Page 313 - 2014 Printable Abstract Book
P. 313
hippocampus fractions by microdissection. The iTRAQ analysis is validated by immunoblot. Results: We
found significant (p<0.05) up- and down-regulation of critical proteins in multiple canonical pathways.
Interestingly, some of the most significant changes we observed were in proteins vital to mitochondrial
dysfunction, glioma signaling, Huntington and Parkinson’s signaling pathways. Additionally, our proteomic
analysis of hippocampus fraction extracted from Sirt2 wild-type and knockout mice following whole brain
RT suggests that SIRT2-mediated late toxicities may be related to alterations in proteins such as CLTC,
MAPT, PACSAN1 and UCHL1. Conclusions: Several proteins were found to be uniquely and differentially
expressed in the cortex and hippocampus following whole brain RT. Our data demonstrates novel
pathways with potential targets to mitigate neurotoxicity of brain RT.
1
(PS5-46) Metabolic and genomic effect of tumor presence during radiation. Janice A. Zawaski, PhD ;
2
1
1
Omaima M. Sabek, PhD ; Eastwood X. Leung, PhD ; and M. Waleed. Gaber , Baylor College of Medicine,
1
2
Houston, TX and Houston Methodist Hospital, Houston, TX
Radiation therapy (RT) has been shown to cause functional and genomic changes in the brain,
however, the majority of these studies have been carried out in normal rodent brains. In this study, the
long-term effects of irradiation and tumor presence during radiation were investigated. Sprague Dawley
male rats (7wks) were divided among three experimental groups: Sham implant, RT+sham implant, and
RT+C6-GFP tumor implant (glioma). Hypofractionated irradiation (8-6Gy/day for 5 days) was localized to
a 1cm strip of the cranium starting 5 days post implant, which resulted in a complete regression of the
tumor and prolonged survival. The former tumor area was imaged 65 days post implant using a 9.4T
1
Biospec MRI scanner (Bruker) with a 20cm bore using a quadrature rat brain array. H magnetic resonance
spectroscopy (MRS) was performed in the former tumor/implant region using a STEAM sequence with the
3
following parameters: TR=2s/TE=2.22ms/ # of averages =512/ voxel size 56mm . Tissue was biopsied in
3
the area of the implant (~80mm ) 65 days post implant. RNA was isolated and hybridized onto GeneChip
Rat Exon 1.0 ST Array. Data were analyzed using Significant Analysis of Microarray ANOVA analysis and
Ingenuity Pathway Analysis. A total of 84 genes had a false discovery rate of 3.5%. To find the effect of the
tumor we compared RT+sham implant to RT+C6-tumor implant the highest canonical pathway affected
by the presence of the tumor was the acute phase response signaling (p=0.003), an inflammatory
response. The influence of the tumor also affected the networks associated with cancer/cell
morphology/tissue morphology. MRS revealed that both RT+sham implant and RT+C6-GFP tumor groups
had a significant reduction in taurine levels (p <0.04) in the former tumor/implant area. However, the RT+
C6-GFP tumor group also had a significant increase in GABA levels (p=0.02), which may indicate issues
with synaptic neurotransmission. In addition, in both RT+sham implant and RT+C6-GFP tumor groups,
myo-inositol was not significant (p=0.056 and p=0.061, respectively), but is following the downward trend
associated with RT. In conclusion, we have developed a clinically relevant rat brain tumor model that
incorporates the effect of tumor on RT side effects, which showed changes in genomic response and
neurotransmitter levels.
311 | P a g e
found significant (p<0.05) up- and down-regulation of critical proteins in multiple canonical pathways.
Interestingly, some of the most significant changes we observed were in proteins vital to mitochondrial
dysfunction, glioma signaling, Huntington and Parkinson’s signaling pathways. Additionally, our proteomic
analysis of hippocampus fraction extracted from Sirt2 wild-type and knockout mice following whole brain
RT suggests that SIRT2-mediated late toxicities may be related to alterations in proteins such as CLTC,
MAPT, PACSAN1 and UCHL1. Conclusions: Several proteins were found to be uniquely and differentially
expressed in the cortex and hippocampus following whole brain RT. Our data demonstrates novel
pathways with potential targets to mitigate neurotoxicity of brain RT.
1
(PS5-46) Metabolic and genomic effect of tumor presence during radiation. Janice A. Zawaski, PhD ;
2
1
1
Omaima M. Sabek, PhD ; Eastwood X. Leung, PhD ; and M. Waleed. Gaber , Baylor College of Medicine,
1
2
Houston, TX and Houston Methodist Hospital, Houston, TX
Radiation therapy (RT) has been shown to cause functional and genomic changes in the brain,
however, the majority of these studies have been carried out in normal rodent brains. In this study, the
long-term effects of irradiation and tumor presence during radiation were investigated. Sprague Dawley
male rats (7wks) were divided among three experimental groups: Sham implant, RT+sham implant, and
RT+C6-GFP tumor implant (glioma). Hypofractionated irradiation (8-6Gy/day for 5 days) was localized to
a 1cm strip of the cranium starting 5 days post implant, which resulted in a complete regression of the
tumor and prolonged survival. The former tumor area was imaged 65 days post implant using a 9.4T
1
Biospec MRI scanner (Bruker) with a 20cm bore using a quadrature rat brain array. H magnetic resonance
spectroscopy (MRS) was performed in the former tumor/implant region using a STEAM sequence with the
3
following parameters: TR=2s/TE=2.22ms/ # of averages =512/ voxel size 56mm . Tissue was biopsied in
3
the area of the implant (~80mm ) 65 days post implant. RNA was isolated and hybridized onto GeneChip
Rat Exon 1.0 ST Array. Data were analyzed using Significant Analysis of Microarray ANOVA analysis and
Ingenuity Pathway Analysis. A total of 84 genes had a false discovery rate of 3.5%. To find the effect of the
tumor we compared RT+sham implant to RT+C6-tumor implant the highest canonical pathway affected
by the presence of the tumor was the acute phase response signaling (p=0.003), an inflammatory
response. The influence of the tumor also affected the networks associated with cancer/cell
morphology/tissue morphology. MRS revealed that both RT+sham implant and RT+C6-GFP tumor groups
had a significant reduction in taurine levels (p <0.04) in the former tumor/implant area. However, the RT+
C6-GFP tumor group also had a significant increase in GABA levels (p=0.02), which may indicate issues
with synaptic neurotransmission. In addition, in both RT+sham implant and RT+C6-GFP tumor groups,
myo-inositol was not significant (p=0.056 and p=0.061, respectively), but is following the downward trend
associated with RT. In conclusion, we have developed a clinically relevant rat brain tumor model that
incorporates the effect of tumor on RT side effects, which showed changes in genomic response and
neurotransmitter levels.
311 | P a g e
