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Full-Text Articles in Medical Sciences

Echogenic Liposomes For Nitric Oxide Delivery And Breast Cancer Treatment, Soo Yeon Lee Female Aug 2011

Echogenic Liposomes For Nitric Oxide Delivery And Breast Cancer Treatment, Soo Yeon Lee Female

Dissertations & Theses (Open Access)

Liposomes, also known as nontoxic, biodegradable, and non-immunogenic therapeutic delivery vehicles, have been proposed as a carrier for drugs and antitumor agents in cancer chemotherapy. Echogenic liposomes (ELIP) have the potential to entrap air or bioactive gas to enhance acoustic reflectivity in ultrasound and are used as a contrast agent. The innovative part of this study is based on a novel concept to encapsulate nitric oxide (NO) gas into ELIP, deliver it to breast cancer cells, and control its release via direct ultrasound exposure. Studies on the effect of NO in tumor biology have shown that a high levels of …


Insights Into P53-Dependent Apoptotic Signaling And Cell Fate Vis-A-Vis Functional Cooperation Among Bcl-Xl, Cytoplasmic P53, And Puma, John C. Fisher May 2011

Insights Into P53-Dependent Apoptotic Signaling And Cell Fate Vis-A-Vis Functional Cooperation Among Bcl-Xl, Cytoplasmic P53, And Puma, John C. Fisher

Theses and Dissertations (ETD)

Following DNA damage, nuclear p53 induces the expression of PUMA (p53 upregulated modulator of apoptosis), a BH3‑only protein that binds and inhibits the anti‑apoptotic BCL‑2 repertoire, including BCL‑xL. Structural investigations of PUMA and the BCL‑xL×PUMA BH3 domain complex by X‑ray crystallography and nuclear magnetic resonance (NMR) spectroscopy reveal a novel, PUMA‑induced, domain‑swapped dimerization of BCL‑xL that requires a π‑stacking interaction between PUMA W71 and BCL‑xL H113. PUMA is an intrinsically disordered protein, but upon interaction with BCL‑xL, PUMA W71 and the PUMA BH3 domain residues fold into an alpha helix and subtly remodel BCL‑xL to trigger its dimerization. Wild type …


Axogial Communication Mediated By Soluble Neuregulin-1 And Bdnf, Zhenzhong Ma Jan 2011

Axogial Communication Mediated By Soluble Neuregulin-1 And Bdnf, Zhenzhong Ma

Wayne State University Dissertations

During peripheral nervous system development, successful communication between axons and glial cells including Schwann cells in peripheral nervous system and oligodendrocytes in central nervous system, is required for the proper functions of both neurons and glia. Three types of alternatively-spliced proteins belonging to the neuregulin1 (NRG1) gene family of growth and differentiation factors are essential for Schwann cell survival and peripheral nerve development. While membrane-bound NRG1 forms (type III) has been strongly implicated in the regulation of myelination process at late stage of Schwann cell development, little is known about the role of soluble, heparin-binding forms of NRG1 (type I/II) …


Distinct Domains Of Bax Are Involved In Mitochondrial Bioenergetics And Apoptosis, Ge Zhang Jan 2011

Distinct Domains Of Bax Are Involved In Mitochondrial Bioenergetics And Apoptosis, Ge Zhang

Electronic Theses and Dissertations

Apoptosis is essential for cellular homeostasis and is also a pathologic feature of various diseases. The balance between Bcl-2 family proteins determines whether a cell will live or die. Bax, a member of the BCL-2 family proteins, is a pro-apoptotic protein that exists in both a soluble, cytoplasmic form and a membrane-bound form. Upon apoptotic stimuli, Bax undergoes a conformational change and translocates to the mitochondria, initiating apoptotic events. However, little is known about whether Bax is involved in the regulation of mitochondrial function under non-apoptotic conditions, and how Bax binds to mitochondria to exert its activity. Here, we investigate …


Genetically Modified Es Cells Enhance Cardiac Repair And Regeneration In The Infarcted Heart, Carley E. Glass Jan 2011

Genetically Modified Es Cells Enhance Cardiac Repair And Regeneration In The Infarcted Heart, Carley E. Glass

Electronic Theses and Dissertations

Transplanted embryonic stem (ES) cells following myocardial infarction (MI) contribute to limited cardiac repair and regeneration with improved function. Therefore novel strategies are still needed to enhance the efficacy by which ES cells differentiate into cardiac cell types and inhibit adverse remodeling in the infarcted myocardium. Our studies evaluate whether genetic manipulation of transplanted ES cells employing miR- 1, a pro-cardiac microRNA, and TIMP-1, an anti-apoptotic and anti-fibrotic protein, will enhance cardiac myocyte differentiation, inhibit native cardiac apoptosis, and reduce fibrosis in the infarcted myocardium. Furthermore, we assess levels of associated pro- (caspase-3, PTEN) and anti-(Akt) apoptotic proteins as well …


Role Of Calcium-Activated Potassium Channels In Glioblastoma Volume Regulation, Michael Bryan Mcferrin Jan 2011

Role Of Calcium-Activated Potassium Channels In Glioblastoma Volume Regulation, Michael Bryan Mcferrin

All ETDs from UAB

The most common and most malignant gliomas are the Grade IV Glioblastoma Multiforme (GBM), characterized by a highly proliferative tumor mass and extremely invasive phenotype that allows for profuse dispersal of tumor cells throughout the brain. GBM cells must specifically regulate their cell volume to thrive within the edematous tumor mass and infiltrate throughout the tortuous extracellular spaces of the brain. These rapid and directed volume changes are governed by the controlled flux of potassium and chloride ions across the cell membrane, which move osmotically obliged water. The goal of this dissertation was to investigate the role of calcium-activated potassium …