Faculty of Medicine School of Medicine Oncopathology and morphopathology


Assistant Professor

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Degree 【 display / non-display

  • 学士(医学) ( 2015.3   宮崎大学 )

Research Areas 【 display / non-display

  • Life Science / Human pathology


Papers 【 display / non-display

  • Patient-Derived Organoids of Colorectal Cancer: A Useful Tool for Personalized Medicine Invited Reviewed

    Kiwaki T., Kataoka H.

    Journal of Personalized Medicine   12 ( 5 )   2022.5

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    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Journal of Personalized Medicine  

    Colorectal cancer is one of the most important malignancies worldwide, with high incidence and mortality rates. Several studies have been conducted using two-dimensional cultured cell lines; however, these cells do not represent a study model of patient tumors very well. In recent years, advancements in three-dimensional culture methods have facilitated the establishment of patient-derived organoids, which have become indispensable for molecular biology-related studies of colorectal cancer. Patient-derived organoids are useful in both basic science and clinical practice; they can help predict the sensitivity of patients with cancer to chemotherapy and radiotherapy and provide the right treatment to the right patient. Regarding precision medicine, combining gene panel testing and organoid-based screening can increase the effectiveness of medical care. In this study, we review the development of three-dimensional culture methods and present the most recent information on the clinical application of patient-derived organoids. Moreover, we discuss the problems and future prospects of organoid-based personalized medicine.

    DOI: 10.3390/jpm12050695



  • Adrenomedullin alleviates mucosal injury in experimental colitis and increases claudin-4 expression in the colonic epithelium. Reviewed

    Kawaguchi M, Kataoka H, Kiwaki T, Liang W, Nagata S, Kitamura K, Fukushima T

    FEBS open bio   13 ( 4 )   713 - 723   2023.2

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:FEBS Open Bio  

    Adrenomedullin (AM) is a peptide with pleiotropic physiological functions that attenuates intestinal mucosal inflammation. However, the mechanism underpinning mucosal protection by AM is not fully understood, and its effect on intestinal epithelial cells remains unclear. Here, we investigated the effects of AM on junctional molecules in primary-cultured murine intestinal epithelial cells and discovered that AM upregulates claudin-4 expression. In a mouse model of dextran sulfate sodium-induced colitis, AM administration also enhanced claudin-4 expression and accelerated mucosal regeneration. Furthermore, AM reversed TNFα-mediated downregulation of claudin-4 and loss of cell–cell adhesion of the HCT116 human intestinal epithelial cell line in vitro. These results indicate that AM may enhance intestinal epithelial integrity by upregulating claudin-4 expression.

    DOI: 10.1002/2211-5463.13577



  • Possible role of combined therapy targeting MET and pro-HGF activation for renal cell carcinoma: analysis by human HGF-producing SCID mice. Reviewed

    Fujii M, Akioka T, Kimura S, Nagai T, Kiwaki T, Fukushima T, Mukai S, Kamoto T

    Human cell   36 ( 2 )   775 - 785   2023.1

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Human Cell  

    MET is a high-affinity receptor tyrosine kinase of HGF (hepatocyte growth factor). HGF is secreted as an inactive single-chain precursor (pro-HGF), which requires proteolytic activation for conversion to an active form. HGF activator inhibitor (HAI)-2 is a transmembrane Kunitz-type serine protease inhibitor, which inhibits all pro-HGF-activating enzymes. In RCC, increased expression of MET and decreased expression of HAI-2 were reported to be poor prognostic factors. In the current study, we tried to inhibit the growth of RCC cells by dual inhibition of both MET phosphorylation and pro-HGF-activation using MET inhibitor and HAI-2 overexpression. A transgenic mouse model which expressed human HGF (HGF mouse) was used for in vivo analysis to evaluate the HGF/MET signaling axis accurately. Initially, doxycycline-induced HAI-2 overexpression RCC cells (786-O-HAI2) were prepared. The cells were cultured with pro-HGF, and inhibitory effect of MET inhibitor (SCC244) and HAI-2 was evaluated by phosphorylation of MET and cell proliferation. Next, the cells were subcutaneously implanted to HGF mice and the growth inhibition was determined by SCC244 and HAI-2. Single use of each inhibitor showed significant inhibition in MET phosphorylation, migration and proliferation of 786-O-HAI2 cells; however, the strongest effect was observed by combined use of both inhibitors. Although in vivo analysis also showed apparent downregulation of MET phosphorylation and growth inhibition in combined treatment, statistical significance was not observed compared with single use of MET inhibitor. Combined treatment with MET-TKI and HAI-2 suggested to consider as a candidate for new strong therapy for RCC.

    DOI: 10.1007/s13577-023-00857-y



  • Epithelioid Angiomyolipoma with Tumor Thrombus into Inferior Vena Cava Presurgically Treated with Combination Therapy of Pembrolizumab and Axitinib: A Case Report Reviewed

    Kawasoe C., Miyamoto Y., Ito K., Murashima T., Nagai T., Takamori H., Kiwaki T., Kamimura T., Mukai S., Kamoto T.

    Research and Reports in Urology   15   447 - 452   2023

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Research and Reports in Urology  

    Epithelioid angiomyolipoma (EAML) is a rare variant of AML with malignant potential. It is occasionally difficult to distinguish EAML from renal cell carcinoma (RCC) on imaging. A 72-year-old woman was admitted to our hospital for the treatment of a left renal tumor with relatively high blood flow and a tumor thrombus extending to the inferior vena cava, suggesting RCC. The patient underwent presurgical combination therapy with axitinib and pembrolizumab. This treatment significantly shortened the thrombus, and radical nephrectomy was performed. The pathological findings were compatible with EAML, and the treatment effects were observed. We report a case treated pre-surgically with a combined therapy of pembrolizumab and axitinib, with a favorable response as a treatment option for EAML.

    DOI: 10.2147/RRU.S425887


  • Skin Ulcer Localized to the Scalp Due to Granulomatous Vasculitis with Positive Proteinase 3-antineutrophil Cytoplasmic Antibody Reviewed

    CHOSA Nobuaki, TSUMORI Shinichiro, HACHISUKA Hiroshi, KIWAKI Takumi, OGATA Katsumi

    The Nishinihon Journal of Dermatology   84 ( 6 )   512 - 516   2022.12

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Western Division of Japanese Dermatological Association  

    DOI: 10.2336/nishinihonhifu.84.512


    CiNii Research

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Presentations 【 display / non-display

  • ヒト HGF 導入 SCID マウスを用いた HGF-MET シグナル解析と阻害治療の開発 Invited

    木脇 拓道


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    Event date: 2020.8.22 - 2020.8.23

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

  • A synthetic small molecule inhibitor of pro-HGF activation, ZFH7116, suppresses the growth of SAS squamous cell carcinoma line in human HGF knock-in SCID mice: A pilot study International conference

    Takumi Kiwaki, Makiko Kawaguchi, Koji Yamamoto, James W. Janetka, Hiroaki Kataoka

    ASBMB Symposia: Serine Proteases in Pericellular Proteolysis and Signaling  (Potomac, Md., USA)  American Society for Biochemistry and Molecular Biology

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    Event date: 2019.9.12 - 2019.9.15

    Language:English   Presentation type:Poster presentation  

    Venue:Potomac, Md., USA  

Awards 【 display / non-display

  • Best Case Report Award (Young Pathologist Encouragement Award) from the Kyushu-Okinawa Branch of the Japanese Society of Pathology

    2020.5   The Kyushu-Okinawa Branch of the Japanese Society of Pathology  

    Takumi Kiwaki

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    Award type:Award from Japanese society, conference, symposium, etc.  Country:Japan

Grant-in-Aid for Scientific Research 【 display / non-display

  • がん細胞の HGF 活性制御分子に着目した HGF-MET 依存性転移機構の解明

    Grant number:23K06444  2023.04 - 2026.03

    日本学術振興会  科学研究費助成事業  基盤研究(C)

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    Authorship:Principal investigator 

  • がん組織におけるHGF-METシグナル活性化機構の解明と、その阻害療法の開発

    Grant number:20K16175  2020.04 - 2023.03

    独立行政法人日本学術振興会  科学研究費補助金  若手研究

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    Authorship:Principal investigator