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The involvement of sphingolipid metabolism in anticancer agent - resistant melanoma cells

Research Project

Project/Area Number 15K08094
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Medical pharmacy
Research InstitutionGifu University

Principal Investigator

Seishima Mariko  岐阜大学, 大学院医学系研究科, 教授 (00171314)

Co-Investigator(Kenkyū-buntansha) 藤澤 智美  岐阜大学, 大学院医学系研究科, 非常勤講師 (20585583)
加納 宏行  岐阜大学, 大学院医学系研究科, 准教授 (40566494)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords悪性黒色腫 / 抗がん剤耐性 / FTY720 / BRAF阻害薬 / スフィンゴ脂質代謝 / S1P受容体アンタゴニスト / 抗がん耐性
Outline of Final Research Achievements

We investigated the effects of combination of FTY720, phosphorylated and binds to sphingosine-1-phosphate receptors, and vemurafenib, an inhibitor of BRAFV600- mutant protein, on cell death induction and molecular mechanisms in vemurafenib-resistant melanoma cells. Combination of FTY720 and vemurafenib reduced cell viability and increased expression of cleaved PARP. The expression of phosphorylated ERK was decreased by this combination. Furthermore, vemurafenib-resistant SK-Mel-28 cells (R-SK-Mel) were established by culturing the SK-Mel-28 cell. In R-SK-Mel cells, the cell viability was also reduced and the expression of cleaved PARP was increased by the combination with FTY720 and vemurafenib. Moreover, the expression of phosphorylated ERK and Akt were reduced by this treatment. These findings suggest that FTY720 and vemurafenib synergistically induce cell death through downregulation of proliferation and survival signaling pathways in vemurafenib-resistant melanoma cells.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (34 results)

All 2017 2016 2015

All Journal Article (25 results) (of which Peer Reviewed: 25 results,  Open Access: 18 results) Presentation (9 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] α2AP regulates vascular alteration by inhibiting VEGF signaling in systemic sclerosis: the roles of α2AP in vascular dysfunction in systemic sclerosis.2017

    • Author(s)
      Kanno Y, Shu E, Kanoh H, Matsuda A, Seishima M.
    • Journal Title

      Arthritis Res Ther.

      Volume: 19 Issue: 1 Pages: 22-22

    • DOI

      10.1186/s13075-017-1227-y

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Potential inhibition of development of rapidly progressive interstitial lung disease by prompt and sufficient immunosuppressive treatment in patients with anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis.2017

    • Author(s)
      Shu E, Kanoh H, Murakami A, Seishima M.
    • Journal Title

      J Dermatol.

      Volume: 44 Issue: 5

    • DOI

      10.1111/1346-8138.13659

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enhanced dendritic cells and regulatory T cells in the dermis of porokeratosis2017

    • Author(s)
      Matsuyama Kanako、Mizutani Yoko、Takahashi Tomoko、Shu En、Kanoh Hiroyuki、Miyazaki Tatsuhiko、Seishima Mariko
    • Journal Title

      Archives of Dermatological Research

      Volume: 309 Issue: 9 Pages: 749-756

    • DOI

      10.1007/s00403-017-1779-3

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Uveitis induced by programmed cell death protein 1 inhibitor therapy with nivolumab in metastatic melanoma patient2017

    • Author(s)
      Kanno H, Ishida K, Yamada W, Nishida T, Takahashi N, Mochizuki K, Mizuno Y, Matsuyama K, Takahashi T, Seishima M
    • Journal Title

      J Infect Chemother

      Volume: 11 Issue: 11 Pages: 774-777

    • DOI

      10.1016/j.jiac.2017.04.007

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Multiple familial trichoepithelioma with a novel mutation of the CYLD gene.2017

    • Author(s)
      Fujii A, Matsuyama K, Mizutani Y, Kanoh H, Nakano H, Seishima M.
    • Journal Title

      J Dermatol

      Volume: 44 Issue: 9

    • DOI

      10.1111/1346-8138.13901

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sweet's Syndrome Successfully Treated with Granulocyte and Monocyte Adsorption Apheresis.2017

    • Author(s)
      Fujii A, Mizutani Y, Hattori Y, Takahashi T, Ohnishi H, Yoshida S, Seishima M.
    • Journal Title

      Case Rep Dermatol.

      Volume: 22 Issue: 2 Pages: 13-18

    • DOI

      10.1159/000475878

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bullous Pemphigoid Successfully Treated With a Combination Therapy of Plasmapheresis Followed by Intravenous High Dose Immunoglobulin.2017

    • Author(s)
      Hattori Y, Takahashi T, Seishima M.
    • Journal Title

      Ther Apher Dial.

      Volume: 21 Issue: 4 Pages: 421-423

    • DOI

      10.1111/1744-9987.12536

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Symmetrical drug-related intertriginous and flexural exanthema possibly due to thiamine disulfide.2017

    • Author(s)
      Hattori Y, Matsuyama K, Shu E, Kanoh H, Seishima M.
    • Journal Title

      J Dermatol.

      Volume: 44 Issue: 6

    • DOI

      10.1111/1346-8138.13776

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pyoderma Gangrenosum, Acne and Suppurative Hidradenitis Syndrome Treated with Granulocyte and Monocyte Adsorption Apheresis.2016

    • Author(s)
      Mizutani Y, Okano T, Takahashi T, Ohnishi H, Ohara O, Sano A, Seishima M.
    • Journal Title

      Acta Derm Venereol.

      Volume: - Issue: 2 Pages: 275-276

    • DOI

      10.2340/00015555-2507

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Contact allergy to liquorice flavonoids: Analysis using liquid chromatography-mass spectrometry2016

    • Author(s)
      Kanoh H, Banno Y, Nakamura M, Seishima M
    • Journal Title

      Contact Dermatitis

      Volume: 74 Issue: 3 Pages: 191-192

    • DOI

      10.1111/cod.12511

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The anti-fibrotic effect of α2AP neutralization in systemic sclerosis dermal fibroblasts and mouse models of systemic sclerosis2016

    • Author(s)
      Kanno Y, Shu E, Kanoh H, Seishima M
    • Journal Title

      J Invest Dermatol

      Volume: 136 Issue: 4 Pages: 762-769

    • DOI

      10.1016/j.jid.2015.12.028

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sonographic detection of subcutaneous foreign bodies in 3 cases2016

    • Author(s)
      Matsuno H, Watanabe T, Tada S, Sekine A, Nohisa Y, Shinoda K, Furuta N, Ito H, Shu E, Seishima M
    • Journal Title

      Acta Dermatovenerol Croat

      Volume: 24 Pages: 299-302

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Acquired palmoplantar keratoderma associated with hypothyroidism2016

    • Author(s)
      Mizutani Y, Ito M, Fujisawa T, Takahashi T, Seishima M
    • Journal Title

      J Dermatol

      Volume: 43 Issue: 10 Pages: 1246-1247

    • DOI

      10.1111/1346-8138.13363

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Recurrent superficial cellulitis-like erythema associated with Helicobacter cinaedi bacteremia2016

    • Author(s)
      Adachi Y, Moriya C, Fujisawa T, Shu E, Kanoh H, Nakayama A, Yonetamari J, Seishima M
    • Journal Title

      J Dermatol

      Volume: 43 Issue: 7 Pages: 844-846

    • DOI

      10.1111/1346-8138.13282

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cutaneous B cell pseudolymphoma in a psoriatic patient treated with cyclosporine2016

    • Author(s)
      Takahashi T, Hata M, Iwata H, Seishima M
    • Journal Title

      Acta Derm Venereol

      Volume: 96 Pages: 824-825

    • DOI

      10.2340/00015555-2387

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mutation analyses of patients with dyschromatosis symmetrica hereditaria:Ten novel mutations of the ADAR1 gene2015

    • Author(s)
      Okamura K, Abe Y, Fukai K, Tsuruta D, Suga Y, Nakamura M, Funasaka Y, Oka M,
    • Journal Title

      J Dermatol Sci

      Volume: 79 Issue: 1 Pages: 88-90

    • DOI

      10.1016/j.jdermsci.2015.04.004

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Localized scleroderma presenting as port-wine stains: report of two cases and a literature review2015

    • Author(s)
      Kanoh H, Shu E, Ichiki Y, Seishima M
    • Journal Title

      Acta Derm Venereol

      Volume: 95 Issue: 8 Pages: 1003-1004

    • DOI

      10.2340/00015555-2100

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sonographic findings of subcutaneous sarcoidosis in 3 cases2015

    • Author(s)
      Tada S, Watanabe T, Suzuki C, Nohisa Y, Shinoda K, Furuta N, Ito H, Okumura Y, Shu E, Seishima M
    • Journal Title

      J Ultrasound Med

      Volume: 34 Issue: 8 Pages: 1485-1488

    • DOI

      10.7863/ultra.34.8.1485

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A case of Felty’s syndrome associated with skin ulcers and extranodal NK/T-cell lymphoma2015

    • Author(s)
      Shu E, Kanoh H, Kito Y, Seishima M
    • Journal Title

      Acta Derm Venereol

      Volume: 95 Issue: 6 Pages: 754-755

    • DOI

      10.2340/00015555-2067

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Granulocyte and monocyte adsorption apheresis for generalized pustular psoriasis: therapeutic outcomes in three refractory patients2015

    • Author(s)
      Fujisawa T, Suzuki S, Mizutani Y, Doi T, Yoshida S, Ogura S, Seishima M
    • Journal Title

      Ther Apher Dial

      Volume: 19 Issue: 4 Pages: 336-341

    • DOI

      10.1111/1744-9987.12342

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Drug-induced hypersensitivity syndrome followed by subacute thyroiditis2015

    • Author(s)
      Sato M, Mizuno Y, Matsuyama K, Shu E, Kanoh H, Suwa T, Seishima M
    • Journal Title

      Case Rep Dermatol

      Volume: 7 Issue: 2 Pages: 161-165

    • DOI

      10.1159/000437251

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anti-SRP antibody-positive myopathy with universal alopecia and multiple vitiligo2015

    • Author(s)
      Tokuzumi M, Fujisawa T, Shu E, Kanoh H, Saigo C, Miyazaki T, Hamaguchi Y, Seishima M
    • Journal Title

      Acta Derm Venereol

      Volume: 95 Issue: 4 Pages: 497-498

    • DOI

      10.2340/00015555-1985

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Eosinophilic fasciitis associated with myositis2015

    • Author(s)
      Adachi Y, Mizutani Y, Shu E, Kanoh H, Miyazaki T, Seishima M
    • Journal Title

      Case Rep Dermatol

      Volume: 7 Issue: 1 Pages: 79-83

    • DOI

      10.1159/000381845

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Familial Mediterranean fever variant with repeated atypical skin eruptions2015

    • Author(s)
      Takahashi T, Fujisawa T, Kimura M, Ohnishi H, Seishima M
    • Journal Title

      J Dermatol

      Volume: 42 Issue: 9 Pages: 903-905

    • DOI

      10.1111/1346-8138.12929

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Merkel cell polyomavirus-positive Merkel cell carcinoma in a patient with epidermodysplasia verruciformis2015

    • Author(s)
      Mizuno Y, et al. 8名
    • Journal Title

      Acta Derm Venereol

      Volume: 95 Issue: 1 Pages: 98-99

    • DOI

      10.2340/00015555-1868

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Treatments for sarcoid vasculitis with cutaneous involvement2017

    • Author(s)
      Seishima M, Niwa H, Hattori Y, Matsuyama K, Takahashi T, Shu E, Kanoh H, Miyazaki T
    • Organizer
      The 18th International Vasculitis & ANCA Workshop
    • Related Report
      2017 Annual Research Report
  • [Presentation] A combination therapy of plasmapheresis followed by intravenous high dose immunoglobulin for severe bullous pemphigoid2017

    • Author(s)
      Seishima M, Hattori Y, Takahashi T, Shu E, Yoshida S
    • Organizer
      The 11th International Society for Apheresis Congress 2017
    • Related Report
      2017 Annual Research Report
  • [Presentation] IFN-γ may disrupt skin barrier function through reduction of long-chain fatty acid ceramides in mite-induced dermatitis2017

    • Author(s)
      Kanoh H, Ishitsuka A, Fujine E, Matsuhana S, Nakamura M, Inagaki N, Ito H, Banno Y, Seishima M
    • Organizer
      Society for Investigative Dermatology 76th Annual Meeting
    • Related Report
      2017 Annual Research Report
  • [Presentation] Gastric cancer developed six years after the onset of anti-TIF1γ antibody-positive dermatomyositis2017

    • Author(s)
      Shu E, Kanoh H, Miyazaki T, Seishima M
    • Organizer
      The 26th European Academy of Dermatology and Venereology Congress
    • Related Report
      2017 Annual Research Report
  • [Presentation] Recurrent sweet syndrome successfully treated with granulocyte and monocyte adsorption apheresis2017

    • Author(s)
      Hattori Y, Mizutani Y, Takahashi T, Yoshida S, Ohnishi H, Seishima M
    • Organizer
      The 11th International Society for Apheresis Congress 2017
    • Related Report
      2017 Annual Research Report
  • [Presentation] A case of malignant melanoma occurred in an area of palmoplantar keratoderma (Nagashima-type)2016

    • Author(s)
      Takahashi T, Tokuzumi M, Matsuyama K, Shu E, Seishima M, Kubo A
    • Organizer
      The 4th Eastern Asia Dermatology Congress
    • Place of Presentation
      Urayasu
    • Year and Date
      2016-11-16
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] BRAF阻害剤抵抗性メラノーマ細胞株に対するsphigosine 1-phophate受容体アンタゴニストFTY720の併用効果2016

    • Author(s)
      高橋智子,阿部奈緒子,石塚麻子,松山加奈子,坂野喜子,加納宏行,清島真理子
    • Organizer
      第27回日本色素細胞学会
    • Place of Presentation
      岐阜市
    • Year and Date
      2016-11-12
    • Related Report
      2016 Research-status Report
  • [Presentation] Pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH) syndrome treated with granulocyte and monocyte adsorption apheresis2016

    • Author(s)
      Seishima M, Mizutani Y, Takahashi T, Ohnishi H
    • Organizer
      Asia-Pacific Combined Dermatology Research Conference
    • Place of Presentation
      Noosa, Australia
    • Year and Date
      2016-08-25
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] The antifibrotic effect of α2AP neutralization in systemic sclerosis dermal fibroblasts and mouse models of systemic sclerosis2015

    • Author(s)
      Kanno Y, Shu E, Kanoh H, Seishima M
    • Organizer
      第40回日本研究皮膚科学会学術大会
    • Place of Presentation
      岡山
    • Year and Date
      2015-12-11
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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