Language：Japanese   Publisher：Western Division of Japanese Dermatological Association  

DOI： 10.2336/nishinihonhifu.86.571

CiNii Research

Language：Japanese   Publisher：Western Division of Japanese Dermatological Association  

DOI： 10.2336/nishinihonhifu.86.609

CiNii Research

Language：English   Publisher：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

Language：English   Publisher：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

Language：Japanese   Publisher：Western Division of Japanese Dermatological Association  

DOI： 10.2336/nishinihonhifu.85.366

Scopus

CiNii Research

Event date： 2018.6

Language：English   Presentation type：Oral presentation (general)  

Country：China  

Event date： 2018.6

Language：English   Presentation type：Oral presentation (general)  

Country：China  

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.

Event date： 2017.9

Language：English   Presentation type：Oral presentation (general)  

Country：Germany  

Event date： 2017.4

Language：English   Presentation type：Oral presentation (general)  

Country：United States  

Language：English  

Language：Japanese   Publisher：(株)メディカルレビュー社  

Language：Japanese   Publisher：日本皮膚科学会-西部支部