研究者詳細 - 宇原　久

論文 - 宇原　久

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メラノーマに特化したシーケンスパネルの開発

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

日本皮膚科学会雑誌 ( (公社)日本皮膚科学会 ) 131 ( 3 ) 541 - 542 2021年03月

工業用セメントによる全身性接触皮膚炎の1例

菅裕司, 半田稔也, 箕輪智幸, 神谷崇文, 宇原久, 澄川靖之

日本皮膚科学会雑誌 ( (公社)日本皮膚科学会 ) 131 ( 1 ) 131 - 131 2021年01月

肺扁平上皮癌に合併したBazex症候群の1例

塩野谷愛香, 肥田時征, 西坂尚大, 汐谷心, 宇原久

臨床皮膚科 ( (株)医学書院 ) 74 ( 13 ) 1101 - 1106 2020年12月

＜文献概要＞70歳代,男性.初診の4ヵ月前から掌蹠,臀部,膝に角化性紅斑局面と爪甲の変形が出現した.Bazex症候群を疑い全身精査を行ったが異常はなかった.乾癬型薬疹も考え,被疑薬を中止したが皮疹は増悪したため,初診の4ヵ月後にCTを撮像したところ,右下肺野に結節が発見された.肺扁平上皮癌(pT3N0M0)であった.根治術後に皮疹と爪症状が著明に軽快した.Bazex症候群の本邦報告例(26例)を解析した結果,84%が皮疹先行例,11%が悪性腫瘍先行例であった.皮疹先行例のうち,腫瘍診断のタイミングは1年以内が73%,3年以内が95%であった.四肢末端に治療抵抗性の角化性紅斑と爪変形が出現した場合は本症候群を疑い,初診時に悪性腫瘍が発見されなくても2〜3年程度は,画像検査や内視鏡検査を含めた定期的な内臓癌の検査をする必要があると考えた.

工業用セメントによる全身性接触皮膚炎の一例

菅裕司, 澄川靖之, 半田稔也, 箕輪智幸, 神谷崇文, 宇原久

日本皮膚免疫アレルギー学会総会学術大会プログラム・抄録集 ( (一社)日本皮膚免疫アレルギー学会 ) 50回 209 - 209 2020年12月

Cigarette Smoke Underlies the Pathogenesis of Palmoplantar Pustulosis via an IL-17A-Induced Production of IL-36γ in Tonsillar Epithelial Cells.

Keiju Kobayashi, Ryuta Kamekura, Junji Kato, Shiori Kamiya, Takafumi Kamiya, Kenichi Takano, Shingo Ichimiya, Hisashi Uhara

The Journal of investigative dermatology 141 ( 6 ) 1533 - 1541 2020年11月 [国際誌]

Palmoplantar pustulosis (PPP) is characterized by sterile pustules on the palms and soles. A strong association between PPP and tobacco smoking has been reported, and it has been speculated that the IL-17A pathway may play an important role in PPP. Recent studies have suggested that IL-36 plays a pivotal role in the pathogenesis of psoriasis and its subtypes. The relationships among IL-36, smoking, and PPP have not been examined. Here, we investigated the relationships among the smoking index, severity of the clinical condition of PPP, and in vitro dynamics of IL-36 in human tonsillar epithelial cells under the condition of exposure to a cigarette smoke extract. The results demonstrated that the Palmoplantar Pustulosis Area and Severity Index was strongly and positively correlated with the smoking index in female patients. Immunohistochemical examinations showed that IL-36γ was highly expressed in tonsillar epithelial cells from patients with PPP but not in those from patients with recurrent tonsillitis without PPP. The in vitro study revealed that IL-17A synergistically induced a release of IL-36γ under cigarette smoke extract exposure. These results suggest that local production of IL-36γ by epithelial cells induced by cigarette smoke exposure plays an important role in the pathogenesis of PPP.

DOI PubMed

Case of pneumatosis cystoides intestinalis with pemphigus vulgaris.

Eri Kobayashi, Yuji Kan, Takafumi Kamiya, Ayako Kumagai, Hisashi Uhara

The Journal of dermatology 47 ( 11 ) e412-e413 2020年11月 [国際誌]

DOI PubMed

Neurofibromatosis type 1 without cutaneous neurofibromas: a rare genotype-phenotype correlation?

Tokimasa Hida, Masashi Idogawa, Aki Ishikawa, Miyako Mizukami, Junji Kato, Yasuyuki Sumikawa, Masae Okura, Takashi Tokino, Hisashi Uhara

European journal of dermatology : EJD 30 ( 5 ) 608 - 609 2020年10月 [国際誌]

DOI PubMed

Two cases of angioedema without wheals induced by exercising or bathing.

Tomoyuki Minowa, Yasuyuki Sumikawa, Ayako Kumagai, Takafumi Kamiya, Hisashi Uhara

Allergology international : official journal of the Japanese Society of Allergology 69 ( 4 ) 648 - 649 2020年10月 [国際誌]

DOI PubMed

Cold urticaria comorbid with heat urticaria: A case report.

Takahiro Ohashi, Yuji Kan, Hiroyuki Takahashi, Daisuke Yoneta, Kimi Kase, Yasuyuki Sumikawa, Hisashi Uhara

The Journal of dermatology 47 ( 9 ) e325-e326 2020年09月 [国際誌]

DOI PubMed

Elucidation of Melanogenesis Cascade for Identifying Pathophysiology and Therapeutic Approach of Pigmentary Disorders and Melanoma.

Tokimasa Hida, Takafumi Kamiya, Akinori Kawakami, Jiro Ogino, Hitoshi Sohma, Hisashi Uhara, Kowichi Jimbow

International journal of molecular sciences 21 ( 17 ) 2020年08月 [国際誌]

Melanogenesis is the biological and biochemical process of melanin and melanosome biosynthesis. Melanin is formed by enzymic reactions of tyrosinase family proteins that convert tyrosine to form brown-black eumelanin and yellow-red pheomelanin within melanosomal compartments in melanocytes, following the cascades of events interacting with a series of autocrine and paracrine signals. Fully melanized melanosomes are delivered to keratinocytes of the skin and hair. The symbiotic relation of a melanocyte and an associated pool of keratinocytes is called epidermal melanin unit (EMU). Microphthalmia-associated transcription factor (MITF) plays a vital role in melanocyte development and differentiation. MITF regulates expression of numerous pigmentation genes for promoting melanocyte differentiation, as well as fundamental genes for maintaining cell homeostasis. Diseases involving alterations of EMU show various forms of pigmentation phenotypes. This review introduces four major topics of melanogenesis cascade that include (1) melanocyte development and differentiation, (2) melanogenesis and intracellular trafficking for melanosome biosynthesis, (3) melanin pigmentation and pigment-type switching, and (4) development of a novel therapeutic approach for malignant melanoma by elucidation of melanogenesis cascade.

DOI PubMed

Final analysis of a phase II study of nivolumab in combination with ipilimumab for unresectable chemotherapy-naive advanced melanoma.

Kenjiro Namikawa, Yoshio Kiyohara, Tatsuya Takenouchi, Hisashi Uhara, Hiroshi Uchi, Shusuke Yoshikawa, Sumiko Takatsuka, Hiroshi Koga, Naoko Wada, Hironobu Minami, Masahiro Hatsumichi, Yoshinobu Namba, Naoya Yamazaki

The Journal of dermatology 47 ( 11 ) 1257 - 1266 2020年08月 [査読有り] [国際誌]

Nivolumab plus ipilimumab combination is currently one of the preferred regimens for advanced melanoma in recently updated clinical practice guidelines. However, the evidence on the efficacy of the combination for acral or mucosal subtypes remains less robust. This is the final analysis of a multicenter, open-label, uncontrolled phase II study that investigated the long-term efficacy and safety in treatment-naive Japanese patients with advanced melanoma, including acral or mucosal subtypes, and subsequent therapy after discontinuation of the investigational agents. Patients received four doses of nivolumab (1 mg/kg i.v.) in combination with ipilimumab (3 mg/kg i.v.) at 3-week intervals, followed by doses of nivolumab (3 mg/kg i.v.) at 2-week intervals. The median follow-up period was 20.8 months (range, 5.2-35.0). The centrally and locally assessed objective response rates were both 43.3% (13/30; 95% confidence interval [CI], 25.5-62.6). Median progression-free survival was not reached (95% CI, 3.02-not reached), and median overall survival was also not reached (95% CI, 19.52-not reached). The 30-month progression-free survival and overall survival rates were 50.3% and 54.2%, respectively. No new safety concerns were detected. After discontinuation of the investigational agents, 83.3% of patients received some form of subsequent therapy including 43.3% of patients who received nivolumab monotherapy and 26.7% of patients who received radiotherapy. Of the four patients who discontinued the investigational agents because of immune-related adverse events, two received subsequent therapy (nivolumab and ipilimumab, respectively) and the other two showed long-term treatment-free survival (659 and 590 days, respectively). Long-term survival with nivolumab plus ipilimumab was observed in Japanese patients with melanoma including acral and mucosal subtypes, which is consistent with the CheckMate 067 study. Many patients continued to receive some form of treatment safely after stopping treatment with nivolumab plus ipilimumab.

DOI PubMed

Usefulness of neuron-specific enolase as a serum marker of metastatic melanoma.

Sayuri Sato, Junji Kato, Masahide Sawada, Kohei Horimoto, Masae Okura, Tokimasa Hida, Hisashi Uhara

The Journal of dermatology 2020年07月 [国際誌]

Treatment strategies for advanced melanoma are dramatically changing, due to immune-checkpoint inhibitors and BRAF/MEK inhibitors. Nevertheless, reliable serum markers for evaluation of treatment responses and the outcome are still limited. Some previous reports suggested that serum neuron-specific enolase (sNSE) may be a useful marker for melanoma; however, its usefulness is controversial. Moreover, NSE has not been examined in vitro by using melanoma cell lines. We retrospectively evaluated sNSE and serum lactate dehydrogenase (sLDH) levels at the initial diagnosis and during therapy in 33 melanoma patients of various stages. We analyzed the NSE concentrations in cell lysates and supernatants from melanoma cell lines by enzyme-linked immunosorbent assay. The median sNSE was significantly higher in stage IV patients compared with stages I/II and III (16.3, 12.7 and 12.1 ng/mL, respectively). sNSE was elevated in 20% (2/10) of stage III and 61.1% (11/18) of stage IV patients but not in stages I/II. sNSE and sLDH tended to correspond to the total tumor volume (P = 0.48 and 0.58; 95% confidence intervals, 0.005-0172 and 0.776-0.836, respectively). The coincidence rate of sNSE and sLDH in stage IV at the initial diagnosis was 11 of 18 (61.1%). Of the remaining patients, elevated sNSE but not sLDH was observed in five patients (27.8%) and elevated sLDH but not sNSE was observed in two (11.1%). Four of the five patients showing elevated sNSE and normal sLDH were of the mucosal type. NSE was detected in both supernatant and cell lysate of all four melanoma cell lines (0.30-237.32 ng/mL and 137-483.04 ng/mg, respectively). Two cell lines with a high supernatant NSE level contained many dead cells in the supernatant. The combination of sNSE and sLDH could contribute to the early detection of distant metastasis and disease condition evaluations for advanced melanoma patients.

DOI PubMed

Homozygous promoter variant of SLC45A2 causes diverse hair color and patterns.

Tokimasa Hida, Katsuhiko Tsukamoto, Masae Okura, Hisashi Uhara

The Journal of dermatology 2020年07月 [国際誌]

DOI PubMed

Regular sweating activities for the treatment of cholinergic urticaria with or without acquired idiopathic generalized anhidrosis.

Tomoyuki Minowa, Yasuyuki Sumikawa, Yuji Kan, Takafumi Kamiya, Hisashi Uhara

Dermatologic therapy 33 ( 4 ) e13647 2020年07月 [国際誌]

Cholinergic urticaria (CholU) decreases affected individuals' quality of life because they must avoid stimuli including exercise and hot bathing. Although case reports have indicated that regular sweating activities are effective for CholU with hypohidrosis, little evidence is available. This retrospective medical record review examined CholU patients who received any form of treatment at our hospital. Twenty-seven cases (78% men; median age 22 years, range 12-70 years) were analyzed. Fourteen (52%) patients had acquired idiopathic generalized anhidrosis (AIGA). Among the 12 patients receiving sweating therapy (4 with, 8 without AIGA), improvement of symptoms was confirmed in 11 (92%; sweating therapy alone: n = 5, with H1 blocker: n = 5, with steroid pulse: n = 1) including 8 (67%) showing complete response (CR). In this sweating-therapy group, CR was achieved by six of the eight (75%) patients without AIGA and two of the four (50%) patients with AIGA. Among the 15 patients without sweating therapy, symptom improvement was observed in 9 (60%; steroid pulse: n = 7, H1 blocker: n = 2) including 1 (7%) achieving CR. Sweating therapy was safely undertaken except in one case in which the patient showed angioedema and anaphylaxis. Regular sweating activities could be a potential therapeutic option for CholU patients.

DOI PubMed

Real-world safety and efficacy data of ipilimumab in Japanese radically unresectable malignant melanoma patients: A postmarketing surveillance.

Naoya Yamazaki, Yoshio Kiyohara, Hisashi Uhara, Tetsuya Tsuchida, Keiko Maruyama, Naoki Shakunaga, Eijun Itakura, Akira Komoto

The Journal of dermatology 2020年06月 [査読有り] [国際誌]

Treatment with immune checkpoint inhibitors has improved prognosis among patients with cutaneous melanoma, but there are still unmet medical needs in Japan, especially for mucosal melanoma and acral lentiginous melanoma (ALM) subtypes. Ipilimumab, a fully human monoclonal antibody that specifically blocks cytotoxic T-lymphocyte-associated antigen 4 and potentiates antitumor T-cell response, was approved in Japan in 2015 for the treatment of radically unresectable malignant melanoma. This postmarketing surveillance (prospective, non-interventional, multicenter, observational study) evaluated the safety (occurrence of adverse drug reactions [ADR]) and efficacy (overall survival [OS]) of ipilimumab in a real-world setting in Japan. All patients with radically unresectable malignant melanoma undergoing treatment with ipilimumab in Japan during the registration period between August 2015 and February 2017 were enrolled. In total, 547 patients were analyzed; 67.5% were 60 years old or more, 85.7% had an Eastern Cooperative Oncology Group performance status of 0-1, 50.3% had melanoma of the skin (mainly of the ALM subtype) and 73.5% had negative BRAF mutation status. Most patients had experienced recurrence and received multiple treatments. The overall incidence of ADR and serious ADR was 69.5% and 40.8%, respectively. The most common ADR and serious ADR were liver disorder, colitis and diarrhea. The most common ADR of special interest were liver-related ADR (22.5%), skin-related ADR (22.1%), gastrointestinal-related ADR (20.3%) and endocrine system-related ADR (16.3%). Most of these events had recovered or were in remission by the last evaluation. The median OS was 7.52 months (95% confidence interval, 6.47-8.74). Median OS was 6.31 and 8.44 months in patients with mucosal melanoma and melanoma of the skin; 9.43 and 3.75 months in patients with and without ADR; and 10.32 and 6.11 months in patients with and without serious ADR, respectively. Ipilimumab was tolerable and showed efficacy in improving OS for these patients.

DOI PubMed

Anti-PD1 checkpoint inhibitor therapy in acral melanoma: A multicentre study of 193 Japanese patients.

Y Nakamura, K Namikawa, K Yoshino, S Yoshikawa, H Uchi, K Goto, Y Nakamura, S Fukushima, Y Kiniwa, T Takenouchi, H Uhara, T Kawai, N Hatta, T Funakoshi, Y Teramoto, A Otsuka, H Doi, D Ogata, S Matsushita, T Isei, T Hayashi, Y Shibayama, N Yamazaki

Annals of oncology : official journal of the European Society for Medical Oncology 2020年06月 [査読有り] [国際誌]

BACKGROUND: Acral melanoma (AM) is an epidemiologically and molecularly distinct entity that is underrepresented in clinical trials on immunotherapy in melanoma. We aimed to analyze the real-world efficacy of anti-PD-1 antibodies in advanced AM. PATIENTS AND METHODS: We retrospectively evaluated unresectable stage III or stage IV AM patients treated with an anti-PD-1 antibody in any line at 21 Japanese institutions between 2014 and 2018. The clinicobiologic characteristics, objective response rate (ORR, Response Evaluation Criteria in Solid Tumors), survival estimated using Kaplan-Meier analysis, and toxicity (Common Terminology Criteria for Adverse Events 4.0.) were analyzed to estimate the efficacy of the anti-PD-1 antibodies. RESULTS: In total, 193 patients (nail apparatus, 70; palm and sole, 123) were included in the study. Anti-PD-1 antibody was used as first-line therapy in 143 patients (74.1%). Baseline lactate dehydrogenase (LDH) was within normal level in 102 patients (52.8%). The ORR of all patients was 16.6% (complete response, 3.1%; partial response, 13.5%), and the median overall survival (OS) was 18.1 months. Normal LDH levels showed a significantly stronger association with better OS than abnormal levels (median OS 24.9 vs 10.7 months; P<0.001). Although baseline characteristics were similar between the nail apparatus and the palm and sole groups, ORR was significantly lower in the nail apparatus group (6/70 patients [8.6%] vs 26/123 patients [21.1%]; P=0.026). Moreover, the median OS in this group was significantly poorer (12.8 vs 22.3 months; P=0.03). CONCLUSIONS: Anti-PD-1 antibodies have limited efficacy in AM patients. Notably, patients with nail apparatus melanoma had poorer response and survival, making nail apparatus melanoma a strong candidate for further research on the efficacy of novel combination therapies with immune checkpoint inhibitors.

DOI PubMed

Koebner phenomenon of vitiligo associated with Coffin-Siris syndrome.

Tokimasa Hida, Aki Ishikawa, Miyako Mizukami, Hisashi Uhara

European journal of dermatology : EJD 30 ( 3 ) 310 - 311 2020年06月 [国際誌]

DOI PubMed

【まるわかり皮膚科生体検査診断ツールを完全マスター】(Part.2)皮膚の機能を評価しよう遺伝子検査皮膚悪性腫瘍

肥田時征, 宇原久

Visual Dermatology ( (株)学研メディカル秀潤社 ) 19 ( 臨時増刊号 ) 139 - 143 2020年06月

進行期悪性黒色腫のバイオマーカーとしての血清NSEの有用性

佐藤さゆり, 加藤潤史, 堀本浩平, 黄倉真恵, 肥田時征, 宇原久

日本皮膚科学会雑誌 ( (公社)日本皮膚科学会 ) 130 ( 5 ) 1248 - 1248 2020年05月

コリン性蕁麻疹における定期的な発汗刺激の有効性に関する後方視的検討

箕輪智幸, 澄川靖之, 菅裕司, 神谷崇文, 宇原久

日本皮膚科学会雑誌 ( (公社)日本皮膚科学会 ) 130 ( 5 ) 1217 - 1217 2020年05月

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