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Theses/Dissertations

2018

Angiogenesis

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The Role Of Tbx3 In Early Breast Cancer Progression, Milica Krstic Dec 2018

The Role Of Tbx3 In Early Breast Cancer Progression, Milica Krstic

Electronic Thesis and Dissertation Repository

TBX3 is a transcriptional regulator involved in embryonic development and in tumorigenesis of several cancer types. There are two isoforms of TBX3 (TBX3iso1 and TBX3iso2) with different DNA binding domains. The large-scale functional roles of TBX3iso1 and TBX3iso2 were characterized in a breast cancer context. Both TBX3 isoforms induced invasiveness and an epithelial-to-mesenchymal (EMT) phenotype. Coupling data from genome-wide ChIP-array and RNA-Seq studies provided a novel list of genes regulated by each isoform. Both TBX3 isoforms regulate expression of several EMT-related genes, including SLUG and TWIST1. Importantly, TBX3 is a direct regulator of SLUG, and SLUG expression is required for …


Effects Of Hydrogen Sulfide In Hyperhomocysteinemia-Mediated Skeletal Muscle Myopathy., Avisek Majumder Dec 2018

Effects Of Hydrogen Sulfide In Hyperhomocysteinemia-Mediated Skeletal Muscle Myopathy., Avisek Majumder

Electronic Theses and Dissertations

Although hyperhomocysteinemia (HHcy) occurs due to a deficiency in cystathionine-β-synthase (CBS), causing skeletal muscle myopathy, it is still unclear whether this effect is mediated through oxidative, endoplasmic reticulum (ER) stress, both or something else. Cystathionine γ-lyase (CSE) and CBS are the main H2S producing enzymes, which produce Hydrogen sulfide (H2S) from Hcy in the transsulfuration reaction. H2S is an anti-oxidant compound and patients with a CBS deficiency cannot produce enough H2S, thus rendering them vulnerable to excess Hcy-mediated damage. Both in-vitro (C2C12 cells) and in-vivo (CBS+/- mice) models were used to …


The Effect Of Wild Blueberry Bioactives On Endothelial Cell Migration And Angiogenesis: An In Vitro Mechanistic, Genomic And Proteomic Approach, Panagiotis Tsakiroglou Sep 2018

The Effect Of Wild Blueberry Bioactives On Endothelial Cell Migration And Angiogenesis: An In Vitro Mechanistic, Genomic And Proteomic Approach, Panagiotis Tsakiroglou

Electronic Theses and Dissertations

The goal of this study is to investigate the effects of wild blueberry fractions (Anthocyanins and Phenolic acids) on vascular function and physiology. More specifically the potential effects of the above fractions and their combination in physiological concentrations on endothelial cell migration, angiogenesis, gene expression and proteins synthesis of markers related to the above processes. The objectives are to study whether anthocyanins, phenolic acids and their combinations (ACNs:PAs) affect: a) cell proliferation, b) speed of endothelial cell migration, c) angiogenesis, d) gene expression of genes critical for cell migration and angiogenesis such as RAC1, RHOA, AKT1, eNOS and VEGF and …


Nanoparticles For Gene Therapy And Protein Delivery To Induce Angiogenesis As An Alternative Treatment For Peripheral Arterial Disease, Linda Christellia Noukeu Aug 2018

Nanoparticles For Gene Therapy And Protein Delivery To Induce Angiogenesis As An Alternative Treatment For Peripheral Arterial Disease, Linda Christellia Noukeu

Bioengineering Dissertations

Peripheral arterial disease (PAD) is defined as a slow, progressive disorder of the lower extremity arterial vessels characterized by chronic narrowing that often results in occlusion and is associated with loss of functional capacity. Although the PAD occurrence rate is increasing in the elderly population, outcomes with current treatment strategies are suboptimal. Hence, there is an urgent need to develop new technologies that overcome limitations of traditional modalities for PAD detection and therapy. In this research, nanoparticles have been developed and used as carriers for various therapeutic agents to treat PAD. In particular, via protein/gene delivery, we developed and formulated …


Tissue Engineered Micro And Macrovasculature Utilizing Stromal Vascular Fraction., Joseph Samir Zakhari May 2018

Tissue Engineered Micro And Macrovasculature Utilizing Stromal Vascular Fraction., Joseph Samir Zakhari

Electronic Theses and Dissertations

This dissertation describes the use of stromal vascular fraction to tissue engineer 3D microvasculature and macrovasculature. Stromal vascular fraction is an easily isolatable cell source from adipose tissue depots. It has demonstrated remarkable potential both in vitro and in vivo for forming microcirculation capable of perfusion upon implantation. SVF is clinically utilized as a therapeutic cell source for anti-inflammation for osteoarthritis and is being studied for ischemic tissue application to stimulate revascularization. The work described herein is divided within four chapters. Chapter I provides an introductory overview and lists the aims and hypothesis for the dissertation. Chapter II describes experiments …


Tumor Multicomponent Targeting Polymer-Lipid Hybrid Nanoparticles To Overcome Drug Resistance In Renal Cell Carcinoma, Hashem Obaid Alsaab Jan 2018

Tumor Multicomponent Targeting Polymer-Lipid Hybrid Nanoparticles To Overcome Drug Resistance In Renal Cell Carcinoma, Hashem Obaid Alsaab

Wayne State University Dissertations

Renal Cell Carcinoma (RCC) contributes to more than 90% of the most common form of kidney tumor and remains one of the ten leading causes of cancer death in the United States. Although surgery remains an option for operable tumors, high metastatic index and resistance to radiation and chemotherapies prompted recent development of therapeutics that target the RCC angiogenesis and cell proliferation pathways. Tyrosine kinase inhibitors or TKIs (Cabozantinib, Axitinib, Sorafenib, and Sunitinib) and mammalian target of rapamycin (mTOR) inhibitors (Temsirolimus and Everolimus) have increased the therapeutic options for treating RCC. Although the impact towards decreasing disease progression is encouraging, …


Characterization Of Early Acute Inflammation In A Mouse Calvarial Critical-Sized Defect: Augmentation Via Rhbmp-2 And Pglcnac Administration, Zachary James Grey Jan 2018

Characterization Of Early Acute Inflammation In A Mouse Calvarial Critical-Sized Defect: Augmentation Via Rhbmp-2 And Pglcnac Administration, Zachary James Grey

MUSC Theses and Dissertations

Background: Currently, the gold standard intervention for substantially large bone wounds is autologous bone grafting. While effective, this therapy is complicated by creation of an invasive second surgical site and limited material available for harvest. INFUSE® Bone Graft (rhBMP-2 delivered via an absorbable collagen sponge or ACS) has been widely used as a graft substitute, resulting in robust bone formation, but at the cost of increased inflammation and often poor healing outcomes. A better understanding of the mechanisms by which rhBMP-2 influences inflammatory processes and how these processes can be modulated through other therapies will inform future novel pharmacological avenues …


Investigations Of Interleukin-1 Alpha As A Novel Stroke Therapy In Experimental Ischemic Stroke, Kathleen Elizabeth Salmeron Jan 2018

Investigations Of Interleukin-1 Alpha As A Novel Stroke Therapy In Experimental Ischemic Stroke, Kathleen Elizabeth Salmeron

Theses and Dissertations--Neuroscience

Stroke is a leading cause of death and disability worldwide. Although rapid recognition and prompt treatment have dropped mortality rates, most stroke survivors are left with permanent disability. Approximately 87% of all strokes result from the thromboembolic occlusion of the cerebrovasculature (ischemic strokes). Potential stroke therapeutics have included anti-inflammatory drugs, as well as many other targets with the goal of mitigating the acute and chronic inflammatory responses typically seen in an ischemic stroke. While these approaches have had great success in preclinical studies, their clinical translation has been less successful. Master inflammatory cytokines, such as IL-1, are of particular interest. …


Exosomes Released From Multiple Myeloma Cells Influence The Angiogenic Function Of Endothelial Cells By Regulating Microrna-29b, Qinmao Ye Jan 2018

Exosomes Released From Multiple Myeloma Cells Influence The Angiogenic Function Of Endothelial Cells By Regulating Microrna-29b, Qinmao Ye

Browse all Theses and Dissertations

Multiple myeloma is a hematological malignancy characterized by clonal proliferation of plasma cells generally caused by chromosomal abnormalities. It occurs in the bone marrow, which is the microenvironment of multiple myeloma. Exosomes (EXs) are 30-100 nm membrane-derived micro-vesicles containing various of bioactive molecules, such as microRNAs, to mediate the cell-cell interaction. Numerous studies reported that exosomes play a significant role in tumor microenvironment. Angiogenesis has the important implication in tumor exacerbation to supply nutrients to promote the progression of cancer cells through endothelial cells (ECs). Some studies demonstrated that microRNA-29b (miR-29b) can suppress tumor development and inhibit angiogenesis. Therefore, in …


A Novel, Orally Active Hydrogen Sulfide-Releasing Compound, Sg1002, Improves Left Ventricular Function With An Associated Induction Of Angiogenesis In A Murine Model Of Ischemia/Reperfusion, Om A. Evani Jan 2018

A Novel, Orally Active Hydrogen Sulfide-Releasing Compound, Sg1002, Improves Left Ventricular Function With An Associated Induction Of Angiogenesis In A Murine Model Of Ischemia/Reperfusion, Om A. Evani

Theses and Dissertations

Hydrogen sulfide (H2S) is the newest member of the gasotransmitter family and is becoming well known for its cardioprotective effects in preclinical trials. Many recent studies have shown the benefits of exogenous H2S in the setting of acute myocardial infarction (AMI) and pressure overload-induced heart failure, but current formulations are derived from inorganic salts which have shortcomings in the precision and control of release of H2S. The main objective of this thesis was to determine if the novel, orally active, slow-releasing compound, SG1002, can attenuate the severity of damage and adverse remodeling caused by …