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Extraction, Purification And Evaluation Of Prmt5-Inhibitory Phytochemical Compounds For The Treatment Of Prostate Adenocarcinoma, Oliver H. Richmond III 2019 Clark Atlanta University

Extraction, Purification And Evaluation Of Prmt5-Inhibitory Phytochemical Compounds For The Treatment Of Prostate Adenocarcinoma, Oliver H. Richmond Iii

Electronic Theses & Dissertations Collection for Atlanta University & Clark Atlanta University

The development and advancement of prostate cancer is supported by a plethora of genetic and proteomic abnormalities, including events of post-translational modifications. The protein arginine methyltransferase 5 (PRMT5) enzyme regulates epigenetic events of histone modifications and protein post-translational modifications within protein signaling pathways. PRMT5 functions by catalyzing the symmetric dimethylation of terminal arginine residues on target protein substrates. Under abnormal conditions of overexpression and upregulation, PRMT5 methyltransferase activity constitutively drives the growth and proliferation of dysregulated cells. Overexpression or upregulation of PRMT5 correlates with disease progression as observed among numerous cancer types, including breast, colorectal, leukemia, lung, melanoma and prostate ...


Reversal Of P-Glycoprotein And Breast Cancer Resistance Protein Mediated Multidrug Resistance In Vitro Using In Silico Identified Novel Compounds, Amila Nanayakkara 2019 Southern Methodist University

Reversal Of P-Glycoprotein And Breast Cancer Resistance Protein Mediated Multidrug Resistance In Vitro Using In Silico Identified Novel Compounds, Amila Nanayakkara

Biological Sciences Theses and Dissertations

Multidrug resistance (MDR) is a major cause of chemotherapy failure. Overexpression of ATP-binding cassette (ABC) transporters, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are two well-studied drug transporters which are associated with MDR. These two transporters also act as a major functional unit of the blood brain barrier to protect the brain from xenobiotics and toxins. Lack of clinically approved P-gp and BCRP inhibitors renders chemotherapy treatments of many MDR cancers ineffective and obstructs drug uptake into the brain.

Using computational methods, we have identified new compounds that inhibit P-gp (Brewer et al., Mol. Pharmacol. 2014). Several of these ...


Impact Of Pharmacogenomics On Clinical Outcomes In Major Depressive Disorder In The Guided Trial: A Large, Patient- And Rater-Blinded, Randomized, Controlled Study, John F. Greden, Anthony J. Rothschild 2019 University of Michigan-Ann Arbor

Impact Of Pharmacogenomics On Clinical Outcomes In Major Depressive Disorder In The Guided Trial: A Large, Patient- And Rater-Blinded, Randomized, Controlled Study, John F. Greden, Anthony J. Rothschild

Open Access Articles

Current prescribing practices for major depressive disorder (MDD) produce limited treatment success. Although pharmacogenomics may improve outcomes by identifying genetically inappropriate medications, studies to date were limited in scope. Outpatients (N=1167) diagnosed with MDD and with a patient- or clinician-reported inadequate response to at least one antidepressant were enrolled in the Genomics Used to Improve DEpression Decisions (GUIDED) trial - a rater- and patient-blind randomized controlled trial. Patients were randomized to treatment as usual (TAU) or a pharmacogenomics-guided intervention arm in which clinicians had access to a pharmacogenomic test report to inform medication selections (guided-care). Medications were considered congruent ('use ...


Thioredoxin Modulates Protein Arginine Deiminase 4 (Pad4)-Catalyzed Citrullination, Mitesh Nagar, Ronak Tilvawala, Paul R. Thompson 2019 University of Massachusetts Medical School

Thioredoxin Modulates Protein Arginine Deiminase 4 (Pad4)-Catalyzed Citrullination, Mitesh Nagar, Ronak Tilvawala, Paul R. Thompson

Open Access Articles

Protein citrullination is a post-translational modification catalyzed by the protein arginine deiminases (PADs). This modification plays a crucial role in the pathophysiology of numerous autoimmune disorders including RA. Recently, there has been a growing interest in investigating physiological regulators of PAD activity to understand the primary cause of the associated disorders. Apart from calcium, it is well-documented that a reducing environment activates the PADs. Although the concentration of thioredoxin (hTRX), an oxidoreductase that maintains the cellular reducing environment, is elevated in RA patients, its contribution toward RA progression or PAD activity has not been explored. Herein, we demonstrate that hTRX ...


Analyzing Drug Release Kinetics From Water-Soluble Polymers, Sean M. Kelly, Arun K. Upadhyay, Akash Mitra, Balaji Narasimhan 2019 Iowa State University

Analyzing Drug Release Kinetics From Water-Soluble Polymers, Sean M. Kelly, Arun K. Upadhyay, Akash Mitra, Balaji Narasimhan

Chemical and Biological Engineering Publications

The ability to develop predictive mathematical models of therapeutic release from pharmaceutical formulations has enormous potential to enhance our understanding of such systems and improve the controlled release of the payload. The current work describes the development and testing of a one-dimensional model of drug transport from amorphous, swelling/dissolving polymers. Model parameters such as the diffusivities of water and drug, the initial loading of the drug, the polymer dissolution rate, drug-polymer interactions, and the tablet thickness were varied, demonstrating the ability to tune the release to be controlled by either drug diffusion or polymer chain disentanglement. In addition, predictions ...


5-Ht2a Deletion Protects Against Clozapine-Induced Hyperglycemia, Radhika Sudhir Joshi, Shishu Pal Singh, Mitradas M. Panicker 2019 University of Massachusetts Medical School

5-Ht2a Deletion Protects Against Clozapine-Induced Hyperglycemia, Radhika Sudhir Joshi, Shishu Pal Singh, Mitradas M. Panicker

Open Access Articles

Clozapine is an antipsychotic known for its superior efficacy in treating drug-resistant Schizophrenia. However, Clozapine induces various side effects such as hyperglycemia, agranulocytosis, weight gain etc. The mechanisms of these Clozapine-induced side effects have remained largely elusive though an important role is ascribed to 5-HT2A (Serotonin receptor subtype-2A). In this pilot study, we report for the first time that the 5-HT2A 'global' knockout mice (Htr2a(-/-)) are resistant to the Clozapine-induced hyperglycemia. Importantly though, the Htr2a(-/-) mice exhibit near normal basal glucose metabolism in the glucose tolerance tests. Collectively, the Htr2a(-/-) mice provide an important tool to study the Clozapine-induced hyperglycemia.


A Data Analytics Approach For Rational Design Of Nanomedicines With Programmable Drug Release, Adam S. Mullis, Scott R. Broderick, Andrea M. Binnebose, Nathan Peroutka-Bigus, Bryan H. Bellaire, Krishna Rajan, Balaji Narasimhan 2019 Iowa State University

A Data Analytics Approach For Rational Design Of Nanomedicines With Programmable Drug Release, Adam S. Mullis, Scott R. Broderick, Andrea M. Binnebose, Nathan Peroutka-Bigus, Bryan H. Bellaire, Krishna Rajan, Balaji Narasimhan

Chemical and Biological Engineering Publications

Drug delivery vehicles can improve the functional efficacy of existing antimicrobial therapies by improving biodistribution and targeting. A critical property of such nanomedicine formulations is their ability to control the release kinetics of their payloads. The combination of (and interactions between) polymer, drug, and nanoparticle properties gives rise to nonlinear behavioral relationships and a large data space. These factors complicate both first-principles modeling and screening of nanomedicine formulations. Predictive analytics may offer a more efficient approach toward rational design of nanomedicines by identifying key descriptors and correlating them to nanoparticle release behavior. In this work, antibiotic release kinetics data were ...


Ectopic High Endothelial Venules In Pancreatic Ductal Adenocarcinoma: A Unique Site For Targeted Delivery, Baharak Bahmani, Mayuko Uehara, Farideh Ordikhani, Xiaofei Li, Liwei Jiang, Naima Banouni, Takaharu Ichimura, Vivek Kasinath, Siawosh K. Eskandari, Nasim Annabi, Jonathan S. Bromberg, Leonard D. Shultz, Dale L. Greiner, Reza Abdi 2018 Harvard Medical School

Ectopic High Endothelial Venules In Pancreatic Ductal Adenocarcinoma: A Unique Site For Targeted Delivery, Baharak Bahmani, Mayuko Uehara, Farideh Ordikhani, Xiaofei Li, Liwei Jiang, Naima Banouni, Takaharu Ichimura, Vivek Kasinath, Siawosh K. Eskandari, Nasim Annabi, Jonathan S. Bromberg, Leonard D. Shultz, Dale L. Greiner, Reza Abdi

Open Access Articles

BACKGROUND: Nanomedicine offers an excellent opportunity to tackle treatment-refractory malignancies by enhancing the delivery of therapeutics to the tumor site. High endothelial venules (HEVs) are found primarily in lymph nodes or formed de novo in peripheral tissues during inflammatory responses. They express peripheral node addressin (PNAd), which is recognized by the monoclonal antibody MECA79.

METHODS: Here, we demonstrated that HEVs form de novo in human pancreatic ductal adenocarcinoma (PDAC). We engineered MECA79 coated nanoparticles (MECA79-NPs) that recognize these ectopic HEVs in PDAC.

FINDINGS: The trafficking of MECA79-NPs following intravenous delivery to human PDAC implanted in a humanized mouse model was ...


Targeted Delivery Of Bioactive Molecules For Vascular Intervention And Tissue Engineering, Hannah A. Strobel, Elisabet I. Qendro, Eben Alsberg, Marsha W. Rolle 2018 Worcester Polytechnic Institute

Targeted Delivery Of Bioactive Molecules For Vascular Intervention And Tissue Engineering, Hannah A. Strobel, Elisabet I. Qendro, Eben Alsberg, Marsha W. Rolle

Open Access Articles

Cardiovascular diseases are the leading cause of death in the United States. Treatment often requires surgical interventions to re-open occluded vessels, bypass severe occlusions, or stabilize aneurysms. Despite the short-term success of such interventions, many ultimately fail due to thrombosis or restenosis (following stent placement), or incomplete healing (such as after aneurysm coil placement). Bioactive molecules capable of modulating host tissue responses and preventing these complications have been identified, but systemic delivery is often harmful or ineffective. This review discusses the use of localized bioactive molecule delivery methods to enhance the long-term success of vascular interventions, such as drug-eluting stents ...


The Pharmaceutical Industry: A Pharmacy Student's Guide, Christian Egly, Yaman Kaakeh 2018 Purdue University

The Pharmaceutical Industry: A Pharmacy Student's Guide, Christian Egly, Yaman Kaakeh

Purdue Journal of Service-Learning and International Engagement

Christian Egly is a fourth-year (P4) pharmacy student in the Purdue University College of Pharmacy. During his years at Purdue, he worked in labs performing bench research in clinical pharmacology and biochemistry. He plans to work in the pharmaceutical industry after graduation. During his fourth year, he completed rotations in business development at Kashiv Pharma, LLC, and was hired there for an internship in 2017. In the article, Christian describes his personal experiences at Kashiv Pharma, LLC, and how industry can positively affect patient communities.


Pyronaridine Exerts Potent Cytotoxicity On Human Breast And Hematological Cancer Cells Through Induction Of Apoptosis, Alberto Martinez, Paulina J. Villanueva, Sarah T. Baca, Rebecca E. DeJesus, Manuel Larragoity, Lisett Contreras, Denisse A. Gutierrez, Armando Varela-Ramirez, Renato J. Aguilera 2018 NYC College of Technology

Pyronaridine Exerts Potent Cytotoxicity On Human Breast And Hematological Cancer Cells Through Induction Of Apoptosis, Alberto Martinez, Paulina J. Villanueva, Sarah T. Baca, Rebecca E. Dejesus, Manuel Larragoity, Lisett Contreras, Denisse A. Gutierrez, Armando Varela-Ramirez, Renato J. Aguilera

Publications and Research

The potent antimalarial drug pyronaridine (PND) was tested for its potential as an anticancer drug. After exposing cancerous (17) and non-cancerous (2) cells to PND for 72 hr, PND was found to exhibit consistent and potent cytotoxic activity at low micromolar (μM) concentrations that ranged from 1.6 μM to 9.4 μM. Moreover, PND exerted a significant selective cytotoxicity index (SCI) on five out of seven breast cancer cell lines tested, with favorable values of 2.5 to 4.4, as compared with the non-cancerous breast MCF-10A cell line. By using the same comparison, PND exhibited a significant SCI ...


T Cell Epitope Engineering: An Avian H7n9 Influenza Vaccine Strategy For Pandemic Preparedness And Response, Leonard Moise, Bethany M. Biron, Christine M. Boyle, Nese Kurt Yilmaz, Hyesun Jang, Celia A. Schiffer, Ted M. Ross, William D. Martin, Anne S. De Groot 2018 University of Rhode Island

T Cell Epitope Engineering: An Avian H7n9 Influenza Vaccine Strategy For Pandemic Preparedness And Response, Leonard Moise, Bethany M. Biron, Christine M. Boyle, Nese Kurt Yilmaz, Hyesun Jang, Celia A. Schiffer, Ted M. Ross, William D. Martin, Anne S. De Groot

Schiffer Lab Publications

The delayed availability of vaccine during the 2009 H1N1 influenza pandemic created a sense of urgency to better prepare for the next influenza pandemic. Advancements in manufacturing technology, speed and capacity have been achieved but vaccine effectiveness remains a significant challenge. Here, we describe a novel vaccine design strategy called immune engineering in the context of H7N9 influenza vaccine development. The approach combines immunoinformatic and structure modeling methods to promote protective antibody responses against H7N9 hemagglutinin (HA) by engineering whole antigens to carry seasonal influenza HA memory CD4(+) T cell epitopes - without perturbing native antigen structure - by galvanizing HA-specific memory ...


Preparation And Characterization Of Functionalized Heparin-Loaded Poly-Ɛ-Caprolactone Fibrous Mats To Prevent Infection With Human Papillomaviruses, Daniela Gonzalez, Jorge Ragusa, Peter C. Angeletti, Gustavo F. Larsen 2018 University of Nebraska-Lincoln

Preparation And Characterization Of Functionalized Heparin-Loaded Poly-Ɛ-Caprolactone Fibrous Mats To Prevent Infection With Human Papillomaviruses, Daniela Gonzalez, Jorge Ragusa, Peter C. Angeletti, Gustavo F. Larsen

Chemical and Biomolecular Engineering -- All Faculty Papers

In this study, heparin-loaded poly-ε-caprolactone (PCL) fibrous mats were prepared and characterized based on their physical, cytotoxic, thermal, and biological properties. The main objective of the work described here was to test the hypothesis that incorporation of heparin into a PCL carrier could serve as bio-compatible material capable of inhibiting Human Papillomavirus (HPV) infection. The idea of firmly anchoring heparin to capture soluble virus, vs. a slow heparin release to inhibit a virus in solution was tested. Thus, one material was produced via conventional heparin matrix encapsulation and electrohydrodynamic fiber processing in one step. A second type of material was ...


Assembly Of Human C-Terminal Binding Protein (Ctbp) Into Tetramers, Andrew G. Bellesis, Anne M. Jecrois, Janelle A. Hayes, Celia A. Schiffer, William E. Royer 2018 University of Massachusetts Medical School

Assembly Of Human C-Terminal Binding Protein (Ctbp) Into Tetramers, Andrew G. Bellesis, Anne M. Jecrois, Janelle A. Hayes, Celia A. Schiffer, William E. Royer

Schiffer Lab Publications

C-terminal binding protein 1 (CtBP1) and CtBP2 are transcriptional coregulators that repress numerous cellular processes, such as apoptosis, by binding transcription factors and recruiting chromatin-remodeling enzymes to gene promoters. The NAD(H)-linked oligomerization of human CtBP is coupled to its co-transcriptional activity, which is implicated in cancer progression. However, the biologically relevant level of CtBP assembly has not been firmly established; nor has the stereochemical arrangement of the subunits above that of a dimer. Here, multi-angle light scattering (MALS) data established the NAD(+)- and NADH-dependent assembly of CtBP1 and CtBP2 into tetramers. An examination of subunit interactions within CtBP1 ...


Radical Social Ecology As Deep Pragmatism: A Call To The Abolition Of Systemic Dissonance And The Minimization Of Entropic Chaos, Arielle Brender 2018 Fordham University

Radical Social Ecology As Deep Pragmatism: A Call To The Abolition Of Systemic Dissonance And The Minimization Of Entropic Chaos, Arielle Brender

Student Theses 2015-Present

This paper aims to shed light on the dissonance caused by the superimposition of Dominant Human Systems on Natural Systems. I highlight the synthetic nature of Dominant Human Systems as egoic and linguistic phenomenon manufactured by a mere portion of the human population, which renders them inherently oppressive unto peoples and landscapes whose wisdom were barred from the design process. In pursuing a radical pragmatic approach to mending the simultaneous oppression and destruction of the human being and the earth, I highlight the necessity of minimizing entropic chaos caused by excess energy expenditure, an essential feature of systems that aim ...


Structure Based Drug Design Of High Affinity Kras Inhibitors, Michael McCarthy 2018 The University of Texas MD Anderson UTHealth Graduate School of Biomedical Sciences

Structure Based Drug Design Of High Affinity Kras Inhibitors, Michael Mccarthy

UT GSBS Dissertations and Theses (Open Access)

RAS, one of the most well characterized membrane-associated small GTPases, is a notorious oncogene with >15% of all tumors harboring RAS mutations. When RAS is mutated it becomes constitutively active sending cell growth, survival and proliferation into overdrive, which subsequently leads to cancer. Although, RAS has been aggressively targeted with drug design efforts for more than 30 years an FDA approved direct inhibitor has not yet been developed. There are three isoforms of RAS in cells; HRAS, NRAS and KRAS. We focused on KRAS since it is the most frequently mutated isoform in cancer. To identify novel non-covalent small molecules ...


Investigation Of Bacteria From The Trachymyrmex Septentrionalis Fungus Garden For Potential Antibacterial Drug Leads, Brendan Stewart 2018 University of Connecticut

Investigation Of Bacteria From The Trachymyrmex Septentrionalis Fungus Garden For Potential Antibacterial Drug Leads, Brendan Stewart

University Scholar Projects

Bacterial and fungal strains are growing resistance to antibiotics and antifungal agents at an alarming rate. According to the Centers for Disease Control and Prevention, over two million people in the United States in 2016 were diagnosed with an infection resistant to antibiotics. As such, there has been increased interest in natural products as sources of novel compounds that are essential to the development of new drugs and treatment methods. Within the environment, there are various host-microbe symbioses, one of which is the Trachymyrmex septentrionalis leaf-cutter ant community. The microbes in symbioses like the T. septentrionalis community are hypothesized to ...


Investigation Of Bacteria From The Trachymyrmex Septentrionalis Fungus Garden For Potential Antibacterial Drug Leads, Brendan Stewart 2018 University of Connecticut

Investigation Of Bacteria From The Trachymyrmex Septentrionalis Fungus Garden For Potential Antibacterial Drug Leads, Brendan Stewart

Honors Scholar Theses

Bacterial and fungal strains are growing resistance to antibiotics and antifungal agents at an alarming rate. According to the Centers for Disease Control and Prevention, over two million people in the United States in 2016 were diagnosed with an infection resistant to antibiotics. As such, there has been increased interest in natural products as sources of novel compounds that are essential to the development of new drugs and treatment methods. Within the environment, there are various host-microbe symbioses, one of which is the Trachymyrmex septentrionalis leaf-cutter ant community. The microbes in symbioses like the T. septentrionalis community are hypothesized to ...


Anntibiotic Resistance: Plasmid Transfer Among Bacterial Species Using Antibiotics Of The Tetracycline, Cephalosporin, And Carbapenem Classes, Natalie Lindgren, Lisa Ann Blankinship 2018 University of North Alabama

Anntibiotic Resistance: Plasmid Transfer Among Bacterial Species Using Antibiotics Of The Tetracycline, Cephalosporin, And Carbapenem Classes, Natalie Lindgren, Lisa Ann Blankinship

UNA Research Days

Antibiotic resistance makes the treatment of illness a constantly evolving obstacle in drug development. Under ideal conditions, antimicrobial drugs work by either killing bacterial organisms or inhibiting replication. However, bacterial species are able to improve their genetic composition through plasmid conjugation, enabling neutralization of, removal of, or protection from drugs. In a hospital setting, resistant pathogens lead to multi-drug resistant bacterial strains that endanger the lives of patients. The purpose of this project will be to study bacteria that exhibit resistance to antibiotics in the tetracycline, cephalosporin, and carbapenem classes and transfer that resistance to an antibiotic sensitive organism. Tetracycline ...


Evaluating The Aryl Hydrocarbon Receptor As A Target For Pharmacologic Activity Of Repurposed Drugs, Teofilo Borunda Duque 2018 University of New Mexico

Evaluating The Aryl Hydrocarbon Receptor As A Target For Pharmacologic Activity Of Repurposed Drugs, Teofilo Borunda Duque

Pharmaceutical Sciences ETDs

The discovery of new pharmacologic targets is important for the advancement of pharmacotherapy and identification of new indications for current drugs. The aryl hydrocarbon receptor (AHR) is a physiologic sensor of both chemical environmental pollutants and ligands of natural origin. Given the broad spectrum of ligands that activate the AHR and its relationship with toxicology, the AHR is not thought to be a traditional target for pharmacotherapy. However, multiple studies have shown potential for the AHR as a novel pharmacologic target Therefore, identifying less toxic agents that modulate the AHR may elucidate mechanisms for pharmacological targeting of the AHR. The ...


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