Browsing by Author "Sledge, George W., Jr"

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    Avoidant Coping and Self-efficacy Mediate Relationships between Perceived Social Constraints and Symptoms among Long-term Breast Cancer Survivors
    (Wiley, 2016) Adams, Rebecca N.; Mosher, Catherine E.; Cohee, Andrea A.; Stump, Timothy E.; Monahan, Patrick O.; Sledge, George W., Jr; Cella, David; Champion, Victoria L.; Department of Psychology, School of Science
    Objective Many breast cancer survivors feel constrained in discussing their cancer experience with others. Limited evidence suggests that social constraints (e.g., avoidance and criticism) from loved ones may negatively impact breast cancer survivors' global health, but research has yet to examine relationships between social constraints and common physical symptoms. Informed by social cognitive processing theory, this study examined whether perceived social constraints from partners and healthcare providers (HCPs) were associated with fatigue, sleep disturbance, and attentional functioning among long-term breast cancer survivors (N = 1052). In addition, avoidant coping and self-efficacy for symptom management were examined as potential mediators of these relationships. Methods Long-term breast cancer survivors (mean years since diagnosis = 6) completed questionnaires assessing social constraints from partners and HCPs, avoidant coping, self-efficacy for symptom management, and symptoms (i.e., fatigue, sleep disturbance, and attentional functioning). Structural equation modeling was used to evaluate the hypothesized relationships among variables in two models: one focused on social constraints from partners and one focused on social constraints from HCPs. Results Both models demonstrated good fit. Consistent with theory and prior research, greater social constraints from both partners and HCPs were associated with greater symptom burden (i.e., greater fatigue and sleep disturbance, poorer attentional functioning). In addition, all relationships were mediated by avoidant coping and self-efficacy for symptom management. Conclusions Findings are consistent with social cognitive processing theory and suggest that symptom management interventions may be enhanced by addressing the impact of social constraints from survivors' partners and HCPs on their coping and self-efficacy.
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    Wnt signaling in triple negative breast cancer is associated with metastasis
    (BioMed Central, 2013-11) Dey, Nandini; Barwick, Benjamin G.; Moreno, Carlos S.; Ordanic-Kodani, Maja; Chen, Zhengjia; Oprea-Ilies, Gabriella; Tang, Weining; Catzavelos, Charles; Kerstann, Kimberly F.; Sledge, George W., Jr; Abramovitz, Mark; Bouzyk, Mark; De, Pradip; Leyland-Jones, Brian R.; Department of Medicine, IU School of Medicine
    Background Triple Negative subset of (TN) Breast Cancers (BC), a close associate of the basal-like subtype (with limited discordance) is an aggressive form of the disease which convey unpredictable, and poor prognosis due to limited treatment options and lack of proven effective targeted therapies. Methods We conducted an expression study of 240 formalin-fixed, paraffin-embedded (FFPE) primary biopsies from two cohorts, including 130 TN tumors, to identify molecular mechanisms of TN disease. Results The annotation of differentially expressed genes in TN tumors contained an overrepresentation of canonical Wnt signaling components in our cohort and others. These observations were supported by upregulation of experimentally induced oncogenic Wnt/β-catenin genes in TN tumors, recapitulated using targets induced by Wnt3A. A functional blockade of Wnt/β-catenin pathway by either a pharmacological Wnt-antagonist, WntC59, sulidac sulfide, or β-catenin (functional read out of Wnt/β-catenin pathway) SiRNA mediated genetic manipulation demonstrated that a functional perturbation of the pathway is causal to the metastasis- associated phenotypes including fibronectin-directed migration, F-actin organization, and invasion in TNBC cells. A classifier, trained on microarray data from β-catenin transfected mammary cells, identified a disproportionate number of TNBC breast tumors as compared to other breast cancer subtypes in a meta-analysis of 11 studies and 1,878 breast cancer patients, including the two cohorts published here. Patients identified by the Wnt/β-catenin classifier had a greater risk of lung and brain, but not bone metastases. Conclusion These data implicate transcriptional Wnt signaling as a hallmark of TNBC disease associated with specific metastatic pathways.