Updated on 2026/06/18

Information

 

写真a

 
OTSUBO YOSHIKI
 
Organization
Kyushu University Hospital Breast Surgery (1) Assistant Professor
Title
Assistant Professor
External link

Research History

  •  Kyushu University Hospital Breast Surgery (1)  Assistant Professor 

    2026.4 - Present

Papers

  • 乳癌術後再発治療中に超急性に発症した傍腫瘍性小脳変性症の1例 Reviewed

    森崎 隆史, 中原 千晶, 中釜 英将, 落合 百合菜, 大坪 慶志輝, 林 早織, 久松 雄一, 佐藤 瑶, 溝口 公久, 中村 雅史, 久保 真

    乳癌の臨床   40 ( 5 )   355 - 362   2025.10   （ ISSN:0911-2251 ）

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    Language：Japanese   Publisher：(株)篠原出版新社  

    患者は71歳,女性.右乳癌に対して右乳房全切除術およびセンチネルリンパ節生検を施行し,術後補助化学療法を行ったが,1年半後に内胸リンパ節転移,肝転移を認め再発と診断した.Paclitaxel + Bevacizumab療法を施行し転移巣は消失したが,約2年後に肝転移が再出現し,同時に超急性に構音障害・体幹失調症状を認めた.病状は急速に進行し数日で寝たきりとなり,嚥下機能障害のため食事摂取困難となった.精査の結果,傍腫瘍性神経症候群による小脳変性症と診断した.免疫学的治療の効果は乏しかったが,trastuzumab deruxtecanによる化学療法を開始したところ,腫瘍が縮小し治療開始約1ヵ月後より構音障害,運動機能が急速に改善し,入院80日後に自宅退院した.乳癌治療中に原因不明の神経症候を認めた場合は,傍腫瘍性神経症候群を考慮する必要がある.(著者抄録)

  • Therapeutic Strategies Targeting Proline Isomerase (Pin1) for Triple Negative Breast Cancer Reviewed

    Mizoguchi, K; Kubo, M; Morisaki, T; Sato, Y; Hayashi, S; Otsubo, Y; Ochiai, Y; Koikawa, K; Nakamura, M

    CANCER SCIENCE   116   348 - 348   2025.1   （ ISSN:1347-9032 eISSN:1349-7006 ）

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  • Current status and characteristics of <i>BRCA</i> examination at our hospital Reviewed

    Mizoguchi Kimihisa, Morisaki Takafumi, Ochiai Yurina, Sato Yo, Otsubo Yoshiki, Hayashi Saori, Yamada Mai, Matsuzaki Sawako, Nakamura Masafumi, Kubo Makoto

    Journal of Hereditary Tumors   24 ( 2 )   142 - 146   2024.10   （ eISSN:24356808 ）

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    Language：Japanese   Publisher：The Japanese Society for Hereditary Tumors  

    <p>　Hereditary breast and ovarian cancer (HBOC) is an autosomal dominant form of cancer susceptibility syndrome, which is caused by germline pathological variants of<i> BRCA1</i> or<i> BRCA2</i> in the narrow sense of the term. The selection of patients for<i> BRCA</i> examination to confirm HBOC is based on the HBOC practice guidelines of the Japanese Organization for Comprehensive Treatment of Hereditary Breast and Ovarian Cancer and the testing criteria of the NCCN guidelines, which differ in some respects, and therefore, so do the test subjects. The criteria for testing are partially different between the two guidelines, so the target population for testing is also different. In this study, we examined the degree to which both testing criteria were met in 58 of 220 patients who were tested positive for <i>BRCA</i> between January 2019 and November 2022 at our hospital. The number of <i>BRCA1/2</i>-positive patients who did not meet the HBOC and NCCN guidelines did not differ significantly, but there were some patients who did not meet the criteria due to cancer or family history of cancer. We believe that the testing criteria should be reviewed in order to increase the number of <i>BRCA</i>-positive patients in the future.</p>

    DOI： 10.18976/jsht.24.2_142

    CiNii Research

  • 当院におけるBRCA遺伝学的検査の現状とその特徴 Reviewed

    溝口 公久, 森崎 隆史, 落合 百合菜, 佐藤 瑶, 大坪 慶志輝, 林 早織, 山田 舞, 松崎 佐和子, 中村 雅史, 久保 真

    遺伝性腫瘍   24 ( 2 )   142 - 146   2024.10

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    Language：Japanese   Publisher：(一社)日本遺伝性腫瘍学会  

    遺伝性乳癌卵巣癌(HBOC)は,狭義にはBRCA1あるいはBRCA2の生殖細胞系列の病的バリアントに起因する乳癌および卵巣癌をはじめとするがんの易罹患性症候群である.どのような人にHBOCの遺伝学的検査を提供するかは重要な課題である.HBOC確認のためのBRCA遺伝学的検査の対象者の選定として,日本遺伝性乳癌卵巣癌総合診療制度機構のHBOC診療ガイドラインとNCCNガイドラインの検査基準があるが,両者の基準は一部異なっている.今回,2019年1月～2022年11月に当院でBRCA遺伝学的検査を施行した220名のうち陽性であった58名を対象に,双方の検査基準をどの程度満たしているかを検討した.また,乳癌発症のBRCA1/2病的バリアント保持者30名についても傾向を調査した.双方の検査基準を満たさなかった人数に大きな差は見られなかったが,発症がんや家族歴によって基準を満たさない症例も一部見られた.今後はより多くのBRCA病的バリアントを広い上げるためにも検査基準の見直しが必要と考える.(著者抄録)

  • Microenvironmental changes in familial adenomatous polyposis during colorectal cancer carcinogenesis Reviewed

    Hisano, K; Mizuuchi, Y; Ohuchida, K; Kawata, J; Torata, N; Zhang, JH; Katayama, N; Tsutsumi, C; Nakamura, S; Okuda, S; Otsubo, Y; Tamura, K; Nagayoshi, K; Ikenaga, N; Shindo, K; Nakata, K; Oda, Y; Nakamura, M

    CANCER LETTERS   589   216822   2024.5   （ ISSN:0304-3835 eISSN:1872-7980 ）

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    Language：English   Publisher：Cancer Letters  

    Familial adenomatous polyposis (FAP) is a heritable disease that increases the risk of colorectal cancer (CRC) development because of heterozygous mutations in APC. Little is known about the microenvironment of FAP. Here, single-cell RNA sequencing was performed on matched normal tissues, adenomas, and carcinomas from four patients with FAP. We analyzed the transcriptomes of 56,225 unsorted single cells, revealing the heterogeneity of each cell type, and compared gene expression among tissues. Then we compared the gene expression with that of sporadic CRC. Furthermore, we analyzed specimens of 26 FAP patients and 40 sporadic CRC patients by immunohistochemistry. Immunosuppressiveness of myeloid cells, fibroblasts, and regulatory T cells was upregulated even in the early stages of carcinogenesis. CD8<sup>+</sup> T cells became exhausted only in carcinoma, although the cytotoxicity of CD8<sup>+</sup> T cells was gradually increased according to the carcinogenic step. When compared with those in the sporadic CRC microenvironment, the composition and function of each cell type in the FAP-derived CRC microenvironment had differences. Our findings indicate that an immunosuppressive microenvironment is constructed from a precancerous stage in FAP.

    DOI： 10.1016/j.canlet.2024.216822

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  • Beckwith-Wiedemann syndrome with juvenile fibrous nodules and lobular breast tumors: a case report and review of the literature Reviewed

    Sato, Y; Watanabe, Y; Morisaki, T; Hayashi, S; Otsubo, Y; Ochiai, Y; Mizoguchi, K; Takao, Y; Yamada, M; Mizuuchi, Y; Nakamura, M; Kubo, M

    SURGICAL CASE REPORTS   10 ( 1 )   69   2024.3   （ ISSN:2198-7793 ）

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  • Tumor-infiltrating monocytic myeloid-derived suppressor cells contribute to the development of an immunosuppressive tumor microenvironment in gastric cancer Reviewed

    Tsutsumi, C; Ohuchida, K; Katayama, N; Yamada, Y; Nakamura, S; Okuda, S; Otsubo, Y; Iwamoto, C; Torata, N; Horioka, K; Shindo, K; Mizuuchi, Y; Ikenaga, N; Nakata, K; Nagai, E; Morisaki, T; Oda, Y; Nakamura, M

    GASTRIC CANCER   27 ( 2 )   248 - 262   2024.3   （ ISSN:1436-3291 eISSN:1436-3305 ）

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    Language：English   Publisher：Gastric Cancer  

    Background: Gastric cancer (GC) is characterized by an immunosuppressive and treatment-resistant tumor immune microenvironment (TIME). Here, we investigated the roles of different immunosuppressive cell types in the development of the GC TIME. Methods: Single-cell RNA sequencing (scRNA-seq) and multiplex immunostaining of samples from untreated or immune checkpoint inhibitor (ICI)-resistant GC patients were used to examine the correlation between certain immunosuppressive cells and the prognosis of GC patients. Results: The results of the scRNA-seq analysis revealed that tumor-infiltrating monocytic myeloid-derived suppressor cells (TI-M-MDSCs) expressed higher levels of genes with immunosuppressive functions than other immunosuppressive cell types. Additionally, M-MDSCs in GC tissues expressed significantly higher levels of these markers than adjacent normal tissues. The M-MDSCs were most enriched in GC tissues relative to adjacent normal tissues. Among the immunosuppressive cell types assessed, the M-MDSCs were most enriched in GC tissues relative to adjacent normal tissues; moreover, their presence was most strongly associated with a poor prognosis. Immediate early response 3 (IER3), which we identified as a differentially expressed gene between M-MDSCs of GC and adjacent normal tissues, was an independent poor prognostic factor in GC patients (P = 0.0003). IER3<sup>+</sup> M-MDSCs expressed higher levels of genes with immunosuppressive functions than IER3<sup>−</sup> M-MDSCs and were abundant in treatment-resistant GC patients. Conclusions: The present study suggests that TI-M-MDSCs, especially IER3<sup>+</sup> ones, may play a predominant role in the development of the immunosuppressive and ICI-resistant GC TIME.

    DOI： 10.1007/s10120-023-01456-4

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  • 胃癌における免疫抑制性微小環境の形成に寄与する腫瘍浸潤単球系骨髄由来抑制細胞(Tumor-infiltrating monocytic myeloid-derived suppressor cells contribute to the development of an immunosuppressive tumor microenvironment in gastric cancer) Reviewed

    Tsutsumi Chikanori, Ohuchida Kenoki, Katayama Naoki, Yamada Yutaka, Nakamura Shoichi, Okuda Sho, Otsubo Yoshiki, Iwamoto Chika, Torata Nobuhiro, Horioka Kohei, Shindo Koji, Mizuuchi Yusuke, Ikenaga Naoki, Nakata Kohei, Nagai Eishi, Morisaki Takashi, Oda Yoshinao, Nakamura Masafumi

    Gastric Cancer   27 ( 2 )   248 - 262   2024.3   （ ISSN:1436-3291 ）

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    Language：English   Publisher：シュプリンガー・ジャパン(株)  

    胃癌の腫瘍免疫微小環境(TIME)の形成における各種免疫抑制細胞の役割を調べた。病理所見から胃癌および食道扁平上皮癌と診断された患者30例由来の検体を用いて、シングルセルRNAシーケンス(scRNA-seq)などを行い、特定の免疫抑制細胞と胃癌患者の予後との相関を調べた。scRNA-seq解析の結果、腫瘍浸潤単球系骨髄由来抑制細胞(TI-M-MDSC)は、他の免疫抑制細胞よりも免疫抑制機能を持つ遺伝子を高レベルで発現していた。さらに、胃癌組織中のM-MDSCは、隣接する正常組織よりもこれらのマーカーを有意に高発現していた。評価した免疫抑制細胞の中で、M-MDSCは隣接する正常組織と比較して胃癌組織で最も豊富に認められ、M-MDSCの存在は予後不良と強く関連していた。胃癌のM-MDSCと隣接する正常組織で発現が異なる遺伝子として同定されたimmediate early response 3(IER3)は、胃癌患者における独立した予後不良因子であった。

  • 思春期に線維性結節と乳房小葉腫瘍を発症したBeckwith-Wiedemann症候群　1症例報告と文献レビュー(Beckwith-Wiedemann syndrome with juvenile fibrous nodules and lobular breast tumors: a case report and review of the literature) Reviewed

    Sato Yo, Watanabe Yusuke, Morisaki Takafumi, Hayashi Saori, Otsubo Yoshiki, Ochiai Yurina, Mizoguchi Kimihisa, Takao Yuka, Yamada Mai, Mizuuchi Yusuke, Nakamura Masafumi, Kubo Makoto

    Surgical Case Reports   10   1 of 7 - 7 of 7   2024.3

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    Language：English   Publisher：(一社)日本外科学会  

    症例は17歳女児。出生時に臍帯ヘルニア、高インスリン血症、左半身の肥大を認め、Beckwith-Wiedemann症候群と診断されていた。左乳房が急速に肥大したため当科紹介となった。初診時の診察では、左乳房は右乳房より著しく大きく、触診で約10cm大の2つの腫瘤が確認された。マンモグラフィー、乳房超音波検査、造影CTなどでも左乳房に約10cmの腫瘍が2つ認められ、コア針生検の所見から急速に肥大する若年性線維腺腫(FA)と診断した。2つの乳房腫瘍を外科的に切除した。術後は容体安定し、術後2日後に退院した。切除標本の病理所見から、若年性FAと診断された。免疫組織化学染色では、FAの乳管上皮細胞にIGF2の過剰発現が認められた。臨床的特徴とIGF2の過剰発現から、11番染色体の父性片親性ダイソミーやimprinting center 1の過剰メチル化などの分子遺伝学的背景を含む11p15.5の異常が疑われた。術後9年後の時点で再発は認められていない。

  • Homologous Recombination Repair Gene Alterations Are Associated with Tumor Mutational Burden and Survival of Immunotherapy Reviewed

    Ito, M; Kubo, M; Kawaji, H; Otsubo, Y; Kurata, K; Abutani, H; Suyama, M; Oda, Y; Yoshizumi, T; Nakamura, M; Baba, E

    CANCERS   15 ( 23 )   2023.12   （ ISSN:2072-6694 eISSN:2072-6694 ）

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    Language：English   Publisher：Cancers  

    Background: Comprehensive genomic profiling (CGP) has become generally accepted practice in cancer care since CGP has become reimbursed by national healthcare insurance in Japan in 2019. However, its usefulness for cancer patients is insufficient for several reasons. Methods: In an observational clinical study of FoundationOne<sup>®</sup> CDx, potential biomarkers were explored and the cause of testing failure was investigated. A total of 220 cancer patients were enrolled in the study during the period from 2018 to 2019 at Kyushu University Hospital. Results: The primary tumor sites of the 220 cases were breast (115), colon (29), stomach (19), and pancreas (20). The present dataset suggested that homologous recombination repair (HRR) gene alterations were positively associated with tumor mutational burden-high (TMB-high) (p = 0.0099). A public dataset confirmed that patients with HRR gene alterations had a higher TMB and showed significantly longer survival of immunotherapy. In the present study, 18 cases failed sequencing. A lower percentage of tumor cell nuclei was the most common reason for testing failures (p = 0.037). Cases that received neoadjuvant chemotherapy before sampling tended to fail testing. Conclusions: HRR gene alterations can be a potential biomarker predicting TMB-high and a good response to immunotherapy. For successful sequencing, samples with lower percentages of tumor cell nuclei and previous neoadjuvant chemotherapy should be avoided.

    DOI： 10.3390/cancers15235608

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