Diseases Commons^™

The Role Of Progesterone Receptor Membrane Component 1 In Receptor Trafficking And Disease, Kaia K. Hampton

Theses and Dissertations--Pharmacology and Nutritional Sciences

The progesterone receptor membrane component 1 (PGRMC1) is a multifunctional protein with a heme-binding domain that promotes cellular signaling via receptor trafficking, and is essential for some elements of tumor growth and metastasis. PGRMC1 is upregulated in breast, colon, lung and thyroid tumors. We expanded the analysis of PGRMC1 in the clinical setting, and report the first analysis of PGRMC1 in human oral cavity and ovarian tumors and found PGRMC1 to correlate with lung and ovarian cancer patient survival. Furthermore, we discovered a specific role for PGRMC1 in cancer stem cell viability. PGRMC1 directly associates with the epidermal growth factor …

Characterization Of Staphylococcal Nuclease And Tudor Domain Containing Protein 1 (Snd1) As A Molecular Target In Hepatocellular Carcinoma And Non-Alcoholic Steatohepatitis, Nidhi H. Jariwala

Theses and Dissertations

CHARACTERIZATION OF STAPHYLOCOCCAL NUCLEASE AND TUDOR DOMAIN CONTAINING PROTEIN 1 (SND1) AS A MOLECULAR TARGET IN HEPATOCELLULAR CARCINOMA AND NON-ALCOHOLIC STEATOHEPATITIS

Nidhi Jariwala, PhD

A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Integrative Life Sciences

Virginia Commonwealth University, 2017

Devanand Sarkar, M.B.B.S., PhD.

Associate Professor, Department of Human and Molecular Genetics

Virginia Commonwealth University

Richmond, Virginia

SND1, a subunit of the miRNA regulatory complex RISC, has been implicated as an oncogene in hepatocellular carcinoma (HCC). Oncoprotein SND1 regulates gene expression at a post-transcriptional level in multiple cancers including hepatocellular carcinoma (HCC). …

Yap And The Hippo Pathway In Pediatric Cancer., Atif Ahmed, Abdalla D. Mohamed, Melissa Gener, Weijie Li, Eugenio Taboada

Manuscripts, Articles, Book Chapters and Other Papers

The Hippo pathway is an important signaling pathway that controls cell proliferation and apoptosis. It is evolutionarily conserved in mammals and is stimulated by cell-cell contact, inhibiting cell proliferation in response to increased cell density. During early embryonic development, the Hippo signaling pathway regulates organ development and size, and its functions result in the coordinated balance between proliferation, apoptosis, and differentiation. Its principal effectors, YAP and TAZ, regulate signaling by the embryonic stem cells and determine cell fate and histogenesis. Dysfunction of this pathway contributes to cancer development in adults and children. Emerging studies have shed light on the upregulation …

Establishing A Clinically Relevant Mouse Model Of Human Aml To Test Novel Transmethylation Inhibitors., Aditya Barve

Electronic Theses and Dissertations

Acute myeloid leukemia (AML) is a highly heterogeneous clonal disorder characterized by an accumulation of malignant immature myeloid progenitors in the bone marrow (BM) that hinder normal hematopoiesis. Patient AML exhibits a dramatic heterogeneity in terms of cytogenetics, disease morphology, and associated prognoses and/or chemotherapeutic sensitivity. Thus it becomes clearly evident that the investigation of novel therapeutics for AML will require model systems that are capable of recapitulating this stark heterogeneity in a patient specific manner. Furthermore, it is now understood that the surrounding bone marrow (BM) microenvironment and supporting cells play a critical role in leukemic progression as well …

Current And Emerging Uses Of Statins In Clinical Therapeutics: A Review, Jonathan T. Davies, Spencer F. Delfino, Chad E. Feinberg, Meghan F. Johnson, Veronica L. Nappi, Joshua T. Olinger, Anthony P. Schwab, Hollie I. Swanson

Pharmacology and Nutritional Sciences Faculty Publications

Statins, a class of cholesterol-lowering medications that inhibit 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, are commonly administered to treat atherosclerotic cardiovascular disease. Statin use may expand considerably given its potential for treating an array of cholesterol-independent diseases. However, the lack of conclusive evidence supporting these emerging therapeutic uses of statins brings to the fore a number of unanswered questions including uncertainties regarding patient-to-patient variability in response to statins, the most appropriate statin to be used for the desired effect, and the efficacy of statins in treating cholesterol-independent diseases. In this review, the adverse effects, costs, and drug–drug and drug–food interactions associated with statin …

The Roles Of Nuclear Receptor Nr4a1 In Cancer Cell Proliferation And Skeletal Muscle Differentiation, Alexa Farmer

Theses and Dissertations (ETD)

Nuclear receptors (NRs) constitute a major class of drug targets in the treatment of various cancer types. NRs respond to cellular signals and become activated upon ligand binding to transcriptionally modulate expression of target genes. NR4A1 (Nur77) is a member of the NR4A family of nuclear receptors and displays an oncogenic profile in many cancer models. It is often upregulated in adult solid malignancies and is known to promote cell proliferation and survival. Knockdown studies of NR4A1 in cancer cell lines results in decreased cell growth and angiogenesis and increased apoptosis, suggesting NR4A1 is an oncogenic protein. Due to the …

Mechanism Of Action And Applications Of Interleukin 24 In Immunotherapy, Leah Persaud, Dayenny De Jesus, Oliver Brannigan, Maria Richiez-Paredes, Jeannette Huaman, Giselle Alvarado, Linda Riker, Gissete Mendez, Jordan Dejoie, Moira Sauane

Publications and Research

Interleukin 24 (IL-24) is an important pleiotropic immunoregulatory cytokine, whose gene is located in human chromosome 1q32-33. IL-24’s signaling pathways have diverse biological functions related to cell differentiation, proliferation, development, apoptosis, and inflammation, placing it at the center of an active area of research. IL-24 is well known for its apoptotic effect in cancer cells while having no such effect on normal cells. IL-24 can also be secreted by both immune and non-immune cells. Downstream effects of IL-24, after binding to the IL-20 receptor, can occur dependently or independently of the JAK/STAT signal transduction pathway, which is classically involved in …

Novel Oncogenic Drivers In Pediatric Gliomagenesis, Alexander K. Diaz

Theses and Dissertations (ETD)

Pediatric high-grade gliomas (pHGGs), with a two-year survival rate of less than 20%, are some of the most aggressive human cancers. This dissertation begins with our analysis of 127 pHGGs, including brainstem (BS) and non-brainstem (NBS) tumors, from 118 patients using next-generation sequencing technologies. Nearly one-third of BS-HGGs, also known as diffuse intrinsic pontine gliomas (DIPGs), harbored somatic heterozygous missense mutations in ACVR1, coding for a receptor serine-threonine kinase involved in bone morphogenetic protein (BMP) signaling. These alterations led to gain-of-function as evidenced by increased phosphorylation of downstream targets in primary astrocytes and zebrafish embryo ventralization. Whole-genome sequencing and …

Overcoming Cancer Multidrug Resistance Through Inhibition Of Microparticles, Sora Vysotski, Rivka Winzelberg, Mariana Babayeva

Touro College of Pharmacy (New York) Publications and Research

One of the main obstacles to success of chemotherapy agents is the development of cancer resistance. Cancer multidrug resistance (MDR) is thought to arise from over-expression of efflux transporters on cancer cells’ plasma membranes. Recently, microparticles (MP) were found to play a major role in mediating the resistance to antineoplastic agents. Microparticles can confer MDR phenotype to cancer cells though 3 complimentary pathways: 1) Intercellular transfer of P-gp and MRP1; 2) Intercellular transfer of regulatory nucleic acids that ensure acquisition of MDR phenotype; and 3) Internal sequestration of anticancer drugs to reduce the amount of free active drug. Compounds that …

Evaluating Human Cell Survival And Dna Damage After Exposure To Various Amounts Of Chlorine Dioxide And Exploring Its Use As A Potential Cancer Chemotherapy Agent, Niuska Mariana Alvarez Fuenmayor

SURF - Summer Undergraduate Research Fellowship Projects

Chlorine Dioxide (ClO₂) is a synthetic, green-yellowish gas with a chlorine-like, irritating odor that is used for the treatment of drinking water and food preservation. The aim of this study was to evaluate the genotoxic potential of the chlorine dioxide in mammalian cells and to determine what dose of ClO₂ is tolerable by normal cells and cells with aberrant DNA repair genes. Human and mouse embryonic cells were treated with various ClO₂ dilutions ranging from 2.5 mM to 25 mM. The cell viability and metabolic activity was determined via MTT, a colorimetric assay. Human HEK293 cells …

Feasibility Of Integrating Tripterygium Wilfordii Into Modern Cancer Therapy For Increased Efficacy With Minimal Toxicity, Andy Vo

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Cancer is the second leading cause of death in the U.S., and millions of novel cancer cases are being diagnosed each year. While chemotherapy and ionizing radiation are effective treatments against these malignant tumors, the adverse effects that accompany such treatments are devastating. In order to find alternative treatment methods with less side effects, we turn to Eastern herbal medicine. Recent scientific research has found that Tripterygium wilfordii, an herbal medicine traditionally used to treat inflammation in China, contains compounds (triptolide and celastrol) that prevent the growth of solid tumors, induce apoptosis, and prevent metastasis of developed tumors. Investigations on …

Selective Action Of Aqueous Maté Extract On Human Breast Cancer, Catherine Nguyen, Kenisha Nisbett, Vanessa Halvorsen, Calvin He, Amina Sadik

College of Osteopathic Medicine (TUN) Publications and Research

Ilex paraguariensis, Yerba Maté, is a subtropical plant native to South America, where it is consumed several times daily as a tea made with roasted leaves. Several studies have been conducted to elucidate the beneficial effects of this plant. A recent study has shown that saponins isolated from Yerba Maté extract induce apoptosis in human colon cancer cells, while another study indicated that the consumption of Maté tea causes higher incidence of esophageal cancer. Our study looked into the effects Yerba Maté extract have on human breast cancer cells and non-cancer cells from the same tissue. The findings show …

A Novel Caspase 8 Selective Small Molecule Potentiates Trail-Induced Cell Death, Octavian Bucur, Gabriel Gaidos, Achani Yatawara, Bodvael Pennarun, Chamila Rupasinghe, Jérémie Roux, Stefan Andrei, Bingqian Guo, Alexandra Panaitiu, Maria Pellegrini, Dale Mierke, Roya Khosravi-Far

Dartmouth Scholarship

Recombinant soluble TRAIL and agonistic antibodies against TRAIL receptors (DR4 and DR5) are currently being created for clinical cancer therapy, due to their selective killing of cancer cells and high safety characteristics. However, resistance to TRAIL and other targeted therapies is an important issue facing current cancer research field. An attractive strategy to sensitize resistant malignancies to TRAIL-induced cell death is the design of small molecules that target and promote caspase 8 activation. For the first time, we describe the discovery and characterization of a small molecule that directly binds caspase 8 and enhances its activation when combined with TRAIL, …

The Effect Of An Educational Intervention On Knowledge And Intent To Participate In Cervical Cancer Screening, Ann Marie Trapp

Evidence-Based Practice Project Reports

Globally, cervical cancer ranks third among cancers affecting women (Arbyn et al., 2013). In the United States, approximately 12,000 women are diagnosed with cervical cancer and approximately 4,000 women die yearly (Centers for Disease Control and Prevention, 2014). Papanicolaou (Pap) screening is an effective means of detecting precancerous cell changes of the cervix with early cervical cancer diagnosis carrying a 91% five-year survival rate (Gonzalez et al., 2012). The purpose of this evidence-based practice project was to identify interventions that increase adherence to cervical cancer screening and to implement best practices to reduce unnecessary deaths related to late diagnoses of …

Active Immunotherapy And Adoptive Cell Transfer As An Effective Cancer Treatment, Philip Jay Cynamon

The Science Journal of the Lander College of Arts and Sciences

There are many ways to fight cancer using the body’s own immune system. Some methods include the administration of vaccines while others involve stimulatory factors injected near tumors. One promising method is enlisting the help of T cells. To fight cancer effectively, T cells must be able to recognize cancerous antigens and the environment in which these T cells reside must be conducive to their function, survival, and proliferation. This paper discusses a method of providing such an environment called adoptive cell transfer, as well as the elements that effect this protocol and the ways in which the environment can …

Cancer Stem Cells In The Screening Of Anticancer Drugs For Central Nervous System Tumors, Sarah Elizabeth Daron-Mathis

Theses, Dissertations and Capstones

There is a growing need (in the medical field) to design personalized therapy for cancer patients. Decades of cancer research have found no silver bullet that can cure all or even most patients. This study evaluated four patients affected by central nervous system (CNS) tumors (Ependymoma and Glioblastoma), and found that tumors with the same histology had unique responses to treatment. Each sample presented different levels of heterogeneity in expressed biomarkers and responded to drugs at varying levels.

Oncologists conventionally treat cancer patients with drugs tested in large clinical trials. However, often patients do not experience positive outcomes following treatments …

Drug-Induced Cardiotoxicity Of Oncological Agents: Monitoring Parameters, Prevention, And Future Chemotherapy, Sarah Nguyen, Mary Nguyen, Laura Tsu

Pharmacy Faculty Articles and Research

The goal of this article is to educate pharmacists of the impact of cardiotoxicity on chemotherapy regimens including key cancer agents, monitoring parameters, prevention, and the future of chemotherapy.

Transposon Based Gene Therapy As A Treatment For Cancer, Jacob Stauber

The Science Journal of the Lander College of Arts and Sciences

Gene therapy is the use of genes to treat or prevent diseases. Diseases such as cancer, which are difficult to treat using conventional methods, can be treated using gene therapy. The transport of the therapeutic transgene can be accomplished using viral or non-viral methods. However, widespread use of viral vectors is limited due to its high cost of manufacture and safety concern. Non-viral vectors are limited in their effectiveness. The use of transposons such as the Sleeping Beauty transposon system can effectively deliver the transgene with less concern than viral vectors. This review discusses the various vectors and treatment strategies …

Epigenetics As A Cure For Cancer, Sara Rivka Margolis

The Science Journal of the Lander College of Arts and Sciences

Epigenetics is an emerging research topic that is being tested as a potential cure for cancer. Epigenetics is a non-genetic influence that shapes the phenotype. Epigenetics effects gene expression, but does not cause any changes in the DNA. DNA methylation patterns is one such epigenetic change in the cell that has huge potential for cancer treatment. Scientists have observed that many cancerous genes express signs of either hypermethylation or hypomethylation. The key for the treatment is that epigenetic changes are reversible, which opens the door to potential drugs to cure cancer and other diseases.

Why Are People With Laron Syndrome Immune To Cancer?, Raquel Margolis

The Science Journal of the Lander College of Arts and Sciences

Laron syndrome is a congenital autosomal recessive disorder that is caused by a mutation in the growth hormone receptor. People with this syndrome have an insensitivity to growth hormone. Insulin-like growth factor 1 is produced by the liver in response to GH stimulus. It is responsible for systemic GH activities. If there is something wrong with the growth hormone receptor there will be decreased levels of IGF-1. Low IGF-1 levels cause physical deformities notable short stature. Additionally, people with low levels of IGF-1 have a natural resistance to cancer. This article discusses the ways that the decreased levels of IGF-1 …

Clinical And Pathologic Significance Of Integrin Α6Β4 Expression In Human Malignancies, Rachel L. Stewart

Theses and Dissertations--Clinical and Translational Science

Integrins are cellular adhesion molecules that bind cells to the extracellular matrix. The integrin α6β4, a receptor for laminins, is predominantly expressed on epithelial cells where it is present at the basal surface adjacent to the basement membrane. This integrin plays a critical role in maintaining normal cellular functions, yet has also been implicated in promoting invasion and metastasis in human malignancies. While overexpression of the integrin α6β4 has been detected in select human cancers, the clinical significance of integrin α6β4 expression in a number of malignancies has not been determined. The purpose of this study was to examine integrin …

Killing Adherent And Nonadherent Cancer Cells With The Plasma Pencil, Mounir Laroussi, Soheila Mohades, Nazir Barekzi

Electrical & Computer Engineering Faculty Publications

The application of low temperature plasmas in biology and medicine may lead to a paradigm shift in the way various diseases can be treated without serious side effects. Low temperature plasmas generated in gas mixtures that contain oxygen or air produce several chemically reactive species that have important biological implications when they interact with eukaryotic or prokaryotic cells. Here, a review of the effects of low temperature plasma generated by the plasma pencil on different cancerous cells is presented. Results indicate that plasma consistently shows a delayed killing effect that is dose dependent. In addition, there is some evidence that …

Curcumin: A Folklore Remedy From Kitchen On The Way To Clinic As Cancer Drug, Debasish Bandyopadhyay

School of Integrative Biological & Chemical Sciences (Formerly Dept. of Chemistry)

Numerous compounds are widely distributed in nature and many of these possess medicinal/biological/pharmacological activity. Curcumin, a polyphenol derived from the rhizomes (underground stems) of Curcuma longa Linn (a member of the ginger family, commonly known as turmeric) is a culinary spice and therapeutic used in India for thousands of years to induce color and flavor in food as well as to treat a wide array of diseases. The origin of turmeric as spice and folklore medicine is so old that it is lost in legend. Curcumin has many beneficial pharmacological effects which includes, but are not limited with, antimicrobial, anti-inflammatory, …

Dual Pi3k/Mtor Inhibition With Bez235 Augments The Therapeutic Efficacy Of Doxorubicin In Cancer Without Influencing Cardiac Function, David E. Durrant

Theses and Dissertations

Cancer continues to be a leading cause death in the United States despite improved treatments. Cancerous lesions form after acquiring oncogenic driver mutations or losing tumor suppressor function in normal cells. Traditional therapies have included use of genotoxic substances that take advantage of the increased growth rate and loss of tumor suppressor function to cause cell death. One such drug is the anthracycline antibiotic doxorubicin (DOX). DOX interchelates into DNA and disrupts transcriptional machinery while also poisoning topoisomerase II. This results in single and double stranded DNA breaks, which if severe enough leads to either necrotic or apoptotic cell death. …

Lung Cancer Survival Disparities In Nevada, Chima Osuoha

UNLV Theses, Dissertations, Professional Papers, and Capstones

Lung cancer is the leading cause of cancer death in both men and women in the United States. Nevada shows moderate incidence rates of lung cancer for men but high rates for women. Little is known about the lung cancer experience and survival characteristics of the nearly 2000 new cases occurring every year in the State. The purpose of this study was to measure the extent to which geographic area of residency, gender, race, health insurance, social economic status (SES) and stage at diagnosis were associated with survival in patients diagnosed with lung cancer in Nevada. This was a retrospective …

Novel Biomarkers Can Be Used As Targets To Combat Cancer, Harini Krishnan

Graduate School of Biomedical Sciences Theses and Dissertations

Cancer kills almost 8 million people per year worldwide. Therefore, about 13 people die from cancer every minute. Clearly, current cancer treatments are not completely effective. Moreover, many chemotherapeutic reagents are not very specific for cancer cells.

These agents attack rapidly dividing cells, including a wide array of normal cells, in addition to cancer cells, in the body. This lack of specificity can cause collateral damage and significant side effects in patients. More targeted therapies are needed to successfully combat cancer. Specific cancer biomarkers need to identified and characterized in order to develop better targeted anti-cancer drugs.

Tumor cells can …

Concepts Of Cancer And A Novel Cancer Therapy: Treating Tumors As An Aggressive Organ, Stephen J. Beebe

Bioelectrics Publications

No abstract provided.

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

University Scholar Projects

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

Honors Scholar Theses

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …

Lrh1 As A Driving Factor For Cancer Development, Alissa M. Margraf

Senior Honors Projects

LRH1 as a driving factor for cancer development

Alissa Margraf, Qi Tang, Qiushi Lin, Xiaoqun Dong

Department of Biomedical and Pharmaceutical Science, College of Pharmacy, The University of Rhode Island, Pharmacy Building, 7 Greenhouse Road, Kingston, RI 02881 USA

Cancer is a major public health problem worldwide. Colon cancer ranks as the third most common causes of cancer mortality in the United States, with an estimated 96,830 new cases and 50,310 deaths in 2014. Colon cancer develops in the digestive tract where benign growths called polyps transform into malignant tumors. Colon cancer cells invade and destroy nearby tissue and can …