Nakamura, Yoshio

写真a

Affiliation

School of Medicine, Department of Dermatology （Shinanomachi）

Position

Assistant Professor/Senior Assistant Professor
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Career 【 Display / hide 】

  • 2006.04
    -
    2008.03

    Tokyo Kosei Nenkin Hospital

  • 2008.04
    -
    2009.06

    Department of Dermatology, Keio University School of Medicine

  • 2009.07
    -
    2011.10

    Ogikubo Hospital

  • 2011.10
    -
    2014.06

    Department of Dermatology, Keio University School of Medicine

  • 2014.07
    -
    2016.06

    National Cancer Center Hospital

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Academic Background 【 Display / hide 】

  • 2000.04
    -
    2006.03

    Kanazawa University, School of Medicine, Department of Medicine

    University, Graduated

  • 2014.04
    -
    2018.03

    Keio University, Graduate School of Medicine, Medical Science

    Graduate School, Withdrawal after completion of doctoral course requirements

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Academic Degrees 【 Display / hide 】

  • Ph.D., Keio University, Coursework, 2019.01

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Licenses and Qualifications 【 Display / hide 】

  • Medical License, 2006.04

  • The Japanese Dermatological Association Board certified dermatologist, 2011.10

  • Japanese Board of Cancer Therapy certified General Clinical Oncologist, 2014.04

  • The Japanese Dermatological Association Board certified Skin Cancer Educator, 2017.04

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Research Areas 【 Display / hide 】

  • Life Science / Dermatology

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Research Keywords 【 Display / hide 】

  • Skin Cancer

  • SUrgical Oncology

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Papers 【 Display / hide 】

  • Role of androgen signaling in androgen receptor-positive extramammary Paget's disease: Establishment of organoids and their biological analysis as a novel therapeutic target

    Nakamura Y., Mizukami H., Tanese K., Fusumae T., Hirai I., Amagai M., Takamatsu R., Nakamura K., Nishihara H., Takimoto T., Ueno M., Saya H., Funakoshi T.

    Journal of Dermatological Science （Journal of Dermatological Science)  112 （ 1 ） 23 - 30 2023.10

    ISSN  09231811

    　View Summary

    Background: Extramammary Paget's disease (EMPD) is a rare intraepithelial adenocarcinoma that mainly affects the anogenital and axillary regions. Although its etiology has not been fully elucidated, there is evidence that androgen receptors (AR) are expressed in most cases of EMPD. However, the role of androgen signaling in the pathogenesis of EMPD remains unclear. Objective: To evaluate the role of androgen signaling in tumor growth of AR-positive EMPD. Methods: Patient-derived organoids were established and cultured from two AR-positive EMPD patients: one man and one woman. Cultured organoids were treated with androgen agonists and/or antagonists, then subjected to analysis of changes in organoid proliferation, as well as changes in androgen signaling pathway-specific genes. Results: Organoid cultures were established from each EMPD sample. These organoids were immunohistologically and genetically identical to the original tumor. For each organoid sample, viable cell number increased in response to androgen exposure. The mRNA level of Fkbp5, a known AR target gene, increased in a concentration-dependent manner in organoids exposed to the synthetic androgen R1881. Conversely, the AR inhibitor darolutamide suppressed the viable cell number in a concentration-dependent manner. The mRNA expression levels of MKI67 and Fkbp5 were also suppressed by darolutamide. Conclusion: Our results indicate that androgen signaling is a key pathway involved in the growth of AR-positive EMPD. Therefore, androgen signaling inhibition may be a novel treatment option for EMPD patients who require systemic therapy.

  • Clinicopathological significance of androgen receptor expression in extramammary Paget disease: An analysis of 92 patients

    Kuramoto J., Kobayashi K., Hirai I., Nakamura Y., Funakoshi T., Kanai Y.

    Pathology Research and Practice （Pathology Research and Practice)  249   154775 2023.09

    ISSN  03440338

    　View Summary

    Extramammary Paget disease (EMPD) is a rare cutaneous malignant neoplasm arising in apocrine gland-rich areas. Although – like normal apocrine glands – EMPD frequently expresses androgen receptor (AR), the clinical significance of AR expression remains unclear. The present study investigated the clinicopathological impact of AR expression in EMPD. Immunohistochemistry for AR was performed in a retrospective cohort of 92 EMPD patients with 108 EMPD lesions, including 102 primary lesions, five lymph node [LN] metastases and one local recurrence. The total AR staining score was calculated as staining intensity score (IS 0–3) × positive-cell percentage score (PS 1–4). Expression levels were graded as Grade 1 (scores 0 and 1), Grade 2 (scores 2–4), and Grade 3 (scores 6–12). Higher expression grade was correlated with tumor thickness (P = 0.011), LN metastasis (P = 0.008), and higher EMPD stage (P = 0.023). Grade 1 EMPDs did not invade into the dermis and did not generate metastatic and/or recurrent lesions, whereas only Grade 2 or 3 EMPDs did so. AR expression in invasive components was significantly higher (P = 0.023) than in non-invasive components remaining within the epidermis. AR expression was further elevated in metastatic and/or recurrent lesions relative to locally invasive lesions (P = 0.014). These results clearly indicate that increased AR expression is associated with malignant progression of EMPD and that androgen blockade might be an effective therapy. Furthermore, AR expression assessed by immunohistochemistry may have potential for prediction of LN metastasis and local recurrence in EMPD.

  • Outcomes in extramammary Paget's disease patients with brain metastasis: a retrospective analysis.

    Fusumae T, Fukuda K, Hirai I, Nakamura Y, Tanese K, Iwata T, Funakoshi T

    Journal of the American Academy of Dermatology  2020.05

    ISSN  0190-9622

  • Weekly docetaxel monotherapy for metastatic extramammary Paget’s disease: Retrospective single-institute analysis

    Nakamura Y., Tanese K., Hirai I., Fukuda K., Kawakami Y., Amagai M., Funakoshi T.

    Journal of Dermatology （Journal of Dermatology)  47 （ 4 ） 418 - 422 2020.04

    ISSN  03852407

    　View Summary

    © 2020 Japanese Dermatological Association Monthly docetaxel (DTX) monotherapy is the first-line regimen that is preferably used for metastatic extramammary Paget’s disease (EMPD). However, the high-dose DTX regimen frequently causes severe hematological adverse events (AE). To overcome such safety concerns, a weekly low-dose DTX monotherapy has been proposed for use in the treatment of various cancer types. In this study, we aimed to evaluate the feasibility and efficacy of weekly DTX (25 mg/m2) monotherapy for metastatic EMPD by retrospectively analyzing the clinical courses of 14 patients treated with this regimen. Weekly DTX monotherapy was well tolerated and all patients completed the treatment schedule without treatment withdrawal, dose reduction or treatment-related death. While five cases (35.7%) experienced hematological AE, their severity was mild. The response rate was 35.7% (5/14 cases), which included five partial responses. The mean progression-free survival (PFS) and overall survival were 7.1 (95% confidence interval [CI], 5.1–9.1) and 26.4 months (95% CI, 16.7–36.1), respectively. Furthermore, the median PFS was 7.3 months (95% CI, 4.5–10.0) in patients aged 65 years and younger and 7.1 months (95% CI, 4.4–9.9) in patients older than 65 years. These results suggest that weekly DTX monotherapy may be a useful regimen that has a high treatment continuation rate with low levels of hematological toxicity, regardless of the patient’s age for metastatic EMPD.

  • Metastatic cutaneous squamous cell carcinoma in liver successfully treated with partial hepatectomy and adjuvant irinotecan chemotherapy

    Asahina Y., Nakamura Y., Tanese K., Hirai I., Fukuda K., Amagai M., Funakoshi T.

    In Vivo （In Vivo)  34 （ 2 ） 825 - 828 2020

    ISSN  0258851X

    　View Summary

    © 2020 International Institute of Anticancer Research. All rights reserved. Background: The management of distant metastatic cutaneous squamous cell carcinoma (cSCC) relies mainly on chemotherapies and radiotherapy. Management of patients with cSCC with surgically resectable distant metastatic lesions is not clear. Case Report: A 59-year-old male had 4×10 cmsized cSCC on the perianal skin with inguinal lymph node metastasis. Surgical resection was performed followed by radiation and adjuvant carboplatin and farmorubicin combination therapy. Six months later, 25 mm-sized solitary metastatic nodule arose on the liver. Base on his favorable overall condition fulfilling the criteria of tumor resectability for the treatment of tumors in liver and having good performance status, laparoscopic partial hepatectomy and six courses of adjuvant irinotecan therapy were performed. The surgical margin was negative and the patient has maintained complete remission for over 3 years. Conclusion: The clinical course of the present case suggests that surgical approaches should also be considered as candidate additional therapy for resectable distant metastatic cSCC.

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Papers, etc., Registered in KOARA 【 Display / hide 】

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Reviews, Commentaries, etc. 【 Display / hide 】

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Presentations 【 Display / hide 】

  • Analysis Of The Appropriate Margin Of Pigmented Bcc: A Single Institute Retrospective Study In Japan

    Yoshio Nakamura

    World congress on cancers of the skin (Sydney) , 

    2018.08

  • Retrospective Study Of Chemotherapy Using Carboplatin And Epirubicin For Advanced Epithelial Malignancy Of The Skin. World congress on cancers of the skin

    Yoshio Nakamura

    World congress on cancers of the skin (Sydney) , 

    2018.08

  • Pretreatment prognostic factors and early markers for outcome in advanced melanoma treated with nivolumab

    Yoshio Nakamura

    ESMO 2016 congress (Copenhagen) , 

    2016.10
    , 

    ESMO

  • Outcomes of local treatment for malignant melanoma brain metastases: a single institution retrospective study

    Yoshio Nakamura

    European Cancer Congress (Vienna) , 

    2015.09

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

  • Analysis of the three-dimensional structure of Extramammary Paget's disease using the tissue clearing method

    2021.04
    -
    2023.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Early-Career Scientists , Principal investigator

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