Study on marker and control of cancer sarcopenia

• Project/Area Number: 18K10788
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59010:Rehabilitation science-related
• Research Institution: Nara Medical University
• Principal Investigator: Fujii Kiyomu 奈良県立医科大学, 医学部, 研究員 (60284189)
• Co-Investigator(Kenkyū-buntansha): 國安 弘基 奈良県立医科大学, 医学部, 教授 (00253055) ; 羅 奕 奈良県立医科大学, 医学部, 研究員 (30633797) ; 川原 勲 奈良県立医科大学, 医学部, 研究員 (80524975)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: がん性サルコペニア / HMGB1 / 中鎖脂肪酸 / 炎症性サイトカイン / 悪液質 / 骨格筋萎縮 / オートファジー / ミトコンドリア / がん悪液質 / サイトカイン / TNF-α / Warburg効果 / エネルギー代謝

Outline of Final Research Achievements

In this study, we elucidated the mechanism of HMGB1 inducing sarcopenia in cancer sarcopenia and showed that it is useful as a blood marker for cancer sarcopenia in human patients. Furthermore, we found that HMGB1 was reduced by dietary intervention with medium-chain fatty acids and reduced cancer sarcopenia. For these reasons, measuring blood HMGB1 in cancer patients is effective in predicting and evaluating the degree of cancer sarcopenia. It has been also suggested that control of HMGB1 by dietary intervention leads to prevention and improvement of cancer sarcopenia.

Academic Significance and Societal Importance of the Research Achievements

本研究で示唆されたHMGB1によるがん性サルコペニアの予測・評価はがん性サルコペニアを簡便に評価・治療することを可能にする。さらに、中鎖脂肪酸という栄養成分を用いた食事介入がHMGB1を制御できることは、簡便かつ低価格ながん性サルコペニアの予防・改善をもたらす。今後の臨床応用が期待される。

Research Products

• [Int'l Joint Research] 南通大学(中国)
• [Int'l Joint Research] Nantong University(中国)
• [Int'l Joint Research] 南通大学(中国)
• [Journal Article] Evaluation of cancer-derived myocardial impairments using a mouse model (2020)
  • Author(s): Miyagawa Yoshihiro、Nukaga Shota、Mori Takuya、Fujiwara-Tani Rina、Fujii Kiyomu、Mori Shiori、Goto Kei、Kishi Shingo、Sasaki Takamitsu、Nakashima Chie、Ohmori Hitoshi、Kawahara Isao、Luo Yi、Kuniyasu Hiroki
  • Journal Title: Oncotarget Volume: 11 Issue: 41 Pages: 3712-3722
  • DOI: 10.18632/oncotarget.27759
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Combined administration of lauric acid and glucose improved cancer‐derived cardiac atrophy in a mouse cachexia model (2020)
  • Author(s): Nukaga Shota、Mori Takuya、Miyagawa Yoshihiro、Fujiwara‐Tani Rina、Sasaki Takamitsu、Fujii Kiyomu、Mori Shiori、Goto Kei、Kishi Shingo、Nakashima Chie、Ohmori Hitoshi、Kawahara Isao、Luo Yi、Kuniyasu Hiroki
  • Journal Title: Cancer Science Volume: 111 Issue: 12 Pages: 4605-4615
  • DOI: 10.1111/cas.14656
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Diabetes mellitus is associated with liver metastasis of colorectal cancer through production of biglycan-rich cancer stroma (2020)
  • Author(s): Fujiwara-Tani Rina、Sasaki Takamitsu、Fujii Kiyomu、Luo Yi、Mori Takuya、Kishi Shingo、Mori Shiori、Matsushima-Otsuka Sayako、Nishiguchi Yukiko、Goto Kei、Kawahara Isao、Kondoh Masuo、Sho Masayuki、Kuniyasu Hiroki
  • Journal Title: Oncotarget Volume: 11 Issue: 31 Pages: 2982-2994
  • DOI: 10.18632/oncotarget.27674
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Malic enzyme 1 is associated with tumor budding in oral squamous cell carcinomas. (2020)
  • Author(s): Nakashima C, Kirita T, Yamamoto K, Mori S, Luo Y, Sasaki T, Fujii K, Ohmori H, Kawahara I, Mori T, Goto K, Kishi S, Fujiwara-Tani R, Kuniyasu H
  • Journal Title: Int J Mol Sci Volume: 21 Issue: 19 Pages: 7149-7149
  • DOI: 10.3390/ijms21197149
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Role of Nuclear Claudin-4 in Renal Cell Carcinoma (2020)
  • Author(s): Owari Takuya、Sasaki Takamitsu、Fujii Kiyomu、Fujiwara-Tani Rina、Kishi Shingo、Mori Shiori、Mori Takuya、Goto Kei、Kawahara Isao、Nakai Yasushi、Miyake Makito、Luo Yi、Tanaka Nobumichi、Kondoh Masuo、Fujimoto Kiyohide、Kuniyasu Hiroki
  • Journal Title: International Journal of Molecular Sciences Volume: 21 Issue: 21 Pages: 8340-8340
  • DOI: 10.3390/ijms21218340
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Giving combined medium‐chain fatty acids and glucose protects against cancer‐associated skeletal muscle atrophy (2019)
  • Author(s): Mori Takuya、Ohmori Hitoshi、Luo Yi、Mori Shiori、Miyagawa Yoshihiro、Nukaga Shota、Goto Kei、Fujiwara‐Tani Rina、Kishi Shingo、Sasaki Takamitsu、Fujii Kiyomu、Kawahara Isao、Kuniyasu Hiroki
  • Journal Title: Cancer Science Volume: 110 Issue: 10 Pages: 3391-3399
  • DOI: 10.1111/cas.14170
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Concurrent Expression of CD47 and CD44 in Colorectal Cancer Promotes Malignancy (2019)
  • Author(s): Fujiwara-Tani Rina、Sasaki Takamitsu、Ohmori Hitoshi、Luo Yi、Goto Kei、Nishiguchi Yukiko、Mori Shiori、Nakashima Chie、Mori Takuya、Miyagawa Yoshihiro、Kawahara Isao、Fujii Kiyomu、Kishi Shingo、Tatsumoto Naokuni、Kuniyasu Hiroki
  • Journal Title: Pathobiology Volume: 86 Issue: 4 Pages: 182-189
  • DOI: 10.1159/000496027
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Concurrent expression of CD47 and CD44 in colorectal cancer promotes malignancy (2019)
  • Author(s): Fujiwara-Tani R, Sasaki T, Ohmori H, Luo Y, Goto K, Nishiguchi Y, Mori S, Nakashima C, Mori T, Miyagawa Y, Kawahara I, Fujii K, Kishi S, Tatsumoto N, Kuniyasu H
  • Journal Title: Pathobiology Volume: in press
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Intermittent calorie restriction enhances epithelial- mesenchymal transition through alteration of energy metabolism in a mouse tumor model. (2018)
  • Author(s): Kusuoka O, Fujiwara-Tani R, Nakashima C, Fujii K, Ohmori H, Mori T, Kishi S, Miyagawa Y, Goto K, Kawahara I, Kuniyasu H
  • Journal Title: Int J Oncol Volume: 52 Pages: 413-423
  • DOI: 10.3892/ijo.2017.4229
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Expression of cytosolic malic enzyme (ME1) is associated with disease progression in human oral squamous cell carcinoma (2018)
  • Author(s): Nakashima C, Yamamoto K, Fujiwara-Tani R, Luo Y, Matsushima S, Fujii K, Ohmori H, Sasahira T, Sasaki T, Kitadai Y, Kirita T, Kuniyasu H
  • Journal Title: Cancer Sci Volume: in press Issue: 6 Pages: 2036-2045
  • DOI: 10.1111/cas.13594
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Pro-metastatic signaling of elaidic acid, a trans fatty acid, is associated with lipid rafts. (2018)
  • Author(s): Kishi S, Fujiwara-Tani R, Luo Y, Kawahara I, Goto K, Fujii K, Ohmori H, Nakashima C, Sasaki T, Kuniyasu H
  • Journal Title: Oncol Lett Volume: 15 Pages: 4423-4426
  • DOI: 10.3892/ol.2018.7817
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Expression of the long-chain fatty acid receptor GPR40 was associated with cancer progression in colorectal cancer. (2018)
  • Author(s): Nakashima C, Kishi S, Fujiwara-Tani R, Luo Y, Kawahara I, Goto K, Fujii K, Ohmori H, Kuniyasu H*
  • Journal Title: Oncol Lett Volume: 15 Pages: 8641-8646
  • DOI: 10.3892/ol.2018.8383
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Significance of intranuclear angiotensin-II type 2 receptor in oral squamous cell carcinoma (2018)
  • Author(s): Matsushima-Otsuka S, Fujiwara-Tani R, Sasaki T, Ohmori H Nakashima C, Kishi S, Nishiguchi Y, Fujii K, Luo Y, Kuniyasu H
  • Journal Title: Oncotarget 9(93): , 2018 Volume: 9 Issue: 93 Pages: 36561-36574
  • DOI: 10.18632/oncotarget.26337
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Intake of medium-chain fatty acids induces oxidative stress and to atrophy the myocardium (2018)
  • Author(s): Miyagawa Y, Mori T, Goto K, Fujiwara-Tani R, Kishi S, Sasaki T, Fujii K, Ohmori H, Kawahara I, Kuniyasu H
  • Journal Title: Lipids in Health and Disease Volume: 17 Issue: 1 Pages: 258-258
  • DOI: 10.1186/s12944-018-0908-0
  • Peer Reviewed / Open Access
• [Journal Article] Anti-claudin-4 extracellular domain antibody enhances the antitumoral effects of chemotherapeutic and antibody drugs in colorectal cancer (2018)
  • Author(s): Fujiwara-Tani R, Sasaki T, Luo Y, Ohmori H, Nishiguchi Y, Kishi S, Mori S, Goto K, Kondoh M, Kuniyasu H*
  • Journal Title: Oncotarget Volume: 9 Issue: 100 Pages: 37367-37378
  • DOI: 10.18632/oncotarget.26427
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 糖質と中鎖脂肪酸の併用経口投与は悪液質における癌関連骨格筋萎縮を抑制する (2020)
  • Author(s): 森 拓也、 大森 斉、川原 勲、宮川良博、後藤 桂、額賀翔太、森 汐莉、岸 真五、谷 里奈、國安弘基
  • Organizer: 第109回日本病理学会総会
• [Presentation] がん悪液質における心筋ミトコンドリア機能障害に対する中鎖脂肪酸の影響 (2020)
  • Author(s): 額賀翔太、大森 斉、森 拓也、宮川良博、後藤 桂、川原 勲、谷 里奈、岸 真吾、森 汐莉、國安弘基
  • Organizer: 第109回日本病理学会総会
• [Presentation] Effects of medium-chain fatty acids on cancer-derived myocardial atrophy (2020)
  • Author(s): Nukaga S, Mori T, Luo Y, Kawahara I, Miyagawa Y, Goto K, Fujiwara-Tani R, Kishi S, Mori S, Ohmori H, Kuniyasu H
  • Organizer: 79th Annual Meeting of Japanese Association for Cancer
• [Presentation] Parameters for cancer-induced sarcopenia in patients autopsied after death from colorectal cancer (2020)
  • Author(s): Mori T, Ohmori H, Luo Y, Kawahara I, Nukaga S, Miyagawa Y, Goto K, Kuniyasu H
  • Organizer: 79th Annual Meeting of Japanese Association for Cancer
• [Presentation] Effect of lauric acid intake on skeletal muscle atrophy caused by 5-FU treatment in CT26 colon cancer mouse model. (2020)
  • Author(s): Kawahara I, Mori T, Luo Y, Nukaga S, Miyagawa Y, Goto K, Ohmori H, Kuniyasu H
  • Organizer: 79th Annual Meeting of Japanese Association for Cancer
• [Presentation] がん悪液質は心筋細胞内の酸化ストレスの蓄積、オートファジーを亢進し、細胞の萎縮を誘導する (2019)
  • Author(s): 宮川良博，森 拓也，後藤 桂，川原 勲，藤井 澄、大森 斉、國安弘基
  • Organizer: 第108回日本病理学会総会
• [Remarks] 奈良県立医科大学分子病理学HP
  • URL: http://www.naramed-u.ac.jp/~molepath/