Sestrin Family of Genes and their Role in Cancer-related Fatigue

Cancer-related fatigue (CRF) continues to be a prevalent and distressing symptom experienced by cancer patients and survivors. CRF is defined by the National Comprehensive Cancer Network as a “distressing, persistent, subjective sense of tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and that interferes with usual functioning [1].” Although there is currently no optimal management and scant molecular evidence to guide the development of effective CRF therapies, several pathophysiological mechanisms have been proposed to explain the development of CRF [2, 3]. These pathophysiological mechanisms of CRF are believed to be complex and involve a cascade of events including the dysregulation of several physiological and biochemical systems, such as oxidative stress, inflammation, immune modulation, circadian rhythms modulation, growth factors, serotonin dysregulation, hypothalamic-pituitary-adrenal-axis disruption, vagal afferent activation, and hematopoietic dysfunction [2,3,4]. Although these proposed mechanisms of CRF pathophysiology are yet to be independently investigated, recent evidence suggest a critical role of mitochondrial dysfunction/oxidative stress in CRF [4, 5]

Comparing Genomic Profiles of Women With and Without Fibromyalgia.

Fibromyalgia syndrome (FMS), a chronic musculoskeletal condition characterized by diffuse pain, fatigue, sleep impairment, and cognitive dysfunction, is associated with significant functional disability. Its underlying biological mechanisms are unknown. This study investigated differentially expressed genes between women with FMS and healthy volunteers

Understanding the association of fatigue with other symptoms of fibromyalgia: Development of a cluster model

To develop a symptoms cluster model that can describe factors of fibromyalgia syndrome (FMS) associated with fatigue severity as reported by the sample and to explore FMS clinical symptom subclusters based on varying symptom intensities

Clinical Predictors of Fatigue in Men With Non-Metastatic Prostate Cancer Receiving External Beam Radiation Therapy

The goal of this study is to evaluate clinical predictors of worsening fatigue during external beam radiation therapy (EBRT) in men with non-metastatic prostate cancer

Expression of Sestrin Genes in Radiotherapy for Prostate Cancer and Its Association With Fatigue: A Proof-of-Concept Study

Genetic factors that influence inflammation and energy production/expenditure in cells may affect patient outcomes following treatment with external beam radiation therapy (EBRT). Sestrins, stress-inducible genes with antioxidant properties, have recently been implicated in several behaviors including fatigue. This proof-of-concept study explored whether the sestrin family of genes (SESN1, SESN2, and SESN3) were differentially expressed from baseline to the midpoint of EBRT in a sample of 26 Puerto Rican men with nonmetastatic prostate cancer. We also examined whether changes in expression of these genes were associated with changes in fatigue scores during EBRT. Method: Participants completed the 13-item Functional Assessment of Cancer Therapy—Fatigue subscale, Spanish version. Whole blood samples were collected at baseline and at the midpoint of EBRT. Gene expression data were analyzed using the limma package in the R (version R 2.14.0.) statistical software. Linear models and empirical Bayes moderation, adjusted for radiation fraction (total number of days of prescribed radiation treatment), were used to examine potential associations between changes in gene expression and change in fatigue scores. Results: Expression of SESN3 (adjusted p \u3c .01, log fold change −0.649) was significantly downregulated during EBRT, whereas the expressions of SESN1 and SESN2 remained unchanged. After adjustment for radiation fraction, change in SESN3 expression was associated with change in fatigue during EBRT (false discovery rate \u3c.01). Conclusions: Downregulation of SESN3, a novel pharmacoactive stress response gene, was associated with fatigue intensification during EBRT. SESN3 may serve as an interventional target and a biomarker for the cellular and molecular events associated with EBRT-related fatigue