PURPOSE: Neuroinflammatory mechanisms are associated with fatigue in neurodegenerative conditions such as Parkinson's. The symptoms in Parkinson's including fatigue are thought to be related to α-synuclein overexpression. This study investigated genomic correlates of fatigue experienced by men with prostate cancer receiving external beam radiation therapy (EBRT). PATIENTS AND METHODS: Sixteen men with non-metastatic prostate cancer who were scheduled to receive EBRT were enrolled. Fatigue scores and blood were obtained at baseline (prior to EBRT, D0); one hour following initiation of EBRT (D1), day 7 (D7), day 14 (D14), midpoint (days 19-21, D21), completion (days 38-42, D42), and four weeks post-EBRT (days 68-72, D72). Gene expression profiling using microarray analysis was performed from peripheral blood and confirmatory qPCR and protein (ELISA) analyses verified the microarray results. Correlations between fatigue and gene/protein expressions were determined using a mixed model approach. RESULTS: Microarray data showed significant, differential expression of 463 probesets following EBRT. SNCA had a 2.95-fold change at D21 from baseline. SNCA expression was confirmed by qPCR (p<0.001) and ELISA (p<0.001) over time during EBRT. Fatigue scores were significantly correlated with SNCA gene expression on D14 (r=0.55, p<0.05) and plasma α-synuclein concentrations on D42 of EBRT (r=0.54, p=0.04). CONCLUSION: Fatigue experienced during EBRT may be mediated by α-synuclein overexpression. Alpha-synuclein may serve as a useful biomarker to understand the mechanisms and pathways related to the development of fatigue in this population. Published by Elsevier Inc.
PURPOSE: Neuroinflammatory mechanisms are associated with fatigue in neurodegenerative conditions such as Parkinson's. The symptoms in Parkinson's including fatigue are thought to be related to α-synuclein overexpression. This study investigated genomic correlates of fatigue experienced by men with prostate cancer receiving external beam radiation therapy (EBRT). PATIENTS AND METHODS: Sixteen men with non-metastatic prostate cancer who were scheduled to receive EBRT were enrolled. Fatigue scores and blood were obtained at baseline (prior to EBRT, D0); one hour following initiation of EBRT (D1), day 7 (D7), day 14 (D14), midpoint (days 19-21, D21), completion (days 38-42, D42), and four weeks post-EBRT (days 68-72, D72). Gene expression profiling using microarray analysis was performed from peripheral blood and confirmatory qPCR and protein (ELISA) analyses verified the microarray results. Correlations between fatigue and gene/protein expressions were determined using a mixed model approach. RESULTS: Microarray data showed significant, differential expression of 463 probesets following EBRT. SNCA had a 2.95-fold change at D21 from baseline. SNCA expression was confirmed by qPCR (p<0.001) and ELISA (p<0.001) over time during EBRT. Fatigue scores were significantly correlated with SNCA gene expression on D14 (r=0.55, p<0.05) and plasma α-synuclein concentrations on D42 of EBRT (r=0.54, p=0.04). CONCLUSION:Fatigue experienced during EBRT may be mediated by α-synuclein overexpression. Alpha-synuclein may serve as a useful biomarker to understand the mechanisms and pathways related to the development of fatigue in this population. Published by Elsevier Inc.
Authors: Ian Thompson; James Brantley Thrasher; Gunnar Aus; Arthur L Burnett; Edith D Canby-Hagino; Michael S Cookson; Anthony V D'Amico; Roger R Dmochowski; David T Eton; Jeffrey D Forman; S Larry Goldenberg; Javier Hernandez; Celestia S Higano; Stephen R Kraus; Judd W Moul; Catherine M Tangen Journal: J Urol Date: 2007-06 Impact factor: 7.450
Authors: V Mock; A Atkinson; A Barsevick; D Cella; B Cimprich; C Cleeland; J Donnelly; M A Eisenberger; C Escalante; P Hinds; P B Jacobsen; P Kaldor; S J Knight; A Peterman; B F Piper; H Rugo; P Sabbatini; C Stahl Journal: Oncology (Williston Park) Date: 2000-11 Impact factor: 2.990
Authors: Christine Miaskowski; Steven M Paul; Bruce A Cooper; Kathryn Lee; Marylin Dodd; Claudia West; Bradley E Aouizerat; Patrick S Swift; William Wara Journal: J Pain Symptom Manage Date: 2008-03-20 Impact factor: 3.612
Authors: Marie Westerlund; Andrea Carmine Belin; Anna Anvret; Anna Håkansson; Hans Nissbrandt; Charlotta Lind; Olof Sydow; Lars Olson; Dagmar Galter Journal: FASEB J Date: 2008-07-07 Impact factor: 5.191
Authors: Jacqueline Burré; Manu Sharma; Theodoros Tsetsenis; Vladimir Buchman; Mark R Etherton; Thomas C Südhof Journal: Science Date: 2010-08-26 Impact factor: 47.728
Authors: Colton Linnertz; Laura Saucier; Dongliang Ge; Kenneth D Cronin; James R Burke; Jeffrey N Browndyke; Christine M Hulette; Kathleen A Welsh-Bohmer; Ornit Chiba-Falek Journal: PLoS One Date: 2009-10-16 Impact factor: 3.240
Authors: Elena Flowers; Christine Miaskowski; Yvette Conley; Marilyn J Hammer; Jon Levine; Judy Mastick; Steven Paul; Fay Wright; Kord Kober Journal: Support Care Cancer Date: 2017-09-25 Impact factor: 3.603
Authors: Elena Flowers; Annesa Flentje; Jon Levine; Adam Olshen; Marilyn Hammer; Steven Paul; Yvette Conley; Christine Miaskowski; Kord M Kober Journal: Biol Res Nurs Date: 2019-01-31 Impact factor: 2.522
Authors: Kord M Kober; Laura Dunn; Judy Mastick; Bruce Cooper; Dale Langford; Michelle Melisko; Alan Venook; Lee-May Chen; Fay Wright; Marilyn Hammer; Brian L Schmidt; Jon Levine; Christine Miaskowski; Bradley E Aouizerat Journal: Biol Res Nurs Date: 2016-03-08 Impact factor: 2.522