(C) 2014 Elsevier Ltd. All rights reserved.”
“Purpose: Predictive assays for acute radiation toxicities would be clinically relevant in radiation oncology. We prospectively examined the predictive role of the survival
fraction at 2 Gy (SF2) and of gamma H2AX (double-strand break [DSB]DNA marker) expression kinetics in peripheral blood mononuclear cells (PBMCs) from cancer patients before radiation therapy. AZD5582 molecular weight Methods and Materials: SF2 was measured with Trypan Blue assay in the PBMCs from 89 cancer patients undergoing radiation therapy at 4 hours (SF2([4h])) and 24 hours (SF2([24h])) after ex vivo irradiation. Using Western blot analysis and band densitometry, we further assessed the expression of gamma H2AX in PBMC DNA at 0 hours, 30 minutes, and 4 hours (33 patients) and 0 hour, 4 hours, and 24 hours (56 patients), following ex vivo irradiation with 2 Gy. Appropriate ratios were used to characterize each patient, and these were retrospectively correlated with early radiation therapy toxicity grade. Results: The SF2((4h)) was inversely correlated with the toxicity grade
(P=.006). The gamma H2AX-ratio(30min) (band density of irradiated/ non-irradiated cells at 30 minutes) revealed, similarly, a significant inverse association (P=.0001). The DSB DNA repair rate from 30 minutes to 4 hours, calculated as the relative R gamma H2AX-ratio Small molecule library (gamma H2AX-ratio((4h))/gamma H2AX-ratio(30min)) showed a significant direct association with BAY 63-2521 datasheet high
toxicity grade (P=.01). Conclusions: Our results suggest that SF2 is a significant radiation sensitivity index for patients undergoing radiation therapy. gamma H2AX Western blot densitometry analysis provided 2 important markers of normal tissue radiation sensitivity. Low gamma H2AX expression at 30 minutes was linked with high toxicity grade, suggesting that poor gamma H2AX repair activity within a time frame of 30 minutes after irradiation predicts for poor radiation tolerance. On the other hand, rapid gamma H2AX content restoration at 4 hours after irradiation, compatible with efficient DSB repair ability, predicts for increased radiation tolerance. (C) 2015 Elsevier Inc. All rights reserved.”
“Background: Neuropeptide Y (NPY) has been implicated in the modulation of pain. Under normal conditions, NPY is found in interneurons in the dorsal horn of the spinal cord and in sympathetic postganglionic neurons but is absent from the cell bodies of sensory neurons. Following peripheral nerve injury NPY is dramatically upregulated in the sensory ganglia. How NPY expression is altered in the peripheral nervous system, distal to a site of nerve lesion, remains unknown.