Abstract

Individual differences in intrinsic cellular radiosensitivity account for at least part of the observed variation in normal tissue responses in radiotherapy patients. This conclusion is based on clinical correlations between early passage fibroblast radiosensitivity and the severity of normal tissue damage in patients. However, normal tissue response to radiation is also influenced by signals of growth, proliferation, and differentiation, which are responses that change with age and physiological conditions. This proposal aims to extend the initial findings of the investigators with additional clinical studies comparing fibroblast radiosensitivity with normal tissue reactions to radiotherapy, to develop alternative or adjuvant non-clonogenic endpoints for in vitro radiation sensitivity measurements, and to test the hypothesis that biological features associated with aging, cellular senescence and radiation-induction of cellular senescence are important for the clinical response of normal tissues to radiotherapy.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
2P01CA006294-36
Application #
6268508
Study Section
Project Start
1998-03-06
Project End
1999-02-28
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
36
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
University of Texas MD Anderson Cancer Center
Department
Type
DUNS #
001910777
City
Houston
State
TX
Country
United States
Zip Code
77030

  Publications

Edmondson, Elijah F; Hunter, Nancy R; Weil, Michael M et al. (2015) Tumor Induction in Mice After Localized Single- or Fractionated-Dose Irradiation: Differences in Tumor Histotype and Genetic Susceptibility Based on Dose Scheduling. Int J Radiat Oncol Biol Phys 92:829-36
Neskey, David M; Osman, Abdullah A; Ow, Thomas J et al. (2015) Evolutionary Action Score of TP53 Identifies High-Risk Mutations Associated with Decreased Survival and Increased Distant Metastases in Head and Neck Cancer. Cancer Res 75:1527-36
Keck, Michaela K; Zuo, Zhixiang; Khattri, Arun et al. (2015) Integrative analysis of head and neck cancer identifies two biologically distinct HPV and three non-HPV subtypes. Clin Cancer Res 21:870-81
Alsbeih, Ghazi; Brock, Williams; Story, Michael (2014) Misrepair of DNA double-strand breaks in patient with unidentified chromosomal fragility syndrome and family history of radiosensitivity. Int J Radiat Biol 90:53-9
Komaki, Ritsuko; Paulus, Rebecca; Blumenschein Jr, George R et al. (2014) EGFR expression and survival in patients given cetuximab and chemoradiation for stage III non-small cell lung cancer: a secondary analysis of RTOG 0324. Radiother Oncol 112:30-6
Cortez, Maria Angelica; Valdecanas, David; Zhang, Xiaochun et al. (2014) Therapeutic delivery of miR-200c enhances radiosensitivity in lung cancer. Mol Ther 22:1494-1503
Bhardwaj, Vikas; Cascone, Tina; Cortez, Maria Angelica et al. (2013) Modulation of c-Met signaling and cellular sensitivity to radiation: potential implications for therapy. Cancer 119:1768-75
Skinner, Heath D; Sandulache, Vlad C; Ow, Thomas J et al. (2012) TP53 disruptive mutations lead to head and neck cancer treatment failure through inhibition of radiation-induced senescence. Clin Cancer Res 18:290-300
Story, Michael; Ding, Liang-hao; Brock, William A et al. (2012) Defining molecular and cellular responses after low and high linear energy transfer radiations to develop biomarkers of carcinogenic risk or therapeutic outcome. Health Phys 103:596-606
Raju, Uma; Riesterer, Oliver; Wang, Zhi-Qiang et al. (2012) Dasatinib, a multi-kinase inhibitor increased radiation sensitivity by interfering with nuclear localization of epidermal growth factor receptor and by blocking DNA repair pathways. Radiother Oncol 105:241-9

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