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Articles 1 - 8 of 8
Full-Text Articles in Cell and Developmental Biology
Modulatory Effects Of Deacetylated Sialic Acids On Breast Cancer Resistance Protein-Mediated Multidrug Resistance And Receptor Tyrosine Kinase-Targeted Therapy, Isaac Tuffour
Electronic Theses and Dissertations
Multidrug resistance (MDR) remains a major challenge in cancer treatment, accounting for over 90% of chemotherapeutic failures. Cancers utilize sugar residues to engage in multidrug resistance. The underlying mechanism of action involving glycans, specifically the glycan sialic acid (Sia) and its various functional group alterations, has not been explored. ATP-binding cassette (ABC) transporter proteins, key proteins utilized by cancers to engage in MDR pathways, contain Sias in their extracellular domains. Modulating the expression of acetylated-Sias on Breast Cancer Resistance Protein (BCRP), a significant ABC transporter implicated in MDR, in lung and colon cancer cells directly impacted the ability of cancer …
Cannabinoids And Retinal Fibrotic Disorders., Lucy June Sloan
Cannabinoids And Retinal Fibrotic Disorders., Lucy June Sloan
Electronic Theses and Dissertations
Retinal fibrosis is detrimental to vision. Retinal pigment epithelial (RPE) cells contribute to several retinal fibrotic diseases. Upon exposure to TGF-β, a key fibrotic cytokine, RPE cells trans-differentiate to myofibroblasts marked by the integration of α-SMA fibers into F-actin stress fibers, which confer strong contractility. Myofibroblasts produce and contract the collagen-rich fibrotic scar and disrupt retinal architecture. In this study, we investigated the in vitro effects of the putative endocannabinoid compound N-oleoyl dopamine (OLDA) on TGF-β2 induced porcine RPE cell contraction and α-SMA expression. Using an in vitro collagen matrix contraction assay, we found that OLDA inhibited TGF-β2 induced contraction …
Paraoxonase 2 Is Critical For Non-Small Cell Lung Carcinoma Proliferation., Aaron Whitt
Paraoxonase 2 Is Critical For Non-Small Cell Lung Carcinoma Proliferation., Aaron Whitt
Electronic Theses and Dissertations
Non-small cell lung carcinoma (NSCLC) comprises 85% of lung cancer diagnoses and is plagued by drug resistance. Thus, elucidating the underlying mechanisms of NSCLC is paramount to expand future treatment options. Paraoxonase 2 (PON2), an intracellular enzyme with arylesterase and lactonase functions, has well-established anti-atherosclerotic activity. Recent studies show PON2 is overexpressed in a variety of tumors and confers drug resistance, although these interactions have not been thoroughly examined in NSCLC. Thus, we sought to investigate the role of PON2 in cellular proliferation using PON2-knockout mice, primary mouse cells, and NSCLC cell lines. Using these approaches, we demonstrate that PON2 …
Epidermal Growth Factor-Like Ligands Regulate Dimer Selection., Jamie S. Rush
Epidermal Growth Factor-Like Ligands Regulate Dimer Selection., Jamie S. Rush
Electronic Theses and Dissertations
There are thirteen known endogenous EGF-like ligands. We previously reported that Betacellulin (BTC) increases ligand-mediated corneal wound healing more than Epidermal Growth Factor (EGF) [Peterson et al. (2014) IOVS 55(5):2870-80], although the molecular reason for this is unknown. Despite being better at promoting wound healing via enhanced cell migration, BTC has reduced receptor affinity and weaker induction of EGFR phosphorylation. These data indicate that BTC’s response is not due to enhanced affinity or EGFR-kinase activity. Receptor phosphorylation and proximity ligation assays indicate that BTC treatment significantly increases ErbB3 phosphorylation and EGFR:ErbB3 heterodimers. BTC traffics EGFR at a faster rate than …
Egfr Signaling From The Early Endosome., Julie A. Gosney
Egfr Signaling From The Early Endosome., Julie A. Gosney
Electronic Theses and Dissertations
The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is an integral component of proliferative signaling. When activated by a ligand at the plasma membrane, EGFR dimerizes with another ErbB family receptor, leading to kinase domain activation and transphosphorylation of C-terminus tyrosine residues. These phosphotyrosines act as crucial regulators of EGFR signaling as effector proteins dock to the receptor at these sites. The receptor undergoes clathrin-mediated endocytosis into early endosomes, where it can then be trafficked to a lysosome for degradation. However, the kinase domain of EGFR retains its activity during trafficking, suggesting that EGFR can continue …
Pharmacokinetics, Tissue Distribution, Synergistic Activity, And Antitumor Activity Of Two Isomeric Flavones, Crystal L. Whitted
Pharmacokinetics, Tissue Distribution, Synergistic Activity, And Antitumor Activity Of Two Isomeric Flavones, Crystal L. Whitted
Electronic Theses and Dissertations
Flavonoids are polyphenolic secondary metabolites found in plants that have bioactive properties including antiviral, antioxidant, and anticancer. Two isomeric flavone were extracted from Gnaphalium elegans and Achyrocline bogotensis, plants used by the people from the Andean region of South America as remedies for cancer. 5,7-dihydroxy-3,6,8-trimethoxy-2-phenyl-4H-chromen-4-one (5, 7–dihydroxy- 3, 6, 8 trimethoxy flavone/ flavone A) and 3,5-dihydroxy-6,7,8-trimethoxy-2-phenyl-4H-chromen-4-one (3, 5–dihydroxy-6, 7, 8–trimethoxy flavone/ flavone B) have shown antineoplastic activity against colon cancer cell lines dependent upon their differentiation status. Pharmacokinetic studies reported herein were used to determine dosing for antitumor assays, as well as determine target tissue concentration. These included the …
Isolation Of Egfr-Containing Early Endosomes., Julie A. Gosney
Isolation Of Egfr-Containing Early Endosomes., Julie A. Gosney
Electronic Theses and Dissertations
The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase (RTK) that is an integral component of proliferative signaling. When activated by a ligand at the plasma membrane, EGFR undergoes clathrin-mediated endocytosis. This spatial regulation of the receptor is an important regulator of receptor expression as it mediates its degradation. Endocytosis also has implications on EGFR downstream signaling, though the details are not fully understood. The goal of this thesis is to develop a method to isolate early endosomes in order to study downstream effectors associated with activated EGFR in this compartment. HeLa cells were used to test various …
Comparison Of Beta-Adrenoceptor Coupled Camp Production In Cultured Human Mononuclear Leukocytes And Myometrial Cells, Yu-Li Liu
Electronic Theses and Dissertations
$\beta\sb2$-Adrenoceptor ($\beta\sb2$-AR) agonists, such as terbutaline, are used as tocolytic agents in the treatment of preterm labor. $\beta$-Adrenoceptor stimulation relaxes myometrium through specific receptors coupled through Gs to adenylyl cyclase (AC) that catalyzes the conversion of ATP to cAMP. The purpose of this study was to compare $\beta$-adrenoceptors and cAMP production in cultured human leukocytes and myometrial cells, and to determine the importance of $\beta$-adrenoceptors and cAMP production in isoproterenol-induced myometrial relaxation. $\sp{125}$I-iodopindolol was used to assess $\beta$-adrenoceptor affinity and number cAMP levels were analyzed before and after stimulation by isoproterenol, AlF$\sb4\sp-$, forskolin, and PGE$\sb1$. Isometric recording was used to …