Page 332 - 2014 Printable Abstract Book
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various macrophage and inflammatory markers. Relative to untreated controls, mitigation of radiation-
induced skin injury in mice receiving MW-151 was highly dependent on the timing of therapy initiation.
Initiation on day 3 post-irradiation had no effect, initiation on day 7 yielded maximal mitigating effects,
and initiation on day 14 yielded sub-optimal mitigating effects. The response to MW-151 therapy in
individual animals was essentially all-or-none and the relative benefits associated with the timing of
therapy initiation primarily reflected differences in the number of responders. These data support the
hypothesis that proinflammatory cytokines/chemokines play complex roles in orchestrating the response
to radiation-induced skin injury and suggest that there is a critical period during which they initiate the
pathogenesis resulting in late effects. The mitigating strategies that we have identified using MW-151
illustrate the importance of therapeutically targeting the pathogenesis of radiation-induced skin injury at
critical periods during its development.
(PS6-14) Global plasma protein kinetics of irradiated minipigs. Jordan N. Smith; Erin Baker; Paul D.
Piehowski; Kristin E. Burnum-Johnson; Bobbie-Jo M. Webb-Robertson; Jamie Lovaglio; Richard D.Smith;
Karla D. Thrall, PNNL, Richland, WA
Improved biomarkers of acute radiation exposure are needed for determining clinical dosimetry,
triage and treatment decisions, and therapeutic development in humans. In order to better understand
the onset and progression of acute radiation syndrome, we characterized the kinetics of global plasma
proteome after acute whole-body irradiation in the Göttingen minipig using novel mass spectrometric
techniques. Minipigs were irradiated at historical 0 (sham), LD25/45, LD50/45, and LD75/45 dose levels using
60 Co as the radiation source. After irradiation, minipigs received minimal supportive care, which included
antibiotics and fluid support to post-irradiation day 30. Plasma was collected pre exposure and at regular
intervals ranging from 6 hr to 45 d post exposure. Plasma samples were depleted of major albumin and
IgG proteins, digested with trypsin, and analyzed with liquid chromatography coupled with ion mobility
spectrometry and time of flight mass spectrometry (LC-IMS-TOF MS). Identification and quantification of
the detected peptide peaks were performed utilizing the Accurate Mass and Time tag approach.
Preliminary results from ongoing statistical analyses suggest that peptide abundances change in control
versus irradiated minipigs as well as on survival outcome at the high dose (~18% difference in peptide
abundances across all time points). Several targeted biomarkers were quantified using enzyme-linked
immunosorbent assay (ELISA) including interlukin-6 (IL-6), C-reactive protein, and serum amyloid A and
will be used to validate proteins discovered with LC-IMS-TOF MS. This approach will serve as a valuable
tool for biomarker discovery and support the use of the Göttingen minipig as an animal model to evaluate
medical countermeasures for acute radiation exposure. Work supported under Biomedical Advanced
Research and Development Authority (BARDA) Contract No. HHSO100201100010I and PNNL Laboratory
Directed Research. Key Words: Gottingen minipig, radiation, biomarker
(PS6-15) Identification and verification of novel plasma protein radiation biomarkers by liquid
chromatography tandem mass spectrometry: from animal models to human radiotherapy patients. Hua
1
1
1
1
1
1
1
Lin ; Thomas A. Shaler ; Sophia Chen ; Polly Chang ; Robert P. Balog ; Annalisa D’Andrea ; Travis Harrison ;
1
1
2
1
2
Susan J. Knox ; Shirley Lee ; Lei Shura ; and David E. Cooper , SRI International, Menlo Park, CA and
Department of Radiation Oncology, Stanford University, Stanford, CA
2
330 | P a g e
induced skin injury in mice receiving MW-151 was highly dependent on the timing of therapy initiation.
Initiation on day 3 post-irradiation had no effect, initiation on day 7 yielded maximal mitigating effects,
and initiation on day 14 yielded sub-optimal mitigating effects. The response to MW-151 therapy in
individual animals was essentially all-or-none and the relative benefits associated with the timing of
therapy initiation primarily reflected differences in the number of responders. These data support the
hypothesis that proinflammatory cytokines/chemokines play complex roles in orchestrating the response
to radiation-induced skin injury and suggest that there is a critical period during which they initiate the
pathogenesis resulting in late effects. The mitigating strategies that we have identified using MW-151
illustrate the importance of therapeutically targeting the pathogenesis of radiation-induced skin injury at
critical periods during its development.
(PS6-14) Global plasma protein kinetics of irradiated minipigs. Jordan N. Smith; Erin Baker; Paul D.
Piehowski; Kristin E. Burnum-Johnson; Bobbie-Jo M. Webb-Robertson; Jamie Lovaglio; Richard D.Smith;
Karla D. Thrall, PNNL, Richland, WA
Improved biomarkers of acute radiation exposure are needed for determining clinical dosimetry,
triage and treatment decisions, and therapeutic development in humans. In order to better understand
the onset and progression of acute radiation syndrome, we characterized the kinetics of global plasma
proteome after acute whole-body irradiation in the Göttingen minipig using novel mass spectrometric
techniques. Minipigs were irradiated at historical 0 (sham), LD25/45, LD50/45, and LD75/45 dose levels using
60 Co as the radiation source. After irradiation, minipigs received minimal supportive care, which included
antibiotics and fluid support to post-irradiation day 30. Plasma was collected pre exposure and at regular
intervals ranging from 6 hr to 45 d post exposure. Plasma samples were depleted of major albumin and
IgG proteins, digested with trypsin, and analyzed with liquid chromatography coupled with ion mobility
spectrometry and time of flight mass spectrometry (LC-IMS-TOF MS). Identification and quantification of
the detected peptide peaks were performed utilizing the Accurate Mass and Time tag approach.
Preliminary results from ongoing statistical analyses suggest that peptide abundances change in control
versus irradiated minipigs as well as on survival outcome at the high dose (~18% difference in peptide
abundances across all time points). Several targeted biomarkers were quantified using enzyme-linked
immunosorbent assay (ELISA) including interlukin-6 (IL-6), C-reactive protein, and serum amyloid A and
will be used to validate proteins discovered with LC-IMS-TOF MS. This approach will serve as a valuable
tool for biomarker discovery and support the use of the Göttingen minipig as an animal model to evaluate
medical countermeasures for acute radiation exposure. Work supported under Biomedical Advanced
Research and Development Authority (BARDA) Contract No. HHSO100201100010I and PNNL Laboratory
Directed Research. Key Words: Gottingen minipig, radiation, biomarker
(PS6-15) Identification and verification of novel plasma protein radiation biomarkers by liquid
chromatography tandem mass spectrometry: from animal models to human radiotherapy patients. Hua
1
1
1
1
1
1
1
Lin ; Thomas A. Shaler ; Sophia Chen ; Polly Chang ; Robert P. Balog ; Annalisa D’Andrea ; Travis Harrison ;
1
1
2
1
2
Susan J. Knox ; Shirley Lee ; Lei Shura ; and David E. Cooper , SRI International, Menlo Park, CA and
Department of Radiation Oncology, Stanford University, Stanford, CA
2
330 | P a g e
