Cardiovascular complication and DNA damage in radiation therapy

• Project/Area Number: 17K10449
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: Fukushima Medical University
• Principal Investigator: Ishida Takafumi 福島県立医科大学, 医学部, 教授 (40346482)
• Co-Investigator(Kenkyū-buntansha): 石田 万里 広島大学, 医系科学研究科(医), 准教授 (30359898) ; 鈴木 義行 福島県立医科大学, 医学部, 教授 (60334116)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: DNA損傷 / DNA損傷応答 / 放射線治療 / 心血管病

Outline of Final Research Achievements

Radiotherapy for head and neck cancer increases the risk of exacerbation of carotid atherosclerotic lesions and thereby that of stroke. This study examined the effect of radiation on DNA damage/DNA damage response in patients receiving radiotherapy for head and neck cancer. Peripheral mononuclear cells from patients with head and neck cancers were isolated before and after radiotherapy. gammaH2AX were measured as a marker for DNA double-strand breaks by immunofluorescent study, and dicentric chromosomes were quantified as a marker for chromosome aberration by FISH. Both gammaH2AX and dicentric chromosomes in mononuclear cells were increased after radiotherapy. The expression of inflammatory cytokines were also increased. Immunoblot showed NF-kappaB activity was increased after radiotherapy. Thus, DNA damage and DNA damage response may mediate acceleration of atherosclerosis in patients with head and neck cancer by radiotherapy.

Academic Significance and Societal Importance of the Research Achievements

放射線治療による動脈硬化性病変の増悪にDNA損傷あるいはDNA損傷応答が関与することが示唆された。この経路を定量することにより、動脈硬化性病変が増悪する患者を予知する手がかりとなり得ることが示唆された。またこの経路を標的とすることが、放射線治療の副作用を最小限に留めつつ、その恩恵を最大限に享受する方策を作るうえで重要な手がかりとなり得る。

Research Products

• [Journal Article] Biological Effects of Low-Dose Chest CT on Chromosomal DNA (2020)
  • Author(s): Sakane Hiroaki、Ishida Mari、Shi Lin、Fukumoto Wataru、Sakai Chiemi、Miyata Yoshihiro、Ishida Takafumi、Akita Tomoyuki、Okada Morihito、Awai Kazuo、Tashiro Satoshi
  • Journal Title: Radiology Volume: 295 Issue: 2 Pages: 439-445
  • DOI: 10.1148/radiol.2020190389
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Associations of benzodiazepine with adverse prognosis in heart failure patients with insomnia. (2020)
  • Author(s): Sato Y, Yoshihisa A, Hotsuki Y, Watanabe K, Kimishima Y, Kiko T, Kanno Y, Yokokawa T, Abe S, Misaka T, Sato T, Oikawa M, Kobayashi A, Yamaki T, Kunii H, Nakazato K, Ishida T, Takeishi Y
  • Journal Title: J Am Heart Assoc Volume: 9 Issue: 7
  • DOI: 10.1161/jaha.119.013982
  • Peer Reviewed / Open Access
• [Journal Article] Cardiac Troponin I Predicts Elevated B-type Natriuretic Peptide in Patients Treated with Anthracycline-Containing Chemotherapy (2020)
  • Author(s): Oikawa Masayoshi、Yoshihisa Akiomi、Yokokawa Tetsuro、Misaka Tomofumi、Yaegashi Daiki、Miyata Makiko、Nakazato Kazuhiko、Ishida Takafumi、Takeishi Yasuchika
  • Journal Title: Oncology Volume: - Issue: 9 Pages: 1-8
  • DOI: 10.1159/000507585
  • Peer Reviewed
• [Journal Article] DNA Damage and Senescence-Associated Inflammation in Cardiovascular Disease (2019)
  • Author(s): Ishida T, Ishida M, Tashiro S, Takeishi Y
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 42 Issue: 4 Pages: 531-537
  • DOI: 10.1248/bpb.b18-00865
  • NAID: 130007622128
  • ISSN: 0918-6158, 1347-5215
  • Year and Date: 2019-04-01
  • Peer Reviewed / Open Access
• [Journal Article] Circulating acetoacetate is associated with poor prognosis in heart failure patients (2019)
  • Author(s): Yokokawa Tetsuro、Yoshihisa Akiomi、Kanno Yuki、Abe Satoshi、Misaka Tomofumi、Yamada Shinya、Kaneshiro Takashi、Sato Takamasa、Oikawa Masayoshi、Kobayashi Atsushi、Nakazato Kazuhiko、Ishida Takafumi、Takeishi Yasuchika
  • Journal Title: IJC Heart & Vasculature Volume: 25 Pages: 100432-100432
  • DOI: 10.1016/j.ijcha.2019.100432
  • Peer Reviewed
• [Journal Article] A Multiple Biomarker Approach in Patients with Cardiac Sarcoidosis (2018)
  • Author(s): Kiko Takatoyo、Yoshihisa Akiomi、Kanno Yuki、Yokokawa Tetsuro、Abe Satoshi、Miyata-Tatsumi Makiko、Misaka Tomofumi、Oikawa Masayoshi、Kobayashi Atsushi、Ishida Takafumi、Takeishi Yasuchika
  • Journal Title: International Heart Journal Volume: 59 Issue: 5 Pages: 996-1001
  • DOI: 10.1536/ihj.17-695
  • NAID: 130007490569
  • ISSN: 1349-2365, 1349-3299
  • Year and Date: 2018-09-01
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Change of Exhaled Acetone Concentration Levels in Patients with Acute Decompensated Heart Failure (2018)
  • Author(s): Yokokawa Tetsuro、Sato Takamasa、Suzuki Satoshi、Oikawa Masayoshi、Yoshihisa Akiomi、Kobayashi Atsushi、Yamaki Takayoshi、Kunii Hiroyuki、Nakazato Kazuhiko、Suzuki Hitoshi、Saitoh Shu-ichi、Ishida Takafumi、Shimouchi Akito、Takeishi Yasuchika
  • Journal Title: International Heart Journal Volume: 59 Issue: 4 Pages: 808-812
  • DOI: 10.1536/ihj.17-482
  • NAID: 130007428099
  • ISSN: 1349-2365, 1349-3299
  • Year and Date: 2018-07-31
  • Peer Reviewed / Open Access
• [Journal Article] Valvular heart disease as a possible predictor of?trastuzumab?induced cardiotoxicity in patients with breast cancer (2018)
  • Author(s): Sato Akihiko、Yoshihisa Akiomi、Miyata?Tatsumi Makiko、Oikawa Masayoshi、Kobayashi Atsushi、Ishida Takafumi、Ohtake Tohru、Takeishi Yasuchika
  • Journal Title: Molecular and Clinical Oncology Volume: 10 Pages: 37-42
  • DOI: 10.3892/mco.2018.1764
  • Peer Reviewed / Open Access
• [Journal Article] Chromosomal Abnormalities in Human Lymphocytes after Computed Tomography Scan Procedure (2018)
  • Author(s): Shi L, Fujioka K, Sakurai-Ozato N, Fukumoto W, Satoh K, Sun J, Awazu A, Tanaka K, Ishida M, Ishida T, Nakano Y, Kihara Y, Hayes CN, Aikata H, Chayama K, Ito T, Awai K, Tashiro S
  • Journal Title: Radiation Research Volume: 190 Issue: 4 Pages: 424-432
  • DOI: 10.1667/rr14976.1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinical Significance of Get With the Guidelines?Heart Failure Risk Score in Patients With Chronic Heart Failure After Hospitalization (2018)
  • Author(s): Suzuki Satoshi、Yoshihisa Akiomi、Sato Yu、Kanno Yuki、Watanabe Shunsuke、Abe Satoshi、Sato Takamasa、Oikawa Masayoshi、Kobayashi Atsushi、Yamaki Takayoshi、Kunii Hiroyuki、Nakazato Kazuhiko、Ishida Takafumi、Takeishi Yasuchika
  • Journal Title: Journal of the American Heart Association Volume: 7 Issue: 17
  • DOI: 10.1161/jaha.117.008316
  • Peer Reviewed / Open Access
• [Journal Article] Associations between diabetes mellitus and pulmonary hypertension in chronic respiratory disease patients (2018)
  • Author(s): Takahashi Tomoko、Yoshihisa Akiomi、Sugimoto Koichi、Yokokawa Tetsuro、Misaka Tomofumi、Kaneshiro Takashi、Oikawa Masayoshi、Kobayashi Atsushi、Nakazato Kazuhiko、Ishida Takafumi、Takeishi Yasuchika
  • Journal Title: PLOS ONE Volume: 13 Issue: 10 Pages: e0205008-e0205008
  • DOI: 10.1371/journal.pone.0205008
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Sympathetic nervous remodeling is induced in the intermediolateral nucleus after myocardial infarction ? Role of BDNF-TrkB axis- (2018)
  • Author(s): Nodera Minoru、Oikawa Masayoshi、Nakazato Kazuhiko、Ishida Takafumi、Takeishi Yasuchika
  • Journal Title: Neuroscience Letters Volume: 685 Pages: 114-123
  • DOI: 10.1016/j.neulet.2018.08.004
  • Peer Reviewed
• [Journal Article] Utility of heart rate turbulence and T-wave alternans to assess risk for readmission and cardiac death in hospitalized heart failure patients (2018)
  • Author(s): Yamada Shinya、Yoshihisa Akiomi、Sato Yu、Sato Takamasa、Kamioka Masashi、Kaneshiro Takashi、Oikawa Masayoshi、Kobayashi Atsushi、Suzuki Hitoshi、Ishida Takafumi、Takeishi Yasuchika
  • Journal Title: Journal of Cardiovascular Electrophysiology Volume: 29 Issue: 9 Pages: 1257-1264
  • DOI: 10.1111/jce.13639
  • Peer Reviewed
• [Journal Article] Relation of Testosterone Levels to Mortality in Men With Heart Failure (2018)
  • Author(s): Yoshihisa Akiomi、Suzuki Satoshi、Sato Yu、Kanno Yuki、Abe Satoshi、Miyata Makiko、Sato Takamasa、Oikawa Masayoshi、Kobayashi Atsushi、Yamaki Takayoshi、Kunii Hiroyuki、Nakazato Kazuhiko、Ishida Takafumi、Takeishi Yasuchika
  • Journal Title: The American Journal of Cardiology Volume: 121 Issue: 11 Pages: 1321-1327
  • DOI: 10.1016/j.amjcard.2018.01.052
  • Peer Reviewed / Open Access
• [Journal Article] Usefulness of Urinary N-Terminal Fragment of Titin to Predict Mortality in Dilated Cardiomyopathy (2018)
  • Author(s): Yoshihisa Akiomi、Kimishima Yusuke、Kiko Takatoyo、Sato Yu、Watanabe Shunsuke、Kanno Yuki、Abe Satoshi、Miyata Makiko、Sato Takamasa、Suzuki Satoshi、Oikawa Masayoshi、Kobayashi Atsushi、Yamaki Takayoshi、Kunii Hiroyuki、Nakazato Kazuhiko、Ishida Takafumi、Takeishi Yasuchika
  • Journal Title: The American Journal of Cardiology Volume: 121 Issue: 10 Pages: 1260-1265
  • DOI: 10.1016/j.amjcard.2018.01.046
  • Peer Reviewed / Open Access
• [Journal Article] Association of Serum Zinc Level With Prognosis in Patients With Heart Failure (2018)
  • Author(s): Yoshihisa Akiomi、Abe Satoshi、Kiko Takatoyo、Kimishima Yusuke、Sato Yu、Watanabe Shunsuke、Kanno Yuki、Miyata-Tatsumi Makiko、Misaka Tomofumi、Sato Takamasa、Suzuki Satoshi、Oikawa Masayoshi、Kobayashi Atsushi、Yamaki Takayoshi、Kunii Hiroyuki、Nakazato Kazuhiko、Ishida Takafumi、Takeishi Yasuchika
  • Journal Title: Journal of Cardiac Failure Volume: 24 Issue: 6 Pages: 375-383
  • DOI: 10.1016/j.cardfail.2018.02.011
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Association between sleep-disordered breathing and arterial stiffness in heart failure patients with reduced or preserved ejection fraction (2018)
  • Author(s): Suzuki Satoshi、Yoshihisa Akiomi、Sato Yu、Watanabe Shunsuke、Yokokawa Tetsuro、Sato Takamasa、Oikawa Masayoshi、Kobayashi Atsushi、Yamaki Takayoshi、Kunii Hiroyuki、Nakazato Kazuhiko、Suzuki Hitoshi、Saitoh Shu-ichi、Ishida Takafumi、Takeishi Yasuchika
  • Journal Title: ESC Heart Failure Volume: 5 Issue: 3 Pages: 284-291
  • DOI: 10.1002/ehf2.12273
  • Peer Reviewed / Open Access
• [Journal Article] Liver fibrosis marker, 7S domain of collagen type IV, in patients with pre-capillary pulmonary hypertension (2018)
  • Author(s): 8.Yoshihisa A, Kimishima Y, Kiko T, Sato Y, Watanabe S, Kanno Y, Abe S, Miyata-Tatsumi M, Sato T, Suzuki S, Oikawa M, Kobayashi A, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Ishida T, Takeishi Y
  • Journal Title: Int J Cardiol Volume: 258 Pages: 269-274
  • DOI: 10.1016/j.ijcard.2018.01.138
  • Peer Reviewed / Open Access
• [Journal Article] Fish oil omega-3 polyunsaturated fatty acids attenuate oxidative stress-induced DNA damage in vascular endothelial cells (2017)
  • Author(s): Sakai Chiemi、Ishida Mari、Ohba Hideo、Yamashita Hiromitsu、Uchida Hitomi、Yoshizumi Masao、Ishida Takafumi
  • Journal Title: PLOS ONE Volume: 12 Issue: 11 Pages: e0187934-e0187934
  • DOI: 10.1371/journal.pone.0187934
  • Peer Reviewed / Open Access
• [Presentation] DNA損傷と動脈硬化 (2019)
  • Author(s): 石田隆史
  • Organizer: 脳心血管抗加齢研究会 2019
  • Invited