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Mathematical Models for Carcinogenesis Based on the Evidence of Molecular Biology and Its Application to Data Analysis

Research Project

Project/Area Number 14380123
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Statistical science
Research InstitutionHIROSHIMA UNIVERSITY

Principal Investigator

OHTAKI Megu  Hiroshima University, Research Institute for Radiation Biology and Medicine, Professor, 原爆放射線医科学研究所, 教授 (20110463)

Co-Investigator(Kenkyū-buntansha) KAI Mitiaki  Oita University of Nursing and Health Sciences, Faculty of Health Sciences, Professor, 看護学部, 教授 (10185697)
IZUMI Shizue  Oita University, Faculty of Technique, Associate Professor, 工学部, 助教授 (70344413)
SATOH Kenichi  Hiroshima University, Research Institute for Radiation Biology and Medicine, Assistant Professor, 原爆放射線医科学研究所, 講師 (30284219)
NIWA Ohtsura  Kyoto University, Radiation Biology Center, Professor, 放射線生物研究センター, 教授 (80093293)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
KeywordsMulti-target model / Apoptsis / Individual difference / Dose-response / Age-dependency / Genomic instabnility / 発がん過程 / 多段階モデル / 遺伝的不安定性伝説 / 揺らぎ / 遺伝的不安定性仮説
Research Abstract

We developed multistage models of carcinogenesis and cell death with taking account the effect of genomic instability. As for Armitage-Doll type of multistage models for carcinogenesis, some Monte Carlo simulations on the relationship between the number of stages and mutation rate were done. Using the follow-up data among atomic-bomb survivors and offspring, we examined the property of the models.
The classical multi-target models have been also considered for use in analyzing data of the dose-response relationship. We tried to make some extended models. The target sizes we are concerned with are heterogeneous as simplified using geometric progression. We apply two models for establishing the multi-target models: a Poisson regression model constructed by assuming that the response variable follows Poisson distribution, and a gamma-frailty model as a Poisson mixture model derived by adding random common risks having a gamma distribution.
Based on the theoretical results of our study, we developed several computer programs for analyzing dose-response data, and applied them to many sort of real data sets related to animal experiments, clinical researches and epidemiological studies including atomic bomb survivor's cohort data.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (26 results)

All 2005 2004 Other

All Journal Article (22 results) Patent(Industrial Property Rights) (1 results) Publications (3 results)

  • [Journal Article] Genotyping of single nucleotide polymorphism based on a mathematical model for two-dimensional data2005

    • Author(s)
      K Satoh
    • Journal Title

      Japanese Journal of Biometrics 25

      Pages: 61-67

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Model-based analysis of microarray data : Exploration of differentially expressed genes between two-cell types based on a two-dimensional mixed normal model2005

    • Author(s)
      M Ohtaki
    • Journal Title

      Japanese Journal of Biometrics 26

      Pages: 31-48

    • NAID

      10019034825

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Multi-target models and their application to data analysis of cellular mortality due to radiation exposure.2005

    • Author(s)
      I-M Arcana
    • Journal Title

      Hiroshima Journal of Medical Sciences 54

      Pages: 9-20

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The mutation of myeloma cells correlates with sensitivity to chemotherapeutic agents2005

    • Author(s)
      Y Kuroda
    • Journal Title

      International Journal of Hematology 81

      Pages: 335-341

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Apparent diffusion coefficient of human brain tumors at MR Imaging2005

    • Author(s)
      F Yamasaki
    • Journal Title

      Radiology 235

      Pages: 985-991

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Transcription-independent suppression of DNA synthesis by p53 in spern-irradiated mouse zygotes2005

    • Author(s)
      M Toyoshima
    • Journal Title

      Oncogene

      Pages: 1-7

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Prediction to mouse thymic lymphomas in response to ionizing radiation depends on variant alleles encoding metal-responsive transcription factor-1 (Mtf-1)2005

    • Author(s)
      Y Tamura
    • Journal Title

      Oncogene 24

      Pages: 399-406

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Comparison of properties of spontaneous and radiation-induced mouse thymic lymphomas : Role of trp53 and radiation2005

    • Author(s)
      T Kobata
    • Journal Title

      Radiation Research 163

      Pages: 159-164

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Genotyping of single nucleotide polymorphism based on a mathematical model for two-dimensional data2005

    • Author(s)
      K Satoh
    • Journal Title

      Jpn J of Biomet 25

      Pages: 61-67

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Model-based analysis of microarray data : Exploration of differentially expressed genes between two-cell types based on a two-dimensional mixed normal model2005

    • Author(s)
      M Ohtaki
    • Journal Title

      Jpn J of Biomet 26

      Pages: 31-48

    • NAID

      10019034825

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Multi-target models and their application to data analysis of cellular mortality due to radiation exposure2005

    • Author(s)
      I-M Arcana
    • Journal Title

      Hiroshima J Med.Sci. 54

      Pages: 9-20

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The mutation of myeloma cells correlates with sensitivity to chemotherapeutic agents2005

    • Author(s)
      Y Kuroda
    • Journal Title

      Int.J Hematol. 81

      Pages: 335-341

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Transcription-independent suppression of DNA synthesis by p53 in sperm-irradiated mouse zygotes2005

    • Author(s)
      M Toyoshima
    • Journal Title

      Oncogene

      Pages: 1-7

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Comparison of properties of spontaneous and radiation-induced mouse thymic lymphomas : Role of trp53 and radiation2005

    • Author(s)
      T Kobata
    • Journal Title

      Radiat.Res. 163

      Pages: 159-164

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Differentially expressed genes throughout the cellular immortalization process are quite different between normal human fibroblasts and endothelial cells2005

    • Author(s)
      Keiko Hiyama, Keiko Otani, Megu Ohtaki, Kenichi Satoh
    • Journal Title

      International Journal of Oncology 26(in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Comparison of properies of spontaneous and radiation induced mouse thymic lymphomas : Role of Trp53 and radiation.2005

    • Author(s)
      Kubota T, Yoshikai Y, Tamura Y, Mishima Y, Aoyagi Y, Niwa O, Kominami R.
    • Journal Title

      Radiation Research 163

      Pages: 159-164

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Aspects of the Armitage-Doll gamma frailty model for cancer incidence data2004

    • Author(s)
      S Izumi
    • Journal Title

      Environmetrics 15

      Pages: 209-218

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Excess concordance of cancer incidence and lifestyles in married couples (Japan) : Survival analysis of paired rate data2004

    • Author(s)
      S Izumi
    • Journal Title

      Cancer Causes and Control 15

      Pages: 551-558

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 乳癌の腫瘍成長の数理モデルを用いたスクリーニングマンモグラフィの余命延長効果の評価2004

    • Author(s)
      小野 治子
    • Journal Title

      日本乳癌検診学会誌 13

      Pages: 289-297

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Excess concordance of cancer incidence and life styles in married couples (Japan) : Survival analysis of paired rate data2004

    • Author(s)
      S Izumi
    • Journal Title

      Cancer Causes and Control 15

      Pages: 551-558

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Genotyping of single nucleotide polymorphisms based on a mathematical model for two-dimensional data.2004

    • Author(s)
      K.Satoh, K.Ohtani, M.Ushijima, M.Isomura, M.Matsuura, Y.Miki, M.Ohtaki
    • Journal Title

      Japanese Journal of Biometrics 25(2)

      Pages: 61-67

    • NAID

      10014334851

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Multi-target models and their application to data analysis of cellular mortality due to radiation exposure.

    • Author(s)
      I Made Arcana, Megu Ohtaki
    • Journal Title

      Hiroshima Journal of Medical Sciences (in press)

    • NAID

      110004594318

    • Related Report
      2004 Annual Research Report
  • [Patent(Industrial Property Rights)] 順序カテゴリーデータに対する解析手法、解析システム及び解析プログラム2004

    • Inventor(s)
      大瀧 慈, 佐藤 健一, 安東 正貴, 齋藤 彰
    • Industrial Property Rights Holder
      広島大学, 日本電気
    • Industrial Property Number
      2004-202712
    • Filing Date
      2004-07-08
    • Related Report
      2004 Annual Research Report
  • [Publications] Shizue Izumi, Megu Ohtaki: "Aspects of the Armitage-Doll gamma frailty Model for cancer incidence data"Environmetrics. (印刷中).

    • Related Report
      2003 Annual Research Report
  • [Publications] Shiraishi, K.: "Persistent Induction of Somatic Reversions of the Pink-Eyed Unstable Mutation in F1 Mice Born to Fathers Irradiated at the Spermatozoa Stage"Radiation Research. 157. 661-667 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamaguchi, T.: "Enhancement of thymidine kinase-mediated killing of malignant glioma by BimS, a BH3-only cell death activator"Gene Therapy. (in press).

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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