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The role of inflammatory biomarker OLMF4 to the malignancy of inflammatory bowel disease related tumors

Research Project

Project/Area Number 18K07026
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 InstitutionKitasato University

Principal Investigator

Yoshida Tsutomu  北里大学, 医学部, 教授 (90316943)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords炎症性腸疾患 / 潰瘍性大腸炎 / 悪性腫瘍 / Olfactomedin-4 / OLFM4 / クローン病 / 発癌 / olfactomedin-4 / 悪性度 / olfactomedin 4 / 上皮間葉連関
Outline of Final Research Achievements

To elucidate the poorer differentiation and prognosis of inflammatory bowel disease related tumor, we analyzed the association of biomarker OLMF4. OLFM4 binds frizzled-7, which would lead the suppression of WNT/beta-catenin pathway. OLMF4 was secreted in exosome, and exosomal OLMF4 inhibited the expression of activated form of beta-catenin and EMT markers. Expression of OLMF4 in inflammatory foci of UC-related tumors was reduce along with the tumorigenesis, which suggests the relationship with the malignancy of tumors. It is possible that suppression of EMT by OLMF4 secreted in exosome would be the cause of the malignant potential of IBD related tumor.

Academic Significance and Societal Importance of the Research Achievements

潰瘍性大腸炎及びクローン病は若年発症の難病炎症性腸疾患(IBD)で、患者数は増加している。長期罹患により悪性腫瘍を多発発症すると共に、通常型大腸癌に比して低分化で悪性度が高いことが知られているが、その機序は明らかになっていない。今回の研究成果は、申請者がこれまでに明らかにしてきたIBD特異的バイオマーカーであるOLFM4(olfactomedin-4)が、IBD関連腫瘍の高悪性度特性に関わっていることを明らかにするもので、特にexosome型分泌が関与することを明らかにしたことは学術的にも新機軸である。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (18 results)

All 2022 2021 2020 2019 2018 Other

All Journal Article (13 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 13 results,  Open Access: 5 results) Presentation (4 results) Remarks (1 results)

  • [Journal Article] Clinicopathological features of PD-L1 protein expression, EBV positivity, and MSI status in patients with advanced gastric and esophagogastric junction adenocarcinoma in Japan2022

    • Author(s)
      Yoshida Tsutomu、Ogura Go、Tanabe Mikiko、Hayashi Takuo、Ohbayashi Chiho、Azuma Mizutomo、Kunisaki Chikara、Akazawa Yoichi、Ozawa Soji、Matsumoto Sohei、Suzuki Takayoshi、Mitoro Akira、Fukunaga Tetsu、Shimizu Akiko、Fujimoto Go、Yao Takashi
    • Journal Title

      Cancer Biology & Therapy

      Volume: 23 Issue: 1 Pages: 191-200

    • DOI

      10.1080/15384047.2022.2038002

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cytology Reporting System for Lung Cancer from the Japan Lung Cancer Society and the Japanese Society of Clinical Cytology: An Extensive Study Containing More Benign Lesions2021

    • Author(s)
      Yoshizawa Akihiko、Hiroshima Kenzo、Takenaka Akemi、Haba Reiji、Kawahara Kunimitsu、Minami Yuko、Kakinuma Hirokuni、Shibuki Yasuo、Miyake Shinji、Kajio Kenta、Kiyonaga Kana、Nagatomo Moe、Nishimura Sanako、Mano Masayuki、Matsubayashi Jun、Motoi Noriko、Nagao T.、Nakatsuka S.、Yoshida Tsutomu、Satoh Y.
    • Journal Title

      Acta Cytologica

      Volume: 66 Issue: 2 Pages: 124-133

    • DOI

      10.1159/000520426

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of CA2 and CA9 carbonic anhydrases in ulcerative colitis and ulcerative colitis‐associated colorectal cancer2020

    • Author(s)
      Nakada Norihiro、Mikami Tetuo、Horie Kayo、Nagashio Ryo、Sakurai Yasutaka、Sanoyama Itaru、Yoshida Tsutomu、Sada Miwa、Kobayashi Kiyonori、Sato Yuichi、Okayasu Isao、Murakumo Yoshiki
    • Journal Title

      Pathology International

      Volume: 70 Issue: 8 Pages: 523-532

    • DOI

      10.1111/pin.12949

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cytology Reporting System for Lung Cancer from the Japan Lung Cancer Society and Japanese Society of Clinical Cytology: An Interobserver Reproducibility Study and Risk of Malignancy Evaluation on Cytology Specimens2020

    • Author(s)
      Hiroshima K、Yoshizawa A、Takenaka A、Haba R、Kawahara K、Minami Y、Kakinuma H、Shibuki Y、Miyake Si、Kajio K、Miyamoto K、Nagatomo M、Nishimura S、Mano Mi、Matsubayashi J、Motoi N、Nagao T、Nakatsuka S、Yoshida T、Satoh Y
    • Journal Title

      Acta Cytologica

      Volume: - Issue: 5 Pages: 1-11

    • DOI

      10.1159/000506431

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] EGFR mutation genotyping and ALK status determination in liquid-based cytology samples of non-small cell lung cancer2019

    • Author(s)
      Yukitoshi Satoh, Yukiko Matsuo, Tatsuru Kuba, Kazuya Yamashita, Mariko Sawano, Shusaku Tozaka, Hirotsugu Yamazaki, Dai Sonoda, Masashi Mikubo, Nasahiro Naito, Yoshio Matsui, Kazu Shiomi, Tsutomu Yoshida, Yoshiki Murakumo
    • Journal Title

      Virshows Archiv

      Volume: - Issue: 5 Pages: 753-762

    • DOI

      10.1007/s00428-019-02692-9

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] A retrospective study of definitive chemoradiotherapy in patients with resectable small cell neuroendocrine carcinoma of the esophagus.2019

    • Author(s)
      Chikatoshi Katada, Shouko Komori, Tsutomu Yoshida, Shogo Kawakami, Akinori Watanabe, Kenji Ishido, Mizutomo Azuma, Takuya Wada, Kei Hosoda, Keishi Yamashita, Naoki Hiki, Satoshi Tanabe, Hiromichi Ishiyama, Wasaburo Koizumi.
    • Journal Title

      Esophagus

      Volume: 47 Issue: 2 Pages: 716-719

    • DOI

      10.1007/s10388-019-00686-9

    • NAID

      40022193296

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Ciliated muconodular papillary tumors of the lung: Cytologic features and diagnostic pitfalls in intraoperative examinations2019

    • Author(s)
      Mikubo Masashi、Maruyama Raito、Kakinuma Hirokuni、Yoshida Tsutomu、Satoh Yukitoshi
    • Journal Title

      Diagnostic Cytopathology

      Volume: 47 Issue: 7 Pages: 716-719

    • DOI

      10.1002/dc.24169

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Analysis of BRCAness with multiplex ligation-dependent probe amplification using formalin-fixed and paraffin-embedded pancreatic ductal adenocarcinoma tissue obtained via endoscopic ultrasound-guided fine-needle aspiration biopsy2019

    • Author(s)
      Okuwaki Kosuke、Masutani Hironori、Imaizumi Hiroshi、Yoshida Tsutomu、Kida Mitsuhiro、Iwai Tomohisa、Yamauchi Hiroshi、Tadehara Masayoshi、Adachi Kai、Watanabe Masafumi、Kurosu Takahiro、Koizumi Wasaburo
    • Journal Title

      Pancreatology

      Volume: 19 Issue: 3 Pages: 419-423

    • DOI

      10.1016/j.pan.2019.02.010

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Proposal for an Organ-Specific Chronic Inflammation - Remodeling - Carcinoma Sequence2019

    • Author(s)
      Okayasu Isao、Ichinoe Masaaki、Yoshida Tsutomu
    • Journal Title

      Gastrointestinal Disorders

      Volume: 1 Issue: 3 Pages: 341-357

    • DOI

      10.3390/gidisord1030028

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Vascular endothelial growth factor receptor 1 tyrosine kinase signaling facilitates healing of DSS-induced colitis by accumulation of Tregs in ulcer area2019

    • Author(s)
      Betto Tomohiro、Amano Hideki、Ito Yoshiya、Eshima Koji、Yoshida Tsutomu、Matsui Yoshio、Yamane Sakiko、Inoue Tomoyoshi、Otaka Fumisato、Kobayashi Kiyonori、Koizumi Wasaburo、Shibuya Masabumi、Majima Masataka
    • Journal Title

      Biomedicine & Pharmacotherapy

      Volume: 111 Pages: 131-141

    • DOI

      10.1016/j.biopha.2018.12.021

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Peroxiredoxin 1 expression in active ulcerative colitis mucosa identified by proteome analysis and involvement of thioredoxin based on immunohistochemistry2019

    • Author(s)
      Horie Kayo、Mikami Tetuo、Yoshida Tsutomu、Sato Yuichi、Okayasu Isao
    • Journal Title

      Oncology Letters

      Volume: 15 Pages: 2364-2372

    • DOI

      10.3892/ol.2017.7549

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reducing DNA damage by formaldehyde in liquid‐based cytology preservation solutions to enable the molecular testing of lung cancer specimens2018

    • Author(s)
      Matsuo Yukiko、Yoshida Tsutomu、Yamashita Kazuya、Satoh Yukitoshi
    • Journal Title

      Cancer Cytopathology

      Volume: 126 Issue: 12 Pages: 1011-1021

    • DOI

      10.1002/cncy.22069

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular alterations in a new cell line (KU-Lu-MPPt3) established from a human lung adenocarcinoma with a micropapillary pattern2018

    • Author(s)
      Matsuo Yukiko、Shiomi Kazu、Sonoda Dai、Mikubo Masashi、Naito Masahito、Matsui Yoshio、Yoshida Tsutomu、Satoh Yukitoshi
    • Journal Title

      Journal of Cancer Research and Clinical Oncology

      Volume: 144 Issue: 1 Pages: 75-87

    • DOI

      10.1007/s00432-017-2541-0

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 日本人胃癌におけるPD-L1発現、MSI status及びEBV陽性評価:多施設共同後方視的観察研究2019

    • Author(s)
      吉田 功、小倉豪、田辺美樹子、林大久生、大林千穂、東瑞智、國崎主税、赤澤陽一、小澤壯治、松本壮平、鈴木孝良、美登路昭、福永哲、清水晶子、藤本豪、八尾隆史
    • Organizer
      第57回日本癌治療学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] JSCC-JLCSによる新たな判定基準の提案.2019

    • Author(s)
      廣島健三、佐藤之俊、吉田 功、柿沼廣邦、長尾俊孝、松林純、三宅真司、中塚伸一、眞能正幸、竹中明美、元井紀子、澁木康雄、南優子、吉澤明彦、羽場礼次、河原邦光
    • Organizer
      第60回日本臨床細胞学会春期大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 炎症性バイオマーカーOLFM4からみた炎症性腸疾患関連腫瘍の特異性の解明.2019

    • Author(s)
      横山 慧、吉田 功、橋村美紀、三枝 信
    • Organizer
      第108回日本病理学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Olfactomedin-4の炎症性腸疾患関連腫瘍発生における役割.2018

    • Author(s)
      横山 慧、吉田 功、橋村美紀、三枝 信.
    • Organizer
      第107回日本病理学会総会
    • Related Report
      2018 Research-status Report
  • [Remarks] 北里大学医学部病理学(三枝単位)

    • URL

      https://www.kitasato-u.ac.jp/med/research/departments/medicine/byouri-s.html

    • Related Report
      2020 Research-status Report 2019 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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