Project description:Cancer-related fatigue is one of the most frequent complaints among breast cancer survivors, with a major negative impact on general life. However, the etiology behind this syndrome is still unraveled. Gene expression analysis was performed on whole blood samples from breast cancer survivors classified as either fatigued or non-fatigued at two consecutive time points. The analysis identified several gene sets concerning plasma and B cell pathways as different between the fatigue and non-fatigue groups, suggesting that a deregulation in these pathways might underlie the fatigue syndrome. The fatigue group also showed a higher mean level of leucocytes, lymphocytes and neutrophiles compared with the non-fatigue group, thus further implicating the immune system in the biology behind the fatigue syndrome. Keywords: Blood RNA and late side effects Breast cancer survivors treated with adjuvant radiotherapy at The Norwegian Radium Hospital between 1998 and 2002 were invited to participate in a study assessing late treatment effects in breast cancer survivors. In the present study, gene expression analysis was performed on whole blood samples from breast cancer survivors with and without persistent fatigue, to look for different expression patterns that might shed light on the biology behind cancer-related fatigue.
Project description:Cancer-related fatigue is one of the most frequent complaints among breast cancer survivors, with a major negative impact on general life. However, the etiology behind this syndrome is still unraveled. Gene expression analysis was performed on whole blood samples from breast cancer survivors classified as either fatigued or non-fatigued at two consecutive time points. The analysis identified several gene sets concerning plasma and B cell pathways as different between the fatigue and non-fatigue groups, suggesting that a deregulation in these pathways might underlie the fatigue syndrome. The fatigue group also showed a higher mean level of leucocytes, lymphocytes and neutrophiles compared with the non-fatigue group, thus further implicating the immune system in the biology behind the fatigue syndrome. Keywords: Blood RNA and late side effects
Project description:The etiology behind cancer-related fatigue (CRF) is currently unknown. The physiological mechanisms of CRF are based on limited evidence that genetic factors, energy expenditure, metabolism, aerobic capacity, and the individual's immune response to inflammation are responsible for the experience of CRF. Gene expression profiling using microarray analysis from white blood cells of men with non-metastatic prostate cancer shows significant, differential expression of 463 probesets during localized external beam radiation therapy (EBRT). Pathway analysis shows a central role of SNCA (alpha-synuclein gene) among these differentially expressed probesets. Significant expression of SNCA was confirmed by qPCR (p<.001) and ELISA (p<.001) over time during EBRT. A significant correlation was noted between averaged fatigue scores and delta CT values of SNCA expression using confirmatory qPCR over time during EBRT (R=-.90, p=.006). Development of fatigue experienced by these men during EBRT may be mediated by SNCA expression. Pathways related to alpha-synuclein may serve as useful biomarkers to understand the mechanisms behind the development of fatigue. A longitudinal design exploring the association between changes in gene expression and fatigue symptoms of men with non-metastatic prostate cancer receiving external beam radiation therapy. Blood samples were collected from ten subjects at 7 timepoints for microarray analysis: baseline (before EBRT); days 1, 7, 14, 21, 42 of EBRT; and 30 days post-EBRT. Baseline data obtained from subjects were compared to data obtained from age-, race-, and gender-matched healthy controls.
Project description:The etiology behind cancer-related fatigue (CRF) is currently unknown. The physiological mechanisms of CRF are based on limited evidence that genetic factors, energy expenditure, metabolism, aerobic capacity, and the individual's immune response to inflammation are responsible for the experience of CRF. Gene expression profiling using microarray analysis from white blood cells of men with non-metastatic prostate cancer shows significant, differential expression of 463 probesets during localized external beam radiation therapy (EBRT). Pathway analysis shows a central role of SNCA (alpha-synuclein gene) among these differentially expressed probesets. Significant expression of SNCA was confirmed by qPCR (p<.001) and ELISA (p<.001) over time during EBRT. A significant correlation was noted between averaged fatigue scores and delta CT values of SNCA expression using confirmatory qPCR over time during EBRT (R=-.90, p=.006). Development of fatigue experienced by these men during EBRT may be mediated by SNCA expression. Pathways related to alpha-synuclein may serve as useful biomarkers to understand the mechanisms behind the development of fatigue.
Project description:HIV-related fatigue is multi-causal in origin and potentially related to mitochondrial dysfunction caused by toxicity from nucleoside reverse transcriptase inhibitor (NRTI) antiretroviral therapy. CD14+ cells are undifferentiated macrophages, vulnerable to HIV infection, and easily accessible for gene expression experiments in a purified cell population. We utilized a novel mitochondrially-specific gene expression microarray to assess mitochondrial and nuclear genes in CD14+ cells of low- and high-fatigued, NRTI-treated HIV/AIDS patients (n=5 each). Novel Bayesian and liquid association network methods identified 33 genes predictive of low versus high fatigue and 32 genes predictive of healthy versus HIV infection. Sulfotransferase 2B1 (SULT2B1) is relevant to both the cholesterol and testosterone pathway, and like several inner mitochondrial membrane genes also identified, predictive of fatigue status, while outer mitochondrial membrane genes were predictive of HIV status. A surprising finding was that adenylate cyclase 2 (ADCY2) was a predictor of both HIV and fatigue; it had the highest Kendallâs Tau association value in the HIV group, but in reverse, the lowest Tau value in the fatigue group. Assaying CD14+ cells may provide an alternative to muscle biopsy and a minimally invasive procedure to evaluate patient mitochondrial function, and Bayesian and network tools are useful to identify the link between subjective symptom perceptions and underlying biologically pathways. Fatigue status in HIV patients treated with NRTIs was found to be linked to RNA expression differences related to mitochondrial function. Additional studies are needed to confirm the relevance of our findings in CD14+ cells in other tissues (e. g. skeletal muscle) and to understand the significance of key genes such as SULT2B and ADCY2 in fatigue and HIV disease. The design was a comparison of HIV high fatigue to HIV low fatigue. Low fatigue was determined as 3-7 on the Revised Piper Fatigue Score and High fatigue was a score of 7 or greater. Five HIV negative control samples were used to compare normal fatigue and non-disease status.
Project description:HIV-related fatigue is multi-causal in origin and potentially related to mitochondrial dysfunction caused by toxicity from nucleoside reverse transcriptase inhibitor (NRTI) antiretroviral therapy. CD14+ cells are undifferentiated macrophages, vulnerable to HIV infection, and easily accessible for gene expression experiments in a purified cell population. We utilized a novel mitochondrially-specific gene expression microarray to assess mitochondrial and nuclear genes in CD14+ cells of low- and high-fatigued, NRTI-treated HIV/AIDS patients (n=5 each). Novel Bayesian and liquid association network methods identified 33 genes predictive of low versus high fatigue and 32 genes predictive of healthy versus HIV infection. Sulfotransferase 2B1 (SULT2B1) is relevant to both the cholesterol and testosterone pathway, and like several inner mitochondrial membrane genes also identified, predictive of fatigue status, while outer mitochondrial membrane genes were predictive of HIV status. A surprising finding was that adenylate cyclase 2 (ADCY2) was a predictor of both HIV and fatigue; it had the highest Kendall’s Tau association value in the HIV group, but in reverse, the lowest Tau value in the fatigue group. Assaying CD14+ cells may provide an alternative to muscle biopsy and a minimally invasive procedure to evaluate patient mitochondrial function, and Bayesian and network tools are useful to identify the link between subjective symptom perceptions and underlying biologically pathways. Fatigue status in HIV patients treated with NRTIs was found to be linked to RNA expression differences related to mitochondrial function. Additional studies are needed to confirm the relevance of our findings in CD14+ cells in other tissues (e. g. skeletal muscle) and to understand the significance of key genes such as SULT2B and ADCY2 in fatigue and HIV disease.
Project description:Genome-wide analysis of DNA methylation profiles from patients with Sjögren's syndrome with high versus low fatigue levels using the Illumina Infinium HumanMethylation450 Beadchip array. Background Chronic fatigue is a common, disabling, and poorly understood phenomenon. Recent studies indicate that epigenetic mechanisms may be involved in the expression of fatigue, a prominent feature of primary Sjögrenâs syndrome (pSS). The aim of this study was to investigate whether DNA methylation profiles of whole blood are associated with fatigue in patients with pSS. Methods 48 pSS patients with high (n=24) or low (n=24) fatigue as measured by a visual analogue scale were included. Genome-wide DNA methylation was investigated using the Illumina HumanMethylation450 BeadChip array. Case-case study including Sjögren's patients with high fatigue (n=24) and patients with low fatigue levels (n=24)
Project description:This research is being done to find out if using a smartphone app as digital treatment to reduce Cancer Related Fatigue is feasible and easy to use.
This research study is evaluating a smartphone application named the "Untire" app. The Untire app was designed as a digital treatment plan for people experiencing Cancer Related Fatigue (CRF).