Development of novel melanoma therapy targeting SIRT1

• Project/Area Number: 22591228
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Dermatology
• Research Institution: Sapporo Medical University
• Principal Investigator: YAMASITA Tosiharu 札幌医科大学, 医学部, 教授 (50167706)
• Co-Investigator(Kenkyū-buntansha): HORIO Yosiyuki 札幌医科大学, 医学部, 教授 (30181530) ; HIDA Tokimasa 札幌医科大学, 医学部, 助教 (90464487)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 分子腫瘍学 / 色素細胞学 / 悪性黒色腫 / メラノーマ / SIRT1 / B16F1メラノーマ細胞 / 細胞移動 / 転移 / lamellipodium / 悪性黒色腫(メラノーマ) / 悪性黒色腫 SIRT1 / B16F1メラノーマ細胞転移

Research Abstract

SIRT1 was localized in the cytoplasm of melanoma cells and the SIRT1 inhibitor nicotinamide suppressed their migration. SIRT1 was detected with F -actin in the protuberance of the cell membrane and accumulated with PIP-3 and AKT. Nicotinamide inhibited the peritoneal invasion and lymph node metastasis of transplanted B16F1 cells in C57BL mice and extended their life span. These results indicate that SIRT1 inhibition may be applicable for the suppression of metastatic melanoma.

Research Products

• [Journal Article] Mechanism of putative neo-antigen formation from N-propionyl-4-S-cysteaminylphenol, a tyrosinase substrate, in melanoma models (2012)
  • Author(s): Ito S, Nishigaki A, Ishii-Osai Y, Ojika M, Wakamatsu K, Yamashita T, Tamura Y, Ito A, Honda H, Nakayama E, Jimbow K
  • Journal Title: Biochemical Pharmacology Volume: 84 Pages: 646-53
• [Journal Article] T-cell receptor repertoires of tumor-infiltrating lymphocytes after hyperthermia using functionalized magnetite nanoparticles (2012)
  • Author(s): Ito A, Yamaguchi M, Okamoto N, Sanematsu Y,Kawabe Y, Wakamatsu K, Ito S, Honda H, Kobayashi T, Nakayama E, Tamura Y, Okura M, Yamashita T, Jimbow K, Kamihara M
  • Journal Title: Nanomedicine Volume: (epub ahead of print) Issue: 6 Pages: 891-902
  • DOI: 10.2217/nnm.12.142
  • Peer Reviewed
• [Journal Article] Imiquimod Suppresses Propagation of Herpes Simplex Virus 1 by Upregulation of Cystatin A via the Adenosine Receptor A1 Pathway (2012)
  • Author(s): Kan Y, Okabayashi T, Yokota S, Yamamoto S, Fujii N, Yamashita T
  • Journal Title: J Virol 86 Volume: 10338-46 Pages: 10338-46
• [Journal Article] N-propionyl-4-S-cysteaminylphenol induces apoptosis in B16F1 cells and mediates tumor-specific T-cell immune responses in a mouse melanoma model (2012)
  • Author(s): Ishii-Osai Y, Yamashita T, Tamura Y, Sato N, Ito A, Honda H, Wakamatsu K, Ito S, Nakayama E, Okura M, Jimbow K
  • Journal Title: J Dermatol Sci 67 Pages: 51-60
• [Journal Article] Applicability of radiocolloids, blue dye and fluorescent indocyanine green to sentinel node biopsy in melanoma. (2012)
  • Author(s): Uhara H
  • Journal Title: J Dermatol Volume: 39 Pages: 336-338
  • Peer Reviewed
• [Journal Article] Research paper: mechanism of putative neo-antigen formation from N-propionyl-4-S-cysteaminylphenol, a tyrosinase substrate, in melanoma models. (2012)
  • Author(s): Ito S
  • Journal Title: Biochemical Pharmacology Volume: 84 Pages: 646-653
  • Peer Reviewed
• [Journal Article] A novel approach to cancer treatment using structural hybrids of the p53 gene family. (2012)
  • Author(s): Sasaki Y
  • Journal Title: Cancer Gene Therapy Volume: 19 Pages: 749-756
  • Peer Reviewed
• [Journal Article] Imiquimod Suppresses Propagation of Herpes Simplex Virus 1 by Upregulation of Cystatin A via the Adenosine Receptor A1 Pathway. (2012)
  • Author(s): Kan Y
  • Journal Title: J Virol Volume: 86 Pages: 10338-10346
  • Peer Reviewed
• [Journal Article] N-propionyl-4-S-cysteaminylphenol induces apoptosis in B16F1 cells and mediates tumor-specific T-cell immune responses in a mouse melanoma model. (2012)
  • Author(s): Ishii-Osai Y
  • Journal Title: J Dermatol Sci Volume: 67 Pages: 51-60
  • Peer Reviewed
• [Journal Article] Pigmented mammary Paget’s disease mimicking melanoma: report of three cases. (2012)
  • Author(s): Hida T
  • Journal Title: Eur J Dermatol Volume: 22 Pages: 121-124
  • Peer Reviewed
• [Journal Article] Pigmented Mammary Paget's Disease Mimicking Melanoma : Report of Three Cases (2012)
  • Author(s): Hida T, Yamashita T, et al.
  • Journal Title: Eur J Dermatol Volume: 22 Pages: 121-124
  • Peer Reviewed
• [Journal Article] Pigmented Mammary Paget's Disease Mimicking Melanoma : Report of Three Cases (2012)
  • Author(s): Hida T, Yamashita T, et al
  • Journal Title: Eur J Dermatol Volume: 22(1) Pages: 121-124
  • Peer Reviewed
• [Journal Article] Etanercept-induced lichen planus-like eruptions following the lines of Blaschko (2012)
  • Author(s): Utsu M, Yamashita T, et al
  • Journal Title: Eur J Dermatol Volume: (印刷中)(in press)
  • Peer Reviewed
• [Journal Article] Cellular and molecular effects of sirtuins in health and disease (2011)
  • Author(s): Horio Y, Hayashi T, Kuno A, Kunimoto R
  • Journal Title: Clin Sci Volume: 121 Issue: 5 Pages: 191-203
  • DOI: 10.1042/cs20100587
• [Journal Article] Resveratrol ameliorates muscular pathology in the dystrophic mdx mouse (2011)
  • Author(s): Hori SY, Kuno A, Hosoda R, Tanno M, Miura T, Shimamoto K and Horio Y
  • Journal Title: a model for Duchenne muscular dystrophy. J Pharmacol Exp Ther 338 Pages: 784-794
• [Journal Article] Rab7 is a critical mediator in vesicular transport of tyrosinase-related protein 1 in melanocytes (2011)
  • Author(s): Hida T, Sohma H, Kokai Y, Kawakami A, Hirosaki K, Okura M, Tosa N, Yamashita T, Jimbow K
  • Journal Title: J Dermatol 38 Pages: 432-441
• [Journal Article] A case of cystic basal cell carcinoma which shows a homogenous blue/black area under dermatoscopy (2011)
  • Author(s): Yoneta A, Yamashita T, et al
  • Journal Title: J Skin Cancer
  • Peer Reviewed
• [Journal Article] Rab7 is a critical mediator in vesicular transport of tyrosinase-related protein 1 in melanocytes (2011)
  • Author(s): Hida T
  • Journal Title: J Dermatol Volume: 38 Issue: 5 Pages: 432-441
  • DOI: 10.1111/j.1346-8138.2010.01004.x
  • Peer Reviewed
• [Journal Article] Melanoma-targeted chemo-thermo- immuno (CTI) -therapy using N-propionyl-4-S-cysteaminylphenol-magnetite nanoparticles elicits CTL response via heat shock protein-peptide complex release (2010)
  • Author(s): Sato A, Tamura Y, Sato N, Yamashita T, Takada T, Sato M, Osai Y, Okura M, Ono I, Ito A, Honda H, Wakamatsu K, Ito S, Jimbow K
  • Journal Title: Cancer Science 101 Pages: 1939-1946
  • NAID: 10027831209
• [Journal Article] Induction of manganese superoxide dismutase by nuclear translocation and activation of SIRT1 promotes cell survival in chronic heart failure (2010)
  • Author(s): Tanno M, Kuno A, Yano T, Miura T, Hisahara S, Ishikawa S, Shimamoto K, Horio Y
  • Journal Title: J Biol Chem 285 Volume: 285 Issue: 11 Pages: 8375-8382
  • DOI: 10.1074/jbc.m109.090266
• [Journal Article] Protein deacetylase SIRT1 in the cytoplasm promotes nerve growth factor-induced neurite outgrowth in PC12 cells (2010)
  • Author(s): Sugino T, Maruyama M, Tanno M, Kuno A, Houkin K, Horio Y
  • Journal Title: FEBS Lett 584 Volume: 584 Issue: 13 Pages: 2821-2826
  • DOI: 10.1016/j.febslet.2010.04.063
• [Journal Article] Increased caspase-2 activity is associated with induction of apoptosis in IFN-betasensitive melanoma cell lines. (2010)
  • Author(s): Kamiya T, Yamashita T, et al.
  • Journal Title: J Interferon Cytokine Res Volume: 30(5) Pages: 349-357
  • Peer Reviewed
• [Journal Article] Rab7 is a critical mediator in vesicular transport of tyrosinase-relatoteinl in melanocytes. (2010)
  • Author(s): Hida T, Yamashita T, et al.
  • Journal Title: J Dermatol Volume: 37 Pages: 1-10
  • Peer Reviewed
• [Journal Article] Melanoma-targeted chemo-thermo-immuno (CTI)-therapy using N-propionyl-4-S-cysteaminylphenol-magnetite nanoparticles elicits CTL response via heat shock protein-peptide complex release. (2010)
  • Author(s): Sato A, Yamashita T, et al.
  • Journal Title: Cancer Sci Volume: 101 Pages: 1939-1946
  • NAID: 10027831209
  • Peer Reviewed
• [Presentation] Conjugation of MagnetiteNanoparticles with Melanogenesis Substrate, NPrCAP Provides Melanoma Targeted, in Situ Peptide Vaccine Immunotherapy through HSP Production by Chemo-Thermotherapy (2012)
  • Author(s): Jimbow K, Tamura Y, Yoneta A, Kamiya T, Ono I, Yamashita T, Ito A, Honda H,Wakamatsu K, Ito S, Nohara S, Nakayama E, Kobayashi T
  • Organizer: J Biomat Nanobiotech
• [Presentation] Development of novel NPrCAP-magnetite nanoparticles and evaluation of antitumor and immunotherapeutic effect by chemo-thermo-immunotherapy for malignant melanoma. (2012)
  • Author(s): Yoneta A
  • Organizer: 37th annual meeting of the Japanese Society for Investigateive Dermatology
  • Place of Presentation: Nara
• [Presentation] Resveratrol ameliorates muscle pathogenesis in mdx mouse (2011)
  • Author(s): Yusuke S. Hori Y, Hayashi T, Kuno A, Hosoda R, Horio Y
  • Organizer: a model for Duchenne muscular dystrophy. Society for Neurosci. Washington DC
• [Presentation] N-Propionyl-4-S-Cysteminylphenol generates reactive oxygen species and mediates apoptosis in pigmented melanoma cells (2011)
  • Author(s): Ishii-Osai Y, Yamashita T, Okura M, Tamura Y, Sato N, Ito A, Honda H, Wakamatsu K, Ito S, Jimbow K
  • Organizer: International Pigment Cell Conference
  • Place of Presentation: Bordeaux, France
• [Presentation] Resveratrol ameliorates dystrophic muscle pathogenesis in mdx mouse, a model for Duchenne muscular dystrophy. Gordon Research Coference Muscle Myogenesis (2011)
  • Author(s): Hori Y, Kuno A, Hosoda R, Tanno M, Miura T, Shimamoto K, Horio Y
  • Organizer: New Horizons for Myogenesis
  • Place of Presentation: Waterville Valley Resort, Waterville Valley, NH, USA
• [Presentation] Two cases of advanced melanoma treated with dendritic cell vaccination therapy (2011)
  • Author(s): Yoneta A, Yamashita T, et al
  • Organizer: 22nd World Congress of Dermatology
  • Place of Presentation: Seoul, Korea
• [Presentation] Expression in carcinogenesis of melanoma and drugsensitive factors by epigenetic change (2011)
  • Author(s): Nishizaka T, Yamashita T, et al
  • Organizer: 22nd World Congress of Dermatology
  • Place of Presentation: Seoul, Korea
• [Presentation] Development and evaluation of antitumor effect of novel NPrCAP-magnetite nanoparticles for chemothermo-immunotherapy in malignant melanoma (2011)
  • Author(s): Yoneta A, Yamashita T, et al
  • Organizer: XXIst International Pigment Cell Conference
  • Place of Presentation: Bordeaux, France
• [Presentation] N-Propionyl-4-S-Cysteminylphenol generates reactive oxygen species and mediates apoptosis in pigmented melanoma cells (2011)
  • Author(s): Ishii-Osai Y, Yamashita T, et al
  • Organizer: XXIst International Pigment Cell Conference
  • Place of Presentation: Bordeaux, France
• [Presentation] Effects of a low-molecular-weight polyphenol(oligonol)on the growth and melanogenesis of primary melanocvtes and melanoma cells (2011)
  • Author(s): Okura M, Yaraashita T, et al
  • Organizer: 22nd World Congress of Dermatology
  • Place of Presentation: Seoul, Korea
• [Presentation] N-propionyl-4-S-cysteaminylphenol mediates apoptosis in pigmented raelanoma cells in association with ROS production (2011)
  • Author(s): Ishii-Osai Y, Yamashita T, et al
  • Organizer: The 36th Annual Meeting of Japanese Society for Investigative Dermatology
  • Place of Presentation: Kyoto, Japan
• [Presentation] Inhibition of protein deacetylase SIRT1 suppresses in vitro and in vivo invasion of melanoma cells. (2010)
  • Author(s): Kunimoto R, Yamashita T, et al.
  • Organizer: The 40^<th> Annual Meeting of the European Society for Dermatological Research (ESDR)
  • Place of Presentation: Helsinki, Finland
  • Year and Date: 2010-09-11
• [Presentation] Inhibition of protein deacetylase SIRT1 suppresses in vitro and in vivo invasionof melanoma cells (2010)
  • Author(s): Kunimoto R, Jimbow K, Yamashita T, Okura M, Hirobe T, Sato M, Hisahara S, Horio Y
  • Organizer: The 40thAnnual Meeting of the European Society for Deramatolo- gical Resarch (ESDR)
  • Place of Presentation: Helsinki, Finland
• [Book] 紅皮症 今日の治療方針2012 (2012)
  • Author(s): 山下 利春
  • Total Pages: 1
  • Publisher: 医学書院
• [Book] 凍瘡 皮膚疾患最新の治療 2013-2014 (2012)
  • Author(s): 山下 利春
  • Total Pages: 1
  • Publisher: 南江堂