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1. Mechanism of action of adapalene for treating EGFR‐TKI‐induced skin disorder

Author

Chihiro Mimura, Tatsuya Nagano, Nanako Miwa, Kanoko Matsumura, Jun Yamada, Hiroki Satoh, Ratoe Suraya, Daisuke Hazama, Daisuke Tamura, Masatsugu Yamamoto, Motoko Tachihara, Yoshihiro Nishimura, and Kazuyuki Kobayashi

Subjects
acneiform eruption, afatinib, erlotinib, molecular‐targeting agent, skin disorder, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Skin disorders are the most common side effect associated with epidermal growth factor receptor‐tyrosine kinase inhibitor (EGFR‐TKI) therapy. It is important to manage skin lesions. Adapalene has been used to treat skin lesions caused by EGFR‐TKIs in some cases. The aim of this study was to investigate the functional mechanism of adapalene in erlotinib‐induced skin disorder. Methods To analyze the effect of adapalene on skin rash, afatinib and adapalene were administered to mice. The relationship between the concentration of adapalene and skin disorders was also examined by analyzing AQP3 expression. A skin lesion model was experimentally established in human skin keratinocytes (HaCaT) by using erlotinib with TNF‐α and IL‐1β. We used qRT–PCR to analyze chemokine‐induced inflammation and western blotting to analyze the effects of adapalene on the NF‐κB signaling pathway. Antimicrobial peptides and adhesion factors were also examined using qRT–PCR. Results Mice administered 0.01% adapalene had less skin inflammation than mice treated with afatinib alone. The expression level of AQP3 decreased in an adapalene concentration‐dependent manner. The mRNA levels of proinflammatory cytokines such as CCL2 and CCL27 in HaCaT cells were significantly reduced by adapalene. The expression of an antimicrobial peptide, hBD3, was upregulated after adapalene treatment. Adhesion factors, such as E‐cadherin, were significantly downregulated by EGFR‐TKI and significantly upregulated by adapalene treatment. Western blot analysis suggested that erlotinib‐induced phosphorylation of p65 was decreased by adapalene. Conclusion We suggest that adapalene may be a possible treatment option for skin disorders induced by EGFR‐TKIs.

Published
2024
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2. Retrospective analysis of the effect of inhaler education on improvements in inhaler usage

Author

Yuichiro Yasuda, Takeo Nakajima, Kazuyuki Kobayashi, Masahiro Katsurada, Reina Sekiya, Yoshihiro Nishimura, Daisuke Hojo, Nanako Miwa, and Tatsuya Nagano

Subjects
Adult, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, education, Drug Delivery Systems, Sex Factors, Primary outcome, Patient Education as Topic, Older patients, Administration, Inhalation, Retrospective analysis, Humans, Medicine, Aged, Retrospective Studies, Asthma, Inhalation, business.industry, Nebulizers and Vaporizers, Medical record, Inhaler, Age Factors, Middle Aged, Japanese population, medicine.disease, Self Care, Physical therapy, Female, business, Procedures and Techniques Utilization
Abstract

Introduction Various types of inhalation devices have been released, and it is necessary to acquire the skills for using each of them. The factors that have been previously associated with poor inhalator usage include gender, duration of disease, age, and the type of device. However, it is unclear whether these factors also apply to the Japanese population. The number of education sessions needed to acquire inhaler usage skills is also not established. Patients and methods We performed a retrospective review of the medical records of selected patients and their subjective assessments of their inhaler usage skills between January 2016 and March 2018. The primary outcome was the effect of inhaler education for each inhaler device. The secondary outcomes were the factors affecting the effectiveness of inhaler education, the effects of inhalation education stratified by age, and the number of inhaler education sessions needed to improve inhaler usage skills. Results Data from 399 patients were analyzed. Age and the type of delivery device affected the mastery of inhaler usage skills. Approximately half of the patients had acquired inhaler usage skills during baseline evaluation. Approximately 90% of patients acquired inhalation usage skills after two education sessions, regardless of the type of inhalation device. Among the older patients, 35.0% had acquired inhaler usage skills during the baseline evaluation, and 86.8% acquired them after two education sessions. Conclusions Inhaler usage skills significantly improved, regardless of the device, after inhalation education, and this was also observed in elderly patients after two education sessions.

Published
2021

3. Caspase Recruitment Domain-Containing Protein 9 Expression is a Novel Prognostic Factor for Lung Adenocarcinoma

Author

Nanako Miwa, Yoshihiro Nishimura, Yugo Tanaka, Tomoo Itoh, Ryota Dokuni, Naoe Jimbo, Masahiro Katsurada, Tatsuya Nagano, Tatsunori Kiriu, Yuichiro Yasuda, Kazuyuki Kobayashi, Motoko Tachihara, Masatsugu Yamamoto, Yoshimasa Maniwa, and Chihiro Mimura

Subjects
0301 basic medicine, Lung, biology, business.industry, medicine.disease, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, Oncology, Tumor progression, 030220 oncology & carcinogenesis, Cancer cell, medicine, biology.protein, Cancer research, Adenocarcinoma, Immunohistochemistry, Pharmacology (medical), Bone marrow, business, Lung cancer, Caspase
Abstract

Purpose Caspase recruitment domain-containing protein 9 (CARD9) is expressed at high levels in bone marrow cells and has a crucial role in innate immunity. Current studies indicate that CARD9 also plays a key role in tumor progression, but there are few reports on the role of CARD9 in lung cancer. The aim of this study was to clarify the role of CARD9 in lung adenocarcinoma. Patients and methods Lung adenocarcinoma tumor samples from 74 patients who underwent complete resection at Kobe University Hospital from January 2014 to December 2014 were analyzed by immunohistochemistry. The role of CARD9 in cancer cells was analyzed using lung cancer cell lines treated with CARD9 siRNA. Results High expression of CARD9 was observed in 32.4% of tumors, and compared to low expression of CARD9, high expression was associated with poorer overall survival (P = 0.0365). Univariate and multivariate analyses showed that high expression of CARD9 was an independent prognostic factor. Knockdown of CARD9 in lung adenocarcinoma cells inhibited proliferation but did not increase apoptosis. In addition, CARD9 activated the NF-κB pathway in a lung adenocarcinoma cell line. Conclusion CARD9 was shown to be an independent prognostic factor of poor outcome for lung cancer and may represent a molecular target for treatment.

Published
2020

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