• Extracellular Matrix Biomarkers are Time Dependent and Regional Specific in Experimental Diffuse Brain Injury

      Jenkins, Taylor; The University of Arizona College of Medicine - Phoenix; Lifshitz, Jonathan (The University of Arizona., 2017-05-09)
      The extracellular matrix (ECM) provides structural support for neuronal, glial and vascular components of the brain, and regulates intercellular signaling required for cellular morphogenesis, differentiation and homeostasis through constant remodeling. We hypothesize that the ECM is susceptible to degradation and accumulation of glycoproteins, which serve as biomarkers specific to diffuse brain injury severity and region. Experimental TBI was induced in male Sprague Dawley rats (325‐375g) by midline fluid percussion injury (FPI) at sham (n=6), mild (1.4 atm, n=16) and moderate (2.0 atm, n=16) severity. Tissue from the cortex, hippocampus and thalamus was collected at 15 minutes, 1, 2, 6 and 18 hours post‐injury as well as 1, 3, 7 and 14 days post‐injury. All samples were quantified by western blot for glycoproteins: reelin, fibronectin, laminin, and tenascin‐c. Band intensities were normalized to sham and relative to β‐actin. In the cortex fibronectin decreased significantly at 15 minutes, 1 hour and 2 hours postinjury, while tenacin‐C decreased significantly at 7 and 14 days post‐injury. In the thalamus, reelin decreased significantly at 2 hours, 3 and 14 days post‐injury. In the hippocampus, tenacin‐C increased significantly at 15 minutes and 7 days post‐injury. Changes in levels of these glycoproteins at acute time points suggest that they may be useful diagnostic biomarkers in an emergency room setting. Further investigation into breakdown products and penetrance into blood is needed. The specificity and sensitivity of these biomarkers remain to be validated as clinically useful tools.
    • The Vaginal and Gastrointestinal Microbiomes in Gynecologic Cancers: A Review of Applications in Etiology, Symptoms and Treatment

      Goulder, Alison; The University of Arizona College of Medicine - Phoenix; Chase, Dana (The University of Arizona., 2017-05-26)
      The human microbiome is the collection of microorganisms in the body that exist in a mutualistic relationship with the host. Recent studies indicate that perturbations in the microbiome may be implicated in a number of diseases, including cancer. More specifically, changes in the gut and vaginal microbiomes may be associated with a variety of gynecologic cancers, including cervical cancer, uterine cancer, and ovarian cancer. Current research and gaps in knowledge regarding the association between the gut and vaginal microbiomes and the development, progression, and treatment of gynecologic cancers are reviewed here. In addition, the potential use of probiotics to manage symptoms of these gynecologic cancers is discussed. A better understanding of how the microbiome composition is altered at these sites and its interaction with the host may aid in prevention, optimization of current therapies, development of new therapeutic agents and/or dosing regimens, and possibly limit the side effects associated with cancer treatment.