを用い、肝内胆管癌ではKRAS変異陽性群がとりわけ予後不良な一群であること、そして、KRAS変異が蔟出形態をもたらすことで遠隔転移をきたしやすくなるため予後不良に寄与することを見出し論文報告している(Liver Int. 2022)。さらに本年度は、特異的融合遺伝子をもつ一群について、予後が良く、病理組織学的形態のspectrumが広いことを見出した(論文投稿後minor revision中)。今年度までの本研究の成果は、胆管分化を示す肝癌において、臨床的転帰とゲノム異常ならびに病理組織学的形態を結び付け、臨床的転帰に結び付いた亜分類を描出している点で個別化医療において非常に重要な意義がある。

Current Status of Research Progress
Current Status of Research Progress

3: Progress in research has been slightly delayed.

Reason

胆管分化を示す肝癌の解析症例総数の蓄積は順調に推移している。一方で、混合型肝癌については手術検体として得られる数が少なく、前向きな検体採取に関連した解析についてはやや遅れている。

Strategy for Future Research Activity

混合型肝癌症例の解析を進める。

Report

(2 results)
  • 2023 Research-status Report
  • 2022 Research-status Report
  • Research Products

    (34 results)

All 2024 2023 2022

All Journal Article (23 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 23 results,  Open Access: 10 results) Presentation (10 results) Book (1 results)

  • [Journal Article] Intraductal Papillary Mucinous Neoplasm Surveillance Leads to Early Diagnosis and Better Outcomes of Concomitant Cancer2024

    • Author(s)
      Oyama Hiroki、Hamada Tsuyoshi、Nakai Yousuke、Tanaka Mariko、Takagi Kaoru、Fukuda Rintaro、Hakuta Ryunosuke、Ishigaki Kazunaga、Kanai Sachiko、et al.
    • Journal Title

      Annals of Surgery

      Volume: -

    • DOI

      10.1097/sla.0000000000006268

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Thick silk fibroin vascular graft: A promising tissue-engineered scaffold material for abdominal vein grafts in middle-sized mammals.2024

    • Author(s)
      Fukuda K, Kaneko J, Kiritani S, Sawa Y, Morito M, Tanaka M, Ushiku T, Cheng CJ, Tanaka T, Tanaka R, Asakura T, Kawaguchi Y, Akamatsu N, Hasegawa K.
    • Journal Title

      Int J Artif Organs.

      Volume: 47 Issue: 3 Pages: 190-197

    • DOI

      10.1177/03913988241234547

    • Related Report
      2023 Research-status Report
    • Peer Reviewed
  • [Journal Article] Increased expression of TNFRSF14 and LIGHT in biliary epithelial cells of patients with primary sclerosing cholangitis2024

    • Author(s)
      Kanai S, Fujiwara H, Mizuno S, Kishikawa T, Nakatsuka T, Hamada T, Tanaka M, Arita J, Nakai Y, Isayama H, Kasuga M, Tateishi R, Tateishi K, Ushiku T, Hasegawa K, Koike K, Fujishiro M.
    • Journal Title

      Dig Liver Dis .

      Volume: 56(2) Issue: 2 Pages: 305-311

    • DOI

      10.1016/j.dld.2023.08.057

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Post-operative mortality and recurrence patterns in pancreatic cancer according to KRAS mutation and CDKN2A, p53, and SMAD4 expression.2023

    • Author(s)
      Masugi Y, Takamatsu M, Tanaka M(Co-first author), Hara K, Inoue Y, Hamada T, Suzuki T, Arita J, Hirose Y, Kawaguchi Y, Nakai Y, Oba A, Sasahira N, Shimane G, Takeda T, Tateishi K, Uemura S, Fujishiro M, Hasegawa K, Kitago M, Takahashi Y, Ushiku T, Takeuchi K, Sakamoto M; GTK Pancreatic Cancer Study Group in Japan.
    • Journal Title

      J Pathol Clin Res.

      Volume: 9 Issue: 5 Pages: 339-353

    • DOI

      10.1002/cjp2.323

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Systematic review of challenging issues in pathology of intraductal papillary mucinous neoplasms2023

    • Author(s)
      Wood LD, Adsay NV, Basturk O, Brosens LAA, Fukushima N, Hong SM, Kim SJ, Lee JW, Luchini C, Noe M, Pitman MB, Scarpa A, Singhi AD, Tanaka M, Furukawa T.
    • Journal Title

      Pancreatology.

      Volume: 23 Issue: 7 Pages: 878-891

    • DOI

      10.1016/j.pan.2023.08.002

    • Related Report
      2023 Research-status Report
    • Peer Reviewed
  • [Journal Article] Real-Time Fluorescence Imaging to Identify Cholangiocarcinoma in the Extrahepatic Biliary Tree Using an Enzyme-Activatable Probe.2023

    • Author(s)
      Takahashi R, Ishizawa T, Inagaki Y, Tanaka M, Ogasawara A, Kuriki Y, Fujita K, Kamiya M, Ushiku T, Urano Y, Hasegawa K.
    • Journal Title

      Liver Cancer.

      Volume: 12 Issue: 6 Pages: 590-602

    • DOI

      10.1159/000530645

    • Related Report
      2023 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical trajectory of intraductal papillary mucinous neoplasms progressing to pancreatic carcinomas during long-term surveillance: a prospective series of 100 carcinoma cases.2023

    • Author(s)
      Oyama H, Hamada T, Nakai Y, Tanaka M, Endo G, Hakuta R, Ishida K, Ishigaki K, Kanai S, Kurihara K, Saito T, Sato T, Suzuki T, Suzuki Y, Takaoka S, Tange S, Tokito Y, Takahara N, Ushiku T, Fujishiro M.
    • Journal Title

      J Gastroenterol.

      Volume: 58 Issue: 10 Pages: 1068-1080

    • DOI

      10.1007/s00535-023-02028-0

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Intraductal oncocytic papillary neoplasm of the pancreas: clinical and radiological features compared to those of intraductal papillary mucinous neoplasm.2023

    • Author(s)
      Nakaya M, Nakai Y, Takahashi M, Fukukura Y, Sato K, Kameda A, Tashiro Y, Kageyama S, Sofue K, Nakano T, Yoshimitsu K, Marugami N, Takeyama N, Tanaka M, Hasegawa K, Watadani T.
    • Journal Title

      Abdom Radiol (NY).

      Volume: 48 Issue: 8 Pages: 2483-2493

    • DOI

      10.1007/s00261-023-03985-z

    • Related Report
      2023 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical Outcomes of Intraductal Papillary Mucinous Neoplasms With Dilatation of the Main Pancreatic Duct2023

    • Author(s)
      Hamada Tsuyoshi、Oyama Hiroki、Nakai Yousuke、Tateishi Keisuke、Ushiku Tetsuo、Hasegawa Kiyoshi、Fujishiro Mitsuhiro
    • Journal Title

      Clinical Gastroenterology and Hepatology

      Volume: - Issue: 7 Pages: 792-1801

    • DOI

      10.1016/j.cgh.2023.01.032

    • Related Report
      2023 Research-status Report 2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical utility of postablation liver tumor biopsy and possibility of gene mutation analysis.2023

    • Author(s)
      Nakatsuka T, Nakagawa H, Uchino K, Rokutan H, Tanaka M, Moriyama M, Fukumoto T, Yamada T, Wake T, Nakagomi R, Sato M, Minami T, Kudo Y, Ushiku T, Fujishiro M, Tateishi R.
    • Journal Title

      Hepatol Res.

      Volume: 53 Issue: 11 Pages: 1117-1125

    • DOI

      10.1111/hepr.13944

    • Related Report
      2023 Research-status Report
    • Peer Reviewed
  • [Journal Article] Acute pancreatitis as the initial manifestation of acute myeloid leukemia with chromosome 16 rearrangements.2023

    • Author(s)
      Fukushima H, Morita K, Ikemura M, Tanaka M, Nakai Y, Maki H, Suzuki T, Mizuno S, Nakai Y, Kurokawa M.
    • Journal Title

      Int J Hematol.

      Volume: 118 Issue: 3 Pages: 381-387

    • DOI

      10.1007/s12185-023-03580-4

    • Related Report
      2023 Research-status Report 2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Autoimmunity and immunodeficiency associated with monoallelic LIG4 mutations via haploinsufficiency2023

    • Author(s)
      Jauch AJ, Bignucolo O, Seki S, Ghraichy M, Delmonte OM, et al.
    • Journal Title

      Journal of Allergy and Clinical Immunology

      Volume: S0091-6749 Issue: 2 Pages: 00422-0

    • DOI

      10.1016/j.jaci.2023.03.022

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Lymphoproliferative disorder during temozolomide therapy; a representative case of a formidable complication and management challenges.2023

    • Author(s)
      Sato D, Takami H, Takayanagi S, Taoka K, Tanaka M, Matsuura R, Tanaka S, Saito N.
    • Journal Title

      BMC Neurol.

      Volume: 23 Issue: 1 Pages: 224-224

    • DOI

      10.1186/s12883-023-03274-8

    • Related Report
      2023 Research-status Report
    • Peer Reviewed
  • [Journal Article] A case of intravascular lymphoma presenting with a lesion in the splenium of the corpus callosum.2023

    • Author(s)
      Masuzawa H, Suzuki F, Amemiya S, Orimo K, Ishiura H, Hara R, Toda T, Nakazawa T, Honda A, Tanaka M, Hinata M, Abe O
    • Journal Title

      Radiol Case Rep.

      Volume: 18 Issue: 5 Pages: 1929-1932

    • DOI

      10.1016/j.radcr.2023.02.025

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification of odontogenic ameloblast associated as a novel target gene of the Wnt/β‐catenin signaling pathway2022

    • Author(s)
      Yamaguchi Kiyoshi、Horie Chiaki、Takane Kiyoko、Ikenoue Tsuneo、Nakagawa Saya、Isobe Yumiko、Ota Yasunori、Ushiku Tetsuo、Tanaka Mariko、Fujishiro Jun、Hoshino Noriko、Arisue Atsuhiro、Nishizuka Satoshi、Aikou Susumu、Shida Dai、Furukawa Yoichi
    • Journal Title

      Cancer Science

      Volume: 114 Issue: 3 Pages: 948-960

    • DOI

      10.1111/cas.15657

    • Related Report
      2023 Research-status Report 2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Assessment of liver function-related mRNA expression and fluorescence imaging in outflow-obstructed regions in rats2022

    • Author(s)
      Ito Daisuke、Kawaguchi Yoshikuni、Inagaki Yoshinori、Ito Kyoji、Mihara Yuichiro、Kaneko Junichi、Tanaka Mariko、Fukayama Masashi、Kokudo Norihiro、Hasegawa Kiyoshi
    • Journal Title

      Surgery Today

      Volume: 53 Issue: 4 Pages: 513-521

    • DOI

      10.1007/s00595-022-02588-3

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] MNX1-HNF1B Axis Is Indispensable for Intraductal Papillary Mucinous Neoplasm Lineages2022

    • Author(s)
      Kato H, Tateishi K, Fujiwara H, Nakatsuka T, Yamamoto K, Kudo Y, Hayakawa Y, Nakagawa H, Tanaka Y, Ijichi H, Otsuka M, Iwadate D, Oyama H, Kanai S, Noguchi K, Suzuki T, Sato T, Hakuta R, Ishigaki K, Saito K, Saito T, Takahara N, Kishikawa T, Hamada T, Takahashi R, Miyabayashi K, et al.
    • Journal Title

      Gastroenterology

      Volume: 162 Issue: 4 Pages: 1272-1287

    • DOI

      10.1053/j.gastro.2021.12.254

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Multiple Brain Metastases in a Patient with ROS1 Fusion-Positive Lung Adenocarcinoma as a Disease Flare due to Crizotinib Cessation Caused by Disseminated Aseptic Inflammation from Crizotinib-Associated Renal Cysts: A Case Report.2022

    • Author(s)
      Amano Y, Kage H, Tanaka G, Sato Y, Tanaka M, Nagase T.
    • Journal Title

      Case Rep Oncol.

      Volume: 15 Issue: 1 Pages: 338-344

    • DOI

      10.1159/000523737

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] High-grade transformation of pancreatic neuroendocrine tumor associated with TP53 mutations: A diagnostic pitfall mimicking neuroendocrine carcinoma.2022

    • Author(s)
      Tanaka M, Shinozaki-Ushiku A, Kunita A, Yasunaga Y, Akamatsu N, Hasegawa K, Ushiku T.
    • Journal Title

      Pathol Int.

      Volume: 72(8) Issue: 8 Pages: 411-418

    • DOI

      10.1111/pin.13252

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] KRAS variant allele frequency, but not mutation positivity, associates with survival of patients with pancreatic cancer2022

    • Author(s)
      Suzuki T, Masugi Y, Inoue Y, Hamada T, Tanaka M, Takamatsu M, Arita J, Kato T, Kawaguchi Y, Kunita A, Nakai Y, Nakano Y, Ono Y, Sasahira N, Takeda T, Tateishi K, Uemura S, Koike K, Ushiku T, Takeuchi K, Sakamoto M, Hasegawa K, Kitago M, Takahashi Y, Fujishiro M.
    • Journal Title

      Cancer Science

      Volume: - Issue: 9 Pages: 3097-3109

    • DOI

      10.1111/cas.15398

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Diagnostic Categories and Key Features for Pathological Diagnosis of Endoscopic Ultrasound-Guided Fine Needle Aspiration Biopsy Samples of Pancreatic Lesions: A Consensus Study.2022

    • Author(s)
      Naito Y, Notohara K, Omori Y, Aishima S, Itoi T, Ohike N, Okabe Y, Kojima M, Tajiri T, Tanaka M, Tsuneki M, Nakagohri T, Norose T, Hirabayashi K, Fukumura Y, Mitsuhashi T, Yamaguchi H, Fukushima N, Furukawa T.
    • Journal Title

      Pancreas.

      Volume: 51(9) Issue: 9 Pages: 1105-1111

    • DOI

      10.1097/mpa.0000000000002179

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] KRAS mutation in intrahepatic cholangiocarcinoma: linkage with metastasis-free survival and reduced E-cadherin expression.2022

    • Author(s)
      Tanaka M, Kunita A, Yamagishi M, Ishikawa S, Katoh H, Yamamoto H, Abe J, Arita J, Hasegawa K, Shibata T, and Ushiku T.
    • Journal Title

      Liver Int.

      Volume: 42 Issue: 10 Pages: 2329-2340

    • DOI

      10.1111/liv.15366

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] A case of a tiny neuroendocrine carcinoma in a large flat-elevated rectal tumor causing multiple liver metastases.2022

    • Author(s)
      Ohki D, Tsuji Y, Tanaka M, Ushiku T, Fujishiro M.
    • Journal Title

      Clin J Gastroenterol.

      Volume: 15(6) Issue: 6 Pages: 1078-1082

    • DOI

      10.1007/s12328-022-01691-9

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Presentation] 膵胆道癌とがんゲノム医療の実際.2024

    • Author(s)
      田中麻理子.
    • Organizer
      第113回日本病理学会総会
    • Related Report
      2023 Research-status Report
  • [Presentation] 若年発症膵癌の臨床病理学的特徴.2023

    • Author(s)
      田中麻理子, 濱田毅, 国田朱子, 長谷川潔, 牛久哲男.
    • Organizer
      第112回日本病理学会総会
    • Related Report
      2023 Research-status Report
  • [Presentation] 胸膜肺芽腫の前立腺転移再発と前立腺胎児型横紋筋肉腫との鑑別が問題となったDICER1症候群の一例.2023

    • Author(s)
      外園晋夫, 田中麻理子, 井上秀太郎, 加藤元博, 牛久哲男.
    • Organizer
      第98回日本病理学会関東支部学術集会
    • Related Report
      2023 Research-status Report
  • [Presentation] 癌との鑑別に難渋したタキサン系抗癌剤による十二指腸乳頭部粘膜傷害の1例.2023

    • Author(s)
      岩原加奈, 田中麻理子, 牛久哲男.
    • Organizer
      第100回日本病理学会関東支部学術集会
    • Related Report
      2023 Research-status Report
  • [Presentation] 胃壁など腹腔内に多発したCalcifying fibrous tumorの一例2023

    • Author(s)
      山本周、田中麻理子、辻陽介、吉村俊太郎、谷島翔、牛久哲男
    • Organizer
      第97回日本病理学会関東支部学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] 膵intraductal oncocytic papillary neoplasm(IOPN)の7例 Seven cases of intraductal oncocytic papillary neoplasm of the pancreas2022

    • Author(s)
      仲谷元、中井雄大、渡谷岳行、石田尚利、渡邉祐亮、五ノ井渉 、田中麻理子、牛久哲男、有田淳一、阿部修
    • Organizer
      第35回日本腹部放射線学会
    • Related Report
      2022 Research-status Report
  • [Presentation] 組織学的に扁平上皮癌との鑑別が困難であったhypertrophic lichen planus様の皮膚irAEの一例2022

    • Author(s)
      名和純一 、日向宗利 、田中麻理子 、池村雅子、秋山佑子、久住藍、永井幸司郎、 佐藤伸一、牛久哲男
    • Organizer
      第94回日本病理学会関東支部学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] 頭蓋底原発脊索腫の乳腺転移の一例2022

    • Author(s)
      明賀伊織、瀬田章、竹内裕子、田中麻理子
    • Organizer
      第61回日本臨床細胞学会秋季大会
    • Related Report
      2022 Research-status Report
  • [Presentation] TP53変異付加により悪性度が高まったと考えられる膵神経内分泌腫瘍の進展過程をとらえた剖検例2022

    • Author(s)
      近藤篤史、田中麻理子、大澤一太、牛久綾、国田朱子、安永瑛一、赤松延久、小峯弓子、鈴木伸三、藤城光弘、長谷川潔、牛久哲男
    • Organizer
      第68回日本病理学会秋期特別総会
    • Related Report
      2022 Research-status Report
  • [Presentation] TP53 変異に伴い退形成性変化をきたした膵神経内分泌腫瘍:膵内分泌癌との鑑別ピットフォール2022

    • Author(s)
      田中麻理子、牛久綾、国田朱子、安永瑛一、赤松延久、長谷川潔、牛久哲男
    • Organizer
      第111回日本病理学会総会
    • Related Report
      2022 Research-status Report
  • [Book] 十二指腸非乳頭部腺腫・癌の病理診断. 臨牀消化器内科2023

    • Author(s)
      名和純一, 田中麻理子, 牛久哲男.
    • Total Pages
      7
    • Publisher
      日本メディカルセンター
    • Related Report
      2023 Research-status Report

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Published: 2022-04-19   Modified: 2024-12-25  

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