Degree 【 display / non-display 】

Degree 【 display / non-display 】

• MD, PhD

Research Experience 【 display / non-display 】

Research Experience 【 display / non-display 】

• 2024.04

  -

  Now

  Sapporo Medical University   Deparetment of Dermatology   Associate Professor

  病院教授

• 2022.06

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  2024.03

  Sapporo Medical University   Department of Dermatology   Associate Professor

• 2014.04

  -

  2022.05

  Sapporo Medical University   Department of Dermatology   Assistant Professor

• 2005.08

  -

  2007.08

  St George's University of London   Basic Medical Sciences   Visiting Research Fellow

  Visiting Research Fellow

• 2005.04

  -

  2014.03

  Sapporo Medical University   Department of Dermatology   Instructor

  Instructor

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Professional Memberships 【 display / non-display 】

Professional Memberships 【 display / non-display 】

• 　

  　

  　

  Japanese Cancer Association

• 　

  　

  　

  THE JAPAN SOCIETY OF HUMAN GENETICS

• 　

  　

  　

  日本臨床皮膚科医会

• 　

  　

  　

  Japanese Skin Cancer Society

• 　

  　

  　

  JAPANESE DERMATOLOGICAL ASSOCIATION

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Research Areas 【 display / non-display 】

Research Areas 【 display / non-display 】

• Life sciences   Medical biochemistry   clinical genetics

• Life sciences   Dermatology   skin cancers

• Life sciences   Dermatology   melanogenesis

Affiliation 【 display / non-display 】

Affiliation 【 display / non-display 】

• Sapporo Medical University   School of Medicine, Dept.of Dermatology   Associate Professor   病院教授  

Research Interests 【 display / non-display 】

Research Interests 【 display / non-display 】

• genodermatosis

• melanin

• melanoma

• genetics

• clinical genetics

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Papers 【 display / non-display 】

Papers 【 display / non-display 】

• Distinct induction pathways of heat shock protein 27 in human keratinocytes: Heat stimulation or capsaicin through phosphorylation of heat shock factor 1 at serine 326 and/or suppression of ΔNp63.

  Terufumi Kubo, Kenta Sasaki, Sayuri Sato, Tomoyuki Minowa, Tokimasa Hida, Kenji Murata, Takayuki Kanaseki, Tomohide Tsukahara, Yoshihiko Hirohashi, Hisashi Uhara, Toshihiko Torigoe

  Biochemical and biophysical research communications   708   149817 - 149817  2024.03  [International journal]

  　View Summary

  Epidermal keratinocytes, forming the outermost layer of the human body, serve as a crucial barrier against diverse external stressors such as ultraviolet radiation. Proper keratinocyte differentiation and effective responses to external stimuli are pivotal for maintaining barrier integrity. Heat is one such stimulus that triggers the synthesis of heat shock proteins (HSPs) when cells are exposed to temperatures above 42 °C. Additionally, activation of the transient receptor potential cation channel subfamily V member 1 (TRPV1) occurs at 42 °C. Here, we explore the interplay between TRPV1 signaling and HSP induction in human keratinocytes. Both heat and capsaicin, a TRPV1 agonist, induce expression of HSP27, HSP70, and HSP90 in keratinocytes. Interestingly, pharmacological inhibition of TRPV1 attenuates heat-induced HSP27 expression, but not that of HSP70 or HSP90. Furthermore, both heat and capsaicin stimulation result in distinct phosphorylation patterns of heat shock factor 1 (HSF1), with phosphorylation at serine 326 being a common feature. Notably, genetic manipulation to mimic dephosphorylation of HSF1 at serine 326 reduces HSP27 levels. Additionally, ΔNp63, a key regulator of epidermal differentiation, negatively modulates HSP27 expression independently of HSF1 phosphorylation status. While heat stimulation has no effect on ΔNp63 expression, capsaicin reduces its levels. The precise role of TRPV1 signaling in keratinocytes warrants further investigation for a comprehensive understanding of its impact on barrier function.

  DOI PubMed

• Melanoma incidence on the non-weight-bearing areas of the sole.

  Kazuki Furudate, Junji Kato, Kohei Horimoto, Sayuri Sato, Tokimasa Hida, Masahide Sawada, Tomoyuki Minowa, Hisashi Uhara

  The Journal of dermatology    2024.02  [International journal]

  DOI PubMed

• Significant and Various Effects of ML329-Induced MITF Suppression in the Melanoma Cell Line.

  Nami Nishikiori, Megumi Watanabe, Tatsuya Sato, Masato Furuhashi, Masae Okura, Tokimasa Hida, Hisashi Uhara, Hiroshi Ohguro

  Cancers   16 ( 2 )  2024.01  [International journal]

  　View Summary

  To study the inhibitory effects on microphthalmia-associated transcription factor (MITF)-related biological aspects in malignant melanomas (MMs) in the presence or absence of the low-molecular MITF specific inhibitor ML329, cell viability, cellular metabolic functions, and three-dimensional (3D) spheroid formation efficacy were compared among MM cell lines including SK-mel-24, A375, dabrafenib- and trametinib-resistant A375 (A375DT), and WM266-4. Upon exposure to 2 or 10 μM of ML329, cell viability was significantly decreased in WM266-4, SK-mel-24, and A375DT cells, but not A375 cells, in a dose-dependent manner, and these toxic effects of ML329 were most evident in WM266-4 cells. Extracellular flux assays conducted using a Seahorse bioanalyzer revealed that treatment with ML329 increased basal respiration, ATP-linked respiration, proton leakage, and non-mitochondrial respiration in WM266-4 cells and decreased glycolytic function in SK-mel-24 cells, whereas there were no marked effects of ML329 on A375 and A375DT cells. A glycolytic stress assay under conditions of high glucose concentrations also demonstrated that the inhibitory effect of ML329 on the glycolytic function of WM266-4 cells was dose-dependent. In addition, ML329 significantly decreased 3D-spheroid-forming ability, though the effects of ML329 were variable among the MM cell lines. Furthermore, the mRNA expression levels of selected genes, including STAT3 as a possible regulator of 3D spheroid formation, KRAS and SOX2 as oncogenic-signaling-related factors, PCG1a as the main regulator of mitochondrial biogenesis, and HIF1a as a major hypoxia transcriptional regulator, fluctuated among the MM cell lines, possibly supporting the diverse ML329 effects mentioned above. The findings of diverse ML329 effects on various MM cell lines suggest that MITF-associated biological activities are different among various types of MM.

  DOI PubMed

• Characterization of CD4 T-cell phenotype in human leukocyte antigen class II-positive acral melanoma.

  Nayuha Shogase, Tomoyuki Minowa, Junji Kato, Kohei Horimoto, Sayuri Sato, Tokimasa Hida, Yoshihiko Hirohashi, Toshihiko Torigoe, Hisashi Uhara

  The Journal of dermatology    2023.12  [International journal]

  DOI PubMed

• Four cases of gnathostomiasis due to the ingestion of raw <i>Salangichthys microdon</i>

  Takahiko Abe, Tokimasa Hida, Takafumi Kamiya, Kanako Ebata, Shintaro Sugita, Rie Kaneko, Mio Tanaka, Haruhiko Maruyama, Akira Suzuki, Hisashi Uhara

  The Journal of Dermatology ( Wiley )   2023.10  [Refereed]

  DOI

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Misc 【 display / non-display 】

Misc 【 display / non-display 】

• 【新規知見の乏しい皮膚疾患】aquagenic wrinkling of the palmsの2例

  小松 彩友香, 肥田 時征, 黄倉 真恵, 宇原 久

  皮膚病診療 ( (株)協和企画 )  45 ( 9 ) 802 - 805  2023.09

  　View Summary

  ＜文献概要＞症例のポイント ・aquagenic wrinkling of the palmsは手掌を浸水させると容易に白色浸軟化し,ときおり疼痛を伴う後天性の疾患である.治療法は確立されていない.・掌蹠に角化を伴う場合,本邦で頻度の高い長島型掌蹠角化症も鑑別になるが,そのほかに特徴的な臨床症状を伴い,SERPINB7遺伝子に病原性バリアントが検出される.

• メラノーマの治療選択におけるがん遺伝子パネル検査

  肥田 時征

  日本皮膚科学会雑誌 ( (公社)日本皮膚科学会 )  133 ( 5 ) 1275 - 1275  2023.05

• MYO5A-NTRK3融合遺伝子を検出したatypical Spitz tumor

  佐藤 さゆり, 肥田 時征, 井戸川 雅史, 黄倉 真恵, 宇原 久

  日本皮膚科学会雑誌 ( (公社)日本皮膚科学会 )  132 ( 5 ) 1363 - 1363  2022.05

• Melanoma and Non-Melanoma Skin Cancers メラノーマ・皮膚癌 メラノーマのゲノム異常

  肥田 時征

  癌と化学療法 ( (株)癌と化学療法社 )  49 ( 4 ) 409 - 412  2022.04

• 【遺伝性疾患と遺伝カウンセリング】Cowden症候群/PTEN過誤腫症候群

  塩野谷 愛香, 肥田 時征, 水上 都, 菅原 太郎, 長谷川 匡, 菅野 康吉, 宇原 久

  皮膚病診療 ( (株)協和企画 )  44 ( 3 ) 210 - 214  2022.03

  　View Summary

  ＜文献概要＞症例のポイント ・体幹に繰り返し出現する皮疹は尋常性疣贅として治療されていた.・皮膚粘膜症状と多臓器の腫瘍性病変の既往から本症を疑い,遺伝カウンセリング後に遺伝子診断を行った.・本症は内臓悪性腫瘍の検索が必要であり,早期の診断に皮膚科医が果たす役割は大きい.

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Research Projects 【 display / non-display 】

Research Projects 【 display / non-display 】

• Comprehensive analysis of genetic mutations and fusions in Japanese melanoma

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2021.04

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  2024.03

   

  肥田 時征, 井戸川 雅史

• 美白化合物のメラノーマ細胞障害作用を利用した新規メラノーマ治療薬の開発

  奨励研究

  Project Year :

  2019

  　

  　

   

  黄倉 真恵, 宇原 久, 肥田 時征

  　View Summary

  BRAF遺伝子変異を有するメラノーマには分子標的薬が奏効するものの、のちに薬剤耐性が生じる場合が多い。本研究は、分子標的薬の耐性をアスコルビン酸、ロドデノールの併用で克服できるかどうかを検討した。結果、アスコルビン酸はBRAF/MEK阻害剤耐性メラノーマ細胞株SK-me1-23DT, ロドデノールはBRAF/MEK阻害剤耐性メラノーマ細胞株A375DTに強い細胞障害を誘発した。以上の結果から、アスコルビン酸とロドデノールは、分子標的薬(BRAF/MEK阻害薬)による耐性を克服しうる治療薬の候補となり得ることがわかった。

• Identification and analysis of tumor-associated genes of melanoma by functional assay

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2013.04

  -

  2016.03

   

  Yamashita Toshiharu

  　View Summary

  We aimed to examine the epigenetically silenced miRNA and its involvement in the induction of apoptosis of cultured melanoma cells. A screen for miRNAs induced by 5-aza-2’deoxycytidine (5-aza-dC) and interferon-beta (IFN-β) in TXM18 melanoma cells identified six species of miRNAs including miR-7, miR-203, miR-215 and miR-596. The CpG island of the miR-596 gene was strongly methylated in all melanoma cell lines tested (n = 20) whereas methylation levels were limited in melanocytes (n=4). Transfection of a precursor of miR-596 into melanoma cells induced growth suppression, indicating that the effect of 5-aza-dC plus IFN-β is in part due to induction of miR-596. Methylation levels of miR-596 were significantly higher in clinical specimens of melanoma as compared to benign melanocytic nevi.

• Analysis of melanosome transfer between melanocytes and keratinocytes

  Grant-in-Aid for Young Scientists (B)

  Project Year :

  2011

  -

  2013

   

  HIDA Tokimasa

  　View Summary

  A new co-culture method for melanocytes and keratinocytes has been developed. By using this method, melanosomal transfer from melanocytes to keratinocytes could be visualized with electron and optical microscopes and the melanin content of transferred melanosomes could be analyzed. The effect of inhibitors of melanin synthesis on melanosomal transfer could also be analyzed. To apply the result for clinical practice, the melanin distribution in the nipple skin of patients with pigmented mammary Paget's disease was examined with histopathology, immunohistochemistry and dermoscopy. It was suggested that tumor cells transferred melanin from reactive melanocytes are subject to passive elimination from the epidermis and form characteristic dermoscopic patterns. This finding is useful in diagnosing pigmented mammary Paget's disease.

• Development of novel melanoma therapy targeting SIRT1

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2010

  -

  2012

   

  YAMASITA Tosiharu, HORIO Yosiyuki, HIDA Tokimasa

  　View Summary

  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.

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Presentations 【 display / non-display 】

Presentations 【 display / non-display 】

• Mutation landscape of melanomas among Japanese: Custom panel sequencing of 77 cases

  Hida T, Idogawa M, Kato J, Horimoto K, Sato S, Kiniwa Y, Okura M, Okuyama R, Tokino T, Uhara H

  25th World Congress of Dermatology 

  Presentation date： 2023.07

  Event date：

  2023.07

  　

  　

• Copy number variations and fusion genes in driver mutation-negative melanoma

  Hida T, Idogawa M, Kato J, Horimoto K, Sato S, Kiniwa Y, Sugita S, Okura M, Okuyama R, Tokino T, Uhara H

  25th International Pigment Cell Conference 

  Presentation date： 2023.05

  Event date：

  2023.05

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  2023.06

• 線状の脱色素斑を伴ったfamilial progressive hyperpigmentation with or without hypopigmentationの１例

  肥田時征, 宇原 久

  第31回日本色素細胞学会学術大会 

  Presentation date： 2022.11

  Event date：

  2022.11

  　

  　

• 教育講演. 神経線維腫症1型 up date

  肥田 時征  [Invited]

  第424回日本皮膚科学会北海道地方会 

  Presentation date： 2020.12

  Event date：

  2020.12

  　

  　

• 教育講演．メラノーマの分子生物学的背景

  肥田時征  [Invited]

  第121回日本皮膚科学会総会 

  Presentation date： 2022.06

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Committee Memberships 【 display / non-display 】

Committee Memberships 【 display / non-display 】

• 2021

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  Now

    理事

• 2020

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  Now

    代議員

• 2018.04

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  Now

    特別委員

• 2017.12

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  Now

    評議員