研究者詳細 - 宇原　久

論文 - 宇原　久

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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年10月

DOI

Pemphigus vulgaris as an immune-related adverse event in recurrent metastatic esophageal squamous cell carcinoma treated with ipilimumab plus nivolumab: a case report and literature review

Hajime Nakamura, Aika Shionoya, Yohei Arihara, Naotaka Hayasaka, Tomohiro Kubo, Makoto Usami, Shintaro Sugita, Hisashi Uhara, Kohichi Takada

Frontiers in Immunology ( Frontiers Media SA ) 14 2023年09月

Ipilimumab plus nivolumab therapy is approved for patients with unresectable advanced esophageal squamous cell carcinoma (ESCC). Although a combination of immune checkpoint inhibitors (ICIs), compared to conventional chemotherapy, can improve overall survival in patients with advanced ESCC, this increases the incidence of immune-related adverse events (irAEs). Here, we describe an ESCC case that developed pemphigus vulgaris (PV), an extremely rare cutaneous irAE, during ipilimumab plus nivolumab treatment. The patient achieved a partial response to treatment. The PV was successfully managed after the cessation of ipilimumab and the use of a topical steroid. We should thus re-treat ESCC with nivolumab monotherapy. In the era of ICIs as standard cancer therapeutics, diagnostic criteria for blistering diseases need to be established to properly manage patients with cutaneous irAEs.

DOI

Effects of temozolomide on tumor mutation burden and microsatellite instability in melanoma cells.

Masahide Sawada, Tokimasa Hida, Takafumi Kamiya, Tomoyuki Minowa, Junji Kato, Masae Okura, Masashi Idogawa, Takashi Tokino, Hisashi Uhara

The Journal of dermatology 2023年09月 [国際誌]

The efficacy of combination therapy with an immune checkpoint inhibitor (ICI) and cytotoxic chemotherapeutic agents has been investigated in cancer, including melanoma. Before ICIs were introduced, dacarbazine or temozolomide (TMZ) were used to treat melanoma. Several studies using glioma or colorectal cancer cells showed that TMZ can increase the tumor mutation burden (TMB) and induce mismatch repair (MMR) deficiency associated with microsatellite instability (MSI). These could increase immunoreactivity to an ICI, but this has not been evaluated in melanoma cells. We investigated the effects of TMZ on MSI status and TMB in melanoma cells. To evaluate the TMB, we performed whole-exome sequencing using genomic DNA from the human melanoma cell lines Mel18, A375, WM266-4, G361, and TXM18 before and after TMZ treatment. Polymerase chain reaction amplification of five mononucleotide repeat markers, BAT25, BAT26, NR21, NR24, and MONO27, was performed, and we analyzed changes in the MSI status. In all cell lines, the TMB was increased after TMZ treatment (the change amount of TMB with ≤ 5% variant allele frequency [VAF] was 18.0-38.3 mutations per megabase) even in the condition without obvious cytological damage. MSI after TMZ treatment was not observed in any cells. TMZ increased TMB but did not change MSI status in melanoma cells.

DOI PubMed

【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年09月

Relationships between tumor thickness and the risk of sentinel node metastasis in acral and non-acral melanoma.

Junji Kato, Tokimasa Hida, Takafumi Kamiya, Kohei Horimoto, Sayuri Sato, Masahide Sawada, Tomoyuki Minowa, Toshiya Handa, Sayuka Komatsu, Hisashi Uhara

International journal of dermatology 2023年06月 [国際誌]

DOI PubMed

メラノーマ細胞におけるtumor mutation burden及びmicrosatellite instabilityに対するtemozolomideの影響

澤田匡秀, 肥田時征, 神谷崇文, 箕輪智幸, 加藤潤史, 黄倉真恵, 井戸川雅史, 時野隆至, 宇原久

日本皮膚悪性腫瘍学会学術大会プログラム・抄録集 ( (一社)日本皮膚悪性腫瘍学会 ) 39回 229 - 229 2023年06月

A Japanese patient with hereditary angioedema caused by deep intron variation in the SERPING1 gene.

Tokimasa Hida, Aki Ishikawa, Masae Okura, Mari Kishibe, Hisashi Uhara

The Journal of dermatology 2023年05月 [国際誌]

DOI PubMed

SUFUの体細胞変異を検出したbasaloid follicular hamartomaの1例

浜田茉里奈, 肥田時征, 神谷宗文, 井戸川雅史, 山下利春, 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 ) 133 ( 5 ) 1403 - 1404 2023年05月

北海道在住者におけるシラウオ生食による皮膚爬行症

阿部貴彦, 肥田時征, 神谷崇文, 江畑加奈子, 杉田真太朗, 兼古理恵, 鈴木昭, 田中美緒, 丸山治彦, 宇原久

日本臨床皮膚科医会雑誌 ( 日本臨床皮膚科医会 ) 40 ( 3 ) 471 - 471 2023年05月

Analyzing the relationship between the efficacy of first-line immune checkpoint inhibitors and cumulative sun damage in Japanese patients with advanced BRAF wild-type nonacral cutaneous melanoma: A retrospective real-world, multicenter study.

Takashi Inozume, Kenjiro Namikawa, Hiroshi Kato, Shusuke Yoshikawa, Yukiko Kiniwa, Koji Yoshino, Satoru Mizuhashi, Takamichi Ito, Tatsuya Takenouchi, Shigeto Matsushita, Yasuhiro Fujisawa, Takamitsu Matsuzawa, Satoru Sugihara, Jun Asai, Hiroshi Kitagawa, Takeo Maekawa, Taiki Isei, Masahito Yasuda, Naoya Yamazaki, Hisashi Uhara, Yasuhiro Nakamura

Journal of dermatological science 110 ( 1 ) 19 - 26 2023年03月 [国際誌]

BACKGROUND: Efficacy of anti-PD-1 antibody monotherapy (PD1) or anti-PD-1 plus anti-CTLA-4 combination therapy (PD1 +CTLA4) for melanoma is affected by its clinical subtype. The amount of tumor mutation burden (TMB) caused by cumulative sun damage (CSD) is occasionally used to explain this; however, their relationship in Japanese nonacral cutaneous melanoma (NACM) is still unclear. OBJECTIVE: To analyze the ICI efficacy and its relationship with CSD of the primary lesion in Japanese patients with NACM. METHODS: Japanese patients with advanced BRAF wild-type NACM who received first-line ICIs were recruited. Objective response rate (ORR), progression-free survival (PFS), and overall survival (OS), and the degree of solar elastosis (SE) were evaluated. RESULTS: A total of 146 patients (PD1 group 113 and PD1 +CTLA4 group 33) were included. No significant differences in ORR were observed between the PD1 and PD1 +CTLA4 groups (35 % vs. 36 %; P = 0.67) or PFS and OS (median PFS 6.1 months vs. 8.5 months; P = 0.46, median OS 28.1 months vs. not reached; P = 0.59). Multivariate survival analysis revealed that PD1 +CTLA4 did not prolong the PFS and OS. The SE score had no effect on either PFS or OS. CONCLUSIONS: ICI efficacy was not as high as those reported in Western countries, and PD1 +CTLA4 did not present better clinical efficacy compared to PD1. Indicators of CSD did not serve as a predictor for clinical advantage. These findings may partially support the theory that ICI efficacy is affected by CSD; however, other unrecognized factors may also exist.

DOI PubMed

経カテーテル的大動脈弁植え込み術後の親水性ポリマー塞栓の1例

竹林文彦, 菅裕司, 佐藤知世, 肥田時征, 宇原久, 櫻田心太郎, 村上直人

日本皮膚科学会雑誌 ( (公社)日本皮膚科学会 ) 133 ( 3 ) 541 - 541 2023年03月

シラウオ生食後の皮膚爬行症の1例

阿部貴彦, 肥田時征, 宇原久, 杉田真太朗, 兼古理恵, 田中美緒, 丸山治彦

日本皮膚科学会雑誌 ( (公社)日本皮膚科学会 ) 133 ( 3 ) 542 - 542 2023年03月

3D Spheroid Configurations Are Possible Indictors for Evaluating the Pathophysiology of Melanoma Cell Lines.

Hiroshi Ohguro, Megumi Watanabe, Tatsuya Sato, Fumihito Hikage, Masato Furuhashi, Masae Okura, Tokimasa Hida, Hisashi Uhara

Cells 12 ( 5 ) 2023年02月 [国際誌]

To study the molecular mechanisms responsible for inducing the spatial proliferation of malignant melanomas (MM), three-dimension (3D) spheroids were produced from several MM cell lines including SK-mel-24, MM418, A375, WM266-4, and SM2-1, and their 3D architectures and cellular metabolisms were evaluated by phase-contrast microscopy and Seahorse bio-analyzer, respectively. Several transformed horizontal configurations were observed within most of these 3D spheroids, and the degree of their deformity was increased in the order: WM266-4, SM2-1, A375, MM418, and SK-mel-24. An increased maximal respiration and a decreased glycolytic capacity were observed within the lesser deformed two MM cell lines, WM266-4 and SM2-1, as compared with the most deformed ones. Among these MM cell lines, two distinct cell lines, WM266-4 and SK-mel-24, whose 3D appearances were the closest and farthest, respectively, from being horizontally circular-shaped, were subjected to RNA sequence analyses. Bioinformatic analyses of the differentially expressed genes (DEGs) identified KRAS and SOX2 as potential master regulatory genes for inducing these diverse 3D configurations between WM266-4 and SK-mel-24. The knockdown of both factors altered the morphological and functional characteristics of the SK-mel-24 cells, and in fact, their horizontal deformity was significantly reduced. A qPCR analysis indicated that the levels of several oncogenic signaling related factors, including KRAS and SOX2, PCG1α, extracellular matrixes (ECMs), and ZO1 had fluctuated among the five MM cell lines. In addition, and quite interestingly, the dabrafenib and trametinib resistant A375 (A375DT) cells formed globe shaped 3D spheroids and showed different profiles in cellular metabolism while the mRNA expression of these molecules that were tested as above were different compared with A375 cells. These current findings suggest that 3D spheroid configuration has the potential for serving as an indicator of the pathophysiological activities associated with MM.

DOI PubMed

抗PD-1抗体が著効したNF1変異型末端型メラノーマの1例

松田宇充, 加藤潤史, 肥田時征, 堀本浩平, 佐藤さゆり, 黄倉真恵, 宇原久, 井戸川雅史, 時野隆至

日本皮膚科学会雑誌 ( (公社)日本皮膚科学会 ) 133 ( 2 ) 271 - 272 2023年02月

Bacillus Calmette-Guérin-induced lupus vulgaris in a patient with Mendelian susceptibility to mycobacterial disease caused by a novel STAT1 variation.

Aika Shionoya, Yuko Yoto, Tokimasa Hida, Aki Ishikawa, Tadashi Hasegawa, Takeshi Tsugawa, Hisashi Uhara

The British journal of dermatology 188 ( 1 ) 142 - 143 2023年01月 [国際誌]

DOI PubMed

Functional Interplay between IL-9 and Peptide YY Contributes to Chronic Skin Inflammation.

Shiori Kamiya, Ippei Ikegami, Masahiro Yanagi, Hiromi Takaki, Ryuta Kamekura, Taiki Sato, Keiju Kobayashi, Takafumi Kamiya, Yuka Kamada, Takaya Abe, Ken-Ichi Inoue, Tokimasa Hida, Hisashi Uhara, Shingo Ichimiya

The Journal of investigative dermatology 142 ( 12 ) 3222 - 3231 2022年12月 [国際誌]

Complex interactions between keratinocytes and various cell types, such as inflammatory cells and stromal cells, contribute to the pathogenesis of chronic inflammatory skin lesions. In proinflammatory cytokine‒mediated disease settings, IL-9 plays a pathological role in inflammatory dermatitis. However, IL-9‒related mechanisms remain incompletely understood. In this study, we established tamoxifen-induced keratinocyte-specific IL-9RA-deficient mice (K14CRE/ERTIl9raΔ/Δ mice) to examine the role of IL-9 in multicellular interactions under chronic skin inflammatory conditions. Studies using an imiquimod-induced psoriasis-like model showed that K14CRE/ERTIl9raΔ/Δ mice exhibited a significantly reduced severity of dermatitis and mast cell infiltration compared with control K14WTIl9rafl/fl mice. Transcriptome analyses of psoriasis-like lesions showed that the level of peptide Y-Y (Pyy), a member of the neuropeptide Y family, was markedly downregulated in K14CRE/ERTIl9raΔ/Δ epidermis. Pyy blockade suppressed epidermal thickening and mast cell numbers in imiquimod-treated wild-type mice. Together with in vitro studies indicating that Pyy induced IL-9 production and chemotactic activity in bone marrow‒derived mast cells, these findings suggest that Pyy-mediated interplay between keratinocytes and mast cells contributes to psoriasiform inflammation. Further investigation focusing on the IL-9‒Pyy axis may provide valuable information for the development of new treatment modalities for inflammatory dermatitis.

DOI PubMed

Clinical history analysis of Japanese melanoma cases and characteristics of melanoma with childhood onset.

Akane Minagawa, Hisashi Uhara, Atsuko Ashida, Hiroshi Koga, Ryuhei Okuyama

The Journal of dermatology 49 ( 12 ) 1334 - 1337 2022年12月 [国際誌]

It remains debatable whether melanoma with a clinical history of early childhood onset truly arises from a nevus. To clarify the clinical and genetic characteristics of melanoma detected at birth or several years afterwards, 249 melanoma cases seen at Shinshu University Hospital between 2006 and 2015 were retrospectively analyzed. Ten (4.0%) cases (median age 39.5 years, range 19-70 years; male/female 2/8; lesion site, 6 extremities, 2 trunk, 1 head, 1 face; cumulative sun damage [CSD] skin, 9 low-CSD, 1 high-CSD; detection at birth 3) had recorded early childhood onset. Median Breslow's tumor thickness in those cases was 6.0 mm (range: 0.4-17.5 mm). The frequency of lesions detected at <20 years of age was significantly higher for low-CSD melanoma (17.5%) than for high-CSD (3.3%) and acral (0.8%) melanoma. Although melanoma with a history of early childhood onset is rare, the characteristics of such cases should be established since most have progressed to an advanced stage at the initial visit.

DOI PubMed

Linear lichen planus after COVID-19 vaccination.

Junji Kato, Takafumi Kamiya, Toshiya Handa, Eri Kobayashi, Tokimasa Hida, Toshiharu Yamashita, Hisashi Uhara

The Australasian journal of dermatology 63 ( 4 ) e385-e387 2022年11月 [国際誌]

DOI PubMed

顔に繰り返した壊疽性膿皮症の1例

松田宇充, 菅裕司, 古舘和樹, 小栗瑛実, 小松彩友香, 細川夕菜, 藤岡茉生, 大橋隆宏, 米田大介, 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 ) 132 ( 12 ) 2697 - 2697 2022年11月

抗PD-1抗体が著効したNF1-mutant acral melanoma肝転移の1例

松田宇充, 加藤潤史, 肥田時征, 堀本浩平, 佐藤さゆり, 黄倉真恵, 宇原久, 井戸川雅史, 時野隆至

日本皮膚科学会雑誌 ( (公社)日本皮膚科学会 ) 132 ( 12 ) 2699 - 2699 2022年11月

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