U19 project two

project two:

lung model for nuclear dispersion event

The principal goal of this project is directed at gaining a deeper understanding of the basis for the normal tissue late effects that are observed in the lung at low external doses and, more importantly, in the whole body from the exposure that occurs as a result of a radiological and/or nuclear dispersion event. In a dispersion event, one component of the risk of radiation exposure will come from the inhalation of radionuclides, whose characteristics will be determined by the nature of the isotope used and the device itself. Thus, an important aspect of such an event is that the resultant radiation exposure can occur internally, and may be localized depending on the physical and chemical nature of the radioactive material(s) involved.

Project Two Personnel

Members of Project Two: (top, L to R), Carl Johnston PhD, Jacob Finkelstein PhD, Eric Hernady; (bottom, L to R), Jacky Williams PhD, Chris Reed.

Thoracic and whole-body long-term pre-clinical studies (Specific Aim 1) have been completed; the full spectrum of proposed analyses are underway; the irradiations for Phase II have been completed. Time points have been completed to 9-months post-radiation in Phase II. As suggested by our Biostatistics Core, the Phase II study has been expanded to include a group that undergoes serial bleeds in order to correlate cytokine profiles from early time points to the late events in the same subject. From the tissues and samples collected to date, cytokine profiles using bead arrays have been generated for a panel of cytokines and growth factors of interest; the membrane array data from the early time points (1 hour to 1 month) for both phases have been completed. Final analysis is now underway, in collaboration with our Biostatistics Core.
The phase I studies of Specific Aim 2 examining the distribution of inhaled particles have been completed. Gold particles of varying sizes were administered to our pre-clinical model by various routes (inhalation versus instillation versus injection) and their distribution was assessed following neutron activation by our collaborators at McMaster University.
As part of the final two aims, our pre-clinical examination of the cytokine response in neonates has begun, and our early results are suggesting a differential response between young and adult subjects. In addition, intervention studies are currently underway using our proposed agents. Early studies are analyzing the effects of these agents on the cytokine profile identified in Phases I and II of Specific Aim 1. These studies will continue with agents identified by Project 1 and will be extended to look at later time points.

Project 2: Communications & Publications

• Jacqueline P. Williams, Eric Hernady, Carl Johnston, Christina Reed, Günter Oberdörster, Paul Okunieff, Jacob N. Finkelstein. Early alterations in cytokine expression after low dose radiation: markers or mediators? 53rd Annual meeting of the Radiation Research Society, Philadelphia, November 5-8, 2006 (oral presentation).
• Jacob N. Finkelstein, Eric Hernady, Carl Johnston, Christina Reed, Günter Oberdörster, Paul Okunieff, Jacqueline P. Williams. Changes in the pulmonary cellular response following low dose radiation. 53rd Annual meeting of the Radiation Research Society, Philadelphia, November 5-8, 2006 (poster presentation).
• Jacqueline P. Williams, Eric Hernady, Carl Johnston, Christina Reed, Günter Oberdörster, Paul Okunieff, Jacob N. Finkelstein. Early alterations in cytokine expression after low dose radiation: markers or mediators? 11th Annual Scientific Symposium, James P. Wilmot Cancer Center, University of Rochester, November 16, 2006 (poster presentation).
• Jacob N. Finkelstein, Eric Hernady, Carl Johnston, Christina Reed, Günter Oberdörster, Paul Okunieff, Jacqueline P. Williams. Changes in the pulmonary cellular response following low dose radiation. 11th Annual Scientific Symposium, James P. Wilmot Cancer Center, University of Rochester, November 16, 2006 (poster presentation).
• J.P. Williams, C. Johnston, E. Hernady, C. Reed, J.N. Finkelstein. Cytokines and radiation treatment: mitigators or mitigating targets. 13th International Congress of Radiation Research, San Francisco, July 8-12, 2007 (invited speaker).
• J.N. Finkelstein, J.P. Williams, E. Hernady, C. Reed, P. Okunieff, C.J. Johnston. Early alterations in pulmonary interleukin expression and cellular responses after low dose radiation. 13th International Congress of Radiation Research, San Francisco, July 8-12, 2007.
• C.J. Johnston, J.P. Williams, E. Hernady, J.N. Finkelstein. Radiation injury during postnatal lung development. 13th International Congress of Radiation Research, San Francisco, July 8-12, 2007.
• J. P. Williams, C. Johnston, E. Hernady, C. Reed, J. N. Finkelstein. Potential use of early cytokine changes as surrogate markers in adults versus children following a terrorist event. 49th Annual Meeting of the American Society for Therapeutic Radiology and Oncology, Los Angeles, October 28-November 1, 2007.

Project 2 has made substantial progress toward development of a model for the inhalation of radioactive particles. This unique model will be used to assess the utility of potential mitigating agents in several population models (i.e., pediatric, elderly). Priority agents for testing will include the foremost candidate agents from Project 1, as well as agents developed within the CMCR network. This model also offers the opportunity to test the efficacy of decorporation agents. As in Project 1, a major goal of this Project is to develop a panel of cytokine/growth factor proteins that play a critical role in the progression towards pulmonary late effects following radiation exposure and then use this panel of biomarkers as an assessment tool. We have made considerable progress on this goal. Long term studies of toxicity are underway.

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	project two: lung model for nuclear dispersion event

			The principal goal of this project is directed at gaining a deeper understanding of the basis for the normal tissue late effects that are observed in the lung at low external doses and, more importantly, in the whole body from the exposure that occurs as a result of a radiological and/or nuclear dispersion event. In a dispersion event, one component of the risk of radiation exposure will come from the inhalation of radionuclides, whose characteristics will be determined by the nature of the isotope used and the device itself. Thus, an important aspect of such an event is that the resultant radiation exposure can occur internally, and may be localized depending on the physical and chemical nature of the radioactive material(s) involved.













Project Two Personnel



			Members of Project Two: (top, L to R), Carl Johnston PhD, Jacob Finkelstein PhD, Eric Hernady; (bottom, L to R), Jacky Williams PhD, Chris Reed.



				Thoracic and whole-body long-term pre-clinical studies (Specific Aim 1) have been completed; the full spectrum of proposed analyses are underway; the irradiations for Phase II have been completed. Time points have been completed to 9-months post-radiation in Phase II. As suggested by our Biostatistics Core, the Phase II study has been expanded to include a group that undergoes serial bleeds in order to correlate cytokine profiles from early time points to the late events in the same subject. From the tissues and samples collected to date, cytokine profiles using bead arrays have been generated for a panel of cytokines and growth factors of interest; the membrane array data from the early time points (1 hour to 1 month) for both phases have been completed. Final analysis is now underway, in collaboration with our Biostatistics Core. The phase I studies of Specific Aim 2 examining the distribution of inhaled particles have been completed. Gold particles of varying sizes were administered to our pre-clinical model by various routes (inhalation versus instillation versus injection) and their distribution was assessed following neutron activation by our collaborators at McMaster University. As part of the final two aims, our pre-clinical examination of the cytokine response in neonates has begun, and our early results are suggesting a differential response between young and adult subjects. In addition, intervention studies are currently underway using our proposed agents. Early studies are analyzing the effects of these agents on the cytokine profile identified in Phases I and II of Specific Aim 1. These studies will continue with agents identified by Project 1 and will be extended to look at later time points.





Project 2: Communications & Publications • Jacqueline P. Williams, Eric Hernady, Carl Johnston, Christina Reed, Günter Oberdörster, Paul Okunieff, Jacob N. Finkelstein. Early alterations in cytokine expression after low dose radiation: markers or mediators? 53rd Annual meeting of the Radiation Research Society, Philadelphia, November 5-8, 2006 (oral presentation). • Jacob N. Finkelstein, Eric Hernady, Carl Johnston, Christina Reed, Günter Oberdörster, Paul Okunieff, Jacqueline P. Williams. Changes in the pulmonary cellular response following low dose radiation. 53rd Annual meeting of the Radiation Research Society, Philadelphia, November 5-8, 2006 (poster presentation). • Jacqueline P. Williams, Eric Hernady, Carl Johnston, Christina Reed, Günter Oberdörster, Paul Okunieff, Jacob N. Finkelstein. Early alterations in cytokine expression after low dose radiation: markers or mediators? 11th Annual Scientific Symposium, James P. Wilmot Cancer Center, University of Rochester, November 16, 2006 (poster presentation). • Jacob N. Finkelstein, Eric Hernady, Carl Johnston, Christina Reed, Günter Oberdörster, Paul Okunieff, Jacqueline P. Williams. Changes in the pulmonary cellular response following low dose radiation. 11th Annual Scientific Symposium, James P. Wilmot Cancer Center, University of Rochester, November 16, 2006 (poster presentation). • J.P. Williams, C. Johnston, E. Hernady, C. Reed, J.N. Finkelstein. Cytokines and radiation treatment: mitigators or mitigating targets. 13th International Congress of Radiation Research, San Francisco, July 8-12, 2007 (invited speaker). • J.N. Finkelstein, J.P. Williams, E. Hernady, C. Reed, P. Okunieff, C.J. Johnston. Early alterations in pulmonary interleukin expression and cellular responses after low dose radiation. 13th International Congress of Radiation Research, San Francisco, July 8-12, 2007. • C.J. Johnston, J.P. Williams, E. Hernady, J.N. Finkelstein. Radiation injury during postnatal lung development. 13th International Congress of Radiation Research, San Francisco, July 8-12, 2007. • J. P. Williams, C. Johnston, E. Hernady, C. Reed, J. N. Finkelstein. Potential use of early cytokine changes as surrogate markers in adults versus children following a terrorist event. 49th Annual Meeting of the American Society for Therapeutic Radiology and Oncology, Los Angeles, October 28-November 1, 2007.

				Project 2 has made substantial progress toward development of a model for the inhalation of radioactive particles. This unique model will be used to assess the utility of potential mitigating agents in several population models (i.e., pediatric, elderly). Priority agents for testing will include the foremost candidate agents from Project 1, as well as agents developed within the CMCR network. This model also offers the opportunity to test the efficacy of decorporation agents. As in Project 1, a major goal of this Project is to develop a panel of cytokine/growth factor proteins that play a critical role in the progression towards pulmonary late effects following radiation exposure and then use this panel of biomarkers as an assessment tool. We have made considerable progress on this goal. Long term studies of toxicity are underway.


about these images		contact us			website amy k. huser