Updated on 2025/08/22

写真a

 
UHARA Hisashi
 
Organization
School of Medicine Department of Dermatology Professor
Title
Professor
Profile
学歴、職歴(2018/10/1現在)

1979年 長野県立須坂高等学校卒
1986年 北海道大学医学部卒
信州大学医学部附属病院皮膚科 研修医
1987年 信州大学医学部附属病院皮膚科 助手
1988年 国立がんセンター研究所病理部及び附属病院皮膚科 任意研修医
1990年 諏訪赤十字病院皮膚科
1991年 信州大学医学部附属病院皮膚科 助手
1995年 信州大学医学部附属病院皮膚科 講師
2011年 信州大学医学部皮膚科 准教授
2017年 札幌医科大学医学部皮膚科学講座 教授

所属学会
日本皮膚科学会(代議員)
日本皮膚悪性腫瘍学会(評議員)
日本色素細胞学会(理事)
日本研究皮膚科学会(評議員)
日本臨床皮膚医会
日本皮膚病理組織学会
日本癌学会
日本癌治療学会
日本臨床腫瘍学会
The American Society of Clinical Oncology(ASCO)
The European Society for Medical Oncology(ESMO)
委員他
日本皮膚悪性腫瘍学会・悪性黒色腫薬物療法の手引作成委員
JCOG皮膚腫瘍グループ代表委員
日本臨床腫瘍学会 免疫チェックポイント阻害薬ガイドライン委員
WHO Classification of Skin Tumours, 4th edition 2018(協力著者)
著書
皮膚科診断をきわめる-目を閉じて診る、もうひとつの診断学(秀潤社、2016刊)
どう診る、どう治す、皮膚診療はじめの一歩(羊土社、2013刊)
皮膚科への一歩(電子書籍)
Web
うはら皮膚科(仮想クリニック)uhara.org

Hisashi Uhara, M.D., Ph.D.
CURRICULUM VITAE

PRESENT POSITION:
Professor & Chairman, Department of Dermatology
Sapporo Medical University School of Medicine, Sapporo, Japan
OFFICE ADDRESS: South 1, West 16, Chuo-ku, 060-8543, Japan
E-MAIL: uharah@sapmed.ac.jp
PHONE: +81-11-611-2111
FAX: +81-11-613-3739

EDUCATION AND TRAINING:
1986 MD: Hokkaido University School of Medicine, Sapporo, Japan
1986-1987 Resident in Dermatology, Shinshu University School of Medicine
1988-1990 Resident (Voluntary) in Pathology and Dermatology, National Cancer Center, Tokyo, Japan
1994 PhD: Shinshu University School of Medicine
2009 Visiting Scholar in Department of Pathology and Laboratory Medicine, UCLA (Prof. Cochran), CA, USA

APPOINTMENT:
1987 Assistant, Shinshu University School of Medicine
1990 Chief,Dermatology Clinic, Japanese Red Cross Society Suwa Hospital, Suwa, Japan
1991 Assistant, Shinshu University School of Medicine
1993-2003 Visiting instructor, Matsumoto Dental University, Shiojiri, Japan
1995 Senior Assistant Professor, Shinshu University School of Medicine
2011 Associate Professor, Shinshu University School of Medicine
2017 Professor & Chairman, Department of Dermatology, Sapporo Medical University School of Medicine

LICENSURE AND CERTIFICATE:
1986 National License of Physician
1995 Board Certificated Dermatologist
2008-2013 Specialist of Cutaneous Oncology

HONORS:
2007 Certificate of Recognition for Outstanding Posters in Diagnostic tools, The 21st World Congress of Dermatology (Buenos Aires)
2008 Best Clinical Award, the 72nd Annual Meeting of the Eastern Japan Division of Japanese Dermatological Association (Akita)
2010- The Best Doctors in Japan

EDITORIAL ACTIVITY:
2010- Editorial Board, International Journal of Clinical Oncology

MEMBERSHIP OF SCIENTIFIC SOCIETY:
Japanese Dermatological Association (representative)
The Japan Clinical Oncology Group (JCOG), Dermatologic Oncology Group (committee)
Japanese Skin Cancer Society (representative)
Japanese Society for Pigment Cell Research (representative)
Japan Society of Clinical Oncology
Japanese Cancer Association
ESMO
ASCO

MAJOR SCIENTIFIC INTERESTS:
Skin Cancers (management & oncogenesis), Liquid biopsy, Dermoscopy, Sonography, Lymphatic drainage pathway, Drug allergy, Sweating test
External link

Degree

  • Doctor of Medicine

Research Interests

  • dermoscopy

  • Ultrasonography

  • melanoma

  • genetics

  • skin cancer

  • cancer immunology

  • immune related adverse events

  • liquid biopsy

Research Areas

  • Life Science / Dermatology

Education

  • Hokkaido University   Faculty of Medicine

    - 1986

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Research History

  • Shinshu University School of Medicine

    1990.2 - 2017.1

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  • 諏訪赤十字病院皮膚科

    1990.2 - 1991.1

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  • Resident in Dermatology, Shinshu University School of Medicine

    1986.6 - 1988.8

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Professional Memberships

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Committee Memberships

  • 日本皮膚悪性腫瘍学会   評議員、予後統計調査委員会委員  

       

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  • 日本皮膚科学会   代議員、ガイドライン作成委員会委員  

       

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    Committee type:Academic society

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Papers

  • Dominant inheritance in hereditary angioedema associated with carboxypeptidase N deficiency. International journal

    Tokimasa Hida, Masashi Idogawa, Masae Okura, Takashi Tokino, Hisashi Uhara

    Allergology international : official journal of the Japanese Society of Allergology   2025.4

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  • Efficacy of eribulin monotherapy for bone marrow carcinomatosis of breast cancer in a patient with Werner syndrome.

    Akihito Fujimi, Yasuhiro Nagamachi, Naofumi Yamauchi, Riku Hasebe, Naoki Onoyama, Naotaka Hayasaka, Teppei Matsuno, Kazuhiko Koike, Yoshiro Gotoh, Kohji Ihara, Junji Kato, Takuji Nishisato, Kazuyuki Murase, Goro Kutomi, Tokimasa Hida, Hisashi Uhara, Kohichi Takada

    Geriatrics & gerontology international   2025.1

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    Various complications and potential risks of serious adverse events lessens the intensity of chemotherapy in patients with Werner syndrome. Bone marrow carcinomatosis of breast cancer was developed in a patient with Werner syndrome. Eribulin proved well tolerated and effective in improving severe thrombocytopenia, leading to platelet transfusion-free status.

    DOI: 10.1111/ggi.15070

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  • The genomic landscape of cutaneous squamous cell carcinoma in Japan. International journal

    Junji Kato, Tokimasa Hida, Masashi Idogawa, Takashi Tokino, Hisashi Uhara

    The Journal of dermatology   2024.12

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    Comprehensive studies of the genetic profiles of cutaneous squamous cell carcinoma (cSCC) in Japanese patients have been lacking, although an understanding of these profiles is crucial for improving treatment outcomes. Since 2019, comprehensive genomic profiling (CGP) has been covered by Japan's health insurance, and the resulting data have been compiled into a comprehensive database by the country's Center for Cancer Genomics and Advanced Therapeutics (C-CAT). In this retrospective study, we used CGP data from the C-CAT database to analyze genomic characteristics of cSCC in Japanese patients. The patients' clinical and genomic data, including the chemotherapy regimens, tumor mutational burden (TMB), and survival status, were obtained. We analyzed the cases of 152 patients, with only those evaluated by the FoundationOne® CDx included for accuracy. Among the 152 patients, the most common gene oncogenic alterations were observed in TP53 (67%), CDKN2A (54%), TERT (49%), CDKN2B (33%), and NOTCH1 (18%). TMB-high (≥10 mut/Mb) was observed in 27% (n = 41) of the patients, with a median age of 75 years for this group. TMB-low (<10 mut/Mb) was observed in 73% (n = 111) of the patients; their median age was 67 years.

    DOI: 10.1111/1346-8138.17592

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  • Single-cell profiling of acral melanoma infiltrating lymphocytes reveals a suppressive tumor microenvironment. International journal

    Tomoyuki Minowa, Kenji Murata, Yuka Mizue, Aiko Murai, Munehide Nakatsugawa, Kenta Sasaki, Serina Tokita, Terufumi Kubo, Takayuki Kanaseki, Tomohide Tsukahara, Toshiya Handa, Sayuri Sato, Kohei Horimoto, Junji Kato, Tokimasa Hida, Yoshihiko Hirohashi, Hisashi Uhara, Toshihiko Torigoe

    Science translational medicine   16 ( 776 )   eadk8832   2024.12

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    Acral lentiginous melanoma (ALM) is the most common melanoma subtype in non-Caucasians. Despite advances in cancer immunotherapy, current immune checkpoint inhibitors remain unsatisfactory for ALM. Hence, we conducted comprehensive immune profiling using single-cell phenotyping with reactivity screening of the T cell receptors of tumor-infiltrating T lymphocytes (TILs) in ALM. Compared with cutaneous melanoma, ALM showed a lower frequency of tumor-reactive CD8 clusters and an enrichment of regulatory T cells with direct tumor recognition ability, suggesting a suppressive immune microenvironment in ALM. Tumor-reactive CD8 TILs showed heterogeneous expression of coinhibitory molecules, including KLRC1 (NKG2A), in subpopulations with therapeutic implications. Overall, our study provides a foundation for enhancing the efficacy of immunotherapy in ALM.

    DOI: 10.1126/scitranslmed.adk8832

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  • Genetic Characteristics of Cutaneous, Acral, and Mucosal Melanoma in Japan. International journal

    Tokimasa Hida, Masashi Idogawa, Junji Kato, Yukiko Kiniwa, Kohei Horimoto, Sayuri Sato, Masahide Sawada, Shoichiro Tange, Masae Okura, Ryuhei Okuyama, Takashi Tokino, Hisashi Uhara

    Cancer medicine   13 ( 22 )   e70360   2024.11

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    BACKGROUND: Acral and mucosal melanomas are more prevalent in Asians than in Caucasians, unlike cutaneous melanomas, which are predominant in Caucasians. Recent studies have suggested that non-Caucasian cutaneous melanomas responded less to immune checkpoint inhibitors, highlighting the need for genetic profiling across ethnicities. This study aimed to elucidate the genetic characteristics of Japanese melanomas, which is an under-researched topic. METHODS: Single-nucleotide variants, indels, and copy number alterations in 104 Japanese melanoma patients (37 cutaneous, 52 acral, and 15 mucosal) were analyzed using custom panel sequencing. RESULTS: Driver events were detected in 94% of the cases. Among cutaneous melanoma cases, 76% had BRAF mutations, and 8% had NRAS mutations. In acral melanoma, BRAF (9%), NRAS (17%), KRAS (8%), KIT (19%), and NF1 (7%) mutations were detected. Major driver mutations in mucosal melanoma were detected in NRAS, KRAS, NF1, PTEN, GNAQ, and KIT. The median tumor mutational burden across all melanoma types was 4.6 mutations/Mb, with no significant difference between the cutaneous and acral/mucosal types. Of the 21 patients with both primary and metastatic lesions, 11 showed distinct mutations in each. Potentially actionable mutations were detected in 58 patients in addition to BRAF V600E/K mutations in 31. CONCLUSIONS: This study highlights distinct genetic abnormalities and actionable alterations in Japanese melanoma patients. This suggests a lower tumor mutational burden in East Asian cutaneous melanoma, which may affect the efficacy of immune checkpoint inhibitors. The heterogeneity of driver mutations across and within individuals highlights the need for personalized treatment approaches.

    DOI: 10.1002/cam4.70360

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  • Extramammary Paget's disease treated with of anti-programmed cell death protein 1 therapy after docetaxel therapy failure. International journal

    Midori Narasaki, Junji Kato, Sayuri Sato, Tokimasa Hida, Kohei Horimoto, Yoshiyuki Matsui, Nobuaki Shigyo, Hisashi Uhara

    The Journal of dermatology   2024.10

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    Extramammary Paget's disease (EMPD) is a rare skin cancer with no standard treatment for advanced-stage disease. Although docetaxel-based chemotherapy is common, no standard treatment exists. Pembrolizumab is approved for solid tumors with a high tumor mutation burden (TMB) and/or high microsatellite instability, and nivolumab was approved in Japan in February 2024 for unresectable advanced or recurrent epithelial skin malignancies. However, there is a lack of real-world data regarding the efficacy of anti-programmed cell death protein 1 (PD-1) therapy for EMPD. We present the case details of three EMPD patients treated with anti-PD-1 therapy after docetaxel treatment, with TMB values of 17.8, 14.3, and 5.0 mut/Mb, respectively, and we review similar reported cases. Even in the cases with a high TMB, the response to anti-PD-1 therapy was not sufficient. Most cases involve second-line or later treatments, so further research is needed to determine the precise effectiveness of anti-PD-1 therapy as a first-line treatment.

    DOI: 10.1111/1346-8138.17500

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  • Application of Single Cell Type-Derived Spheroids Generated by Using a Hanging Drop Culture Technique in Various In Vitro Disease Models: A Narrow Review. International journal

    Hiroshi Ohguro, Megumi Watanabe, Tatsuya Sato, Nami Nishikiori, Araya Umetsu, Megumi Higashide, Toshiyuki Yano, Hiromu Suzuki, Akihiro Miyazaki, Kohichi Takada, Hisashi Uhara, Masato Furuhashi, Fumihito Hikage

    Cells   13 ( 18 )   2024.9

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    Cell culture methods are indispensable strategies for studies in biological sciences and for drug discovery and testing. Most cell cultures have been developed using two-dimensional (2D) culture methods, but three-dimensional (3D) culture techniques enable the establishment of in vitro models that replicate various pathogenic conditions and they provide valuable insights into the pathophysiology of various diseases as well as more precise results in tests for drug efficacy. However, one difficulty in the use of 3D cultures is selection of the appropriate 3D cell culture technique for the study purpose among the various techniques ranging from the simplest single cell type-derived spheroid culture to the more sophisticated organoid cultures. In the simplest single cell type-derived spheroid cultures, there are also various scaffold-assisted methods such as hydrogel-assisted cultures, biofilm-assisted cultures, particle-assisted cultures, and magnet particle-assisted cultures, as well as non-assisted methods, such as static suspension cultures, floating cultures, and hanging drop cultures. Since each method can be differently influenced by various factors such as gravity force, buoyant force, centrifugal force, and magnetic force, in addition to non-physiological scaffolds, each method has its own advantages and disadvantages, and the methods have different suitable applications. We have been focusing on the use of a hanging drop culture method for modeling various non-cancerous and cancerous diseases because this technique is affected only by gravity force and buoyant force and is thus the simplest method among the various single cell type-derived spheroid culture methods. We have found that the biological natures of spheroids generated even by the simplest method of hanging drop cultures are completely different from those of 2D cultured cells. In this review, we focus on the biological aspects of single cell type-derived spheroid culture and its applications in in vitro models for various diseases.

    DOI: 10.3390/cells13181549

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  • A case of familial progressive hyperpigmentation with or without hypopigmentation presenting with hypopigmented striae along the lines of Blaschko. International journal

    Tokimasa Hida, Masashi Idogawa, Aki Ishikawa, Masae Okura, Satoru Sasaki, Takashi Tokino, Hisashi Uhara

    The Journal of dermatology   2024.9

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    Familial progressive hyperpigmentation with or without hypopigmentation (FPHH) is an autosomal dominant disorder characterized by widespread skin hyperpigmentation, café-au-lait spots, and hypopigmented circular macules, resulting from KITLG variants. KITLG, expressed by keratinocytes, binds to KIT on melanocytes, stimulating melanogenesis. Disturbances in the KITLG-KIT interaction result in diffuse hyperpigmentation in FPHH. However, the mechanisms behind hypopigmented macule formation remain unclear. This report presents a unique FPHH case in a patient with a novel KITLG mutation (Ser78Leu). Notably, the patient showed multiple hypopigmented macules and striae along the lines of Blaschko. Digital polymerase chain reaction analysis of the DNA from skin and blood tissues indicated a copy-neutral loss of heterozygosity at the KITLG locus, only in the hypopigmented macule. These findings suggest that the hypopigmented macules might result from revertant mosaicism. Conversely, café-au-lait spots do not follow the lines of Blaschko and can superimpose on the hypopigmented striae, indicating a distinct pathogenesis. This case contributes to the understanding of the genetic mechanisms in FPHH.

    DOI: 10.1111/1346-8138.17459

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  • Genomic landscape of cutaneous, acral, mucosal, and uveal melanoma in Japan: analysis of clinical comprehensive genomic profiling data.

    Tokimasa Hida, Junji Kato, Masashi Idogawa, Takashi Tokino, Hisashi Uhara

    International journal of clinical oncology   2024.9

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    BACKGROUND: Cutaneous melanoma (CM) is the most common type in Caucasians, while acral melanoma (AM) and mucosal melanoma (MM), which are resistant to immunotherapies and BRAF/MEK-targeted therapies, are more common in East Asians. Genomic profiling is essential for treating melanomas, but such data are lacking in Japan. METHODS: Comprehensive genomic profiling data compiled in the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) were analyzed. RESULTS: A total of 380 melanomas was analyzed, including 136 CM, 46 AM, 168 MM, and 30 uveal melanoma (UM). MM included conjunctival, sinonasal, oral, esophageal, anorectal, and vulvovaginal melanomas. No significant difference in the median tumor mutational burden (TMB) of CM (3.39 mutations/megabase), AM (2.76), and MM (3.78) was the key finding. Microsatellite instability-high status was found in one case. BRAF V600E/K was found in only 45 patients (12%). Key driver mutations in CM were BRAF (38%), NRAS (21%), NF1 (8%), and KIT (10%), with frequent copy number alterations (CNAs) of CDKN2A, CDKN2B, and MYC. AM was characterized by altered KIT (30%), NRAS (26%), and NF1 (11%) and CDKN2A, CDKN2B, CDK4, MDM2, and CCND1 CNAs. MM was characterized by altered NRAS (24%), KIT (21%), and NF1 (17%) and MYC, KIT, and CDKN2A CNAs, with differences based on anatomical locations. UM bore GNAQ or GNA11 driver mutations (87%) and frequent mutations in SF3B1 or BAP1. CONCLUSION: The distinct genomic profiling in Japanese patients, including lower TMB, compared to Caucasians, is associated with poorer treatment outcomes. This result underscores the need for more effective therapeutic agents.

    DOI: 10.1007/s10147-024-02615-y

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  • Mosaic SUFU mutation associated with a mild phenotype of multiple hereditary infundibulocystic basal cell carcinoma syndrome. International journal

    Marina Hamada, Tokimasa Hida, Masashi Idogawa, Shoichiro Tange, Takafumi Kamiya, Masae Okura, Toshiharu Yamashita, Takashi Tokino, Hisashi Uhara

    The Journal of dermatology   2024.8

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    Multiple hereditary infundibulocystic basal cell carcinoma syndrome (MHIBCC), an autosomal dominant disorder caused by variants in SUFU, is characterized by numerous infundibulocystic basal cell carcinomas (IBCCs). In this report, we present a possible case of mosaic MHIBCC. A 57-year-old woman underwent the removal of four papules on her face, which were diagnosed as IBCCs. Exome sequencing revealed a SUFU c.1022+1G>A mutation within the skin tumor. The same mutation was detected in her blood but at a lower allele frequency. TA cloning revealed that the allele frequency of the mutation in the blood was 0.07. Additionally, tumor assessment revealed loss of heterozygosity (LOH) in chromosome 10, including the SUFU locus. These results indicate the patient had mosaicism for the SUFU mutation in normal tissues, aligning with the mosaic MHIBCC diagnosis. This, combined with LOH, likely contributed to IBCC development. Mosaic MHIBCC may present with milder symptoms. However, it may still increase the risk of developing brain tumors and more aggressive basal cell carcinoma. The possibility of mosaicism should be investigated in mild MHIBCC cases, where standard genetic tests fail to detect SUFU germline variants.

    DOI: 10.1111/1346-8138.17434

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  • Genomic profiles of Merkel cell carcinoma in Japan. International journal

    Junji Kato, Tokimasa Hida, Masashi Idogawa, Takashi Tokino, Hisashi Uhara

    The Journal of dermatology   2024.7

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    DOI: 10.1111/1346-8138.17401

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  • ざ瘡症状が遷延した慢性再発性多発性骨髄炎(CRMO)の1例

    半田 稔也, 菅 裕司, 熊谷 綾子, 肥田 時征, 宇原 久, 木澤 敏毅, 岡田 葉平

    日本皮膚科学会雑誌   134 ( 6 )   1660 - 1660   2024.5

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  • 当科における円形脱毛症に対するバリシチニブの治療経験

    畠山 瑞季, 菅 裕司, 松田 宇充, 濱田 茉里奈, 織田 美琴, 安食 さえ子, 熊谷 綾子, 肥田 時征, 宇原 久

    日本皮膚科学会雑誌   134 ( 6 )   1657 - 1657   2024.5

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  • Analysis of the immune microenvironment in the indolent form of primary cutaneous extranodal natural killer/T-cell lymphoma: A case report. International journal

    Risako Maeda, Tomoyuki Minowa, Junji Kato, Kohei Horimoto, Sayuri Sato, Yoshihiko Hirohashi, Toshihiko Torigoe, Hisashi Uhara

    The Journal of dermatology   51 ( 4 )   e137-e138   2024.4

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  • Long-term follow-up results from KEYNOTE-041: Phase 1b study of pembrolizumab in Japanese patients with advanced melanoma. International journal

    Kenji Yokota, Tatsuya Takenouchi, Yasuhiro Fujisawa, Satoshi Fukushima, Hiroshi Uchi, Takashi Inozume, Yoshio Kiyohara, Hisashi Uhara, Kazuhiko Nakagawa, Hiroshi Furukawa, Shirong Han, Masaru Watanabe, Kazuo Noguchi, Naoya Yamazaki

    The Journal of dermatology   2024.3

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    Pembrolizumab demonstrated an acceptable safety profile and promising antitumor activity in Japanese patients with advanced melanoma in the phase 1b KEYNOTE-041 (Study of Pembrolizumab [MK-3475] in Participants With Advanced Melanoma) trial. To evaluate the long-term efficacy and safety of pembrolizumab in Japanese patients with advanced melanoma in KEYNOTE-041. The current analysis reports results of additional follow-up of approximately 12 months since the initial analysis. Eligible patients had locally advanced (unresectable stage III) or metastatic (stage IV) melanoma not amenable to local therapy and had received two or fewer prior systemic therapies. Pembrolizumab 2 mg/kg was given every 3 weeks for up to 2 years or until confirmed progression or unacceptable toxicity. Primary end points included safety, tolerability, and overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 by independent central review. The data cutoff for this analysis was August 30, 2017. Forty-two patients were followed up for a median of 22.3 months (range, 2.63-30.82 months). The ORR was 24.3% (nine of 37 evaluable patients [95% confidence interval (CI), 11.8%-41.2%]). Two patients with partial response at the time of the initial analysis achieved complete response. The median overall survival (OS) was 25.1 months (95% CI, 13.1-not reached] and the 30-month OS rate was 46.3% (95% CI, 29.8%-61.3%). The median duration of response was not reached. Treatment-related adverse events (TRAEs) were reported in 78.6% of patients; the incidence of grade 3 to 5 TRAEs was 23.8%. No additional treatment-related deaths occurred since the initial analysis. Pembrolizumab provided durable antitumor activity and an acceptable safety profile in Japanese patients with advanced melanoma.

    DOI: 10.1111/1346-8138.17002

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  • Distinct induction pathways of heat shock protein 27 in human keratinocytes: Heat stimulation or capsaicin through phosphorylation of heat shock factor 1 at serine 326 and/or suppression of ΔNp63. International journal

    Terufumi Kubo, Kenta Sasaki, Sayuri Sato, Tomoyuki Minowa, Tokimasa Hida, Kenji Murata, Takayuki Kanaseki, Tomohide Tsukahara, Yoshihiko Hirohashi, Hisashi Uhara, Toshihiko Torigoe

    Biochemical and biophysical research communications   708   149817 - 149817   2024.3

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    Epidermal keratinocytes, forming the outermost layer of the human body, serve as a crucial barrier against diverse external stressors such as ultraviolet radiation. Proper keratinocyte differentiation and effective responses to external stimuli are pivotal for maintaining barrier integrity. Heat is one such stimulus that triggers the synthesis of heat shock proteins (HSPs) when cells are exposed to temperatures above 42 °C. Additionally, activation of the transient receptor potential cation channel subfamily V member 1 (TRPV1) occurs at 42 °C. Here, we explore the interplay between TRPV1 signaling and HSP induction in human keratinocytes. Both heat and capsaicin, a TRPV1 agonist, induce expression of HSP27, HSP70, and HSP90 in keratinocytes. Interestingly, pharmacological inhibition of TRPV1 attenuates heat-induced HSP27 expression, but not that of HSP70 or HSP90. Furthermore, both heat and capsaicin stimulation result in distinct phosphorylation patterns of heat shock factor 1 (HSF1), with phosphorylation at serine 326 being a common feature. Notably, genetic manipulation to mimic dephosphorylation of HSF1 at serine 326 reduces HSP27 levels. Additionally, ΔNp63, a key regulator of epidermal differentiation, negatively modulates HSP27 expression independently of HSF1 phosphorylation status. While heat stimulation has no effect on ΔNp63 expression, capsaicin reduces its levels. The precise role of TRPV1 signaling in keratinocytes warrants further investigation for a comprehensive understanding of its impact on barrier function.

    DOI: 10.1016/j.bbrc.2024.149817

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  • Melanoma incidence on the non-weight-bearing areas of the sole. International journal

    Kazuki Furudate, Junji Kato, Kohei Horimoto, Sayuri Sato, Tokimasa Hida, Masahide Sawada, Tomoyuki Minowa, Hisashi Uhara

    The Journal of dermatology   2024.2

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  • 【メラノーマ診療Up-To-Date】メラノーマの治療選択における包括的がんゲノムプロファイリング検査

    肥田 時征, 加藤 潤史, 井戸川 雅史, 宇原 久

    皮膚病診療   46 ( 1 )   28 - 33   2024.1

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    Language:Japanese   Publisher:(株)協和企画  

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  • Characterization of CD4 T-cell phenotype in human leukocyte antigen class II-positive acral melanoma. International journal

    Nayuha Shogase, Tomoyuki Minowa, Junji Kato, Kohei Horimoto, Sayuri Sato, Tokimasa Hida, Yoshihiko Hirohashi, Toshihiko Torigoe, Hisashi Uhara

    The Journal of dermatology   2023.12

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  • SJS進展型TENを発症した小児患者の2例

    勝賀瀬 なゆは, 菅 裕司, 熊谷 綾子, 小松 彩友香, 小栗 瑛実, 箕輪 智幸, 宇原 久

    日本皮膚科学会雑誌   133 ( 12 )   2853 - 2853   2023.11

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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   2023.10

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    DOI: 10.1111/1346-8138.16977

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  • 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   14   2023.9

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    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: 10.3389/fimmu.2023.1259071

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

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

    The Journal of dermatology   2023.9

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    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: 10.1111/1346-8138.16925

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  • 【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   45 ( 9 )   802 - 805   2023.9

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

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

    International journal of dermatology   2023.6

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    DOI: 10.1111/ijd.16771

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  • 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   39回   229 - 229   2023.6

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

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

    The Journal of dermatology   2023.5

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  • 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   40 ( 3 )   471 - 471   2023.5

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  • 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   133 ( 5 )   1403 - 1404   2023.5

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  • 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. International journal

    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   2023.3

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    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: 10.1016/j.jdermsci.2023.03.008

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  • 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   133 ( 3 )   541 - 541   2023.3

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  • 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   133 ( 3 )   542 - 542   2023.3

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

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

    Cells   12 ( 5 )   2023.2

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    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: 10.3390/cells12050759

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  • 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   133 ( 2 )   271 - 272   2023.2

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

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

    The British journal of dermatology   188 ( 1 )   142 - 143   2023.1

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    DOI: 10.1093/bjd/ljac009

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

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

    The Journal of dermatology   49 ( 12 )   1334 - 1337   2022.12

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    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: 10.1111/1346-8138.16545

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

    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   2022.12

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    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: 10.1016/j.jid.2022.06.021

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  • 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   132 ( 12 )   2699 - 2699   2022.11

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  • Linear lichen planus after COVID-19 vaccination. International journal

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

    The Australasian journal of dermatology   63 ( 4 )   e385-e387   2022.11

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    DOI: 10.1111/ajd.13902

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  • 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   132 ( 12 )   2697 - 2697   2022.11

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  • 顔面に多発したbasaloid follicular hamartomaの1例

    濱田 茉里奈, 肥田 時征, 神谷 崇文, 宇原 久, 井戸川 雅史, 山下 利春

    日本皮膚科学会雑誌   132 ( 12 )   2704 - 2704   2022.11

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  • Dermoscopy for Acral Melanocytic Lesions: Revision of the 3-step Algorithm and Refined Definition of the Regular and Irregular Fibrillar Pattern. International journal

    Toshiaki Saida, Hiroshi Koga, Hisashi Uhara

    Dermatology practical & conceptual   12 ( 3 )   e2022123   2022.7

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    DOI: 10.5826/dpc.1203a123

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  • Immunomodulation of Melanoma by Chemo-Thermo-Immunotherapy Using Conjugates of Melanogenesis Substrate NPrCAP and Magnetite Nanoparticles: A Review International journal

    Yasuaki Tamura, Akira Ito, Kazumasa Wakamatsu, Takafumi Kamiya, Toshihiko Torigoe, Hiroyuki Honda, Toshiharu Yamashita, Hisashi Uhara, Shosuke Ito, Kowichi Jimbow

    International Journal of Molecular Sciences   23 ( 12 )   2022.6

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    A major advance in drug discovery and targeted therapy directed at cancer cells may be achieved by the exploitation and immunomodulation of their unique biological properties. This review summarizes our efforts to develop novel chemo-thermo-immunotherapy (CTI therapy) by conjugating a melanogenesis substrate, N-propionyl cysteaminylphenol (NPrCAP: amine analog of tyrosine), with magnetite nanoparticles (MNP). In our approach, NPrCAP provides a unique drug delivery system (DDS) because of its selective incorporation into melanoma cells. It also functions as a melanoma-targeted therapeutic drug because of its production of highly reactive free radicals (melanoma-targeted chemotherapy). Moreover, the utilization of MNP is a platform to develop thermo-immunotherapy because of heat shock protein (HSP) expression upon heat generation in MNP by exposure to an alternating magnetic field (AMF). This comprehensive review covers experimental in vivo and in vitro mouse melanoma models and preliminary clinical trials with a limited number of advanced melanoma patients. We also discuss the future directions of CTI therapy.

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  • Difference in immunohistochemical findings among anti-PD-L1 antibodies and their relationships with CD4+ and CD8+ T cells in Japanese melanoma patients.

    Daisuke Yoneta, Junji Kato, Takafumi Kamiya, Kohei Horimoto, Sayuri Sato, Masahide Sawada, Tomoyuki Minowa, Tokimasa Hida, Shintaro Sugita, Hisashi Uhara

    International journal of clinical oncology   27 ( 8 )   1364 - 1371   2022.6

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    BACKGROUND: The immunohistochemical evaluation of programmed death ligand 1 (PD-L1) is important for selecting treatments. Several antibodies are available for such evaluations, but data regarding the differences in the antibodies' positivity are limited in melanoma, particularly the acral and mucosal types. We investigated the differences in melanoma tissues' PD-L1 expression among the commonly used PD-L1 antibodies and then evaluated the relationship between PD-L1+ tumor cells and tumor-infiltrating lymphocytes (TILs). PATIENTS AND METHODS: We examined 56 primary lesions and 8 metastatic lymph node samples from 56 Japanese patients with melanoma (28 acral melanoma, 8 mucosal melanoma, 18 cutaneous melanoma, 2 unknown). Immunohistochemical staining was performed using three primary antibodies against PD-L1 (E1L3N, SP142, and 28-8). PD-L1-positive staining in tumor cells was defined as ≥ 1% expression. RESULTS: The positive rates were 25.0% for 28-8, 34.0% for E1L3N, and 34.0% for SP142 in 64 samples. The positive rates of acral melanoma were 10.7% for 28-8, 21.4% for E1L3N, and 21.4% for SP142. The positive rate of mucosal melanoma for which all three antibodies reacted was 12.5%. The positive rates of cutaneous melanoma were 55.6% for 28-8, 66.7% for E1L3N, and 66.7% for SP142. Significant relationships were observed among the PD-L1+ tumor cells, CD4+ TILs, and CD8+ TILs (p < 0.001). CONCLUSION: The staining results by E1L3N, SP142, and 28-8 antibodies were within the allowable range, although the positive rates by E1L3N and P142 were slightly higher than that of 28-8. CD4+ TILs and CD8+ TILs were quantitatively correlated with PD-L1-positive tumor cells.

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  • Difference in immunohistochemical findings among anti-PD-L1 antibodies and their relationships with CD4+ and CD8+ T cells in Japanese melanoma patients

    Daisuke Yoneta, Junji Kato, Takafumi Kamiya, Kohei Horimoto, Sayuri Sato, Masahide Sawada, Tomoyuki Minowa, Tokimasa Hida, Shintaro Sugita, Hisashi Uhara

    International Journal of Clinical Oncology   2022.6

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    Other Link: https://link.springer.com/article/10.1007/s10147-022-02189-7/fulltext.html

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  • クロタミトンによる肛囲・会陰皮膚潰瘍の2例

    半田 稔也, 神谷 崇文, 箕輪 智幸, 菅 裕司, 肥田 時征, 澄川 靖之, 宇原 久

    日本皮膚科学会雑誌   132 ( 5 )   1303 - 1303   2022.5

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  • Delayed-onset abscopal effect after palliative radiotherapy for acral melanoma treated with anti-PD-1 therapy. International journal

    Hiroshi Sasaki, Junji Kato, Kohei Horimoto, Sayuri Sato, Yuna Hosokawa, Toshiya Handa, Eri Kobayashi, Kazuki Furudate, Haruka Sigyo, Takaaki Tsuchiya, Masanori Someya, Hisashi Uhara

    The Journal of dermatology   49 ( 8 )   e255-e256   2022.3

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  • Prognoses of patients with melanoma who continue/discontinue anti-programmed death-1 therapy after achieving a complete response in a real-world setting: a multicentre retrospective study. International journal

    Junji Kato, Kenjiro Namikawa, Jiro Uehara, Motoo Nomura, Yasuhiro Nakamura, Hisashi Uhara, Hiroshi Uchi, Shusuke Yoshikawa, Yukiko Kiniwa, Yoshiyuki Nakamura, Takuya Miyagawa, Shigeto Matsushita, Tatsuya Takenouchi, Naohito Hatta, Fumitaka Ohno, Taku Maeda, Satoshi Fukushima, Naoya Yamazaki

    The British journal of dermatology   187 ( 4 )   594 - 596   2022.3

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  • Primary cutaneous diffuse large B‐cell lymphoma, leg type, of the face that appeared on pre‐existing T‐cell pseudolymphoma clinically resembling actinic reticuloid

    Yuna Hosokawa, Takafumi Kamiya, Shintaro Sugita, Tokimasa Hida, Kohichi Takada, Yasuyuki Sumikawa, Hiroyuki Takahashi, Hisashi Uhara

    The Journal of Dermatology   2022.3

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    Other Link: https://onlinelibrary.wiley.com/doi/full-xml/10.1111/1346-8138.16331

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  • Anogenital skin necrosis with fibrin thrombosis induced by crotamiton. International journal

    Toshiya Handa, Takafumi Kamiya, Yuji Kan, Tokimasa Hida, Yasuyuki Sumikawa, Tomoyuki Minowa, Hisashi Uhara

    Contact dermatitis   86 ( 3 )   221 - 223   2022.3

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    DOI: 10.1111/cod.14001

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  • 【遺伝性疾患と遺伝カウンセリング】Cowden症候群/PTEN過誤腫症候群

    塩野谷 愛香, 肥田 時征, 水上 都, 菅原 太郎, 長谷川 匡, 菅野 康吉, 宇原 久

    皮膚病診療   44 ( 3 )   210 - 214   2022.3

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  • 【診断に苦慮した症例】初診時の主訴が上肢の片側性皮膚硬化であったWerner症候群

    古舘 和樹, 肥田 時征, 黄倉 真恵, 宇原 久

    皮膚病診療   44 ( 1 )   52 - 55   2022.1

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  • Case of immunoglobulin (Ig)M/IgG immune complex vasculitis associated with multicentric Castleman's disease. International journal

    Aika Shionoya, Tokimasa Hida, Hiroshi Ikeda, Shintaro Sugita, Keiko Segawa, Tadashi Hasegawa, Hisashi Uhara

    The Journal of dermatology   48 ( 12 )   e614-e615   2021.12

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  • Expression of programmed cell death ligand 1 (PD-L1) at in situ and invasive extramammary Paget's disease and literature review. International journal

    Junji Kato, Shintaro Sugita, Kohei Horimoto, Sayuri Sato, Daisuke Yoneta, Masahide Sawada, Mao Fujioka, Tadashi Hasegawa, Hisashi Uhara

    The Australasian journal of dermatology   62 ( 3 )   412 - 414   2021.8

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    DOI: 10.1111/ajd.13607

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  • Genetic analyses of a secondary poroma and trichoblastoma in a HRAS-mutated sebaceous nevus. International journal

    Tomoyuki Minowa, Takafumi Kamiya, Tokimasa Hida, Masae Okura, Junji Kato, Masashi Idogawa, Shoichiro Tange, Tomomi Hirano, Takashi Tokino, Hisashi Uhara

    The Journal of dermatology   48 ( 8 )   1268 - 1272   2021.8

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    A sebaceous nevus is a congenital skin hamartoma caused by postzygotic HRAS or KRAS mosaic mutations. With age, affected individuals may develop secondary tumors within a sebaceous nevus. RAS mutations are harbored from the onset of sebaceous nevus, and further mutations can be expected to be required in order to explain the initiation of secondary tumors. However, genetic analyses of the secondary tumors have not been conducted. Herein, we describe the rare coexistence of a poroma and a trichoblastoma arising in a sebaceous nevus. This is the first report of an investigation of multiple genes in a secondary tumor in an SN. First, HRAS c.37G>C, which is the common mutation in sebaceous nevus, was detected in all three lesions (sebaceous nevus, poroma, and trichoblastoma). Next, to elucidate the potential second-hit mutations in the secondary poroma and trichoblastoma, we applied a panel sequencing for skin cancers that was newly developed in our institution. Our comparison of the mutational profile of 95 skin cancer-related genes in each of the three lesions newly revealed TP53 p.R158P in the poroma and NOTCH2 p.G329S in the trichoblastoma. TP53 p.R158P has been determined as a pathogenic mutation in other tumors, and NOTCH2 p.G329S was a novel mutation. We identified two novel mutations that may have contributed to the pathogenesis of the secondary tumor's development. The roles of the mutations remain unclear.

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  • Five-year survival with nivolumab in previously untreated Japanese patients with advanced or recurrent malignant melanoma. International journal

    Hisashi Uhara, Yoshio Kiyohara, Jiro Uehara, Yasuhiro Fujisawa, Tatsuya Takenouchi, Masaki Otsuka, Hiroshi Uchi, Satoshi Fukushima, Hironobu Minami, Masahiro Hatsumichi, Naoya Yamazaki

    The Journal of dermatology   48 ( 5 )   592 - 599   2021.5

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    We report the 5-year follow-up results from a single-arm, open-label, multicenter phase II study (ONO-4538-08) conducted in Japan. Twenty-four patients with treatment-naïve, recurrent, or unresectable stage III/IV malignant melanoma received 3 mg/kg nivolumab every 2 weeks until progressive disease or unacceptable toxicity occurred. The 5-year overall survival (OS) rate was 26.1%. Five years after the start of nivolumab treatment, there were six survivors. The 5-year OS rate was 66.7% for patients with a superficial spreading type, 14.3% for acral lentiginous type, and 16.7% for mucosal type. The 5-year progression-free survival rate was 17.2%. No new cases of partial response or complete response were observed after 3 years, and overall response and disease control rates were similar to those reported at 3 years. The treatment-related adverse events reported between the 3- and 5-year follow-up periods were anemia (grade 2), white blood cell count decrease (grade 2), and psoriasiform dermatitis (grade 2) in one patient each. No new grade 3 or higher treatment-related adverse events occurred in this period. In conclusion, first-line treatment with nivolumab in Japanese patients with unresectable or metastatic melanoma resulted in confirmed long-term survival. No new safety signals were reported in the studied population.

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  • 病理組織学的に顕著なロゼット様構造を呈したALK陽性atypical Spitz tumor

    箕輪 智幸, 肥田 時征, 堀本 浩平, 加藤 潤史, 神谷 崇文, 杉田 真太朗, 井戸川 雅史, 宇原 久

    日本皮膚科学会雑誌   131 ( 5 )   1417 - 1417   2021.5

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  • カスタムパネルシーケンスを用いた日本人メラノーマのドライバー遺伝子の検出

    肥田 時征, 井戸川 雅史, 堀本 浩平, 加藤 潤史, 佐藤 さゆり, 藤岡 茉生, 丹下 正一朗, 時野 隆至, 宇原 久

    日本皮膚科学会雑誌   131 ( 5 )   1363 - 1363   2021.5

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  • ALK-positive atypical Spitz tumour with conspicuous rosette-like structures. International journal

    Tomoyuki Minowa, Tokimasa Hida, Kohei Horimoto, Junji Kato, Takafumi Kamiya, Shintaro Sugita, Masashi Idogawa, Toshiaki Saida, Tadashi Hasegawa, Takashi Tokino, Hisashi Uhara

    European journal of dermatology : EJD   31 ( 2 )   256 - 258   2021.4

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    DOI: 10.1684/ejd.2021.3997

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  • IL-13 modulates ∆Np63 levels causing altered expression of barrier- and inflammation-related molecules in human keratinocytes: A possible explanation for chronicity of atopic dermatitis. International journal

    Terufumi Kubo, Sayuri Sato, Tokimasa Hida, Tomoyuki Minowa, Yoshihiko Hirohashi, Tomohide Tsukahara, Takayuki Kanaseki, Kenji Murata, Hisashi Uhara, Toshihiko Torigoe

    Immunity, inflammation and disease   9 ( 3 )   734 - 745   2021.4

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    BACKGROUND: Barrier disruption and an excessive immune response in keratinocytes are now considered to have important roles in the pathophysiology of atopic dermatitis (AD). Furthermore, disturbed keratinocyte differentiation is considered to underlie AD. ΔNp63, a p53-like transcription factor, is a major regulator of keratinocyte differentiation. However, the functional significance of ΔNp63 in AD has not been clarified. OBJECTIVE: In this study, we aimed to investigate the influence of the type 2 inflammatory environment on ΔNp63 expression and AD-associated molecules regulated by ΔNp63 in keratinocytes. METHODS: The immunohistochemical expression profiles of ΔNp63 and AD-related molecules were evaluated in human skin tissue. The function of ΔNp63 in the regulation of AD-related molecules and the influence of the type 2 inflammatory environment on ΔNp63 expression were investigated using human primary keratinocytes. Expression of ΔNp63 was manipulated using the RNA interfering method. RESULTS: In healthy skin tissue, we observed an inverse expression pattern between ∆Np63 and some barrier-related proteins including filaggrin, caspase-14, claudin-1, and claudin-4. ΔNp63 regulated expression of these genes and proteins. In addition, production of IL-1β and IL-33, pro-inflammatory cytokines, was modulated by ΔNp63. Furthermore, prolonged IL-13 exposure increased the thickness of the three-dimensional culture of keratinocytes. IL-13 interfered with ΔNp63 downregulation during calcium-induced keratinocyte differentiation. IL-13 modulated some barrier-related and inflammation-related molecules, which were regulated by ΔNp63. CONCLUSIONS: We have shown that ΔNp63 modulated AD-related barrier and inflammatory molecules. In addition, ΔNp63 expression was affected by IL-4/IL-13. IL-13-ΔNp63 axis would integrate two major factors of AD pathogenesis: dysregulated barrier and inflammation.

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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   131 ( 3 )   541 - 542   2021.3

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  • 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   131 ( 1 )   131 - 131   2021.1

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  • 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   50回   209 - 209   2020.12

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  • 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   74 ( 13 )   1101 - 1106   2020.12

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

    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   2020.11

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    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: 10.1016/j.jid.2020.09.028

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  • Case of pneumatosis cystoides intestinalis with pemphigus vulgaris. International journal

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

    The Journal of dermatology   47 ( 11 )   e412-e413   2020.11

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

    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   2020.10

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

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

    Allergology international : official journal of the Japanese Society of Allergology   69 ( 4 )   648 - 649   2020.10

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  • Cold urticaria comorbid with heat urticaria: A case report. International journal

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

    The Journal of dermatology   47 ( 9 )   e325-e326   2020.9

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

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

    International journal of molecular sciences   21 ( 17 )   2020.8

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    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: 10.3390/ijms21176129

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

    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   2020.8

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    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.

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

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

    The Journal of dermatology   2020.7

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    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.

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

    Tokimasa Hida, Katsuhiko Tsukamoto, Masae Okura, Hisashi Uhara

    The Journal of dermatology   2020.7

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

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

    Dermatologic therapy   33 ( 4 )   e13647   2020.7

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    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.

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

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

    The Journal of dermatology   2020.6

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    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.

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

    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   2020.6

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    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.

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  • Koebner phenomenon of vitiligo associated with Coffin-Siris syndrome. International journal

    Tokimasa Hida, Aki Ishikawa, Miyako Mizukami, Hisashi Uhara

    European journal of dermatology : EJD   30 ( 3 )   310 - 311   2020.6

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    DOI: 10.1684/ejd.2020.3778

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  • 【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   19 ( 臨時増刊号 )   139 - 143   2020.6

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  • 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   130 ( 5 )   1217 - 1217   2020.5

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  • 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   130 ( 5 )   1248 - 1248   2020.5

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  • 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   130 ( 5 )   1217 - 1217   2020.5

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  • 悪性黒色腫における各種PD-L1抗体による染色性の差異についての検証

    米田 大介, 加藤 潤史, 箕輪 智幸, 澤田 匡秀, 神谷 崇文, 宇原 久

    日本皮膚科学会雑誌   130 ( 5 )   1248 - 1248   2020.5

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  • Genetic analyses of mosaic neurofibromatosis type 1 with giant café-au-lait macule, plexiform neurofibroma and multiple melanocytic nevi. Reviewed International journal

    Tokimasa Hida, Masashi Idogawa, Masae Okura, Shintaro Sugita, Taro Sugawara, Yasushi Sasaki, Takashi Tokino, Toshiharu Yamashita, Hisashi Uhara

    The Journal of dermatology   47 ( 6 )   658 - 662   2020.4

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    Neurofibromatosis type 1 (NF1) is a genodermatosis caused by heterozygous germ line variations in the NF1 gene. A second-hit NF1 aberration results in the formation of café-au-lait macules, cutaneous neurofibroma and plexiform neurofibroma (PNF). Mosaic NF1 (mNF1), caused by a postzygotic NF1 mutation, is characterized by localized or generalized NF1-related manifestations. Although NF1 and mNF1 are associated with pigmentary skin lesions, clinically recognizable melanocytic nevi that developed over PNF have not been reported. Here, we report the first case of multiple melanocytic nevi that developed on a giant café-au-lait macule and PNF. The PNF had biallelic NF1 deletions, a whole deletion of NF1 and a novel intragenic deletion involving exons 25-30. The deletions were not detected in the blood, which resulted in the diagnosis of mNF1. Furthermore, the nevus cells had not only biallelic NF1 deletions but also NRAS Q61R, a common mutation found in congenital melanocytic nevi. These analyses revealed the coexistence of the two different mosaic diseases, mNF1 and congenital melanocytic nevi. For a diagnosis of cases with atypical NF1-like symptoms, genetic analyses using blood and lesional tissues are useful and aid in genetic counseling.

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  • Blastic plasmacytoid dendritic cell neoplasm(BPDCN)の2例

    執行 延明, 西田 彩華, 菅野 莉英, 藤岡 茉生, 大橋 隆宏, 堀本 浩平, 加藤 潤史, 肥田 時征, 宇原 久, 村瀬 和幸, 井山 諭, 須釜 佑介, 前田 和男

    日本皮膚科学会雑誌   130 ( 3 )   418 - 418   2020.3

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  • 神経線維腫を伴わない神経線維腫症1型2家系の遺伝子解析

    肥田 時征, 井戸川 雅史, 石川 亜貴, 水上 都, 加藤 潤史, 澄川 靖之, 時野 隆至, 宇原 久

    日本レックリングハウゼン病学会学術大会プログラム・抄録集   11回   15 - 15   2020.2

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  • 腹部に生じた巨大な尖圭コンジローマ

    石田 倫子, 三苫 千景, 中原 真希子, 内 博史, 肥田 時征, 黄倉 真恵, 宇原 久, 古江 増隆

    西日本皮膚科   82 ( 1 )   3 - 4   2020.2

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  • Successful therapy for diffuse cutaneous systemic sclerosis-induced digital ulcer treated with hyperbaric oxygen therapy. International journal

    Yuji Kan, Takafumi Kamiya, Ayako Kumagai, Yuna Hosokawa, Hisashi Uhara

    The Journal of dermatology   47 ( 2 )   e62-e64   2020.2

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  • Prognostic Factors and Long-Term Efficacy of Tonsillectomy in 17 Patients with Pustulotic Arthro-Osteitis. Reviewed International journal

    Yuji Kan, Yasuyuki Sumikawa, Tokimasa Hida, Saeko Ajiki, Hisashi Uhara

    The Eurasian journal of medicine   52 ( 1 )   103 - 105   2020.2

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    In this case study, we aimed to evaluate the disease condition of patients with pustulotic arthro-osteitis (PAO) at 36-month post-tonsillectomy. A retrospective analysis of the cases of 17 patients with PAO who were resistant to initial systemic treatments and underwent tonsillectomy at our hospital in 2006-2016 was conducted. The patients' disease condition at 1-, 24-, and 36-month post-tonsillectomy was assessed by the visual analog scale (VAS) score for osteoarthropathic pain, the disease duration, the area of palmoplantar lesions, and the Palmoplantar Pustular Psoriasis Area Severity Index (ppPASI). In the minimum follow-up of 36-month post-tonsillectomy in 17 patients, the median ppPASI and VAS scores decreased from 12 to 1 and from 80 to 20, respectively. Thirteen patients with ≥70% improvement in their VAS scores maintained the same good condition after ≥36 months, whereas four patients with <70% improvement in their VAS scores did not show remarkable improvement after that time point. Furthermore, we found that the improvement in VAS score was not associated with the disease duration or the patients' pre-tonsillectomy ppPASI values. Tonsillectomy might be an alternative treatment option for patients with PAO. Long-term efficacy against pain can be predicted by evaluating a patient's improvement at 1-month post-tonsillectomy.

    DOI: 10.5152/eurasianjmed.2019.19099

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  • Significance of 5-S-Cysteinyldopa as a Marker for Melanoma. Reviewed International journal

    Kazumasa Wakamatsu, Satoshi Fukushima, Akane Minagawa, Toshikazu Omodaka, Tokimasa Hida, Naohito Hatta, Minoru Takata, Hisashi Uhara, Ryuhei Okuyama, Hironobu Ihn

    International journal of molecular sciences   21 ( 2 )   2020.1

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    Melanoma is one of the most lethal and malignant cancers and its incidence is increasing worldwide, and Japan is not an exception. Although there are numerous therapeutic options for melanoma, the prognosis is still poor once it has metastasized. The main concern after removal of a primary melanoma is whether it has metastasized, and early detection of metastatic melanoma would be effective in improving the prognosis of patients. Thus, it is very important to identify reliable methods to detect metastases as early as possible. Although many prognostic biomarkers (mainly for metastases) of melanoma have been reported, there are very few effective for an early diagnosis. Serum and urinary biomarkers for melanoma diagnosis have especially received great interest because of the relative ease of sample collection and handling. Several serum and urinary biomarkers appear to have significant potential both as prognostic indicators and as targets for future therapeutic methods, but still there are no efficient serum and urinary biomarkers for early detection, accurate diagnosis and prognosis, efficient monitoring of the disease and reliable prediction of survival and recurrence. Levels of 5-S-cysteinyldopa (5SCD) in the serum or urine as biomarkers of melanoma have been found to be significantly elevated earlier and to reflect melanoma progression better than physical examinations, laboratory tests and imaging techniques, such as scintigraphy and echography. With recent developments in the treatment of melanoma, studies reporting combinations of 5SCD levels and new applications for the treatment of melanoma are gradually increasing. This review summarizes the usefulness of 5SCD, the most widely used and well-known melanoma marker in the serum and urine, compares 5SCD and other useful markers, and finally its application to other fields.

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  • 発汗指導を行ったコリン性蕁麻疹12症例の検討

    箕輪 智幸, 澄川 靖之, 菅 裕司, 兼古 理恵, 宇原 久

    日本皮膚科学会雑誌   130 ( 1 )   80 - 80   2020.1

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  • 中毒疹様皮疹を契機に診断に至った全身性エリテマトーデス(SLE)の1例

    西田 彩華, 小林 英理, 細川 夕菜, 箕輪 智幸, 熊谷 綾子, 菅 裕司, 神谷 崇文, 宇原 久

    日本皮膚科学会雑誌   130 ( 1 )   39 - 39   2020.1

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  • カルシフィラキシスにガス壊疽を合併した1例

    小林 英理, 堀本 浩平, 西田 彩華, 執行 延明, 菅野 莉英, 箕輪 智幸, 藤岡 茉生, 肥田 時征, 宇原 久

    日本皮膚科学会雑誌   130 ( 1 )   39 - 39   2020.1

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  • メルケル細胞癌に対してアベルマブ投与を行った2例

    執行 延明, 細川 夕菜, 箕輪 智幸, 藤岡 茉生, 佐藤 さゆり, 堀本 浩平, 加藤 潤史, 肥田 時征, 宇原 久

    日本皮膚科学会雑誌   130 ( 1 )   40 - 40   2020.1

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  • Renal angiomyolipoma (AML) harboring a missense mutation of TSC2 with copy-neutral loss of heterozygosity (CN-LOH). Reviewed International journal

    Masashi Idogawa, Tokimasa Hida, Toshiaki Tanaka, Noriaki Ohira, Shoichiro Tange, Yasushi Sasaki, Hisashi Uhara, Naoya Masumori, Takashi Tokino, Hiroshi Natori

    Cancer biology & therapy   1 - 5   2019.12

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    Angiomyolipoma (AML) is classified as a perivascular epithelioid cell neoplasm, mostly occurring in the kidney. Twenty percent of patients with renal AML have tuberous sclerosis complex (TSC) caused by germline variation in the TSC1 or TSC2 gene. In this paper, we report the first case of renal AML harboring somatic missense mutations of the TSC2 gene and concomitant copy-neutral loss of heterozygosity (CN-LOH). The patient presented with solitary renal AML and pulmonary lymphangiomyomatosis and without other findings suggestive of TSC. Exome sequencing analysis of the renal AML, however, identified a pathogenic somatic missense mutation in the TSC2 gene (NM_000548:c.5228G>A:p. R1743Q), although no other somatic mutation was detected. Furthermore, no germline mutation in TSC1 or TSC2 was detected. Interestingly, the mutant allele ratio was too high for a somatic heterozygous mutation without loss of heterozygosity (LOH). Furthermore, no copy number variation was detected around the TSC2 locus (16p13.3). To clarify the allelic status, we analyzed heterozygous single-nucleotide polymorphisms (SNPs) in chromosome 16. In these SNPs, an unbalanced allele ratio was accumulated inside the 16p13.3 region. These results suggested copy-neutral LOH (CN-LOH). Consequently, we concluded that the missense mutation of the TSC2 gene and CN-LOH of the TSC2 locus caused renal AML.

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  • Eosinophilic fasciitis in a 2-year-old child treated with a combination of methotrexate and corticosteroids. International journal

    Yuji Kan, Hisashi Uhara, Shiori Kamiya, Ayako Kumagai, Toshiya Handa

    The Journal of dermatology   46 ( 12 )   e474-e475   2019.12

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  • Current clinical issue of skin lesions in patients with inflammatory bowel disease. Reviewed

    Tomoya Iida, Tokimasa Hida, Minoru Matsuura, Hisashi Uhara, Hiroshi Nakase

    Clinical journal of gastroenterology   12 ( 6 )   501 - 510   2019.12

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    Inflammatory bowel disease (IBD) is associated with a number of extraintestinal complications, including skin lesions. Most reports have shown that skin lesions are found in 10-15% of IBD cases, although this depends on the definition of skin lesions. The representative skin lesions in patients with IBD are erythema nodosum, pyoderma gangrenosum, Sweet's syndrome, and so on. These lesions are often associated with IBD progression, and intestinal lesions in particular require appropriate treatment. Recently, another clinical issue regarding skin lesions in patients with IBD, a so-called paradoxical reaction, during the treatment with anti-tumor necrosis factor (TNF)-α agents has emerged. These reactions are termed paradoxical reactions because the skin lesions sometimes resemble psoriasis, although the anti-TNF-α agents have been historically used to treat psoriasis. Paradoxical reactions are reportedly found in approximately 5-10% of patients using anti-TNF-α agents and are no longer rare. Now that the use of biologics is at its culmination, reports regarding paradoxical reactions are predicted to increase in number; thus, we must recognize skin lesions with IBD patients including this type of adverse events and manage them appropriately while consulting with dermatologists.

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  • Durable response after cessation of anti-programmed death 1 therapy in four melanoma patients. Reviewed International journal

    Toshiya Handa, Junji Kato, Yasuyuki Sumikawa, Tokimasa Hida, Kohei Horimoto, Sayuri Sato, Masahide Sawada, Mao Fujioka, Tomoyuki Minowa, Yoshiyuki Matsui, Hisashi Uhara

    The Journal of dermatology   46 ( 12 )   e461-e462 - e462   2019.12

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  • Adjuvant therapy with nivolumab versus ipilimumab after complete resection of stage III/IV melanoma: Japanese subgroup analysis from the phase 3 CheckMate 238 study. Reviewed International journal

    Kenji Yokota, Hiroshi Uchi, Hisashi Uhara, Shusuke Yoshikawa, Tatsuya Takenouchi, Takashi Inozume, Kentaro Ozawa, Hironobu Ihn, Yasuhiro Fujisawa, Anila Qureshi, Veerle de Pril, Yasushi Otsuka, Jeffrey Weber, Naoya Yamazaki

    The Journal of dermatology   46 ( 12 )   1197 - 1201   2019.12

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    The multinational phase 3 CheckMate 238 trial compared adjuvant therapy with nivolumab versus ipilimumab among patients with resected stage III or IV melanoma (N = 906). In this Japanese subgroup analysis of CheckMate 238 (n = 28; nivolumab, n = 18; ipilimumab, n = 10), both the 12- and 18-month recurrence-free survival rates were 56% for nivolumab and 30% for ipilimumab (hazard ratio, 0.66; 97.56% confidence interval, 0.19-2.24; P = 0.4390). No new safety signals were reported for Japanese patients. Results were consistent with those from the CheckMate 238 global population, indicating that nivolumab has the potential to be a treatment option for Japanese patients with resected melanoma who are at high risk of recurrence.

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  • Japanese real-world study of sequential nivolumab and ipilimumab treament in melanoma. Reviewed International journal

    Arata Tsutsumida, Satoshi Fukushima, Kenji Yokota, Shusuke Yoshikawa, Osamu Yamasaki, Atsushi Tanemura, Ryuhei Okuyama, Hisashi Uhara, Yusuke Muto, Azusa Miyashita, Masashi Akiyama, Tatsuya Kaji, Hiroshi Koga, Junji Kato, Teruaki Katayama, Eijun Itakura, Naoya Yamazaki, Yoshio Kiyohara

    The Journal of dermatology   46 ( 11 )   947 - 955   2019.11

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    To describe the treatment patterns of nivolumab and ipilimumab in Japan, a retrospective observational study was conducted in melanoma patients who received nivolumab and ipilimumab sequentially. Patients who received nivolumab and ipilimumab in combination were excluded from this study. Efficacy was evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) in terms of the overall response rate (ORR), progression-free survival (PFS), and disease control rate (DCR). Overall survival (OS) was also evaluated. Safety was assessed by the Common Terminology Criteria for Adverse Events (CTCAE). The treatment for all 68 patients enrolled involved switching from nivolumab to ipilimumab in 61 patients and switching from ipilimumab to nivolumab in seven patients. Switching occurred because of progressive disease in 55 patients and adverse events in eight patients. The median number of ipilimumab doses was three. Ipilimumab treatment achieved an ORR and DCR of 4.9% and 21.3%, respectively, and the median OS from start of ipilimumab was 7.0 months. During the study period, no new safety signals were noted. Independent factors which were indicative of poor prognosis for PFS were high neutrophil-to-lymphocyte ratio (NLR) and high C-reactive protein (CRP) levels before ipilimumab treatment. An evaluation over a washout period indicated that no significant relationship existed with efficacy or safety. For the sequential administration of nivolumab and ipilimumab in Japanese melanoma patients, switch from nivolumab to ipilimumab was common, and the major reason for switching was progressive disease. The major prognostic factors for ipilimumab PFS after nivolumab were NLR and CRP before ipilimumab treatment.

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  • 腹部に生じた巨大尖圭コンジローマの1例

    石田 倫子, 中原 真希子, 内 博史, 和田 尚子, 宮崎 玲子, 辻 学, 中原 剛士, 三苫 千景, 肥田 時征, 黄倉 真恵, 宇原 久, 古江 増隆

    西日本皮膚科   81 ( 5 )   438 - 438   2019.10

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  • 体温上昇により誘発された血管浮腫の2例

    箕輪 智幸, 澄川 靖之, 宇原 久

    アレルギーの臨床   39 ( 11 )   915 - 918   2019.10

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  • 自己免疫性水疱症例における免疫グロブリン大量療法後の血小板減少についての検討

    小林 英理, 菅 裕司, 細川 夕菜, 箕輪 智幸, 米田 大介, 熊谷 綾子, 神谷 崇文, 澄川 靖之, 宇原 久

    日本皮膚科学会雑誌   129 ( 11 )   2335 - 2335   2019.10

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  • メラノーマにおける抗PD-1抗体治療中止後の効果持続について

    加藤 潤史, 半田 稔也, 松井 馨之, 箕輪 智幸, 藤岡 茉生, 澤田 匡秀, 佐藤 さゆり, 堀本 浩平, 肥田 時征, 澄川 靖之, 宇原 久

    日本癌治療学会学術集会抄録集   57回   P160 - 2   2019.10

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  • 肘に全周性に発症した熱傷瘢痕癌の1例

    西田 彩華, 堀本 浩平, 執行 延明, 半田 稔也, 菅野 莉英, 松井 馨之, 藤岡 茉生, 大橋 隆宏, 加藤 潤史, 肥田 時征, 宇原 久

    日本皮膚科学会雑誌   129 ( 11 )   2336 - 2336   2019.10

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  • ニボルマブによってリウマチ性多発筋痛症様症状を呈した1例

    執行 延明, 西田 彩華, 菅野 莉英, 箕輪 智幸, 藤岡 茉生, 堀本 浩平, 加藤 潤史, 肥田 時征, 宇原 久, 津田 玲子, 高橋 裕樹

    日本皮膚科学会雑誌   129 ( 11 )   2336 - 2336   2019.10

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  • 放射線治療を行った基底細胞癌症例の検討

    西田 彩華, 堀本 浩平, 加藤 潤史, 執行 延明, 菅野 莉英, 藤岡 茉生, 大橋 隆宏, 肥田 時征, 宇原 久

    日本皮膚科学会雑誌   129 ( 9 )   1909 - 1909   2019.8

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  • Blastic plasmacytoid dendritic cell neoplasm(BPDCN)の1例

    執行 延明, 西田 彩華, 菅野 莉英, 藤岡 茉生, 大橋 隆宏, 堀本 浩平, 加藤 潤史, 肥田 時征, 宇原 久, 井山 諭, 前田 和男, 須釜 佑介

    日本皮膚科学会雑誌   129 ( 9 )   1910 - 1910   2019.8

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  • 尋常性天疱瘡の治療中に腸管気腫症をきたした1例

    小林 英理, 菅 裕司, 半田 稔也, 松井 馨之, 細川 夕菜, 箕輪 智幸, 熊谷 綾子, 神谷 崇文, 澄川 靖之, 宇原 久

    日本皮膚科学会雑誌   129 ( 9 )   1909 - 1909   2019.8

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  • 転移性悪性黒色腫のNivolumab治療における血清5-S-CDの有用性

    面高 俊和, 皆川 茜, 古賀 弘志, 奥山 隆平, 若松 一雅, 宇原 久

    日本皮膚科学会雑誌   129 ( 8 )   1648 - 1648   2019.7

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  • 末梢血中の腫瘍由来DNAを用いた悪性黒色腫に対するニボルマブの治療効果の評価

    芦田 敦子, 境澤 香里, 奥山 隆平, 宇原 久

    日本皮膚科学会雑誌   129 ( 8 )   1647 - 1647   2019.7

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  • Long-term follow up of nivolumab in previously untreated Japanese patients with advanced or recurrent malignant melanoma. Reviewed International journal

    Naoya Yamazaki, Yoshio Kiyohara, Hisashi Uhara, Jiro Uehara, Yasuhiro Fujisawa, Tatsuya Takenouchi, Masaki Otsuka, Hiroshi Uchi, Hironobu Ihn, Masahiro Hatsumichi, Hironobu Minami

    Cancer science   110 ( 6 )   1995 - 2003   2019.6

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    The immune checkpoint inhibitor nivolumab inhibits the programmed death 1 receptor and suppresses the immune resistance of cancer cells. This is a long-term follow up of a single-arm, open-label, multicenter, phase II study of nivolumab in untreated Japanese patients with stage III/IV or recurrent melanoma. In addition, a post-hoc subgroup analysis stratified by melanoma types was performed. Nivolumab was administered intravenously at a dose of 3 mg/kg every 2 weeks. The primary endpoint was the overall response rate (ORR), and secondary endpoints included overall survival (OS), progression-free survival (PFS), best overall response, the disease control rate and change in tumor diameter. Safety was assessed by recording treatment-related adverse events (TRAE), including select immune-related adverse events. Of the 24 patients initially included in the primary phase II study, 10 survived for over 3 years (41.7%). The ORR was 34.8% (90% confidence interval [CI]: 20.8, 51.9) for all patients. When analyzing by melanoma type, the ORR was 66.7% (90% CI: 34.7, 88.3) for superficial spreading, 33.3% (90% CI: 11.7, 65.3) for mucosal, and 28.6% (90% CI: 10.0, 59.1) for acral lentiginous tumors. The median OS was 32.9 months, the 3-year OS rate was 43.5%, and the 3-year PFS rate was 17.2%. A long-term response was observed in all the tumor types. The most common TRAE included skin toxicity (45.8%) and endocrine disorders (29.2%). This study demonstrated the long-term efficacy and tolerability of nivolumab in patients with advanced or recurrent melanoma, irrespective of melanoma type.

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  • 局所麻酔薬アレルギー疑い患者の皮膚テスト陽性率と発作時の症状の検討

    澄川 靖之, 江畑 加奈子, 神谷 崇文, 菅 裕司, 石井 泰江, 肥田 時征, 加藤 潤史, 堀本 浩平, 宇原 久

    西日本皮膚科   81 ( 3 )   253 - 253   2019.6

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  • Docetaxel therapy for classic Kaposi's sarcoma. Reviewed International journal

    Yuna Hosokawa, Junji Kato, Tokimasa Hida, Kohei Horimoto, Sayuri Sato, Masahide Sawada, Hiroshi Sasaki, Yoshiyuki Matsui, Toshiya Handa, Hisashi Uhara

    Asia-Pacific journal of clinical oncology   15 ( 3 )   181 - 182   2019.6

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  • Clinical and Histopathologic Characteristics of Melanocytic Lesions on the Volar Skin Without Typical Dermoscopic Patterns. International journal

    Yasutomo Mikoshiba, Akane Minagawa, Hiroshi Koga, Yoshiharu Yokokawa, Hisashi Uhara, Ryuhei Okuyama

    JAMA dermatology   155 ( 5 )   578 - 584   2019.5

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    Importance: It is challenging to differentiate melanoma from melanocytic nevus on the volar skin in the absence of typical dermoscopic patterns. Objective: To identify the frequency and clinical and dermoscopic characteristics of melanocytic lesions on the volar skin not displaying a parallel furrow pattern, lattice-like pattern, fibrillar pattern, or parallel ridge pattern on results of dermoscopy. Design, Setting, and Participants: In this retrospective cohort study, a total of 504 melanocytic lesions on the volar skin were evaluated in the Shinshu University Hospital department of dermatology between January 1, 2000, and December 31, 2012. Dermoscopic images were independently assessed by 3 dermoscopists for the presence of established dermoscopic criteria. Statistical analysis was performed from October 1, 2017, to April 30, 2018. Main Outcomes and Measures: Frequency of dermoscopic criteria and corresponding clinical (patient age and size and location of lesion) and histopathologic features. Results: Of 504 lesions, 110 (21.8%) (melanocytic nevus, 97; melanoma, 8; and equivocal melanocytic lesion, 5) from 108 patients (68 female and 40 male patients; mean age, 40.1 years [range, 1-86 years]) did not show a parallel furrow pattern, lattice-like pattern, fibrillar pattern, or parallel ridge pattern. Among them, the mean patient age was significantly higher for melanoma than for melanocytic nevus (65.3 vs 38.0 years; P < .001), as was mean maximum lesion diameter (11.8 vs 5.7 mm; P < .001). Melanomas and equivocal melanocytic lesions tended to be distributed on weight-bearing areas of the foot sole, such as the heel, while nevi were spread over non-weight-bearing regions. Dermoscopically, 95 melanocytic nevi (97.9%) were symmetrical in 1 or 2 axes while melanomas were not. A total of 91 melanocytic nevi (93.8%) had 1 or 2 colors per lesion, and 4 melanomas (50.0%) had more than 2 colors. Vascular structures were seen in 3 melanocytic nevi (3.1%) and 3 melanomas (37.5%). Blue-white structures were seen in 18 melanocytic nevi (18.6%) and 3 melanomas (37.5%). Dots and globules were seen in 22 melanocytic nevi (22.7%) and 4 melanomas (50.0%). Vascular structures, blue-white structures, and dots and globules were irregularly distributed in the melanomas. Ulcer, hyperkeratosis, and irregular streaks were observed only in melanomas. Conclusions and Relevance: More than one-fifth of melanocytic lesions on the volar skin did not display typical dermoscopic patterns. Asymmetry, numerous colors (≥3), and other melanoma-specific dermoscopic findings were more frequently observed for melanomas. Clinical information, including patient age and lesion size and location, was helpful in differentiating melanoma from melanocytic nevus. Further prospective clinical studies are warranted to clarify the diagnostic accuracy of dermoscopy combined with clinical information.

    DOI: 10.1001/jamadermatol.2018.5926

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  • 悪性黒色腫における抗PD-1抗体と放射線治療

    加藤 潤史, 肥田 時征, 堀本 浩平, 佐藤 さゆり, 澤田 匡秀, 藤岡 茉生, 箕輪 智幸, 松井 馨之, 宇原 久

    日本皮膚科学会雑誌   129 ( 5 )   1177 - 1177   2019.5

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  • ダーモスコピーで診断困難であった脂漏性角化症の臨床的特徴

    皆川 茜, 古賀 弘志, 高沢 裕子, 宇原 久, 奥山 隆平

    日本皮膚科学会雑誌   129 ( 4 )   560 - 560   2019.4

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  • ペムブロリズマブの投与にて完全奏功を維持している陰部悪性黒色腫の1例

    堀本 浩平, 加藤 潤史, 松井 馨之, 佐々木 洋, 細川 夕菜, 澤田 秀匡, 佐藤 さゆり, 肥田 時征, 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   35回   116 - 116   2019.4

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  • Bowen病に合併したMerkel細胞癌の1例

    辻 あすか, 大橋 敦子, 三宅 知美, 上條 史尚, 古賀 弘志, 宇原 久, 奥山 隆平

    日本皮膚科学会雑誌   129 ( 4 )   560 - 560   2019.4

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  • Efficacy of combined radiotherapy and anti-programmed death 1 therapy in acral and mucosal melanoma. Reviewed International journal

    Junji Kato, Tokimasa Hida, Masanori Someya, Sayuri Sato, Masahide Sawada, Kohei Horimoto, Mao Fujioka, Tomoyuki Minowa, Yoshiyuki Matsui, Takaaki Tsuchiya, Mio Kitagawa, Kensei Nakata, Koh-Ichi Sakata, Toshihiko Torigoe, Hisashi Uhara

    The Journal of dermatology   46 ( 4 )   328 - 333   2019.4

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    DOI: 10.1111/1346-8138.14805

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  • 小児期発症の病歴を持つメラノーマの病理組織学的検討

    皆川 茜, 宇原 久, 芦田 敦子, 境澤 香里, 古賀 弘志, 奥山 隆平

    日本皮膚病理組織学会抄録集   35回   50,31 - 50,31   2019.4

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  • 根治切除不能な化学療法未治療の悪性黒色腫に対するニボルマブとイピリムマブ併用第II相試験(最終報告)

    内 博史, 清原 祥夫, 竹之内 辰也, 宇原 久, 古賀 弘志, 山崎 直也

    日本皮膚悪性腫瘍学会学術大会プログラム・抄録集   35回   114 - 114   2019.4

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  • Decrease of Anti-DSG3, but Not Anti-DSG1 Antibody, After Cessation of Sitagliptin Treatment in a Patient With Pemphigus Vulgaris. International journal

    Toshiya Handa, Takafumi Kamiya, Yasuyuki Sumikawa, Tomoyuki Minowa, Ayako Kumagai, Masahide Sawada, Hisashi Uhara

    JAMA dermatology   155 ( 3 )   391 - 393   2019.3

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    DOI: 10.1001/jamadermatol.2018.5379

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  • 結節性硬化症の皮膚病変に対するシロリムス外用療法の効果

    肥田 時征, 神谷 崇文, 宇原 久, 石川 亜貴

    日本皮膚科学会雑誌   129 ( 3 )   356 - 356   2019.3

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  • アザチオプリンを投与中に汎発性帯状疱疹と汎血球減少を発症した1例

    松井 馨之, 澄川 靖之, 箕輪 智幸, 熊谷 綾子, 神谷 崇文, 宇原 久

    日本皮膚科学会雑誌   129 ( 3 )   356 - 356   2019.3

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  • 抗PD-1抗体治療で著効し、治療中断後も再発のない悪性黒色腫の4例

    半田 稔也, 加藤 潤史, 松井 馨之, 箕輪 智幸, 藤岡 茉生, 澤田 匡秀, 佐藤 さゆり, 堀本 浩平, 肥田 時征, 澄川 靖之, 宇原 久

    日本皮膚科学会雑誌   129 ( 3 )   353 - 353   2019.3

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  • A case of childhood-onset cutaneous mastocytosis with loss of wild-type KIT allele. Reviewed

    Hida T, Okura M, Kamiya T, Yamamoto M, Hori T, Uhara H

    Journal of the European Academy of Dermatology and Venereology : JEADV   2019.2

  • リツキシマブが原因と考えられたTEN型薬疹の1例

    松井 馨之, 澄川 靖之, 箕輪 智幸, 熊谷 綾子, 神谷 崇文, 宇原 久, 村瀬 和幸

    日本皮膚科学会雑誌   129 ( 1 )   45 - 45   2019.1

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  • クローン型脂漏性角化症(clonal seborrheic keratosis)のダーモスコピー所見

    半田 稔也, 加藤 潤史, 藤岡 茉生, 堀本 浩平, 肥田 時征, 宇原 久

    日本皮膚科学会雑誌   129 ( 1 )   47 - 47   2019.1

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  • Dermoscopy of Melanoma and Non-melanoma Skin Cancers. International journal

    Junji Kato, Kohei Horimoto, Sayuri Sato, Tomoyuki Minowa, Hisashi Uhara

    Frontiers in medicine   6   180 - 180   2019

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    Dermoscopy is a widely used non-invasive technique for diagnosing skin tumors. In melanocytic tumors, e.g., melanoma and basal cell carcinoma (BCC), the effectiveness of dermoscopic examination has been fully established over the past two decades. Moreover, dermoscopy has been used to diagnose non-melanocytic tumors. Here, we review novel findings from recent reports concerning dermoscopy of melanoma and non-melanoma skin cancers including BCC, sebaceous carcinoma, actinic keratosis, Bowen's disease, squamous cell carcinoma (SCC), Merkel cell carcinoma (MCC), extramammary Paget's disease (EMPD), and angiosarcoma.

    DOI: 10.3389/fmed.2019.00180

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  • Efficacy and safety of nivolumab in combination with ipilimumab in Japanese patients with advanced melanoma: An open-label, single-arm, multicentre phase II study. Reviewed International journal

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

    European journal of cancer (Oxford, England : 1990)   105   114 - 126   2018.12

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    AIM: The aim of the study was to evaluate the efficacy and safety of nivolumab combined with ipilimumab in treatment-naïve Japanese patients with advanced melanoma. METHODS: In this multicentre, single-arm study, treatment-naïve Japanese patients with unresectable stage III/IV or recurrent melanoma received nivolumab (1 mg/kg) plus ipilimumab (3 mg/kg) every 3 weeks for four doses, followed by biweekly doses of nivolumab (3 mg/kg). The primary end-point was centrally assessed objective response rate (ORR). Secondary end-points included overall survival (OS), progression-free survival (PFS), disease control rate and safety. RESULTS: The subtypes of the thirty patients enrolled were: 12, mucosal; eight, non-acral cutaneous; seven, acral; two, uveal and one, unknown primary melanoma. The ORR was 43.3% (95% confidence interval [CI]: 25.5, 62.6) with central and local assessment. The centrally and locally assessed disease control rate (95% CI) were 73.3% (54.1, 87.7) and 86.7% (69.3, 96.2), respectively. At the median follow-up period of 14.1 months (range 5.2-27.7), median OS and centrally assessed PFS were not reached. OS (95% CI) at 6, 12, 18 and 24 months was 93.3% (75.9, 98.3), 83.3% (64.5, 92.7), 72.9% (50.0, 86.5) and 65.6% (40.4, 82.2), respectively. Treatment-related adverse events (AEs) occurred in all patients. Grade III-IV and serious AEs occurred, mostly during the combination phase, in 23 (76.7%) and 20 (66.7%) patients, respectively. No treatment-related deaths occurred. CONCLUSIONS: This study confirmed the efficacy and safety of nivolumab plus ipilimumab in treatment-naïve Japanese patients with advanced melanoma including rare subtypes. Incidence rates for grade III-IV AEs were high but manageable with appropriate medical attention and treatment. TRIAL REGISTRATION: JapicCTI-152869.

    DOI: 10.1016/j.ejca.2018.09.025

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  • 【皮膚科で使うMTXの完全マニュアル】(Part4)乾癬以外の皮膚疾患へのMTXの応用(case (16)) リンパ腫様丘疹症

    神谷 崇文, 宇原 久

    Visual Dermatology   18 ( 1 )   96 - 97   2018.12

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  • Halo formations around senile hemangiomas in diffuse plane normolipemic xanthomatosis associated with monoclonal gammopathy. Reviewed International journal

    Tokimasa Hida, Hiroki Takahashi, Kohichi Takada, Hisashi Uhara

    JAAD case reports   4 ( 10 )   1034 - 1036   2018.11

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  • DPP-4阻害薬内服中に発症した尋常性天疱瘡の1例

    半田 稔也, 神谷 崇文, 丸尾 亜紀, 箕輪 智幸, 大橋 隆宏, 江畑 加奈子, 熊谷 綾子, 澄川 靖之, 宇原 久, 澤田 匡秀, 兼古 理恵

    日本皮膚科学会雑誌   128 ( 12 )   2665 - 2665   2018.11

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  • 血清CYFRA21-1値が病勢を反映した汗孔癌の1例

    松井 馨之, 加藤 潤史, 藤岡 茉生, 澤田 匡秀, 佐藤 さゆり, 堀本 浩平, 肥田 時征, 宇原 久

    日本皮膚科学会雑誌   128 ( 12 )   2666 - 2666   2018.11

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  • Transient hypogammaglobulinemia of infancy with no evidence of immunodeficiency other than atopic dermatitis: A case report and review of literature Reviewed

    Minowa T, Sumikawa Y, Hida T, Uhara H

    J Cutan Immunol Allergy   1 ( 5 )   174 - 175   2018.11

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    DOI: 10.1002/cia2.12037

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  • Topline results from phase II of combination treatment with canerpaturev (HF10), an oncolytic viral immunotherapy, and ipilimumab in patients with unresectable or metastatic melanoma after anti-PD-1 therapy Reviewed

    T. Isei, K. Yokota, H. Uhara, Y. Fujisawa, T. Takenouchi, Y. Kiyohara, H. Uchi, H. Saruta, H. Ihn, T. Inozume, D. Watanabe, A. Takahashi, S. Fukushima, M. Tanaka, N. Yamazaki

    Annals of oncology : official journal of the European Society for Medical Oncology   29   viii452 - viii453   2018.10

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    DOI: 10.1093/annonc/mdy289.023

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  • 痔核硬化剤に添加された亜硫酸塩の過敏症と考えられた1例

    半田 稔也, 箕輪 智幸, 大橋 隆宏, 江畑 加奈子, 熊谷 綾子, 神谷 崇文, 澄川 靖之, 宇原 久

    日本皮膚免疫アレルギー学会雑誌   2 ( 1 )   184 - 184   2018.10

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  • 体温上昇により誘発された血管浮腫の2例

    箕輪 智幸, 澄川 靖之, 半田 稔也, 熊谷 綾子, 神谷 崇文, 宇原 久

    日本皮膚免疫アレルギー学会雑誌   2 ( 1 )   164 - 164   2018.10

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  • 小児毛孔性紅色粃糠疹にビタミンA製剤が奏効した1例

    菅 裕司, 澄川 靖之, 宇原 久

    日本皮膚免疫アレルギー学会雑誌   2 ( 1 )   181 - 181   2018.10

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  • Prognostic role of neutrophil to lymphocyte ratio in advanced melanoma treated with anti-programmed death-1 therapy. Reviewed International journal

    Tomoyuki Minowa, Junji Kato, Tokimasa Hida, Kohei Horimoto, Sayuri Sato, Masahide Sawada, Hisashi Uhara

    The Journal of dermatology   45 ( 9 )   e250-e251 - 251   2018.9

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  • ピロ亜硫酸ナトリウムによる過敏症と診断した1例

    半田 稔也, 箕輪 智幸, 大橋 隆宏, 江畑 加奈子, 熊谷 綾子, 神谷 崇文, 澄川 靖之, 宇原 久

    日本皮膚科学会雑誌   128 ( 8 )   1664 - 1664   2018.7

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  • 温熱負荷によって誘発されたangioedemaの1例

    箕輪 智幸, 澄川 靖之, 半田 稔也, 熊谷 綾子, 神谷 崇文, 宇原 久

    日本皮膚科学会雑誌   128 ( 8 )   1665 - 1665   2018.7

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  • ニボルマブ投与中に発症した扁平苔癬の1例

    松井 馨之, 加藤 潤史, 藤岡 茉生, 澤田 匡秀, 佐藤 さゆり, 堀本 浩平, 肥田 時征, 宇原 久

    日本皮膚科学会雑誌   128 ( 8 )   1665 - 1665   2018.7

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  • 【皮膚科専門医が教える! がん治療に伴う"危険な"皮膚障害の診かたと考えかた】 Reviewed

    宇原久

    Cancer Board Square   4 ( 2 )   204 - 231   2018.7

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  • BRAF/MEK阻害薬が奏効したG-CSF産生悪性黒色腫の1例

    箕輪 智幸, 加藤 潤史, 江畑 可奈子, 高橋 仁美, 澤田 匡秀, 佐藤 さゆり, 堀本 浩平, 肥田 時征, 宇原 久, 佐藤 勉

    西日本皮膚科   80 ( 3 )   290 - 290   2018.6

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  • 抗PD-1抗体で治療した悪性黒色腫における好中球リンパ球比、血小板リンパ球比、リンパ球単球比の意義

    箕輪 智幸, 加藤 潤史, 松井 馨之, 澤田 匡秀, 佐藤 さゆり, 堀本 浩平, 肥田 時征, 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   34回   127 - 127   2018.6

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  • 根治切除不能な化学療法未治療の悪性黒色腫に対するニボルマブ(NIV)とイピリムマブ(IPI)併用第II相試験

    竹之内 辰也, 清原 祥夫, 宇原 久, 古賀 弘志, 内 博史, 山崎 直也

    日本皮膚悪性腫瘍学会学術大会プログラム・抄録集   34回   149 - 149   2018.6

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  • 膝窩にセンチネルリンパ節を同定した足原発の悪性黒色腫の当科におけるまとめ

    堀本 浩平, 加藤 潤史, 肥田 時征, 佐藤 さゆり, 澤田 匡秀, 佐々木 洋, 井上 夕菜, 松井 馨之, 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   34回   163 - 163   2018.6

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  • ニボルマブ投与後にイピリムマブを使用した進行期悪性黒色腫の9例

    佐藤 美聡, 宇原 久, 古賀 弘志, 奥山 隆平

    西日本皮膚科   80 ( 3 )   301 - 301   2018.6

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  • 直腸癌の多発皮膚転移

    加瀬 貴美, 加藤 潤史, 澄川 靖之, 肥田 時征, 杉田 真太朗, 宇原 久

    西日本皮膚科   80 ( 3 )   181 - 182   2018.6

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  • Cytokeratin 19 expression as a risk factor for metastasis in cutaneous squamous cell carcinoma. Reviewed

    Uhara Hisashi, Kato Junji, Hida Tokimasa

    JOURNAL OF CLINICAL ONCOLOGY   36 ( 15 )   2018.5

  • 乳房外Paget病に対するセカンドラインとしてのTS-1療法

    加藤 潤史, 肥田 時征, 堀本 浩平, 佐藤 さゆり, 澤田 匡秀, 藤岡 茉生, 松井 馨之, 宇原 久

    日本皮膚科学会雑誌   128 ( 5 )   1221 - 1221   2018.5

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  • 悪性黒色腫における好中球・リンパ球比,血小板・リンパ球比,リンパ球・単球比と病期との関連

    松井 馨之, 加藤 潤史, 箕輪 智幸, 澤田 匡秀, 佐藤 さゆり, 堀本 浩平, 神谷 崇文, 肥田 時征, 澄川 靖之, 宇原 久

    日本皮膚科学会雑誌   128 ( 5 )   1235 - 1235   2018.5

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  • Safety and efficacy of nivolumab in Japanese patients with malignant melanoma: An interim analysis of a postmarketing surveillance Reviewed

    Yoshio Kiyohara, Hisashi Uhara, Yoshihiko Ito, Noritake Matsumoto, Tetsuya Tsuchida, Naoya Yamazaki

    Journal of Dermatology   45 ( 4 )   408 - 415   2018.4

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    DOI: 10.1111/1346-8138.14227

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  • 膝窩センチネルリンパ節を同定した右母趾悪性黒色腫の1例

    佐々木 洋, 堀本 浩平, 加藤 潤史, 肥田 時征, 佐藤 さゆり, 澤田 匡秀, 井上 夕菜, 松井 馨之, 宇原 久

    日本皮膚科学会雑誌   128 ( 4 )   608 - 608   2018.4

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  • Dermoscopic features distinctive for extraocular sebaceous carcinoma. Reviewed International journal

    Kohei Horimoto, Junji Kato, Yasuyuki Sumikawa, Tokimasa Hida, Takafumi Kamiya, Sayuri Sato, Hitomi Takahashi, Masahide Sawada, Toshiharu Yamashita, Hisashi Uhara

    The Journal of dermatology   45 ( 4 )   487 - 490   2018.4

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    We examined dermoscopic features of three cases of extraocular sebaceous carcinoma and reviewed the literatures. The yellowish structures, polymorphous vessels and ulceration were common findings in our cases and all cases of the previous reports. The appearance of whitish-pink areas has not been described previously. Our results suggested that the combination of four dermoscopic features, whitish-pink areas, yellowish structures, polymorphous vessels and ulceration might be distinctive in extraocular sebaceous carcinoma.

    DOI: 10.1111/1346-8138.14170

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  • 右示指の黒色斑を伴った紅色結節

    箕輪 智幸, 神谷 崇文, 亀倉 南穂, 加藤 潤史, 肥田 時征, 宇原 久

    日本皮膚病理組織学会抄録集   34回   52,19 - 52,19   2018.4

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  • アトピー性皮膚炎を合併したtransient hypogammaglobulinemia of infancyの1例

    箕輪 智幸, 澄川 靖之, 肥田 時征, 宇原 久

    日本皮膚科学会雑誌   128 ( 4 )   607 - 607   2018.4

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  • 乳児臀部肉芽腫の1例

    丸尾 亜紀, 箕輪 智幸, 江畑 加奈子, 大橋 隆宏, 神谷 崇文, 澄川 靖之, 宇原 久

    日本皮膚科学会雑誌   128 ( 4 )   608 - 608   2018.4

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  • ドセタキセル療法が奏効した古典型カポジ肉腫の1例

    井上 夕菜, 加藤 潤史, 肥田 時征, 堀本 浩平, 佐藤 さゆり, 澤田 匡秀, 佐々木 洋, 松井 馨之, 宇原 久

    日本皮膚科学会雑誌   128 ( 4 )   609 - 609   2018.4

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  • 寒冷蕁麻疹の2例

    大橋 隆宏, 澄川 靖之, 高橋 宏征, 米田 大介, 山口 華央, 加瀬 貴美, 菅 裕司, 宇原 久

    日本皮膚科学会雑誌   128 ( 4 )   607 - 607   2018.4

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  • Recent advances in therapeutic strategies for unresectable or metastatic melanoma and real-world data in Japan Reviewed

    Hisashi Uhara

    International Journal of Clinical Oncology   1437-7772 (Electronic)   1 - 7   2018.2

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    DOI: 10.1007/s10147-018-1246-y

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  • Imiquimod 5% cream as a therapeutic option for extramammary Paget's disease. Reviewed International journal

    Masahide Sawada, Junji Kato, Toshiharu Yamashita, Akihiro Yoneta, Tokimasa Hida, Kohei Horimoto, Sayuri Sato, Hisashi Uhara

    The Journal of dermatology   45 ( 2 )   216 - 219   2018.2

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    A wide local excision is the standard treatment for extramammary Paget's disease (EMPD), though this treatment often leads to permanent anogenital mutilation and functional impairment. The purpose of our study is to evaluate the efficacy and safety of the topical application of imiquimod 5% cream for non-invasive EMPD. We examined nine patients with EMPD. Eight of the nine patients were treated with imiquimod 5% cream three times per week for 16 weeks; one case was treated for 6 weeks. The response rate was 100% including five complete remissions. Local irritation was observed in three patients, which was controlled by a provisional withdrawal of the treatment. These results suggest that imiquimod 5% cream may be considered an alternative therapeutic option for the treatment of non-invasive EMPD.

    DOI: 10.1111/1346-8138.14117

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  • 巨大な褐色斑と多発性色素性母斑を伴ったびまん性神経線維腫

    肥田 時征, 杉田 真太朗, 菅原 太郎, 山下 利春, 宇原 久

    日本レックリングハウゼン病学会学術大会プログラム・抄録集   9回   30 - 30   2018.2

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  • 悪性黒色腫患者における好中球・リンパ球比の有用性

    松井 馨之, 加藤 潤史, 箕輪 智幸, 澤田 匡秀, 佐藤 さゆり, 堀本 浩平, 肥田 時征, 宇原 久

    日本皮膚科学会雑誌   128 ( 1 )   62 - 62   2018.1

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  • Successful TS-1 monotherapy as the second-line treatment for advanced extramammary Paget's disease: A report of two cases. Reviewed International journal

    Junji Kato, Tokimasa Hida, Toshiharu Yamashita, Shiori Kamiya, Kohei Horimoto, Sayuri Sato, Hitomi Takahashi, Masahide Sawada, Mao Yamada, Hisashi Uhara

    The Journal of dermatology   45 ( 1 )   80 - 82   2018.1

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    There is no standard chemotherapeutic treatment for advanced extramammary Paget's disease, though the effectiveness of some chemotherapy regimens, including docetaxel, has been reported. In this report, we report that TS-1 monotherapy was effective in two patients with advanced extramammary Paget's disease after docetaxel treatment failure. TS-1 monotherapy may be useful as the second-line treatment for patients with advanced extramammary Paget's disease.

    DOI: 10.1111/1346-8138.14017

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  • 局所麻酔薬による即時型アレルギーが疑われた38例についての検討

    江畑 加奈子, 澄川 靖之, 肥田 時征, 神谷 崇文, 石井 泰江, 菅 裕司, 加藤 潤史, 堀本 浩平, 宇原 久

    日本皮膚科学会雑誌   128 ( 1 )   62 - 62   2018.1

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  • 乳房Paget病のダーモスコピー所見の検討

    江畑 加奈子, 肥田 時征, 澄川 靖之, 宇原 久, 久冨 五郎, 前田 和男, 疋田 政博, 松本 光博

    日本皮膚科学会雑誌   128 ( 1 )   59 - 59   2018.1

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  • 肺扁平上皮癌を合併したBazex症候群の1例

    塩野谷 愛香, 肥田 時征, 宇原 久, 西坂 尚大, 汐谷 心

    日本皮膚科学会雑誌   128 ( 1 )   63 - 63   2018.1

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  • Serum 5-S-cysteinyldopa behavior in the early phase of nivolumab treatment of 12 melanoma patients Reviewed

    Omodaka, T. Minagawa, A. Uhara, H. Wakamatsu, K. Koizumi, T. Yokokawa, Y. Koga, H. Okuyama, R

    J Dermatol   1346-8138 (Electronic)   2018

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  • Rechallenge With Nivolumab After Vemurafenib Treatment of Initially Nivolumab-Resistant Advanced Melanoma Reviewed

    Kato, J. Hida, T. Kamiya, T. Sato, S. Takahashi, H. Torigoe, T. Uhara, H

    JAMA Dermatol   154 ( 5 )   621 - 622   2018

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  • Successful rechallenge with nivolumab therapy after radiotherapy in mucosal melanoma Reviewed

    Kato, J. Hida, T. Horimoto, K. Sato, S. Kobayashi, K. Sawada, M. Fujioka, M. Tsuchiya, T. Someya, M. Uhara, H

    J Dermatol   1346-8138 (Electronic)   2018

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  • Cytokeratin 19 expression is a risk factor for metastasis in cutaneous squamous cell carcinoma Reviewed

    Kato, J. Hida, T. Sugita, S. Hasegawa, T. Kamiya, S. Horimoto, K. Sato, S. Sawada, M. Uhara, H

    J Eur Acad Dermatol Venereol   32 ( 7 )   299 - 301   2018

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  • Characteristics of adverse drug reactions in a vemurafenib early post-marketing phase vigilance study in Japan Reviewed

    Uhara, H. Kiyohara, Y. Tsuda, A. Takata, M. Yamazaki, N

    Clin Transl Oncol   20 ( 2 )   169 - 175   2018

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  • A case of subepidermal autoimmune bullous disease with autoantibodies against 200 and 290-kDa antigens Reviewed

    Sawada, M. Hida, T. Ujiie, H. Iwata, H. Uhara, H

    J Eur Acad Dermatol Venereol   1468-3083 (Electronic)   2018

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  • Prognostic role of platelet to lymphocyte and lymphocyte to monocyte ratios in advanced melanoma treated with anti-programmed death-1 Reviewed

    Minowa, T. Kato, J. Hida, T. Horimoto, K. Sato, S. Sawada, M. Uhara, H

    Eur J Dermatol   1952-4013 (Electronic)   2018

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  • Granulocyte colony-stimulating factor-producing melanoma treated with the combination of dabrafenib and trametinib Reviewed

    Minowa, T. Kato, J. Hida, T. Horimoto, K. Sato, S. Sawada, M. Takahashi, H. Uhara, H

    Int J Dermatol   57 ( 7 )   31 - 33   2018

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  • Efficacy and toxicity of ipilimumab used after nivolumab in patients with melanoma Reviewed

    Sato, M. Uhara, H. Koga, H. Okuyama, R

    J Dermatol   45 ( 10 )   287 - 289   2018

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  • Association between PD-L1 expression and lymph node metastasis in cutaneous squamous cell carcinoma Reviewed

    Kamiya, S. Kato, J. Kamiya, T. Yamashita, T. Sumikawa, Y. Hida, T. Horimoto, K. Sato, S. Takahashi, H. Sawada, M. Kubo, T. Torigoe, T. Uhara, H

    Asia Pac J Clin Oncol   1743-7563 (Electronic)   2018

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  • Nevus cells of cardiofaciocutaneous syndrome bear BRAF germ-line and somatic double mutations Reviewed

    Hida, T. Sato, S. Okura, M. Uhara, H

    Eur J Dermatol   1952-4013 (Electronic)   2018

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  • Xeroderma pigmentosum group D: Report of a novel combination of ERCC2 variations and its phenotype Reviewed

    Hida, T. Okura, M. Kobayashi, K. Yamashita, T. Nishigori, C. Uhara, H

    J Dermatol   1346-8138 (Electronic)   2018

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  • Unique dermoscopic feature of a long-standing pencil core granuloma on the head Reviewed

    Yoshikawa, M. Kamiya, T. Sumikawa, Y. Uhara, H

    J Dermatol   1346-8138 (Electronic)   2018

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  • Multiple Melanonychia Striata as a Sign of Connective Tissue Disorders Reviewed

    Edamitsu, T. Uhara, H. Minagawa, A. Okuyama, R

    J Am Acad Dermatol   1097-6787 (Electronic)   2018

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  • Circulating tumour DNA for monitoring treatment response to anti-PD-1 immunotherapy in melanoma patients Reviewed

    Atsuko Ashida, Kaori Sakaizawa, Hisashi Uhara, Ryuhei Okuyama

    Acta Dermato-Venereologica   97 ( 10 )   1212 - 1218   2017.11

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    DOI: 10.2340/00015555-2748

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  • Phase 2 study to evaluate efficacy and safety of combination therapy with nivolumab (NIVO) and ipilimumab(IPI) in patients with previously untreated melanoma

    Y. Kiyohara, T. Takenouchi, H. Uhara, H. Koga, H. Uchi, N. Yamazaki

    Annals of Oncology   28   x113 - x114   2017.11

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    DOI: 10.1093/annonc/mdx667.002

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  • Circulating tumor DNA for monitoring treatment response to anti-PD-1 immunotherapy in melanoma patients Reviewed

    A. Ashida, K. Sakaizawa, H. Uhara, R. Okuyama

    JOURNAL OF INVESTIGATIVE DERMATOLOGY   137 ( 10 )   S291 - S291   2017.10

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  • 抗PD-1抗体をベースとした各種併用療法 Reviewed

    宇原久

    がん免疫療法   1 ( 2 )   90 - 91   2017.9

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  • Nail apparatus melanoma thickness is associated with side and age Reviewed

    A. Minagawa, T. Omodaka, H. Koga, Y. Yokokawa, H. Uhara, R. Okuyama

    BRITISH JOURNAL OF DERMATOLOGY   177 ( 3 )   E65 - E66   2017.9

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  • 【免疫チェックポイント阻害薬 がん薬物療法の新時代】 各腫瘍における免疫チェックポイント阻害薬の現状 悪性黒色腫 Reviewed

    宇原久

    薬事   59 ( 12 )   2403 - 2407   2017.9

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  • Nivolumab-related myasthenia gravis with myositis and myocarditis in Japan Reviewed

    Shigeaki Suzuki, Nobuhisa Ishikawa, Fumie Konoeda, Nobuhiko Seki, Satoshi Fukushima, Kikuko Takahashi, Hisashi Uhara, Yoshikazu Hasegawa, Shinichiro Inomata, Yasushi Otani, Kenji Yokota, Takashi Hirose, Ryo Tanaka, Norihiro Suzuki, Makoto Matsui

    NEUROLOGY   89 ( 11 )   1127 - 1134   2017.9

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    DOI: 10.1212/WNL.0000000000004359

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  • 【がん分子標的薬の効果と副作用-期待される効果と評価-】 抗体薬 抗PD-1抗体薬、抗CTLA-4抗体薬 Reviewed

    宇原久

    日本臨床   75 ( 9 )   1359 - 1364   2017.9

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  • 複数の自己抗体を検出した自己免疫性表皮下水疱症の1例

    澤田 匡秀, 肥田 時征, 氏家 英之, 泉 健太郎, 西江 渉, 宇原 久

    日本皮膚科学会雑誌   127 ( 9 )   2117 - 2117   2017.8

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  • BRAF/MEK阻害薬が奏効した悪性黒色腫の2例

    箕輪 智幸, 加藤 潤史, 江畑 加奈子, 高橋 仁美, 澤田 匡秀, 佐藤 さゆり, 堀本 浩平, 肥田 時征, 宇原 久, 西川 武志

    日本皮膚科学会雑誌   127 ( 9 )   2121 - 2121   2017.8

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  • 強皮症に合併した指尖部潰瘍に対し高圧酸素療法が奏功した1例

    安食 さえ子, 菅 裕司, 高橋 宏征, 米田 大介, 山口 華央, 神谷 詩織, 加瀬 貴美, 澄川 靖之, 米田 明弘, 宇原 久

    日本皮膚科学会雑誌   127 ( 9 )   2118 - 2118   2017.8

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  • Efficacy and safety of nivolumab in Japanese patients with previously untreated advanced melanoma: A phase II study. Reviewed International journal

    Naoya Yamazaki, Yoshio Kiyohara, Hisashi Uhara, Jiro Uehara, Manabu Fujimoto, Tatsuya Takenouchi, Masaki Otsuka, Hiroshi Uchi, Hironobu Ihn, Hironobu Minami

    Cancer science   108 ( 6 )   1223 - 1230   2017.6

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    Treating advanced or recurrent melanoma remains a challenge. Cancer cells can evade the immune system by blocking T-cell activation through overexpression of the inhibitory receptor programmed death 1 (PD-1) ligands. The PD-1 inhibitor nivolumab blocks the inhibitory signal in T cells, thus overcoming the immune resistance of cancer cells. Nivolumab has shown promising anticancer activity in various cancers. We carried out a single-arm, open-label, multicenter, phase II study to investigate the efficacy and safety of nivolumab in previously untreated Japanese patients with advanced melanoma. Twenty-four patients with stage III/IV or recurrent melanoma were enrolled and received i.v. nivolumab 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was overall response rate evaluated by an independent radiology review committee. The independent radiology review committee-assessed overall response rate was 34.8% (90% confidence interval, 20.8-51.9), and the overall survival rate at 18 months was 56.5% (90% confidence interval, 38.0-71.4). Treatment-related adverse events (AEs) of grade 3 or 4 only occurred in three patients (12.5%). Two patients discontinued nivolumab because of AEs, but all AEs were considered manageable by early diagnosis and appropriate treatment. Subgroup analyses showed that nivolumab was clinically beneficial and tolerable regardless of BRAF genotype, and that patients with treatment-related select AEs and with vitiligo showed tendency for better survival. In conclusion, nivolumab showed favorable efficacy and safety profiles in Japanese patients with advanced or recurrent melanoma, with or without BRAF mutations. (Trial registration no. JapicCTI-142533.).

    DOI: 10.1111/cas.13241

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  • Efficacy and safety of nivolumab in Japanese patients with previously untreated advanced melanoma: A phase II study Reviewed

    Naoya Yamazaki, Yoshio Kiyohara, Hisashi Uhara, Jiro Uehara, Manabu Fujimoto, Tatsuya Takenouchi, Masaki Otsuka, Hiroshi Uchi, Hironobu Ihn, Hironobu Minami

    CANCER SCIENCE   108 ( 6 )   1223 - 1230   2017.6

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    DOI: 10.1111/cas.13241

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  • 眼瞼外脂腺癌のダーモスコピー所見と対応する皮膚病理所見の検討

    堀本 浩平, 加藤 潤史, 澤田 匡秀, 高橋 仁美, 佐藤 さゆり, 石井 泰江, 神谷 崇文, 肥田 時征, 澄川 靖之, 宇原 久

    日本皮膚病理組織学会抄録集   33回   59,36 - 59,36   2017.6

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  • 脂腺母斑に生じた基底細胞癌のダーモスコピー所見

    皆川 茜, 古賀 弘志, 宇原 久, 奥山 隆平

    西日本皮膚科   79 ( 3 )   313 - 314   2017.6

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  • Blue gray ovoid nestとarborizing vesselsを示した上眼瞼の紅色結節

    皆川 茜, 代田 志保, 古賀 弘志, 宇原 久, 安齋 眞一, 奥山 隆平

    日本皮膚病理組織学会抄録集   33回   55,32 - 55,32   2017.6

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  • Cytokine biomarkers to predict antitumor responses to nivolumab suggested in a phase 2 study for advanced melanoma. Reviewed International journal

    Naoya Yamazaki, Yoshio Kiyohara, Hisashi Uhara, Hajime Iizuka, Jiro Uehara, Fujio Otsuka, Yasuhiro Fujisawa, Tatsuya Takenouchi, Taiki Isei, Keiji Iwatsuki, Hiroshi Uchi, Hironobu Ihn, Hironobu Minami, Hideaki Tahara

    Cancer science   108 ( 5 )   1022 - 1031   2017.5

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    Promising antitumor activities of nivolumab, a fully humanized IgG4 inhibitor antibody against the programmed death-1 protein, were suggested in previous phase 1 studies. The present phase 2, single-arm study (JAPIC-CTI #111681) evaluated the antitumor activities of nivolumab and explored its predictive correlates in advanced melanoma patients at 11 sites in Japan. Intravenous nivolumab 2 mg/kg was given repeatedly at 3-week intervals to 35 of 37 patients enrolled from December 2011 to May 2012 until they experienced unacceptable toxicity, disease progression, or complete response. Primary endpoint was objective response rate. Serum levels of immune modulators were assessed at multiple time points. As of 21 October 2014, median response duration, median progression-free survival, and median overall survival were 463 days, 169 days, and 18.0 months, respectively. The overall response rate and 1- and 2-year survival rates were 28.6%, 54.3%, and 42.9%, respectively. Thirteen patients remained alive at the end of the observation period and no deaths were drug related. Grade 3-4 drug-related adverse events were observed in 31.4% of patients. Pretreatment serum interferon-γ, and interleukin-6 and -10 levels were significantly higher in the patients with objective tumor responses than in those with tumor progression. In conclusion, giving repeated i.v. nivolumab had potent and durable antitumor effects and a manageable safety profile in advanced melanoma patients, strongly suggesting the usefulness of nivolumab for advanced melanoma and the usefulness of pretreatment serum cytokine profiles as correlates for predicting treatment efficacy.

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  • 有棘細胞癌におけるサイトケラチン19の発現の検討

    加藤 潤史, 澤田 匡秀, 高橋 仁美, 佐藤 さゆり, 神谷 詩織, 堀本 浩平, 肥田 時征, 山下 利春, 宇原 久

    日本皮膚科学会雑誌   127 ( 5 )   1138 - 1138   2017.5

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  • 小児期発症の病歴を持つメラノーマの特徴

    皆川 茜, 宇原 久, 芦田 敦子, 境澤 香里, 古賀 弘志, 奥山 隆平

    日本皮膚科学会雑誌   127 ( 5 )   1140 - 1140   2017.5

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  • 乳房外Paget病に対するイミキモドの有効性に関する検討

    澤田 匡秀, 加藤 潤史, 高橋 仁美, 佐藤 さゆり, 堀本 浩平, 石井 泰江, 肥田 時征, 米田 明弘, 山下 利春, 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   33回   169 - 169   2017.5

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  • ベムラフェニブ投与後にPD-L1の発現が増加した悪性黒色腫の1例

    加藤 潤史, 高橋 仁美, 澤田 匡秀, 佐藤 さゆり, 堀本 浩平, 神谷 崇文, 肥田 時征, 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   33回   147 - 147   2017.5

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  • Detection of BRAF(V600K) mutant tumor-derived DNA in the pleural effusion from a patient with metastatic melanoma Reviewed

    Kaori Sakaizawa, Atsuko Ashida, Hisashi Uhara, Ryuhei Okuyama

    CLINICAL CHEMISTRY AND LABORATORY MEDICINE   55 ( 4 )   E92 - E95   2017.4

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  • Phase 1b study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in Japanese patients with advanced melanoma (KEYNOTE-041). Reviewed International journal

    Naoya Yamazaki, Tatsuya Takenouchi, Manabu Fujimoto, Hironobu Ihn, Hiroshi Uchi, Takashi Inozume, Yoshio Kiyohara, Hisashi Uhara, Kazuhiko Nakagawa, Hiroshi Furukawa, Hidefumi Wada, Kazuo Noguchi, Takashi Shimamoto, Kenji Yokota

    Cancer chemotherapy and pharmacology   79 ( 4 )   651 - 660   2017.4

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    PURPOSE: This phase I b study evaluated the safety and anti-tumor activity of pembrolizumab in Japanese patients with advanced melanoma. METHODS: Pembrolizumab (2 mg/kg) was given every 3 weeks (Q3W) for up to 2 years or until confirmed progression or unacceptable toxicity. The tumor response was assessed as per the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by both investigator review and central review. RESULTS: Forty-two patients with advanced melanoma received pembrolizumab. A primary cutaneous histology was observed in 34 patients (81.0%), while a primary mucosal histology was observed in 8 patients (19.0%). Thirty-four patients (81.0%) experienced treatment-related adverse events (AEs). The most common treatment-related AEs were pruritus, maculopapular rash, malaise, and hypothyroidism. Grade 3-5 treatment-related AEs occurred in 8 patients (19.0%). The only grade 3-5 treatment-related AE reported in at least two patients was anemia. There were two treatment-related deaths (unknown cause and cerebral hemorrhage). Among the 37 evaluable patients, the confirmed overall response rates (ORRs) determined by central review were 24.1% (95% CI 10.3-43.5) for cutaneous melanoma and 25.0% (95% CI 3.2-65.1) for mucosal melanoma. The responses were durable, and the median duration of response was not reached in either population. The median overall survival (OS) was not reached, with a 12-month OS of 82.7% for cutaneous melanoma and 51.4% for mucosal melanoma. CONCLUSION: The safety profile of pembrolizumab in Japanese patients was similar to that reported in the previous clinical studies. Pembrolizumab provided promising anti-tumor activity in Japanese patients with advanced melanoma.

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  • 【がん免疫療法-がん完治に向けての新たな治療法の探索-】 免疫チェックポイント阻害薬 悪性黒色腫に対する治療 Reviewed

    宇原久

    日本臨床   75 ( 2 )   216 - 220   2017.2

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  • A randomized double-blind trial of intravenous immunoglobulin for bullous pemphigoid. Reviewed International journal

    Masayuki Amagai, Shigaku Ikeda, Takashi Hashimoto, Masato Mizuashi, Akihiro Fujisawa, Hironobu Ihn, Yasushi Matsuzaki, Mikio Ohtsuka, Hiroshi Fujiwara, Junichi Furuta, Osamu Tago, Jun Yamagami, Akiko Tanikawa, Hisashi Uhara, Akimichi Morita, Gen Nakanishi, Mamori Tani, Yumi Aoyama, Eiichi Makino, Masahiko Muto, Motomu Manabe, Takayuki Konno, Satoru Murata, Seiichi Izaki, Hideaki Watanabe, Yukie Yamaguchi, Setsuko Matsukura, Mariko Seishima, Koji Habe, Yuichi Yoshida, Sakae Kaneko, Hajime Shindo, Kimiko Nakajima, Takuro Kanekura, Kenzo Takahashi, Yasuo Kitajima, Koji Hashimoto

    Journal of dermatological science   85 ( 2 )   77 - 84   2017.2

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    BACKGROUND: Patients with steroid-resistant bullous pemphigoid (BP) require an appropriate treatment option. OBJECTIVE: A multicenter, randomized, placebo-controlled, double-blind trial was conducted to investigate the therapeutic effect of high-dose intravenous immunoglobulin (IVIG; 400mg/kg/day for 5days) in BP patients who showed no symptomatic improvement with prednisolone (≥0.4mg/kg/day) administered. METHODS: We evaluated the efficacy using the disease activity score on day15 (DAS15) as a primary endpoint, and changes in the DAS over time, the anti-BP180 antibody titer, and safety for a period of 57days as secondary endpoints. RESULTS: We enrolled 56 patients in this study. The DAS15 was 12.5 points lower in the IVIG group than in the placebo group (p=0.089). The mean DAS of the IVIG group was constantly lower than that of the placebo group throughout the course of observation, and a post hoc analysis of covariance revealed a significant difference (p=0.041). Furthermore, when analyzed only in severe cases (DAS≥40), the DAS15 differed significantly (p=0.046). The anti-BP180 antibody titers showed no difference between the two groups. CONCLUSION: IVIG provides a beneficial therapeutic outcome for patients with BP who are resistant to steroid therapy.

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  • Nail apparatus melanoma in a Japanese population: a comparative study of surgical procedures and prognoses in a large series of 151 cases Reviewed

    Ogata, D. Uhara, H. Tsutsumida, A. Yamazaki, N. Mochida, K. Amano, M. Yoshikawa, S. Kiyohara, Y. Tsuchida, T

    Eur J Dermatol   27 ( 6 )   620 - 626   2017

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  • Quantitative analysis of the BRAF V600E mutation in circulating tumor-derived DNA in melanoma patients using competitive allele-specific TaqMan PCR Reviewed

    Atsuko Ashida, Kaori Sakaizawa, Asuka Mikoshiba, Hisashi Uhara, Ryuhei Okuyama

    International Journal of Clinical Oncology   21 ( 5 )   981 - 988   2016.10

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    DOI: 10.1007/s10147-016-0976-y

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  • メラノーマ患者におけるcirculating tumor DNAによるニボルマブ治療の評価

    芦田 敦子, 境澤 香里, 宇原 久, 奥山 隆平

    日本癌学会総会記事   75回   P - 2322   2016.10

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  • 肢端黒子型悪性黒色腫の解剖学的分布

    面高 俊和, 皆川 茜, 古賀 弘志, 芦田 敦子, 宇原 久, 奥山 隆平

    日本皮膚科学会雑誌   126 ( 11 )   2131 - 2131   2016.10

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  • パクリタキセルにより強皮症様皮膚硬化を呈した1例

    大橋 敦子, 芦田 敦子, 古賀 弘志, 宇原 久, 奥山 隆平

    日本皮膚科学会雑誌   126 ( 11 )   2128 - 2128   2016.10

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  • Phase I study of pegylated interferon-alpha-2b as an adjuvant therapy in Japanese patients with malignant melanoma Reviewed

    Naoya Yamazaki, Hisashi Uhara, Hidefumi Wada, Kenji Matsuda, Keiko Yamamoto, Takashi Shimamoto, Yoshio Kiyohara

    JOURNAL OF DERMATOLOGY   43 ( 10 )   1146 - 1153   2016.10

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    DOI: 10.1111/1346-8138.13338

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  • Late onset of acute urticaria after bee stings Reviewed

    Yuko Asai, Hisashi Uhara, Atsushi Miyazaki, Minoru Saiki, Ryuhei Okuyama

    Case Reports in Dermatology   8 ( 3 )   341 - 343   2016.9

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    DOI: 10.1159/000449033

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  • A proposal for a TNM staging system for extramammary Paget disease: Retrospective analysis of 301 patients with invasive primary tumors Reviewed

    Kuniaki Ohara, Yasuhiro Fujisawa, Koji Yoshino, Yoshio Kiyohara, Takafumi Kadono, Yozo Murata, Hisashi Uhara, Naohito Hatta, Hiroshi Uchi, Shigeto Matsushita, Tatsuya Takenouchi, Toshihiko Hayashi, Kenichi Yoshimura, Manabu Fujimoto

    JOURNAL OF DERMATOLOGICAL SCIENCE   83 ( 3 )   234 - 239   2016.9

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    DOI: 10.1016/j.jdermsci.2016.06.004

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  • BRAF変異を有する悪性黒色腫における免疫応答と予後解析

    中村 謙太, 芦田 敦子, 木庭 幸子, 宇原 久, 奥山 隆平

    日本臨床免疫学会会誌   39 ( 4 )   423 - 423   2016.8

  • Frequency of level II and III axillary nodes metastases in patients with positive sentinel lymph nodes in melanoma: a multi-institutional study in Japan. Reviewed

    Arata Tsutsumida, Akira Takahashi, Kenjiro Namikawa, Naoya Yamazaki, Hisashi Uhara, Yukiko Teramoto, Tatsuya Takenouchi, Satoshi Fukushima, Kenji Yokota, Jiro Uehara, Shigeto Matsushita, Yoshitsugu Shibayama, Naohito Hatta, Yuri Masui, Hiroshi Uchi, Yasuhiro Fujisawa, Dai Ogata

    International journal of clinical oncology   21 ( 4 )   796 - 800   2016.8

  • Water-based correction fluid is a useful skin marker for determination of the tumor margin of basal cell carcinoma under high-frequency ultrasound Reviewed

    Koichi Hayashi, Ryuhei Okuyama, Hisashi Uhara

    Journal of Dermatology   43 ( 7 )   823 - 825   2016.7

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    DOI: 10.1111/1346-8138.13260

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  • Usefulness of docetaxel as first-line chemotherapy for metastatic extramammary Paget's disease Reviewed

    Koji Yoshino, Yasuhiro Fujisawa, Yoshio Kiyohara, Takafumi Kadono, Yozo Murata, Hisashi Uhara, Naohito Hatta, Hiroshi Uchi, Shigeto Matsushita, Tatsuya Takenouchi, Toshihiko Hayashi, Kuniaki Ohara

    JOURNAL OF DERMATOLOGY   43 ( 6 )   633 - 637   2016.6

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    DOI: 10.1111/1346-8138.13200

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  • Fish collagen is an important panallergen in the Japanese population Reviewed

    Y. Kobayashi, H. Akiyama, J. Huge, H. Kubota, S. Chikazawa, T. Satoh, T. Miyake, H. Uhara, R. Okuyama, R. Nakagawara, M. Aihara, N. Hamada-Sato

    Allergy: European Journal of Allergy and Clinical Immunology   71 ( 5 )   720 - 723   2016.5

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    DOI: 10.1111/all.12836

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  • 足底のメラノーマは物理的荷重部位に好発する

    皆川 茜, 古賀 弘志, 面高 俊和, 宇原 久, 奥山 隆平

    日本皮膚悪性腫瘍学会学術大会プログラム・抄録集   32回   124 - 124   2016.5

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  • 血液循環腫瘍DNAよりBRAF変異が検出できた進行期悪性黒色腫症例

    芦田 敦子, 御子柴 飛鳥, 熊谷 尚美, 境澤 香里, 古賀 弘志, 宇原 久, 奥山 隆平

    日本皮膚科学会雑誌   126 ( 5 )   975 - 975   2016.5

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  • Melanoma Reviewed

    Hisashi Uhara

    Japanese Journal of Cancer and Chemotherapy   43 ( 4 )   404 - 407   2016.4

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  • 爪部メラノーマの好発部位と腫瘍厚の関連

    皆川 茜, 古賀 弘志, 面高 俊和, 宇原 久, 奥山 隆平

    日本皮膚科学会雑誌   126 ( 4 )   436 - 436   2016.4

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  • 【メラノーマ-基礎から最新薬物療法まで】分子異常

    芦田 敦子, 木庭 幸子, 宇原 久

    カレントテラピー   34 ( 4 )   344 - 349   2016.4

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  • Eccrine porocarcinoma shares dermoscopic characteristics with eccrine poroma: A report of three cases and review of the published work Reviewed

    Tomohiro Edamitsu, Akane Minagawa, Hiroshi Koga, Hisashi Uhara, Ryuhei Okuyama

    Journal of Dermatology   43 ( 3 )   332 - 335   2016.3

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    DOI: 10.1111/1346-8138.13082

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  • Nivolumab-induced organizing pneumonia in a melanoma patient Reviewed

    Tasuku Sano, Hisashi Uhara, Yasutomo Mikoshiba, Aya Kobayashi, Ryuhei Uchiyama, Kazunari Tateishi, Hiroshi Yamamoto, Ryuhei Okuyama

    Japanese Journal of Clinical Oncology   46 ( 3 )   270 - 272   2016.3

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    DOI: 10.1093/jjco/hyv199

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  • Acetylcholine receptor binding antibody-associated myasthenia gravis and rhabdomyolysis induced by nivolumab in a patient with melanoma Reviewed

    Takushi Shirai, Tasuku Sano, Fuminao Kamijo, Nana Saito, Tomomi Miyake, Minori Kodaira, Nagaaki Katoh, Kenichi Nishie, Ryuhei Okuyama, Hisashi Uhara

    Japanese Journal of Clinical Oncology   46 ( 1 )   86 - 88   2016.1

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    DOI: 10.1093/jjco/hyv158

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  • Melanoma with BRAF Mutation in Circulating Cell-free DNA despite no Mutation in the Primary Lesion: A Case Report Reviewed

    Atsuko Ashida, Hisashi Uhara, Asuka Mikoshiba, Kaori Sakaizawa, Naomi Kumagai, Hiroshi Koga, Ryuhei Okuyama

    ACTA DERMATO-VENEREOLOGICA   96 ( 1 )   128 - 129   2016

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    DOI: 10.2340/00015555-2194

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  • 進行期メラノーマ患者におけるcastPCR法を用いたBRAFV600E血液循環腫瘍DNAの検出

    芦田 敦子, 境澤 香里, 宇原 久, 奥山 隆平

    日本癌学会総会記事   74回   P - 3303   2015.10

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  • Clinical characteristics associated with BRAF, NRAS and KIT mutations in Japanese melanoma patients. Reviewed International journal

    Kaori Sakaizawa, Atsuko Ashida, Aya Uchiyama, Takamichi Ito, Yasuhiro Fujisawa, Dai Ogata, Shigeto Matsushita, Kazuyasu Fujii, Satoshi Fukushima, Yoshitsugu Shibayama, Naohito Hatta, Tatsuya Takenouchi, Jiro Uehara, Ryuhei Okuyama, Naoya Yamazaki, Hisashi Uhara

    Journal of dermatological science   80 ( 1 )   33 - 7   2015.10

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    DOI: 10.1016/j.jdermsci.2015.07.012

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  • 【家族性腫瘍学-家族性腫瘍の最新研究動向-】症候群 Familial atypical multiple mole melanoma syndrome(家族性多発性メラノーマ症候群、家族性異型多発母斑黒色腫症候群)

    芦田 敦子, 宇原 久

    日本臨床   73 ( 増刊6 家族性腫瘍学 )   99 - 102   2015.8

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  • Notch down-regulation in regenerated epidermis contributes to enhanced expression of interleukin-36α and suppression of keratinocyte differentiation during wound healing Reviewed

    Yuko Takazawa, Eisaku Ogawa, Rumiko Saito, Ryuhei Uchiyama, Shuntaro Ikawa, Hisashi Uhara, Ryuhei Okuyama

    Journal of Dermatological Science   79 ( 1 )   10 - 19   2015.7

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    DOI: 10.1016/j.jdermsci.2015.04.003

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  • 信州大学における悪性黒色腫245例(2000〜2009年)の臨床統計

    中村 謙太, 皆川 茜, 芦田 敦子, 古賀 弘志, 木庭 幸子, 奥山 隆平, 宇原 久

    日本皮膚科学会雑誌   125 ( 8 )   1587 - 1592   2015.7

  • The role of sentinel lymph node biopsy in the management of invasive extramammary Paget's disease: Multi-center, retrospective study of 151 patients Reviewed

    Yasuhiro Fujisawa, Koji Yoshino, Yoshio Kiyohara, Takafumi Kadono, Yozo Murata, Hisashi Uhara, Naohito Hatta, Hiroshi Uchi, Shigeto Matsushita, Tatsuya Takenouchi, Toshihiko Hayashi, Manabu Fujimoto, Kuniaki Ohara

    JOURNAL OF DERMATOLOGICAL SCIENCE   79 ( 1 )   38 - 42   2015.7

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    DOI: 10.1016/j.jdermsci.2015.03.014

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  • A Case of Vulval Extramammary Paget Disease With Dermal Invasion Showing Mucinous Carcinoma Reviewed

    Shiho Asaka, Akihiko Yoshizawa, Kenji Sano, Hisashi Uhara, Takayuki Honda, Hiroyoshi Ota

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY   34 ( 4 )   396 - 400   2015.7

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    DOI: 10.1097/PGP.0000000000000169

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  • Phase I/II study of vemurafenib in patients with unresectable or recurrent melanoma with BRAF(V600) mutations Reviewed

    Naoya Yamazaki, Yoshio Kiyohara, Naofumi Sugaya, Hisashi Uhara

    JOURNAL OF DERMATOLOGY   42 ( 7 )   661 - 666   2015.7

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    DOI: 10.1111/1346-8138.12873

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  • 全身性サルコイドーシスに伴い黒色刺青部のみが隆起した刺青サルコイドーシスの1例

    中村 謙太, 河内 繁雄, 大橋 敦子, 古賀 弘志, 宇原 久, 江石 義信, 奥山 隆平

    臨床皮膚科   69 ( 7 )   469 - 473   2015.6

  • II. BRAF inhibitor and MEK inhibitor Reviewed

    Hisashi Uhara

    Japanese Journal of Cancer and Chemotherapy   42 ( 4 )   428 - 433   2015.4

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  • 皮膚癌の術後出血が診断の契機となった後天性13因子欠乏症の1例

    三宅 知美, 芦田 敦子, 宇原 久, 奥山 隆平, 福澤 正男, 一瀬 白帝

    日本皮膚科学会雑誌   125 ( 4 )   955 - 955   2015.4

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  • 【メラノーマ最新情報】日本人におけるMAPK系の遺伝子変異率と遺伝子検査の実際

    芦田 敦子, 宇原 久

    Derma.   ( 230 )   63 - 68   2015.4

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  • 地中海沿岸地域以外で認められた、CYP4F22遺伝子変異による葉状魚鱗癬症例

    杉浦 一充, 武市 拓也, 棚橋 華奈, 秋山 真志, 古庄 知己, 宇原 久, 奥山 隆平, 才田 謙

    角化症研究会記録集   29   24 - 27   2015.3

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  • Combination chemotherapy of low-dose 5-fluorouracil and cisplatin for advanced extramammary Paget's disease Reviewed

    Yasutaka Tokuda, Fuyuko Arakura, Hisashi Uhara

    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY   20 ( 1 )   194 - 197   2015.2

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    DOI: 10.1007/s10147-014-0686-2

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  • Melanocytic Naevus Shows Parallel Ridge Pattern due to the Melanin Columns Under the Ridges Reviewed

    Tasuku Sano, Akane Minagawa, Hiroshi Koga, Hisashi Uhara, Ryuhei Okuyama

    Acta Dermato-Venereologica   95 ( 1 )   95 - 96   2015

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    DOI: 10.2340/00015555-1865

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  • A melanocyte-melanoma precursor niche in sweat glands of volar skin Reviewed

    Natsuko Okamoto, Takahiro Aoto, Hisashi Uhara, Satoshi Yamazaki, Hidenori Akutsu, Akihiro Umezawa, Hiromitsu Nakauchi, Yoshiki Miyachi, Toshiaki Saida, Emi K. Nishimura

    Pigment Cell and Melanoma Research   27 ( 6 )   1039 - 1050   2014.11

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    DOI: 10.1111/pcmr.12297

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  • BRAF変異をともなう日本人黒色腫患者の臨床的特徴

    宇原 久, 境澤 香里, 芦田 敦子, 奥山 隆平

    日本皮膚科学会雑誌   124 ( 10 )   1943 - 1943   2014.9

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  • Toll-Like receptor 4 signaling promotes the migration of human melanoma cells Reviewed

    Yuko Takazawa, Yukiko Kiniwa, Eisaku Ogawa, Aya Uchiyama, Atsuko Ashida, Hisashi Uhara, Yasufumi Goto, Ryuhei Okuyama

    Tohoku Journal of Experimental Medicine   234 ( 1 )   57 - 65   2014.8

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  • メラノサイト系腫瘍での良性悪性の鑑別における5-Hydroxymethylcytocineの有用性

    内山 龍平, 宇原 久, 小川 英作, 古賀 弘志, 奥山 隆平

    日本皮膚科学会雑誌   124 ( 4 )   828 - 828   2014.4

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  • 肢端黒子型悪性黒色腫の解剖学的分布

    面高 俊和, 皆川 茜, 古賀 弘志, 芦田 敦子, 宇原 久, 奥山 隆平

    日本皮膚科学会雑誌   124 ( 4 )   829 - 829   2014.4

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  • (ス)膵転移をきたした隆起性皮膚線維肉腫/線維肉腫(DFSP/FS)の1例

    大橋 敦子, 芦田 敦子, 村田 浩, 宇原 久, 奥山 隆平, 吉田 香奈子

    日本皮膚科学会雑誌   124 ( 3 )   355 - 355   2014.3

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  • (ス)長期間症状が遷延している薬剤過敏症症候群(DIHS)の1例

    上條 史尚, 芦田 敦子, 葭矢 裕之, 佐藤 勇樹, 小林 彩, 村田 浩, 宇原 久, 奥山 隆平, 福澤 正男

    日本皮膚科学会雑誌   124 ( 3 )   355 - 355   2014.3

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  • 汗孔角化症のダーモスコピー所見

    宇原 久, 古賀 弘志, 奥山 隆平, 斎田 俊明

    茨城県臨床医学雑誌   ( 49 )   88 - 88   2014.2

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  • NRAS mutations in primary and metastatic melanomas of Japanese patients Reviewed

    Hisashi Uhara, Atsuko Ashida, Hiroshi Koga, Eisaku Ogawa, Aya Uchiyama, Ryuhei Uchiyama, Koichi Hayashi, Yukiko Kiniwa, Ryuhei Okuyama

    International Journal of Clinical Oncology   19 ( 3 )   544 - 548   2014

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    DOI: 10.1007/s10147-013-0573-2

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  • IgA/IgG pemphigus with infiltration of neutrophils and eosinophils in an ulcerative colitis patient Reviewed

    Ryuhei Uchiyama, Norito Ishii, Fuyuko Arakura, Yukiko Kiniwa, Koh Nakazawa, Hisashi Uhara, Takashi Hashimoto, Ryuhei Okuyama

    Acta Dermato-Venereologica   94 ( 6 )   737 - 738   2014

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    DOI: 10.2340/00015555-1836

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  • A case of anti-BP180-type mucous membrane pemphigoid with esophageal, genital and ophthalmic lesions Reviewed

    Toshikazu Omodaka, Hisashi Uhara, Ryuhei Uchiyama, Tasuku Sano, Hitomi Kubo, Norito Ishii, Takashi Hashimoto, Ryuhei Okuyama

    Nishinihon Journal of Dermatology   76 ( 4 )   345 - 348   2014

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    DOI: 10.2336/nishinihonhifu.76.345

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  • 日本人の悪性黒色腫患者におけるNRAS遺伝子変異の解析(Assessment of NRAS mutation in Japanese melanoma patients)

    芦田 敦子, 宇原 久, 奥山 隆平

    日本癌学会総会記事   72回   518 - 518   2013.10

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  • パクリタキセルにより強皮症様皮膚硬化を呈した1例

    大橋 敦子, 芦田 敦子, 古賀 弘志, 宇原 久, 奥山 隆平

    日本皮膚悪性腫瘍学会学術大会プログラム・抄録集   29回   140 - 140   2013.8

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  • 【皮膚悪性腫瘍-基礎と臨床の最新研究動向-】有棘細胞癌(日光角化症・Bowen病) 有棘細胞癌の治療 化学療法 化学療法(最新の分子標的薬を含む)

    古賀 弘志, 宇原 久, 奥山 隆平

    日本臨床   71 ( 増刊4 皮膚悪性腫瘍 )   507 - 511   2013.8

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  • 【皮膚悪性腫瘍-基礎と臨床の最新研究動向-】悪性黒色腫 悪性黒色腫の治療 分子標的薬 その他のMAPK系阻害剤

    古賀 弘志, 宇原 久, 奥山 隆平

    日本臨床   71 ( 増刊4 皮膚悪性腫瘍 )   392 - 396   2013.8

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  • 【皮膚悪性腫瘍-基礎と臨床の最新研究動向-】悪性黒色腫 悪性黒色腫の分子生物学 分子生物学 チロシンキナーゼ KIT

    芦田 敦子, 木庭 幸子, 宇原 久, 奥山 隆平

    日本臨床   71 ( 増刊4 皮膚悪性腫瘍 )   134 - 138   2013.8

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  • 【皮膚悪性腫瘍-基礎と臨床の最新研究動向-】悪性黒色腫 悪性黒色腫の分子生物学 分子生物学 MAPキナーゼ経路 NRAS、BRAF、MEK

    芦田 敦子, 木庭 幸子, 宇原 久, 奥山 隆平

    日本臨床   71 ( 増刊4 皮膚悪性腫瘍 )   126 - 129   2013.8

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  • Clinical effects of stereotactic radiation surgery in patients with metastatic melanoma Reviewed

    Asuka Mikoshiba, Hisashi Uhara, Hiroshi Murata, Ryuhei Okuyama

    Journal of Dermatology   40 ( 8 )   626 - 628   2013.8

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    DOI: 10.1111/1346-8138.12179

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  • 日本人のメラノーマのおけるBRAF、NRAS、KITの遺伝子変異の解析

    芦田 敦子, 宇原 久, 奥山 隆平

    日本皮膚悪性腫瘍学会学術大会プログラム・抄録集   29回   137 - 137   2013.8

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  • A case of hypocomplementaemic urticarial vasculitis with a high serum level of rheumatoid factor Reviewed

    Atsuko Ashida, Hiroshi Murata, Atsuko Ohashi, Eisaku Ogawa, Hisashi Uhara, Ryuhei Okuyama

    Australasian Journal of Dermatology   54 ( 3 )   e62 - e63   2013.8

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    DOI: 10.1111/j.1440-0960.2011.00873.x

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  • 汗孔角化症のダーモスコピー所見

    宇原 久, 古賀 弘志, 奥山 隆平, 斎田 俊明

    日本皮膚科学会雑誌   123 ( 8 )   1559 - 1559   2013.7

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  • Platinum and anthracycline therapy for advanced cutaneous squamous cell carcinoma Reviewed

    Kenta Nakamura, Ryuhei Okuyama, Toshiaki Saida, Hisashi Uhara

    International Journal of Clinical Oncology   18 ( 3 )   506 - 509   2013.6

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    DOI: 10.1007/s10147-012-0411-y

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  • Clinical course of drug-induced hypersensitivity syndrome treated without systemic corticosteroids Reviewed

    H. Uhara, M. Saiki, S. Kawachi, A. Ashida, S. Oguchi, R. Okuyama

    Journal of the European Academy of Dermatology and Venereology   27 ( 6 )   722 - 726   2013.6

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    DOI: 10.1111/j.1468-3083.2012.04547.x

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  • 腹部に生じた隆起性皮膚線維肉腫(DFSP)病変を伴う線維肉腫の1例

    大橋 敦子, 芦田 敦子, 村田 浩, 宇原 久, 奥山 隆平, 吉田 香奈子

    日本皮膚科学会雑誌   123 ( 2 )   172 - 172   2013.2

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  • マイコプラズマ感染により発症したStevens Johnson症候群(SJS)の1例

    御子柴 育朋, 大橋 敦子, 芦田 敦子, 村田 浩, 宇原 久, 奥山 隆平

    日本皮膚科学会雑誌   123 ( 2 )   171 - 171   2013.2

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  • 全身性サルコイドーシスに伴った刺青サルコイドーシスの1例

    中村 謙太, 大橋 敦子, 古賀 弘志, 宇原 久, 奥山 隆平

    日本皮膚科学会雑誌   123 ( 2 )   174 - 174   2013.2

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  • 小児膿疱性乾癬の1例

    御子柴 育朋, 村田 浩, 赤羽 聡子, 佐藤 勇樹, 芦田 敦子, 宇原 久, 奥山 隆平

    日本皮膚科学会雑誌   123 ( 2 )   174 - 174   2013.2

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  • 喉頭狭窄をきたした後天性表皮水疱症の1例

    木庭 幸子, 大橋 敦子, 芦田 敦子, 宇原 久, 奥山 隆平, 小口 真司

    日本皮膚科学会雑誌   123 ( 2 )   171 - 171   2013.2

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  • 魚介による口腔アレルギー症候群の1例

    御子柴 育朋, 斉藤 奈那, 大橋 敦子, 芦田 敦子, 村田 浩, 宇原 久, 奥山 隆平

    日本皮膚科学会雑誌   123 ( 2 )   173 - 173   2013.2

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  • Dermoscopic characteristics of acquired melanocytic naevus in childhood affecting the acral region Reviewed

    Akane Minagawa, Hiroshi Koga, Hisashi Uhara, Ryuhei Okuyama

    Acta Dermato-Venereologica   93 ( 6 )   751 - 752   2013

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    DOI: 10.2340/00015555-1587

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  • Epidermal-type FABP is a predictive marker of clinical response to systemic treatment and ultraviolet therapy in psoriatic skin lesions. Reviewed

    Miyake T, Ogawa E, Mikoshiba A, Kobayashi A, Hosoe H, Kashiwabara S, Uhara H, Owada Y, Okuyama R

    Journal of dermatological science   68 ( 3 )   199 - 202   2012.12

  • 日本人の悪性黒色腫患者におけるBRAF、KIT遺伝子変異の解析(Assessment of BRAF and KIT mutations in Japanese melanoma patients)

    芦田 敦子, 宇原 久, 村田 浩, 後藤 康文, 奥山 隆平

    日本癌学会総会記事   71回   359 - 359   2012.8

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  • シクロスポリンが著効した小児膿疱性乾癬の1例

    御子柴 育朋, 村田 浩, 赤羽 聡子, 佐藤 勇樹, 芦田 敦子, 宇原 久, 奥山 隆平

    日本皮膚科学会雑誌   122 ( 9 )   2336 - 2336   2012.8

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  • Cutaneous angiosarcoma of the leg showing radiation sensitivity Reviewed

    Atsuko Ohashi, Hitomi Kubo, Maiko Iwade, Junko Shiohara, Minoru Takata, Hisashi Uhara, Ryuhei Okuyama

    Australasian Journal of Dermatology   53 ( 3 )   e51 - e53   2012.8

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    DOI: 10.1111/j.1440-0960.2011.00746.x

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  • 【膿疱を伴う皮膚疾患(2)】<臨床例>治療に難渋した小児膿疱性乾癬

    御子柴 育朋, 芦田 敦子, 村田 浩, 宇原 久, 奥山 隆平

    皮膚病診療   34 ( 7 )   683 - 686   2012.7

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  • 頭部血管肉腫の5例

    葭矢 裕之, 芦田 敦子, 村田 浩, 宇原 久, 奥山 隆平

    日本皮膚悪性腫瘍学会学術大会プログラム・抄録集   28回   132 - 132   2012.6

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  • ダーモスコピー、サージカルテープ、高周波エコーの併用による基底細胞癌の境界の推測

    林 宏一, 宇原 久, 古賀 弘志, 奥山 隆平

    日本皮膚悪性腫瘍学会学術大会プログラム・抄録集   28回   126 - 126   2012.6

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  • Surgical treatment of nail apparatus melanoma in situ: The use of artificial dermis in reconstruction Reviewed

    Koichi Hayashi, Hisashi Uhara, Hiroshi Koga, Ryuhei Okuyama, Toshiaki Saida

    Dermatologic Surgery   38 ( 4 )   692 - 694   2012.4

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    DOI: 10.1111/j.1524-4725.2011.02217.x

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  • Applicability of radiocolloids, blue dyes and fluorescent indocyanine green to sentinel node biopsy in melanoma Reviewed

    Hisashi Uhara, Naoya Yamazaki, Minoru Takata, Yuji Inoue, Akihiro Sakakibara, Yasuhiro Nakamura, Keisuke Suehiro, Akifumi Yamamoto, Riei Kamo, Kosuke Mochida, Hideya Takenaka, Toshiharu Yamashita, Tatsuya Takenouchi, Shusuke Yoshikawa, Akira Takahashi, Jiro Uehara, Mikio Kawai, Hiroaki Iwata, Takafumi Kadono, Yoshitaka Kai, Shoichi Watanabe, Satoru Murata, Tetsuya Ikeda, Hidekazu Fukamizu, Toshihiro Tanaka, Naohito Hatta, Toshiaki Saida

    JOURNAL OF DERMATOLOGY   39 ( 4 )   336 - 338   2012.4

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    DOI: 10.1111/j.1346-8138.2011.01340.x

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  • Mutation analysis of BRAF and KIT in circulating melanoma cells at the single cell level Reviewed

    K. Sakaizawa, Y. Goto, Y. Kiniwa, A. Uchiyama, K. Harada, S. Shimada, T. Saida, S. Ferrone, M. Takata, H. Uhara, R. Okuyama

    British Journal of Cancer   106 ( 5 )   939 - 946   2012.2

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    DOI: 10.1038/bjc.2012.12

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  • Prediction of additional lymph node positivity and clinical outcome of micrometastases in sentinel lymph nodes in cutaneous melanoma: a multi-institutional study of 450 patients in Japan. Reviewed International journal

    Kenjiro Namikawa, Naoya Yamazaki, Yasuo Nakai, Hironobu Ihn, Yasushi Tomita, Hisashi Uhara, Tatsuya Takenouchi, Yoshio Kiyohara, Yoichi Moroi, Yuhei Yamamoto, Fujio Otsuka, Hideki Kamiya, Hajime Iizuka, Naohito Hatta, Takafumi Kadono

    The Journal of dermatology   39 ( 2 )   130 - 7   2012.2

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    Various microscopic classifications of metastatic sentinel lymph nodes (SLN) have been reported along with predictors of additional lymph node positivity and their correlations with the prognosis. The purpose of this study was to re-evaluate these classifications in the Japanese population. We selected the following three classifications, based on the procedural simplicity of the measurements: maximum diameter (maximum diameter of the largest tumor lesion in the SLN; <0.1, 0.1-1.0, >1.0 mm), invasion depth (depth of tumor invasion measured from the capsule in the SLN; SI ≤ 0.3 mm, SII >0.3 to ≤ 1.0 mm, SIII >1.0 mm), and microanatomic location (microanatomic location of the tumor deposits within the SLN; "subcapsular", "parenchymal", "combined", "multifocal", "extensive"). A retrospective study, using prescribed survey forms, was carried out. Among the 450 patients, including the 149 cases with SLN metastasis, an additional lymph node positivity rate of 0% could be predicted only in patients with a maximum diameter category of less than 0.1 mm. As compared with that in the SLN metastasis-negative cases, however, the prognosis was poorer in cases with SLN metastasis, even those with lesions falling under the maximum diameter category of less than 0.1 mm, invasion depth category of SI (≤ 0.3 mm) and microanatomic location category of subcapsular. The prognosis is particularly poor for the microanatomic location category of extensive, which should thus be regarded as a macrometastasis. A prospective study with standardized procedures, including pathological evaluation, is needed in order to confirm our conclusion.

    DOI: 10.1111/j.1346-8138.2011.01318.x

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  • 温熱負荷試験で誘発できた血管浮腫の1例

    小林 彩, 芦田 敦子, 木庭 幸子, 宇原 久

    日本皮膚科学会雑誌   122 ( 2 )   418 - 418   2012.2

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  • 温熱負荷試験で誘発できた血管浮腫の1例

    小林 彩, 芦田 敦子, 木庭 幸子, 宇原 久

    日本皮膚科学会雑誌   122 ( 1 )   106 - 107   2012.1

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  • A case of advanced malignant melanoma responding to single-dose dacarbazine

    UCHIYAMA Ryuhei, IDE Yoko, MINAGAWA Akane, KOGA Hiroshi, KINIWA Yukiko, UHARA Hisashi, TAKATA Minoru, SAIDA Toshiaki, KURAI Makoto

    Skin Cancer   26 ( 2 )   139 - 142   2011.9

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    We report a 44-year-old man with brain, lung and retroperitoneum metastasis from malignant melanoma treated with dacarbazine. The primary lesion was not detected. He received stereotactic radiosurgery for the brain metastasis, followed by single-dose dacarbazine (250mg/m<sup>2</sup>/day &times; 5 days). After 3 courses, a 55.8% reduction in lung metastasis was observed, without serious adverse reaction. After 6 courses, the lung metastasis was removed surgically. Four months after surgical resection, new metastatic lesions were detected in the mediastinum, pancreas, and mesentery. He was treated with stereotactic radiosurgery for increased brain metastasis, followed by one single course of dacarbazine (250mg/m<sup>2</sup>/day &times; 5 days) and 2 single courses of cisplatin (100mg/m<sup>2</sup>/day &times; 1 day). He died 20 months after the first consultation with us. The combination therapy composed of single dacarbazine, stereotactic radiosurgery and surgery might have contributed to durable survival without serious adverse effect in this case.[<i>Skin Cancer (Japan)</i> 2011 ; 26 : 139-142]

    DOI: 10.5227/skincancer.26.139

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  • Characteristic distribution of melanin columns in the cornified layer of acquired acral nevus: An important clue for histopathologic differentiation from early acral melanoma Reviewed

    Toshiaki Saida, Hiroshi Koga, Yasufumi Goto, Hisashi Uhara

    American Journal of Dermatopathology   33 ( 5 )   468 - 473   2011.7

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    DOI: 10.1097/DAD.0b013e318201ac8f

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  • Thermal angiooedema induced by hot water Reviewed

    Aya Kobayashi, Hisashi Uhara, Atsuko Ashida, Yukiko Kiniwa, Ryuhei Okuyama

    Acta Dermato-Venereologica   91 ( 3 )   343 - 344   2011.5

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    DOI: 10.2340/00015555-1020

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  • 喉頭狭窄をきたした後天性表皮水疱症の1例

    木庭 幸子, 大橋 敦子, 芦田 敦子, 宇原 久, 鬼頭 良輔, 福田 俊平, 橋本 隆, 奥山 隆平

    日本皮膚科学会雑誌   121 ( 3 )   585 - 585   2011.3

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  • Key point in dermoscopic differentiation between early nail apparatus melanoma and benign longitudinal melanonychia Reviewed

    Hiroshi Koga, Toshiaki Saida, Hisashi Uhara

    Journal of Dermatology   38 ( 1 )   45 - 52   2011.1

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    DOI: 10.1111/j.1346-8138.2010.01175.x

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  • Key points in dermoscopic differentiation between early acral melanoma and acral nevus Reviewed

    Toshiaki Saida, Hiroshi Koga, Hisashi Uhara

    Journal of Dermatology   38 ( 1 )   25 - 34   2011.1

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    DOI: 10.1111/j.1346-8138.2010.01174.x

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  • ホワイトボードマーカーによる皮野の染色はダーモスコピー診断に役立つ

    宇原 久, 古賀 弘志, 高田 実, 斎田 俊明

    日本皮膚科学会雑誌   120 ( 3 )   747 - 747   2010.3

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  • Tetracycline and niacinamide control bullous pemphigoid but not pemphigus foliaceus when these conditions coexist Reviewed

    Junko Shiohara, Kanako Yoshida, Junichi Hasegawa, Hisashi Uhara, Minoru Takata, Toshiaki Saida, Bungo Oyama, Takashi Hashimoto

    Journal of Dermatology   37 ( 7 )   657 - 661   2010

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    DOI: 10.1111/j.1346-8138.2010.00920.x

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  • High-frequency 30-MHz sonography in preoperative assessment of tumor thickness of primary melanoma: Usefulness in determination of surgical margin and indication for sentinel lymph node biopsy Reviewed

    Koichi Hayashi, Hiroshi Koga, Hisashi Uhara, Toshiaki Saida

    International Journal of Clinical Oncology   14 ( 5 )   426 - 430   2009.10

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    DOI: 10.1007/s10147-009-0894-3

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  • Transient myeloproliferative disorder with vesiculopustular eruption: Early smear is useful for quick diagnosis Reviewed

    Hisashi Uhara, Masaaki Shiohara, Atsushi Baba, Junko Shiohara, Toshiaki Saida

    Journal of the American Academy of Dermatology   60 ( 5 )   869 - 871   2009.5

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    DOI: 10.1016/j.jaad.2008.09.029

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  • Reversible extensive leukoencephalopathy in Sweet disease: A case report Reviewed

    Kazuhiro Fukushima, Akiyo Hineno, Minori Kodaira, Kazuko Machida, Wataru Ishii, Tomoki Kaneko, Hisashi Shimojo, Hisashi Uhara, Kanji Yamamoto, Hiroshi Morita, Kunihiro Yoshida, Shu-ich Ikeda

    Journal of the Neurological Sciences   275 ( 1-2 )   178 - 180   2008.12

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    DOI: 10.1016/j.jns.2008.08.006

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  • Surgical treatment for anorectal malignant melanoma: report of five cases and review of 79 Japanese cases Reviewed

    Satoshi Ishizone, Naohiko Koide, Fumitoshi Karasawa, Noriyuki Akita, Futoshi Muranaka, Hisashi Uhara, Shinichi Miyagawa

    INTERNATIONAL JOURNAL OF COLORECTAL DISEASE   23 ( 12 )   1257 - 1262   2008.12

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    DOI: 10.1007/s00384-008-0529-6

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  • Neutrophilic dermatoses with acute myeloid leukemia associated with an increase of serum colony-stimulating factor Reviewed

    Hisashi Uhara, Toshiaki Saida, Hideyuki Nakazawa, Toshiro Ito

    Journal of the American Academy of Dermatology   59 ( 2 )   S10 - S12   2008.8

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    DOI: 10.1016/j.jaad.2007.08.026

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  • A case of primary Epstein-Barr virus-associated cutaneous diffuse large B-cell lymphoma unassociated with iatrogenic or endogenous immune dysregulation Reviewed

    Yasutaka Tokuda, Mana Fukushima, Koh Nakazawa, Shinji Oguchi, Yoko Koganehira, Maki Yamaura, Miwako Iijima, Hiroshi Murata, Hisashi Uhara, Minoru Takata, Toshiaki Saida, Tsutomu Katsuyama, Sigeo Nakamura

    Journal of Cutaneous Pathology   35 ( 7 )   666 - 671   2008.7

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    DOI: 10.1111/j.1600-0560.2007.00859.x

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  • The Relationship between Tumor Thickness and the Metastatic Rate of Sentinel Lymph Nodes in Japanese Patients with Melanoma

    Uhara Hisashi, Yamamoto Akifumi, Kiyohara Yoshio, Saida Toshiaki

    The Japanese Journal of Dermatology   118 ( 14 )   3083 - 3088   2008

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    Objective: To establish the relationship between tumor thickness (TT) and metastatic rate of the sentinel lymph nodes (SLN) in Japanese patients with melanoma. Methods: A retrospective review of 259 patients who underwent successful SLN mapping and biopsy in 13 facilities in Japan from April of 2003 to June of 2006. The data were analyzed with the χ<sup>2</sup> or Fisherʼs tests. Result: The metastatic rate of SLN in each T-classification category was as follows: pTis: 0% (0/36), pT1: 11.3% (6/56), pT2: 21.0% (13/63), pT3: 34.0% (35/103), and pT4: 62.4% (63/101). Two of T1 cases with SLN metastasis were T1b, and the remaining 4 cases with SLN metastasis were T1a, in which TT was 1.0, 0.8, 0.55, and 0.50 mm. Metastatic rates of SLN in patients with primary lesions over 4 mm in thickness were as follows: 4.01–5 mm: 40.0%, 5.01–6 mm: 57.9%, 6.01–7 mm: 53.8%, 7.01–8 mm: 62.5%, 8.01–9 mm: 87.5%, 9.01–10 mm: 87.5%, and 10 mm<: 72.0%. The metastatic rates of SLN were significantly higher in cases with ulcerated primary lesions than in those without ulceration in T1–T4 and T1–T3 groups (p<0.001). Conclusion: In melanoma patients with thicker primary lesions, the indication for SLN biopsy should be decided taking into consideration the predictive metastatic rates and locations of SLN. Further study is needed to define criteria for performing SLN biopsy in patients with melanomas less than 1.0 mm thick.

    DOI: 10.14924/dermatol.118.3083

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  • A pilot study of human interferon β gene therapy for patients with advanced melanoma by in vivo transduction using cationic liposomes Reviewed

    Kazuhiko Matsumoto, Hitomi Kubo, Hiroshi Murata, Hisashi Uhara, Minoru Takata, Shinichi Shibata, Satoshi Yasue, Akihiro Sakakibara, Yasushi Tomita, Toshiro Kageshita, Yutaka Kawakami, Masaaki Mizuno, Jun Yoshida, Toshiaki Saida

    Japanese Journal of Clinical Oncology   38 ( 12 )   849 - 856   2008

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  • Multiple hypersonographic spots in basal cell carcinoma Reviewed

    Hisashi Uhara, Koichi Hayashi, Hiroshi Koga, Toshiaki Saida

    Dermatologic Surgery   33 ( 10 )   1215 - 1219   2007.10

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    DOI: 10.1111/j.1524-4725.2007.33256.x

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  • Eccrine porocarcinoma: Clinical and pathological studies of 12 cases Reviewed

    Junko Shiohara, Hiroshi Koga, Hisashi Uhara, Minoru Takata, Toshiaki Saida

    Journal of Dermatology   34 ( 8 )   516 - 522   2007.8

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    DOI: 10.1111/j.1346-8138.2007.00324.x

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  • Estrogen-receptor-alpha-positive extramammary Paget's disease treated with hormonal therapy Reviewed

    M. Iijima, H. Uhara, Y. Ide, S. Sakai, H. Onuma, M. Muto, K. Hayashi, F. Mitsura, S. Kobayashi, A. Yoshizawa, T. Saida

    Dermatology   213 ( 2 )   144 - 146   2006.8

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    DOI: 10.1159/000093854

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  • 【透析と皮膚】臨床例 血栓性微小血管症を伴う高血圧性腎クリーゼを発症した全身性強皮症

    古賀 弘志, 宇原 久, 斎田 俊明

    皮膚病診療   25 ( 5 )   533 - 536   2003.5

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  • CD30陽性cutaneous large T cell lymphoma

    吉澤 さえ子, 太田 桂子, 宮嵜 敦, 芦田 敦子, 六波羅 詩穂, 宇原 久, 斎田 俊明

    日本皮膚科学会雑誌   113 ( 5 )   815 - 815   2003.4

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  • Lymphangitis of the foot demonstrating lymphatic drainage pathways from the sole Reviewed

    Hisashi Uhara, Toshiaki Saida, Tomomi Watanabe, Yoshihiro Takizawa

    Journal of the American Academy of Dermatology   47 ( 4 )   502 - 504   2002.10

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    DOI: 10.1067/mjd.2002.122754

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  • Evaluation of 5-S-cysteinyidopa as a marker of melanoma progression: 10 years' experience Reviewed

    K Wakamatsu, T Kageshita, M Furue, N Hatta, Y Kiyohara, J Nakayama, T Ono, T Saida, M Takata, T Tsuchida, H Uhara, A Yamamoto, N Yamazaki, A Naito, S Ito

    MELANOMA RESEARCH   12 ( 3 )   245 - 253   2002.6

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    DOI: 10.1097/00008390-200206000-00008

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  • Docetaxel induced durable response in advanced extramammary Paget's disease: A case report Reviewed

    S Oguchi, M Kaneko, H Uhara, T Saida

    JOURNAL OF DERMATOLOGY   29 ( 1 )   33 - 37   2002.1

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  • Chemotherapy and chemoimmunotherapy for advanced malignant melanoma

    Hisashi Uhara, Toshiaki Saida

    Biotherapy   16 ( 3 )   227 - 232   2002

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  • Proposition of Guidelines for Chemotherapy of Malignant Melanoma Based on the Data Obtained from Relevant Literatures

    SAIDA Toshiaki, UHARA Hisashi

    Skin Cancer   16 ( 2 )   158 - 169   2001.10

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    As members of the expert committee of the Japan Society of Clinical Oncology for the proposition of guidelines for cancer chemotherapy, we collected and evaluated relevant literatures of chemotherapy of malignant melanoma. Each literature was critically evaluated using an evaluation form and quality of evidence of each study was classified into 4 grades. Summing up all the available information, recommendation statements were described on several issues concerning chemotherapy of malignant melanoma, and strength of each recommendation was evaluated using standardized criteria. Critical response from readers to this paper is welcomed. [<i>Skin Cancer (Japan)</i> 2001; 16: 158-169]

    Other Link: http://search.jamas.or.jp/link/ui/2002103269

    DOI: 10.5227/skincancer.16.158

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  • Sequential biochemotherapy with cisplatin, interleukin-2 and interferon α or βin patients with metastatic melanoma

    UHARA Hisashi, SAIDA Toshiaki

    Skin Cancer   15 ( 3 )   309 - 314   2000.12

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    We evaluated efficacy and toxicity of the combination of cisplatin, interleulin-2 (IL-2) and interferon (IFN) α or β in patients with metastatic melanoma. Ten patients received cisplatin, 50 or 80 mg/m<sup>2</sup> intravenously on day 1, IL-2, 70×10<sup>4</sup> IU intravenously on days 4-7, 18-22 and IFN β, 300×10<sup>4</sup> IU subcutaneously or intravenously on every second days (regimen A). Six patients received cisplatin 80 mg/m<sup>2</sup> intravenously on day 1, IL-2, 140×10<sup>4</sup> IU subcutaneously on days 2-8 and IFNα, 500×10<sup>4</sup> IU subcutaneously on days 2, 4, 6, 8 (regimen B). The induction cycle was repeated on day 29 in both regimens. There was no responder in 6 patients (A) and 4 patients (B) assessed for clinical response. Main toxisities were thrombocytopenia, neutropenia, anemia and nausea. Vitiligo-like depigmentation was seen in one patient, whose disease progressed during the therapy. There were no treatment-related death. These regimens had low activities in the treatment of advanced malignant melanoma. [<i>Skin Cancer (Japan)</i> 2000; 15: 309-314]

    Other Link: http://search.jamas.or.jp/link/ui/2001149655

    DOI: 10.5227/skincancer.15.309

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  • Solid facial edema in a patient with rosacea Reviewed

    Hisashi Uhara, Shigeo Kawachi, Toshiaki Saida

    Journal of Dermatology   27 ( 3 )   214 - 216   2000

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    DOI: 10.1111/j.1346-8138.2000.tb02152.x

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  • Newest knowledge of chemotherapy and chemoimmunotherapy for advanced malignant melanoma.

    UHARA Hisashi, SAIDA Toshiaki

    Skin Cancer   14 ( 1 )   15 - 23   1999

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    Recently developed regimens for the treatment of patients with advanced malignant melanoma were reviewed. Combination chemotherapy of CDDP/BCNU/DTIC/tamoxifen (Dartmouth regimen) and sequential (concurrent) chemoimmunotherapy composed of CDDP based chemotherapy associated with IL-2 and IFN α have been reported to increase overall response rates and CR rates. However, they are still in the clinical trial setting. Temozolomide is an analogue of DTIC that has the advantage of being orally absorbed and crossing into the central nervous system (CNS). Fotemustine, a new nitrosourea, is also active in CNS metastasis. Results of the following two clinical trials of our study group were also described: DAC-Tam therapy using DTIC, ACNU, CDDP and tamoxifen, and sequential biochemotherapy using CDDP, IL-2 and IFN β.

    Other Link: http://search.jamas.or.jp/link/ui/1999257724

    DOI: 10.5227/skincancer.14.15

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  • Immunohistochemical detection of CDK4 and p16(INK4) proteins in cutaneous malignant melanoma Reviewed

    YL Wang, H Uhara, Y Yamazaki, T Nikaido, T Saida

    BRITISH JOURNAL OF DERMATOLOGY   134 ( 2 )   269 - 275   1996.2

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  • Expression of α subunit of guanine nucleotide‐binding protein Go in Merkel cell carcinoma Reviewed

    Hisashi Uhara, Yu‐Lai Wang, Sachiyo Matsumoto, Shigeo Kawachi, Toshiaki Saida

    Journal of Cutaneous Pathology   22 ( 2 )   146 - 148   1995

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    DOI: 10.1111/j.1600-0560.1995.tb01397.x

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  • Primary cutaneous plasmacytosis: Report of three cases and review of the literature Reviewed

    H. Uhara, T. Saida, S. Ikegawa, Y. Yamazaki, H. Mikoshiba, S. Nijoh, K. Kitano, C. S. Koh

    Dermatology   189 ( 3 )   251 - 255   1994

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    DOI: 10.1159/000246848

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  • Detection of Epstein‐Barr Virus DNA in a Japanese Case of Lymphoepithelioma‐like Thymic Carcinoma Reviewed

    Yoshihiro Matsuno, Kiyoshi Mukai, Hisashi Uhara, Ichiro Akao, Shuichiroh Furuya, Yuichi Sato, Setsuo Hirohashi, Yukio Shimosato

    Japanese Journal of Cancer Research   83 ( 2 )   127 - 130   1992

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    DOI: 10.1111/j.1349-7006.1992.tb00075.x

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  • Detection of epstein-barr virus dna in formalin-fixed paraffin-embedded tissue of nasopharyngeal carcinoma using polymerase chain reaction and in situ hybridization Reviewed

    Ichiro Akao, Yuichi Sato, Kiyoshi Muka, Hisashi Uhara, Shuichiro Furuya, Tomohide Hoshikawa, Yukio Shimosato, Isamu Takeyama

    Laryngoscope   101 ( 3 )   279 - 283   1991

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  • Detection of human papillomavirus DNA in laryngeal squamous cell carcinomas by polymerase chain reaction Reviewed

    Tomohide Hoshikawa, Takashi Nakajima, Hisashi Uhara, Masahiro Gotoh, Yukio Shimosato, Kouichiro Tsutsumi, Isamu Ono, Satoshi Ebihara

    Laryngoscope   100 ( 6 )   647 - 650   1990

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  • Detection of Epstein‐Barr Virus DNA in Reed‐Sternberg Cells of Hodgkin's Disease Using the Polymerase Chain Reaction and in situ Hybridization Reviewed

    Hisashi Uhara, Yuichi Sato, Kiyoshi Mukai, Ichiro Akao, Yoshihiro Matsuno, Shuichiroh Furuya, Tomohide Hoshikawa, Yukio Shimosato, Toshiaki Saida

    Japanese Journal of Cancer Research   81 ( 3 )   272 - 278   1990

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    DOI: 10.1111/j.1349-7006.1990.tb02561.x

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  • BOWENS DISEASE WITH INVASIVE-CARCINOMA SHOWING SWEAT GLAND DIFFERENTIATION Reviewed

    T SAIDA, Y OKABE, H UHARA

    JOURNAL OF CUTANEOUS PATHOLOGY   16 ( 4 )   222 - 226   1989.8

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  • Phytohemagglutinin-binding sites in the skin: A useful histochemical marker of acrosyringium and distal portions of intradcrnial sweat ducts Reviewed

    Toshiaki Saida, Hisashi Uhara, Hajime Mikoshiba

    Dermatology   179 ( 1 )   25 - 28   1989

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    DOI: 10.1159/000248095

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  • Heterophile hanganutziu-deicher antigen in ganglioside fractions of human melanoma tissues Reviewed

    Shigeo Kawachi, Toshiaki Saida, Hisashi Uhara, Uemura Kei-Ichi, Tamotsu Taketomi, Kyoichi Kano

    International Archives of Allergy and Immunology   85 ( 3 )   381 - 383   1988

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    DOI: 10.1159/000234536

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▼display all

Books

  • WHO Classification of Skin Tumours, 4th edition 2018

    UHARA Hisashi( Role: Joint authormelanoma, melanocytic nevus, mongolian spot)

    World Health Organization  2018.9 

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  • Comprehensive single-cell immune profiling of tumor-infiltrating lymphocytes in acral melanoma

    箕輪智幸, 箕輪智幸, 村田憲治, 廣橋良彦, 宇原久, 鳥越俊彦

    日本病理学会会誌   112 ( 1 )   2023

  • MYO5A-NTRK3融合遺伝子を検出したatypical Spitz tumor

    佐藤 さゆり, 肥田 時征, 井戸川 雅史, 黄倉 真恵, 宇原 久

    日本皮膚科学会雑誌   132 ( 5 )   1363 - 1363   2022.5

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  • カスタムパネルシーケンスを用いた日本人メラノーマのドライバー遺伝子の検出

    肥田 時征, 井戸川 雅史, 堀本 浩平, 加藤 潤史, 佐藤 さゆり, 藤岡 茉生, 丹下 正一朗, 時野 隆至, 宇原 久

    日本皮膚科学会雑誌   131 ( 5 )   1363 - 1363   2021.5

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  • 病理組織学的に顕著なロゼット様構造を呈したALK陽性atypical Spitz tumor

    箕輪 智幸, 肥田 時征, 堀本 浩平, 加藤 潤史, 神谷 崇文, 杉田 真太朗, 井戸川 雅史, 宇原 久

    日本皮膚科学会雑誌   131 ( 5 )   1417 - 1417   2021.5

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  • Immunotherapy for advanced melanoma: Current situation in Japan

    Junji Kato, Hisashi Uhara

    Japanese Journal of Clinical Oncology   51 ( 1 )   3 - 9   2021.1

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    DOI: 10.1093/jjco/hyaa188

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  • Cutaneous apocrine carcinoma with elevated serum cytokeratin 19 fragment 21-1 (CYFRA 21-1)

    Mao Fujioka, Junji Kato, Yasuyuki Sumikawa, Sayuri Sato, Masahide Sawada, Hisashi Uhara

    Journal of Dermatology   46 ( 10 )   e387 - e388   2019.10

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    DOI: 10.1111/1346-8138.14915

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  • Efficacy and management of adverse events of ipilimumab including combination therapy with nivolumab

    Hisashi Uhara, Eijun Itakura

    Japanese Journal of Cancer and Chemotherapy   46 ( 6 )   1017 - 1026   2019.6

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  • Real-world efficacy of anti-PD-1 antibodies in advanced acral melanoma patients: A retrospective, multicenter study (JAMP study).

    Yasuhiro Nakamura, Kenjiro Namikawa, Koji Yoshino, Shusuke Yoshikawa, Hiroshi Uchi, Katsunobu Goto, Yoshiyuki Nakamura, Satoshi Fukushima, Yukiko Kiniwa, Tatsuya Takenouchi, Hisashi Uhara, Toru Kawai, Naohito Hatta, Takeru Funakoshi, Yukiko Teramoto, Atsushi Otsuka, Haruki Doi, Dai Ogata, Shigeto Matsushita, Naoya Yamazaki

    JOURNAL OF CLINICAL ONCOLOGY   37 ( 15 )   2019.5

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    DOI: 10.1200/JCO.2019.37.15_suppl.9529

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  • 悪性黒色腫(1)悪性黒色腫と色素細胞母斑の病理組織学的鑑別 (特集 皮膚悪性腫瘍の病理組織診断プラクティス)

    神谷 崇文, 宇原 久

    デルマ   ( 280 )   44 - 50   2019.3

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  • 日本人進行性悪性黒色腫患者を対象としたペムブロリズマブの第Ib相試験の最終解析

    藤澤 康弘, 横田 憲二, 竹之内 辰也, 尹 浩信, 内 博史, 猪爪 隆史, 清原 祥夫, 宇原 久, 山崎 直也

    日本皮膚悪性腫瘍学会学術大会プログラム・抄録集   34回   149 - 149   2018.6

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  • 直腸癌の多発皮膚転移

    加瀬 貴美, 加藤 潤史, 澄川 靖之, 肥田 時征, 杉田 真太朗, 宇原 久

    西日本皮膚科   80 ( 3 )   181 - 182   2018.6

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  • 悪性黒色腫におけるニボルマブとイピリムマブの逐次的治療の臨床研究 多施設後ろ向き観察研究

    福島 聡, 横田 憲二, 清原 祥夫, 山崎 修, 種村 篤, 奥山 隆平, 宇原 久, 片山 輝昭, 板倉 英潤, 堤田 新

    日本皮膚悪性腫瘍学会学術大会プログラム・抄録集   34回   163 - 163   2018.6

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  • 根治切除不能な化学療法未治療の悪性黒色腫を対象としたニボルマブ国内第II相試験(ONO-4538-08)長期追跡

    清原 祥夫, 山崎 直也, 宇原 久, 上原 治朗, 藤本 学, 竹之内 辰也, 大塚 正樹, 内 博史, 尹 浩信, 南 博信

    日本皮膚悪性腫瘍学会学術大会プログラム・抄録集   34回   149 - 149   2018.6

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  • 悪性黒色腫と色素細胞母斑の病理組織学的鑑別 (特集 形成外科医のための皮膚病理講座にようこそ)

    神谷 崇文, 宇原 久

    Pepars   ( 132 )   69 - 77   2017.12

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    Other Link:: http://search.jamas.or.jp/link/ui/2018079995

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  • 【がん転移学(上)-がん転移のメカニズムと治療戦略:その基礎と臨床-】 がん転移学の基礎研究 がんの発生進展の分子機構 皮膚悪性黒色腫の分子遺伝学

    肥田 時征, 加藤 潤史, 宇原 久

    日本臨床   75 ( 増刊8 がん転移学(上) )   246 - 251   2017.11

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  • Clinical and genetic characteristics of cutaneous melanoma with clinical history of early childhood onset

    A. Minagawa, H. Uhara, K. Sakaizawa, H. Koga, A. Ashida, R. Okuyama

    JOURNAL OF INVESTIGATIVE DERMATOLOGY   137 ( 10 )   S196 - S196   2017.10

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  • メラノーマ診療

    加藤 潤史, 肥田 時征, 宇原 久

    皮膚病診療   39 ( 9 )   1002 - 1007   2017.9

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    Ichushi

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  • KEYNOTE-041 日本人進行性悪性黒色腫患者を対象としたペムブロリズマブの第Ib相試験

    竹之内 辰也, 横田 憲二, 藤澤 康弘, 尹 浩信, 内 博史, 猪爪 隆史, 清原 祥夫, 宇原 久, 山崎 直也

    日本皮膚悪性腫瘍学会学術大会プログラム・抄録集   33回   122 - 122   2017.5

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  • 根治切除不能なIII/IV又は再発の化学療法未治療の悪性黒色腫を対象としたニボルマブ国内第II相試験の成績

    清原 祥夫, 山崎 直也, 宇原 久, 上原 治朗, 藤本 学, 竹之内 辰也, 大塚 正樹, 内 博史, 尹 浩信, 南 博信

    日本皮膚悪性腫瘍学会学術大会プログラム・抄録集   33回   120 - 120   2017.5

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  • Serum 5-s-cysteinyldopa for identifying non-responders to nivolumab treatment of melanoma.

    Toshikazu Omodaka, Akane Minagawa, Hisashi Uhara, Kazumasa Wakamatsu, Tomonobu Koizumi, Hiroshi Koga, Ryuhei Okuyama

    JOURNAL OF CLINICAL ONCOLOGY   35   2017.5

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    DOI: 10.1200/JCO.2017.35.15_suppl.e21068

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  • Orange pigmentation spots on the sole may be from a stink bug

    Hisashi Uhara, Tasuku Sano, Tomomi Miyake, Ryuhei Okuyama

    Journal of Dermatology   43 ( 10 )   1247 - 1248   2016.10

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    DOI: 10.1111/1346-8138.13367

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  • 皮膚 メラノーマ・他 KEYNOTE-041 進行性悪性黒色腫の日本人患者を対象としたMK-3475の第Ib相試験

    横田 憲二, 竹之内 辰也, 藤本 学, 尹 浩信, 内 博史, 猪爪 隆史, 清原 祥夫, 宇原 久, 中川 和彦, 古川 洋志, 和田 秀文, 野口 一夫, 嶋本 隆司, 山崎 直也

    日本癌治療学会学術集会抄録集   54回   WS30 - 1   2016.10

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  • 5-Hydroxymethylcytosine as a putative marker for erosive adenomatosis of the nipple

    Yuko Takazawa, Tomohiro Edamitsu, Kazuma Maeno, Eisaku Ogawa, Hisashi Uhara, Shigeo Kawachi, Ken-Ichi Ito, Ryuhei Okuyama

    Journal of Dermatology   43 ( 5 )   579 - 580   2016.5

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    DOI: 10.1111/1346-8138.13237

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  • Inhibition of epidermal growth factor receptor induces tumor necrosis factor-α via activation of peroxisome proliferator-activated receptor-γ and nuclear factor-κB in sebocytes: A possible pathogenesis of papulopustular rash

    Atsuko Ashida, Eisaku Ogawa, Hisashi Uhara, Tomonobu Koizumi, Ryuhei Okuyama

    Journal of Dermatological Science   82 ( 1 )   53 - 56   2016.4

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    DOI: 10.1016/j.jdermsci.2015.12.004

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  • 5-Hydroxymethylcytosine is a useful marker to differentiate between dermatofibrosarcoma protuberans and dermatofibroma

    Y. Mikoshiba, E. Ogawa, R. Uchiyama, A. Uchiyama, H. Uhara, R. Okuyama

    Journal of the European Academy of Dermatology and Venereology   30 ( 1 )   130 - 131   2016.1

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    DOI: 10.1111/jdv.12614

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  • A Place for BRAFV600E Mutation-specific Immunohistochemistry Alongside Cell-free DNA Mutation Detection in Melanoma Reply

    Atsuko Ashida, Hisashi Uhara, Asuka Mikoshiba, Kaori Sakaizawa, Naomi Kumagai, Hiroshi Koga, Ryuhei Okuyama

    ACTA DERMATO-VENEREOLOGICA   96 ( 3 )   427 - 427   2016

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  • Violaceous and Petechial Persistent Plantar Plaques: A Quiz

    Atsuko Ashida, Hisashi Uhara, Asuka Mikoshiba, Kaori Sakaizawa, Naomi Kumagai, Hiroshi Koga, Ryuhei Okuyama

    ACTA DERMATO-VENEREOLOGICA   96 ( 3 )   427 - +   2016

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  • Histopathological improvement of scleroderma induced by paclitaxel in a patient with breast cancer

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

    JOURNAL OF DERMATOLOGY   42 ( 12 )   1198 - 1199   2015.12

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    DOI: 10.1111/1346-8138.13085

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  • Phase II study of ipilimumab monotherapy in Japanese patients with advanced melanoma Reviewed International journal

    N. Yamazaki, Y. Kiyohara, H. Uhara, S. Fukushima, H. Uchi, N. Shibagaki, A. Tsutsumida, S. Yoshikawa, R. Okuyama, Y. Ito, T. Tokudome

    Cancer Chemotherapy and Pharmacology   76 ( 5 )   997 - 1004   2015.11

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  • Brown nodule on the lower eyelid: A quiz

    Shiho Shirota, Akane Minagawa, Hiroshi Koga, Masanobu Momose, Hisashi Uhara, Ryuhei Okuyama

    Acta Dermato-Venereologica   95 ( 8 )   1037   2015.11

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    DOI: 10.2340/00015555-2124

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  • Primary cutaneous nocardiosis caused by Nocardia concava

    Kenta Nakamura, Fuminao Kamijo, Tatsuya Negishi, Takehisa Matsumoto, Ryuhei Okuyama, Hisashi Uhara

    Journal of Dermatology   42 ( 11 )   1121 - 1122   2015.11

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    DOI: 10.1111/1346-8138.13036

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  • Phase II study of the immune-checkpoint inhibitor ipilimumab plus dacarbazine in Japanese patients with previously untreated, unresectable or metastatic melanoma Reviewed International journal

    N. Yamazaki, H. Uhara, S. Fukushima, H. Uchi, N. Shibagaki, Y. Kiyohara, A. Tsutsumida, K. Namikawa, R. Okuyama, Y. Otsuka, T. Tokudome

    Cancer Chemotherapy and Pharmacology   76 ( 5 )   969 - 975   2015.11

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  • The role of sentinel lymph node biopsy in the management of invasive extramammary Paget's disease: multi-center, retrospective study of 151 patients (vol 79, pg 38, 2015)

    Yasuhiro Fujisawa, Koji Yoshino, Yoshio Kiyohara, Takafumi Kadono, Yozo Murata, Hisashi Uhara, Naohito Hatta, Hiroshi Uchi, Shigeto Matsushita, Tatsuya Takenouchi, Toshihiko Hayashi, Manabu Fujimoto, Kuniaki Ohara

    JOURNAL OF DERMATOLOGICAL SCIENCE   80 ( 1 )   79 - 79   2015.10

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  • Phase 2 study of Nivolumab (Anti-PD-1; ONO-4538/BMS-936558) in Japanese patients with advanced melanoma: Preliminary report

    N. Yamazaki, Y. Kiyohara, H. Uhara

    EUROPEAN JOURNAL OF CANCER   51   S110 - S110   2015.9

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  • Molecular target therapies for skin cancers

    73 ( 8 )   1391 - 1397   2015.8

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  • 進行期悪性黒色腫におけるipilimumabの2つの国内第2相試験における安全性マネージメント

    宇原 久, 山崎 直也, 清原 祥夫, 内 博史, 福島 聡, 柴垣 直孝, 堤田 新, 奥山 隆平, 吉川 周佐, 並川 健二郎, 徳留 拓人

    日本皮膚悪性腫瘍学会学術大会プログラム・抄録集   31回   149 - 149   2015.7

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  • 化学療法未治療進行期悪性黒色腫患者におけるipilimumabのDTIC併用国内第2相臨床試験

    内 博史, 宇原 久, 福島 聡, 柴垣 直孝, 清原 祥夫, 堤田 新, 奥山 隆平, 並川 健二郎, 大塚 康司, 山崎 直也

    日本皮膚悪性腫瘍学会学術大会プログラム・抄録集   31回   149 - 149   2015.7

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  • 進行期悪性黒色腫患者におけるipilimumab単独療法第2相臨床試験

    福島 聡, 清原 祥夫, 宇原 久, 内 博史, 柴垣 直孝, 堤田 新, 吉川 周佐, 奥山 隆平, 伊藤 嘉紀, 山崎 直也

    日本皮膚悪性腫瘍学会学術大会プログラム・抄録集   31回   149 - 149   2015.7

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  • 日本人の悪性黒色腫のBRAF、NRAS、KIT変異率と臨床所見

    境澤 香里, 芦田 敦子, 伊東 孝通, 藤澤 康弘, 緒方 大, 松下 茂人, 藤井 一恭, 福島 聡, 柴山 慶継, 八田 尚人, 竹之内 辰也, 上原 治朗, 奥山 隆平, 山崎 直也, 宇原 久

    日本皮膚科学会雑誌   125 ( 4 )   940 - 940   2015.4

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  • これからのがん免疫療法と今後の展望

    清原 祥夫, 山崎 直也, 宇原 久, 福島 聡, 山口 研成, 室 圭, 山本 信之, 里内 美弥子, 瀬戸 貴司, 井上 彰, 後藤 功一, 鵜殿 平一郎, 西川 博嘉, 山中 竹春

    Immuno-Oncology Frontier   1 ( 1 )   14 - 21   2015.1

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  • Alteration of dermoscopic features in a juvenile xanthogranuloma during follow-up of 43 months

    Toshinori Unno, Akane Minagawa, Hiroshi Koga, Hisashi Uhara, Ryuhei Okuyama

    International Journal of Dermatology   53 ( 12 )   e590 - e591   2014.12

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    DOI: 10.1111/ijd.12530

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  • Anti-CTLA-4 antibodies for the treatment of malignant melanoma

    14 ( 5 )   427 - 433   2014.11

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  • Fibrosarcomatous variant of dermatofibrosarcoma protuberans with pancreatic metastasis

    Hiroshi Murata, Atsuko Ohashi, Atsuko Ashida, Hisashi Uhara, Ryuhei Okuyama, Takenari Nakata, Kunihiko Shingu

    International Journal of Dermatology   53 ( 2 )   e140 - e142   2014.2

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    DOI: 10.1111/j.1365-4632.2012.05698.x

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  • Marked histiocytic infiltration in neonatal lupus erythematosus

    Nagisa Okada, Ryuhei Okuyama, Hisashi Uhara

    Journal of Dermatology   41 ( 2 )   192 - 193   2014.2

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    DOI: 10.1111/1346-8138.12381

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  • Successful treatment of rheumatoid vasculitis-associated skin ulcer with a TNF-α antagonist

    Atsuko Ashida, Hiroshi Murata, Yasutomo Mikoshiba, Atsuko Ohashi, Aya Kobayashi, Hiroshi Koga, Hisashi Uhara, Ryuhei Okuyama

    International Journal of Dermatology   53 ( 2 )   e154 - e156   2014.2

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    DOI: 10.1111/j.1365-4632.2012.05529.x

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  • Unilateral pigmented purpuric dermatosis associated with deep thrombosis

    Yasutomo Mikoshiba, Hisashi Uhara, Ryuhei Okuyama, Minoru Saiki

    International Journal of Dermatology   53 ( 2 )   e87 - e88   2014.2

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    DOI: 10.1111/j.1365-4632.2012.05492.x

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  • 5-Hydroxymethylcytosine as a useful marker to differentiate between malignant melanomas and benign melanocytic nevi

    Ryuhei Uchiyama, Hisashi Uhara, Aya Uchiyama, Eisaku Ogawa, Yuko Takazawa, Atsuko Ashida, Hiroshi Koga, Koichi Hayashi, Yukiko Kiniwa, Ryuhei Okuyama

    JOURNAL OF DERMATOLOGICAL SCIENCE   73 ( 2 )   161 - 163   2014.2

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    DOI: 10.1016/j.jdermsci.2013.09.008

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  • Usefulness of high-frequency sonography for the diagnosis of asymptomatic myopathy in Löfgren's syndrome

    Atsuko Ohashi, Hiroshi Koga, Koichi Hayashi, Hisashi Uhara, Ryuhei Okuyama

    International Journal of Dermatology   53 ( 1 )   e62 - e63   2014.1

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    DOI: 10.1111/j.1365-4632.2012.05489.x

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  • Detection of the tumor margin of basal-cell carcinoma using dermoscopy and high-frequency ultrasound with narrow pieces of surgical tape as skin markers

    Koichi Hayashi, Hisashi Uhara, Ryuhei Okuyama

    Dermatologic Surgery   40 ( 6 )   704 - 706   2014

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    DOI: 10.1111/dsu.0000000000000015

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  • Generalized pustulosis associated with disseminated Mycobacterium avium infection in a non-AIDS patient

    Yuko Asai, Yukiko Kiniwa, Nagisa Okada, Toshimasa Futatsugi, Atsuhito Ushiki, Hisashi Uhara, Ryuhei Okuyama

    European Journal of Dermatology   24 ( 3 )   402 - 403   2014

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    DOI: 10.1684/ejd.2014.2334

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  • Combination chemotherapy of carboplatin and paclitaxel for metastatic melanoma

    Yuki Sato, Hisashi Uhara, Atsuko Ashida, Ryuhei Okuyama

    Journal of Dermatology   40 ( 12 )   1050 - 1051   2013.12

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    DOI: 10.1111/1346-8138.12306

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  • Lamellar ichthyosis in a collodion baby caused by CYP4F22 mutations in a non-consanguineous family outside the Mediterranean

    Kazumitsu Sugiura, Takuya Takeichi, Kana Tanahashi, Yasutomo Ito, Tomoki Kosho, Ken Saida, Hisashi Uhara, Ryuhei Okuyama, Masashi Akiyama

    Journal of Dermatological Science   72 ( 2 )   193 - 195   2013.11

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    DOI: 10.1016/j.jdermsci.2013.06.008

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  • Bullous formation in a patient with familial amyloid polyneuropathy type I

    Aya Kobayashi, Hisashi Uhara, Kenji Kido, Yoshiki Sekijima, Kana Tojo, Shu-ichi Ikeda, Ryuhei Okuyama

    International Journal of Dermatology   52 ( 11 )   1398 - 1400   2013.11

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    DOI: 10.1111/j.1365-4632.2011.05146.x

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  • S-1 induced a durable response in metastatic extramammary Paget's disease

    Yasutomo Mikoshiba, Hisashi Uhara, Hitomi Kubo, Ryuhei Okuyama

    Journal of Dermatology   40 ( 8 )   664 - 665   2013.8

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    DOI: 10.1111/1346-8138.12177

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  • Age-related prevalence of dermoscopic patterns in acquired melanocytic nevus on acral volar skin

    Akane Minagawa, Hiroshi Koga, Hisashi Uhara, Yoshiharu Yokokawa, Ryuhei Okuyama

    JAMA Dermatology   149 ( 8 )   989 - 990   2013.8

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    DOI: 10.1001/jamadermatol.2013.4452

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  • Effectiveness of topical maxacalcitol for acquired perforating disorder

    Hiroyuki Yoshiya, Ryuhei Okuyama, Hisashi Uhara

    Journal of the American Academy of Dermatology   68 ( 6 )   e181 - e182   2013.6

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    DOI: 10.1016/j.jaad.2012.10.044

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  • A regulation of keratinocyte differentiation and proliferation by transcription factors Runx1 and Runx3

    R. Uchiyama, E. Ogawa, Y. Kiniwa, H. Uhara, W. F. Wong, K. Kofu, S. Ikawa, M. Satake, R. Okuyama

    JOURNAL OF INVESTIGATIVE DERMATOLOGY   133   S105 - S105   2013.5

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  • E-FABP is a predictive marker of clinical response to systemic treatment and ultraviolet therapy in psoriatic skin lesions

    E. Ogawa, T. Miyake, A. Mikoshiba, A. Kobayashi, H. Uhara, R. Okuyama

    JOURNAL OF INVESTIGATIVE DERMATOLOGY   133   S166 - S166   2013.5

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  • A pediatric case of pityriasis lichenoides chronica successfully treated with narrow-band UVB therapy

    YOSHIKAWA Mika, KINIWA Yukiko, KOGA Hiroshi, UHARA Hisashi, OKUYAMA Ryuhei

    32 ( 1 )   45 - 48   2013.2

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  • Case of a cutaneous angiomyolipoma in the ear

    Yasutomo Mikoshiba, Hiroshi Murata, Atsuko Ashida, Nana Saito, Hiroshi Koga, Hisashi Uhara, Ryuhei Okuyama

    Journal of Dermatology   39 ( 9 )   808 - 809   2012.9

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    DOI: 10.1111/j.1346-8138.2011.01426.x

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  • Assessment of BRAF and KIT mutations in Japanese melanoma patients

    Atsuko Ashida, Hisashi Uhara, Yukiko Kiniwa, Misae Oguchi, Hiroshi Murata, Yasufumi Goto, Aya Uchiyama, Eisaku Ogawa, Koichi Hayashi, Hiroshi Koga, Ryuhei Okuyama

    Journal of Dermatological Science   66 ( 3 )   240 - 242   2012.6

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    DOI: 10.1016/j.jdermsci.2012.03.005

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  • Rapid progression of Hidradenitis suppurativa in the lower leg of a patient with psoriasis vulgaris

    Asuka Tanaka, Yasufumi Goto, Maiko Iwade, Hisashi Uhara, Ryuhei Okuyama

    Acta Dermato-Venereologica   92 ( 1 )   105 - 106   2012.1

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    DOI: 10.2340/00015555-1182

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  • A case of mycobacterial skin disease caused by mycobacterium peregrinum, and a review of cutaneous infection

    Fuminao Kamijo, Hisashi Uhara, Hitomi Kubo, Kazue Nakanaga, Yoshihiko Hoshino, Norihisa Ishii, Ryuhei Okuyama

    Case Reports in Dermatology   4 ( 1 )   76 - 79   2012.1

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    DOI: 10.1159/000337825

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  • Response to a comment on rapid progression of hidradenitis suppurativa in the lower leg of a patient with psoriasis vulgaris

    Hisashi Uhara, Ryuhei Okuyama

    Acta Dermato-Venereologica   92 ( 4 )   447   2012

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    DOI: 10.2340/00015555-1347

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  • Sweat test with water-erasable ink

    Hisashi Uhara, Kenta Nakamura, Yasutomo Mikoshiba, Tomomi Miyake, Ryuhei Okuyama

    Acta Dermato-Venereologica   92 ( 4 )   432 - 433   2012

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    DOI: 10.2340/00015555-1300

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  • Leg ulcers associated with positive lupus anticoagulant in two cases of klinefelter's syndrome

    Yasufumi Goto, Hisashi Uhara, Hiroshi Murata, Hiroshi Koga, Tomoki Kosho, Masahide Yamazaki, Minoru Takata, Ryuhei Okuyama

    Acta Dermato-Venereologica   91 ( 1 )   90 - 91   2011

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    DOI: 10.2340/00015555-0957

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  • Open pores with plugs in porokeratosis clearly visualized with the dermoscopic furrow ink test: Report of 3 cases

    Hisashi Uhara, Fuminao Kamijo, Ryuhei Okuyama, Toshiaki Saida

    Archives of Dermatology   147 ( 7 )   866 - 868   2011

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    DOI: 10.1001/archdermatol.2011.174

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  • Calciphylaxis in poems syndrome: A case treated with etidronate

    Mika Yoshikawa, Hisashi Uhara, Fuyuko Arakura, Hiroshi Murata, Hitomi Kubo, Minoru Takata, Kunihiro Yoshida, R. Okuyama

    Acta Dermato-Venereologica   91 ( 1 )   98 - 99   2011

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    DOI: 10.2340/00015555-0968

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  • Takayasu's arteritis with pyoderma gangrenosum and necrotizing vasculitis

    A. Minagawa, H. Uhara, T. Saida

    Clinical and Experimental Dermatology   35 ( 3 )   329 - 330   2010.4

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    DOI: 10.1111/j.1365-2230.2009.03534.x

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  • Sentinel lymph node biopsy in Japan

    Hisashi Uhara, Minoru Takata, Toshiaki Saida

    International Journal of Clinical Oncology   14 ( 6 )   490 - 496   2009.12

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    Language:English   Publishing type:Book review, literature introduction, etc.  

    DOI: 10.1007/s10147-009-0941-0

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  • The whiteboard marker as a useful tool for the dermoscopic "furrow ink test"

    Hisashi Uhara, Hiroshi Koga, Minoru Takata, Toshiaki Saida

    Archives of Dermatology   145 ( 11 )   1331 - 1332   2009.11

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    DOI: 10.1001/archdermatol.2009.275

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  • Herpes zoster histopathologically mimicking CD30-positive anaplastic large cell lymphoma

    J. Shiohara, H. Koga, H. Uhara, M. Takata, T. Saida, T. Uehara

    Journal of the European Academy of Dermatology and Venereology   23 ( 5 )   618 - 619   2009.5

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    DOI: 10.1111/j.1468-3083.2008.02986.x

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  • 濾胞性リンパ腫に伴った腫瘍随伴性天疱瘡の1例

    光楽 文生, 鶴田 恭子, 内山 龍平, 井出 葉子, 皆川 茜, 古賀 弘志, 木庭 幸子, 村田 浩, 宇原 久, 斎田 俊明, 伊藤 俊朗, 野網 淑子

    日本皮膚科学会雑誌   118 ( 10 )   2018 - 2018   2008.9

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    Ichushi

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  • Systemic plasmacytosis with aseptic bone necrosis and high fever [3]

    Masao Fukuzawa, Maki Yamaura, Hisashi Uhara, Toshiaki Saida

    Journal of Dermatology   31 ( 8 )   696 - 698   2004

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    Language:English   Publishing type:Rapid communication, short report, research note, etc. (scientific journal)   Publisher:Japanese Dermatological Association  

    DOI: 10.1111/j.1346-8138.2004.tb00581.x

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  • Urticaria and anaphylaxis due to sting by an ant (Brachyponera chinensis) [2]

    M. Fukuzawa, F. Arakura, Y. Yamazaki, H. Uhara, T. Saida

    Acta Dermato-Venereologica   82 ( 1 )   59   2002

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    DOI: 10.1080/000155502753600939

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Awards

  • Best Doctors in Japan (2010-)

    2010  

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  • 第72回日本皮膚科学会東部支部学術大会学会賞(Best Clinical Award)

    2008  

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  • Certificate of Recognition for Outstanding Posters in the Category Invasive&non invasive techniques - Diagnostic tools

    2007  

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Research Projects

  • メラノーマにおける複数の変異遺伝子を候補とした個別化リキッドバイオプシー法の確立

    Grant number:22K08388  2022.4 - 2025.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    宇原 久

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    Grant amount:\4160000 ( Direct Cost: \3200000 、 Indirect Cost:\960000 )

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  • Characterization of the intratumoral ecosystem in melanoma by single-cell RNA-seq analysis

    Grant number:19K08752  2019.4 - 2022.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    UHARA HISASHI

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    Grant amount:\4420000 ( Direct Cost: \3400000 、 Indirect Cost:\1020000 )

    The aim of the study is to establish of the method to obtain the single-cell gene expression of RNA in melanoma cells from the resected tumor samples. The method is planned according to the following steps (Hashimoto S, Scientic Reports 7;14225, 2017). In the first case, over expression of MAPK pathway-related molecules and HLA class 1 and lower expression of HLA class 2 and PD-L1 were observed in melanoma cells in 2 of 5 clusters. However, in next 5 examined cases, synthesis of cDNA of a single cell was not stable. We thought that melanin blocked the enzyme activity. We have tried several methods to remove melanin from tissue samples, however it has not been sufficient yet. Now, we test other methods including filters.

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  • 美白化合物のメラノーマ細胞障害作用を利用した新規メラノーマ治療薬の開発

    Grant number:19H00333  2019

    日本学術振興会  科学研究費助成事業  奨励研究

    黄倉 真恵, 宇原 久, 肥田 時征

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    Grant amount:\540000 ( Direct Cost: \540000 )

    BRAF遺伝子変異を有するメラノーマには分子標的薬が奏効するものの、のちに薬剤耐性が生じる場合が多い。本研究は、分子標的薬の耐性をアスコルビン酸、ロドデノールの併用で克服できるかどうかを検討した。結果、アスコルビン酸はBRAF/MEK阻害剤耐性メラノーマ細胞株SK-me1-23DT, ロドデノールはBRAF/MEK阻害剤耐性メラノーマ細胞株A375DTに強い細胞障害を誘発した。以上の結果から、アスコルビン酸とロドデノールは、分子標的薬(BRAF/MEK阻害薬)による耐性を克服しうる治療薬の候補となり得ることがわかった。

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  • メラノーマ患者の血液循環腫瘍由来RNAを用いた病勢モニタリング法の確立

    2016 - 2018

    日本学術振興会  科学研究費補助金 

    宇原久

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    Authorship:Principal investigator  Grant type:Competitive

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  • 血液循環腫瘍DNAを用いたメラノーマ患者の遺伝子解析

    2014 - 2016

    日本学術振興会  科学研究補助金 

    芦田敦子

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  • EGFR阻害剤による皮脂腺細胞の変化と治療薬探索モデルの構築に関する研究

    2013 - 2015

    日本学術振興会  科学研究費補助金 

    宇原久

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  • Phase I/IIa clinical trial of gene therapy for advanced melanoma using cationic liposomes containing interferon beta gene

    Grant number:15390340  2003 - 2006

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    SAIDA Toshiaki, MATSUMOTO Kazuhiko, UHARA Hisashi, KUBO Hitomi

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    Grant amount:\14000000 ( Direct Cost: \14000000 )

    We constructed cationic liposomes containing interferon beta gene expression plasmid in collaboration with Dr. Yoshida at Nagoya University. In vitro and in vivo studies revealed anti-melanoma effects of this material and its safety was confirmed by animal experiments. Based on these data, we prepared the protocol and other forms for the clinical trial and got permission from the institutional ethical committee and from the committee of the Ministry of Health and Welfare of Japan. Thereafter, Using this reagent, we started a phase I/IIa clinical trial of interferon beta gene therapy for patients with advanced melanoma. A total of 5 patients were treated with this therapy : 4 patients in stage IV and one patient in stage III. The following doses of DNA were injected into metastatic nodular skin lesions : 10 ug for nodules up to 1 cm in diameter and 30 ug for 1 to 2 cm in diameter. Up to 3 lesions were simultaneously treated when multiple small lesions were present, but maximum total dose at one treatment was 30 ug/body. The injections were performed 3 times a week for 2 weeks. All the patients received a total 6 times injection. No significant adverse effects were observed in any patients. The clinical response was as follows : mixed response in one patient, no change in one patient and progressive disease in 3 patients. In the patient who showed mixed response, not only the injected metastatic nodule but also several non-injected nodules disappeared completely, however, a few new metastatic lesions appeared during the course. Histopathologically, in the regressed lesions, degeneration of melanoma cells was observed along with dense infiltrate of CD8 and CD4 T cells within the lesions.

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  • CGH法による悪性黒色腫の早期病変における遺伝子変化の検索

    Grant number:09770620  1997 - 1998

    日本学術振興会  科学研究費助成事業  奨励研究(A)

    宇原 久

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    Grant amount:\1800000 ( Direct Cost: \1800000 )

    これまで新鮮凍結標本を用いて、研究方法の確立および結果の再現性について検討を行ってきた。(材料および方法)本邦人に発生し、かつ日光紫外線の関与が少ないタイプの悪性黒色腫原発巣10例(全てlevel III以上)、皮膚転移巣4例、リンパ節転移巣2例(計16例)、脂漏性角化症3例、ケラトアカントーマ3例の新鮮材料よりDNAを抽出後、Nick translation法でspectrumgreen-dUTPを用いて標識した。同様に正常人リンパ球から抽出したDNAをspectrumred-dUTPで標識した。DNAの純化後、Cot-1 DNAを加え、その後熱処理による変性を行った。常法通り作成し保存してある正常人末梢リンパ球染色体標本を熱変性後、脱水し、上記標識後の腫瘍細胞DNAおよび正常リンパ球DNAを標本上に乗せハイブリダイズを行った。DAPIによる染色体の対比染色を行った後に蛍光顕微鏡下でspectrumgreen、spectrumred、DAPIそれぞれの染色像を1検体当たり約20個の染色体標本についてCCDカメラでデジタルgray scaleイメージとして取り込み、それぞれに疑似カラーを与え重ねた後、3種の合成イメージを作った。合成色のシグナル強度をスキャンし欠失あるいは増幅している染色体部位を特定した(Cyto Vision A/W,APPLIED IMAGING社を使用)。(結果)解析が可能であった悪性黒色腫症例は16例中13検体で、2症例は原発巣と転移巣の比較が可能であった。1検体当たりの解析可能染色体標本数は8〜24個であった。原発巣におけるchromosomeimbalancesは欠失が染色体1,9,11,13-16,19,21に、増幅が10,15,16,21,22,XYを除く染色体にみられたが症例毎にかなりの多様性を示した。また、原発巣と転移巣間の比較では、両者間の染色体の変化は概ね一致しており、さらに1例は6q,8,14qに、もう1例は1p,4q,9pに転移後の変化がみられ、CGH法がこの種の比較に非常に有用であるとの印象を持った。現在、原発巣と転移巣の両者の病変を持つ症例を増やすと共に良性病変についても検討を進めている。

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  • X染色体不活化の検出による皮膚前癌病変におけるクローナリティに関する研究

    Grant number:07770657  1995

    日本学術振興会  科学研究費助成事業  奨励研究(A)

    宇原 久

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    Grant amount:\900000 ( Direct Cost: \900000 )

    本研究は、1992年 Allenらによって明らかにされたアンドロゲン受容体遺伝子塩基配列をもとに、女性の約90%に保存されているCAG繰り返し配列部分をPCR法によって検出することにより、皮膚腫瘍において良性、境界型、悪性に分類されているものについてそのモノクローナリテイの有無を検出することにより、腫瘍細胞の単一性という面から再評価することを目的とする。
    本年度はまず、安定した実験方法の確率をめざした.8例の女性メラノーマ患者より得られたホルマリン固定パラフィン包埋組織より腫瘍部分と非腫瘍部分を切り出しDNAを抽出後、サンプルの一部を制限酵素Hhalで処理した。次にアンドロゲン受容体遺伝子のCGA繰り返し配列部分をはさむ形で作成したプライマーを用いて、制限酵素処理後のサンプルと未処理のサンプルについてPCR法で増幅を試みた。 しかし、当初期待していた程度のDNAの増幅が得られなかった。 メラニンによる阻害作用あるいはサンプル内に混入しているポリメラーゼ阻害物質の存在が疑われたためキレートビーズなどによるサンプルの洗浄を行いインターナルコントロールの増幅は可能となったが、アンドロゲン受容体遺伝子の増幅が不良(8例中1例のみ増幅した)のため、さらにプライマー位置を変更し再度増幅を試みている。また増幅された1例のサンプルについてはプライマーの一方のみを標識しPCR法による増幅後ポリアクリルアミドゲル上での泳動を行っている。

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  • 各種皮膚疾患におけるエラスチンm-RNAのスプライシングの違いに関する研究

    Grant number:06770635  1994

    日本学術振興会  科学研究費助成事業  奨励研究(A)

    宇原 久

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    Grant amount:\900000 ( Direct Cost: \900000 )

    本年度は、(1)エラスチン代謝異状で疑われている皮膚疾患(弾力線維性仮性黄色腫.早老症など)及び(2)皮膚線維性腫瘍について、(1)病的な異状の有無(2)'良性悪性の鑑別点となるパターンが存在するか否かについて明らかにすることを目的とした。
    まず生検材料、手術材料よりm-RNAを抽出し(腫瘍部or病変部、周辺正常部)C-DNAを合成後、エラスチン遺伝子の中のエクソン22,23,24,26A,32,33のスプライシングを検索するために設定したプライマーを用いて、PCR法を行った。電気泳動により、合成産物の塩基長の違い、パターン、特定バンドの消失の有無を調べた。本年度は、上記(1)に相当する患者がいなかったため、(2)については皮膚線維腫、持久性隆起性皮膚線維肉腫について検討した。その結果、両者側に今のところ明らかに有意と思われる違いを見い出すことはできないでいる。この点についてはさらに他のエクソンについての検討や、また点突然変異などの微小な変化の存在している可能性もあり、症例を増やすと共に上記の点について検討を進めている。

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