Molecular mechanism of sarcopenia in cancer patients

• Project/Area Number: 16K19310
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General internal medicine(including psychosomatic medicine)
• Research Institution: Gifu University
• Principal Investigator: Nakamura Nobuhiko 岐阜大学, 大学院医学系研究科, その他 (80550087)
• Research Collaborator: NINOMIYA SORANOBU
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: サルコペニア / トリプトファン / 癌

Outline of Final Research Achievements

Our data show for the first time that tryptophan(Trp) deficiency underlies skeletal muscle atrophy in cancer-related sarcopenia, and we have established a direct link between cancer-related sarcopenia and Trp. Given that evaluations of cancer-related sarcopenia are useful for predicting the prognoses of some cancers and decision-making in relation to treatment strategies, we postulate that the serum Trp level might become a valuable biomarker of sarcopenia development and progression. The results from the present study also indicate that targeting the Trp and kynurenine pathway that is mediated by IDO, might be a promising tactic for preventing or treating sarcopenia in patients with cancer.

Academic Significance and Societal Importance of the Research Achievements

本研究による成果により、これまで十分明らかになっていなかった癌患者におけるサルコペニア発症機序の一因を示した。癌患者では発症早期よりアミノ酸バランス異常が起きており、特にトリプトファンの低下が報告されている。このトリプトファン欠乏が骨格筋萎縮を引き起こしていることがわかり、今後サルコペニア発症の予測因子、発症予防、さらには治療ターゲットとして臨床応用されることが期待される。

Research Products

• [Journal Article] Serum concentrations of l-kynurenine predict clinical outcomes of patients with peripheral T-cell lymphoma, not otherwise specified. (2016)
  • Author(s): Shibata Y, Hara T, Matsumoto T, Nakamura N, Nakamura H, Ninomiya S, Kitagawa J, Goto N, Nannya Y, Ito H, Kito Y, Miyazaki T, Takeuchi T, Saito K, Seishima M, Takami T, Moriwaki H, Shimizu M, Tsurumi H.
  • Journal Title: Hematological Oncology Volume: - Issue: 4 Pages: 637-644
  • DOI: 10.1002/hon.2318
  • Peer Reviewed / Open Access
• [Journal Article] Garenoxacin Prophylaxis for Febrile Neutropenia after Chemotherapy in Hematological Malignancies. (2016)
  • Author(s): Nakamura, N. , Hara, T. , Ninomiya, S. , Shibata, Y. , Matsumoto, T. , Nakamura, H. , Kitagawa, J. , Nannya, Y. , Shimizu, M. , Murakami, N. and Tsurumi, H.
  • Journal Title: Open Journal of Internal Medicine Volume: 6 Issue: 04 Pages: 128-138
  • DOI: 10.4236/ojim.2016.64018
  • Peer Reviewed
• [Presentation] Sarcopenia in patients with diffuse large B-cell lymphoma is caused by the deficiency of essential amino acid tryptophan (2018)
  • Author(s): Soranobu Ninomiya, Nobuhiko Nakamura, Yuto Kaneda, Takuro Matsumoto, Hiroshi Nakamura, Junichi Kitagawa, Masahito Shimizu, Takeshi Hara, Hisashi Tsurumi
  • Organizer: 第８０回日本血液学会学術集会
• [Presentation] Benefit of consolidative radiotherapy in patients with limited stage diffuse large B-cell lymphoma in the rituximab era. (2016)
  • Author(s): Nakamura N, Shibata Y, Matsumoto T, Ninomiya S, Kitagawa J, Shimizu M, Hara T, Tsurumi H.
  • Organizer: 58th ASH Annual Meeting and Exposition
  • Place of Presentation: San Diego, USA
  • Int'l Joint Research
• [Remarks] 岐阜血液疾患研究グループ
  • URL: http://seesaawiki.jp/ghsp/