Pharmacy and Pharmaceutical Sciences Commons^™

Fibroblast Growth Factor-2 (Fgf2) And Syndecan-1 (Sdc1) Are Potential Biomarkers For Putative Circulating Cd15+/Cd30+ Cells In Poor Outcome Hodgkin Lymphoma Patients., Rajendra Gharbaran, Andre Goy, Takemi Tanaka, Jongwhan Park, Chris Kim, Nafis Hasan, Swathi Vemulapalli, Sreeja Sarojini, Madalina Tuluc, Kip Nalley, Pritish Bhattacharyya, Andrew Pecora, K Stephen Suh

College of Pharmacy Faculty Papers

BACKGROUND: High risk, unfavorable classical Hodgkin lymphoma (cHL) includes those patients with primary refractory or early relapse, and progressive disease. To improve the availability of biomarkers for this group of patients, we investigated both tumor biopsies and peripheral blood leukocytes (PBL) of untreated (chemo-naïve, CN) Nodular Sclerosis Classic Hodgkin Lymphoma (NS-cHL) patients for consistent biomarkers that can predict the outcome prior to frontline treatment.

METHODS AND MATERIALS: Bioinformatics data mining was used to generate 151 candidate biomarkers, which were screened against a library of 10 HL cell lines. Expression of FGF2 and SDC1 by CD30+ cells from HL patient samples …

Turning Stealth Liposomes Into Cationic Liposomes For Anticancer Drug Delivery, Vijay Gyanani

University of the Pacific Theses and Dissertations

Targeting the anticancer agents selectively to cancer cells is desirable to improve the efficacy and to reduce the side effects of anticancer therapy. Previously reported passive tumor targeting by PEGylated liposomes (stealth liposomes) have resulted in their higher tumor accumulation. However their interaction with cancer cells has been minimal due to the steric hindrance of the PEG coating. This dissertation reports two approaches to enhance the interaction of stealth liposomes with cancer cells. First, we designed a lipid-hydrazone-PEG conjugate that removes the PEG coating at acidic pH as in the tumor interstitium. However, such a conjugate was highly unstable on …

Bioassay Guided Fractionation Of American Ginseng. A Hexane Fraction Of American Ginseng Suppresses Colitis And Associated Colon Cancer. Mechanism Of Action., Deepak Poudyal

Theses and Dissertations

Inflammatory Bowel Disease (IBD) [Ulcerative colitis (UC) and Crohn's Disease (CD)] is a group of chronic disorders of unknown etiology characterized by inflammation in the gastrointestinal tract associated with a high colon cancer risk. UC is characterized by periods of active disease ("flare-ups"), followed by periods when the disease is inactive ("remission"). The end result is an abnormal immune response with repeated episodes of colonic inflammation. Conventional treatment of UC by aminosalicylates, TNFα inhibitors, and steroids have modest effects, and come with a high risk of side effects including dyspeptic symptoms, gastric ulceration and sometimes hospitalization and deaths. Because of …

Effects Of Dna Damage And Cdk Inhibitors On The Nucleoli, Vineet Garg

Theses and Dissertations

The nucleolus is the primary site of ribogenesis and consists of three compartments, namely, fibrillar center (FC), dense fibrillar component (DFC) and granular component (GC). Recent studies have observed a novel structure distinct from these three compartments which forms in the nucleolus upon DNA damage called Intranucleolar body (INoB). Previous studies in our laboratory have found INoBs forming in HT1080 fibrosarcoma cell lines after ectopic overexpression of damage-inducible cell cycle inhibitor p21. This INoB formation has been observed to be decreased by Senexin A which is an inhibitor of transcription regulating kinases CDK8/CDK19.

Here we show that INoB formation correlates …

K+ Channels And Beta3 Adrenergic Receptors As New Pharmacological Targets For Overactive Bladder Treatment, Serge Amani Yao Afeli

Theses and Dissertations

Overactive bladder (OAB) is a pathophysiological condition which is characterized by the urinary bladder's failure to achieve proper storage of urine. OAB has a tremendous impact on the patient's quality of life by disturbing his sleep, work, and sexual activity. About 17% of Americans are affected with this disease and most patients experience symptoms of urgency, frequent urination, and abnormally elevated detrusor smooth muscle (DSM) contractility. Despite, numerous attempts to treat the disorder in the past with antimuscarinics and now with beta3 adrenergic receptors (beta3-AR agonists), OAB still remains a serious public health issue because the long term efficacy of …

A Novel Approach To The Design Of Selective Inhibitors For Cell Cycle Cyclin Dependent Kinases, Tracy Perkins

Theses and Dissertations

CDK2/cyclin A and CDK4/cyclin D1 are proven targets for cancer drug discovery. The development of novel CDK inhibitors, with high selectivity, are being investigated by targeting the cyclin binding groove (CBG) located on the cyclin, the regulatory subunit of CDK. The CBG is a shallow area that is involved in signaling and the inhibition of cell cycle CDKs via endogenous tumor suppressors. Currently, non-peptidic inhibitors are being developed based on the recognition amino acid sequence, HAKRRLIF, of the C-terminal peptide sequence of the CDK inhibitor p21WAF1. Computational design and the utilization of non-natural amino acids are being proposed to identify …

Snail Induces Mesenchymal Transition And Promotes Egfr Tki Resistance In Nsclc Cells Harboring Efgr Kinase Domain Mutations, Rutu Gandhi

Master's Theses

Lung cancer is the leading cause of cancer related death, accounting for one third of all deaths from cancer worldwide. About 85-90% of lung cancers are non-small cell lung cancers (NSCLCs). Molecular targeted therapies such as epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) provide an effective treatment option for oncogene addicted NSCLC. However, the development of resistance to EGFR TKIs continues to be the major limitation in the treatment of NSCLC. Resistance to EGFR TKIs has been associated with the loss of canonical epithelial protein E-cadherin, suggesting involvement of epithelial to mesenchymal transition (EMT) in conferring EGFR TKI …

Development Of Cell Based Reporter Assay To Measure Pkc-Delta Promoter Activity, Kushal Prajapati

Master's Theses

Protein kinase C- δ (PKC-δ) acts as a tumor suppressor in skin cancer and is lost in 30% of human Squamous Cell Carcinoma (SCC). This loss is at the transcriptional level and involves the pathway leading to PKC-δ promoter repression after activation of Ras,PI3K,Fyn, and NF-κB. We proposed development of a high throughput, cell-based luciferase reporter assay on Ras transformed keratinocyte cell line, HaCaT-Ras to screen compounds having potential to inhibit this pathway and re-induce PKC-δ expression. First we developed a stable, PKC-δ promoter-reporter transfected HaCaT-Ras cell line. Next, we tested 13 compounds for their abilities to induce PKC-δ …

The Incidence And Aetiology Of Hospitalised Community-Acquired Pneumonia Among Vietnamese Adults: A Prospective Surveillance In Central Vietnam, Kensuke Takahashi, Motoi Suzuki, Le Minh, Nguyen Anh, Luu Thi Huong, Tran Vo Son, Phan Long, Nguyen Thi Ai, Le Tho, Konosuke Morimoto, Paul E. Kilgore, Dang Anh, Koya Ariyoshi, Lay Yoshida

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Lower respiratory tract infection (LRTI) including Community-acquired pneumonia (CAP) is a common infectious disease that is associated with significant morbidity and mortality. The patterns of aetiological pathogens differ by region and country. Special attention must be paid to CAP in Southeast Asia (SEA), a region facing rapid demographic transition. Estimates burden and aetiological patterns of CAP are essential for the clinical and public health management. The purposes of the study are to determine the incidence, aetiological pathogens, clinical pictures and risk factors of community-acquired pneumonia (CAP) in the Vietnamese adult population.

Methods

A prospective surveillance for hospitalised adult …

Prevalence Of Anti-Diabetic And Antilipidemic Medications In Children And Adolescents Treated With Atypical Antipsychotics In A Virginia Medicaid Population, Della Varghese

Theses and Dissertations

Objective: To determine if the prevalence of anti-diabetic and antilipidemic medication use among children treated with atypical antipsychotics is higher than those not treated with antipsychotics. Methods: Virginia Medicaid beneficiaries (2-17 years) continuously enrolled from August 1, 2010 to July 31, 2011 with at least two prescription claims for atypical antipsychotics were the exposed group. All other subjects during the study period were the non-exposed group. Prevalence of anti-diabetic and antilipidemic medication use in both groups were computed and compared using Chi-square test (α=0.05). Results: A total of 299,593 and 4,922 subjects were identified as the non-exposed and exposed groups, …

Kinetics And Mechanisms Of Accumulation For Liposomal Ciprofloxacin Into Rat Alveolar Macrophages, Sayeed Mossadeq

Theses and Dissertations

The kinetics and mechanism of accumulation for liposomal ciprofloxacin (Lipo-CPFX) into the rat alveolar macrophage NR8383 cells were studied in vitro, in comparison to unformulated ciprofloxacin (CPFX). Upon incubation with CPFX or Lipo-CPFX, cellular drug accumulation was determined from the cell lysates or efflux was from the extracellular media by fluorescence-HPLC. The accumulation for Lipo-CPFX reached the asymptotic values at ≥ 2 hours, which was a result of uptake and efflux. The uptake appeared to be due to liposomes, mediated via cellular energy-independent mechanism like lipid fusion. In contrast, the efflux appeared to be due to ciprofloxacin, partly cellular energy-dependent, …

In Vitro Lung Epithelial Cell Transport And Anti-Inflammatory Activity For Liposomal Ciprofloxacin, Ruba Darweesh

Theses and Dissertations

Liposomal ciprofloxacin (Lipo-CPFX) is being developed for inhalation, with a goal of sustaining the therapeutic activity, compared to unformulated ciprofloxacin (CPFX). However, the kinetics and mechanism of its sustained local lung retention and pharmacological activity are yet to be fully characterized. This project hypothesized that Lipo-CPFX enables slower and sustained lung epithelial transport and uptake, compared to CPFX, thereby producing prolonged local pharmacological actions. The human bronchial epithelial Calu-3 cells were used as monolayers to characterize the kinetics and mechanism of transport and/or uptake, and to assess the effects of such slow kinetics for Lipo-CPFX on its inhibition against lipopolysaccharide …

Regulation Of Over-The-Counter Derivatives: A Comparative Study Of Proposals In Singapore And Hong Kong, Chao-Hung Christopher Chen

Research Collection Yong Pung How School Of Law

This chapter identifies some of the potential legal and policy issues involved in the future regulation of over-the-counter (OTC) derivatives. First, regulators must be cautious in the regulation and solvency of some mammoth clearing- houses. Second, Singapore and Hong Kong both face challenges in the areas of global regulatory cooperation and extra-territorial regulatory effects. Third, the exact scope of a clearing obligation determines whether there is any regulatory competition or room for regulatory arbitrage in the future. Fourth, there are legal definition problems with the term ‘derivative’ and its sub-categories that must be addressed. Fifth, there are potential privacy and …

Novel Therapy For Nicotine Addiction In Alcohol Dependent Rats, Bethany Ann Stennett

UNF Graduate Theses and Dissertations

The co-dependence of nicotine and alcohol addiction occurs at high rates, complicates treatment, and is often associated with significant morbidity and mortality. Treatment options of alcohol and tobacco co-dependence are limited. Currently, there are drugs available for nicotine dependence or alcohol dependence. However, there are no therapeutic drugs available on the market for the co-dependence of nicotine and alcohol. Therefore, and important opportunity of new therapeutic options and drug development has presented itself. NT69L, a non-selective neurotensin (NT) agonist, provides a potential novel therapy for nicotine addiction in alcoholics by interacting with the common neurotransmitter circuits supporting the rewarding process …

Research News: 2012, No. 2, University Of Mississippi. School Of Pharmacy

Research News: Grants and Publications (2000-2014)

Grants and contracts recently awarded

Preparasi, Karakterisasi Dan Evaluasi Pelepasan Obat Dari Beads Kalsium Alginat Deksametason Dengan Metode Gelasi Ionik, Christye Aulia, Joshita Djajadisastra

Majalah Ilmu Kefarmasian

Inflammatory Bowel Disease (IBD) is a disease of inflammation in the colon. Targeted delivery systems for the treatment of IBD is designed to increase the drug concentration in the local tissue. Dexamethasone is a drug having anti-inflammatory and antifibrosis effects which is used to repair scar tissue arising from postoperative IBD. This research purpose to create calciumalginate beads dexamethasone to be released only in the colon. Beads were made by using sodium-alginate and Ca2+ as crosslinker by ionic gelation method, with ratio between sodium alginate-dexamethasone (3:1). A concentration of solution sodium alginate 3 % b/v with variation concentration of crosslinker …

Treatment Of Klebsiella Pneumoniae Carbapenemase (Kpc) Infections: A Review Of Published Case Series And Case Reports, Grace C. Lee, David S. Burgess

Pharmacy Practice and Science Faculty Publications

The emergence of Klebsiella pneumoniae carbapenemases (KPCs) producing bacteria has become a significant global public health challenge while the optimal treatment remains undefined. We performed a systematic review of published studies and reports of treatment outcomes of KPC infections using MEDLINE (2001-2011). Articles or cases were excluded if one of the following was fulfilled: no individual patient data provided, no treatment regimen specified, no treatment outcome specified, report of colonization, or greater than three antibiotics were used to treat the KPC infection. Data extracted included patient demographics, site of infection, organism, KPC subtype, antimicrobial therapy directed at KPC-infection, and treatment …

The Economic Burden Of Opioid Poisoning In The United States And Determinants Of Increased Costs In Opioid Poisoning, Timothy Inocencio

Theses and Dissertations

Introduction: Opioid poisoning has been rapidly increasing in the past decade, and has been driven in large part due to increases in opioid prescribing. This has been accompanied by intervention efforts aimed at preventing and reversing opioid poisoning through naloxone prescription programs. Current literature have not quantified the economic burden of opioid poisoning. Understanding this information can help inform these efforts and bring light to this growing problem. In addition understanding various determinants of increased costs can help to identify the types of populations more likely to have greater costs. Main Objectives: The objectives are 1) to quantify the economic …

Medication-Related Problems Experienced By Patients During Transitions To Assisted Living, Deanna Flora

Theses and Dissertations

Medication reconciliation is a systematic and comprehensive review of medication regimens during care transitions aiming to prevent adverse drug events. Poorly executed transitions negatively impact patient welfare and cause financial burden. Medication-related problems (MRPs) experienced during transitions to an assisted living facility (ALF) were evaluated. Data was collected from pharmacy records for transitions to an ALF over three months, including demographics, medications, potentially inappropriate medications, and MRPs. MRPs were categorized and summarized using descriptive statistics. Forty-five patients (71% female) experienced 59 transitions. Average age was 85.6 years. Median length of stay away from the ALF was three days. There were …

Binding Of An Indenoisoquinoline To The Topoisomerase-Dna Complex Induces Reduction Of Linker Mobility And Strengthening Of Protein-Dna Interaction., Giordano Mancini, Ilda D'Annessa, Andrea Coletta, Giovanni Chillemi, Yves Pommier, Mark S. Cushman, Alessandro Desideri

Borch Department of Medicinal Chemistry and Molecular Pharmacology Faculty Publications

Long-duration comparative molecular dynamics simulations of the DNA-topoisomerase binary and DNA-topoisomerase-indenoisoquinoline ternary complexes have been carried out. The analyses demonstrated the role of the drug in conformationally stabilizing the protein-DNA interaction. In detail, the protein lips, clamping the DNA substrate, interact more tightly in the ternary complex than in the binary one. The drug also reduces the conformational space sampled by the protein linker domain through an increased interaction with the helix bundle proximal to the active site. A similar alteration of linker domain dynamics has been observed in a precedent work for topotecan but the molecular mechanisms were different …