記述言語：日本語   出版者・発行元：日本皮膚科学会西部支部  

<p>43 歳，女性。10 年以上前から右外鼻孔の黄白色丘疹を自覚していた。5 年前に近医で皮膚生検を施行されたが線維硬化性毛包上皮腫の診断であった。丘疹は緩徐に増大し，当院初診 1 カ月前に前医を受診した。皮膚生検の結果，微小囊胞性付属器癌（microcystic adnexal carcinoma：以下 MAC）が疑われたため，加療目的に当科を紹介され受診した。腫瘍を切除し，病理組織学的所見より MAC と診断した。MAC の発症機序はまだよくわかっておらず，過去の報告をもとに自験例の切除切片を用いて免疫組織化学染色を行った。その結果，過去の報告と同様に p53 の発現が亢進しており TP53 の変異がある可能性が示唆された。一方で phospho-STAT3，c-myc，bcl-2 の発現は亢進していなかった。MAC はしばしば良性腫瘍との鑑別が難しいことがあり，これらの免疫組織化学染色は今後の診断の一助となる可能性がある。</p>

DOI： 10.2336/nishinihonhifu.86.609

CiNii Research

記述言語：日本語   出版者・発行元：日本皮膚科学会西部支部  

<p>70 代，女性。新型コロナウイルスワクチン 6 回目の接種後翌日から接種部位を中心に滲出性紅斑が出現した。皮疹は一部標的状を呈し融合傾向のある紅斑からなり，次第に顔面を含むほぼ全身に拡大した。ステロイド外用と抗ヒスタミン薬内服の処方を行うも，38℃以上の発熱と前腕に水疱形成を認めた。多形紅斑と診断し，ステロイド全身投与を追加した。皮膚症状は改善し，再燃なく経過した。新型コロナウイルスワクチン接種後に発症する皮膚症状の多くは蕁麻疹や接種部位反応などの即時型反応で，多形紅斑の報告は少ない。自験例での DLST は新型コロナウイルスワクチン残薬で陰性，内服薬 2 種（トリパミド，アセトアミノフェン）で陽性を示した。DLST は結果の解釈が困難で，陰性のみを理由に因果関係は否定できず，自験例では接種部位を中心に滲出性紅斑が出現したことを重視して，ワクチン接種が関与している可能性が高いと判断した。新型コロナウイルスワクチンの副反応の病態解析には，症例蓄積と今後のさらなる研究が必要である。</p>

DOI： 10.2336/nishinihonhifu.86.571

CiNii Research

記述言語：英語   出版者・発行元：International Journal of Molecular Sciences  

Atopic dermatitis (AD) is characterized by chronic inflammation, barrier dysfunction, and pruritus, exacerbated by external stimuli, such as scratching. This study investigates the role of extracellular adenosine triphosphate (ATP) in the pathophysiology of AD and assesses the therapeutic potential of clodronate, an ATP release inhibitor. Our research demonstrates that extracellular ATP impairs skin barrier function by reducing the filaggrin expression in the keratinocytes, a critical protein for barrier integrity. Furthermore, ATP release, triggered by IL-4 and mechanical stimuli, amplifies inflammation by promoting cytokine and chemokine production by the immune cells. Clodronate, by inhibiting ATP release, restores the filaggrin levels in the keratinocytes, reduces TARC production in the dendritic cells, and alleviates AD symptoms in a mouse model. These findings suggest that targeting extracellular ATP could offer a novel therapeutic approach to improving skin barrier function and reducing inflammation in AD. Future studies should explore the long-term efficacy and safety of ATP-targeted therapies in clinical settings.

DOI： 10.3390/ijms252212294

Web of Science

Scopus

PubMed

記述言語：英語   出版者・発行元：Frontiers in Medicine  

Background: Anti-programmed death-1 (PD-1) antibodies are the mainstay for the treatment of unresectable or high-risk melanoma. However, real-world data on the safety profile of their extended-interval doses (EDs) are limited, particularly in Asian patients with melanoma. Materials and methods: In this single-center retrospective study, we analyzed the risks of immune-related adverse events (irAEs) among 71 Japanese patients (36 males; mean age, 65.0 years) who received anti-PD-1 monotherapy for melanoma at our institute. Patients who were administered ipilimumab prior to anti-PD-1 monotherapy were excluded. Patients were divided into three groups: canonical-interval dose (CD) group (n = 50, body weight-based dosing or 240 mg Q2W for nivolumab and body weight-based dosing or 200 mg Q3W for pembrolizumab), ED group (n = 14, 480 mg Q4W for nivolumab and 400 mg Q6W for pembrolizumab), and dose-switch (DS) group (n = 7, upfront CD followed by ED). Results: The CD group received nivolumab more frequently in the metastatic setting. There were no significant differences in baseline characteristics among the three groups, including in sex, age, primary tumor site, tumor subtype, and follow-up period. irAEs occurred in 36.6% (26 patients) of all patients (32.0% of the CD group, 35.7% of the ED group, and 71.4% of the DS group), while severe (grade ≥ 3) irAEs occurred in only two patients, both of whom were in the CD group. Most of the irAEs occurred during the first 6 months of anti-PD-1 therapy and, interestingly, all of the irAEs in the DS group occurred before the switch (during the CD). There was no significant difference among the three groups in the probability of irAE estimated by the Kaplan–Meier method. Conclusion: These findings may highlight the safety of ED of anti-PD-1 monotherapy in the treatment of Asian patients with melanoma.

DOI： 10.3389/fmed.2023.1293397

Web of Science

Scopus

PubMed

記述言語：日本語   出版者・発行元：日本皮膚科学会西部支部  

<p>46 歳，男性。幼少時からアトピー性皮膚炎があり難治性のため当科受診 3 年前よりデュピルマブを投与されていた。1 年前より左下腿前面に紅色丘疹が出現し前医の切除生検で皮膚原発性 CD30 陽性 T 細胞リンパ増殖症と診断され，精査加療目的に紹介された。当科初診時採血で好酸球増多があり，可溶性 IL-2R は若干高値で血液内科と併診し，全身 CT や PET の画像検査で明らかな転移巣は認めなかった。近年，デュピルマブ（デュピクセント^®）の長期投与における皮膚 T 細胞性リンパ腫の発症の報告が増えているが関連性については不明な点も多く，更なる研究に加えて経過観察と症例蓄積が必要と考えられる。</p>

DOI： 10.2336/nishinihonhifu.85.366

Scopus

CiNii Research

開催年月日： 2018年6月

記述言語：英語   会議種別：口頭発表（一般）  

国名：中華人民共和国  

Melanoma is one of the most aggressive neoplasia that exhibits poor prognosis and resistance against classic chemotherapy. Currently, immune-checkpoint therapy including anti-programmed cell death 1/ligand 1 (PD-1/PD-L1) antibodies proves to be a clinically effective anti-melanoma treatment. Although much attention has been paid on the PD-1/PD-L1 and T cell pathway, little is known about relationship among this pathway, periostin and M2 macrophage infiltration. We immunohistologically examined the expression of PD-L1, stromal periostin and the infiltration of CD163+ M2 macrophages, and statistically analyzed the association among these variables with the patients’ histological features, clinical stage and prognosis. The PD-L1 expression in melanoma cells was significantly associated with poor prognosis. In addition, either stromal periostin expression or the number of infiltrated CD163+ M2 macrophages had a significant association with poor prognosis. Notably, melanomas with PD-L1 expression had significantly larger number of infiltrated CD163+ M2 macrophages, while the expression of PD-L1 was not correlated with the expression of periostin. These findings pointed a potential linkage between PD-L1 and M2 macrophage in melanoma progression.

開催年月日： 2018年6月

記述言語：英語   会議種別：口頭発表（一般）  

開催地：現地開催   国名：中華人民共和国  

Periostin is a multifunctional matricellular protein that has an important role in regulating melanoma behavior. Periostin is also involved induction in tolerogenic CD163+ M2 macrophages. However, a comprehensive study about the relation among periostin, CD163+ M2 macrophages and melanoma progression has poorly investigated. Thus, we examined the prognostic values of periostin and infiltrated M2 macrophages in human and murine melanoma. In human melanoma, we immunohistologically examined the expression of stromal periostin and the infiltration of CD163+ M2 macrophages, and statistically analyzed the associations of these variables with the patients’ histological features, clinical stage, and prognosis. In addition, we established a murine inflammatory skin model that expressed stromal periostin, and investigated the relationship among periostin expression, the number of CD163+ M2 macrophages, and melanoma progression. In human melanomas, high expression of periostin and a large number of infiltrated M2 macrophages were significantly correlated with poor prognosis. In our murine model, B16 melanoma cell growth in the inflamed periostin-high skin was significantly faster than that in control skin. Intriguingly, significantly more number of CD163+ M2 macrophages were recruited in the melanomas in the inflamed periostin-high skin than those in control skin. Both in human and murine melanoma, periostin receptor αVβ5 integrin was preferentially expressed in melanoma cells whereas CD163+ M2 macrophages mainly harbored periostin receptor αVβ3 integrin. These findings stress a critical role of periostin and M2 macrophages in melanoma progression and prognosis irrespective of human and mouse, indicating that periostin may be a potential target in treating progressive melanoma.

開催年月日： 2017年9月

記述言語：英語   会議種別：口頭発表（一般）  

国名：ドイツ連邦共和国  

It is widely accepted that chronic inflammation initiates and promotes carcinogenesis and tumor progression in various cell types. However, such a paradigm has not been fully investigated in melanoma. Stromal expression of periostin (S-periostin) is one of the clues to link “inflammation” to “melanoma progression”, because 1) S-periostin is induced in various cutaneous inflammation, 2) S-periostin is involved in tolerogenic M2 macrophage induction, and 3) S-periostin is associated with histological grading of human melanoma. In this study, we first evaluated the prognostic value of S-periostin and found that the intensity of S-periostin was indeed a significant, unfavorable prognostic factor for melanoma (N=94) and that it was also significantly associated with the number of infiltrated M2 macrophages. In murine chronic inflammation model, S-periostin was induced by repeated application of 1% trinitrochlorobenzene every other day for 2 weeks. We then inoculated B16 melanoma cells intradermally into the normal or inflamed murine skin. Three weeks after the inoculation, tumor size in the inflamed skin was significantly larger than that in control skin. Although the number of infiltrated CD3+ T cells was comparable between two groups, significantly more number of CD163+ M2 macrophages were recruited in the melanomas in the inflamed skin than those in control skin. Notably, peritumoral S-periostin was significantly enhanced in the inflamed skin than control. Moreover, periostin receptor αVβ5 integrin was expressed in B16 melanoma cells and periostin significantly upregulated the migration of B16 melanoma cells in vitro. These findings stress a critical role of S-periostin in human and murine melanoma progression and probably prognosis. Furthermore, S-periostin may be implicated in inflammation-associated melanoma progression.

開催年月日： 2017年4月

記述言語：英語   会議種別：口頭発表（一般）  

国名：アメリカ合衆国  

It is widely accepted that chronic inflammation initiates and promotes carcinogenesis and tumor progression in various cell types. However, such a paradigm has not been fully investigated in melanoma. In this study, we inoculated B16 melanoma cells intradermally into the normal or inflamed murine back skin. Chronic inflammation was induced by repeated application of 1% trinitrochlorobenzene every other day for 2 weeks which successfully provided Th1/Th2-intermingled milieu. In a few weeks after inoculation, tumor size in the inflamed skin was significantly larger than that in control skin. Although the number of infiltrated CD3+ T cells was comparable between two groups, significantly more number of CD163+ M2 macrophages were accumulated in the tumor nests of inflamed skin than those in control skin. Notably, tumor nests of inflamed skin were surrounded by higher intensity of periostin compared with those in control skin. In parallel, periostin did promote the tumor growth of B16 melanoma cells in vitro. These findings suggest that chronic inflammation plays a critical role in melanoma progression possibly via periostin induction. In clinical settings, the biologic properties of acral melanomas may be affected by chronic inflammatory events such as repeated friction, trauma and fungal infection.

記述言語：英語  

記述言語：日本語   出版者・発行元：(株)メディカルレビュー社  

記述言語：日本語   出版者・発行元：日本皮膚科学会-西部支部