Updated on 2024/11/25

写真a

 
KINOSHITA FUMIHIKO
 
Organization
Kyushu University Hospital Health Networking Center Assistant Professor
Kyushu University Hospital Health Networking Center(Concurrent)
Title
Assistant Professor
Contact information
メールアドレス
Tel
0926425466
Profile
2014年に九州大学医学部医学科を卒業し、2年間の初期臨床研修後、2016年に九州大学大学院消化器・総合外科に入学し、胸部悪性腫瘍の研究に従事し、「Interleukin-38は肺癌微小環境においてCD8+リンパ球浸潤を抑制することで腫瘍形成に寄与する」(Kinoshita F, et al. Cancer Immunol Immunother. 2021)のテーマで学位を取得した。その後、国立病院機構九州がんセンターで呼吸器外科の臨床に従事した後、2023年4月より九州大学大学院消化器・総合外科、九州大学病院呼吸器外科に異動し、呼吸器外科の臨床・研究に加え、医学部学生・大学院生の指導を行っている。
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Degree

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Research History

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Research Interests・Research Keywords

  • Research theme: Development and validation of machine learning prognosis prediction model for surgically resected non-small cell lung cancer.

    Keyword: artificial intelligence, machine learning, non-small cell lung cancer, surgery, prediction of prognosis

    Research period: 2020.4 - 2024.4

  • Research theme: Research on the significance and therapeutic applications of the IL-36 family in the tumor microenvironment of lung cancer.

    Keyword: lung cancer, tumor microenvironment, immunotherapy, interleukin-36 family

    Research period: 2020.4 - 2024.4

Papers

  • Development of artificial intelligence prognostic model for surgically resected non-small cell lung cancer. Reviewed International journal

    Kinoshita F, Takenaka T, Yamashita T, Matsumoto K, Oku Y, Ono Y, Wakasu S, Haratake N, Tagawa T, Nakashima N, Mori M.

    Sci Rep   2023.9

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    Language:English   Publishing type:Research paper (scientific journal)  

  • Interleukin-38 promotes tumor growth through regulation of CD8+ tumor-infiltrating lymphocytes in lung cancer tumor microenvironment. Reviewed International journal

    Kinoshita F, Tagawa T, Akamine T, Takada K, Yamada Y, Oku Y, Kosai K, Ono Y, Tanaka K, Wakasu S, Oba T, Osoegawa A, Shimokawa M, Oda Y, Hoshino T, Mori M.

    Cancer Immunol Immunother.   2021.1

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    Language:English   Publishing type:Research paper (scientific journal)  

  • Assessment of the Therapeutic Potential of Enhancer of Zeste Homolog 2 Inhibition in a Murine Model of Bronchiolitis Obliterans Syndrome

    Matsudo, K; Takamori, S; Takenaka, T; Shimokawa, M; Hashinokuchi, A; Nagano, T; Kinoshita, F; Akamine, T; Kohno, M; Toyokawa, G; Yoshizumi, T

    TRANSPLANT INTERNATIONAL   37   13227   2024.10   ISSN:0934-0874 eISSN:1432-2277

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    Language:English   Publisher:Transplant International  

    Bronchiolitis obliterans syndrome (BOS) is a chronic complication following lung transplantation that limits the long-term survival. Although the enhancer of zeste homolog 2 (EZH2) is involved in post-transplantation rejection, its involvement in BOS pathogenesis remains unclear. We aimed to investigate the therapeutic potential of EZH2 inhibition in BOS. 3-deazaneplanocin A (DZNep) was administered intraperitoneally to heterotopic tracheal transplant recipient model mice. Tracheal allografts were obtained on days 7, 14, 21, and 28 after transplantation. The obstruction ratios of the DZNep and control groups on days 7, 14, 21, and 28 were 15.1% ± 0.8% vs. 20.4% ± 3.6% (p = 0.996), 16.9% ± 2.1% vs. 67.7% ± 11.5% (p < 0.001), 47.8% ± 7.8% vs. 92.2% ± 5.4% (p < 0.001), and 60.0% ± 9.6% vs. 95.0% ± 2.3% (p < 0.001), respectively. The levels of interleukin (IL)-6 and interferon-γ on day 7 and those of IL-2, tumor necrosis factor, and IL-17A on days 14, 21, and 28 were significantly reduced following DZNep treatment. DZNep significantly decreased the number of infiltrating T-cells on day 14. In conclusion, DZNep-mediated EZH2 inhibition suppressed the inflammatory reactions driven by pro-inflammatory cytokines and T cell infiltration, thereby alleviating BOS symptoms.

    DOI: 10.3389/ti.2024.13227

    Web of Science

    Scopus

    PubMed

  • Clinical significance of CD155 expression in surgically resected lung squamous cell carcinoma

    Nagano, T; Takada, K; Hashinokuchi, A; Matsudo, K; Kinoshita, F; Akamine, T; Kohno, M; Shimokawa, M; Takenaka, T; Oda, Y; Yoshizumi, T

    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY   2024.10   ISSN:1341-9625 eISSN:1437-7772

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    Language:English   Publisher:International Journal of Clinical Oncology  

    Background: Cluster of differentiation 155 (CD155) is expressed in many tumor types. CD155 is involved in the immune avoidance of tumor cells and contributes to tumor development and progression. Therefore, CD155 is a novel target for cancer immunotherapy. The clinical significance of CD155 expression in lung squamous cell carcinoma (LUSC) has not been fully elucidated. Materials and methods: We performed a retrospective analysis of 264 patients with surgically resected LUSC. Immunohistochemistry was used to evaluate CD155 expression. The association of CD155 expression with clinicopathological features and clinical outcomes was assessed. We also analyzed the relationship between CD155 expression and programmed cell death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes. Results: Among the 264 patients, 137 patients (51.9%) were classified in the high CD155 expression group. High CD155 expression was significantly associated with pleural invasion, vascular invasion, PD-L1 positivity, and high CD3, CD4, and CD8 expressions. In multivariate analysis, the presence of pleural invasion and PD-L1 positivity were independent predictors of high CD155 expression. Kaplan–Meier curve analysis showed that high CD155 expression was significantly associated with shorter disease-free survival and overall survival. In multivariate analysis, high CD155 expression was an independent poor prognostic factor for overall survival, but not for disease-free survival. Subgroup analyses revealed that the prognostic effect of CD155 expression was observed in the PD-L1 positive group but not the PD-L1 negative group. Conclusion: Our analysis revealed that high CD155 expression significantly predicted poor prognosis in patients with surgically resected LUSC, especially in patients with PD-L1-positive tumors.

    DOI: 10.1007/s10147-024-02640-x

    Web of Science

    Scopus

    PubMed

  • Data-driven prediction of prolonged air leak after video-assisted thoracoscopic surgery for lung cancer: Development and validation of machine-learning-based models using real-world data through the ePath system

    Tou, S; Matsumoto, K; Hashinokuchi, A; Kinoshita, F; Nakaguma, H; Kozuma, Y; Sugeta, R; Nohara, Y; Yamashita, T; Wakata, Y; Takenaka, T; Iwatani, K; Soejima, H; Yoshizumi, T; Nakashima, N; Kamouchi, M

    LEARNING HEALTH SYSTEMS   2024.10   ISSN:2379-6146

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    Publisher:Learning Health Systems  

    Introduction: The reliability of data-driven predictions in real-world scenarios remains uncertain. This study aimed to develop and validate a machine-learning-based model for predicting clinical outcomes using real-world data from an electronic clinical pathway (ePath) system. Methods: All available data were collected from patients with lung cancer who underwent video-assisted thoracoscopic surgery at two independent hospitals utilizing the ePath system. The primary clinical outcome of interest was prolonged air leak (PAL), defined as drainage removal more than 2 days post-surgery. Data-driven prediction models were developed in a cohort of 314 patients from a university hospital applying sparse linear regression models (least absolute shrinkage and selection operator, ridge, and elastic net) and decision tree ensemble models (random forest and extreme gradient boosting). Model performance was then validated in a cohort of 154 patients from a tertiary hospital using the area under the receiver operating characteristic curve (AUROC) and calibration plots. Results: To mitigate bias, variables with missing data related to PAL or those with high rates of missing data were excluded from the dataset. Fivefold cross-validation indicated improved AUROCs when utilizing key variables, even post-imputation of missing data. Dichotomizing continuous variables enhanced performance, particularly when fewer variables were employed in the decision tree ensemble models. Consequently, regression models incorporating seven key variables in complete case analysis demonstrated superior discriminatory ability for both internal (AUROCs: 0.77–0.84) and external cohorts (AUROCs: 0.75–0.84). These models exhibited satisfactory calibration in both cohorts. Conclusions: The data-driven prediction model implementing the ePath system exhibited adequate performance in predicting PAL post-video-assisted thoracoscopic surgery, optimizing variables and considering population characteristics in a real-world setting.

    DOI: 10.1002/lrh2.10469

    Web of Science

    Scopus

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Presentations

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Professional Memberships

  • 日本外科学会

  • 日本呼吸器外科学会

  • 日本胸部外科学会

  • 日本肺癌学会

Research Projects

  • Elucidation of the significance of the Interleukin(IL)-36 Family in the lung cancer microenvironment and development of novel immunotherapy

    Grant number:24K18487  2024 - 2026

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Early-Career Scientists

    木下 郁彦

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    Authorship:Principal investigator  Grant type:Scientific research funding

    本研究の目的はInterleukin(IL)-36 Familyの肺癌微小環境での役割を明らかにし、新規治療法開発を探求することである。IL-36 FamilyにはIL-36α、β、γの3つのサブフォームがあり、2001年に発見されたIL-38も属する。IL-36 Familyと悪性腫瘍の関連は注目を集めており、我々も肺癌マウスモデルを用いてIL-38が腫瘍へのCD8陽性リンパ球浸潤を抑制し腫瘍形成を促進することを報告した。以上よりIL-36 Familyが肺癌微小環境で重要な役割を担うと考えられ、IL-36 Familyを標的とした新規治療法開発のための基礎的検討を行う。

    CiNii Research

  • Interleukin-36 Familyの肺癌微小環境における意義

    2022 - 2023

    Grants-in-Aid for Scientific Research  上原記念生命科学財団研究奨励金

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    Authorship:Principal investigator  Grant type:Competitive funding other than Grants-in-Aid for Scientific Research

  • Interleukin(IL)-36 Family の肺癌微小環境における役割の解明

    2022 - 2023

    Grants-in-Aid for Scientific Research  がん集学的治療研究財団助成金

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    Authorship:Principal investigator  Grant type:Competitive funding other than Grants-in-Aid for Scientific Research

  • Interleukin(IL)-38を標的とした肺癌の新規免疫療法の開発

    Grant number:21K15507  2021 - 2023

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Early-Career Scientists

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    Authorship:Principal investigator  Grant type:Scientific research funding

  • 新規サイトカインInterleukin-38の肺移植直後閉塞性細気管支炎(Bronchiolitis Obliterans Syndrome : BOS)における意義の検討と新規治療モデルの開発

    2020 - 2021

    Grants-in-Aid for Scientific Research  一般財団法人横山臨床薬理研究助成基金

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    Authorship:Principal investigator  Grant type:Competitive funding other than Grants-in-Aid for Scientific Research

Educational Activities

  • ①医学部4年性、5年生および6年生に対して、ベッドサイドを中心に呼吸器外科の臨床および研究について指導する。
    ②大学院博士課程学生および博士号未取得医員に対して、呼吸器外科学、胸部悪性腫瘍学に関する実験、学会報告、論文作成について指導する。

Outline of Social Contribution and International Cooperation activities

  • ① 呼吸器外科領域の患者紹介を積極的に受け入れ、地域医療に貢献する。
    ② 院内の他科と連携し、呼吸器外科疾患患者の診療に当たる。
    ③ 国内外の呼吸器外科領域の学会に積極的に参加し、最新の知見を得るとともに、情報発信を行う。

Specialized clinical area

  • Biology / Medicine, Dentistry and Pharmacy / Surgical Clinical Medicine / Respiratory Surgery

Clinician qualification

  • Specialist

    Japan Surgical Society(JSS)

  • Specialist

    The Japanese Association for Chest Surgery

Year of medical license acquisition

  • 2014

Notable Clinical Activities

  • 呼吸器外科専門医として、胸部疾患の患者さんを対象に安全かつ親身な診療を心がけています。 臨床試験などの活動にも積極的に参加して最新の知見に基づいた最良の医療を行うとともに、新たなエビデンス構築のための活動も行っています。