Updated on 2024/11/27

Information

 

写真a

 
MOTOMURA YUSHI
 
Organization
Beppu Hospital Department of Radiology Assistant Professor
Title
Assistant Professor
Tel
0977271600
Profile
As a radiotherapist, he treats various malignant tumors and conducts research to overcome radiotherapy resistance in tumors. His research includes the detection of radiotherapy-resistant gene mutations in esophageal cancer from blood ("Elucidation of the genetic mechanism of post-CRT recurrence of esophageal cancer and study of the implementation of a panel-based ctDNA evaluation method" ）
External link

Research Interests・Research Keywords

  • Research theme： Elucidation of the immune microenvironment involved in resistance to chemoradiotherapy for esophageal cancer using spatial gene expression analysis

    Keyword： Esophageal cancer, Chemoradiotherapy, Treatment resistance, Spatial gene expression analysis

    Research period： 2022.5 - 2024.5

  • Research theme： Elucidation of genetic mechanisms of post-CRT recurrence in esophageal cancer and implementation of ctDNA evaluation method by panel

    Keyword： Esophageal cancer,Radiotherapy,ctDNA,Radiation therapy resistance

    Research period： 2019.5 - 2021.5

Awards

  • 令和２年度別府市医師会学術集会　若手臨床医賞

    2021.2   別府医師医師会  

Papers

  • 集学的治療を行い、アテゾリズマブ+ベバシズマブ併用療法によって完全奏効を達成した90歳の肝細胞癌再発患者の症例(Successful multidisciplinary treatment with complete response to atezolizumab plus bevacizumab in a 90-year-old patient with hepatocellular carcinoma recurrence)

    Hosoda Kiyotaka, Toshima Takeo, Takahashi Junichi, Yonemura Yusuke, Hisamatsu Yuichi, Hirose Kosuke, Masuda Takaaki, Motomura Yushi, Abe Tadashi, Ando Yuki, Dairaku Katsushi, Nakano Yusuke, Hashimoto Masahiro, Hiraki Yoshiki, Soejima Yuji, Yoshizumi Tomoharu, Mimori Koshi

    International Cancer Conference Journal   12 ( 4 )   274 - 278   2023.10

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

    症例は90歳女性。非B非C型肝炎であり、18ヵ月前に原発性肝細胞癌に対して腹腔鏡下肝切除術が施行された。術後6ヵ月、肝細胞癌再発に対して経カテーテル的肝動脈化学塞栓療法(TACE)が施行されたが、その1年後に2回目の再発が認められた。レンバチニブ(LEN)8mg/日投与を開始したところ、1週間後に極度の疲労や食欲不振などの重篤な有害事象(AE)が出現し、投与量を4mg/日に減量したがAEの管理は困難であった。そこで、LEN導入から1ヵ月後に化学療法をアテゾリズマブ+ベバシズマブ併用療法に変更した。その結果、副作用はほとんど認められず、腫瘍の退縮が認められた。本レジメンを8ヵ月間、10サイクル続け、最終的に完全奏効(CR)を達成した。CR達成後1年経過しても再発はみられていない。

  • Successful multidisciplinary treatment with complete response to atezolizumab plus bevacizumab in a 90-year-old patient with hepatocellular carcinoma recurrence

    Hosoda, K; Toshima, T; Takahashi, J; Yonemura, Y; Hisamatsu, Y; Hirose, K; Masuda, T; Motomura, Y; Abe, T; Ando, Y; Dairaku, K; Nakano, Y; Hashimoto, M; Hiraki, Y; Soejima, Y; Yoshizumi, T; Mimori, K

    INTERNATIONAL CANCER CONFERENCE JOURNAL   12 ( 4 )   274 - 278   2023.10   （ ISSN:2192-3183 ）

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  • Convergent genomic diversity and novel BCAA metabolism in intrahepatic cholangiocarcinoma

    Kitagawa, A; Osawa, T; Noda, M; Kobayashi, Y; Aki, S; Nakano, Y; Saito, T; Shimizu, D; Komatsu, H; Sugaya, M; Takahashi, J; Kosai, K; Takao, S; Motomura, Y; Sato, K; Hu, QJ; Fujii, A; Wakiyama, H; Tobo, T; Uchida, H; Sugimachi, K; Shibata, K; Utsunomiya, T; Kobayashi, S; Ishii, H; Hasegawa, T; Masuda, T; Matsui, Y; Niida, A; Soga, T; Suzuki, Y; Miyano, S; Aburatani, H; Doki, Y; Eguchi, H; Mori, M; Nakayama, KI; Shimamura, T; Shibata, T; Mimori, K

    BRITISH JOURNAL OF CANCER   128 ( 12 )   2206 - 2217   2023.6   （ ISSN:0007-0920 eISSN:1532-1827 ）

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    Language：English   Publisher：British Journal of Cancer  

    Background: Driver alterations may represent novel candidates for driver gene-guided therapy; however, intrahepatic cholangiocarcinoma (ICC) with multiple genomic aberrations makes them intractable. Therefore, the pathogenesis and metabolic changes of ICC need to be understood to develop new treatment strategies. We aimed to unravel the evolution of ICC and identify ICC-specific metabolic characteristics to investigate the metabolic pathway associated with ICC development using multiregional sampling to encompass the intra- and inter-tumoral heterogeneity. Methods: We performed the genomic, transcriptomic, proteomic and metabolomic analysis of 39–77 ICC tumour samples and eleven normal samples. Further, we analysed their cell proliferation and viability. Results: We demonstrated that intra-tumoral heterogeneity of ICCs with distinct driver genes per case exhibited neutral evolution, regardless of their tumour stage. Upregulation of BCAT1 and BCAT2 indicated the involvement of ‘Val Leu Ile degradation pathway’. ICCs exhibit the accumulation of ubiquitous metabolites, such as branched-chain amino acids including valine, leucine, and isoleucine, to negatively affect cancer prognosis. We revealed that this metabolic pathway was almost ubiquitously altered in all cases with genomic diversity and might play important roles in tumour progression and overall survival. Conclusions: We propose a novel ICC onco-metabolic pathway that could enable the development of new therapeutic interventions. [Figure not available: see fulltext.]

    DOI： 10.1038/s41416-023-02256-4

    Web of Science

    Scopus

    PubMed

  • Successful multidisciplinary treatment with complete response to atezolizumab plus bevacizumab in a 90-year-old patient with hepatocellular carcinoma recurrence

    International Cancer Conference Journal   2023.6

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  • Transducin beta-like 2 (TBL2) on chromosome 7 is a candidate driver gene of lung adenocarcinoma (LUAD)

    Ono, Y; Masuda, T; Kosai, K; Shibuta, S; Miyata, Y; Ando, Y; Motomura, Y; Abe, T; Takahashi, J; Hisamatsu, Y; Toshima, T; Yonemura, Y; Takenaka, T; Yoshizumi, T; Mimori, K

    CANCER SCIENCE   114   1843 - 1843   2023.2   （ ISSN:1347-9032 eISSN:1349-7006 ）

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  • Identification of candidate driver gene C3orf1 by chromosome copy number analysis in ESCC

    Hiraki, Y; Masuda, T; Motomura, Y; Dairaku, K; Mochizuki, K; Abe, T; Ando, Y; Takahashi, J; Nakano, Y; Hashimoto, M; Hosoda, K; Hisamatsu, Y; Toshima, T; Yonemura, Y; Mimori, K

    CANCER SCIENCE   114   2050 - 2050   2023.2   （ ISSN:1347-9032 eISSN:1349-7006 ）

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  • Genomic characterizations of Japanese breast cancer

    Ando, Y; Masuda, T; Hosoda, K; Hashimoto, M; Nakano, Y; Dairaku, K; Mochizuki, K; Abe, T; Hiraki, Y; Motomura, Y; Takahashi, J; Hisamatsu, Y; Toshima, T; Yonemura, Y; Mimori, K

    CANCER SCIENCE   114   2162 - 2162   2023.2   （ ISSN:1347-9032 eISSN:1349-7006 ）

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  • Dynamic changes in peripheral systemic immunity markers during various chemotherapies in advanced breast cancer

    Masuda, T; Ando, Y; Motomura, Y; Abe, T; Hashimoto, M; Nakano, Y; Dairaku, K; Hiraki, Y; Hosoda, K; Takahashi, J; Hisamatsu, Y; Toshima, T; Yonemura, Y; Mimori, K

    CANCER SCIENCE   114   2151 - 2151   2023.2   （ ISSN:1347-9032 eISSN:1349-7006 ）

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  • Convergent genomic diversity and novel BCAA metabolism in intrahepatic cholangiocarcinoma Invited Reviewed International journal

    Kitagawa A, Osawa T, Noda M, Kobayashi Y, Aki S, Nakano Y, Saito T, Shimizu D, Komatsu H, Sugaya M, Takahashi J, Kosai K, Takao S, Motomura Y, Sato K, Hu Q, Fujii A, Wakiyama H, Tobo T, Uchida H, Sugimachi K, Shibata K, Utsunomiya T, Kobayashi S, Ishii H, Hasegawa T, Masuda T, Matsui Y, Niida A, Soga T, Suzuki Y, Miyano S, Aburatani H, Doki Y, Eguchi H, Mori M, Nakayama KI, Shimamura T, Shibata T, Mimori K.

    British Journal of Cancer   2023.1

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

    Background
    Driver alterations may represent novel candidates for driver gene-guided therapy; however, intrahepatic cholangiocarcinoma (ICC) with multiple genomic aberrations makes them intractable. Therefore, the pathogenesis and metabolic changes of ICC need to be understood to develop new treatment strategies. We aimed to unravel the evolution of ICC and identify ICC-specific metabolic characteristics to investigate the metabolic pathway associated with ICC development using multiregional sampling to encompass the intra- and inter-tumoral heterogeneity.

    Methods
    We performed the genomic, transcriptomic, proteomic and metabolomic analysis of 39–77 ICC tumour samples and eleven normal samples. Further, we analysed their cell proliferation and viability.

    Results
    We demonstrated that intra-tumoral heterogeneity of ICCs with distinct driver genes per case exhibited neutral evolution, regardless of their tumour stage. Upregulation of BCAT1 and BCAT2 indicated the involvement of ‘Val Leu Ile degradation pathway’. ICCs exhibit the accumulation of ubiquitous metabolites, such as branched-chain amino acids including valine, leucine, and isoleucine, to negatively affect cancer prognosis. We revealed that this metabolic pathway was almost ubiquitously altered in all cases with genomic diversity and might play important roles in tumour progression and overall survival.

    Conclusions
    We propose a novel ICC onco-metabolic pathway that could enable the development of new therapeutic interventions.

    Other Link： https://www.nature.com/articles/s41416-023-02256-4#citeas

  • Clinical significance of SETBP1 expression in breast cancer.

    Ando, Y; Masuda, T; Hayashi, N; Mochizuki, K; Abe, T; Saito, H; Ozato, Y; Nakano, T; Koike, K; Motomura, Y; Takahashi, J; Toshima, T; Hisamatsu, Y; Yonemura, Y; Mimori, K

    CANCER SCIENCE   113   741 - 741   2022.2   （ ISSN:1347-9032 eISSN:1349-7006 ）

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  • The evolving genomic landscape of esophageal squamous cell carcinoma resistant to chemoradiotherapy

    Hirata, H; Niida, A; Masuda, T; Kageyama, SI; Motomura, Y; Akimoto, T; Mimori, K

    CANCER SCIENCE   113   470 - 470   2022.2   （ ISSN:1347-9032 eISSN:1349-7006 ）

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  • Low expression of transmembrane glycoprotein GPA33 is a poor prognostic factor in colorectal cancer.

    Abe, T; Masuda, T; Saito, H; Dairaku, K; Hashimoto, M; Nakano, Y; Hiraki, Y; Mochizuki, K; Ozato, Y; Ando, Y; Nakano, T; Koike, K; Takahashi, J; Motomura, Y; Toshima, T; Mimori, K

    CANCER SCIENCE   113   455 - 455   2022.2   （ ISSN:1347-9032 eISSN:1349-7006 ）

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  • High expression of the glycolytic enzyme gene PGK1 is a prognostic factor in esophageal cancer

    Saito, H; Masuda, T; Mochizuki, K; Abe, T; Ozato, Y; Ando, Y; Nakano, T; Motomura, Y; Koike, K; Takahashi, J; Hisamatsu, Y; Toshima, T; Yonemura, Y; Saeki, H; Mimori, K

    CANCER SCIENCE   113   1196 - 1196   2022.2   （ ISSN:1347-9032 eISSN:1349-7006 ）

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  • GET4 is a novel driver gene regulating the localization of BAG6 in colorectal cancer.

    Koike, K; Masuda, T; Nakano, T; Motomura, Y; Takahashi, J; Ando, Y; Toshima, T; Yonemura, Y; Nakagawa, T; Mimori, K

    CANCER SCIENCE   113   739 - 739   2022.2   （ ISSN:1347-9032 eISSN:1349-7006 ）

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  • FANCE, one of the Fanconi anemia (FA) pathway genes, could be a potential therapeutic target for HCC.

    Takahashi, J; Masuda, T; Kitagawa, A; Ozato, Y; Nakano, T; Kosai, K; Kobayashi, Y; Koike, K; Motomura, Y; Ando, Y; Toshima, T; Hisamatsu, Y; Yonemura, Y; Yoshizumi, T; Mimori, K

    CANCER SCIENCE   113   950 - 950   2022.2   （ ISSN:1347-9032 eISSN:1349-7006 ）

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  • GET4遺伝子は大腸癌の新規ドライバー遺伝子であり、核-細胞質間輸送にかかわる蛋白質であるBAG6の局在を調節する(GET4 is a novel driver gene in colorectal cancer that regulates the localization of BAG6, a nucleocytoplasmic shuttling protein)

    Koike Kensuke, Masuda Takaaki, Sato Kuniaki, Fujii Atsushi, Wakiyama Hiroaki, Tobo Taro, Takahashi Junichi, Motomura Yushi, Nakano Takafumi, Saito Hideyuki, Matsumoto Yoshihiro, Otsu Hajime, Takeishi Kazuki, Yonemura Yusuke, Mimori Koshi, Nakagawa Takashi

    Cancer Science   113 ( 1 )   156 - 169   2022.1   （ ISSN:1347-9032 ）

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    Language：English   Publisher：John Wiley & Sons Australia, Ltd  

    BCL2関連athanogene 6(BAG6)複合体の構成要素であるguided entry of tail-anchored proteins factor 4(GET4)が、大腸癌においてBAG6の細胞内局在を制御していることを明らかにした。癌ゲノムデータベースのデータセットを解析したところ、大腸癌でGET4遺伝子はしばしば増幅しており、ドライバー遺伝子の候補となることが突き止められた。GET4遺伝子は腫瘍細胞でDNAコピー数が増加しているために過剰発現していることが判明し、GET4高発現は予後不良の独立因子となっていた。BAG6には遺伝子変化が認められ、主に腫瘍細胞の細胞質内で過剰発現していた。大腸癌細胞を用いたノックアウト実験によってGET4の生物学的重要性について検討した。その結果、in vitro、in vivoのいずれでもGET4は腫瘍の増殖を促進することが示された。BAG6が媒介するp53のアセチル化が細胞質内で豊富に生じ、次いでp21発現が減少するために細胞周期の進行が促進されていると思われた。以上から、GET4はBAG6の細胞質移行を誘導して大腸癌の進行を促進する新規ドライバー遺伝子であり、予後バイオマーカーにもなることが明らかになった。

  • <i>GET4</i> is a novel driver gene in colorectal cancer that regulates the localization of BAG6, a nucleocytoplasmic shuttling protein

    Koike, K; Masuda, T; Sato, K; Fujii, A; Wakiyama, H; Tobo, T; Takahashi, J; Motomura, Y; Nakano, T; Saito, H; Matsumoto, Y; Otsu, H; Takeishi, K; Yonemura, Y; Mimori, K; Nakagawa, T

    CANCER SCIENCE   113 ( 1 )   156 - 169   2022.1   （ ISSN:1347-9032 eISSN:1349-7006 ）

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    Language：English   Publisher：Cancer Science  

    Colorectal cancer (CRC) is one of the most common types of cancer and a significant cause of cancer mortality worldwide. Further improvements of CRC therapeutic approaches are needed. BCL2-associated athanogene 6 (BAG6), a multifunctional scaffold protein, plays an important role in tumor progression. However, regulation of BAG6 in malignancies remains unclear. This study showed that guided entry of tail-anchored proteins factor 4 (GET4), a component of the BAG6 complex, regulates the intercellular localization of BAG6 in CRC. Furthermore, GET4 was identified as a candidate driver gene on the short arm of chromosome 7, which is often amplified in CRC, by our bioinformatics approach using the CRC dataset from The Cancer Genome Atlas. Clinicopathologic and prognostic analyses using CRC datasets showed that GET4 was overexpressed in tumor cells due to an increased DNA copy number. High GET4 expression was an independent poor prognostic factor in CRC, whereas BAG6 was mainly overexpressed in the cytoplasm of tumor cells without gene alteration. The biological significance of GET4 was examined using GET4 KO CRC cells generated with CRISPR-Cas9 technology or transfected CRC cells. In vitro and in vivo analyses showed that GET4 promoted tumor growth. It appears to facilitate cell cycle progression by cytoplasmic enrichment of BAG6-mediated p53 acetylation followed by reduced p21 expression. In conclusion, we showed that GET4 is a novel driver gene and a prognostic biomarker that promotes CRC progression by inducing the cytoplasmic transport of BAG6. GET4 could be a promising therapeutic molecular target in CRC.

    DOI： 10.1111/cas.15174

    Web of Science

    Scopus

    PubMed

  • Search for Glycolytic Genes as Biomarkers

    Saito H, Hosoda K, Dairaku K, Nakano Y, Hashimoto M, Hiraki Y, Abe T, Ando Y, Motomura Y, Hisamatsu Y, Toshima T, Yonemura Y, Masuda T, Saeki H, Mimori K

    Japan Journal of Molecular Tumor Marker Research   38 ( 0 )   24 - 25   2022   （ eISSN:24338575 ）

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    Language：Japanese   Publisher：Japanese Society for Molecular Tumor Marker Research  

    DOI： 10.11241/jsmtmr.38.24

    CiNii Research

  • Dosimetry of Occupational Eye Lens Dose Using a Novel Direct Eye Dosimeter, DOSIRIS, during Interventional Radiology Procedures

    Hirakawa, M; Nakatake, H; Tsuruta, S; Matsuura, S; Motomura, Y; Hiraki, Y; Mimori, K; Ishigami, K

    INTERVENTIONAL RADIOLOGY   7 ( 2 )   40 - 43   2022   （ eISSN:2432-0935 ）

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Presentations

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Professional Memberships

  • Japan　Society of Clinical Oncology

  • Japanese Cancer Association

  • Japan　Radiological　Society

  • Japanese Society for Radiation Oncology

Research Projects

  • 転写産物のロングリード・シーケンスによる食道癌化学放射線療法抵抗性獲得機構の解明

    Grant number：23K07066  2023.4 - 2026.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    平木 嘉樹, 本村 有史, 平川 雅和, 三森 功士, 井上 大地

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    Grant type：Scientific research funding

    進行食道扁平上皮癌に対する化学放射線療法(CRT)は標準治療の一つとされており高い抗腫瘍効果の期待できる低侵襲な治療法であるが、適応を決めるための感受性(抵抗性)の正確な予測は困難である。CRTによる治療成績向上のためには、感受性（抵抗性）に関与する(変異)転写産物を同定しその予測法の確立あるいは感受性を増感するための治療標的としての意義の確立が望まれる。近年、革新的技術であるロングリード・シーケンスの開発によりRNA全長のシーケンスが可能になった。すなわち発がんのドライバーとしてあるいはがん進展に関連する(変異)転写産物が注目されている。

    CiNii Research

  • 空間的遺伝子発現解析を用いた食道癌CRT抵抗性に関わる免疫微小環境の検討

    Grant number：22K07774  2022 - 2024

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    本村 有史, 山本 学, 三森 功士

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    Authorship：Principal investigator  Grant type：Scientific research funding

    化学放射線治療は進行食道がんに対する標準的治療ながら、治療後再発することも多く、治療効果向上のために再発の原因究明が望まれます。色々ながんが治療抵抗性となる要因として、がん細胞自体の性質の他に、がん細胞を取り巻く周囲環境を構成する細胞も重要であることが示されており、本研究では、食道がんの化学放射線治療の抵抗性とがんを取り巻く環境について、遺伝子解析により検討を行います。従来は遺伝子抽出の過程で組織構造が保てず、腫瘍の内部構造と遺伝子発現の検討が出来ませんでしたが、近年可能となった組織の位置情報を保持しつつ高い解像度で遺伝子発現を取得可能な「空間的遺伝子発現解析」を用いてこの問題に取り組みます。

    CiNii Research

  • 眼の水晶体等価線量限度に関する医療法改正対応への新たな線量計一体型防護眼鏡の開発

    Grant number：21K07702  2021.4 - 2024.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    平川 雅和, 本村 有史, 坂本 勝美, 高尾 誠一朗, 平木 嘉樹

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    Grant type：Scientific research funding

    放射線を使用した画像下治療は手技複雑化等により術者被ばく増加による白内障が懸念される。一方、眼の水晶体等価線量限度に関する医療法施行規則一部改正が2021年4月より施行予定で水晶体等価線量限度低減「5年間の平均で20mSv/年かつ50mSv/年を超えない」と水晶体等価線量評価法の推奨変更「眼の近傍や全面マスクの内側に放射線測定器を装着」とされている。2023年3月までの経過措置はあるものの正確な水晶体等価線量評価と更なる水晶体被ばく防護が必要と考えられる。本研究は、レベルの高い放射線診療を提供しながらも放射線障害防止と法令遵守とを両立した新たな放射線診療体制の整備に貢献可能と考えられる。

    CiNii Research

  • 食道癌のCRT後再発の遺伝的機序解明とパネルによるctDNA評価法の実装性の検討

    Grant number：19K17202  2019 - 2021

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

    本村 有史

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    Authorship：Principal investigator  Grant type：Scientific research funding

    食道扁平上皮癌に対する化学放射線療法(CRT)は標準治療であるが、予後は不良で再発も多い。再発を予測する確立されたバイオマーカーはなく、治療の個別化や再発リスクに応じた治療戦略の検討も困難である。近年我々は、進行大腸癌の原発巣内における遺伝子変異の多様性を明らかにした。食道癌でも、単一腫瘍内の多様なサブクローンのうち特定のものが治療に耐え再発に至ると予想される。再発に関わる遺伝子変異の同定が望まれるが、通常の生検は腫瘍の部分的な評価に過ぎず、少ないサブクローンは物理的に評価困難である。この克服に向け、癌細胞から血中に漏出する循環腫瘍DNAを用いた腫瘍の包括的評価が見込まれる。

    CiNii Research

  • Radiation dosimetry of Interventional radiological operator using direct eye dosimeter corresponding to new radiation dose limit of ICRP

    Grant number：18K07755  2018.4 - 2023.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Hirakawa Masakazu

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    Grant type：Scientific research funding

    In this research, there was no IR (interventional radiology) operators who evaluated the lens dose with neck glass dosimeter outside protective lead glasses and exceed the new occupational lens dose limit (20 mSv/year, averaged over defined periods of 5 years). In high volume center of IR, however, there may be some IR operators who may exceed the new occupational lens dose limit. The lens dose inside lead glasses which was estimated with the shieling effect and the lens dose of neck dosimeter tended to be lower and underestimated, compared to the eye lens dose by using a novel direct eye dosimeter, the DOSIRIS(Hp(3)) under protective glasses. This underestimated eye lens dose may cause the risk of radiation induced cataracts. Finally, To comply with new limit of eye dose and minimize the radiation-induced risk at the eye lenses, protective lead devices and correct evaluation of the eye dose using direct eye dosimeter like DOSIRIS under protective lead glasses might be needed.

    CiNii Research

Media Coverage

  • 高精度放射線治療 Newspaper, magazine

    大分合同新聞, からだを読み解く  2021.9

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    高精度放射線治療

  • 放射線治療　期待される免疫療法との併用効果 Newspaper, magazine

    大分合同新聞, からだを読み解く  2019.7

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    放射線治療　期待される免疫療法との併用効果