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Suppression of Prostate Tumor Cell Growth by Stromal Cell Prostaglandin D Synthase–Derived Products
Research Article Suppression of Prostate Tumor Cell Growth by Stromal Cell Prostaglandin D Synthase–Derived Products Jeri Kim,1 Peiying Yang,2 Milind Suraokar,3 Anita L. Sabichi,3 Norma D. Llansa,3 Gabriela Mendoza,3 Vemparalla Subbarayan,3 Christopher J. Logothetis,1 Robert A. Newman,2 Scott M. Lippman,3 and David G. Menter3 Departments of 1Genitourinary Medical Oncology, 2Experimental Therapeutics, and 3Clinical Cancer Prevention, The University of Texas M.D. Anderson Cancer Center, Houston, Texas Abstract seminal fluid (10). Once PGD2 is made, it forms derivative Stromal-epithelial interactions and the bioactive molecules compounds, most of which can transactivate the peroxisome g g produced by these interactions maintain tissue homeostasis proliferator–activated receptor (PPAR ). One PGD2 derivative, 15-deoxy-D12,14-prostaglandin J (15-d-PGJ ), can slow the growth and influence carcinogenesis. Bioactive prostaglandins pro- 2 2 duced by prostaglandin synthases and secreted by the prostate and induce the partial differentiation of selected cancer cells (12). D12,14 into seminal plasma are thought to support reproduction, but Another PGD2 derivative, 15-deoxy- -PGD2 (15-d-PGD2), has g their endogenous effects on cancer formation remain unre- also been shown to stimulate PPAR transactivation in RAW 264.7 solved. No studies to date have examined prostaglandin cell macrophage cultures as effectively as 15-d-PGJ2 (13). L-PGDS enzyme production or prostaglandin metabolism in normal also binds tritiated testosterone and may play a role in androgen prostate stromal cells. Our results show that lipocalin-type transport (14). In castrated rats, testosterone proprionate induces prostaglandin D synthase (L-PGDS) and prostaglandin D L-PGDS synthesis in the epididymis (15). -
Outpatient Acne Care Guideline
Outpatient Acne Care Guideline Severity Mild Moderate Severe < 20 comedones or < 20-100 comedones or 15-50 > 5 cysts, >100 comedones, or inflammatory lesions inflammatory lesions >50 inflammatory lesions Initial Treatment Initial Treatment Initial Treatment Benzoyl Peroxide (BP) or Topical Combination Therapy Combination Therapy Topical Retinoid Retinoid + BP Oral antibiotic or OR + (Retinoid + Antibiotic) + BP Topical retinoid Topical Combination Therapy or + BP + Antibiotic Retinoid + (BP + Antibiotic) or OR BP Retinoid + BP Oral antibiotic + topical retinoid + +/- or BP Topical antibiotic Retinoid + Antibiotic + BP or Topical Dapsone IF Inadequate Response IF Inadequate Response IF Inadequate Consider dermatology Response referral Change topical retinoid Consider changing oral concentrations, type and/or antibiotic formulation AND or Add BP or retinoid, if not already Change topiocal combination Consider isotretinoin prescribed therapy Consider hormone therapy or and/or (females) Change topical retinoid Add or change oral antibiotic concentrations, type and/or or formulation Consider isotretinoin Additional Considerations or Consider hormone therapy (females) Change topical comination Previous treatment/history Side effects therapy Costs Psychosocial impact Vehicle selection Active scarring Ease of use Regimen complexity Approved Evidence Based Medicine Committee 1-18-17 Reassess the appropriateness of Care Guidelines as condition changes. This guideline is a tool to aid clinical decision making. It is not a standard of care. The physician should deviate from the guideline when clinical judgment so indicates. GOAL: Pediatricians should initiate treatment for cases of “Mild” to “Severe” acne (see algorithms attached). Pediatricians should also counsel patients in order to maximize adherence to acne treatment regimens: 1. Realistic expectations. Patients should be counseled that topical therapies typically take up to 6-8 weeks to start seeing results. -
WHO Drug Information Vol
WHO Drug Information Vol. 24, No. 4, 2010 World Health Organization WHO Drug Information Contents WHO Prequalification Sitaxentan: worldwide withdrawal 307 Programmes Sibutramine: suspension of sales 307 Sibutramine-containing medicines: WHO Prequalification of Medicines withdrawal 308 Programme: survey of service Testosterone transdermal patch: quality provided to manufacturers 293 withdrawal of extension of WHO initiates pilot prequalification of indication application 308 active pharmaceutical ingredients 297 Aliskiren/valsartan: withdrawal of New on-line database for WHO marketing authorization application 308 prequalified vaccines 298 Mometasone furoate/formoterol fumarate: withdrawal of marketing Safety and Efficacy Issues authorization application 309 EMA and US FDA extend confidentiality H1N1 influenza vaccine: narcolepsy 299 arrangements indefinitely 309 Statins: interstitial lung disease 299 Tocilizumab: risk of fatal anaphylaxis 300 Recent Publications, Pioglitazone: potential bladder cancer 301 Information and Events Angiotensin receptor blockers and US Government to share patents with cancer: safety review 301 Medicines Patent Pool 310 GnRH agonists, diabetes and cardio- Clinical trials and global medicines vascular disease 301 development 310 Gadolinium-based contrast agents: Evaluation of future nanomedicines 311 kidney dysfunction 302 Reporting on opioid inaccessibility 311 Lamotrigine: aseptic meningitis Tinzaparin sodium: renal Impairment in elderly 303 Consultation Documents Tamoxifen: drug interactions involving The -
Therapeutic Drug Class
BUREAU FOR MEDICAL SERVICES WEST VIRGINIA MEDICAID EFFECTIVE PREFERRED DRUG LIST WITH PRIOR AUTHORIZATION CRITERIA 04/01/11 This is not an all-inclusive list of available covered drugs and includes only Version 2011.9 managed categories. Refer to cover page for complete list of rules governing this PDL. • Prior authorization for a non-preferred agent in any category will be given only if there has been a trial of the preferred brand/generic equivalent or preferred formulation of the active ingredient, at a therapeutic dose, that resulted in a partial response with a documented intolerance. • Prior authorization of a non-preferred isomer, pro-drug, or metabolite will be considered with a trial of a preferred parent drug of the same chemical entity, at a therapeutic dose, that resulted in a partial response with documented intolerance or a previous trial and therapy failure, at a therapeutic dose, with a preferred drug of a different chemical entity indicated to treat the submitted diagnosis. (The required trial may be overridden when documented evidence is provided that the use of these preferred agent(s) would be medically contraindicated.) • Unless otherwise specified, the listing of a particular brand or generic name includes all legend forms of that drug. OTC drugs are not covered unless specified. • PA criteria for non-preferred agents apply in addition to general Drug Utilization Review policy that is in effect for the entire pharmacy program, including, but not limited to, appropriate dosing, duplication of therapy, etc. • The use of pharmaceutical samples will not be considered when evaluating the members’ medical condition or prior prescription history for drugs that require prior authorization. -
2018 Medicines in Development for Skin Diseases
2018 Medicines in Development for Skin Diseases Acne Drug Name Sponsor Indication Development Phase ADPS topical Taro Pharmaceuticals USA acne vulgaris Phase II completed Hawthorne, NY www.taro.com AOB101 AOBiome acne vulgaris Phase II (topical ammonia oxidizing bacteria) Cambridge, MA www.aobiome.com ASC-J9 AndroScience acne vulgaris Phase II (androgen receptor degradation Solana Beach, CA www.androscience.com enhancer) BLI1100 Braintree Laboratories acne vulgaris Phase II completed Braintree, MA www.braintreelabs.com BPX-01 BioPharmX acne vulgaris Phase II (minocycline topical) Menlo Park, CA www.biopharmx.com BTX1503 Botanix Pharmaceuticals moderate to severe acne vulgaris Phase II (cannabidiol) Plymouth Meeting, PA www.botanixpharma.com CJM112 Novartis Pharmaceuticals acne vulgaris Phase II (IL-17A protein inhibitor) East Hanover, NJ www.novartis.com clascoterone Cassiopea acne vulgaris Phase III (androgen receptor antagonist) Lainate, Italy www.cassiopea.com Medicines in Development: Skin Diseases ǀ 2018 Update 1 Acne Drug Name Sponsor Indication Development Phase CLS001 Cutanea acne vulgaris Phase II (omiganan) Wayne, PA www.cutanea.com DFD-03 Promius Pharma acne vulgaris Phase III (tazarotene topical) Princeton, NJ www.promiuspharma.com DMT310 Dermata Therapeutics moderate to severe acne vulgaris Phase II (freshwater sponge-derived) San Diego, CA www.dermatarx.com finasteride Elorac severe nodulocystic acne Phase II (cholestenone 5-alpha Vernon Hills, IL www.eloracpharma.com reductase inhibitor) FMX101 Foamix moderate to severe -
Lipocalin-Type Prostaglandin D Synthase Regulates Light-Induced Phase Advance of the Central Circadian Rhythm in Mice
ARTICLE https://doi.org/10.1038/s42003-020-01281-w OPEN Lipocalin-type prostaglandin D synthase regulates light-induced phase advance of the central circadian rhythm in mice Chihiro Kawaguchi et al.# 1234567890():,; We previously showed that mice lacking pituitary adenylate cyclase-activating polypeptide (PACAP) exhibit attenuated light-induced phase shift. To explore the underlying mechan- isms, we performed gene expression analysis of laser capture microdissected suprachias- matic nuclei (SCNs) and found that lipocalin-type prostaglandin (PG) D synthase (L-PGDS) is involved in the impaired response to light stimulation in the late subjective night in PACAP- deficient mice. L-PGDS-deficient mice also showed impaired light-induced phase advance, but normal phase delay and nonvisual light responses. Then, we examined the receptors involved in the response and observed that mice deficient for type 2 PGD2 receptor DP2/ CRTH2 (chemoattractant receptor homologous molecule expressed on Th2 cells) show impaired light-induced phase advance. Concordant results were observed using the selective DP2/CRTH2 antagonist CAY10471. These results indicate that L-PGDS is involved in a mechanism of light-induced phase advance via DP2/CRTH2 signaling. #A list of authors and their affiliations appears at the end of the paper. COMMUNICATIONS BIOLOGY | (2020) 3:557 | https://doi.org/10.1038/s42003-020-01281-w | www.nature.com/commsbio 1 ARTICLE COMMUNICATIONS BIOLOGY | https://doi.org/10.1038/s42003-020-01281-w he mammalian circadian clock system comprises the genes (Fig. 1a). Of these 593 genes, we specifically analyzed genes endogenous master pacemaker located within the supra- that were upregulated (>1.7-fold change) or downregulated (>0.6- T −/− chiasmatic nucleus (SCN) in the hypothalamus and coor- fold change) by light stimulation in PACAP and wild-type mice. -
Rosuvastatin and Atorvastatin Are Ligands of the Human Constitutive Androstane Receptor/Retinoid X Receptor a Complex S
Supplemental material to this article can be found at: http://dmd.aspetjournals.org/content/suppl/2017/05/23/dmd.117.075523.DC1 1521-009X/45/8/974–976$25.00 https://doi.org/10.1124/dmd.117.075523 DRUG METABOLISM AND DISPOSITION Drug Metab Dispos 45:974–976, August 2017 Copyright ª 2017 by The American Society for Pharmacology and Experimental Therapeutics Short Communication Rosuvastatin and Atorvastatin Are Ligands of the Human Constitutive Androstane Receptor/Retinoid X Receptor a Complex s Received February 21, 2017; accepted May 17, 2017 ABSTRACT Statins are well known lipid lowering agents that inhibit the enzyme models of CAR/RXRa-LBD were constructed by ligand-based and – 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase. They also structure-based in silico modeling. Experiments and computational Downloaded from activate drug metabolism but their exact receptor-mediated action modeling show that atorvastatin and rosuvastatin bind to the human has not been proven so far. We tested whether atorvastatin and CAR/RXRa-LBD heterodimer, suggesting both can modulate the rosuvastatin are direct ligands of human constitutive androstane activity of CAR through direct interaction with the LBD of this receptor (CAR). We measured binding activities of atorvastatin and receptor. We confirm that atorvastatin and rosuvastatin are direct rosuvastatin to the human constitutive androstane receptor/retinoid ligands of CAR. The clinical consequences of CAR activation by X receptor a ligand-binding domain (CAR/RXRa-LBD) heterodimer statins are in their potential drug-drug interactions, and changes in dmd.aspetjournals.org with surface plasmon resonance (SPR). Additionally, three-dimensional glucose and energy metabolism. -
Patent Application Publication ( 10 ) Pub . No . : US 2019 / 0192440 A1
US 20190192440A1 (19 ) United States (12 ) Patent Application Publication ( 10) Pub . No. : US 2019 /0192440 A1 LI (43 ) Pub . Date : Jun . 27 , 2019 ( 54 ) ORAL DRUG DOSAGE FORM COMPRISING Publication Classification DRUG IN THE FORM OF NANOPARTICLES (51 ) Int . CI. A61K 9 / 20 (2006 .01 ) ( 71 ) Applicant: Triastek , Inc. , Nanjing ( CN ) A61K 9 /00 ( 2006 . 01) A61K 31/ 192 ( 2006 .01 ) (72 ) Inventor : Xiaoling LI , Dublin , CA (US ) A61K 9 / 24 ( 2006 .01 ) ( 52 ) U . S . CI. ( 21 ) Appl. No. : 16 /289 ,499 CPC . .. .. A61K 9 /2031 (2013 . 01 ) ; A61K 9 /0065 ( 22 ) Filed : Feb . 28 , 2019 (2013 .01 ) ; A61K 9 / 209 ( 2013 .01 ) ; A61K 9 /2027 ( 2013 .01 ) ; A61K 31/ 192 ( 2013. 01 ) ; Related U . S . Application Data A61K 9 /2072 ( 2013 .01 ) (63 ) Continuation of application No. 16 /028 ,305 , filed on Jul. 5 , 2018 , now Pat . No . 10 , 258 ,575 , which is a (57 ) ABSTRACT continuation of application No . 15 / 173 ,596 , filed on The present disclosure provides a stable solid pharmaceuti Jun . 3 , 2016 . cal dosage form for oral administration . The dosage form (60 ) Provisional application No . 62 /313 ,092 , filed on Mar. includes a substrate that forms at least one compartment and 24 , 2016 , provisional application No . 62 / 296 , 087 , a drug content loaded into the compartment. The dosage filed on Feb . 17 , 2016 , provisional application No . form is so designed that the active pharmaceutical ingredient 62 / 170, 645 , filed on Jun . 3 , 2015 . of the drug content is released in a controlled manner. Patent Application Publication Jun . 27 , 2019 Sheet 1 of 20 US 2019 /0192440 A1 FIG . -
Crth2: Can Residence Time Help ?
CRTh2: Can Residence Time Help ? RSC-SCI Cambridge Medicinal Chemistry Symposium Churchill College, Cambridge 8-11 September 2013 Rick Roberts Almirall Introduction Paul Ehrlich, The Lancet (1913), 182, 445 “A substance will not work unless it is bound” 100 years on: “What a substance does may depend on how long it is bound” 2 In a nutshell …. Introduction “Applications of Binding Kinetics to Drug Discovery” D. Swinney, Pharm. Med. (2008), 22, 23-34 3 Energetic concept of Residence Time kon Standard model [R] + [L] [RL] k unbound off bound Energy ‡ Binding process (kon) is (R·L) determined by the energy barrier Ea E Ligand concentration a Unbinding process (koff) is determines the number of Ed determined by the energy attempts to get over this barrier Ed barrier [R] + [L] G = Ed -Ea [RL] Reaction coordinate Potency (Ki) is determined by the difference in these energies koff Ki = kon 4 K , k , k i on off -1 -1 kon M s Potency (nM) vs kon vs koff Very fast association 108 10 1 0.1 0.01 0.001 107 100 10 1 0.1 0.01 0.001 fast association 106 1000 100 10 1 0.1 0.01 0.001 105 10 M 1000 100 10 1 0.1 0.01 0.001 slow association 104 10 M 1000 100 10 1 0.1 0.01 Very slow association 103 10 M 1000 100 10 1 0.1 “inactive” 102 10 M 1000 100 10 1 10 10-1 10-2 10-3 10-4 10-5 10-6 10-7 s-1 koff Energy A simple binding measurement gives no clue to how fast the association and dissociation are (R·L)‡ Very slow associating compounds that are very slow dissociating (R·L)‡ slow associating compounds that are slow dissociating Are all fast associating compounds -
Retinoid-Induced Apoptosis in Normal and Neoplastic Tissues
Cell Death and Differentiation (1998) 5, 11 ± 19 1998 Stockton Press All rights reserved 13509047/98 $12.00 Review Retinoid-induced apoptosis in normal and neoplastic tissues Laszlo Nagy1,3,4, Vilmos A. Thomazy1, Richard A. Heyman2 retinoic acid receptor (RAR), which belongs to the superfamily and Peter J.A. Davies1,3 of ligand-activated transcription factors (nuclear receptors) revolutionized our understanding as to how retinoids exert 1 Department of Pharmacology, University of Texas-Houston, Medical School, their pleiotropic effects (for reviews see Chambon (1996); Houston, Texas 77225 USA Mangelsdorf et al (1994)). Members of the nuclear receptor 2 Ligand Pharmaceuticals, San Diego, California, 92121 USA superfamily mediate the biological effects of many hormones, 3 Corresponding author: PJAD, tel: 713-500-7480; fax: 713-500-7455; vitamins and drugs (i.e. steroid hormones, thyroid hormones, e-mail: [email protected] 4 vitamin D, prostaglandin-J (PG-J ) and drugs that activate Present address for correspondence: The Salk Institute for Biological Studies, 2 2 Gene Expression Laboratory, La Jolla, California 92037; peroxisomal proliferation). There are two families of retinoid tel: (619) 453-4100 fax:(619) 455-1349; e-mail: [email protected] receptors, Retinoid X Receptors (RXRs) that bind 9-cis retinoic acid (9-cis RA) and Retinoic Acid Receptors (RARs) Received 18.8.97; revised 19.9.97; accepted 22.9.97 that bind both 9-cis RA and all-trans retinoic acid (ATRA) (for Edited by M. Piacentini reviews see Chambon 1996; Mangelsdorf et al, 1994)). Each of these receptor families includes at least three distinct genes, (RARa,b and g; RXRa,b and g) that through differential Abstract promoter usage and alternative splicing, give rise to a large number of distinct retinoid receptor proteins (for reviews see Vitamin A and its derivatives (collectively referred to as Chambon 1996; Mangelsdorf et al, 1994). -
A Double-Blind Controlled Trial of Etretinate (Tigason) and Ibuprofen in Psoriatic Arthritis
Ann Rheum Dis: first published as 10.1136/ard.44.3.189 on 1 March 1985. Downloaded from Annals of the Rheumatic Diseases, 1985; 44, 189-193 A double-blind controlled trial of etretinate (Tigason) and ibuprofen in psoriatic arthritis R HOPKINS, H A BIRD, H JONES, J HILL, K E SURRALL, C ASTBURY, *A MILLER, AND V WRIGHT From the Clinical Pharmacology Unit, Royal Bath Hospital, Harrogate, and the General Infirmary at Leeds, and *Roche Products Limited, Welwyn Garden City, Hertfordshire SUMMARY Etretinate (Tigason) and ibuprofen have been compared in a double-blind controlled trial in psoriatic arthritis to see if we could confirm a specific action for this vitamin A derivative suggested from earlier uncontrolled studies. Eleven out of 20 patients completed 24 weeks of therapy with etretinate (up to 0-5 mg/kg/day) whereas only 1/20 patients completed 24 weeks of therapy with ibuprofen alone. Etretinate improved skin lesions, and this may have encouraged patients to persist with it. Improvement of statistical significance was seen for articular index in both groups. In addition significant improvement in ESR, haemoglobin, C-reactive protein, and histidine occurred in the etretinate group. The main side effects of etretinate (which may preclude its use at a higher dose in this condition) included cracked and dried lips and sore mouth. copyright. Etretinate (Tigason) is a vitamin A derivative. The provement in 99m technetium scans of the hands and parent vitamin is essential for growth, maintenance feet, and 'no progression of destructive change' on of visual function, and the regulation of prolifera- x-rays.5 Rosenthal et al. -
Solubility Challenges: Unlocking a Drug’S Potential JULY 2015 Pharmtech.Com
JULY 2015 Volume 39 Number 7 Volume 39 Number 7 Cleaning Stability Tablet Count PLUS: Validation of Biologics in Packaging PHARMACEUTICAL TECHNOLOGY Solubility Challenges: Unlocking a Drug’s Potential JULY 2015 2015 JULY PharmTech.com PEER-REVIEWED Using In-Situ Gelling to Optimize Opthalmic Drug Delivery DRUG DELIVERY OPERATIONAL EXCELLENCE API SYNTHESIS & MANUFACTURING Targeting Drugs to the Colon Data Integrity Continuous API Synthesis magentablackcyanyellow ES639585_PT0715_cv1.pgs 07.07.2015 20:54 ADV magentablackcyanyellow ES639144_PT0715_CV2_FP.pgs 07.06.2015 20:46 ADV INTRODUCING Vion IMS QTof When you’re up against complex samples, sometimes resolution and accurate mass aren’t enough to give you all the information you need. Enter Vion IMS QTof with Collision Cross Section (CCS). A new mass spectrometer that brings ion mobility to the benchtop like never before. Now the analytes you didn’t know were there have nowhere to hide. To learn more, visit waters.com/VION PHARMACEUTICAL n HEALTH SCIENCES n FOOD n ENVIRONMENTAL n CHEMICAL MATERIALS magentablackcyanyellow ES639166_PT0715_003_FP.pgs 07.06.2015 20:46 ADV EDITORIAL SALES Editorial Director Rita Peters [email protected] Publisher Mike Tracey [email protected] Senior Editor Agnes Shanley [email protected] Director of Sales Paul Milazzo [email protected] Managing Editor Susan Haigney [email protected] Mid-West Sales Manager Irene Onesto [email protected] Science Editor Adeline Siew, PhD [email protected] East Coast Sales Manager Joel Kern [email protected]