Hirai, Ikuko

写真a

Affiliation

School of Medicine, Department of Dermatology (Shinanomachi)

Position

Project Senior Assistant Professor (Non-tenured)/Project Assistant Professor (Non-tenured)/Project Lecturer (Non-tenured)
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Career 【 Display / hide 】

  • 2008.04
    -
    Present

    Department of Dermatology, Keio University School of Medicine

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Academic Background 【 Display / hide 】

  • 　

    Nippon Medical School

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Research Areas 【 Display / hide 】

  • Life Science / Dermatology

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Research Keywords 【 Display / hide 】

  • skin cancer

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Research Themes 【 Display / hide 】

  • adoptive cell therapy using cultured tumor infiltrating lymphocytes with lympho-depleting non-myeloablative preconditioning for patients with metastatic melanoma, 

    2014.04
    -
    2017.03

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Papers 【 Display / hide 】

  • Apremilast is a potentially useful treatment for severe palmoplantar pustulosis with extra-palmoplantar symptoms

    Fukushima-Nomura A., Takamiyagi S., Kakuta R., Ito Y., Hirai I., Umemoto J., Hanaoka H., Kaneko Y., Tanese K.

    Skin Health and Disease (Skin Health and Disease)  4 ( 2 )  2024.04

    　View Summary

    Palmoplantar pustulosis (PPP) is a chronic inflammatory skin disorder affecting the palms and soles. In rare cases, severe patients develop acute extra-palmoplantar lesions often accompanied by arthralgia. Such cases with extensive symptoms often necessitate systemic treatments with variable efficacy and potential side effects. Apremilast, known for its broad immune response modulation, presents promise as a therapeutic option for severe PPP with joint and extra-palmoplantar lesions. This case highlights apremilast as a potential systemic treatment for such cases with minimal side effects.

  • Pre-existing Interstitial Lung Abnormalities and Immune Checkpoint Inhibitor-Related Pneumonitis in Solid Tumors: A Retrospective Analysis

    Horiuchi K., Ikemura S., Sato T., Shimozaki K., Okamori S., Yamada Y., Yokoyama Y., Hashimoto M., Jinzaki M., Hirai I., Funakoshi T., Mizuno R., Oya M., Hirata K., Hamamoto Y., Terai H., Yasuda H., Kawada I., Soejima K., Fukunaga K.

    Oncologist (Oncologist)  29 ( 1 ) E108 - E117 2024.01

    ISSN  10837159

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    Background: Immune checkpoint inhibitors (ICIs) have demonstrated efficacy over previous cytotoxic chemotherapies in clinical trials among various tumors. Despite their favorable outcomes, they are associated with a unique set of toxicities termed as immune-related adverse events (irAEs). Among the toxicities, ICI-related pneumonitis has poor outcomes with little understanding of its risk factors. This retrospective study aimed to investigate whether pre-existing interstitial lung abnormality (ILA) is a potential risk factor for ICI-related pneumonitis. Materials and Methods: Patients with non-small cell lung cancer, malignant melanoma, renal cell carcinoma, and gastric cancer, who was administered either nivolumab, pembrolizumab, or atezolizumab between September 2014 and January 2019 were retrospectively reviewed. Information on baseline characteristics, computed tomography findings before administration of ICIs, clinical outcomes, and irAEs were collected from their medical records. Pre-existing ILA was categorized based on previous studies. Results: Two-hundred-nine patients with a median age of 68 years were included and 23 (11.0%) developed ICI-related pneumonitis. While smoking history and ICI agents were associated with ICI-related pneumonitis (P = .005 and .044, respectively), the categories of ILA were not associated with ICI-related pneumonitis (P = .428). None of the features of lung abnormalities were also associated with ICI-related pneumonitis. Multivariate logistic analysis indicated that smoking history was the only significant predictor of ICI-related pneumonitis (P = .028). Conclusion: This retrospective study did not demonstrate statistically significant association between pre-existing ILA and ICI-related pneumonitis, nor an association between radiologic features of ILA and ICI-related pneumonitis. Smoking history was independently associated with ICI-related pneumonitis. Further research is warranted for further understanding of the risk factors of ICI-related pneumonitis.

  • 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 2023.09

    ISSN  03440338

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    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.

  • Management and outcomes of hydronephrosis in patients with metastatic extramammary Paget’s disease: A retrospective analysis

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

    Journal of Dermatology (Journal of Dermatology)  49 ( 8 ) 787 - 791 2022.08

    ISSN  03852407

    　View Summary

    Hydronephrosis in extramammary Paget’s disease (EMPD) with distant metastasis (metastatic EMPD) has been observed in medical practice; however, its prognosis remains unclear. Retrospective analyses were performed to assess the management and outcomes of hydronephrosis in metastatic EMPD. During a follow-up of 44 patients with metastatic EMPD, 13 (30%) developed hydronephrosis. Ten (77%) of the 13 patients with hydronephrosis had impaired renal function (estimated glomerular filtration rate: <60 ml/min/1.73 m2), and ureteral stents were placed in every patient with impaired renal function. The stent was placed successfully in all 10 patients, and their renal function recovered within a median period of 7 days. Importantly, each of these patients continued chemotherapy, and none of them experienced stent failure. The median overall survival time (OS) in patients with metastatic EMPD and hydronephrosis (n = 13) was 7.8 months. Treatment for hydronephrosis was not a significant factor for OS, and median OS in patients who underwent ureteral stent replacement (n = 10) was 14.7 months. Collectively, our results indicate that hydronephrosis is relatively common, and ureteral stent placement should be considered in cases of metastatic EMPD with hydronephrosis to maintain renal function and continue chemotherapy toward a better prognosis.

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Reviews, Commentaries, etc. 【 Display / hide 】

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Presentations 【 Display / hide 】

  • Analysis of HER2 expression in metastatic extramammary Paget’s disease.

    Hirai Ikuko

    World Congress on Cancers of the Skin 2018, 

    2018.08
    , 

    Poster presentation

  • 進行期悪性黒色腫に対する骨髄非破壊的前処置および低用量IL-2併用の抗腫瘍自己リンパ球輸注療法feasibility試験

    Hirai Ikuko

    第22回 日本がん免疫学会総会　 (岡山市) , 

    2018.08
    , 

    Oral presentation (general)

  • 進行期悪性黒色腫に対する骨髄非破壊的前処置および低用量IL-2併用の抗腫瘍自己リンパ球輸注療法

    Hirai Ikuko

    第34回日本皮膚悪性腫瘍学会学術大会　 (浜松市) , 

    2018.07
    , 

    Oral presentation (general)

  • Weekly cisplatin, epirubicin, and paclitaxel induced a durable response in two cases of metastatic extramammary Paget’s disease.

    Hirai Ikuko

    2016.08
    , 

    Poster presentation

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

  • 進行期乳房外パジェット病における治療効果予測のバイオマーカーの探索

    2020.04
    -
    2023.03

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

  • ［革新的がん医療実用化研究事業］ 進行期悪性黒色腫(末端黒子型)に対する非骨髄破壊性前処置併用での腫瘍浸潤Tリンパ球輸注療法の安全性試験

    2015
    -
    2017

    AMED（国立研究開発法人日本医療研究開発機構）, No Setting

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Memberships in Academic Societies 【 Display / hide 】

  • Japanese Dermatological Association

    　
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