Medicine and Health Sciences Commons^™

Endostatin Modulates Vegf-Mediated Barrier Dysfunction In The Retinal Microvascular Endothelium, Brenda B. Brankin, M. Campbell, P. Canning, T. Gardiner, A. Stitt

Articles

Recent evidence indicates that the anti-angiogenic peptide endostatin may modulate some of the vasomodulatory effects of vascular endothelial growth factor (VEGF) in the retina, including reduction of blood retinal barrier function although it remains uncertain how endostatin promotes endothelial barrier properties. The current study has sought to examine how physiological levels of endostatin alters VEGF-induced inner BRB function using an in vitro model system and evaluation of occludin and ZO-1 regulatory responses. In addition, the ability of exogenous endostatin to regulate VEGF-mediated retinal vascular permeability in vivo was investigated.

Retinal microvascular endothelial cells (RMEC's) were exposed to various concentrations of …

Combining Cytotoxic And Immune-Mediated Gene Therapy To Treat Brain Tumors, James Curtin, Gwendalyn King, Marianela Candolfi, Remy Greeno, Kurt Kroeger, Pedro Lowenstein, Maria Castro

Articles

Glioblastoma (GBM) is a type of intracranial brain tumor, for which there is no cure. In spite of advances in surgery, chemotherapy and radiotherapy, patients die within a year of diagnosis. Therefore, there is a critical need to develop novel therapeutic approaches for this disease. Gene therapy, which is the use of genes or other nucleic acids as drugs, is a powerful new treatment strategy which can be developed to treat GBM. Several treatment modalities are amenable for gene therapy implementation, e.g. conditional cytotoxic approaches, targeted delivery of toxins into the tumor mass, immune stimulatory strategies, and these will all …

Identification Of Fatty Acid Oxidation Disorder Patients With Lowered Acyl-Coa Thioesterase Activity In Human Skin Fibroblasts, Mary Hunt, Jos Ruiter, Petra Mooyer, Carlo W T Van Roermond, Rob Ofman, Lodewig Ijlst, Ronald J A Wanders

Articles

Background: Acyl-CoA thioesterases are enzymes that hydrolyze acyl-CoAs to the free fatty acid and coenzyme A (CoASH). These enzymes have been identified in several cellular compartments and are thought to regulate intracellular levels of acyl-CoAs, free fatty acids and CoASH. However, to date no patients deficient in acyl-CoA thioesterases have been identified. Design: Acyl-CoA thioesterase activity was measured in human skin fibroblasts. Western blot analysis was used to determine Type-II acyl-CoA thioesterase protein levels in patients. Results: Activity was found in human fibroblasts with all saturated acyl-CoAs from C4:0- to C18:0-CoA, with highest activity detected with lauroyl-CoA and myristoyl-CoA (C12:0 …

Gene Therapy And Targeted Toxins For Glioma, James Curtin, Gwendalyn King, Marianela Candolfi, Kurt Kroeger, Pedro Lowenstein, Maria Castro

Articles

The most common primary brain tumor in adults is glioblastoma. These tumors are highly invasive and aggressive with a mean survival time of nine to twelve months from diagnosis to death. Current treatment modalities are unable to significantly prolong survival in patients diagnosed with glioblastoma. As such, glioma is an attractive target for developing novel therapeutic approaches utilizing gene therapy. This review will examine the available preclinical models for glioma including xenographs, syngeneic and genetic models. Several promising therapeutic targets are currently being pursued in pre-clinical investigations. These targets will be reviewed by mechanism of action, i.e., conditional cytotoxic, targeted …

Biomarkers For Placental Abnormality, Cathal Mccarthy

Doctoral

Obstetrical complications including recurrent miscarriage, pre-eclampsia and intrauterine growth restriction (IUGR) affect 1%-5% of pregnant women (Younis and Samueloff 2003). Dysfunctional trophoblasts, impaired development of spiral arteries, imbalance in systems controlling the dilation and contraction of spiral arteries, placental fibrin clots and intervillous thrombosis are all possible factors that can result in an insufficient placental circulation. The combination of the hypercoagulable state of pregnancy and presence of genetic thrombophilic markets has the potential to induce placental thrombosis and cause placental insufficiency with subsequent obstetrical complications. The initial part of the research work involved examining the relationship between four common genetic …