Kono, Takeyuki

写真a

Affiliation

School of Medicine, Department of Otorhinolaryngology, Head and Neck Surgery (Shinanomachi)

Position

Senior Assistant Professor (Non-tenured)/Assistant Professor (Non-tenured)

Career 【 Display / hide

  • 2009.04
    -
    2010.09

    神奈川県警友会けいゆう病院, 耳鼻咽喉科, 医員

  • 2010.10
    -
    2011.03

    慶應義塾大学病院, 耳鼻咽喉科, 専修医

  • 2011.04
    -
    2013.03

    済生会宇都宮病院, 耳鼻咽喉科, 医員

  • 2013.04
    -
    Present

    慶應義塾大学病院, 耳鼻咽喉科, 助教

Academic Background 【 Display / hide

  • 2001.04
    -
    2007.03

    Keio University, 医学部, 医学科

    University, Graduated

Licenses and Qualifications 【 Display / hide

  • 医師免許, 2007.04

 

Research Areas 【 Display / hide

  • Life Science / Otorhinolaryngology

Research Keywords 【 Display / hide

  • 喉頭科学

  • 頭頸部腫瘍

 

Papers 【 Display / hide

  • Genomic instability and dna damage repair pathways induced by human papillomaviruses

    Kono T., Laimins L.

    Viruses (Viruses)  13 ( 9 )  2021.09

     View Summary

    Human papillomaviruses (HPV) are the causative agents of cervical and other anogenital cancers as well as those of the oropharynx. HPV proteins activate host DNA damage repair factors to promote their viral life cycle in stratified epithelia. Activation of both the ATR pathway and the ATM pathway are essential for viral replication and differentiation-dependent genome amplification. These pathways are also important for maintaining host genomic integrity and their dysregulation or mutation is often seen in human cancers. The APOBEC3 family of cytidine deaminases are innate immune factors that are increased in HPV positive cells leading to the accumulation of TpC mutations in cellular DNAs that contribute to malignant progression. The activation of DNA damage repair factors may corelate with expression of APOBEC3 in HPV positive cells. These pathways may actively drive tumor development implicating/suggesting DNA damage repair factors and APOBEC3 as possible therapeutic targets.

  • Topoisomerase 2β induces dna breaks to regulate human papillomavirus replication

    Kaminski P., Hong S., Kono T., Hoover P., Laimins L.

    mBio (mBio)  12 ( 1 ) 1 - 11 2021.01

    ISSN  21612129

     View Summary

    Topoisomerases regulate higher-order chromatin structures through the transient breaking and religating of one or both strands of the phosphodiester back-bone of duplex DNA. TOP2β is a type II topoisomerase that induces double-strand DNA breaks at topologically associated domains (TADS) to relieve torsional stress aris-ing during transcription or replication. TADS are anchored by CCCTC-binding factor (CTCF) and SMC1 cohesin proteins in complexes with TOP2β. Upon DNA cleavage, a covalent intermediate DNA-TOP2β (TOP2βcc) is transiently generated to allow for strand passage. The tyrosyl-DNA phosphodiesterase TDP2 can resolve TOP2βcc, but failure to do so quickly can lead to long-lasting DNA breaks. Given the role of CTCF/ SMC1 proteins in the human papillomavirus (HPV) life cycle, we investigated whether TOP2β proteins contribute to HPV pathogenesis. Our studies demonstrated that levels of both TOP2β and TDP2 were substantially increased in cells with high-risk HPV genomes, and this correlated with large amounts of DNA breaks. Knockdown of TOP2β with short hairpin RNAs (shRNAs) reduced DNA breaks by over 50% as determined through COMET assays. Furthermore, this correlated with substantially reduced formation of repair foci such as phosphorylated H2AX (γH2AX), phosphorylated CHK1 (pCHK1), and phosphorylated SMC1 (pSMC1) indicative of impaired activation of DNA damage repair pathways. Importantly, knockdown of TOP2β also blocked HPV genome replication. Our previous studies demonstrated that CTCF/SMC1 factors associate with HPV genomes at sites in the late regions of HPV31, and these correspond to regions that also bind TOP2β. This study identifies TOP2β as responsible for enhanced levels of DNA breaks in HPV-positive cells and as a regulator of viral replication.

  • Activation of DNA damage repair factors in HPV positive oropharyngeal cancers

    Kono T., Hoover P., Poropatich K., Paunesku T., Mittal B.B., Samant S., Laimins L.A.

    Virology (Virology)  547   27 - 34 2020.08

    ISSN  00426822

     View Summary

    The mechanisms regulating viral pathogenesis of human papillomavirus (HPV) associated oropharyngeal squamous cell cancers (OPSCC) are not well understood. In the cervix, activation of DNA damage repair pathways is critical for viral replication but little is known about their role in OPSCC. APOBEC factors have been shown to be increased in OPSCC but the significance of this is unclear. We therefore examined activation of DNA damage and APOBEC factors in HPV-induced OPSCC. Our studies show significantly increased levels of pCHK1, FANCD2, BRCA1, RAD51, pSMC1 and γH2AX foci in HPV-positive samples as compared to HPV-negative while the ATM effector kinase, pCHK2, was not increased. Similar differences were observed when the levels of proteins were examined in OPSCC cell lines. In contrast, the levels of APOBEC3B and 3A were found to be similar in both HPV-positive and -negative OPSCC. Our studies suggest members of ATR pathway and FANCD2 may be important in HPV-induced OPSCC.

  • Efficacy of seasonal allergic rhinitis using an 810 nm diode laser system

    Sasaki K., Ohshiro T., Sakio R., Toriumi M., Hatano A., Fukazawa E., Kono T., Yoshihama K., Ogawa K., Ohshiro T.

    Laser Therapy (Laser Therapy)  28 ( 1 ) 11 - 18 2019

    ISSN  08985901

     View Summary

    Background and Aims: Allergic rhinitis annually reach epidemic proportions in Japan. Approximately 30 to 40% of the population suffers from allergic rhinitis during the spring season. Symptoms comprise rhinorrhea, nasal congestion, and sneezing accompanied by irritation and itching of the eyes. The Ohshiro Clinic started using the conventional Nd:YAG laser for the treatment of allergic rhinitis in 1993, and from 2005 we started using a diode laser-pumped Nd:YAG laser. From 2010, we adopted a novel 810 nm diode laser, and the present retrospective study examined the efficacy rate of the treatment of allergic rhinitis in the 2018 season with this system, compared with a previous study in 2011. We aimed to confirm the degree of improvement for each symptom to evaluate effectiveness of the diode laser treatment. Subjects and methods: Between January 8, 2018 and April 30, 2018, a large number of patients consulted our clinic with the major complaint of seasonal allergic rhinitis. They underwent a blood test, and the antigen-specific serum IgE antibody titers were measured for a definitive diagnosis of cedar pollinosis. A total of 211 target patients were treated during the trial period. The average age of the target group was 36.3 years, 134 males, and 77 females. The target patients were treated with lower nasal turbinate mucosal irradiation using a diode laser (ADL-20, Asuka Medical) delivering 810 nm at 7.5 W, with a total energy per treatment of 240 J/cm2. We adopted a five-step evaluation in accordance with the Japanese Guidelines for Allergic Rhinitis 2014 for the symptoms of rhinorrhea, sneezing and nasal obstruction. We assessed the degree of improvement in the severity of these symptoms following diode laser treatment from baseline to one month after treatment, in addition to assessing patient satisfaction with the degree of improvement in their quality of life (QOL). Results: The 211 patients positive for cedar pollinosis by the antigen-specific serum IgE antibody tests were broken down by month by number and by improvement, no change or exacerbation as follows. January, 18 patients: 33.4%, 44.4% and 22.2%, respectively. February, 29: 10.4%, 44.4% and 22.2%, respectively. March, 146: 60.3%, 31.5% and 8.2%, respectively. April, 18: 77.8%, 16.7% and 5.5%, respectively. The monthly respective improvement, no change or worse patient QOL as percentages were as follows: January: 16.7%, 44.4% and 38.9%. February: 17.3%, 13.8% and 68.9%. March: 61.6%, 29.5% and 8.9%. April: 94.4%, 0.0% and 5.6%. The values for prevention of exacerbation versus exacerbation for each month were: January, 77.8% vs 22.2%; February, 41.4% vs 58.6%; March, 91.8% vs 8.2%; and April, 94.4% vs 5.6%. The mean efficacy rate for the trial period in the present study was therefore 52.6% which compared very favorably with the mean efficacy rate in the 2011 study of 53.4%. Conclusions: The results showed that the 810 nm diode laser offered a safe and effective solution for the uncomfortable symptoms of allergic rhinitis and could be well applied during the season of Japanese cedar pollen dispersion. Furthermore, a tendency towards high efficacy was demonstrated for laser treatment in class 6 cedar pollinosis patients, based on the specific IgE antibody test.

  • 症例をどうみるか 無挿管ニューロレプト麻酔下の手術により気管切開を回避できた巨大喉頭乳頭腫の1例

    富永 健裕, 甲能 武幸, 小川 郁

    JOHNS ((株)東京医学社)  34 ( 5 ) 665 - 668 2018.05

    ISSN  0910-6820

     View Summary

    74歳男性。嗄声および咽頭違和感を主訴とした。乳頭腫の診断で経過観察されていたが増大傾向となった。喉頭ファイバーで声門上に右仮声帯を基部とする大きな腫瘍を認め、声門の視認はできなかった。鼻内からの喉頭ファイバー挿管は困難であったため、初回は無挿管ニューロレプト麻酔下手術で腫瘍の減量を行い、二期的に全身麻酔下に喉頭微細手術を行った。残存した腫瘍は、約4ヵ月後に全身麻酔下でCO2レーザーによる蒸散を行った。退院後の外来での喉頭ファイバーでは、肉眼的に腫瘍の残存は認められない。

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

Reviews, Commentaries, etc. 【 Display / hide

  • FANCD2 may serve as prognostic biomarker in HPV related oropharyngeal cancers(和訳中)

    甲能 武幸, 小澤 宏之

    日本外科系連合学会誌 (日本外科系連合学会)  47 ( 3 ) 433 - 433 2022.05

    ISSN  0385-7883

  • 【手術に必要な画像診断-喉頭・気管編】喉頭微細手術

    甲能 武幸, 矢部 はる奈, 富永 健裕, 小川 郁

    JOHNS ((株)東京医学社)  34 ( 6 ) 675 - 680 2018.06

    ISSN  0910-6820

  • 3DCADソフトおよび3D模型を用いた経皮的声帯内注入術刺入法の検討

    富永 健裕, 甲能 武幸, 小川 郁

    日本気管食道科学会会報 ((NPO)日本気管食道科学会)  69 ( 2 ) s55 - s55 2018.04

    ISSN  0029-0645

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

  • HPV関連中咽頭癌におけるDNA損傷修復系と内因性免疫因子APOBEC3の発現

    2020.04
    -
    2023.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Early-Career Scientists , Principal investigator

 

Courses Taught 【 Display / hide

  • PATHOPHYSIOLOGICAL ISSUES IN CHRONIC CARE

    2022

  • LECTURE SERIES, OTORHINOLARYNGOLOGY

    2022

  • LECTURE SERIES, OTORHINOLARYNGOLOGY

    2019

Courses Previously Taught 【 Display / hide

  • 耳鼻咽喉科学

    Keio University

    2017.04
    -
    2018.03

    Autumn Semester, Lecture, Within own faculty, 1h, 30people

    喉頭科学全般

  • 耳鼻咽喉科学

    Keio University

    2016.04
    -
    2017.03

    Autumn Semester, Lecture, Within own faculty, 1h, 30people

    喉頭科学全般

 

Memberships in Academic Societies 【 Display / hide

  • 日本耳鼻咽喉科学会

     
  • 日本気管食道科学会

     
  • 日本喉頭科学会

     
  • 日本頭頸部外科学会