Aging and Carcinogenesis

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Members

Theme Leader :
Toshiyuki Ishiwata, M.D., Ph.D.
Researcher :
Fujiya Gomi, Ph.D., Keisuke Nonaka, M.D., Ph.D.
Adjunct Researcher :
Seiichi Shinji, M.D., Ph.D., Masakazu Fujiwara, Ph.D., Fumio Hasegawa

Keywords

Aging, Cellular Senescence, Elderly Cancer, Pancreatic Cancer, Telomeres, Adrenal Gland, Cancer Stem Cells, Cancer Diversity, Epithelial-Mesenchymal Transition, Long Non-coding RNA, Anticancer Drug Resistance, Cancer Metastasis, Colon Cancer, Growth Factor Receptors, Pathology

Major Research Titles

Pancreatic Cancer Research:

  1. Development of senolytic therapy for pancreatic cancer
  2. Discovery of morphological and functional characteristics of cancer stem cells
  3. Research on the heterogeneity of pancreatic cancer
  4. Elucidation of the metastasis mechanism

Study of telomere length:

  1. Changes in telomere length in the adrenal glands due to aging and stress
  2. Relationship between dementia, smoking and telomere length of nerve cells

Surgical pathological research:

  1. Clinicopathological research on pancreatic cancer and colorectal cancer.

Profile

This group is conducting research on cancer in the elderly, mainly pancreatic cancer, and research on telomeres that shorten with age. Regarding the research on pancreatic cancer, we are doing (1) senolytic therapy for pancreatic cancer, (2) research on the differences in cancer cells among patients, and (3) cancer stem cells, which play a central role in cancer recurrence and metastasis. We are also conducting telomere research, which is drawing attention for its relationship with aging and geriatric diseases, and aim to clarify the relationship between aging, lifestyle, stress and telomere length, and to extend healthy life expectancy.

References

2023

  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. 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
  5. 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

  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

  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.