Browsing by Subject "Adhesion molecules"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Blocking porcine sialoadhesin improves extracorporeal porcine liver xenoperfusion with human blood
    (Wiley, 2013-07) Waldman, Joshua P.; Vogel, Thomas; Burlak, Christopher; Coussios, Constantin; Dominguez, Javier; Friend, Peter; Rees, Michael A.; Surgery, School of Medicine
    BACKGROUND: Patients in fulminant hepatic failure currently do not have a temporary means of support while awaiting liver transplantation. A potential therapeutic approach for such patients is the use of extracorporeal perfusion with porcine livers as a form of "liver dialysis". During a 72-h extracorporeal perfusion of porcine livers with human blood, porcine Kupffer cells bind to and phagocytose human red blood cells (hRBC) causing the hematocrit to decrease to 2.5% of the original value. Our laboratory has identified porcine sialoadhesin expressed on Kupffer cells as the lectin responsible for binding N-acetylneuraminic acid on the surface of the hRBC. We evaluated whether blocking porcine sialoadhesin prevents the recognition and subsequent destruction of hRBCs seen during extracorporeal porcine liver xenoperfusion. METHODS: Ex vivo studies were performed using wild type pig livers perfused with isolated hRBCs for 72-h in the presence of an anti-porcine sialoadhesin antibody or isotype control. RESULTS: The addition of an anti-porcine sialoadhesin antibody to an extracorporeal porcine liver xenoperfusion model reduces the loss of hRBC over a 72-h period. Sustained liver function was demonstrated throughout the perfusion. CONCLUSIONS: This study illustrates the role of sialoadhesin in mediating the destruction of hRBCs in an extracorporeal porcine liver xenoperfusion model.
  • Thumbnail Image
    Item
    Phosphatase of regenerating liver: a novel target for cancer therapy
    (Taylor & Francis, 2014-05) Campbell, Amanda M.; Zhang, Zhong-Yin; Biochemistry & Molecular Biology, School of Medicine
    INTRODUCTION: Phosphatases of regenerating livers (PRLs) are novel oncogenes that interact with many well-established cell signaling pathways that are misregulated in cancer, and are known to drive cancer metastasis when overexpressed. AREAS COVERED: This review covers basic information of the discovery and characteristics of the PRL family. We also report findings on the role of PRL in cancer, cell functions and cell signaling. Furthermore, PRL's suitability as a novel drug target is discussed along with current methods being developed to facilitate PRL inhibition. EXPERT OPINION: PRLs show great potential as novel drug targets for anticancer therapeutics. Studies indicate that PRL can perturb major cancer pathways such as Src/ERK1/2 and PTEN/PI3K/Akt. Upregulation of PRLs has also been shown to drive cancer metastasis. However, in order to fully realize its therapeutic potential, a deeper understanding of the function of PRL in normal tissue and in cancer must be obtained. Novel and integrated biochemical, chemical, biological, and genetic approaches will be needed to identify PRL substrate(s) and to provide proof-of-concept data on the druggability of the PRL phosphatases.