Chemicals and Drugs Commons^™

Toward Earlier Inclusion Of Pregnant And Postpartum Women In Tuberculosis Drug Trials: Consensus Statements From An International Expert Panel., Amita Gupta, Jyoti S. Mathad, Susan M. Abdel-Rahman, Jessica D. Albano, Radu Botgros, Vikki Brown, Renee S. Browning, Liza Dawson, Kelly E. Dooley, Devasena Gnanashanmugam, Beatriz Grinsztejn, Sonia Hernandez-Diaz, Patrick Jean-Philippe, Peter Kim, Anne D. Lyerly, Mark Mirochnick, Lynne M. Mofenson, Grace Montepiedra, Jeanna Piper, Leyla Sahin, Radojka Savic, Betsy Smith, Hans Spiegel, Soumya Swaminathan, D Heather Watts, Amina White

Manuscripts, Articles, Book Chapters and Other Papers

Tuberculosis is a major cause of morbidity and mortality in women of childbearing age (15-44 years). Despite increased tuberculosis risk during pregnancy, optimal clinical treatment remains unclear: safety, tolerability, and pharmacokinetic data for many tuberculosis drugs are lacking, and trials of promising new tuberculosis drugs exclude pregnant women. To advance inclusion of pregnant and postpartum women in tuberculosis drug trials, the US National Institutes of Health convened an international expert panel. Discussions generated consensus statements (>75% agreement among panelists) identifying high-priority research areas during pregnancy, including: (1) preventing progression of latent tuberculosis infection, especially in women coinfected with human …

Is Androgen Excess Masked In Alopecia Areata Patients: A Retrospective Data Analysis Of 1,587 Patients, G. Cheyana Ranasinghe, Melissa Piliang, Wilma Bergfeld

GW Research Days 2016 - 2020

Studies on the pathophysiology and comorbidities associated with alopecia areata (AA) are limited. The purpose of this study was to determine the prevalence of androgen excess in AA and its subtypes, in relation to demographics and comorbidities. Medical records of 1,587 Patchy AA, AT, AU, and ophiasis patients seen in the Department of Dermatology at the Cleveland Clinic Foundation in Ohio between 2005 and 2015 were reviewed. Out of this cohort, 226 patients met the inclusion criteria. There is evidence that patients with AA had significantly greater prevalence of polycystic ovary syndrome (PCOS) than the general population (p<0.001). Androgen excess was identified in 42.5% (n=96) of the 226 patients with AA or any subtype (p<0.001). The androgen excess group was significantly more likely to present with irregular menses, hirsutism, adult acne, PCOS, and/or ovarian cysts (p<0.001). This study was limited by being retrospective. Our study demonstrated that AA is associated with androgen excess.

Perioperative Aspirin Recommendations In Children With Fenestrated Fontan Undergoing Adenotonsillectomy, Mariam Ashraf, Pamela A. Mudd, Jamie Mcelrath Schwartz, Karen Thompson

GW Research Days 2016 - 2020

Objective: Pediatric patients who have undergone the Fontan procedure are often on a long term aspirin regimen which can complicate perioperative management. In high risk procedures such as adenotonsillectomy, hemorrhage can be a significant complication and aspirin use may increase the risk. There is a need for evidence-based protocol on how to manage aspirin intake in the perioperative period for Fontan patients. We report the case of a patient with Fontan palliation who underwent adenotonsillectomy and presented with postoperative hemorrhage.

Methods: PubMed was searched for guidelines, case reports, and reviews on pediatric Fontan patients, adenotonsillectomy, and perioperative aspirin …

Pharmacokinetics And Bioequivalence Of A Liquid Formulation Of Hydroxyurea In Children With Sickle Cell Anemia., Jeremie H. Estepp, Chiara Melloni, Courtney D. Thornburg, Paweł Wiczling, Zora Rogers, Jennifer A. Rothman, Nancy S. Green, Robert Liem, Amanda M. Brandow, Shelley E. Crary, Thomas H. Howard, Maurine H. Morris, Andrew Lewandowski, Uttam Garg, William J. Jusko, Kathleen A. Neville, Best Pharmaceuticals For Children Act-Pediatric Trials Network Administrative Core Committee

Manuscripts, Articles, Book Chapters and Other Papers

Hydroxyurea (HU) is a crucial therapy for children with sickle cell anemia, but its off-label use is a barrier to widespread acceptance. We found HU exposure is not significantly altered by liquid vs capsule formulation, and weight-based dosing schemes provide consistent exposure. HU is recommended for all children starting as young as 9 months of age with sickle cell anemia (SCA; HbSS and HbSβspan(0) thalassemia); however; a paucity of pediatric data exists regarding the pharmacokinetics (PK) or the exposure-response relationship of HU. This trial aimed to characterize the PK of HU in children and to evaluate and compare the bioavailability …

Abnormal Uterine Bleeding Guidelines And Clinical Practice Are Based On Poor Quality Evidence, Mirek Mychajlowycz

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Munro MG, Mainor N, Basu R, Brisinger M, Barreda L. Oral medroxyprogesterone acetate and combination oral contraceptives for acute uterine bleeding: A randomized controlled trial. Obstet Gynecol. 2006 Oct;108(4):924-929. doi:10.1097/01.AOG.0000238343.62063.22

Long-Term Velaglucerase Alfa Treatment In Children With Gaucher Disease Type 1 Naïve To Enzyme Replacement Therapy Or Previously Treated With Imiglucerase., Laurie Smith, William Rhead, Joel Charrow, Suma P. Shankar, Ashish Bavdekar, Nicola Longo, Rebecca Mardach, Paul Harmatz, Thomas Hangartner, Hak-Myung Lee, Eric Crombez, Gregory M. Pastores

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Gaucher Disease type 1 (GD1) often manifests in childhood. Early treatment with enzyme replacement therapy (ERT) may prevent disease complications. We report the assessment of velaglucerase alfa ERT in pediatric GD1 patients who participated in a long-term extension study (HGT-GCB-044, ClinicalTrials.gov Identifier NCT00635427).

METHODS: Safety and efficacy were evaluated in pediatric patients receiving velaglucerase alfa 30-60U/kg by intravenous infusion every other week. In addition to key hematological and visceral efficacy assessments, exploratory assessments conducted specifically in pediatric patients included evaluation of height, bone age, bone marrow burden, and Tanner stage of puberty.

RESULTS: The study included 24 pediatric patients. …

Different Vancomycin Immunoassays Contribute To The Variability In Vancomycin Trough Measurements In Neonates, Janko Samardzic, Anne Smits, Isabel Spriet, Ivan Soldatovic, Andrew Atkinson, Milica Bajcetic, John N. Van Den Anker, Karel Allegaert

Pediatrics Faculty Publications

Substantial interassay variability (up to 20%) has been described for vancomycin immunoassays in adults, but the impact of neonatal matrix is difficult to quantify because of blood volume constraints in neonates. However, we provide circumstantial evidence for a similar extent of variability. Using the same vancomycin dosing regimens and confirming similarity in clinical characteristics, vancomycin trough concentrations measured by PETINIA (2011-2012, n = 400) were 20% lower and the mean difference was 1.93 mg/L compared to COBAS (2012–2014, n =352 ) measurements. The impact of vancomycin immunoassays in neonatal matrix was hereby suggested, supporting a switch to more advanced techniques …

A Single Center Observational Study On Emergency Department Clinician Non-Adherence To Clinical Practice Guidelines For Treatment Of Uncomplicated Urinary Tract Infections, Catherine Zatorski, Mark Zocchi, Sara Cosgrove, Cynthia Rand, Gillian Brooks, Larissa May

Emergency Medicine Faculty Publications

Background

The Emergency Department (ED) is a frequent site of antibiotic use; poor adherence with evidence-based guidelines and broad-spectrum antibiotic overuse is common. Our objective was to determine rates and predictors of inappropriate antimicrobial use in patients with uncomplicated urinary tract infections (UTI) compared to the 2010 International Clinical Practice Guidelines (ICPG).

Methods

A single center, prospective, observational study of patients with uncomplicated UTI presenting to an urban ED between September 2012 and February 2014 that examined ED physician adherence to ICPG when treating uncomplicated UTIs. Clinician-directed antibiotic treatment was compared to the ICPG using a standardized case definition for …

Circulating Fibroblast Growth Factor-2, Hiv-Tat, And Vascular Endothelial Cell Growth Factor-A In Hiv-Infected Children With Renal Disease Activate Rho-A And Src In Cultured Renal Endothelial Cells., Jharna R Das, J Silvio Gutkind, Patricio E. Ray

Pediatrics Faculty Publications

Renal endothelial cells (REc) are the first target of HIV-1 in the kidney. The integrity of REc is maintained at least partially by heparin binding growth factors that bind to heparan sulfate proteoglycans located on their cell surface. However, previous studies showed that the accumulation of two heparin-binding growth factors, Vascular Endothelial Cell Growth Factor-A (VEGF-A) and Fibroblast Growth Factor-2 (FGF-2), in combination with the viral protein Tat, can precipitate the progression of HIV-renal diseases. Nonetheless, very little is known about how these factors affect the behavior of REc in HIV+ children. We carried out this study to determine how …

Comparison Of Drug Delivery With Autoinjector Versus Manual Prefilled Syringe And Between Three Different Autoinjector Devices Administered In Pig Thigh, Robert Hill, John Wilmot, Beth Belluscio, Kevin Cleary, David Lindisch, Robin Tucker, Emmanuel Wilson, Rajesh Shukla

Radiology Faculty Publications

Parenteral routes of drug administration are often selected to optimize actual dose of drug delivered, assure high bioavailability, bypass first-pass metabolism or harsh gastrointestinal environments, as well as maximize the speed of onset. Intramuscular (IM) delivery can be preferred to intravenous delivery when initiating intravenous access is difficult or impossible. Drugs can be injected intramuscularly using a syringe or an automated delivery device (autoinjector). Investigation into the IM delivery dynamics of these methods may guide further improvements in the performance of injection technologies. Two porcine model studies were conducted to compare differences in dispersion of injectate volume for different methods …

Biosimilars: Potential Implications For Clinicians, Misty G. Eleryan, Sophia Akhiyat, Monica Rengifo-Pardo, Alison Ehrlich

Dermatology Faculty Publications

With the expiration of patent protection for several biologics looming, the production of highly similar therapeutic agents has begun to emerge on the pharmaceutical market. These alternative drugs are referred to as biosimilars. Many anticipate that the introduction of these agents will result in a reduction in health care costs, which may create a more affordable biopharmaceutical market and also improve patient access. In contrast to generics, which are exact copies of their original products, biosimilars are not identical to their reference products. Due to concern about the safety and efficacy of biosimilars, separate regulatory approval pathways have been developed …

Multiple Sirna Delivery Against Cell Cycle And Anti-Apoptosis Proteins Using Lipid-Substituted Polyethylenimine In Triplenegative Breast Cancer And Non-Malignant Cells, Manoj B. Parmar, Bárbara E. Arteaga Ballesteros, Timothy Fu, Remant Bahadur Kc, Hamidreza Montazeri Aliabadi, Judith C. Hugh, Raimar Löbenberg, Hasan Uludag

Pharmacy Faculty Articles and Research

Conventional breast cancer therapies have significant limitations that warrant a search for alternative therapies. Short-interfering RNA (siRNA), delivered by polymeric biomaterials and capable of silencing specific genes critical for growth of cancer cells, holds great promise as an effective and more specific therapy. Here, we employed amphiphilic polymers and silenced the expression of two cell cycle proteins, TTK and CDC20, and the anti-apoptosis protein survivin to determine the efficacy of polymer-mediated siRNA treatment in breast cancer cells as well as side effects in non-malignant cells in vitro. We first identified effective siRNA carriers by screening a library of lipid-substituted polyethylenimines …

Effects Of Nox-1 Inhibition On Real-Time Blood Nitric Oxide And Hydrogen Peroxide In Acute Hyperglycemia, Ashley Mawhinney

PCOM Biomedical Studies Student Scholarship

Hyperglycemia has been associated with vascular endothelial dysfunction in part by a reduction in nitric oxide (NO) production and increased oxidative stress (e.g., increased superoxide (SO) and hydrogen peroxide (H₂O₂). Endothelial-derived NO can be significantly reduced by increased SO/H₂O₂ in part by the activation of NADPH oxidase during hyperglycemia. Of the 7 NADPH oxidase isoforms, NADPH oxidase isoform 1 (NOX1) is mainly expressed in the vasculature and may play a major role in hyperglycemia induced oxidative stress and vascular endothelial dysfunction. This hypothesis was tested by measuring blood NO and H2O2 levels in …

Sglt2 Inhibitor Therapy Improves Blood Glucose But Does Not Prevent Diabetic Bone Disease In Diabetic Dba/2j Male Mice, Kathryn M. Thrailkill, R. Clay Bunn, Jeffry S. Nyman, Mallikarjuna R. Rettiganti, Gael E. Cockrell, Elizabeth C. Wahl, Sasidhar Uppuganti, Charles K. Lumpkin, John L. Fowlkes

Barnstable Brown Diabetes Center Faculty Publications

Persons with type 1 and type 2 diabetes have increased fracture risk, attributed to deficits in the microarchitecture and strength of diabetic bone, thought to be mediated, in part, by the consequences of chronic hyperglycemia. Therefore, to examine the effects of a glucose-lowering SGLT2 inhibitor on blood glucose (BG) and bone homeostasis in a model of diabetic bone disease, male DBA/2J mice with or without streptozotocin (STZ)-induced hyperglycemia were fed chow containing the SGLT2 inhibitor, canagliflozin (CANA), or chow without drug, for 10 weeks of therapy. Thereafter, serum bone biomarkers were measured, fracture resistance of cortical bone was assessed by …

Typical Hus: Evidence Of Acute Phase Complement Activation From A Daycare Outbreak, T M. Brady, C Pruette, L F. Loeffler, Darcy Weidemann, J J. Strouse, E Gavriilaki, R A. Brodsky

Manuscripts, Articles, Book Chapters and Other Papers

The clinical manifestations of typical hemolytic uremic syndrome (HUS) encompass a wide spectrum. Despite the potentially severe sequelae from this syndrome, treatment approaches remain supportive. We present the clinical course of a child who contracted Shiga toxin-positive E. coli (STEC) from a daycare center during an outbreak. Utilizing the modified Ham test which is a rapid, serum-based functional assay used to detect activation of the alternative pathway of complement as observed in atypical HUS, patient sera revealed evidence of increased complement activation in the acute phase of the syndrome but not after resolution. Further, this complement activation was attenuated by …

Contraceptive Provision To Adolescent Females Prescribed Teratogenic Medications., Stephani L. Stancil, Melissa K. Miller, Holley Briggs, Daryl Lynch, Kathy Goggin, Gregory Kearns

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND AND OBJECTIVES: Rates of adult women receiving contraceptive provision when simultaneously prescribed a known teratogen are alarmingly low. The prevalence of this behavior among pediatric providers and their adolescent patients is unknown. The objective of this study was to describe pediatric provider behaviors for prescribing teratogens concurrently with counseling, referral, and/or prescribing of contraception (collectively called contraceptive provision) in the adolescent population.

METHODS: A retrospective review was conducted examining visits in 2008-2012 by adolescents aged 14 to 25 years in which a known teratogen (US Food and Drug Administration pregnancy risk category D or X) was prescribed. The electronic …

Genetic Variation In The Histamine Production, Response, And Degradation Pathway Is Associated With Histamine Pharmacodynamic Response In Children With Asthma., Bridgette Jones, Catherine M T Sherwin, Xiaoxi Liu, Hongying Dai, Carrie A. Vyhlidal

Manuscripts, Articles, Book Chapters and Other Papers

Introduction: There is growing knowledge of the wide ranging effects of histamine throughout the body therefore it is important to better understand the effects of this amine in patients with asthma. We aimed to explore the association between histamine pharmacodynamic (PD) response and genetic variation in the histamine pathway in children with asthma. Methods: Histamine Iontophoresis with Laser Doppler Monitoring (HILD) was performed in children with asthma and estimates for area under the effect curve (AUEC), maximal response over baseline (Emax), and time of Emax (Tmax) were calculated using non-compartmental analysis and non-linear mixed-effects model with a linked effect PK/PD …

Design And Testing Of An Ehr-Integrated, Busulfan Pharmacokinetic Decision Support Tool For The Point-Of-Care Clinician., Susan M. Abdel-Rahman, Matthew L. Breitkreutz, Charlie Bi, Brett J. Matzuka, Jignesh Dalal, K Leigh Casey, Uttam Garg, Sara Winkle, J Steven Leeder, Jeanann Breedlove, Brian Rivera

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Busulfan demonstrates a narrow therapeutic index for which clinicians routinely employ therapeutic drug monitoring (TDM). However, operationalizing TDM can be fraught with inefficiency. We developed and tested software encoding a clinical decision support tool (DST) that is embedded into our electronic health record (EHR) and designed to streamline the TDM process for our oncology partners.

METHODS: Our development strategy was modeled based on the features associated with successful DSTs. An initial Requirements Analysis was performed to characterize tasks, information flow, user needs, and system requirements to enable push/pull from the EHR. Back-end development was coded based on the algorithm …

Inhibition Of Bacterial Growth And Prevention Of Bacterial Adhesion With Localized Nitric Oxide Delivery, Julia Osborne

Dissertations, Master's Theses and Master's Reports

Bacterial infections continue to be a problem at the site of an indwelling medical device, and over the years, various bacterial strains have become more resistant to current antibiotic treatments. Bacterial infection at an indwelling medical device can be dangerous and affect the performance of the medical device which can ultimately lead to the failure of the device due to bacterial resistance to treatment.

Nitric Oxide (NO) has been shown to possess antibacterial properties to prevent and inhibit bacterial growth. NO releasing coatings on indwelling medical devices could provide a reduction in bacterial infections that occur at the device site …

Understanding And Targeting The C-Terminal Binding Protein (Ctbp) Substrate-Binding Domain For Cancer Therapeutic Development, Benjamin L. Morris

Theses and Dissertations

Cancer involves the dysregulated proliferation and growth of cells throughout the body. C-terminal binding proteins (CtBP) 1 and 2 are transcriptional co-regulators upregulated in several cancers, including breast, colorectal, and ovarian tumors. CtBPs drive oncogenic properties, including migration, invasion, proliferation, and survival, in part through repression of tumor suppressor genes. CtBPs encode an intrinsic dehydrogenase activity, utilizing intracellular NADH concentrations and the substrate 4-methylthio-2-oxobutyric acid (MTOB), to regulate the recruitment of transcriptional regulatory complexes. High levels of MTOB inhibit CtBP dehydrogenase function and induce cytotoxicity among cancer cells in a CtBP-dependent manner. While encouraging, a good therapeutic would utilize >100-fold …

A Pilot Study Of Propofol As An Anti-Emetic In Laparoscopic, Gynecologic Surgery Patients, Flem-Flam Aaron Flemister

Doctoral Projects

The goal of this project was to use sub-hypnotic doses of propofol to decrease post operative nausea and vomiting (PONV) rates in the immediate post-operative period in females, ages 18-65, undergoing laparoscopic gynecologic surgery.

PONV is one of the largest complications of anesthesia affecting 20-30% of all surgical patients. Risk factors associated with PONV are female gender, laparoscopy, general anesthesia, opioids, volatile agents, and post-operative pain; all of which are frequently encountered. The incidence of PONV can prolong recovery time, delay discharge, increase patient cost, decrease patient satisfaction, and can cause significant medical complications. Propofol has previously demonstrated anti-emetic properties; …

Effect Of Kidney Function On Drug Kinetics And Dosing In Neonates, Infants, And Children., Frederique Rodieux, Melanie Wilbaux, Johannes N. Van Den Anker, Marc Pfister

Pediatrics Faculty Publications

Neonates, infants, and children differ from adults in many aspects, not just in age, weight, and body composition. Growth, maturation and environmental factors affect drug kinetics, response and dosing in pediatric patients. Almost 80% of drugs have not been studied in children, and dosing of these drugs is derived from adult doses by adjusting for body weight/size. As developmental and maturational changes are complex processes, such simplified methods may result in subtherapeutic effects or adverse events. Kidney function is impaired during the first 2 years of life as a result of normal growth and development. Reduced kidney function during childhood …

Essentials Of Herb-Drug Interactions In The Elderly With Cardiovascular Disease, Sulaiman Sultan, Maria Viqar, Rabaiya Ali, A. Jamil Tajik, Arshad Jahangir

Journal of Patient-Centered Research and Reviews

As the number of individuals, particularly the elderly, using herbal products with prescription drugs continues to grow, the risk for adverse interactions increases but remains poorly recognized. The true incidence and nature of adverse herb reactions or herb-drug interactions remains unknown since no postmarketing surveillance mechanism exists. Adverse events are greatly underreported, and information regarding safety mainly comes from case reports and suboptimally conducted studies in a limited number of healthy young volunteers or patients with limited comorbidities. Therefore, convincing evidence for the safety of herbal products in the elderly is lacking, and the true magnitude of problems that herb-drug …

Assessing The Effectiveness Of Implementation Of Unified Workflow In Improvement Of Medication Reconciliation For Aurora St. Luke’S Family Medicine Residency Outpatients, Katherine Meyers, Jessica Konarske, Jessica J.F. Kram, Dennis J. Baumgardner

Journal of Patient-Centered Research and Reviews

Background: Medication errors are the most common errors occurring in hospitals. Preventable adverse drug events are linked with 1 in 5 injuries or deaths; 23% of medication errors in primary care occur due to inaccuracies in the medication list. Quality improvement projects designed to improve accuracy of outpatient medication reconciliations may decrease the number of medication errors and increase patient safety by preventing adverse drug events.

Purpose: To determine whether a unified workflow for medication reconciliation improves the accuracy of ambulatory, electronic medical record (EMR)-based patient medication records.

Methods: Retrospective study of random sample of patients from Aurora Family Medicine …

A Meta-Analysis Of Incidence And Risk Factors Of Trastuzumab-Induced Cardiotoxicity In Breast Cancer, Zeeshan Ali Jawa, Ruth M. Perez, Lydia Garlie, Maharaj Singh, Rubina Qamar, Bijoy K. Khandheria, Arshad Jahangir, Yang Shi

Journal of Patient-Centered Research and Reviews

Background: A monoclonal antibody, trastuzumab targets the human epidermal growth factor receptor 2 (HER2) oncogene that is overexpressed in 25–30% of breast cancers. In combination with first-line therapy, trastuzumab resulted in significant improvement in survival outcomes for those with HER2-positive metastatic breast cancer. Due to its improvement in outcome and prolonged survival, trastuzumab has been established as standard of care in both adjuvant and metastatic settings. However, along with common adverse events, trastuzumab has been found to be associated with cardiotoxicity. An estimated 1–4% of patients treated with trastuzumab will develop heart failure and ~10% of patients will experience a …

Alkali Therapy In Lactic Acidosis, Zeid J. Khitan, Md, Deepak Malhotra, Md, Dominic S. Raj, Md, Antonios H. Tzamaloukas, Md, Joseph I. Shapiro, Md

Marshall Journal of Medicine

This report attempts to frame the debate about clinical administration of sodium bicarbonate in the setting of lactic acidosis in terms of simple questions. Specifically, we address why we develop lactic acidosis in some circumstances, how acute lactic acidosis impairs cardiovascular function and why sodium bicarbonate may have deleterious effects which limit its utility. We also attempt to explore treatment alternatives to sodium bicarbonate.

Topical Administration Of Psychotropic Medications In Pluronic Lecithin Organogel To Treat Patients With Dementia: A Retrospective Observational Study, Cornelius W. Thomas, Md, Suzanne Holroyd, Md. Chair, Department Of Psychiatry

Marshall Journal of Medicine

OBJECTIVE: Treatment of mood and behavioral symptoms in geriatric patients with advanced dementia may be impeded by poor compliance with oral medications. Pluronic lecithin organogel (PLO) is a compounding substrate that can be used for the topical administration of psychotropic medications.

METHODS: Charts of patients treated with psychotropic medications compounded with PLO cream were reviewed for treatment outcomes. All patients were treated by a nursing home outreach service.

RESULTS: Records from twenty-four patients, mean age 86.8 + 5.9, were reviewed. Common psychiatric symptoms included agitation, aggressive behavior, and depression. Medications most commonly administered as a PLO cream included quetiapine and …

Theaflavin-3, 3'-Digallate Decreases Human Ovarian Carcinoma Ovcar-3 Cell-Induced Angiogenesis Via Akt And Notch-1 Pathways, Not Via Mapk Pathways, Ying Gao, Gary O. Rankin, Youying Tu, Yi Charlie Chen

Biochemistry and Microbiology

Theaflavin-3, 3'-digallate (TF3) is a black tea polyphenol produced from polymerization and oxidization of the green tea ployphenols epicatechin gallate and (-)-epigallocatechin-3-gallate (EGCG) during fermentation of fresh tea leaves. TF3 has been reported to have anticancer properties. However, the effect of TF3 on tumor angiogenesis and the underlying mechanisms are not clear. In the present study, TF3 was verified to inhibit tumor angiogenesis. Compared with EGCG, TF3 was more potent. TF3 inhibited human ovarian carcinoma OVCAR-3 cell-induced angiogenesis in human umbilical vein endothelial cell model and in chick chorioallantoic membrane model. TF3 reduced tumor angiogenesis by downregulating HIF-1α and VEGF. …

Real-Time Detection Of Breast Cancer Cells Using Peptidefunctionalized Microcantilever Arrays, Hashem Etayash, Keren Jiang, Sarfuddin Azmi, Thomas Thundat, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Ligand-directed targeting and capturing of cancer cells is a new approach for detecting circulating tumor cells (CTCs). Ligands such as antibodies have been successfully used for capturing cancer cells and an antibody based system (CellSearch®) is currently used clinically to enumerate CTCs. Here we report the use of a peptide moiety in conjunction with a microcantilever array system to selectively detect CTCs resulting from cancer, specifically breast cancer. A sensing microcantilever, functionalized with a breast cancer specific peptide 18-4 (WxEAAYQrFL), showed significant deflection on cancer cell (MCF7 and MDA-MB-231) binding compared to when exposed to noncancerous (MCF10A and HUVEC) cells. …

Myricetin Inhibits Proliferation Of Cisplatin-Resistant Cancer Cells Through A P53-Dependent Apoptotic Pathway, Haizhi Huang, Allen Y. Chen, Xingqian Ye, Bingyun Li, Yon Rojanasakul, Gary O. Rankin, Yi Charlie Chen

Pharmacology, Physiology and Toxicology

Cisplatin is a commonly used drug for cancer treatment by crosslinking DNA, leading to apoptosis of cancer cells, resistance to cisplatin treatment often occurs, leading to relapse. Therefore, there is a need for the development of more effective treatment strategies that can overcome chemoresistance. Myricetin is a flavonoid from fruits and vegetables, showing anticancer activity in various cancer cells. In this study, we found myricetin exhibited greater cytotoxicity than cisplatin in two cisplatin-resistant ovarian cancer cell lines, OVCAR-3 and A2780/CP70, and it was less cytotoxic to the normal ovarian cell line IOSE-364. Myricetin selectively induced apoptosis in both cisplatinresistant cancer …