Study Protocol and Statistical Analysis Plan
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
The Application of a Characterized Pre-Clinical
THE APPLICATION OF A CHARACTERIZED PRE-CLINICAL GLIOBLASTOMA ONCOSPHERE MODEL TO IN VITRO AND IN VIVO THERAPEUTIC TESTING by Kelli M. Wilson A dissertation submitted to Johns Hopkins University in conformity with the requirements for the degree of Doctor of Philosophy Baltimore, Maryland March, 2014 ABSTRACT Glioblastoma multiforme (GBM) is a lethal brain cancer with a median survival time (MST) of approximately 15 months following treatment. A serious challenge facing the development of new drugs for the treatment of GBM is that preclinical models fail to replicate the human GBM phenotype. Here we report the Johns Hopkins Oncosphere Panel (JHOP), a panel of GBM oncosphere cell lines. These cell lines were validated by their ability to form tumors intracranially with histological features of human GBM and GBM variant tumors. We then completed whole exome sequencing on JHOP and found that they contain genetic alterations in GBM driver genes such as PTEN, TP53 and CDKN2A. Two JHOP cell lines were utilized in a high throughput drug screen of 466 compounds that were selected to represent late stage clinical development and a wide range of mechanisms. Drugs that were inhibitory in both cell lines were EGFR inhibitors, NF-kB inhibitors and apoptosis activators. We also examined drugs that were inhibitory in a single cell line. Effective drugs in the PTEN null and NF1 wild type cell line showed a limited number of drug targets with EGFR inhibitors being the largest group of cytotoxic compounds. However, in the PTEN mutant, NF1 null cell line, VEGFR/PDGFR inhibitors and dual PIK3/mTOR inhibitors were the most common effective compounds. -
Daidzein and Genistein Content of Cereals
European Journal of Clinical Nutrition (2002) 56, 961–966 ß 2002 Nature Publishing Group All rights reserved 0954–3007/02 $25.00 www.nature.com/ejcn ORIGINAL COMMUNICATION Daidzein and genistein content of cereals J Liggins1, A Mulligan1,2, S Runswick1 and SA Bingham1,2* 1Medical Research Council Dunn Human Nutrition Unit, Hills Road, Cambridge, UK; and 2European Prospective Investigation of Cancer, University of Cambridge, Cambridge, UK Objective: To analyse 75 cereals and three soy flours commonly eaten in Europe for the phytoestrogens daidzein and genistein. Design: The phytoestrogens daidzein and genistein were extracted from dried foods, and the two isoflavones quantified after hydrolytic removal of any conjugated carbohydrate. Completeness of extraction and any procedural losses of the isoflavones 0 0 were accounted for using synthetic daidzin (7-O-glucosyl-4 -hydroxyisoflavone) and genistin (7-O-glucosyl-4 5-dihydroxyiso- flavone) as internal standards. Setting: Foods from the Cambridge UK area were purchased, prepared for eating, which included cooking if necessary, and freeze dried. Three stock soy flours were also analysed. Results: Eighteen of the foods assayed contained trace or no detectable daidzein or genistein. The soy flours were rich sources, containing 1639 – 2117 mg=kg. The concentration of the two isoflavones in the remaining foods ranged from 33 to 11 873 mg=kg. Conclusion: These analyses will supply useful information to investigators determining the intake of phytoestrogens in cereal products in order to relate intakes to potential biological activities. Sponsorship: This work was supported by the United Kingdom Medical Research Council, Ministry of Agriculture Fisheries and Food (contract FS2034) and the United States of America Army (contract DAMD 17-97-1-7028). -
Recent Topics on the Mechanisms of Immunosuppressive Therapy-Related Neurotoxicities
Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 29 May 2019 doi:10.20944/preprints201905.0358.v1 Peer-reviewed version available at Int. J. Mol. Sci. 2019, 20, 3210; doi:10.3390/ijms20133210 1 of 39 1 Review 2 Recent topics on the mechanisms of 3 immunosuppressive therapy-related neurotoxicities 4 Wei Zhang 1, Nobuaki Egashira 1,2,* and Satohiro Masuda 1,2 5 1 Department of Clinical Pharmacology and Biopharmaceutics, Graduate School of Pharmaceutical Sciences, 6 Kyushu University, Fukuoka 812-8582, Japan 7 2 Department of Pharmacy, Kyushu University Hospital, Fukuoka 812-8582, Japan 8 * Correspondence: [email protected], Tel.: 81-92-642-5920 9 Abstract: Although transplantation procedures have been developed for patients with end-stagec 10 hepatic insufficiency or other diseases, allograft rejection still threatens patient health and lifespan. 11 Over the last few decades, the emergence of immunosuppressive agents, such as calcineurin 12 inhibitors (CNIs) and mammalian target of rapamycin (mTOR) inhibitors, have strikingly 13 increased graft survival. Unfortunately, immunosuppressive agent-related neurotoxicity is 14 commonly occurred in clinical situations, with the majority of neurotoxicity cases caused by CNIs. 15 The possible mechanisms whereby CNIs cause neurotoxicity include: increasing the permeability 16 or injury of the blood-brain barrier, alterations of mitochondrial function, and alterations in 17 electrophysiological state. Other immunosuppressants can also induce neuropsychiatric 18 complications. For example, mTOR inhibitors induce seizures; mycophenolate mofetil induces 19 depression and headache; methotrexate affects the central nervous system; mouse monoclonal 20 immunoglobulin G2 antibody against cluster of differentiation 3 also induces headache; and 21 patients using corticosteroids usually experience cognitive alteration. -
Simultaneous Determination of Daidzein, Genistein and Formononetin in Coffee by Capillary Zone Electrophoresis
separations Article Simultaneous Determination of Daidzein, Genistein and Formononetin in Coffee by Capillary Zone Electrophoresis Feng Luan *, Li Li Tang, Xuan Xuan Chen and Hui Tao Liu College of Chemistry and Chemical Engineering, Yantai University, Yantai 264005, China; [email protected] (L.L.T.); [email protected] (X.X.C.); [email protected] (H.T.L.) * Correspondence: fl[email protected]; Tel.: +86-535-6902063 Academic Editor: Doo Soo Chung Received: 29 October 2016; Accepted: 20 December 2016; Published: 1 January 2017 Abstract: Coffee is a favorite and beverage in Western countries that is consumed daily. In the present study, capillary zone electrophoresis (CE) was applied for the separation and quantification of three isoflavones including daidzein, genistein and formononetin in coffee. Extraction of isoflavones from the coffee sample was carried out by extraction and purification process using ether after the acid hydrolysis with the antioxidant butylated hydroxy-toluene (BHT). The experimental conditions of the CE separation method were: 20 mmol/L Na2HPO4 buffer solution, 25 kV applied voltage, 3 s hydrodynamic injection at 30 mbar, and UV detection at 254 nm. The results show that the three compounds can be tested within 10 min with a linearity of 0.5–50 µg/mL for all three compounds. The limits of detection were 0.0642, 0.134, and 0.0825 µg/mL for daidzein, formononetin and genistein, respectively. The corresponding average recovery was 99.39% (Relative Standard Detection (RSD) = 1.76%), 98.71% (RSD = 2.11%) and 97.37% (RSD = 3.74%). Keywords: capillary zone electrophoresis (CE); daidzein; genistein; formononetin; acid hydrolysis 1. -
Soy Isoflavone Genistein Inhibits an Axillary Osmidrosis Risk Factor ABCC11: in Vitro Screening and Fractional Approach for ABCC11-Inhibitory Activities in Plant Extracts and Dietary
nutrients Article Soy Isoflavone Genistein Inhibits an Axillary Osmidrosis Risk Factor ABCC11: In Vitro Screening and Fractional Approach for ABCC11-Inhibitory Activities in Plant Extracts and Dietary Flavonoids 1,2, 2, , 1 1 1 Hiroki Saito y, Yu Toyoda * y , Hiroshi Hirata , Ami Ota-Kontani , Youichi Tsuchiya , Tappei Takada 2 and Hiroshi Suzuki 2 1 Frontier Laboratories for Value Creation, Sapporo Holdings Ltd., 10 Okatome, Yaizu, Shizuoka 425-0013, Japan; [email protected] (H.S.); [email protected] (H.H.); [email protected] (A.O.-K.); [email protected] (Y.T.) 2 Department of Pharmacy, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan; [email protected] (T.T.); [email protected] (H.S.) * Correspondence: [email protected] These authors contributed equally to this work. y Received: 2 July 2020; Accepted: 12 August 2020; Published: 14 August 2020 Abstract: Axillary osmidrosis (AO) is a common chronic skin condition characterized by unpleasant body odors emanating from the armpits, and its aetiology is not fully understood. AO can seriously impair the psychosocial well-being of the affected individuals; however, no causal therapy has been established for it other than surgical treatment. Recent studies have revealed that human ATP-binding cassette transporter C11 (ABCC11) is an AO risk factor when it is expressed in the axillary apocrine glands—the sources of the offensive odors. Hence, identifying safe ways to inhibit ABCC11 may offer a breakthrough in treating AO. We herein screened for ABCC11-inhibitory activities in 34 natural products derived from plants cultivated for human consumption using an in vitro assay system to measure the ABCC11-mediated transport of radiolabeled dehydroepiandrosterone sulfate (DHEA-S—an ABCC11 substrate). -
Kaempferol Exhibits Progestogenic Effects in Ovariectomized Rats May Fern Toh, Emma Mendonca, Sharon L
s & H oid orm er o t n S f a l o S l c a Journal of i n e r n u c o e J Toh et al., J Steroids Horm Sci 2014, 5:3 ISSN: 2157-7536 Steroids & Hormonal Science DOI: 10.4172/2157-7536.1000136 Research Article Open Access Kaempferol Exhibits Progestogenic Effects in Ovariectomized Rats May Fern Toh, Emma Mendonca, Sharon L. Eddie, Michael P. Endsley, Daniel D. Lantvit, Pavel A. Petukhov, and Joanna E. Burdette* Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60607, USA *Corresponding author: Joanna E. Burdette, 900 S. Ashland Street (M/C 870) Chicago, IL 60607, USA, Tel: 312-996-6153; Fax: 312-996-7107; E-mail: [email protected] Received date: April 15, 2014, Accepted date: June 26, 2014, Published date: July 02, 2014 Copyright: © 2014 Toh MF, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Objective: Progesterone (P4) plays a central role in women's health. Synthetic progestins are used clinically in hormone replacement therapy (HRT), oral contraceptives, and for the treatment of endometriosis and infertility. Unfortunately, synthetic progestins are associated with side effects, including cardiovascular disease and breast cancer. Botanical dietary supplements are widely consumed for the alleviation of a variety of gynecological issues, but very few studies have characterized natural compounds in terms of their ability to bind to and activate progesterone receptors (PR). -
Inhibitory Effect of Genistein and Daidzein on Ovarian Cancer Cell Growth
ANTICANCER RESEARCH 24: 795-800 (2004) Inhibitory Effect of Genistein and Daidzein on Ovarian Cancer Cell Growth CICEK GERCEL-TAYLOR, ANNA K. FEITELSON and DOUGLAS D. TAYLOR Department of Obstetrics, Gynecology and Women’s Health, University of Louisville, School of Medicine, Louisville, KY 40202, U.S.A. Abstract. Background: Survival from ovarian cancer has not Genistein, a soy isoflavanoid, has been intensely studied changed significantly in the past twenty years requiring in relation to breast cancer. Interest first arose upon development of additional treatment protocols. We studied the discovery of the vast difference in breast cancer rates in effect of genistein and daidzein on ovarian cancer cell growth. Asia versus Western countries (1). Large dietary differences Materials and Methods: Five ovarian cancer cell lines from Stage exist, especially in genistein consumption, as the average IIIC disease were evaluated. Sulforhodamine B and colony Asian intake is 20-80 mg/day whereas the average US intake formation assays were used to analyze growth inhibitory effects of is only 1-3 mg (2,3) The dietary and disease discrepancy genistein and daidzein alone and with cisplatin, paclitaxel or prompted further study into the chemopreventive and topotecan. Apoptosis induction was studied by determining potentially therapeutic properties of genistein. caspase-3 activity. Results: Inhibition of growth (50-80%), colony Genistein has been found to inhibit cell proliferation, formation and colony size was seen at 144 Ìm of genistein, 0-23% oncogenesis and clonogenic ability in animal and human reduction was demonstrated at 9 Ìm. At 144 Ìm, the colony size cells (3-5). Several studies have been performed to evaluate was inhibited >75%; at 9 Ìm 4/5 cell lines had >50% reduction. -
Mammalian Target of Rapamycin Inhibitors and Clinical Outcomes in Adult Kidney Transplant Recipients
Article Mammalian Target of Rapamycin Inhibitors and Clinical Outcomes in Adult Kidney Transplant Recipients | Sunil V. Badve,*†‡ Elaine M. Pascoe,* Michael Burke,§ Philip A. Clayton, ¶ Scott B. Campbell,§ Carmel M. Hawley,*§ | Wai H. Lim,** Stephen P. McDonald, ¶ Germaine Wong,†† and David W. Johnson*§ Abstract Background and objectives Emerging evidence from recently published observational studies and an individual – *Australasian Kidney patient data meta analysis shows that mammalian target of rapamycin inhibitor use in kidney transplantation Trials Network, School is associated with increased mortality. Therefore, all-cause mortality and allograft loss were compared of Medicine, between use and nonuse of mammalian target of rapamycin inhibitors in patients from Australia and New University of Zealand, where mammalian target of rapamycin inhibitor use has been greater because of heightened skin Queensland, cancer risk. Brisbane, Australia; †Department of Nephrology, Design, setting, participants, & measurements Our longitudinal cohort study included 9353 adult patients who St. George Hospital, underwent 9558 kidney transplants between January 1, 1996 and December 31, 2012 and had allograft survival Sydney, Australia; ‡ $1 year. Risk factors for all-cause death and all–cause and death–censored allograft loss were analyzed by Renal and Metabolic Division, The George multivariable Cox regression using mammalian target of rapamycin inhibitor as a time-varying covariate. fi Institute for Global Additional analyses evaluated mammalian target of rapamycin inhibitor use at xed time points of baseline and Health, Sydney, 1year. Australia; §Department of Results Patients using mammalian target of rapamycin inhibitors were more likely to be white and have a history Nephrology, Princess Alexandra Hospital, of pretransplant cancer. Over a median follow-up of 7 years, 1416 (15%) patients died, and 2268 (24%) allografts Brisbane, Australia; | were lost. -
Targeting Mtor Signaling Overcomes Acquired Resistance to Combined BRAF and MEK Inhibition in BRAF-Mutant Melanoma
www.nature.com/onc Oncogene ARTICLE OPEN Targeting mTOR signaling overcomes acquired resistance to combined BRAF and MEK inhibition in BRAF-mutant melanoma Beike Wang1,11, Wei Zhang1,11, Gao Zhang 2,10,11, Lawrence Kwong3, Hezhe Lu4, Jiufeng Tan2, Norah Sadek2, Min Xiao2, Jie Zhang 5, 6 2 2 2 2 5 7 6 Marilyne Labrie , Sergio Randell , Aurelie Beroard , Eric Sugarman✉ , Vito W. Rebecca✉ , Zhi Wei , Yiling Lu , Gordon B. Mills , Jeffrey Field8, Jessie Villanueva2, Xiaowei Xu9, Meenhard Herlyn 2 and Wei Guo 1 © The Author(s) 2021 Targeting MAPK pathway using a combination of BRAF and MEK inhibitors is an efficient strategy to treat melanoma harboring BRAF-mutation. The development of acquired resistance is inevitable due to the signaling pathway rewiring. Combining western blotting, immunohistochemistry, and reverse phase protein array (RPPA), we aim to understanding the role of the mTORC1 signaling pathway, a center node of intracellular signaling network, in mediating drug resistance of BRAF-mutant melanoma to the combination of BRAF inhibitor (BRAFi) and MEK inhibitor (MEKi) therapy. The mTORC1 signaling pathway is initially suppressed by BRAFi and MEKi combination in melanoma but rebounds overtime after tumors acquire resistance to the combination therapy (CR) as assayed in cultured cells and PDX models. In vitro experiments showed that a subset of CR melanoma cells was sensitive to mTORC1 inhibition. The mTOR inhibitors, rapamycin and NVP-BEZ235, induced cell cycle arrest and apoptosis in CR cell lines. As a proof-of-principle, we demonstrated that rapamycin and NVP-BEZ235 treatment reduced tumor growth in CR xenograft models. Mechanistically, AKT or ERK contributes to the activation of mTORC1 in CR cells, depending on PTEN status of these cells. -
DE Medicaid MAC List Effective As of 1/5/2018
OptumRx - DE Medicaid MAC List Effective as of 1/5/2018 Generic Label Name & Drug Strength Effective Date MAC Price OTHER IV THERAPY (OTIP) 10/25/2017 77.61750 PENICILLIN G POTASSIUM FOR INJ 5000000 UNIT 3/15/2017 8.00000 PENICILLIN G POTASSIUM FOR INJ 20000000 UNIT 3/15/2017 49.62000 PENICILLIN G SODIUM FOR INJ 5000000 UNIT 10/25/2017 53.57958 PENICILLIN V POTASSIUM TAB 250 MG 1/3/2018 0.05510 PENICILLIN V POTASSIUM TAB 500 MG 12/29/2017 0.10800 PENICILLIN V POTASSIUM FOR SOLN 125 MG/5ML 10/26/2017 0.02000 PENICILLIN V POTASSIUM FOR SOLN 250 MG/5ML 12/22/2017 0.02000 AMOXICILLIN (TRIHYDRATE) CAP 250 MG 12/22/2017 0.03930 AMOXICILLIN (TRIHYDRATE) CAP 500 MG 11/1/2017 0.05000 AMOXICILLIN (TRIHYDRATE) TAB 500 MG 12/28/2017 0.20630 AMOXICILLIN (TRIHYDRATE) TAB 875 MG 10/31/2017 0.08000 AMOXICILLIN (TRIHYDRATE) CHEW TAB 125 MG 10/26/2017 0.12000 AMOXICILLIN (TRIHYDRATE) CHEW TAB 250 MG 10/26/2017 0.24000 AMOXICILLIN (TRIHYDRATE) FOR SUSP 125 MG/5ML 10/28/2017 0.00667 AMOXICILLIN (TRIHYDRATE) FOR SUSP 200 MG/5ML 12/20/2017 0.01240 AMOXICILLIN (TRIHYDRATE) FOR SUSP 250 MG/5ML 12/18/2017 0.00980 AMOXICILLIN (TRIHYDRATE) FOR SUSP 400 MG/5ML 12/28/2017 0.01310 AMPICILLIN CAP 250 MG 9/26/2017 0.07154 AMPICILLIN CAP 500 MG 11/6/2017 0.24000 AMPICILLIN FOR SUSP 125 MG/5ML 3/17/2017 0.02825 AMPICILLIN FOR SUSP 250 MG/5ML 9/15/2017 0.00491 AMPICILLIN SODIUM FOR INJ 250 MG 3/15/2017 1.38900 AMPICILLIN SODIUM FOR INJ 500 MG 7/16/2016 1.02520 AMPICILLIN SODIUM FOR INJ 1 GM 12/20/2017 2.00370 AMPICILLIN SODIUM FOR IV SOLN 1 GM 7/16/2016 15.76300 AMPICILLIN -
Centene Employee
Centene Employee PREFERRED DRUG LIST The Centene Employee Formulary includes a list of drugs covered by your prescription benefit. The formulary is updated often and may change. To get the most up-to-date information, you may view the latest formulary on our website at https://pharmacy.envolvehealth.com/members/formulary.html or call us at 1-844-262-6337. Updated: December 1, 2020 Table of Contents What is the Centene Employee Formulary?...................... .....................................................................ii How are the drugs listed in the categorical list?................................... .................................................ii How much will I pay for my drugs?.......................................................................................................ii How do I find a drug on the Drug List?..................................................................................................iii Are there any limits on my drug coverage?.............................................................................................iv Can I go to any pharmacy?......................................................................................................................iv Can I use a mail order pharmacy?...........................................................................................................v How can I get prior authorization or an exception to the rules for drug coverage?................................v How can I save money on my prescription drugs?.................................................................................v -
The Serine/Threonine Protein Kinase (Akt)/ Protein Kinase B (Pkb) Signaling Pathway in Breast Cancer
Journal of Mind and Medical Sciences Volume 7 Issue 1 Article 7 2020 The Serine/Threonine Protein Kinase (Akt)/ Protein Kinase B (PkB) Signaling Pathway in Breast Cancer Daniela Miricescu FACULTY OF DENTAL MEDICINE, DEPARTMENT OF BIOCHEMISTRY, BUCHAREST, ROMANIA Camelia Cristina Diaconu CAROL DAVILA UNIVERSITY OF MEDICINE AND PHARMACY, CLINICAL EMERGENCY HOSPITAL OF BUCHAREST, INTERNAL MEDICINE CLINIC, BUCHAREST, ROMANIA Constantin Stefani CAROL DAVILA UNIVERSITY OF MEDICINE AND PHARMACY, DEPARTMENT OF FAMILY MEDICINE, BUCHAREST, ROMANIA Ana Maria Alexandra Stanescu CAROL DAVILA UNIVERSITY OF MEDICINE AND PHARMACY, DEPARTMENT OF FAMILY MEDICINE, BUCHAREST, ROMANIA Alexandra Totan FAollowCULT thisY OF and DEN additionalTAL MEDICINE, works at:DEP https:/ARTMEN/scholarT OF.v BIOCHEMISTRalpo.edu/jmmsY, BUCHAREST, ROMANIA Part of the Obstetrics and Gynecology Commons, Oncology Commons, and the Palliative Care SeeCommons next page for additional authors Recommended Citation Miricescu, Daniela; Diaconu, Camelia Cristina; Stefani, Constantin; Stanescu, Ana Maria Alexandra; Totan, Alexandra; Rusu, Ioana Ruxandra; Bratu, Ovidiu Gabriel; Spinu, Dan; and Greabu, Maria (2020) "The Serine/ Threonine Protein Kinase (Akt)/ Protein Kinase B (PkB) Signaling Pathway in Breast Cancer," Journal of Mind and Medical Sciences: Vol. 7 : Iss. 1 , Article 7. DOI: 10.22543/7674.71.P3439 Available at: https://scholar.valpo.edu/jmms/vol7/iss1/7 This Review Article is brought to you for free and open access by ValpoScholar. It has been accepted for inclusion in Journal