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2011 Fiscal Year Annual Research Report

放射線によるがん転移への影響

Research Project

Project/Area Number 23390300
Research InstitutionOsaka University

Principal Investigator

手島 昭樹  大阪大学, 医学系研究科, 教授 (40136049)

Co-Investigator(Kenkyū-buntansha) 松浦 成昭  大阪大学, 医学系研究科, 教授 (70190402)
村上 昌雄  神戸大学, 医学系研究科, 教授 (50210018)
出水 祐介  神戸大学, 医学系研究科, 医学研究員 (50452496)
Keywords放射線腫瘍学 / 細胞動態解析 / がん / 転移 / 浸潤能 / 炭素イオン線 / 陽子線 / 細胞運動
Research Abstract

本年度は種々の放射線照射後のRhoAおよびその下流に存在するMLC (Myosin Light Chain)の発現と活性化について解析した。さらに、放射線照射量と細胞運動の関係を調べる為、細胞運動の方向性と関連するゴルジ体の局在変化について検討した。一方、陽子線照射後の細胞遊走能、浸潤能をX線、炭素イオン線の結果と比較検討した。
1.転移関連遺伝子・タンパク質の発現量:ヒト膵がん細胞株AsPC-1、Panc1に炭素イオン線を照射し、RhoAおよびMLCの活性化を解析した結果、X線照射に比べ、RhoA、MLCの活性低下が示された。また、ヒト肺腺癌細胞株A549にX線を照射後、細胞運動に関連するゴルジ体の局在を検討したところ、低線量のX線照射された細胞は、非照射細胞、高線量照射細胞に比べ、短時間でゴルジ体が運動の方向性を決定した。結果、低線量照射された細胞は、他の条件に比べて細胞運動が亢進し、低線量X線照射が、細胞遊走・浸潤能亢進の一因となる可能性が示された。
2.細胞機能実験と解析:ヒト肺腺癌細胞株A549、血管内皮様細胞株ECV304に対し、陽子線照射後、細胞遊走能、浸潤能を検討し、X線、炭素イオン線と比較した結果、低線量照射された細胞では、X線照射細胞同様、細胞遊走・浸潤能が亢進し、高線量では、炭素イオン線照射細胞同様、遊走・浸潤能が抑制された。これにより、陽子線が細胞運動へ与える影響は、低線量と高線量で異なる可能性が示唆された。
以上より、種々の放射線照射によって生じる細胞運動に与える影響の違いを明らかにし、がんの転移、浸潤の分子メカニズムの解明へと進めた。

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

本年度の目標であった3種の放射線が細胞運動に与える影響を細胞機能実験と解析で明らかにしており、さらにその一因となるタンパク質としてRhoAおよびその下流にあるMLCが粒子線で活性低下することを明らかにした。また、低線量X線で細胞運動が亢進する一因としてゴルジ体の局在変化が関与する可能性を示しており、おおむね順調に進展している。

Strategy for Future Research Activity

着目した遺伝子・タンパクについて、分子を遺伝子レベル、タンパクレベルで阻害し、転移能への影響を細胞実験にて確かめる。遺伝子レベルの阻害にはsiRNA、タンパクレベルの阻害にはinhibitorを用いる。in vivo実験においても、着目した遺伝子をノックアウトさせた細胞をマウスへ皮下注射したxenogrftを用いて転移能への影響を検討し、in vitroとの整合性を分析する。引き続き、生物学的データを集約し研究結果をデータベース化する。データベースは、実験の再現性を高める指標となる一方、統計解析ソフトSASを用いて、遺伝子、タンパク発現量、細胞機能、in vivo実験結果の相関関係を解析して、線質や線量の違いによる転移への影響を明らかにする。

  • Research Products

    (49 results)

All 2012 2011 Other

All Journal Article (18 results) (of which Peer Reviewed: 18 results) Presentation (30 results) Remarks (1 results)

  • [Journal Article] Patterns of radiotherapy practice for patients with cervical cancer in Japan (2003-2005) : Changing trends in the pattern of care process2012

    • Author(s)
      Tomita T., Numasaki H., Teshima T., et al
    • Journal Title

      Int.J.Radiat.Oncol.Biol.Phys.

      Volume: (Epub ahead of print)(in press)

    • DOI

      10.1016/j.ijrobp.2011.10.013

    • Peer Reviewed
  • [Journal Article] National Medical Care System may impede fostering of true specialization of radiation oncologists : Study based on structure survey in Japan2012

    • Author(s)
      Numasaki H., Teshima T., et al
    • Journal Title

      Int.J.Radiat.Oncol.Biol.Phys.

      Volume: 82(1) Pages: 111-17

    • DOI

      10.1016/j.ijrobp.2011.01.029

    • Peer Reviewed
  • [Journal Article] Prospective multi-institutional study of definitive radiotherapy with high-dose rate intracavitary brachytherapy in patients with non-bulky (<4 cm) stage I,II uterine cervical cancer (JAROG0401/JROSG04-2)2012

    • Author(s)
      Toita T., Kodaira T., Numasaki H., Teshima T., et al
    • Journal Title

      Int.J. Radiat.Oncol.Biol.Phys.

      Volume: 82(1) Pages: 49-56

    • DOI

      10.1016/j.ijrobp.2011.01.022

    • Peer Reviewed
  • [Journal Article] Radical external beam radiotherapy for clinically localized prostate cancer in Japan : Changing trends in the Patterns of Care Process Survey2011

    • Author(s)
      Ogawa K., Nakamura K., Onishi H., Koizumi M., Teshima T., et al
    • Journal Title

      Int.J.Radiat.Oncol.Biol.Phys.

      Volume: 81(5) Pages: 1310-18

    • DOI

      10.1016/j.ijrobp.2010.08.014

    • Peer Reviewed
  • [Journal Article] Changing trend in the patterns of pretreatment diagnostic assessment for patients with cervical cancer in Japan2011

    • Author(s)
      Tomita T., Numasaki H., Teshima T., et al
    • Journal Title

      Gynecologic Oncology

      Volume: 123 Pages: 577-80

    • DOI

      10.1016/j.ygyno.2011.08.024

    • Peer Reviewed
  • [Journal Article] Respiratory monitorinig with an acceleration sensor2011

    • Author(s)
      Ono T., Numasaki H., Teshima T., et al
    • Journal Title

      Physics in Medicine Biology

      Volume: 56 Pages: 6279-89

    • DOI

      10.1088/0031-9155/56/19/008

    • Peer Reviewed
  • [Journal Article] Carbon ion irradiation suppresses metastatic potential of human non-small cell lung cancer A549 cells through the phosphatidylinositol-3-kinase/Akt signaling path way2011

    • Author(s)
      Ogata T., Teshima T., et al
    • Journal Title

      J.Radiation Research

      Volume: 52 Pages: 374-9

    • DOI

      10.1269/jrr.10102

    • Peer Reviewed
  • [Journal Article] Measurement of DNA double-strand break yield in human cancer cells by high-current, short-duration bunches of laser-accelerated protons2011

    • Author(s)
      Yogo A., Teshima T.
    • Journal Title

      Jpn.J.Appl.Phys.

      Volume: 50 Pages: 106401-7

    • Peer Reviewed
  • [Journal Article] Examination of fundamental characteristics of a polymer gel detection in a proton beam irradiation2011

    • Author(s)
      Yoshioka M., Teshima T., et al
    • Journal Title

      Radiation Measurements

      Volume: 46(1) Pages: 64-71

    • Peer Reviewed
  • [Journal Article] Japanese structure survey of radiation oncology in 2007 with special reference to designated cancer care hospitals2011

    • Author(s)
      Numasaki H., Koizumi M., Ando Y., Teshima T., et al
    • Journal Title

      Strahlenther.Onkol.

      Volume: 187(3) Pages: 167-74

    • DOI

      10.1007/s00066-010-2205-3

    • Peer Reviewed
  • [Journal Article] Platelet-derived growth factor regulates breast cancer progression via β-catenin expression2011

    • Author(s)
      Yokoyama Y, Matsuura N., et al
    • Journal Title

      Pathobiology

      Volume: 78(5) Pages: 253-60

    • DOI

      10.1159/000328061

    • Peer Reviewed
  • [Journal Article] Aberrant expression of disintegrin-metalloprotease proteins in the formation and progression of uterine cervical cancer2011

    • Author(s)
      Shaker M, Matsuura N., et al
    • Journal Title

      Pathobiology

      Volume: 78(3) Pages: 149-61

    • DOI

      10.1159/000324314

    • Peer Reviewed
  • [Journal Article] Clinical significance of circulating galectins as colorectal cancer markers2011

    • Author(s)
      Watanabe M, Matsuura N., et al
    • Journal Title

      Oncol Rep

      Volume: 25(5) Pages: 1217-26

    • DOI

      10.3892/or.2011.1198

    • Peer Reviewed
  • [Journal Article] Epithelial to mesenchymal transition is a determinant of sensitivity to chemoradiotherapy in non-small cell lung cancer2011

    • Author(s)
      Shintani Y, Matsuura N., et al
    • Journal Title

      Ann Thorac Surg

      Volume: 92(5) Pages: 1794-804

    • DOI

      10.1016/j.athoracsur.2011.07.032

    • Peer Reviewed
  • [Journal Article] OSNA-based novel molecular testing for lymph node metastases in colorectal cancer patients : results from a multicenter clinical performance study in Japan2011

    • Author(s)
      Yamamoto H, Matsuura N., et al
    • Journal Title

      Ann Sure Oncol

      Volume: 18(7) Pages: 1891-8

    • DOI

      10.1245/s10434-010-1539-5

    • Peer Reviewed
  • [Journal Article] The effectiveness of particle radiotherapy for hepatocellular carcinoma associated with inferior vena cava tumor thrombus2011

    • Author(s)
      Komatsu S, Demizu Y, Murakami M., et al
    • Journal Title

      J Gastroenterol

      Volume: 46(7) Pages: 913-20

    • DOI

      10.1007/s00535-011-0398-6

    • Peer Reviewed
  • [Journal Article] Risk factors for survival and local recurrence after particle radiotherapy for single small hepatocellular carcinoma2011

    • Author(s)
      Komatsu S, Murakami M., et al
    • Journal Title

      Br J Surg

      Volume: 98(4) Pages: 558-64

    • DOI

      10.1002/bjs.7397

    • Peer Reviewed
  • [Journal Article] Clinical results and risk factors of proton and carbon ion therapy for hepatocellular carcinoma2011

    • Author(s)
      Komatsu S, Demizu Y, Murakami M., et al
    • Journal Title

      Cancer

      Volume: 117(21) Pages: 4890-904

    • DOI

      10.1002/cncr.26134

    • Peer Reviewed
  • [Presentation] 呼吸性移動下IMRT適応への検討(1)-呼吸性移動を考慮した線量計算ソフトウェアの開発-2012

    • Author(s)
      壽賀正城
    • Organizer
      第24回日本高精度放射線外部照射研究会
    • Place of Presentation
      横浜
    • Year and Date
      2012-02-04
  • [Presentation] 多施設共同臨床試験における治療計画QAシステムの構築2012

    • Author(s)
      端佑士
    • Organizer
      第24回日本高精度放射線外部照射研究会
    • Place of Presentation
      横浜
    • Year and Date
      2012-02-04
  • [Presentation] Simulations concerning particle therapy2011

    • Author(s)
      Masaaki Takashina
    • Organizer
      7^<th> Osaka University Medical Physics Seminar
    • Place of Presentation
      Osaka, Japan
    • Year and Date
      2011-12-07
  • [Presentation] Image-guided adaptive radiotherapy2011

    • Author(s)
      Hideki Takegawa
    • Organizer
      7^<th> Osaka University Medical Physics Seminar
    • Place of Presentation
      Osaka, Japan
    • Year and Date
      2011-12-07
  • [Presentation] Cancer information system2011

    • Author(s)
      Hodaka Numasaki
    • Organizer
      7^<th> Osaka University Medical Physics Seminar
    • Place of Presentation
      Osaka, Japan
    • Year and Date
      2011-12-07
  • [Presentation] Particle beam radiobiology2011

    • Author(s)
      Kazumasa Minami
    • Organizer
      7^<th> Osaka University Medical Physics Seminar
    • Place of Presentation
      Osaka, Japan
    • Year and Date
      2011-12-07
  • [Presentation] Introduction & Overview2011

    • Author(s)
      Teruki Teshima
    • Organizer
      7^<th> Osaka University Medical Physics Seminar
    • Place of Presentation
      Osaka, Japan
    • Year and Date
      2011-12-06
  • [Presentation] 頭頸部2phaseIMRTにおける線量積算法2011

    • Author(s)
      金岡尚利
    • Organizer
      2011年度日本写真学会秋季研究発表会
    • Place of Presentation
      京都
    • Year and Date
      2011-12-05
  • [Presentation] 呼吸コーチングによる呼吸再現性の改善効果2011

    • Author(s)
      小野智博
    • Organizer
      2011年度日本写真学会秋季研究発表会
    • Place of Presentation
      京都
    • Year and Date
      2011-12-05
  • [Presentation] 症例アンケート分析:JASTRO構造調査,mHDR研究会症例調査2011

    • Author(s)
      沼崎穂高
    • Organizer
      マイクロセレクトロンHDR第7回学術研究会
    • Place of Presentation
      東京
    • Year and Date
      2011-12-03
  • [Presentation] JATRO DB委員会支援活動報告2011

    • Author(s)
      沼崎穂高
    • Organizer
      日本放射線腫瘍学会第24回学術大会
    • Place of Presentation
      神戸
    • Year and Date
      2011-11-18
  • [Presentation] 呼吸コーチングによる呼吸再現性の改善効果2011

    • Author(s)
      小野智博
    • Organizer
      日本放射線腫瘍学会第24回学術大会
    • Place of Presentation
      神戸
    • Year and Date
      2011-11-17
  • [Presentation] IHE-ROとJASTRO DBの連携2011

    • Author(s)
      沼崎穂高
    • Organizer
      日本放射線腫瘍学会第24回学術大会
    • Place of Presentation
      神戸
    • Year and Date
      2011-11-17
  • [Presentation] Respiratory monitoring with an acceleration sensor2011

    • Author(s)
      Tomohiro Ono
    • Organizer
      The 6^<th> Japan-Korea Joint Meeting on Medical Physics and the 11^<th> Asia-Oceania Congress of Medical Physics
    • Place of Presentation
      Fukuoka, Japan
    • Year and Date
      2011-09-30
  • [Presentation] Fast analysis of the interplay effect between MLC motion and tumor with respiratory motion2011

    • Author(s)
      Akira Masaoka
    • Organizer
      The 6^<th> Japan-Korea Joint Meeting on Medical Physics and the 11^<th> Asia-Oceania Congress of Medical Physics
    • Place of Presentation
      Fukuoka, Japan
    • Year and Date
      2011-09-30
  • [Presentation] 呼吸性移動を有する動体へのIMRT適用に向けてのQAソフトウェアの開発2011

    • Author(s)
      壽賀正城
    • Organizer
      第298回日本医学放射線学会関西地方会
    • Place of Presentation
      大阪
    • Year and Date
      2011-06-25
  • [Presentation] Overview of JSPS Core-to-Core project2011

    • Author(s)
      Teruki Teshima
    • Organizer
      The University of Groningen-Osaka University Partnership Symposium
    • Place of Presentation
      Groningen, the Netherlands
    • Year and Date
      2011-05-31
  • [Presentation] Monte Carlo simulations concerning particle therapy using PHITS2011

    • Author(s)
      Masaaki Takashina
    • Organizer
      The University of Groningen-Osaka University Partnership Symposium
    • Place of Presentation
      Groningen, the Netherlands
    • Year and Date
      2011-05-31
  • [Presentation] CBCT-based dose calculation in combination with Monte Carlo simulation2011

    • Author(s)
      Hideki Takegawa
    • Organizer
      The University of Groningen-Osaka University Partnership Symposium
    • Place of Presentation
      Groningen, the Netherlands
    • Year and Date
      2011-05-31
  • [Presentation] Cancer information system utilizing IT and Japanese National Cancer Database (JNCDB)2011

    • Author(s)
      Teruki Teshima
    • Organizer
      The University of Groningen-Osaka University Partnership Symposium
    • Place of Presentation
      Groningen, the Netherlands
    • Year and Date
      2011-05-31
  • [Presentation] Particle irradiation has suppressing effects on cancer metastasis2011

    • Author(s)
      Kazumasa Minami
    • Organizer
      The University of Groningen-Osaka University Partnership Symposium
    • Place of Presentation
      Groningen, the Netherlands
    • Year and Date
      2011-05-31
  • [Presentation] CBCT-based dose calculation with Monte Carlo simulation2011

    • Author(s)
      Hideki Takegawa
    • Organizer
      Scientific and Clinical Symposium, Indiana University-Osaka University Partnership Symposium
    • Place of Presentation
      Bloomington, USA
    • Year and Date
      2011-05-26
  • [Presentation] Overview of JSPS Core-to-Core project2011

    • Author(s)
      Teruki Teshima
    • Organizer
      Noon lecture, Indiana University-Osaka University Partnership Symposium
    • Place of Presentation
      Indianapolis, USA
    • Year and Date
      2011-05-25
  • [Presentation] IMRT Dose calculation to account for intrafractional rigid motion2011

    • Author(s)
      Masaki Suga
    • Organizer
      Resident didactic session, Indiana University-Osaka University Partnership Symposium
    • Place of Presentation
      Indianapolis, USA
    • Year and Date
      2011-05-25
  • [Presentation] Dose calculation for high-accuracy radiotherapy, Monte Carlo simulations concerning article therapy2011

    • Author(s)
      Masaaki Takashina
    • Organizer
      Scientific and Clinical Symposium, Indiana University-Osaka University Partnership Symposium
    • Place of Presentation
      Bloomington, USA
    • Year and Date
      2011-05-25
  • [Presentation] Therapeutic Imaging and/or Imaging Application2011

    • Author(s)
      Hideki Takegawa
    • Organizer
      Cancer Informatics and Imaging Technology Workshop, Indiana University-Osaka University Partnership Symposium
    • Place of Presentation
      Indianapolis, USA
    • Year and Date
      2011-05-24
  • [Presentation] Development of the next generation diagnostic devices Diagnostic imaging with a photon counting CdTe line detector2011

    • Author(s)
      Masaaki Takashina
    • Organizer
      Cancer Informatics and Imaging Technology Workshop, Indiana University-Osaka University Partnership Symposium
    • Place of Presentation
      Indianapolis, USA
    • Year and Date
      2011-05-24
  • [Presentation] Cancer Information System Utilizing IT2011

    • Author(s)
      Hodaka Numasaki
    • Organizer
      Cancer Informatics and Imaging Technology Workshop, Indiana University-Osaka University Partnership Symposium
    • Place of Presentation
      Indianapolis, USA
    • Year and Date
      2011-05-24
  • [Presentation] An investigation of sequential boost IMRT versus SIB IMRT for Head and Neck Cancer2011

    • Author(s)
      Hideki Takegawa
    • Organizer
      ESTRO International Oncology Forum
    • Place of Presentation
      London, UK
    • Year and Date
      2011-05-08
  • [Presentation] 加速度センサを用いた呼吸コーチングシステムの精度検証2011

    • Author(s)
      小野智博
    • Organizer
      第297回日本医学放射線学会関西地方会
    • Place of Presentation
      大阪
    • Year and Date
      2011-02-05
  • [Remarks]

    • URL

      http://sahswww.med.osaka-u.ac.jp/~rad-onc/

URL: 

Published: 2013-06-26  

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