研究者詳細 - 宇原　久

論文 - 宇原　久

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顔面に多発したbasaloid follicular hamartomaの1例

濱田茉里奈, 肥田時征, 神谷崇文, 宇原久, 井戸川雅史, 山下利春

日本皮膚科学会雑誌 ( (公社)日本皮膚科学会 ) 132 ( 12 ) 2704 - 2704 2022年11月

Dermoscopy for Acral Melanocytic Lesions: Revision of the 3-step Algorithm and Refined Definition of the Regular and Irregular Fibrillar Pattern.

Toshiaki Saida, Hiroshi Koga, Hisashi Uhara

Dermatology practical & conceptual 12 ( 3 ) e2022123 2022年07月 [国際誌]

DOI PubMed

Immunomodulation of Melanoma by Chemo-Thermo-Immunotherapy Using Conjugates of Melanogenesis Substrate NPrCAP and Magnetite Nanoparticles: A Review

Yasuaki Tamura, Akira Ito, Kazumasa Wakamatsu, Takafumi Kamiya, Toshihiko Torigoe, Hiroyuki Honda, Toshiharu Yamashita, Hisashi Uhara, Shosuke Ito, Kowichi Jimbow

International Journal of Molecular Sciences 23 ( 12 ) 2022年06月 [国際誌]

A major advance in drug discovery and targeted therapy directed at cancer cells may be achieved by the exploitation and immunomodulation of their unique biological properties. This review summarizes our efforts to develop novel chemo-thermo-immunotherapy (CTI therapy) by conjugating a melanogenesis substrate, N-propionyl cysteaminylphenol (NPrCAP: amine analog of tyrosine), with magnetite nanoparticles (MNP). In our approach, NPrCAP provides a unique drug delivery system (DDS) because of its selective incorporation into melanoma cells. It also functions as a melanoma-targeted therapeutic drug because of its production of highly reactive free radicals (melanoma-targeted chemotherapy). Moreover, the utilization of MNP is a platform to develop thermo-immunotherapy because of heat shock protein (HSP) expression upon heat generation in MNP by exposure to an alternating magnetic field (AMF). This comprehensive review covers experimental in vivo and in vitro mouse melanoma models and preliminary clinical trials with a limited number of advanced melanoma patients. We also discuss the future directions of CTI therapy.

DOI PubMed

Difference in immunohistochemical findings among anti-PD-L1 antibodies and their relationships with CD4+ and CD8+ T cells in Japanese melanoma patients.

Daisuke Yoneta, Junji Kato, Takafumi Kamiya, Kohei Horimoto, Sayuri Sato, Masahide Sawada, Tomoyuki Minowa, Tokimasa Hida, Shintaro Sugita, Hisashi Uhara

International journal of clinical oncology 27 ( 8 ) 1364 - 1371 2022年06月 [国内誌]

BACKGROUND: The immunohistochemical evaluation of programmed death ligand 1 (PD-L1) is important for selecting treatments. Several antibodies are available for such evaluations, but data regarding the differences in the antibodies' positivity are limited in melanoma, particularly the acral and mucosal types. We investigated the differences in melanoma tissues' PD-L1 expression among the commonly used PD-L1 antibodies and then evaluated the relationship between PD-L1+ tumor cells and tumor-infiltrating lymphocytes (TILs). PATIENTS AND METHODS: We examined 56 primary lesions and 8 metastatic lymph node samples from 56 Japanese patients with melanoma (28 acral melanoma, 8 mucosal melanoma, 18 cutaneous melanoma, 2 unknown). Immunohistochemical staining was performed using three primary antibodies against PD-L1 (E1L3N, SP142, and 28-8). PD-L1-positive staining in tumor cells was defined as ≥ 1% expression. RESULTS: The positive rates were 25.0% for 28-8, 34.0% for E1L3N, and 34.0% for SP142 in 64 samples. The positive rates of acral melanoma were 10.7% for 28-8, 21.4% for E1L3N, and 21.4% for SP142. The positive rate of mucosal melanoma for which all three antibodies reacted was 12.5%. The positive rates of cutaneous melanoma were 55.6% for 28-8, 66.7% for E1L3N, and 66.7% for SP142. Significant relationships were observed among the PD-L1+ tumor cells, CD4+ TILs, and CD8+ TILs (p < 0.001). CONCLUSION: The staining results by E1L3N, SP142, and 28-8 antibodies were within the allowable range, although the positive rates by E1L3N and P142 were slightly higher than that of 28-8. CD4+ TILs and CD8+ TILs were quantitatively correlated with PD-L1-positive tumor cells.

DOI PubMed

Difference in immunohistochemical findings among anti-PD-L1 antibodies and their relationships with CD4+ and CD8+ T cells in Japanese melanoma patients

Daisuke Yoneta, Junji Kato, Takafumi Kamiya, Kohei Horimoto, Sayuri Sato, Masahide Sawada, Tomoyuki Minowa, Tokimasa Hida, Shintaro Sugita, Hisashi Uhara

International Journal of Clinical Oncology ( Springer Science and Business Media LLC ) 2022年06月

DOI

クロタミトンによる肛囲・会陰皮膚潰瘍の2例

半田稔也, 神谷崇文, 箕輪智幸, 菅裕司, 肥田時征, 澄川靖之, 宇原久

日本皮膚科学会雑誌 ( (公社)日本皮膚科学会 ) 132 ( 5 ) 1303 - 1303 2022年05月

Delayed-onset abscopal effect after palliative radiotherapy for acral melanoma treated with anti-PD-1 therapy.

Hiroshi Sasaki, Junji Kato, Kohei Horimoto, Sayuri Sato, Yuna Hosokawa, Toshiya Handa, Eri Kobayashi, Kazuki Furudate, Haruka Sigyo, Takaaki Tsuchiya, Masanori Someya, Hisashi Uhara

The Journal of dermatology 49 ( 8 ) e255-e256 2022年03月 [国際誌]

DOI PubMed

Prognoses of patients with melanoma who continue/discontinue anti-programmed death-1 therapy after achieving a complete response in a real-world setting: a multicentre retrospective study.

Junji Kato, Kenjiro Namikawa, Jiro Uehara, Motoo Nomura, Yasuhiro Nakamura, Hisashi Uhara, Hiroshi Uchi, Shusuke Yoshikawa, Yukiko Kiniwa, Yoshiyuki Nakamura, Takuya Miyagawa, Shigeto Matsushita, Tatsuya Takenouchi, Naohito Hatta, Fumitaka Ohno, Taku Maeda, Satoshi Fukushima, Naoya Yamazaki

The British journal of dermatology 187 ( 4 ) 594 - 596 2022年03月 [国際誌]

DOI PubMed

Primary cutaneous diffuse large B‐cell lymphoma, leg type, of the face that appeared on pre‐existing T‐cell pseudolymphoma clinically resembling actinic reticuloid

Yuna Hosokawa, Takafumi Kamiya, Shintaro Sugita, Tokimasa Hida, Kohichi Takada, Yasuyuki Sumikawa, Hiroyuki Takahashi, Hisashi Uhara

The Journal of Dermatology ( Wiley ) 2022年03月

DOI

【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年03月

Anogenital skin necrosis with fibrin thrombosis induced by crotamiton.

Toshiya Handa, Takafumi Kamiya, Yuji Kan, Tokimasa Hida, Yasuyuki Sumikawa, Tomoyuki Minowa, Hisashi Uhara

Contact dermatitis 86 ( 3 ) 221 - 223 2022年03月 [国際誌]

DOI PubMed

【診断に苦慮した症例】初診時の主訴が上肢の片側性皮膚硬化であったWerner症候群

古舘和樹, 肥田時征, 黄倉真恵, 宇原久

皮膚病診療 ( (株)協和企画 ) 44 ( 1 ) 52 - 55 2022年01月

Case of immunoglobulin (Ig)M/IgG immune complex vasculitis associated with multicentric Castleman's disease.

Aika Shionoya, Tokimasa Hida, Hiroshi Ikeda, Shintaro Sugita, Keiko Segawa, Tadashi Hasegawa, Hisashi Uhara

The Journal of dermatology 48 ( 12 ) e614-e615 2021年12月 [国際誌]

DOI PubMed

Genetic analyses of a secondary poroma and trichoblastoma in a HRAS-mutated sebaceous nevus.

Tomoyuki Minowa, Takafumi Kamiya, Tokimasa Hida, Masae Okura, Junji Kato, Masashi Idogawa, Shoichiro Tange, Tomomi Hirano, Takashi Tokino, Hisashi Uhara

The Journal of dermatology 48 ( 8 ) 1268 - 1272 2021年08月 [国際誌]

A sebaceous nevus is a congenital skin hamartoma caused by postzygotic HRAS or KRAS mosaic mutations. With age, affected individuals may develop secondary tumors within a sebaceous nevus. RAS mutations are harbored from the onset of sebaceous nevus, and further mutations can be expected to be required in order to explain the initiation of secondary tumors. However, genetic analyses of the secondary tumors have not been conducted. Herein, we describe the rare coexistence of a poroma and a trichoblastoma arising in a sebaceous nevus. This is the first report of an investigation of multiple genes in a secondary tumor in an SN. First, HRAS c.37G>C, which is the common mutation in sebaceous nevus, was detected in all three lesions (sebaceous nevus, poroma, and trichoblastoma). Next, to elucidate the potential second-hit mutations in the secondary poroma and trichoblastoma, we applied a panel sequencing for skin cancers that was newly developed in our institution. Our comparison of the mutational profile of 95 skin cancer-related genes in each of the three lesions newly revealed TP53 p.R158P in the poroma and NOTCH2 p.G329S in the trichoblastoma. TP53 p.R158P has been determined as a pathogenic mutation in other tumors, and NOTCH2 p.G329S was a novel mutation. We identified two novel mutations that may have contributed to the pathogenesis of the secondary tumor's development. The roles of the mutations remain unclear.

DOI PubMed

Expression of programmed cell death ligand 1 (PD-L1) at in situ and invasive extramammary Paget's disease and literature review.

Junji Kato, Shintaro Sugita, Kohei Horimoto, Sayuri Sato, Daisuke Yoneta, Masahide Sawada, Mao Fujioka, Tadashi Hasegawa, Hisashi Uhara

The Australasian journal of dermatology 62 ( 3 ) 412 - 414 2021年08月 [国際誌]

DOI PubMed

カスタムパネルシーケンスを用いた日本人メラノーマのドライバー遺伝子の検出

肥田時征, 井戸川雅史, 堀本浩平, 加藤潤史, 佐藤さゆり, 藤岡茉生, 丹下正一朗, 時野隆至, 宇原久

日本皮膚科学会雑誌 ( (公社)日本皮膚科学会 ) 131 ( 5 ) 1363 - 1363 2021年05月

病理組織学的に顕著なロゼット様構造を呈したALK陽性atypical Spitz tumor

箕輪智幸, 肥田時征, 堀本浩平, 加藤潤史, 神谷崇文, 杉田真太朗, 井戸川雅史, 宇原久

日本皮膚科学会雑誌 ( (公社)日本皮膚科学会 ) 131 ( 5 ) 1417 - 1417 2021年05月

Five-year survival with nivolumab in previously untreated Japanese patients with advanced or recurrent malignant melanoma.

Hisashi Uhara, Yoshio Kiyohara, Jiro Uehara, Yasuhiro Fujisawa, Tatsuya Takenouchi, Masaki Otsuka, Hiroshi Uchi, Satoshi Fukushima, Hironobu Minami, Masahiro Hatsumichi, Naoya Yamazaki

The Journal of dermatology 48 ( 5 ) 592 - 599 2021年05月 [国際誌]

We report the 5-year follow-up results from a single-arm, open-label, multicenter phase II study (ONO-4538-08) conducted in Japan. Twenty-four patients with treatment-naïve, recurrent, or unresectable stage III/IV malignant melanoma received 3 mg/kg nivolumab every 2 weeks until progressive disease or unacceptable toxicity occurred. The 5-year overall survival (OS) rate was 26.1%. Five years after the start of nivolumab treatment, there were six survivors. The 5-year OS rate was 66.7% for patients with a superficial spreading type, 14.3% for acral lentiginous type, and 16.7% for mucosal type. The 5-year progression-free survival rate was 17.2%. No new cases of partial response or complete response were observed after 3 years, and overall response and disease control rates were similar to those reported at 3 years. The treatment-related adverse events reported between the 3- and 5-year follow-up periods were anemia (grade 2), white blood cell count decrease (grade 2), and psoriasiform dermatitis (grade 2) in one patient each. No new grade 3 or higher treatment-related adverse events occurred in this period. In conclusion, first-line treatment with nivolumab in Japanese patients with unresectable or metastatic melanoma resulted in confirmed long-term survival. No new safety signals were reported in the studied population.

DOI PubMed

ALK-positive atypical Spitz tumour with conspicuous rosette-like structures.

Tomoyuki Minowa, Tokimasa Hida, Kohei Horimoto, Junji Kato, Takafumi Kamiya, Shintaro Sugita, Masashi Idogawa, Toshiaki Saida, Tadashi Hasegawa, Takashi Tokino, Hisashi Uhara

European journal of dermatology : EJD 31 ( 2 ) 256 - 258 2021年04月 [国際誌]

DOI PubMed

IL-13 modulates ∆Np63 levels causing altered expression of barrier- and inflammation-related molecules in human keratinocytes: A possible explanation for chronicity of atopic dermatitis.

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

Immunity, inflammation and disease 9 ( 3 ) 734 - 745 2021年04月 [国際誌]

BACKGROUND: Barrier disruption and an excessive immune response in keratinocytes are now considered to have important roles in the pathophysiology of atopic dermatitis (AD). Furthermore, disturbed keratinocyte differentiation is considered to underlie AD. ΔNp63, a p53-like transcription factor, is a major regulator of keratinocyte differentiation. However, the functional significance of ΔNp63 in AD has not been clarified. OBJECTIVE: In this study, we aimed to investigate the influence of the type 2 inflammatory environment on ΔNp63 expression and AD-associated molecules regulated by ΔNp63 in keratinocytes. METHODS: The immunohistochemical expression profiles of ΔNp63 and AD-related molecules were evaluated in human skin tissue. The function of ΔNp63 in the regulation of AD-related molecules and the influence of the type 2 inflammatory environment on ΔNp63 expression were investigated using human primary keratinocytes. Expression of ΔNp63 was manipulated using the RNA interfering method. RESULTS: In healthy skin tissue, we observed an inverse expression pattern between ∆Np63 and some barrier-related proteins including filaggrin, caspase-14, claudin-1, and claudin-4. ΔNp63 regulated expression of these genes and proteins. In addition, production of IL-1β and IL-33, pro-inflammatory cytokines, was modulated by ΔNp63. Furthermore, prolonged IL-13 exposure increased the thickness of the three-dimensional culture of keratinocytes. IL-13 interfered with ΔNp63 downregulation during calcium-induced keratinocyte differentiation. IL-13 modulated some barrier-related and inflammation-related molecules, which were regulated by ΔNp63. CONCLUSIONS: We have shown that ΔNp63 modulated AD-related barrier and inflammatory molecules. In addition, ΔNp63 expression was affected by IL-4/IL-13. IL-13-ΔNp63 axis would integrate two major factors of AD pathogenesis: dysregulated barrier and inflammation.

DOI PubMed

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