Medicine and Health Sciences Commons^™

Using Noninvasive Calibrated Cuff Plethysmography To Observe The Effects Of Cold-Water Immersion On Arterial Compliance, Rita M. Grigorian

Master's Theses

As the prevalence of cardiovascular diseases continues to exponentially grow in populations across the globe, the necessity of determining underlying factors, effective methods of diagnoses, and universally available preventive measures also grows. Early detection of endothelial dysfunction, a proven precursor of cardiovascular diseases, can be extremely impactful in encouraging preventative measures and early intervention before medical conditions become chronic. In recent years, ice plunging, a form of cryotherapy involving full body immersion in cold water, has gained popularity within circles of fitness and health practitioners, gaining the interest of people of all backgrounds. Certain parallels observed between the human physiological …

The Phenomenon Of Multidrug Resistance In Glioblastomas, Alexandr N. Chernov, Diana A. Alaverdian, Elvira S. Galimova, Alessandra Renieri, Elisa Frullanti, Ilaria Meloni, Olga V. Shamova

Hematology/Oncology and Stem Cell Therapy

The most common and aggressive brain tumor in the adult population is glioblastoma (GBM). The lifespan of patients does not exceed 22 months. One of the reasons for the low effectiveness of GBM treatment is its radioresistance and chemoresistance. In the current review, we discuss the phenomenon of multidrug resistance of GBM in the context of the expression of ABC family transporter proteins and the mechanisms of proliferation, angiogenesis, and recurrence. We focused on the search of molecular targets among growth factors, receptors, signal transduction proteins, microRNAs, transcription factors, proto-oncogenes, tumor suppressor genes, and their single-nucleotide polymorphisms.

The Tca Cycle As A Nexus Of Metabolic Vulnerabilities In Cancer, Sunada Khadka

Dissertations & Theses (Open Access)

Uncontrolled proliferation of cancer cells necessitates rewiring of metabolic pathways to meet biosynthetic and bioenergetic demands of proliferation and fortify redox homeostasis. An increasing body of literature suggests that mitochondrial metabolism (tricarboxylic acid cycle (TCA) and oxidative phosphorylation) is imperative for cancer cell growth and proliferation. The scope of the works presented in this dissertation is to explore the importance of mitochondrial metabolism, and primarily the TCA cycle—the anabolic factory of cancer cells and leverage it as a targetable vulnerability in cancer. Cancer cells consume anabolic nutrients that are used to generate biosynthetic precursors in the TCA cycle. Continuous efflux …

Mechanistic Insights On The Role Of Ambrisentan, An Endothelin Type-A Receptor Antagonist, In Breast Cancer, Ruba Saleem Lutfi Amer

Theses

The activation of the endothelin receptor type A (ETAR) by its ligand endothelin-1 (ET-1) is well known for its role in vasoconstriction. Interestingly, ET-1 and ETAR are over-expressed in various human tumours, including breast cancer. Several studies described the important role of ETAR in cancer progression and metastasis. The extensive network of interactions that exist between the ET-1 axis and other signalling pathways can trigger autocrine and paracrine signalling that modulates different tumorigenesis processes, such as cellular proliferation and survival, epithelial-to-mesenchymal transition (EMT) and chemoresistance. The main objective of this study was to investigate the antitumor effects of Ambrisentan, a …

Etv2/Myct1 Axis In The Regulation Of Tumor Angiogenesis And Anti-Tumor Immunity, Ashraf Ul Kabir

Arts & Sciences Electronic Theses and Dissertations

Angiogenesis is a critical determinant of neoplastic growth and metastatic spread. As such, anti-angiogenic approaches have long been tried to throttle down tumor progression. However, current anti-angiogenic treatments so far have produced modest clinical benefits. Further in-depth research has provided rationales behind these disappointing and apparent perplexing clinical outcomes. It is now established that VEGF (vascular endothelial growth factor) and other prominent current angiogenic targets are neither specific to the vascular system nor the pathological conditions explaining the sub-optimal angiogenic control following the existing treatments. This suggests that anti-angiogenesis could still be a viable strategy for cancer patients should there …

Obesity Promotes Cooperation Of Cancer Stem-Like Cells And Macrophages To Enhance Mammary Tumor Angiogenesis, Lauren E. Hillers-Ziemer, Rachel Q. Mcmahon, Margaret Hietpas, Gretchen Paderta, Jennelle Lebeau, Jessica Mccready, Lisa M. Arendt

Biological and Physical Sciences Department Faculty Works

Obesity is correlated with worsened prognosis and treatment resistance in breast cancer. Macrophage-targeted therapies are currently in clinical trials, however, little is known about how obesity may impact treatment efficacy. Within breast adipose tissue, obesity leads to chronic, macrophage-driven inflammation, suggesting that obese breast cancer patients may benefit from these therapies. Using a high fat diet model of obesity, we orthotopically transplanted cancer cell lines into the mammary glands of obese and lean mice. We quantified changes in tumor invasiveness, angiogenesis and metastasis, and examined the efficacy of macrophage depletion to diminish tumor progression in obese and lean mice. Mammary …

Transcriptional Influence Of Retinoic Acid And Its Effects On Angiogenesis Of Murine Salivary Glands., Isaac Feinn

College of Arts & Sciences Senior Honors Theses

Salivary gland hypofunction is a major disorder of salivary glands, and can arise either from diseases such as xerostomia, or from defective epithelial morphogenesis during embryogenesis. Hundreds of thousands of individuals suffer from dry mouth, and there is currently no restorative therapy for these patients. Investigation of salivary gland developmental biology will inform regenerative therapies. Currently it is known that retinoic acid (RA), the biologically active form of Vitamin A, is required for proper development of the salivary gland, but little is known about its cellular mechanism regulating organogenesis. This study sought to analyze salivary gland development in Rdh10 knock …

Kinetics Of The Chromosome 14 Microrna Cluster Ortholog And Its Potential Role During Placental Development In The Pregnant Mare, Pouya Dini, Peter Daels, Shavahn C. Loux, Alejandro Esteller-Vico, Mariano Carossino, Kirsten E. Scoggin, Barry A. Ball

Maxwell H. Gluck Equine Research Center Faculty Publications

Background: The human chromosome 14 microRNA cluster (C14MC) is a conserved microRNA (miRNA) cluster across eutherian mammals, reported to play an important role in placental development. However, the expression kinetics and function of this cluster in the mammalian placenta are poorly understood. Here, we evaluated the expression kinetics of the equine C24MC, ortholog to the human C14MC, in the chorioallantoic membrane during the course of gestation.

Results: We demonstrated that C24MC-associated miRNAs presented a higher expression level during early stages of pregnancy, followed by a decline later in gestation. Evaluation of one member of C24MC (miR-409-3p) by in situ hybridization …

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 …

Novel Mechanisms Of Β-Adrenergic Signaling In Prostate Cancer Progression, Mohit Hulsurkar

Dissertations & Theses (Open Access)

Prostate cancer is the second leading cause of cancer death among American men. The American Cancer Society estimates that 180,890 men will be will be diagnosed with prostate cancer in 2016 in the USA. (http://www.cancer.org/cancer/prostatecancer/detailedguide/prostate-cancer-key-statistics). Androgen deprivation therapy (ADT) is the standard treatment for early stage prostate cancer. But most patients relapse with aggressive variants of prostate cancer, with survival time between 1-3 years. In order to develop cure for such aggressive variants of prostate cancer, our present understanding of the mechanisms underlying its progression needs to be advanced.

Recently, it has been found that activation of β-adrenergic signaling pathway …

The Role Of Capillaries In The Lesser Ailments Of Old Age And In Alzheimer's Disease And Vascular Dementia: The Potential Of Pro-Therapeutic Angiogenesis, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Apart from chronic diseases (arthritis, diabetes, etc.), old age is generally characterized by three lesser ailments: muscle weakness, minor memory lapses, and cold intolerance. This trio of complaints may have a common, underlying cause, namely, the age-associated reduced microcirculation in muscles, brain, skin, and elsewhere in the body. The Angiogenesis Hypothesis proposes that old age is in part a deficiency disease due to the decline in angiogenic (AG) factors, resulting in a reduced capillary density (CD) throughout the body. Over fifty published papers document waning levels of AG factors and/or decreased CD in various organ systems of aged animals and …

Muscle Weakness During Aging: A Deficiency State Involving Declining Angiogenesis, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

This essay begins by proposing that muscle weakness of old age from sarcopenia is due in large part to reduced capillary density in the muscles, as documented in 9 reports of aged persons and animals. Capillary density (CD) is determined by local levels of various angiogenic factors, which also decline in muscles with aging, as reported in 7 studies of old persons and animals. There are also numerous reports of reduced CD in the aged brain and other studies showing reduced CD in the kidney and heart of aged animals. Thus a waning angiogenesis throughout the body may be …

Investigating The Role Of Hydrogen Sulfide In The Survival, Growth And Angiogenic Potential Of Clear Cell Renal Cell Carcinoma Cell Lines And Xenografts, Eric Sonke

Electronic Thesis and Dissertation Repository

Clear cell renal cell carcinoma (ccRCC) is characterized by Von Hippel-Lindau (VHL)-deficiency, resulting in pseudohypoxic, angiogenic and glycolytic tumours. Hydrogen sulfide (H₂S) is an endogenously-produced gasotransmitter that accumulates under hypoxia and has been shown to be pro-angiogenic and cytoprotective in cancer. It was hypothesized that H₂S levels are elevated in VHL-deficient ccRCC, contributing to survival, metabolism, and angiogenesis. Using H₂S-specific probes, it was found that H₂S levels were higher in VHL-deficient ccRCC cell lines compared to cells with wild-type VHL. Inhibition of H₂S-producing enzymes could reduce the proliferation, metabolism …

Src Homology 2 Domain-Containing 5’-Inositol Phosphatase-2 (Ship2) Is An Effector Of Lymphatic Dysfunction, Germaine D. Agollah

Dissertations & Theses (Open Access)

The lymphatic system is essential for the transport of excess fluid, protein, and foreign materials from interstitial tissues to lymph nodes; for immune surveillance, and to maintain fluid homeostasis. Dysregulated lymphatics can be attributed to pathological conditions including tumor metastasis, inflammation, chronic wounds, obesity, blood vascular disorders, and lymphedema. Of these, lymphedema is the most extreme of lymphatic disorders and is represented by a spectrum of symptoms ranging from mild, subtle presentation to severe, disfiguring, overt presentation. Lymphedema is more manageable in the early stages of disease but severely reduces quality of life with progression. Due to lack of molecular …

Cancer Associated Fibroblast Derived Angiogenic Factor Mfap5 In Ovarian Cancer Progression, Sze Lee Cecilia Leung

Dissertations & Theses (Open Access)

Advanced stage ovarian cancer is the most lethal gynecologic malignancy. No major improvement on patient survival has been achieved in the past decade. Therefore, identification of predictive or prognostic markers and further understanding of the molecular mechanisms in ovarian cancer progression are of paramount importance.

While cancer cells have always been the targets for the identification of prognostic and predictive markers, the potential for developing new diagnosis and treatments based on the tumor supporting stromal microenvironment is relatively unexplored. Using transcriptome profiling analysis on microdissected stromal and epithelial components of normal and malignant ovarian tissues, we identified a gene signature …

Mcnamara 2014 Mmb1075 - Low Magnification Confocal Microscopy Of Tumor Angiogenesis, George Mcnamara

George McNamara

McNamara 2014 MMB1075 - Low Magnification Confocal Microscopy of Tumor Angiogenesis

Book chapter from Paddock 2014 Confocal Microscopy

Book is online at http://www.springer.com/us/book/9781588293510

Activation Of The Nf-Κb Pathway As A Mechanism Of Alcohol Enhanced Progression And Metastasis Of Human Hepatocellular Carcinoma, Fei Wang, Jin-Lian Yang, Ke-Ke Yu, Mei Xu, You-Zhi Xu, Li Chen, Yan-Min Lu, Hao-Shu Fang, Xin-Yi Wang, Zhong-Qian Hu, Fei-Fei Li, Lixin Kan, Jia Luo, Si-Ying Wang

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, is the third leading cause of cancer-related death in human. Alcohol is a known risk factor for HCC. However it is still unclear whether and how alcohol enhances the progression and metastasis of existing HCC.

METHODS AND RESULTS: We first retrospectively investigated 52 HCC patients (24 alcohol-drinkers and 28 non-drinkers), and found a positive correlation between alcohol consumption and advanced Tumor-Node-Metastasis (TNM) stages, higher vessel invasion and poorer prognosis. In vitro and in vivo experiments further indicated that alcohol promoted the progression and migration/invasion of HCC. Specifically, in …

Vasculogenesis And Angiogenesis In Vegf Receptor-1 Deficient Mice, Vivienne C. Ho, Guo-Hua Fong

UCHC Articles - Research

Vascular endothelial growth factor receptor-1 (VEGFR-1)/Flt-1 is a transmembrane tyrosine kinase receptor for VEGF-A, VEGF-B, and placental growth factor (PlGF). VEGFR-1 is an enigmatic molecule whose precise role in postnatal angiogenesis remains controversial. Although many postnatal and adult studies have been performed by manipulating VEGFR-1 ligands, including competitive binding by truncated VEGFR-1 protein, neutralization by antibodies, or specific ligand overexpression or knockout, much less is known at the level of the receptor per se, especially in vivo. Perplexingly, while VEGFR-1 negatively regulates endothelial cell differentiation during development, it has been implied in promoting angiogenesis under certain conditions in adult tissues, …

Mapping The Human Vasculature By In Vivo Phage Display, Julianna Bronk

Dissertations & Theses (Open Access)

In vivo phage display screenings by intravenous injection of a random phage-displayed peptide library allow for the selection of peptides that localize to specific vascular beds. At the University of Texas MD Anderson Cancer Center, we have had the opportunity to perform phage display screenings in cancer patients in order to select for cancer specific targets directly in humans. These targets serve to define biochemical diversity of endothelial cell surfaces and can be validated and explored towards the design of vascular-targeted pharmacology. In the most recent patient screen, samples were recovered from hepatocellular carcinoma (HCC) as well as 26 additional …

One-Day Treatment Of Small Molecule 8-Bromo-Cyclic Amp Analogue Induces Cell-Based Vegf Production For In Vitro Angiogenesis And Osteoblastic Differentiation, Kevin W.-H. Lo, Ho Man Kan, Keith A. Gagnon, Cato T. Laurencin

UCHC Articles - Research

Small molecule based regenerative engineering is emerging as a promising strategy for regenerating bone tissue. Small molecule cAMP analogues have been proposed as novel biofactors for bone repair and regeneration, and while promising, the effect that these small molecules have on angiogenesis, a critical requirement for successful bone regeneration, is still unclear. Our previous research demonstrated that the small molecule cAMP analogue 8-bromoadenosine-3’,5’-cyclic monophosphate (8-Br-cAMP) was able to promote initial osteoblast adhesion on a polymeric scaffold via cAMP signaling cascades. Here, we report that 8-Br-cAMP is capable of inducing in vitro cell-based VEGF production for angiogenesis promotion. We first demonstrated …

The Effects Of Hydrostatic Pressure On Early Endothelial Tubulogenic Processes, Ryan M. Underwood

Theses and Dissertations--Biomedical Engineering

The effects of mechanical forces on endothelial cell function and behavior are well documented, but have not been fully characterized. Specifically, fluid pressure has been shown to elicit physical and chemical responses known to be involved in the initiation and progression of endothelial cell-mediated vascularization. Central to the process of vascularization is the formation of tube-like structures. This process—tubulogenesis—is essential to both the physiological and pathological growth of tissues. Given the known effects of pressure on endothelial cells and its ubiquitous presence in the vasculature, we investigated pressure as a magnitude-dependent parameter for the regulation of endothelial tubulogenic activity. To …

A Critical Review Of Endometriosis Pathology, Brittany Lauren Cureton

Theses and Dissertations

Endometriosis is a complex, multifactorial, reproductive disorder present in approximately 10-15% of adult women between the ages of 25-35. This disorder occurs when endometrial glands and stroma grow ectopically on the surface of the ovaries, pelvic peritoneum, fallopian tubes, and the uterus. Endometriosis causes varying degrees of painful symptoms and infertility in infected individuals. Three main theories of endometrial accumulation attempt to explain the etiology of this elusive disease. There have been various staging of endometriosis symptoms that attempt to standardize classification as well as predict pain and infertility. Angiogenesis, necessary to the survival of endometrial tissue, along with immune …

Platelets And Anti-Angiogenic Resistance In Ovarian Carcinoma, Justin N. Bottsford-Miller

Dissertations & Theses (Open Access)

Background: Resistance to targeted anti-angiogenic therapy is a growing clinical concern given the disappointing clinical impact of anti-angiogenic. Platelets represent a component of the tumor microenvironment that are implicated in metastasis and represent a significant reservoir of angiogenic regulators. Thrombocytosis has been shown to be caused by malignancy and associated with adverse clinical outcomes, however the causal connections between these associations remain to be identified.

Materials and Methods: Following IRB approval, patient data were collected on patients from four U.S. centers and platelet levels through and after therapy were considered as indicators of recurrence of disease. In vitro effects of …

Hypoxia-Sensitive Gene Expression In The Gastrocnemius Muscle Following Chronic Hind Limb Ischemia, Andrew Tilton

Biological Sciences

Chronic ischemia, caused by the formation atherosclerotic plaque occlusions in major conduit arteries, is the leading cause of morbidity and mortality in western societies. Vascular remodeling can help compensate for the adverse effects of atherosclerotic plaque formation. Vascular remodeling relies heavily on vascular endothelial growth factor (VEGF), a critical protein that contributes to all forms of vascular formation and remodeling including angiogenesis, arteriogenesisand vasculogenesis. VEGF itself is up-regulated by the transcription factor, hypoxia inducible factor 1 alpha (HIF-1α), which becomes activated in low oxygen environments.

Through the use of animal chronic hindlimb ischemia models, these genes can be evaluated as …

Development Of A Protocol To Measure Gene Expression In The Mouse Tibia, Daniel Hoover

Biomedical Engineering

Numerous molecular factors active in bone tissue direct fracture repair and remodeling which can be altered by disease conditions such as Peripheral Arterial Disease (PAD) and Osteoporosis. Methods of molecular biology are commonly applied to investigate the expression and role of these molecular factors. This project presents a robust three-step protocol for examining gene expression in the mouse tibia. The protocol begins with isolating RNA from a flash frozen tibia sample. The isolated RNA is reverse transcribed into cDNA. Finally, PCR is performed to indentify expressed genes. Establishing this protocol will allow further research into the mechanisms of bone remodeling …

Angiostatin Like Peptides In Milk: Potential Development For Dairy Products Capable Of Cancer Prevention, Erin Stefanutti

Master's Theses

For the past 40 years, antiangiogenic approaches have been of major interest in the development of methods to cure and prevent cancer. Angiogenesis, the development of blood vessels from pre-existing vascularization, is essential for cancer growth and spread of metastasis through the delivery of nutrients and oxygen essential to sustain the metabolic activity of these malignant cells. Blocking access to blood will cause cancerous cells to assume a dormant state creating inactive micro-tumors innocuous to the host. Angiostatin, the internal fragment of the fibrinolytic zymogen plasminogen, has shown great potential in reducing cancer size and number of metastatic colonies in …

Apoptosis Initiation And Angiogenesis Inhibition: Melanoma Targets For Nanosecond Pulsed Electric Fields, Xinhua Chen, Juergen F. Kolb, R. James Swanson, Karl H. Schoenbach, Stephen J. Beebe

Bioelectrics Publications

Many effective anti-cancer strategies target apoptosis and angiogenesis mechanisms. Applications of non-ionizing, nanosecond pulsed electric fields (nsPEFs) induce apoptosis in vitro and eliminate cancer in vivo; however in vivo mechanisms require closer analysis. These studies investigate nsPEF-induced apoptosis and anti-angiogenesis examined by fluorescent microscopy, immunoblots, and morphology. Six hours after treatment with one hundred 300 ns pulses at 40 kV/cm, cells transiently expressed active caspases indicating that caspase-mediated mechanisms. Three hours after treatment transient peaks in Histone 2AX phosphorylation coincided with terminal deoxynucleotidyl transferase dUTP nick end labeling positive cells and pyknotic nuclei, suggesting caspase-independent mechanisms on nuclei/DNA. Large …

A New Pulsed Electric Field Therapy For Melanoma Disrupts The Tumor's Blood Supply And Causes Complete Remission Without Recurrence, Richard Nuccitelli, Xinhua Chen, Andrei G. Pakhomov, Wallace H. Baldwin, Saleh Sheikh, Jennifer L. Pomicter, Wei Ren, Chris Osgood, R. James Swanson, Juergen F. Kolb, Stephen J. Beebe, Karl H. Schoenbach

Bioelectrics Publications

We have discovered a new, ultrafast therapy for treating skin cancer that is extremely effective with a total electric field exposure time of only 180 mu sec. The application of 300 high-voltage (40 kV/cm), ultrashort (300 nsec) electrical pulses to murine melanomas in vivo triggers both necrosis and apoptosis, resulting in complete tumor remission within an average of 47 days in the 17 animals treated. None of these melanomas recurred during a 4-month period after the initial melanoma had disappeared. These pulses generate small, long-lasting, rectifying nanopores in the plasma membrane of exposed cells, resulting in increased membrane permeability to …