Medicine and Health Sciences Commons^™

Translational Study Of Liver Cancer And Hypertrophy: Translich, Mauro Enrique Tun Abraham

Electronic Thesis and Dissertation Repository

Abstract

Background: Associating liver partition with portal vein ligation for staged-hepatectomy (ALPPS) is a technique for inducing accelerated hypertrophy in patients with insufficient future liver remnant (FLR). It remains unknown whether this hypertrophy may lead to rapid cancer cell dissemination and/or alteration of immune cell/function reconstitution in the FLR. We aimed to determine if the rapid hypertrophy during ALPPS procedure results in more circulating tumour cell (CTCs) dissemination and whether the FLR remains immunologically competent in patients with CRLM.

Methods: In our prospective, observational, 2-arm study, we assessed the utility of CTCs as an evaluation tool for disease dissemination. Moreover, …

Identification Of A Nuclear Localization Signal (Nls) Within The Pleckstrin Homology (Ph) Domain Of Rho Guanine Nucleotide Exchange Factor (Rgnef), Michael V. Tavolieri

Electronic Thesis and Dissertation Repository

Rho Guanine Nucleotide Exchange factor (RGNEF) is a 180 kDa protein which forms pathological neuronal cytoplasmic inclusions in degenerating spinal motor neurons in amyotrophic lateral sclerosis (ALS) and for which the gene (ARHGEF28) is mutated in a subset of cases. Despite having previously been shown to localize to the nucleus and to undergo a nuclear cytosolic shift in response to cellular injury, the mechanism of its nuclear import has yet to be elucidated. Here we use site-directed mutagenesis with a combination of subcellular fractionation and confocal microscopy to identify a functional nuclear localization signal (NLS) within the Pleckstrin …

Mechanisms Regulating Stem Cell Phenotype In Infantile Hemangioma, Niamh Richmond

Electronic Thesis and Dissertation Repository

Infantile hemangiomas (IHs) are benign vascular neoplasms characterized by the differentiation of multipotential stem cells (hemSCs) into endothelial cells during the early proliferative phase, and later into adipocytes during spontaneous involution. Transforming growth factor-β (TGFβ) has been shown to be significantly elevated upon IH involution and this coincides with repression of a developmentally-regulated transcription factor T-box 2 (TBX2). These findings implicate both TGFβ and TBX2 in mediating hemSC differentiation during IH evolution. The aim of my study is to understand the role of TGFβ and TBX2 in hemSC differentiation. I performed immunofluorescence staining to localize TBX2 protein in sectioned IH …

Regulation Of Phosphatase And Tensin Homolog Expression And Activity By Transforming Growth-Factor Beta In The Trabecular Meshwork Cells: Implications For Primary Open Angle Glaucoma, Nikoleta Tellios

Electronic Thesis and Dissertation Repository

Glaucoma is a multifactorial condition caused, in part, by fibrosis of the sieve-like trabecular meshwork (TM) tissue, which impedes drainage of aqueous humor (AH), leading to increased intraocular pressure and associated optic nerve damage and blindness. Fibrosis of the TM is mainly caused by the increased levels of active transforming growth factor-β 2 (TGFβ2) in the AH of glaucoma patients.

Previous reports have shown that TGFβ decreases the expression of Phosphatase and Tensin Homolog (PTEN) gene and that PTEN is a major regulator of ECM deposition. In this study we investigate the regulation of PTEN protein expression and …

Oncolytic Virus Therapy For The Treatment Of Metastatic Ovarian Cancer, Jessica Tong

Electronic Thesis and Dissertation Repository

The management of patients with epithelial ovarian cancer (EOC) faces two major challenges which standard treatments fail to effectively address: 1) Diffuse metastasis as a consequence of late stage diagnosis and 2) intra-tumoral heterogeneity, which fuels tumor evolution and drives the acquisition of chemotherapeutic resistance. In this thesis, we tested new therapeutic strategies using a 3-dimensional in vitro spheroid culture model that mimics key steps of epithelial ovarian cancer metastasis; and another model that mimics both temporal and cellular heterogeneity by establishing multiple cell lines from a single patient over the course of disease progression. Using these models, we investigated …