Fukumoto, Keishiro

写真a

Affiliation

School of Medicine, Department of Urology (Shinanomachi)

Position

Instructor
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Papers 【 Display / hide 】

  • Hybridisation chain reaction-based visualisation and screening for lncRNA profiles in clear-cell renal-cell carcinoma

    Kufukihara, R., Tanaka, N., Takamatsu, K., Niwa, N., Fukumoto, K., Yasumizu, Y., Takeda, T., Matsumoto, K., Morita, S., Kosaka, T., Aimono, E., Nishihara, H., Mizuno, R. and Oya, M.

    Br J Cancer (British Journal of Cancer)  127 ( 6 ) 1133 - 1141 2022

    ISSN  00070920

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    BACKGROUND: Analysis of long noncoding RNA (lncRNA) localisation at both the tissue and subcellular levels can provide important insights into the cell types that are important for their function. METHODS: By applying new fluorescent in situ hybridisation technique called hybridisation chain reaction (HCR), we achieved a high-throughput lncRNA visualisation and evaluation of clinical samples. RESULTS: Assessing 1728 pairs of 16 lncRNAs and clear-cell renal-cell carcinoma (ccRCC) specimens, three lncRNAs (TUG1, HOTAIR and CDKN2B-AS1) were associated with ccRCC prognosis. Furthermore, we derived a new lncRNA risk group of ccRCC prognosis by combining the expression levels of these three lncRNAs. Examining genomic alterations underlying this classification revealed prominent features of tumours that could serve as potential biomarkers for targeting lncRNAs. We then derived combination of HCR with expansion microscopy and visualised nanoscale-resolution HCR signals in cell nuclei, uncovering intracellular colocalization of three lncRNA (TUG1, HOTAIR and CDKN2B-AS1) signals such as those located intra- or out of the nucleus or nucleolus in cancer cells. CONCLUSION: LncRNAs are expected to be desirable noncoding targets for cancer diagnosis or treatments. HCR involves plural probes consisting of small DNA oligonucleotides, clinically enabling us to detect cancerous lncRNA signals simply and rapidly at a lower cost.

  • Multiplexed single-cell pathology reveals the association of CD8 T-cell heterogeneity with prognostic outcomes in renal cell carcinoma

    Murakami, T., Tanaka, N., Takamatsu, K., Hakozaki, K., Fukumoto, K., Masuda, T., Mikami, S., Shinojima, T., Kakimi, K., Tsunoda, T., Sawada, K., Imamura, T., Mizuno, R. and Oya, M.

    Cancer Immunol Immunother (Cancer Immunology, Immunotherapy)  70 ( 10 ) 3001 - 3013 2021.10

    ISSN  03407004

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    Despite the high sensitivity of renal cell carcinoma (RCC) to immunotherapy, RCC has been recognized as an unusual disease in which CD8(+) T-cell infiltration into the tumor beds is related to a poor prognosis. To approach the inner landscape of immunobiology of RCC, we performed multiplexed seven-color immunohistochemistry (CD8, CD39, PD-1, Foxp3, PD-L1, and pan-cytokeratin AE1/AE3 with DAPI), which revealed the automated single-cell counts and calculations of individual cell-to-cell distances. In total, 186 subjects were included, in which CD39 was used as a marker for distinguishing tumor-specific (CD39(+)) and bystander (CD39(-)) T-cells. Our clear cell RCC cohort also revealed a poor prognosis if the tumor showed increased CD8(+) T-cell infiltration. Intratumoral CD8(+)CD39(+) T-cells as well as their exhausted CD8(+)CD39(+)PD-1(+) T-cells in the central tumor areas enabled the subgrouping of patients according to malignancy. Analysis using specimens post-antiangiogenic treatment revealed a dramatic increase in proliferative Treg fraction Foxp3(+)PD-1(+) cells, suggesting a potential mechanism of hyperprogressive disease after uses of anti-PD-1 antibody. Our cell-by-cell study platform provided spatial information on tumors, where bystander CD8(+)CD39(-) T-cells were dominant in the invasive margin areas. We uncovered a potential interaction between CD8(+)CD39(+)PD-1(+) T-cells and Foxp3(+)PD-1(+) Treg cells due to cell-to-cell proximity, forming a spatial niche more specialized in immunosuppression under PD-1 blockade. A paradigm shift to the immunosuppressive environment was more obvious in metastatic lesions; rather the infiltration of Foxp3(+) and Foxp3(+)PD-1(+) Treg cells was more pronounced. With this multiplexed single-cell pathology technique, we revealed further insight into the immunobiological standing of RCC.

  • Three-dimensional single-cell imaging for the analysis of RNA and protein expression in intact tumour biopsies

    Tanaka, N., Kanatani, S., Kaczynska, D., Fukumoto, K., Louhivuori, L., Mizutani, T., Kopper, O., Kronqvist, P., Robertson, S., Lindh, C., Kis, L., Pronk, R., Niwa, N., Matsumoto, K., Oya, M., Miyakawa, A., Falk, A., Hartman, J., Sahlgren, C., Clevers, H. and Uhlén, P.

    Nat Biomed Eng 4 ( 9 ) 875 - 888 2020.09

    ISSN  2157-846x

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    Microscopy analysis of tumour samples is commonly performed on fixed, thinly sectioned and protein-labelled tissues. However, these examinations do not reveal the intricate three-dimensional structures of tumours, nor enable the detection of aberrant transcripts. Here, we report a method, which we name DIIFCO (for diagnosing in situ immunofluorescence-labelled cleared oncosamples), for the multimodal volumetric imaging of RNAs and proteins in intact tumour volumes and organoids. We used DIIFCO to spatially profile the expression of diverse coding RNAs and non-coding RNAs at the single-cell resolution in a variety of cancer tissues. Quantitative single-cell analysis revealed spatial niches of cancer stem-like cells, and showed that the niches were present at a higher density in triple-negative breast cancer tissue. The improved molecular phenotyping and histopathological diagnosis of cancers may lead to new insights into the biology of tumours of patients.

  • Umbilical closure using 2-octyl cyanoacrylate in transumbilical laparoscopic adrenalectomy: A randomized controlled trial

    Fukumoto, K., Miyajima, A., Matsumoto, K., Kobayashi, H., Niwa, N., Hongo, H., Kurihara, I., Kikuchi, E. and Oya, M.

    Int J Urol 27 ( 8 ) 670 - 675 2020.08

    ISSN  0919-8172

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    OBJECTIVES: To evaluate postoperative pain and esthetic outcomes in patients undergoing transumbilical laparoscopic adrenalectomy with wound closure using 2-octyl cyanoacrylate. METHODS: A total of 26 patients who underwent laparoscopic adrenalectomy with the transumbilical approach and agreed to participate in this study were included. Patients were randomly divided into two groups: the 2-octyl cyanoacrylate group (Glue group) or the non-use group (non-Glue group). A single surgeon (AM) carried out all procedures between 2014 and 2017. RESULTS: There were no significant differences in the clinical background of the Glue and non-Glue groups. The number of patients with moderate or high levels of pain in the resting/moving period on postoperative days 1, 2 and 3 was 6/10 (46%/77%), 6/9 (46%/69%) and 3/5 (23%/38%) in the non-Glue group, and 5/7 (38%/54%), 2/7 (15%/54%) and 1/3 (8%/23%) in the Glue group. These differences were not significant. In the subgroup analysis of patients aged <50 years, the numbers were 4/6 (57%/86%), 5/7 (71%/100%) and 3/5 (43%/71%) in the non-Glue group, and 3/4 (33%/44%), 1/4 (11%/44%) and 0/1 (0%/11%) in the Glue group in the resting/moving period. On postoperative days 2 and 3, these differences were significant (P = 0.035 and 0.037 in the resting period, and P = 0.017 and 0.013 in the moving period). CONCLUSIONS: 2-octyl cyanoacrylate can be used safely for laparoscopic adrenalectomy with the transumbilical approach, and might be useful for reducing postoperative pain in patients aged <50 years.

  • Bacillus Calmette-Guérin-unresponsive non-muscle-invasive bladder cancer: Its definition and future therapeutic strategies

    Kikuchi, E., Hayakawa, N., Fukumoto, K., Shigeta, K. and Matsumoto, K.

    Int J Urol 27 ( 2 ) 108 - 116 2020.02

    ISSN  0919-8172

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    Bacillus Calmette-Guérin induction with or without maintenance is the gold standard therapy for intermediate-/high-risk non-muscle-invasive bladder cancer; however, one-third of patients treated with adequate bacillus Calmette-Guérin therapy do not achieve sufficient responses, and this is referred to as "bacillus Calmette-Guérin failure." The term, bacillus Calmette-Guérin failure, is ambiguous and includes a very heterogeneous population of patients. By strictly focusing on patients who are unlikely to benefit from additional bacillus Calmette-Guérin therapy and who need to be treated with radical cystectomy, the new concept of "bacillus Calmette-Guérin unresponsive" was recently proposed, and might accelerate the development of novel therapeutic options for bacillus Calmette-Guérin-unresponsive disease. A promising therapeutic strategy for bacillus Calmette-Guérin-unresponsive disease is the blockade of the programmed cell death-1/programmed cell death-ligand 1 pathway, which is considered to be activated by bacillus Calmette-Guérin therapy. Several large clinical trials have been carried out to assess the potential of programmed cell death-1/programmed cell death-ligand 1 blockade in bacillus Calmette-Guérin-naïve high-risk non-muscle-invasive bladder cancer and bacillus Calmette-Guérin-unresponsive disease. Furthermore, clinical trials that are targeting bacillus Calmette-Guérin-unresponsive disease with other strategies, such as vaccines, gene therapy, and targeted and cytotoxic therapies, are ongoing. The findings of these trials are awaited in order to establish appropriate bladder-sparing approaches for patients with bacillus Calmette-Guérin-unresponsive disease.

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

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Presentations 【 Display / hide 】

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

  • The Use of Artificial Intelligence in Urology Robotic-Assisted Surgery and the Construction of Clinically Applicable Systems

    2024.04
    -
    2026.03

    若手研究, Principal investigator

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Courses Taught 【 Display / hide 】

  • LECTURE SERIES, UROLOGY

    2024

  • LECTURE SERIES, UROLOGY

    2023

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