Histologial diversity and T-UCR mechansm of gastrointestinal cancer, and their application to clinical practice

2018 Fiscal Year Annual Research Report

• Project/Area Number: 16K08691
• Research Institution: Hiroshima University
• Principal Investigator: 仙谷 和弘 広島大学, 医歯薬保健学研究科(医), 講師 (30508164)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: T-UCR

Outline of Annual Research Achievements

癌における転写超保存領域T-UCRの意義を明らかにするため、昨年度の前立腺癌におけるUc.160+の解析に引き続き、最終年度である本年度は膀胱癌と腎細胞癌におけるUc.63+とUc.416+Aの意義に関する解析を行った。定量的RT-PCR法による検討ではUc.63+は尿路上皮癌で高発現しており、その発現増加が増殖能を亢進させること、逆に発現低下がアンドロゲン陽性尿路上皮癌細胞株においてシスプラチン感受性を亢進させることを明らかとした。さらに腎細胞癌で高発現するUc.416+Aを発現低下させると増殖能と遊走能が低下し、さらにmiR-153と負の相関を示すことを明らかとするとともにその発現はE-cadherin, vimentin, snailなどを制御し、予後不良な腎細胞癌におけるEMTに深く関わることを明らかとした。研究期間全体を通じて消化管癌や泌尿器系癌におけるUc.416+A、Uc.160+、UC.63+、UC.416+Aなど様々な超保存領域T-UCRの臨床病理学的解析や生物学的機能解析を行い、ドセタキセルやシスプラチンなどの抗がん剤抵抗性を促進する機構やmiR-153やPTENなどの他分子に及ぼす影響、EMTを誘導する機構などを明らかにした。さらに癌関連分子であるclaspinとRCAN2がいずれも増殖能や浸潤能を高めて胃癌の進展を促進することで予後不良因子として働くこと、癌幹細胞マーカーやAKT, ERK1/2のリン酸化に影響を及ぼすこと、などを明らかにした。

Research Products

• [Journal Article] Molecular carcinogenesis of gastric cancer: Lauren classification, mucin phenotype expression, and cancer stem cells. (2019)
  • Author(s): Oue N, Sentani K, Sakamoto N, Uraoka N, Yasui W.
  • Journal Title: Int J Clin Oncol. Volume: 印刷中 Pages: 印刷中
  • DOI: 10.1007/s10147-019-01443-9
  • Peer Reviewed
• [Journal Article] Deficiency of Stomach-Type Claudin-18 in Mice Induces Gastric Tumor Formation Independent of H. Pylori Infection. (2019)
  • Author(s): Suzuki K, Sentani K, Tanaka H, Yano T, Suzuki K, Oshima M, Yasui W, Tamura A, Tsukita S.
  • Journal Title: Cell Mol Gastroenterol Hepatol. Volume: 印刷中 Pages: 印刷中
  • DOI: 10.1016/j.jcmgh.2019.03.003
  • Peer Reviewed / Open Access
• [Journal Article] Transcribed ultraconserved region Uc.63+ promotes resistance to cisplatin through regulation of androgen receptor signaling in bladder cancer. (2019)
  • Author(s): Sekino Y, Sakamoto N, Ishikawa A, Honma R, Shigematsu Y, Hayashi T, Sentani K, Oue N, Teishima J, Matsubara A, Yasui W.
  • Journal Title: Oncol Rep. Volume: 41 Pages: 3111-3118
  • DOI: 10.3892/or.2019.7039
  • Peer Reviewed
• [Journal Article] KIFC1 Inhibitor CW069 Induces Apoptosis and Reverses Resistance to Docetaxel in Prostate Cancer. (2019)
  • Author(s): Sekino Y, Oue N, Koike Y, Shigematsu Y, Sakamoto N, Sentani K, Teishima J, Shiota M, Matsubara A, Yasui W.
  • Journal Title: J Clin Med. Volume: 印刷中 Pages: 印刷中
  • DOI: 10.3390/jcm8020225
  • Peer Reviewed / Open Access
• [Journal Article] Protocadherin B9 promotes resistance to bicalutamide and is associated with the survival of prostate cancer patients. (2019)
  • Author(s): Sekino Y, Oue N, Mukai S, Shigematsu Y, Goto K, Sakamoto N, Sentani K, Hayashi T, Teishima J, Matsubara A, Yasui W.
  • Journal Title: Prostate. Volume: 79 Pages: 234-242
  • DOI: 10.1002/pros.23728
  • Peer Reviewed
• [Journal Article] Clinicopathological significance of RCAN2 production in gastric carcinoma. (2019)
  • Author(s): Hattori Y, Sentani K, Shinmei S, Oo HZ, Hattori T, Imai T, Sekino Y, Sakamoto N, Oue N, Niitsu H, Hinoi T, Ohdan H, Yasui W.
  • Journal Title: Histopathology. Volume: 74 Pages: 430-442
  • DOI: 10.1111/his.13764
  • Peer Reviewed
• [Journal Article] Clinicopathological significance of claspin overexpression and its association with spheroid formation in gastric cancer. (2019)
  • Author(s): Kobayashi G, Sentani K, Hattori T, Yamamoto Y, Imai T, Sakamoto N, Kuraoka K, Oue N, Sasaki N, Taniyama K, Yasui W.
  • Journal Title: Hum Pathol. Volume: 印刷中 Pages: 印刷中
  • DOI: 10.1016/j.humpath.2018.09.001
  • Peer Reviewed
• [Journal Article] Intramural florid cystic endosalpingiosis of the uterus after menopause. (2018)
  • Author(s): Hattori Y, Sentani K, Matsuoka N, Nakayama H, Hattori T, Kudo Y, Yasui W.
  • Journal Title: Pol J Pathol. Volume: 69 Pages: 321-324
  • Peer Reviewed / Open Access
• [Journal Article] Quiz What is your diagnosis? (2018)
  • Author(s): Hattori Y, Sentani K, Matsuoka N, Nakayama H, Hattori T, Kudo Y, Yasui W.
  • Journal Title: Pol J Pathol. Volume: 69 Pages: 206
  • Peer Reviewed / Open Access
• [Journal Article] Uc.416+A promotes epithelial-to-mesenchymal transition through miR-153 in renal cell carcinoma. (2018)
  • Author(s): Sekino Y, Sakamoto N, Goto K, Honma R, Shigematsu Y, Quoc TP, Sentani K, Oue N, Teishima J, Kawakami F, Karam JA, Sircar K, Matsubara A, Yasui W.
  • Journal Title: BMC Cancer. Volume: 18 Pages: 952
  • DOI: 10.1186/s12885-018-4863-y
  • Peer Reviewed / Open Access
• [Journal Article] TDO2 Overexpression Is Associated with Cancer Stem Cells and Poor Prognosis in Esophageal Squamous Cell Carcinoma. (2018)
  • Author(s): Pham QT, Oue N, Sekino Y, Yamamoto Y, Shigematsu Y, Sakamoto N, Sentani K, Uraoka N, Yasui W.
  • Journal Title: Oncology. Volume: 95 Pages: 297-308
  • DOI: 10.1159/000490725
  • Peer Reviewed
• [Journal Article] Preoperative risk classification using neutrophil-lymphocyte ratio and hydronephrosis for upper tract urothelial carcinoma. (2018)
  • Author(s): Kohada Y, Hayashi T, Goto K, Kobatake K, Abdi H, Honda Y, Sentani K, Inoue S, Teishima J, Awai K, Yasui W, Matsubara A.
  • Journal Title: Jpn J Clin Oncol. Volume: 48 Pages: 841-850
  • DOI: 10.1093/jjco/hyy084
  • Peer Reviewed
• [Journal Article] Tubulocystic renal cell carcinoma: a review of literature focused on radiological findings for differential diagnosis. (2018)
  • Author(s): Honda Y, Nakamura Y, Goto K, Terada H, Sentani K, Yasui W, Sekino Y, Hayashi T, Teishima J, Matsubara A, Akagi M, Fuji T, Baba Y, Iida M, Awai K.
  • Journal Title: Abdom Radiol (NY). Volume: 43 Pages: 1540-1545
  • DOI: 10.1007/s00261-018-1643-8
  • Peer Reviewed
• [Journal Article] Clinicopathological and Prognostic Significance of Epithelial Gremlin1 Expression in Gastric Cancer. (2018)
  • Author(s): Honma R, Sakamoto N, Ishikawa A, Taniyama D, Fukada K, Hattori T, Sentani K, Oue N, Tanabe K, Ohdan H, Yasui W.
  • Journal Title: Anticancer Res. Volume: 38 Pages: 1419-1425
  • Peer Reviewed
• [Journal Article] Association between histological features of epicardial adipose tissue and coronary plaque characteristics on computed tomography angiography. (2018)
  • Author(s): Senoo A, Kitagawa T, Torimaki S, Yamamoto H, Sentani K, Takahashi S, Kubo Y, Yasui W, Sueda T, Kihara Y.
  • Journal Title: Heart Vessels. Volume: 33 Pages: 827-836
  • DOI: 10.1007/s00380-018-1129-1
  • Peer Reviewed
• [Journal Article] An extremely rare case of Epstein-Barr virus-associated gastric carcinoma with differentiation to neuroendocrine carcinoma. (2018)
  • Author(s): Shimizu A, Takahashi T, Kushima R, Sentani K, Yasui W, Matsuno Y.
  • Journal Title: Pathol Int. Volume: 68 Pages: 41-46
  • DOI: 10.1111/pin.12613
  • Peer Reviewed
• [Journal Article] Pseudomesotheliomatous carcinoma of the pleura: an autopsy case of metastasis from a G-CSF-producing anaplastic carcinoma of the pancreas. (2018)
  • Author(s): Hattori Y, Sentani K, Hattori T, Oue N, Yasui W.
  • Journal Title: APMIS. Volume: 126 Pages: 166-170
  • DOI: 10.1111/apm.12789
  • Peer Reviewed
• [Journal Article] Overexpression of the Transmembrane Protein IQGAP3 Is Associated with Poor Survival of Patients with Gastric Cancer. (2018)
  • Author(s): Oue N, Yamamoto Y, Oshima T, Asai R, Ishikawa A, Uraoka N, Sakamoto N, Sentani K, Yasui W.
  • Journal Title: Pathobiology. Volume: 85 Pages: 192-200
  • DOI: 10.1159/000481890
  • Peer Reviewed / Open Access
• [Journal Article] Tumor Necrosis Factor-α Gene Expression in Epicardial Adipose Tissue is Related to Coronary Atherosclerosis Assessed by Computed Tomography. (2018)
  • Author(s): Kitagawa T, Yamamoto H, Hattori T, Sentani K, Takahashi S, Senoo A, Kubo Y, Yasui W, Sueda T, Kihara Y.
  • Journal Title: J Atheroscler Thromb. Volume: 25 Pages: 269-280
  • DOI: 10.5551/jat.41178
  • Peer Reviewed / Open Access
• [Presentation] Retrospective clinicopathologic review of gastric cancer in Rwanda-Friendship collaboration study. (2018)
  • Author(s): Nagai S, Mugenzi P, Sentani K, Ingabire C, Akintije AC, Sugimura H, Yasui W, Rugwizangoga B, Musoni E, Sinayobye JD, Nyst JF, Reuck MD, Muvunyi ZT, Rwamasirabo E, Kalengayi MR
  • Organizer: 第90回日本胃癌学会総会
• [Presentation] 胃癌の組織学的多様性と癌関連分子との相関． (2018)
  • Author(s): 仙谷和弘、今井健晴、服部拓也、服部 結、谷山大樹、石川 洸、坂本直也、大上直秀、安井 弥
  • Organizer: 第107回日本病理学会総会
• [Presentation] Continuous gastric acid leakage due to dysfunctional paracellular-barrier function causes gastric tumor via CXCL5 and Wnt signaling with age. (2018)
  • Author(s): Suzuki K, Sentani K, Tanaka H, Yano T, Suzuki K, Yasui W, Tamura A and Tsukita S
  • Organizer: 第91回日本生化学会大会
• [Presentation] 胃癌の組織学的多様性と特徴的な癌関連遺伝子． (2018)
  • Author(s): 仙谷和弘、今井健晴、服部拓也、服部 結、谷山大樹、石川 洸、勝矢脩嵩、城戸 綾、坂本直也、大上直秀、安井 弥
  • Organizer: 第77回日本癌学会学術総会
• [Presentation] Transcribed ultraconserved region Uc.63+ promotes resistance to docetaxel through regulation of androgen receptor signaling in prostate cancer. (2018)
  • Author(s): Sekino Y, Sakamoto N, Goto K, Honma R, Shigematsu Y, Oue N, Sentani K, Teishima J, Yasui W and Matsubara A
  • Organizer: European Association of Urology Annual Meeting 2018
  • Int'l Joint Research
• [Presentation] Expression analysis of transcribed-ultraconserved regions in cancer stem cell population using colorectal cancer organoids. (2018)
  • Author(s): Honma R, Sakamoto N, Ishikawa A, Taniyama D, Fukada K, Sekino Y, Mukai S, Sentani K, Oue N, Hinoi T, Egi H, Ohdan H and Yasui W
  • Organizer: The 109th Annual Meeting of the American Association for Cancer Research
  • Int'l Joint Research
• [Presentation] Pten haploinsufficiency promotes tumor invasion and carcinogenesis in mouse colon epithelium with Apc deficiency. (2018)
  • Author(s): Sada H, Hinoi T, Niitsu H, Kovhi M, Sakamoto N, Sentani K, Oue N, Yasui W and Ohdan H
  • Organizer: The 109th Annual Meeting of the American Association for Cancer Research
  • Int'l Joint Research
• [Presentation] Uc.416+A promotes epithelial-to-mesenchymal transition through miR-153 in renal cell carcinoma. (2018)
  • Author(s): Sekino Y, Thang PQ, Honma R, Shigematsu Y, Sakamoto N, Sentani K, Oue N, Teishima J, Yasui W and Matsubara A
  • Organizer: The 35th Korea-Japan Urological Congress
  • Int'l Joint Research
• [Remarks] 広島大学大学院医系科学研究科分子病理学
  • URL: https://home.hiroshima-u.ac.jp/byori1/index.html