KYUNO Daisuke

写真a

Affiliation

School of Medicine, Department of Pathology (2)

Job title

Assistant Professor

Profile

癌研究、消化器外科手術に関するトランスレーショナルな研究を積極的に実施したいと考えております。

Education 【 display / non-display

  • 2009
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    2013

    Sapporo Medical University   Graduate School of Medicine   外科腫瘍学・消化器外科治療学  

  • 1999
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    2005

    Sapporo Medical University   医学部   医学科  

Degree 【 display / non-display

  • 2013.03   Sapporo Medical University   M.D. and Ph.D.

Research Experience 【 display / non-display

  • 2020.02
    -
    Now

    Sapporo Medical University   Department of Pathology   Assistant professor

  • 2019.04
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    2020.01

    Sapporo Medical University   Department of Surgery, Surcial Oncology and Science   Clinical Associate

  • 2018.12
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    2019.03

    Sapporo Medical University   Department of Surgery, Surgical Oncology and Science   Clinical Fellow

  • 2016.09
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    2018.11

    Heidelberg University Hospital   General, Visceral and Transplantation Surgery, Section Surgical Research   Visiting Research Scholar

  • 2015.04
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    2016.08

    Sapporo Medical University   Department of Surgery, Surgical Oncology and Sciencce   Clinical Associate

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Professional Memberships 【 display / non-display

  • 2023
    -
    Now

    The Japanese Society for Clinical Molecular Morphology

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    日本病理学会

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    日本消化器外科学会

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    日本癌治療学会

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    国際外科学会

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Research Areas 【 display / non-display

  • Life sciences   Digestive surgery  

  • Life sciences   Tumor diagnostics and therapeutics  

  • Life sciences   Experimental pathology  

  • Life sciences   General surgery, pediatric surgery  

  • Life sciences   Molecular biology  

Affiliation 【 display / non-display

  • Sapporo Medical University   消化器・総合、乳腺・内分泌外科  

  • 札幌医科大学   病理学第二講座   助教  

 

Papers 【 display / non-display

  • A case report of carcinoma of the papilla of Vater associated with a hyperplasia-dysplasia-carcinoma sequence by pancreaticobiliary maljunction.

    Takahiro Korai, Yasutoshi Kimura, Kazunori Watanabe, Siew-Kee Low, Masafumi Imamura, Minoru Nagayama, Kazuharu Kukita, Takeshi Murakami, Toru Kato, Yuta Kondo, Daisuke Kyuno, Taro Sugawara, Ayako Murota, Yujiro Kawakami, Yoshiharu Masaki, Hiroshi Nakase, Ichiro Takemasa

    World journal of surgical oncology   22 ( 1 ) 63 - 63  2024.02  [International journal]

     View Summary

    BACKGROUND: Pancreaticobiliary maljunction (PBM) is a known risk factor for biliary tract cancer. However, its association with carcinoma of the papilla of Vater (PVca) remains unknown. We report a case with PVca that was thought to be caused by the hyperplasia-dysplasia-carcinoma sequence, which is considered a mechanism underlying PBM-induced biliary tract cancer. CASE PRESENTATION: A 70-year-old woman presented with white stool and had a history of cholecystectomy for the diagnosis of a non-dilated biliary tract with PBM. Esophagogastroduodenoscopy revealed a tumor in the papilla of Vater, and PVca was histologically proven by biopsy. We finally diagnosed her with PVca concurrent with non-biliary dilated PBM (cT1aN0M0, cStage IA, according to the Union for International Cancer Control, 8th edition), and subsequently performed subtotal stomach-preserving pancreaticoduodenectomy. Pathological findings of the resected specimen revealed no adenomas and dysplastic and hyperplastic mucosae in the common channel slightly upstream of the main tumor, suggesting a PBM related carcinogenic pathway with hyperplasia-dysplasia-carcinoma sequence. Immunostaining revealed positivity for CEA. CK7 positivity, CK20 negativity, and MUC2 negativity indicated that this PVca was of the pancreatobiliary type. Genetic mutations were exclusively detected in tumors and not in normal tissues, and bile ducts from formalin-fixed paraffin-embedded samples included mutated-ERBB2 (Mutant allele frequency, 81.95%). Moreover, of the cell-free deoxyribonucleic acid (cfDNA) extracted from liquid biopsy mutated-ERBB2 was considered the circulating-tumor deoxyribonucleic acid (ctDNA) of this tumor. CONCLUSIONS: Herein, we report the first case of PVca with PBM potentially caused by a "hyperplasia-dysplasia-carcinoma sequence" detected using immunostaining and next-generation sequencing. Careful follow-up is required if pancreaticobiliary reflux persists, considering the possible development of PVca.

    DOI PubMed

  • Eribulin is an immune potentiator in breast cancer that upregulates human leukocyte antigen class I expression via the induction of NOD-like receptor family CARD domain-containing 5.

    Asaka Wada, Yoshihiko Hirohashi, Goro Kutomi, Kenji Murata, Sadahiro Iwabuchi, Yuka Mizue, Aiko Murai, Daisuke Kyuno, Hiroaki Shima, Tomoyuki Minowa, Kenta Sasaki, Terufumi Kubo, Takayuki Kanaseki, Tomohide Tsukahara, Munehide Nakatsugawa, Shinichi Hashimoto, Makoto Osanai, Toshihiko Torigoe, Ichiro Takemasa

    Cancer science   114 ( 12 ) 4511 - 4520  2023.12  [International journal]

     View Summary

    Eribulin inhibits microtubule polymerization and improves the overall survival of patients with recurrent metastatic breast cancer. A subgroup analysis revealed a low neutrophil to lymphocyte ratio (NLR) (<3) to be a prognostic factor of eribulin treatment. We thus hypothesized that eribulin might be related to the immune response for breast cancer cells and we analyzed the effects of eribulin on the immune system. Immunohistochemical staining revealed that human leukocyte antigen (HLA) class I expression was increased in clinical samples after eribulin treatment. In vitro assays revealed that eribulin treatment increased HLA class I expression in breast cancer line cells. RNA-sequencing demonstrated that eribulin treatment increased the expression of the NOD-like family CARD domain-containing 5 (NLRC5), a master regulator of HLA class I expression. Eribulin treatment increased the NY-ESO-1-specific T-cell receptor (TCR) transduced T (TCR-T) cell response for New York oesophageal squamous cell carcinoma 1 (NY-ESO-1) overexpressed breast cancer cells. The eribulin and TCR-T combined therapy model revealed that eribulin and immunotherapy using TCR-T cells has a synergistic effect. In summary, eribulin increases the expression of HLA class 1 via HLA class 1 transactivatior NLRC5 and eribulin combination with immunotherapy can be effective for the treatment of breast cancer.

    DOI PubMed

  • Common pathological findings in the heart in COVID-19-related sudden death cases: An autopsy case series

    Daisuke Kyuno, Masatoshi Tateno, Yusuke Ono, Kazufumi Magara, Kumi Takasawa, Akira Takasawa, Makoto Osanai

    Heliyon    2023.10

    DOI

  • A novel approach to diagnosing crystal-storing histiocytosis: utility of scanning electron microscopy for formalin-fixed paraffin-embedded tissue specimens.

    Magara K, Akira Takasawa, Kikuchi K, Sugawara T, Murakami T, Kyuno D, Ono Y, Takasawa K, Numata Y, Sasaki S, Nakase H, Hasegawa T, Osanai M

    Medical molecular morphology    2023.07  [Domestic journal]

     View Summary

    Crystal-storing histiocytosis (CSH) is a rare disorder that shows infiltration of histiocytes with an aberrant cytoplasmic accumulation of crystalline structures and is often accompanied by lymphoproliferative-plasma cell disorders (LP-PCD) as background diseases. The diagnosis of CSH requires identification of crystalline structures that accumulate in the infiltrating histiocytes, which may be challenging by optical microscopy alone. In this case report, we describe an atypical course of systemic CSH with multifocal fibrosclerosis of an unknown background disease that was diagnosed by ultrastructural observation, including transmission electron microscopy (TEM) and scanning electron microscopy (SEM), in pathological autopsy. In addition, crystalline structures were successfully identified by scanning electron microscopic observations using formalin-fixed and paraffin-embedded (FFPE) tissue from biopsy specimens taken before death. Since CSH was identified by SEM in a tiny biopsy specimen, observation of histiocytic infiltrative lesions by SEM using FFPE tissue may lead to early detection of and initiation of treatment for CSH.

    DOI PubMed

  • Invasive pulmonary aspergillosis with candidiasis: usefulness of molecular and ultrastructural morphological analysis on FFPE tissue for invasive fungal infections.

    Yusaku Kubota, Akira Takasawa, Yusuke Ono, Tomoyuki Aoyama, Kumi Takasawa, Akinori Tada, Kazufumi Magara, Taro Murakami, Fuminori Daimon, Soh Yamamoto, Shota Sato, Yutaro Hiratsuka, Daisuke Kyuno, Makoto Osanai

    Medical molecular morphology   56 ( 2 ) 144 - 151  2023.06  [Domestic journal]

     View Summary

    Invasive pulmonary aspergillosis (IPA) is one of the most frequent forms of invasive fungal infections (IFI); however, it is often difficult to identify the pathogenic fungal species and to select appropriate treatments for patients with IFI including IPA. Here, we describe the detailed pathophysiology of an autopsy case of severe respiratory failure due to IPA with candidiasis. The patient developed severe respiratory failure after influenza infection and died, and the autopsy revealed a mixed disease of IPA with candidiasis. In this study, in addition to the routine pathological examination, we further examined formalin-fixed paraffin-embedded (FFPE) tissues by scanning electron microscopy (SEM) and partial genomic DNA sequencing. Although optical microscopy alone was insufficient to identify the pathogenic organisms, SEM clearly depicted the characteristic morphology of Aspergillus sp. and Candida sp. as closely overlapping in a nested fashion, providing evidence of mixed infection of both fungal species in a focal site. The technique using FFPE tissue in combination with ultrastructural observation by SEM, elemental analysis by SEM-EDX, and DNA sequencing is promising for analyzing the pathophysiology of IFI.

    DOI PubMed

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Books and Other Publications 【 display / non-display

  • インフォームドコンセントのための図説シリーズ 膵がん 改訂3版

    ( Part: Contributor, 術後のフォローアップの方法)

Misc 【 display / non-display

  • 膵癌患者の予後と癌進展におけるJAM-Aの役割(Junctional Adhesion Molecule-A may play a role in the progression of pancreatic cancer)

    及能 大輔, 高澤 啓, 高澤 久美, 真柄 和史, 小山内 誠

    日本癌学会総会記事 ( (一社)日本癌学会 )  81回   J - 2053  2022.09

  • 膵・胆管合流異常関連胆道癌症例の検討

    古来 貴寛, 木村 康利, 今村 将史, 永山 稔, 久木田 和晴, 及能 大輔, 村上 武志, 加藤 透, 近藤 裕太, 竹政 伊知朗

    日本膵・胆管合流異常研究会プロシーディングス ( 日本膵・胆管合流異常研究会 )  46   33 - 34  2023.09

  • 癌幹細胞マーカーに対する自己抗体を利用した乳癌患者の予後予測(Prediction of Prognosis in Breast Cancer Patients Using Autoantibodies to Cancer Stem Cell Markers)

    及能 大輔, 廣橋 良彦, 和田 朝香, 島 宏彰, 九冨 五郎, 真柄 和史, 高澤 久美, 高澤 啓, 竹政 伊知朗, 小山内 誠

    日本癌学会総会記事 ( (一社)日本癌学会 )  82回   2116 - 2116  2023.09

  • MPNSTにおけるPVR発現の意義

    中橋 尚也, 高澤 啓, 江森 誠人, 高澤 久美, 太田 未咲, 真柄 和史, 小野 佑輔, 及能 大輔, 杉田 真太朗, 長谷川 匡, 小山内 誠

    日本整形外科学会雑誌 ( (公社)日本整形外科学会 )  97 ( 8 ) S1975 - S1975  2023.08

  • エリブリンはヒト白血球抗原クラスIのアップレギュレーションによる乳癌の免疫増強因子である(Eribulin is an immune potentiator in breast cancer by up-regulation of human leukocyte antigen class I)

    和田 朝香, 九冨 五郎, 廣橋 良彦, 島 宏彰, 及能 大輔, 空閑 陽子, 鳥越 俊彦, 竹政 伊知朗

    日本乳癌学会総会プログラム抄録集 ( (一社)日本乳癌学会 )  31回   66 - 66  2023.06

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Awards 【 display / non-display

  • 膵臓病研究奨励賞

    2022   日本膵臓病研究財団   タイト結合分子により促進される膵癌の進展機序の解明

  • Young investigator award

    2019.11   Japanese digestive disease week   Exosomes transfer information of cancer cells; reprogramming of nonmetastasizing tumor cells and therapeutic efficacy

    Winner: Daisuke Kyuno

  • Young Investigator Award

    2015   国際外科学会日本部会  

    Winner: 及能大輔

  • 研究奨励賞

    2013   日本消化器癌発生学会   ヒト正常膵管上皮細胞及び膵癌細胞株を用いたPKCシグナル分子を標的とした膵癌分子標的治療の基礎的研究PKCα阻害作用とタイト結合発現調節機構

    Winner: 及能大輔

  • Young Investigator Award

    2012   International Symposium on Pancreas Cancer  

    Winner: Daisuke Kyuno

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Research Projects 【 display / non-display

  • IPMN発生機序に基づいた転写共役因子YAPの役割の解明と臨床応用を目指した研究

    基盤研究(C)

    Project Year :

    2022.04
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    2025.03
     

    山口 洋志, 今村 将史, 永山 稔, 竹政 伊知朗, 及能 大輔, 木村 康利

  • イムノヒストグラムを用いた直腸癌に対する術前化学療法の新規治療効果予測法の開発

    基盤研究(C)

    Project Year :

    2022.04
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    2025.03
     

    奥谷 浩一, 秋月 恵美, 廣橋 良彦, 竹政 伊知朗, 佐藤 雄, 石井 雅之, 浜部 敦史, 沖田 憲司, 及能 大輔

  • Visualization of Cholangiocarcinoma Targeting Claudin 18.2 by Near-Infrared Fluorescently Labeled Antibody

    Grant-in-Aid for Scientific Research (C)

    Project Year :

    2021.04
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    2024.03
     

    及能 大輔, 高澤 啓, 木村 康利

     View Summary

    癌細胞の細胞表面分子において、正常上皮細胞と異なり過剰発現する分子は、適切な抗体の投与下で診断や治療の標的となりえる。胆道癌の細胞表面では、細胞接着に関与するタイト結合分子claudin18(cld18)の過剰発現が報告されている。そこで、cld18が胆道癌において病理学的診断、根治術後の予後へどのように関与するのかを調べた。胆道癌に対して根治的切除術を施行した66例の癌部、異型上皮(BilIN)、正常上皮について免疫染色を行い、cld18の発現強度(0-3)と範囲(0-10)の積を発現スコアとして算出し、病理学的診断に関する有効性を解析した。さらに、癌部のcld18の発現強度と生命予後について生存分析で相関を解析した。 癌とBilINでは細胞膜上にcld18の発現がみられ、正常胆管上皮では発現がほぼみられなかった。cld18発現スコアは、癌、BiLINで正常上皮に比べ高値であり、癌とBiLINの間、またBiLIN-1, -2, -3の間で差は見られなかった。低分化癌で高分化癌よりも発現スコアの低下がみられた。発現スコアのcut offを6点とすると、癌/BilINと正常上皮の鑑別について感度0.96、特異度0.97であった。遠位胆管癌の切除術後の予後と発現スコアの間には相関はみられなかった。Cld18は胆道の癌細胞や異型上皮において高発現し、正常上皮細胞との鑑別に有用であることが示された。その発現機構の解析が、発癌機構の解明へとつながることが期待される。また、正常胆管と癌や異型上皮の鑑別に本技術を活用すべく、研究を続けている。

  • 経時的エクソソーム解析による膵癌術後早期再発ハイリスク症例診断法の開発

    基盤研究(C)

    Project Year :

    2020.04
    -
    2023.03
     

    今村 将史, 永山 稔, 竹政 伊知朗, 及能 大輔, 木村 康利, 山口 洋志

     View Summary

    ①後向き研究として、再発症例3例の血漿サンプルを収集した。 ②前向き研究として、2020年度は33例の血漿サンプルを収集し、同時に臨床データを整備している。 ③臨床研究論文の作成。当該研究に関連して、「膵癌術後早期再発に関連する臨床的リスク因子」について、当施設の過去の膵癌切除症例を解析し、論文を作成した。2021年3月末に「Cancers」に投稿し、現在revise中である。

  • 癌幹細胞マーカーSOX2に対する血中抗体を利用した乳癌の予後予測マーカーの開発と癌幹細胞標的療法の基盤的研究

    Project Year :

    2020.04
    -
    2021.04
     

    及能大輔, 竹政伊知朗, 九冨五郎, 島宏彰, 和田朝香, 里見蕗乃, 鳥越俊彦, 廣橋良彦

    Authorship: Principal investigator

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