高齢者がん研究

メンバー

リーダー 石渡 俊行
研究員 五味 不二也、野中 敬介
非常勤研究員 進士 誠一、志智 優樹、藤原 正和
非常勤技術員 長谷川 文雄、長谷川 康子

キーワード

老化、細胞老化、高齢者がん、膵臓がん、テロメア、副腎、がん幹細胞、がんの多様性、上皮間葉転換、長鎖非コードRNA、抗がん剤耐性、がん転移、大腸がん、増殖因子受容体、病理学

主な研究

  1. 膵臓がん研究
     ① 膵臓がんの老化誘導療法の開発
     ② 膵臓がんの多様性の解明と、個別化治療の開発
     ③ 膵臓がんの転移機序の解明と、転移抑制療法の開発
  2. テロメア長の研究
     ① 加齢や慢性ストレスと副腎のテロメア長の研究
     ② 慢性ストレスや喫煙が、脳組織のテロメア長に及ぼす影響についての研究
  3. 外科病理学的研究
     ① 膵臓がん、大腸がんなどの臨床病理学的研究

研究紹介

 本グループは膵臓がんを中心とした高齢者がんについての研究と、加齢とともに短縮するテロメアの研究を行なっています。膵臓がんの研究については主に、①がん細胞自身を老化誘導し、老化細胞死誘導薬で除去する研究、②患者さんごとのがん細胞の違いの研究、③がんの転移を抑える研究を行っています。また、老化や老年性疾患との関係が注目されているテロメア研究を進め、老化や生活習慣、ストレスとテロメア長の関係を明らかにし、健康寿命を伸ばすことを目指しています。

1.膵臓がんの早期発見と、新たな治療法開発

 膵臓がんは高齢者に多く発症するがんで、近年、日本だけでなく世界的にも急激に増加しています。膵臓がんは早期に発見することが難しく、手術後に再発することも多い予後が悪い難治性がんです。
 最近、私達は膵臓がん細胞を立体的に培養(3次元培養)することにより、患者さんごとにがん細胞の性質が極めて異なっており、有効な抗がん剤にも違いがあることを発見しました(Top 100 downloaded articles in cancer, 2021: Scientific Reports誌)。また、同じ人の膵臓がんの塊の中にもさまざまな種類のがん細胞が混ざっており、「がん幹細胞」と呼ばれる、特に悪性のがん細胞が少数含まれていることが知られています。がん幹細胞は自分と同じがん細胞を作る自己複製能と、さまざまながん細胞を作る多分化能を持っていると考えられています。がん幹細胞は通常は増殖していないため、増殖している細胞に有効な抗がん剤や放射線治療が効きにくく、治療後に生き残り再発を引き起こす可能性があります。またがん幹細胞は動きやすく、周囲の血管やリンパ管に侵入して他の臓器に運ばれ転移を起こすと考えられます。現在、私達は患者さんごとのがん細胞の特徴を解析するとともに、がん幹細胞の研究を行ない個々の患者さんに適した治療法の開発を目指しています。
 正常の細胞は強いDNA傷害などによって増殖が停止し、SASP因子という炎症性タンパク質などを多量に分泌する老化細胞に変化することが知られています。私達は最近、膵臓がん細胞が過剰に発現しているFGFR4という細胞膜にある増殖因子受容体の働きを阻害することで、膵臓がん細胞自身に細胞老化がおこることを発見しました。膵臓がん細胞の老化誘導療法の開発に向けて研究を続けています。

2.老化、老年性疾患とテロメアとの関係の解析

 テロメアは染色体末端に存在し、染色体を保護する役割を担っており、細胞分裂を重ねるとともに短縮します。細胞の分裂に伴ってテロメアが短縮すると染色体が不安定となり、細胞分裂の停止、細胞の不死化やがん化など様々な異常を起こしやすくなります。現在までに、加齢やアルコール過飲などの生活習慣に伴って短縮したテロメアにより引き起こされる染色体の不安定性が、がんの発生と密接な関係があることを解明しました。
 現在は、①加齢や慢性ストレスに伴う、副腎と脳組織の細胞のテロメア長の変化、②喫煙に伴う脳組織のテロメア長変化などの研究を行なっています。将来的には、認知症と脳テロメア長の関係を明らかにしたいと考えています。

3.外科病理学的研究

 高齢者がん研究テーマの医師は本センターの病理診断科の病理診断業務と剖検に参加し、直接、患者さんに貢献しています。診断や剖検を通じて得られた知識と技術を基盤として、膵臓がんや大腸がん、獣医学領域のがんなどについて国内外の多数の大学・研究所と共同で臨床病理学的な研究を進めています。
 私達の研究成果を多くの皆様にも知って頂く目的で、高齢者がん研究テーマの独自のウェブサイトを開設していますので是非ご覧ください。

主要文献

2023年

  1. Shichi Y, Gomi F, Hasegawa Y, Shinji S, Takahashi K, Ishiwata T. Artificial intelligence-based analysis of time-lapse images of sphere formation and process of plate adhesion and spread of pancreatic cancer cells. Front. Cell Dev. Biol., 17 Nov. 2023.
  2. Nonaka K, Takubo K, Aida J, Watai Y, Komatsu A, Gomi F, Shichi Y, Yamazaki Y, Ishiwata T, Sasano H, Arai T. Accelerated telomere shortening in adrenal zona reticularis in patients with prolonged critical illness. Front Endocrinol (Lausanne). 2023 Sep 4:14:1244553.
  3. Doshida Y, Hashimoto S, Iwabuchi S, Takino Y, Ishiwata T, Aigaki T, Ishigami A. Single-cell RNA sequencing to detect age-associated genes that identify senescent cells in the liver of aged mice. Scientific Reports. (2023) 13: 14186.  
  4. 保坂祥介, 小野敏嗣, 中里徹矢, 小松明子, 野中敬介, 石渡俊行, 新井冨生. 加齢による肝胆膵の生理的変化. 肝胆膵 86 (6) 679-683, 2023.
  5. Michishita M, Ochiai K, Nakahira R, Azakami D, Machida Y, Nagashima T, Nakagawa T, Ishiwata T. mTOR pathway as a potential therapeutic target for cancer stem cells in canine mammary carcinoma. Front Oncol. 2023 Jan 27:13:1100602
  6. Arai T, Komatsu A, Kanazawa N, Nonaka K, Ishiwata T. Clinicopathological and molecular characteristics of gastric papillary adenocarcinoma. Pathology International, 2023 Aug;73(8):358-366.

2022年

  1. Sasaki N, Shinji S, Shichi Y, Ishiwata T, Arai T, Yamada T, Takahashi G, Ohta R, Sonoda H, Matsuda A, Iwai T, Takeda K, Yonaga K, Ueda K, Kuriyama Sho, Miyasaka T, Yoshida H. TGF-β1 increases cellular invasion of colorectal neuroendocrine carcinoma cell line through partial epithelial-mesenchymal transition. Biochemistry and Biophysics Reports. 2022 Mar 1;30:101239.
  2. Shinji S, Shichi Y, Yamada T, Takahashi G, Ohta R, Sonoda H, Matsuda A, Yonaga K, Iwai T, Takeda K, Ueda K, Kuriyama S, Miyasaka T, Ueda Y, Sasaki N, Takahashi K, Ohashi R, Ishiwata T, Arai T, Yoshida H. Establishment and characterization of a novel anorectal melanoma cell line derived from primary human rectal tumor. J Nippon Med Sch. 2022 Jan 25.
  3. Aida J, Takubo K, Vieth M, Neuhaus H, Fujiwara M, Arai T, Ishiwata T. Telomere lengths in Barrett's esophagus as a precancerous lesion. Esophagus. 2022 Apr;19(2):287-293.
  4. Shichi Y, Gomi F, Ueda Y, Nonaka K, Hasegawa F, Hasegawa Y, Hinata N,Yoshimura H, Yamamoto M, Takahashi K, Arai T, Ishiwata T. Multiple cystic sphereformation from PK-8 cells in three-dimensional culture. Biochem Biophys Rep. 2022 Sep 7;32:101339.
  5. Ueda Y, Miura Y, Tomishige N, Sugimoto N, Murase M, Kawamura G, Sasaki N, Ishiwata T, Ozawa T. Mechanistic insights into cancer drug resistance through optogenetic PI3K signaling hyperactivation. Cell Chem Biol. 2022 Nov 17;29(11):1576-1587.e5.
  6. Sasaki N, Hirano K, Shichi Y, Itakura Y, Ishiwata T, Toyoda M. PRC2-dependent regulation of ganglioside expression during dedifferentiation contributes to the proliferation and migration of vascular smooth muscle cells. Front Cell Dev Biol. 2022 Oct 13;10:1003349.
  7. Miki A, Matsuda Y, Aida J, Watanabe J, Sanada Y, Sakuma Y, Lefor AK, Fukushima N, Sata N, Arai T, Takubo K, Ishiwata T. Telomere Attrition in Intraductal Papillary Mucinous Neoplasms of the Pancreas Associated With Carcinogenesis and Aging. Pancreas. 2022 Jul 1;51(6):678-683.
  8. Ueda Y, Abe M, Ishiwata T, Ozawa T. Sphingomyelin localization in the intestinal crypt surface. Biochem Biophys Res Commun. 2022 Jun 30;611:14-18.
  9. Shichi Y, Gomi F, Sasaki N, Nonaka K, Arai T, Ishiwata T. Epithelial and Mesenchymal Features of Pancreatic Ductal Adenocarcinoma Cell Lines in Two- and Three-Dimensional Cultures. J Pers Med. 2022 May 4;12(5):746.
  10. Sasaki N, Hirano K, Shichi Y, Gomi F, Yoshimura H, Matsushita A, Toyoda M, Ishiwata T. Gp130-Mediated STAT3 Activation Contributes to the Aggressiveness of Pancreatic Cancer through H19 Long Non-Coding RNA Expression. Cancers (Basel). 2022 Apr 19;14(9):2055.
  11. Nonaka K, Kurata M, Tachibana M, Komatsu A, Shichi Y, Gomi F, Ishiwata T, Miyamoto K, Arai T. Chromosomal analysis of clonally related B-cell lymphomas with discordant immunoglobulin light-chain restrictions at different anatomical sites. Pathol Int. 2022 Dec 12.
  12. Itakura Y, Hasegawa Y, Kikkawa Y, Murakami Y, Sugiura K, Nagai Okatani C, Sasaki N, Umemura M, Takahashi Y, Kimura T, Kuno A, Ishiwata T, Toyoda M. Spatiotemporal changes of tissue glycans depending on localization in cardiac aging. Regenerative Therapy 22 (2023) 68-78.

2021年

  1. Minami F, Sasaki N, Shichi Y, Gomi F, Michishita M, Ohkusu-Tsukada K, Toyoda M, Takahashi K, Ishiwata T.  Morphofunctional analysis of human pancreatic cancer cell lines in 2- and 3-dimensional cultures. Sci Rep. 2021 Mar 24;11(1):6775.
  2. Gomi F, Sasaki N, Shichi Y, Minami F, Shinji S, Toyoda M, Ishiwata T. Polyvinyl alcohol increased growth, migration, invasion, and sphere size in the PK-8 pancreatic ductal adenocarcinoma cell line. Heliyon. 2021 Feb 4;7(2):e06182.
  3. Yoshimura H, Moriya M, Yoshida A, Yamamoto M, Machida Y, Ochiai K, Michishita M, Nakagawa T, Matsuda Y, Takahashi K, Kamiya S, Ishiwata T. Involvement of Nestin in the Progression of Canine Mammary Carcinoma. Vet Pathol. 2021 May 31;3009858211018656.
  4. Sasaki N, Toyoda M, Ishiwata T. Gangliosides as signal regulators in cancer. International Journal of Molecular Sciences, 2021, 22 (10), 5076.

2020

  1. Wang T, Matsuda Y, Nonaka K, Kakizaki M, Ishiwata T, Kanazawa N, Uegaki S,Muramatsu M, Sawabe M, Mori S, Tanaka M, Kitagawa M, Arai T. Clinicopathological characteristics of gastric cancer with carbohydrate antigen 19-9 expressionoccurring in elderly individuals: An autopsy study. Pathol Int. 2020Feb;70(2):92-100.
  2. Sasaki N, Gomi F, Hasegawa F, Hirano K, Fujiwara M, Toyoda M, Ishiwata T.Characterization of the metastatic potential of the floating cell component of MIA PaCa-2, a human pancreatic cancer cell line. Biochem Biophys Res Commun. 2020 Feb 19;522(4):881-888.
  3. Aida J, Yokoyama A, Hara S, Ishizaki T, Fujiwara M, Arai T, Ishiwata T, Takubo K. Telomere shortening in the oral epithelium in relation to alcohol intake,alcohol dehydrogenase (ADH-1B), and acetaldehyde dehydrogenase (ALDH-2) genotypes and clinicopathologic features. J Oral Pathol Med. 2020 Jan;49(1):82-90.
  4. 新井 冨生, 井下 尚子, 野中 敬介, 柿崎 元恒, 高熊 将一朗, 小松 明子, 松川 美保, 上垣 佐登子, 金澤 伸郎, 黒岩 厚二郎,相田 順子, 石渡 俊行, 田久保 海誉,近藤 福雄, 馬場 聡.小宮山 明.食道良性腫瘍および腫瘍様病変の病理.胃と腸 55(3) 237-246 2020年3月
  5. 新井 冨生, 井下 尚子, 野中 敬介,相田 順子, 田久保 海誉,石渡 俊行,松川 美保, 上垣 佐登子, 金澤 伸郎, 黒岩 厚二郎.食道類基底細胞癌. 胃と腸 55(4) 380-383 2020年4月
  6. Sasaki N, Gomi F, Yoshimura H, Yamamoto M, Matsuda Y, Michishita M, Hatakeyama H, Kawano Y, Toyoda M, Korc M, Ishiwata T. FGFR4 Inhibitor BLU9931 Attenuates Pancreatic Cancer Cell Proliferation and Invasion While Inducing Senescence: Evidence for Senolytic Therapy Potential in Pancreatic Cancer. Cancers (Basel). 2020 Oct 14;12(10):2976.

2019

  1. Sasaki N, Hirabayashi K, Michishita M, Takahashi K, Hasegawa F, Gomi F,Itakura Y, Nakamura N, Toyoda M, Ishiwata T. Ganglioside GM2, highly expressed in the MIA PaCa-2 pancreatic ductal adenocarcinoma cell line, is correlated with growth, invasion, and advanced stage. Sci Rep. 2019 Dec 18;9(1):19369.
  2. Shinji S, Sasaki N, Yamada T, Koizumi M, Ohta R, Matsuda A, Yokoyama Y,Takahashi G, Hotta M, Hara K, Takeda K, Ueda K, Kuriyama S, Ishiwata T, Ueda Y,Murakami T, Kanazawa Y, Yoshida H. Establishment and characterization of a novel neuroendocrine carcinoma cell line derived from a human ascending colon tumor. Cancer Sci. 2019 Dec;110(12):3708-3717.
  3. Matsuda Y, Fujii Y, Matsukawa M, Ishiwata T, Nishimura M, Arai T.Overexpression of carbohydrate sulfotransferase 15 in pancreatic cancer stroma isassociated with worse prognosis. Oncol Lett. 2019 Oct;18(4):4100-4105.
  4. Matsuda Y, Kimura W, Matsukawa M, Aida J, Takubo K, Ishiwata T, Furukawa T,Mino-Kenudson M, Arai T. Association Between Pancreatic Cystic Lesions and High-grade Intraepithelial Neoplasia and Aging: An Autopsy Study. Pancreas. 2019 Sep;48(8):1079-1085.
  5. Shichi Y, Sasaki N, Michishita M, Hasegawa F, Matsuda Y, Arai T, Gomi F, Aida J, Takubo K, Toyoda M, Yoshimura H, Takahashi K, Ishiwata T. Enhanced morphological and functional differences of pancreatic cancer with epithelial or mesenchymal characteristics in 3D culture. Sci Rep. 2019 Jul 26;9(1):10871.
  6. Michishita M, Saito N, Nozawa S, Furumoto R, Nakagawa T, Sato T, Ochiai K,Azakami D, Katayama K, Nakahira R, Tazaki H, Machida Y, Ishiwata T. Metabolite profiling in sphere-forming cells from canine mammary adenocarcinoma cell lines using gas chromatography-mass spectrometry. J Vet Med Sci. 2019 Sep 3;81(9):1238-1248.
  7. Nonaka K, Aida J, Takubo K, Yamazaki Y, Takakuma S, Kakizaki M, Matsuda Y,Ishikawa N, Ishiwata T, Chong JM, Arai T, Sasano H. Correlation Between Differentiation of Adrenocortical Zones and Telomere Lengths Measured by Q-FISH.J Clin Endocrinol Metab. 2019 Nov 1;104(11):5642-5650.
  8. Nonaka K, Matsuda Y, Kakizaki M, Takakuma S, Hamamatsu A, Sakashita Y, Matsubara T, Murayama S, Ishiwata T, Yamanaka N, Itabashi M, Takei T, Nakajima N,Hasegawa H, Arai T. Acute Liver Failure Associated with Influenza A Virus Infection: an Autopsy Case Report. Jpn J Infect Dis. 2019 Sep 19;72(5):347-349.
  9. Kawata R, Ii T, Hori T, Machida Y, Ochiai K, Azakami D, Ishiwata T,Michishita M. Leydig cell tumor in an Amur tiger (Panthera tigris altaica). J Vet Med Sci. 2019 Feb 9;81(2):186-189.
  10. 新井 冨生, 井下 尚子, 野中 敬介, 柿崎 元恒, 高熊 将一朗, 小松 明子, 相田 順子, 田久保 海誉, 松川 美保, 上垣 佐登子, 金澤 伸郎, 黒岩 厚二郎, 熊谷 洋一, 石田 秀行.特殊な食道腫瘍の臨床病理学的特徴. 胃と腸 54(10) 1338-1348 2019年9月

2018

  1. Yoshimura H, Matsuda Y, Yamamoto M, Michishita M, Takahashi K, Sasaki N, Ishikawa N, Aida J, Takubo K, Arai T, Ishiwata T. Reduced expression of H19 long non-coding RNA inhibits pancreatic cancer metastasis. Lab Invest. 2018 Mar 26. [Epub ahead of print]
  2. Sasaki N, Ishiwata T, Hasegawa F, Michishita M, Kawai H, Matsuda Y, Arai T, Ishikawa N, Aida J, Takubo K, Toyoda M. Stemness and anti-cancer drug resistance in ABCG2 highly expressed pancreatic cancer is induced on 3D-culture condition. Cancer Sci. 2018 Feb 14. [Epub ahead of print]
  3. Ishiwata T, Hasegawa F, Michishita M, Sasaki N, Ishikawa N, Takubo K, Matsuda Y, Arai T, Aida J. Electron microscopic analysis of different cell types in human pancreatic cancer spheres. Oncol Lett. 15:2485-2490, 2018.
  4. Aoki Y, Aida J, Kawano Y, Nakamura KI, Izumiyama-Shimomura N, Ishikawa N, Arai T, Nakamura Y, Taniai N, Uchida E, Takubo K, Ishiwata T. Correction to: Telomere length of gallbladder epithelium is shortened in patients with congenital biliary dilatation: measurement by quantitative fluorescence in situ hybridization. J Gastroenterol. 53: 302-303, 2018.
  5. Matsuda Y, Seki A, Nonaka K, Kakizaki M, Wang T, Aida J, Ishikawa N, Nakano Y, Kaneda D, Takata T, Takahashi-Fujigasaki J, Murayama S, Takubo K, Ishiwata T, Sawabe M, Arai T. Clinicopathological characteristics of distant metastases of adenocarcinoma, squamous cell carcinoma and urothelial carcinoma: An autopsy study of older Japanese patients. Geriatr Gerontol Int.18(2):211-215, 2018.
  6. Ishiwata T. Role of fibroblast growth factor receptor-2 splicing in normal and cancer cells. Frontiers in Bioscience.1; 23: 626-639, 2018.
  7. Yoshimura H, Matsuda Y, Yamamoto M, Kamiya S, Ishiwata T. Expression and role of long non-coding RNA H19 in carcinogenesis. Frontiers in Bioscience. 1; 23: 614-625, 2018.
  8. Hiraishi N, Terai M, Fujiwara M, Aida J, Izumiyama-Shimomura N, Ishikawa N, Tomita K, Matsuda Y, Arai T, Takubo K, Ishiwata T. Quantitative fluorescence in situ hybridization for investigation of telomere length dynamics in the pituitary gland using samples from 128 autopsied patients. Tissue and Cell. (in press)
  9. Ishiwata T, Matsuda Y, Yoshimura H, Sasaki N, Ishiwata S, Ishikawa N, Takubo K, Arai T, Aida J. Pancreatic cancer stem cells: features and detection methods. Pathol Oncol Res. (in press)
  10. Ueda Y, Ishiwata T, Shinji S, Arai T, Matsuda Y, Aida J, Sugimoto N, Okazaki T, Kikuta J, Ishii M, Sato M. In vivo imaging of T cell lymphoma infiltration process at the colon. Sci Rep. 8: 3978, 2018.
  11. Aida J, Ishizaki T, Arai T, Takubo K. Prognostication of superficial Barrett's carcinoma: a Japanese multicenter study. Hum Pathol. 2018 Mar 10. [Epub ahead of print]
  12. Ishiwata T, Matsuda Y, YoshimuraH, SasakiN, IshiwataS, IshikawaN, TakuboK, AraiT, Aida J. Pancreatic cancer stem cells: features and detection methods. Pathol Oncol Res. 2018 Jun 8. doi: 10.1007/s12253-018-0420-x. [Epub ahead of print] Review.
  13. Arai T, Matsuda Y, Aida J, Takubo K, Ishiwata T. Solid-type poorly differentiated adenocarcinoma of the stomach: clinicopathological and molecular characteristics and histogenesis. Gastric Cancer. 2018 Aug 7. doi: 10.1007/s10120-018-0862-6. [Epub ahead of print]
  14. Tomita K, Aida J, Izumiyama-Shimomura N, Nakamura KI, Ishikawa N, Matsuda Y, Arai T, Ishiwata T, Kumasaka T, Takahashi-Fujigasaki J, Hiraishi N, Yamada M, Fujiwara M, Takubo K. Changes in telomere length with aging in human neurons and glial cells revealed by quantitative fluorescence in situ hybridization analysis. Geriatr Gerontol Int. 2018 Aug 10. doi: 10.1111/ggi.13500. [Epub ahead of print]
  15. Aida S, Aida J, Naoi M, Kato M, Tsuura Y, Natsume I, Takubo K. Measurement of telomere length in cells from pleural effusion: Asbestos exposure causes telomere shortening in pleural mesothelial cells. Pathol Int. 2018 Aug 10. doi:10.1111/pin.12710. [Epub ahead of print]
  16. Matsuda Y, Suzuki A, Esaka S, Hamashima Y, Imaizumi M, Kinoshita M, Shirahata H, Kiso Y, Kojima H, Matsukawa M, Fujii Y, Ishikawa N, Aida J, Takubo K, Ishiwata T, Nishimura M, Arai T. Telomere length determined by the fluorescence in situ hybridisation distinguishes malignant and benign cells in cytological specimens. Cytopathology 29: 262-266, 2018.
  17. 石川直, 相田順子, 田久保海誉, 松田陽子, 新井冨生, 石渡俊行. テロメア短縮と老化および高齢者に好発する疾患との関連. 病理と臨床 36(2): 102-109, 2018.
  18. 新井冨生, 松田陽子, 関敦子, 野中敬介, 柿崎元恒, 相田順子, 石川直, 田久保海誉, 石渡俊行. 加齢に伴う局所的な炎症. 病理と臨床 36(2): 123 -127, 2018.
  19. 新井冨生,松田陽子,相田順子,田久保海誉,石渡俊行. 高齢者がんの臨床病理学的特徴. 腫瘍内科 21(2): 212-220, 2018.
  20. Kawata R, Ii T, Hori T, Machida Y, Ochiai K, Azakami D, Ishiwata T, Michishita M. Leydig cell tumor in an Amur tiger (Panthera tigris altaica). J Vet Med Sci.2018 Dec 12. doi: 10.1292/jvms.18-0573. [Epub ahead of print]
  21. Nonaka K, Matsuda Y, Kakizaki M, Takakuma S, Matsubara T, Murayama S, Ishiwata T, Kameyama M, Ogura K, Kobayashi S, Arai T. Occult mucin-producing urothelial-type adenocarcinoma of the prostate with elevated serum levels of carcinoembryonic antigen and carbohydrate antigen 19-9: Report of an autopsy-proven case. Urol Case Rep. 2018 Nov 15;23:6-9. doi:10.1016/j.eucr.2018.11.005. eCollection 2019 Mar.
  22. Matsuda Y, Esaka S, Suzuki A, Hamashima Y, Imaizumi M, Matsukawa M, Fujii Y,Aida J, Takubo K, Ishiwata T, Nishimura M, Arai T. Abnormal immunolabelling of SMAD4 in cell block specimens to distinguish malignant and benign pancreatic cells. Cytopathology. 2018 Nov 12. doi: 10.1111/cyt.12653. [Epub ahead of print]

2017

  1. Kishimoto TE, Yashima S, Nakahira R, Onozawa E, Azakami D, Ochiai K, Ishiwata T, Takahashi K, MichishitaM. Identification of tumour-initiating cells derived from a canine rhabdomyosarcoma cell line. . J Vet Med Sci. 7;79:1155-1162, 2017.
  2. Terabe F, Aikou S, Aida J, Yamamichi N, Kaminishi M, Takubo K, Seto Y, Nomura S. Columnar metaplasia in three types of surgical mouse models of esophageal reflux. Cell Mol Gastroenterol Hepatol. 4; 4: 115-123, 2017.
  3. Michishita M, Katori Y, Sasaki H, Obara R.D., Furumoto R, Kato M, Nakahira R, Yoshimura H, Soeta S, Ishiwata T, Takahashi K. Cutaneous Angiolymphoid Hyperplasia in a Dog. J Comp Pathol. 157: 57-60, 2017.
  4. Matsuda Y, Furukawa T, Yachida S, Nishimura M, Seki A, Nonaka K, Aida J, Takubo K, Ishiwata T, Kimura W, Arai T, Mino-Kenudson M. The Prevalence and Clinicopathological Characteristics of High-Grade Pancreatic Intraepithelial Neoplasia: Autopsy Study Evaluating the Entire Pancreatic Parenchyma. Pancreas: 46:658-664, 2017.
  5. Matsuda Y, Ishiwata T, Yoshimura H, Yamahatsu K, Minamoto T, Arai T. Nestin phosphorylation at threonines 315 and 1299 correlates with proliferation and metastasis of human pancreatic cancer. Cancer Sci: 108(3):354-361, 2017.
  6. 新井冨生、松田陽子、関敦子、野中敬介、柿崎元恒、近藤福雄、相田順子、田久保海誉、石渡俊行.食道上皮性腫瘍に対する免疫組織化学染色 1)食道腫瘍の免疫染色. 胃と腸 52(8):496-504, 2017
  7. Yoshimura H, Yamamoto M, Moriya M, Endo T, Sugiura N, Kato T, Matsuda Y, Ishiwata T, Kajigaya H, Kamiya S. Teratoma of the ovary in a free-ranging Japanese raccoon dog (Nyctereutes procyonoides viverrinus). J Zoo Wildl Med. Mar;48(1):265-268, 2017.
  8. Kumagai Y, Takubo K, Kawada K, Higashi M, Ishiguro T, Sobajima J, Fukuchi M, Ishibashi KI, Mochiki E, Aida J, Kawano T, Ishida H. A newly developed continuous zoom-focus endocytoscope. Endoscopy. Feb;49(2):176-180, 2017
  9. Yokoyama A, Hirata K, Nakamura R, Omori T, Mizukami T, Aida J, Maruyama K, Yokoyama T. Presence of columnar-lined esophagus is negatively associated with the presence of esophageal varices in Japanese alcoholic men. World J Gastroenterol.23(39): 7150-7159, 2017
  10. 新井冨生,松田陽子,関 敦子,野中敬介,柿﨑元恒,近藤福雄,相田順子,田久保海誉,石渡俊行.食道癌生検検体・内視鏡切除標本の病理診断.消化器・肝臓内科 1(4):337-343, 2017
  11. 新井冨生、松田陽子、関敦子、野中敬介、柿崎元恒、相田順子、田久保海誉、石渡俊行. こうすればわかる食道接合部の病理 消化器内視鏡29(9):1643-1651, 2017
  12. Ishimori M, Michishita M, Yoshimura H, Azakami D, Ochiai K, Ishiwata T and Takahashi K. Disseminated histiocytic sarcoma with hemophagocytosis in a rabbit. J Vet Med Sci. 2;79(9):1503-1506, 2017
  13. Hagiwara K, Michishita M, Yoshimura H, Ochiai K, Azakami D, Ishiwata T, Takahashi K. Pancreatic Colloid Carcinoma in an Elderly Cat. J comp Pathol. 157(4):266-269, 2017
  14. 新井冨生,相田順子,田久保海誉.Barrett食道/食道腺癌の病理学的診断.消化器の臨床20(6): 408-412, 2017.

2016

  1. Matsuda Y, Ishiwata T, Yoshimura H, Yamashita S, Ushijima T, Arai T. Systemic Administration of Small Interfering RNA Targeting Human Nestin Inhibits Pancreatic Cancer Cell Proliferation and Metastasis. Pancreas.45(1):93-100, 2016.
  2. Sumiyoshi H, Matsushita A, Nakamura Y, Matsuda Y, Ishiwata T, Naito Z, Uchida E. Suppression of STAT5b in pancreatic cancer cells leads to attenuated gemcitabine chemoresistance, adhesion and invasion. Oncol Rep. 35(6):3216-26, 2016
  3. Tamura Y, Izumiyama-Shimomura N, Kimbara Y, Nakamura K, Ishikawa N, Aida J, Chiba Y, Matsuda Y, Mori S, Arai T, Fujiwara M, Poon SSS, Ishizaki T, Araki A, Takubo K, Ito H. Telomere attrition in beta and alpha cells with age. Age Jun;38(3):61, 2016.
  4. 相田順子、石崎達郎、石渡俊行、田久保海誉、新井冨生. 表在型Barrett食道癌の転移・再発危険因子―第72回食道色素研究会多施設アンケート調査からー. 胃と腸 151(10), 2016
  5. 新井冨生、松田陽子、関敦子、野中敬介、櫻井うらら、相田順子、田久保海誉、石渡俊行. 老人性アミロイドーシスの病理. 病理と臨床 34(5):496-504, 2016
  6. 新井冨生,松田陽子,関 敦子,野中敬介,柿﨑元恒,相田順子,田久保海誉,石渡俊行.髄様癌Medullary carcinoma.病理と臨床 34 (10): 1080-1084, 2016
  7. Ishiwata T. Cancer stem cells and epithelial-mesenchymal transition: Novel therapeutic targets for cancer. Pathol Int.: 66(11):601-608, 2016.
  8. Kumagai Y, Takubo K, Kawada K, Higashi M, Ishiguro T, Sobajima J, Fukuchi M, Ishibashi K, Mochiki E, Aida J, Kawano T, Ishida H. Endocytoscopic observation of various types of esopahgitis. Dis Eso 28: 269-275, 2016.
  9. Ishikawa N, Nakamura K, Izumiyama-Shimomura N, Aida J, Matsuda Y, Arai T, Takubo K. Changes of telomere status with aging: An update. Geriatr Gerontol Int 16 (Suppl.1): 30-42, 2016.
  10. Tamura Y, Takubo K, Aida J, Araki A, Ito H. Telomere attrition and diabetes mellitus. Geriatr Gerontol Int 16 (Suppl.1): 66-74, 2016
  11. Kumondai M, Hosono H, Orikasa K, Arai Y, Arai T, Sugimura H, Ozono S, Sugiyama T, Takayama T, Sasaki T, Hirasawa N, Hiratsuka M. Genetic polymorphisms of CYP2A6 in a case-control study on bladder cancer in Japanese smokers. Biol Pharm Bull 39 (1): 84-9, 2016
  12. Matsuda Y, Ishiwata T, Yachida S, Suzuki A, Hamashima Y, Hamayasu H, Yoshimura H, Honma N, Aida J, Takubo K, Arai T. Clinicopathological features of 15 occult and 178 clinical pancreatic ductal adenocarcinomas in 8339 autopsied elderly patients. Pancreas 45 (2): 234-40, 2016
  13. Hatakeyama H, Yamazaki H, Nakamura K, Izumiyama-Shimomura N, Aida J, Suzuki H, Tsuchida S, Matsuura M, Takubo K, Ishikawa N. Telomere attrition and restoration in the normal teleost Oryzias latipes are linked to growth rate and telomerase activity at each life stage. AGING 8 (1): 62-76, 2016
  14. Matsuda Y, Ishiwata T, Yoshimura H, Yamashita S, Ushijima T, Arai T. Systemic administration of siRNA targeting human nestin inhibits pancreatic cancer cell proliferation and metastasis. Pancreas 45 (1): 93-100, 2016
  15. Arai T, Yanagisawa A, Kondo F, Aida J, Takubo K. Clinicopathologic characteristics of esophageal primary malignant melanoma. Esophagus 13 (1), 17-24, 2016
  16. Matsuda Y, Yoshimura H, Ishiwata T, Sumiyoshi H, Matsushita A, Nakamura Y, Aida J, Uchida E, Takubo K, Arai T. Mitotic index and multipolar mitosis in routine histologic sections as prognostic markers of pancreatic cancers: a clinicopathological study. Pancreatology 16 (1): 127-32, 2016