A novel therapeutic strategy with SIRT1-targeted therapy for musculoskeletal malignancies.

2012 Fiscal Year Final Research Report

• Project/Area Number: 22791378
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Orthopaedic surgery
• Research Institution: Kobe University
• Principal Investigator: KAWAMOTO Teruya 神戸大学, 医学部附属病院, 助教 (30420558)
• Project Period (FY): 2010 – 2012
• Keywords: 骨軟部肉腫 / SIRT1 / 長寿因子 / 抗アポトーシス

Research Abstract

To establish the molecular targeting therapy focused on an anti-aging gene, SIRT1 for human musculoskeletal malignancies, we assessed the expression of SIRT1 in various musculoskeletal tumors, and evaluated the effect of SIRT1 inhibition in human MFH cell lines. SIRT1 highly expressed in tissues from osteosarcomas and MFHs, compared to benign schwannomas, and the inhibition of SIRT1 decreased the cell viability in human MFH cells. Our findings strongly indicate that SIRT1 can be a novel therapeutic target for molecular targeting therapy on human musculoskeletal malignancies, and further studies on the roles of SIRT1 in musculoskeletal malignancies will be needed.

Research Products

• [Journal Article] Transcutaneous application of carbon dioxide (CO2) enhances chemosensitivity by reducing hypoxic conditions in human malignant fibrous histiocytoma (2012)
  • Author(s): Onishi Y, Kawamoto T, Ueha T, Hara H, Fukase N, Toda M, Harada R, Sakai Y, Miwa M, Nishida K, Kurosaka M, Akisue
  • Journal Title: J Cancer Sci Ther Volume: 4 Pages: 174-181
  • Peer Reviewed
• [Journal Article] Transcutaneous application of carbon dioxide (CO(2)) induces mitochondrial apoptosis in human malignant fibrous histiocytoma in vivo (2012)
  • Author(s): Onishi Y, Kawamoto T, Ueha T, Kishimoto K, Hara H, Fukase N, Toda M, Harada R, Minoda M, Sakai Y, Miwa M, Kurosaka M, Akisue T
  • Journal Title: PLoS One Volume: 7 Pages: e49189
  • Peer Reviewed
• [Journal Article] PKD1 negatively regulates cell invasion migration and proliferation ability of human osteosarcoma (2012)
  • Author(s): Onishi Y, Kawamoto T, Kishimoto K, Hara H, Fukase N, Toda M, Harada R, Kurosaka M, Akisue T
  • Journal Title: Int J Oncol Volume: 40(6) Pages: 1839-1848
  • Peer Reviewed
• [Journal Article] Protein kinase Cdelta in tumorigenesis of human malignant fibrous histiocytoma (2011)
  • Author(s): Fukase N, Kawamoto T, Kishimoto K, Hara H, Okada Y, Onishi Y, Toda M, Kurosaka M, Akisue T
  • Journal Title: Oncol Rep Volume: 26(5) Pages: 1221-1226
  • Peer Reviewed
• [Journal Article] Inhibition of induced autophagy increases apoptosis of Nara-H cells (2011)
  • Author(s): Nakamura O, Hitora T, Akisue T, Kawamoto T, Yamagami Y, Yamamoto T
  • Journal Title: Int J Oncol Volume: 39(6) Pages: 1545-1552
  • Peer Reviewed
• [Journal Article] The Effect of Bevacizumab on Tumour Growth of Malignant Fibrous Histiocytoma in an Animal Model (2010)
  • Author(s): Okada Y, Akisue T, Hara H, Kishimoto K, Kawamoto T, Imabori M, Kishimoto S, Fukase N, Onishi Y, Kurosaka M
  • Journal Title: Anticancer Res Volume: 30(9) Pages: 3391-3395
  • Peer Reviewed
• [Presentation] SIRT1阻害による骨軟部肉腫に対する細胞増殖抑制効果 (2011)
  • Author(s): 河本旭哉
  • Organizer: 第84回日本整形外科学会総会
  • Place of Presentation: 東京
  • Year and Date: 2011-05-12
• [Presentation] Inhibition of SIRT1 Decreased Cell Proliferation of MFH Cells (2011)
  • Author(s): Kawamoto T
  • Organizer: The 57th Annual Meeting of the Orthopaedic Research Society
  • Place of Presentation: Long Beach, USA
  • Year and Date: 2011-01-13
• [Presentation] 骨軟部悪性腫瘍における SIRT1 の発現とその阻害による抗腫瘍効果 (2010)
  • Author(s): 河本旭哉
  • Organizer: 第25回日本整形外科学会基礎学術集会
  • Place of Presentation: 京都
  • Year and Date: 2010-10-14