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The functional analyses and the therapeutic applications of a novel tumor suppressor gene ZNF395 involved in the progression of pancreatic cancers.

Research Project

Project/Area Number 17K08695
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Human pathology
Research InstitutionOita University

Principal Investigator

Murakami Kazunari  大分大学, 医学部, 教授 (00239485)

Co-Investigator(Kenkyū-buntansha) 兒玉 雅明  大分大学, 福祉健康科学部, 教授 (20332893)
泥谷 直樹  大分大学, 医学部, 准教授 (80305036)
守山 正胤  大分大学, 医学部, 教授 (90239707)
沖本 忠義  大分大学, 医学部, 講師 (90381037)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords膵癌 / ZNF395 / がん抑制遺伝子 / 細胞周期 / 免疫組織化学 / 発現誘導 / 増殖能 / シグナルパスウェイ
Outline of Final Research Achievements

To elucidate the functional significance of downregulation of ZNF395 due to 8p loss in pancreatic carcinogenesis, pancreatic cancer cell lines for doxycycline-inducible expression of ZNF395 were established. The proliferation potentials were markedly suppressed through a cell cycle arrest by induction of ZNF395. Immunohistochemical analyses of resected pancreatic cancer tissues revealed that the expression of ZNF395 was observed in cytoplasm of non-tumorous pancreatic ducts and acinar glands. In addition, it was detectable in intraepithelial lesions. On the other hand, ZNF395 expression was significantly reduced in the cancer cells in invasive lesions, especially in these with poor differentiation. Downregulation of ZNF395 showed a tendency to be worse prognosis in the patients with pancreatic cancers.

Academic Significance and Societal Importance of the Research Achievements

膵前癌病変が浸潤癌へ進展する分子メカニズムの一部を明らかにした。8p欠失に伴うZNF395の発現低下は膵癌前駆細胞に細胞周期の脱制御と増殖能亢進をもたらした。今後、ZNF395の下流で活性化されるシグナルパスウェイの同定を目指す。本研究で得られる知見は、新規の膵癌早期診断法および分子標的治療法の開発に応用可能である。予後不良な難治癌である膵癌の治療成績の向上に寄与することを期待する

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (33 results)

All 2020 2019 2018 2017

All Journal Article (21 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 21 results,  Open Access: 13 results) Presentation (12 results) (of which Int'l Joint Research: 6 results,  Invited: 1 results)

  • [Journal Article] Successful endoscopic retrieval of a toothpick stuck in the small intestine using double-balloon enteroscopy.2020

    • Author(s)
      Abe T, Kusatsu K, Nagai T, Murakami K.
    • Journal Title

      Endoscopy

      Volume: 52 Issue: 02 Pages: E45-E46

    • DOI

      10.1055/a-0992-8959

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A transgenic mouse expressing miR-210 in proximal tubule cells shows mitochondrial alteration: possible association of miR-210 with a shift in energy metabolism.2020

    • Author(s)
      Nakada C, Hijiya N, Tsukamoto Y, Yano S, Kai T, Uchida T, Kimoto M, Takahashi M, Daa T, Matsuura K, Shin T, Mimata H, Moriyama M.
    • Journal Title

      J Pathol.

      Volume: in press Issue: 1 Pages: 12-25

    • DOI

      10.1002/path.5394

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Differences in <i>Helicobacter pylori</i> and CagA antibody changes after eradication between subjects developing and not developing gastric cancer2019

    • Author(s)
      Kodama M, Okimoto T, Mizukami K, Fukuda K, Ogawa R, Okamoto K, Matsunari O, Kawahara Y, Hirashita Y, Murakami K.
    • Journal Title

      Journal of Clinical Biochemistry and Nutrition

      Volume: 65 Issue: 1 Pages: 71-75

    • DOI

      10.3164/jcbn.19-30

    • NAID

      130007672120

    • ISSN
      0912-0009, 1880-5086
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epitope peptides of Helicobacter pylori CagA antibodies from sera by whole-peptide mapping2019

    • Author(s)
      Shamshul Ansari ; Junko Akada; Yuichi Matsuo; Seiji Shiota; Yoko Kudo; Tadayoshi Okimoto; Kazunari Murakami; Yoshio Yamaoka
    • Journal Title

      J Gastroenterology

      Volume: 54 Issue: 12 Pages: 1039-1051

    • DOI

      10.1007/s00535-019-01584-8

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Invasive intraductal papillary mucinous neoplasms of the pancreas: relationships between mural nodules detected on thin-section contrast-enhanced MDCT and invasive components.2019

    • Author(s)
      Kamei N, Yamada Y, Hijiya N, Takaji R, Kiyonaga M, Hongo N, Ohta M, Hirashita T, Inomata M, Matsumoto S.
    • Journal Title

      Abdom Radiol

      Volume: 44 Issue: 9 Pages: 3139-3147

    • DOI

      10.1007/s00261-019-02084-2

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chronic hypoxia-induced slug promotes invasive behavior of prostate cancer cells by activating expression of ephrin-B12018

    • Author(s)
      Iwasaki K, Ninomiya R, Shin T, Nomura T, Kajiwara T, Hijiya N, Moriyama M, Mimata H, Hamada F
    • Journal Title

      Cancer Science

      Volume: 109 Issue: 10 Pages: 3159-3170

    • DOI

      10.1111/cas.13754

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Complete Sequences of the Human T-Cell Leukemia Virus Type 1 Proviral Genomes from Newly Established Adult T-Cell Leukemia Cell Lines in Oita Prefecture, Japan2018

    • Author(s)
      Fukumoto T, Ikebe E, Ogata M, Kohno K, Kuramitsu M, Sato Y, Fife N, Matsumoto T, Yahiro T, Ikeda M, Kusano S, Okayama A, Hori M, Hijiya N, Tsukamoto Y, Hirashita Y, Moriyama M, Ahmed K, Hasegawa H, Nishizono A, Saito M, Iha H
    • Journal Title

      Genome Announcements

      Volume: 6 Issue: 25

    • DOI

      10.1128/genomea.00090-18

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association of fibrotic remodeling and cytokines/chemokines content in epicardial adipose tissue with atrial myocardial fibrosis in patients with atrial fibrillation2018

    • Author(s)
      Abe I, Teshima Y, Kondo H, Kaku H, Kira S, Ikebe Y, Saito S, Fukui A, Shinohara T, Yufu K, Nakagawa M, Hijiya N, Moriyama M, Shimada T, Miyamoto S, Takahashi N
    • Journal Title

      Heart Rhythm

      Volume: 15 Issue: 11 Pages: 1717-1727

    • DOI

      10.1016/j.hrthm.2018.06.025

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Endoscopic and Immunohistochemical Characteristics of Gastric Cancer with versus without <b><i>Helicobacter Pylori</i></b> Eradication2018

    • Author(s)
      Kodama Masaaki、Okimoto Tadayoshi、Mizukami Kazuhiro、Abe Hisanori、Ogawa Ryo、Okamoto Kazuhisa、Shuto Mitsutaka、Matsunari Osamu、Hirashita Yuka、Sato Ryugo、Abe Takashi、Nagai Takayuki、Arita Tsuyoshi、Murakami Kazunari
    • Journal Title

      Digestion

      Volume: 97 Issue: 4 Pages: 288-297

    • DOI

      10.1159/000485504

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] No transformation of a fundic gland polyp with dysplasia into invasive carcinoma after 14 years of follow-up in a proton pump inhibitor-treated patient: A case report2018

    • Author(s)
      Fukuda Masahide、Ishigaki Hirohito、Ban Hiromitsu、Sugimoto Mitsushige、Tanaka Eri、Yonemaru Junpei、Kuroe Shinobu、Namura Tomo、Matsubara Akiko、Moritani Suzuko、Murakami Kazunari、Andoh Akira、Kushima Ryoji
    • Journal Title

      Pathology International

      Volume: 68 Issue: 12 Pages: 706-711

    • DOI

      10.1111/pin.12739

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A temporal shift of the evolutionary principle shaping intratumor heterogeneity in colorectal cancer2018

    • Author(s)
      Saito T, Niida A, Uchi R, Hirata H, Kodama M, Okimoto T, Murakami K, Suzuki Y, Ogawa S, Miyano S, Mimori K, et al.
    • Journal Title

      Nature Communications

      Volume: 9 Issue: 1 Pages: 2884-2884

    • DOI

      10.1038/s41467-018-05226-0

    • NAID

      120006551763

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Downregulation of dual-specificity phosphatase 4 enhances cell proliferation and invasiveness in colorectal carcinomas2017

    • Author(s)
      Ichimanda Michihiro、Hijiya Naoki、Tsukamoto Yoshiyuki、Uchida Tomohisa、Nakada Chisato、Akagi Tomonori、Etoh Tsuyoshi、Iha Hidekatsu、Inomata Masafumi、Takekawa Mutsuhiro、Moriyama Masatsugu
    • Journal Title

      Cancer Sci

      Volume: 109 Issue: 1 Pages: 250-258

    • DOI

      10.1111/cas.13444

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Periportal lymphatic system on post-hepatobiliary phase Gd-EOB-DTPA-enhanced MR imaging in normal subjects and patients with chronic hepatitis C2017

    • Author(s)
      Yamada Yasunari、Matsumoto Shunro、Mori Hiromu、Takaji Ryo、Kiyonaga Maki、Hijiya Naoki、Tanoue Rika、Tomonari Kenichiro、Tanoue Shuichi、Hongo Norio、Ohta Masayuki、Seike Masataka、Inomata Masafumi、Murakami Kazunari、Moriyama Masatsugu
    • Journal Title

      Abdom Radiol (NY)

      Volume: 42 Issue: 10 Pages: 2410-2419

    • DOI

      10.1007/s00261-017-1155-y

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Rupture of small cystic pancreatic neuroendocrine tumor with many microtumors2017

    • Author(s)
      Sagami Ryota、Nishikiori Hidefumi、Ikuyama Shoichiro、Murakami Kazunari
    • Journal Title

      World J Gastroenterol.

      Volume: 23 Issue: 37 Pages: 6911-6919

    • DOI

      10.3748/wjg.v23.i37.6911

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Marked improvement in gastric involvement in Beh?et’s disease with adalimumab treatment2017

    • Author(s)
      Sonoda Akira、Ogawa Ryo、Mizukami Kazuhiro、Fukuda Kensuke、Shuto Mitsutaka、Okamoto Kazuhisa、Matsunari Osamu、Okimoto Tadayoshi、Murakami Kazunari
    • Journal Title

      Turk J Gastroenterol.

      Volume: 28 Issue: 5 Pages: 405-407

    • DOI

      10.5152/tjg.2017.17230

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Objective Endoscopic Analysis with Linked Color Imaging regarding Gastric Mucosal Atrophy: A Pilot Study2017

    • Author(s)
      Mizukami Kazuhiro、Ogawa Ryo、Okamoto Kazuhisa、Shuto Mitsutaka、Fukuda Kensuke、Sonoda Akira、Matsunari Osamu、Hirashita Yuka、Okimoto Tadayoshi、Kodama Masaaki、Murakami Kazunari
    • Journal Title

      Gastroenterol Res Pract.

      Volume: 2017 Pages: 1-7

    • DOI

      10.1155/2017/5054237

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Usefulness of semiquantitative PCR-Invader assay for selecting candidates for daclatasvir plus asunaprevir combination therapy among patients with hepatitis C virus genotype 1b2017

    • Author(s)
      Honda Koichi、Seike Masataka、Oribe Junya、Endo Mizuki、Arakawa Mie、Tokoro Masanori、Iwao Masao、Mori Tetsu、Nishimura Junko、Takahashi Yukou、Omori Kaoru、Yamashita Tsutomu、Muro Toyokichi、Murakami Kazunari
    • Journal Title

      Hepatol Res.

      Volume: 48 Issue: 4 Pages: 255-263

    • DOI

      10.1111/hepr.12994

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Deep Ulcers in the Ileum Associated with Mycophenolate Mofetil2017

    • Author(s)
      Sonoda Akira、Wada Kurato、Mizukami Kazuhiro、Fukuda Kensuke、Shuto Mitsutaka、Okamoto Kazuhisa、Ogawa Ryo、Okimoto Tadayoshi、Murakami Kazunari
    • Journal Title

      Internal Medicine

      Volume: 56 Issue: 21 Pages: 2883-2886

    • DOI

      10.2169/internalmedicine.8815-17

    • NAID

      130006191944

    • ISSN
      0918-2918, 1349-7235
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association between Gastric Cancer Risk and Serum Helicobacter pylori Antibody Titers2017

    • Author(s)
      Shuto Mitsutaka、Fujioka Toshio、Matsunari Osamu、Okamoto Kazuhisa、Mizukami Kazuhiro、Okimoto Tadayoshi、Kodama Masaaki、Takigami Shigeru、Seguchi Chuichi、Nonaka Yoshihito、Sato Ryugo、Yamaoka Yoshio、Murakami Kazunari
    • Journal Title

      Gastroenterol Res Pract.

      Volume: 2017 Pages: 1-6

    • DOI

      10.1155/2017/1286198

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gastric lanthanosis (lanthanum deposition) in dialysis patients treated with lanthanum carbonate2017

    • Author(s)
      Shitomi Yuki、Nishida Haruto、Kusaba Takahiro、Daa Tsutomu、Yano Shinji、Arakane Motoki、Kondo Yoshiyuki、Nagai Takayuki、Abe Takashi、Gamachi Ayako、Murakami Kazunari、Etoh Tsuyoshi、Shiraishi Norio、Inomata Masafumi、Yokoyama Shigeo
    • Journal Title

      Pathol Int.

      Volume: 67 Issue: 8 Pages: 389-397

    • DOI

      10.1111/pin.12558

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chest High-resolution Computed Tomography Findings in 601 Patients with Inflammatory Bowel Diseases2017

    • Author(s)
      Sato Haruka、Okada Fumito、Matsumoto Shunro、Sonoda Akira、Murakami Kazunari、Ishida Tetsuya、Takaki Hajime、Wakisaka Masaki、Tokuyama Kouhei、Shimada Ryuichi、Mori Hiromu
    • Journal Title

      Acad Radiol.

      Volume: 25 Issue: 4 Pages: 407-414

    • DOI

      10.1016/j.acra.2017.10.010

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] 胃癌とピロリ菌感染について2019

    • Author(s)
      村上和成
    • Organizer
      第15回日本消化管学会総会学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Differences of Gastric Cancer Characteristics Between With and Without Helicobacter pylori Eradication2019

    • Author(s)
      KodamaM, Okimoto T, Mizukami K, Ogawa R, Okamoto K, Matsunari O, Fukuda K, Murakami K.
    • Organizer
      ACG Annual Scientific Meeting & Postgraduate Course 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Long-term follow up of endoscopic/histological atrophy, serum pepsinogen level and helicobacter pylori antibody level after eradication2019

    • Author(s)
      Okimoto T, Ogawa R, Ozaka S, Matsunari O, Fukuda K, Okamoto K, Mizukami K, Kodama M, Murakami K
    • Organizer
      Digestive Disease Week 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] RAS/BRAF変異型進行大腸癌における早期反応性マーカーを用いたtrametinib感受性予測法の検討2019

    • Author(s)
      平下有香、水上一弘、沖本忠義、兒玉雅明、白下英史、猪俣雅史、守山 正胤、村上和成
    • Organizer
      JDDW2019・第27回日本消化器関連学会週間
    • Related Report
      2019 Annual Research Report
  • [Presentation] 大腸癌におけるDUSP4発現変動の意義2018

    • Author(s)
      一万田 充洋, 泥谷 直樹, 赤木 智徳, 白下 英史, 衛藤 剛, 猪股 雅史, 守山 正胤
    • Organizer
      第118回日本外科学会定期学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 大腸癌におけるDUSP4発現低下は増殖能および浸潤能を亢進させる2018

    • Author(s)
      泥谷 直樹, 一万田 充洋, 塚本 善之, 内田 智久, 中田 知里, 赤木 智徳, 衛藤 剛, 伊波 英克, 猪股 雅史, 守山 正胤
    • Organizer
      第107回日本病理学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Changes of the Gastric Mucosal Glycosylation in H. pylori Infection and Before/After H. pylori Eradication Using Lectin Microarray Analysis2018

    • Author(s)
      Okimoto T, Ogawa R, Ozaka S, Matsunari O, Fukuda K, Okamoto K, Mizukami K, Kodama M, Murakami K
    • Organizer
      ACG Annual Scientific Meeting & Postgraduate Course 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Evaluation of a new Latex agglutination immunoturbidimetry kit, H. pylori-Latex ”SEIKEN”, for the detection of anti-H.pylori antibody in the blood2018

    • Author(s)
      Kodama M, Okimoto T, Mizukami K, Ogawa R, Okamoto K, Fukuda K, Matsunari O, Murakami K
    • Organizer
      ACG Annual Scientific Meeting & Postgraduate Course 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 大腸癌におけるDUSP4発現低下は増殖能・浸潤能に関与する2017

    • Author(s)
      一万田 充洋, 泥谷 直樹, 塚本 善之, 中田 知里, 衛藤 剛, 伊波 英克, 猪股 雅史, 守山 正胤
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 中年男性において破裂を契機に発見された膵粘液性嚢胞性腫瘍の一例2017

    • Author(s)
      清永 麻紀, 山田 康成, 松本 俊郎, 高司 亮, 森 宣, 矢田 一宏, 太田 正之, 猪股 雅史, 泥谷 直樹, 守山 正胤
    • Organizer
      第53回日本医学放射線学会秋季臨床大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Helicobacter pylori Diagnosis, Eradication, and Gastric cancer risk assessment in Japan2017

    • Author(s)
      Murakami Kazunari
    • Organizer
      KSLM 2017 Spring Symposium
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] The availability of Linked Color Imaging, which is a new image-enhanced endoscopy can discriminate the astric mucosal status, especially gastric mucosal atrophic borders2017

    • Author(s)
      Mizukami K, Matsunari O, Ogawa R, Okimoto T, Kodama M, Murakami K
    • Organizer
      Digestive Disease Week 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2021-02-19  

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