In order to evaluate mechanisms of normal tissue injury, adequate in vivo models must be developed. Cell culture does not provide the complex environment that is found in tissues thought to be responsible for the initiation of radiation injury. In addition, experiments assessing late toxicity often require 6 months to determine if the expected injury has occurred. The delivery of radiation with these experiments must be precisely localized to the tissue of interest to prevent possible peripheral effects to confound results. Our laboratory has established an animal program for evaluation of late normal tissue toxicity through initiation of a number of animal protocols designed to develop and further study acute and late toxicity in the esophagus, lung, intestine, and muscle. This has involved the development of specialized radiation treatment immobilizers and shields to deliver the intended dose accurately. Animals have been treated with doses of radiation that we found could reproducibly result in toxicity and samples have been collected for additional high-throughput and hypothesis-driven work to determine the temporal activation of known and yet undescribed pathways in the process of radiation toxicity. In addition, two clinical trials have been initiated, NCI 07-C-0111 and NCI 09-C-0120, that will allow the collection of various biospecimens in patients receiving radiotherapy for gastrointestinal malignancies, breast cancer, and prostate cancer. A number of candidate biomarkers of radiation toxicity will be tested in the context of this clinical trial. An additional trial has recently been opened testing a topical nirtoxide as a posible method to reduce radiation dermatitis. This nitroxide has been studied extensively by the radiation biology branch who is collaborating in this trial.A new line of research has also been developed in this project which involves the use of bone marow stromal cells to mitigate radaition injury. We plan to further develop this project int he coming years to understand better the mechanism of mitigation of radiation injury, optimal delivery techniques, and the molecular interactions responsible for these effects.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC010850-06
Application #
8552863
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2012
Total Cost
$406,583
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Chung, Eun Joo; Sowers, Anastasia; Thetford, Angela et al. (2016) Mammalian Target of Rapamycin Inhibition With Rapamycin Mitigates Radiation-Induced Pulmonary Fibrosis in a Murine Model. Int J Radiat Oncol Biol Phys 96:857-866
Chung, Eun Joo; McKay-Corkum, Grace; Chung, Su et al. (2016) Truncated Plasminogen Activator Inhibitor-1 Protein Protects From Pulmonary Fibrosis Mediated by Irradiation in a Murine Model. Int J Radiat Oncol Biol Phys 94:1163-72
Premo, Christopher; Apolo, Andrea B; Agarwal, Piyush K et al. (2015) Trimodality therapy in bladder cancer: who, what, and when? Urol Clin North Am 42:169-80, vii
Prieto, Darue A; Johann Jr, Donald J; Wei, Bih-Rong et al. (2014) Mass spectrometry in cancer biomarker research: a case for immunodepletion of abundant blood-derived proteins from clinical tissue specimens. Biomark Med 8:269-86
Chung, Eun Joo; Hudak, Kathryn; Horton, Jason A et al. (2014) Transforming growth factor alpha is a critical mediator of radiation lung injury. Radiat Res 182:350-62
Horton, Jason A; Li, Fei; Chung, Eun Joo et al. (2013) Quercetin inhibits radiation-induced skin fibrosis. Radiat Res 180:205-15
Citrin, Deborah E; Shankavaram, Uma; Horton, Jason A et al. (2013) Role of type II pneumocyte senescence in radiation-induced lung fibrosis. J Natl Cancer Inst 105:1474-84
Horton, Jason A; Chung, Eun Joo; Hudak, Kathryn E et al. (2013) Inhibition of radiation-induced skin fibrosis with imatinib. Int J Radiat Biol 89:162-70
Saligan, L N; Hsiao, C P; Wang, D et al. (2013) Upregulation of α-synuclein during localized radiation therapy signals the association of cancer-related fatigue with the activation of inflammatory and neuroprotective pathways. Brain Behav Immun 27:63-70
Citrin, Deborah E; Hitchcock, Ying J; Chung, Eun Joo et al. (2012) Determination of cytokine protein levels in oral secretions in patients undergoing radiotherapy for head and neck malignancies. Radiat Oncol 7:64

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