DOCSLIB.ORG

Topical Tamoxifen Promising for Mastalgia

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Topical Tamoxifen Promising for Mastalgia 14 REPRODUCTIVE ENDOCRINOLOGY JANUARY 2009 • CLINICAL ENDOCRINOLOGY NEWS Topical Tamoxifen Promising for Mastalgia BY BRUCE JANCIN al, of Cardiff (Wales) University. afimoxifene to their breasts daily for 21 dose showed less robust albeit favorable Denver Bureau Oral tamoxifen, bromocriptine, dana- days. At steady state, achieved after 2 trends on all end points, he continued. zol, and progestins have demonstrated weeks of therapy, mean plasma 4-hy- In an interview, Dr. Goyal said he has S AN A NTONIO — Afimoxifene, a efficacy in treating cyclic mastalgia; how- droxytamoxifen levels were just 1/18 of had some success in using oral tamoxifen novel tamoxifen gel applied directly to ever, their systemic side effects render those measured in 19 healthy controls in men with gynecomastia. He plans to the breasts, performed favorably as top- them poorly suited for long-term treat- taking 20 mg/day of oral tamoxifen. study topical afimoxifene for this condi- ical therapy for moderate to severe cyclic Based upon those encouraging find- tion in a placebo-controlled trial. mastalgia in premenopausal women in a After 4 cycles, ings, Dr. Goyal and colleagues next carried Prevention of breast cancer is an ex- phase II clinical trial. pain intensity out the phase II trial involving 127 pre- citing potential application for the topical Although the topical antiestrogen’s de- was 64% lower menopausal women with moderate to selective estrogen-receptor modulator. veloper, ASCEND Therapeutics Inc., in women on severe cyclic mastalgia. They were ran- “The main reason why some women plans to seek an initial indication for afimoxifene than domized to placebo or either 2 mg or 4 mg and some physicians are reluctant to use cyclic mastalgia, there also is strong in- in the placebo of afimoxifene daily for 4 menstrual cycles. oral tamoxifen, even though we know terest in developing afimoxifene as a group. Significant differences in efficacy be- from [a previous] study that it works, is treatment for male gynecomastia as well tween the 4-mg dose and placebo were because of side effects. If we can show as for breast cancer chemoprevention, DR. GOYAL documented after 2 cycles. After 4 cycles, afimoxifene works to prevent breast can- Dr. Amit Goyal said at the San Antonio mean pain intensity measured on a visual cer as well as oral tamoxifen, I think that Breast Cancer Symposium. ment of a chronic problem. In contrast, analog scale for the 7 worst days per cy- would be an important advance,” Dr. Afimoxifene is 4-hydroxytamoxifen, a transdermal afimoxifene is highly effec- cle was 64% lower in women on 4 Goyal said. potent metabolite of tamoxifen, in a pro- tive within the breast yet has very low mg/day of afimoxifene than in the place- The mastalgia trial was supported by prietary hydroalcoholic gel. Its binding systemic levels, thus reducing the risk of bo group. Physician global assessments ASCEND Therapeutics. Dr. Goyal indi- affinity for the alpha– and beta–estrogen systemic toxicities, he continued. of breast nodularity and tenderness cated he has received research funds receptors is two- to threefold greater In a pharmacokinetic study, 16 healthy showed reductions of 70% and 67%, re- from the company but has no other fi- than that of estradiol, explained Dr. Goy- premenopausal women applied 4 mg of spectively, relative to placebo. The 2-mg nancial involvement with ASCEND. ■ Inflammatory Bowel BMI Greater Than 25 May Increase Risk Disease May Speed of Miscarriage of a Normal Fetus Ovarian Follicle Loss BY SHARON WORCESTER preimplantation genetic diagnosis. S AN F RANCISCO — Inflammatory bowel dis- Southeast Bureau In addition to an increase in euploid miscarriage risk ease does not severely alter ovarian reserve but may based on BMI, a trend toward increased risk among accelerate loss of primordial follicles in those aged S AN F RANCISCO — The risk of miscarriage of a ge- women with polycystic ovary syndrome, compared 30 years and older, study results showed. netically normal fetus is significantly increased in over- with those without PCOS, was observed (48% vs. 39%, The investigators measured anti-müllerian hor- weight women, compared with normal weight women, respectively), but the difference did not reach statistical mone—a reliable hormonal marker for evaluating the findings of a retrospective case-control study of 204 significance. Also, no significant differences in euploid ovarian reserve independently of the menstrual cy- miscarriages suggest. miscarriage were seen based on insulin resistance sta- cle—in 44 women aged 20-41 years who had IBD The rate of euploid miscarriage among 204 first tus. However, because all but one of the women with and were in clinical remission after infliximab treat- trimester missed abortions that occurred between 1999 insulin resistance were on insulin-lowering therapy at ment for either Crohn’s disease (37 patients) or ul- and 2008 in women at a single center was 53% in those the time of conception, the conclusions in these popu- cerative colitis (7 patients). with a body mass index of 25 or greater, compared with lations are limited, Dr. Landres noted. The hormone levels were compared with those 37% in those with a BMI of less than 25. The difference The findings, which suggest that BMI over 25 is a risk of 163 age-matched women undergoing in vitro fer- was statistically significant, Dr. Innes V. Landres re- factor for euploid miscarriage, are important, given the tilization who had a normal ovarian response to ported at the annual meeting of the American Society fact that BMI (unlike age) is a modifiable risk factor. Al- controlled ovarian stimulation (5-15 oocytes re- for Reproductive Medicine. though the study is limited by its retrospective nature, trieved) and a normal serum anti-müllerian hor- The mean age of the women in both groups was the lack of power, and multiple confounders for which the mone level (>1.5 mcg/L). same (34 years). Those over age 39 years were exclud- investigators could not control, it is nonetheless im- The anti-müllerian hormone levels did not differ ed because of the increased risk of miscarriage in portant that elevated BMI be identified as a risk factor significantly overall between the IBD and control women with advanced maternal age, noted Dr. Landres, for euploid miscarriage, and that women with elevated patients (2.72 vs. 2.12 mcg/L), Dr. Thomas Fréour a chief resident in obstetrics and gynecology at Stanford BMI be counseled about the importance of lifestyle reported in a poster at the annual meeting of the (Calif.) University. modification. Also, although more study is needed on American Society for Reproductive Medicine. The groups also were similar in types of assisted re- the effects of insulin-lowering medications in this pop- However, when the women were stratified by age productive technologies used and in pregnancy history. ulation, treatment should be considered. 30 years and older vs. age less than 30 years, the anti- The study was undertaken to explore the cytogenet- Additional study of the effects of BMI on endometrial müllerian hormone levels were found to differ in the ic results of miscarriages in relation to maternal weight dysfunction and miscarriage rates, as well as on the ef- older women, with those aged 30 years and older hav- and insulin resistance, Dr. Landres explained. fects of lifestyle modification, is needed, Dr. Landres ing lower levels than controls (2 vs. 2.96 mcg/L). The Both obesity and insulin resistance have been linked concluded. ■ levels in the younger patients remained comparable with spontaneous abortion and recurrent pregnancy in the patients and controls, said Dr. Fréour of the loss. Most spontaneous abortions are a result of fetal University Hospital Center of Nantes (France). aneuploidy, as was the case in 59% of patients overall Inflammatory bowel disease has been shown in in this study—67% in those over age 34 years, and 50% previous studies to be associated with female sub- in those 34 years and younger. There is some evidence, fertility, mainly through tubal dysfunctions, exten- however, that obesity predisposes women to euploid sive adhesions, or chirurgical consequences on miscarriage, and that there is an increased rate of spon- pelvic function, but alteration of ovarian reserve in taneous abortion even among obese women with ovum those with IBD had not been previously studied, Dr. donation. Fréour noted. For the current study, the medical records of women The findings suggest that in reproductive age with first trimester missed abortion, subsequent dilation IVION women 30 years and older who have IBD, a sub- and curettage, and karyotype analysis of the products S stantially accelerated loss of primordial follicles may of conception were reviewed. Among the patients ex- OMAN occur. This loss might be due to chronic inflam- cluded—other than those older than 39 years—were R mation or to IBD treatments, he noted. those patients with a history of diabetes, those using Elevated BMI should be seen as a risk factor for —Sharon Worcester steroids or narcotics, and those with donor eggs or euploid miscarriage, said Dr. Innes V. Landres. .
Load more

Recommended publications
  • Phase II Study of Hormone Therapy with Tamoxifen in Patients with Well Differentiated Neuroendocrine Tumors and Hormone Receptor Positive Expression (HORMONET)
    Phase II study of hormone therapy with tamoxifen in patients with well differentiated neuroendocrine tumors and hormone receptor positive expression (HORMONET) Time of researchers and respective Departments: Rachel Riechelmann (Main Investigador)1, Milton Barros 1, Marcos Camandaroba1,2, Virgilio Souza1,2, Celso Abdon Mello1, Paula Nicole3, Eduardo Nóbrega4, Ludmilla Chinen5, Marina De Brot6, Héber Salvador7. Departaments: 1- Clinical Oncology; 2- postgraduate student; 3- Radiology; 4- Nuclear Medicine; 5-International Research Center (CIPE); 6-Pathologic anatomy; 7- Abdomen Surgery AC Camargo Cancer Center - Brazil Registration Number on Institutional Research Ethics Committee: 2626/18 March,06,2019 Introduction Neuroendocrine tumors (NET) are rare neoplasms, but with increasing incidence and prevalence in the last decades. Although they may manifest in the most diverse tissues, the vast majority of cases will affect organs of the digestive tract and lung. At diagnosis, more than half of the cases present metastatic disease, and among patients with localized disease, up to one-third will have recurrence of the disease. Unfortunately, the minority of patients with metastatic disease are eligible for curative intent.1 Although there are many types of NET, they are often studied together as a group because their cells share common histological findings, have special secretory granules, and the ability to secrete bioactive amines and polypeptide hormones. Approximately 25 percent of the tumors present functional hormonal syndromes (situation of great morbidity for these patients), being the carcinoid syndrome, the most common one. From the molecular point of view, these neoplasias are largely dependent on the activation of the mTOR pathway and neoangiogenesis.2 Another striking feature of neuroendocrine cells is the expression of cell surface hormone receptors whose activation or blockade may exert an important regulatory function.
    [Show full text]
  • A Simple Method to Measure Sulfonation in Man Using Paracetamol As Probe Drug Natália Marto 1,2*, Judit Morello1,3, Alexandra M
    www.nature.com/scientificreports OPEN A simple method to measure sulfonation in man using paracetamol as probe drug Natália Marto 1,2*, Judit Morello1,3, Alexandra M. M. Antunes3, Sofa Azeredo4, Emília C. Monteiro1,5 & Sofa A. Pereira1,5 Sulfotransferase enzymes (SULT) catalyse sulfoconjugation of drugs, as well as endogenous mediators, gut microbiota metabolites and environmental xenobiotics. To address the limited evidence on sulfonation activity from clinical research, we developed a clinical metabolic phenotyping method using paracetamol as a probe substrate. Our aim was to estimate sulfonation capability of phenolic compounds and study its intraindividual variability in man. A total of 36 healthy adult volunteers (12 men, 12 women and 12 women on oral contraceptives) received paracetamol in a 1 g-tablet formulation on three separate occasions. Paracetamol and its metabolites were measured in plasma and spot urine samples using liquid chromatography-high resolution mass spectrometry. A metabolic ratio (Paracetamol Sulfonation Index—PSI) was used to estimate phenol SULT activity. PSI showed low intraindividual variability, with a good correlation between values in plasma and spot urine samples. Urinary PSI was independent of factors not related to SULT activity, such as urine pH or eGFR. Gender and oral contraceptive intake had no impact on PSI. Our SULT phenotyping method is a simple non-invasive procedure requiring urine spot samples, using the safe and convenient drug paracetamol as a probe substrate, and with low intraindividual coefcient of variation. Although it will not give us mechanistic information, it will provide us an empirical measure of an individual’s sulfonator status. To the best of our knowledge, our method provides the frst standardised in vivo empirical measure of an individual’s phenol sulfonation capability and of its intraindividual variability.
    [Show full text]
  • Tanibirumab (CUI C3490677) Add to Cart
    5/17/2018 NCI Metathesaurus Contains Exact Match Begins With Name Code Property Relationship Source ALL Advanced Search NCIm Version: 201706 Version 2.8 (using LexEVS 6.5) Home | NCIt Hierarchy | Sources | Help Suggest changes to this concept Tanibirumab (CUI C3490677) Add to Cart Table of Contents Terms & Properties Synonym Details Relationships By Source Terms & Properties Concept Unique Identifier (CUI): C3490677 NCI Thesaurus Code: C102877 (see NCI Thesaurus info) Semantic Type: Immunologic Factor Semantic Type: Amino Acid, Peptide, or Protein Semantic Type: Pharmacologic Substance NCIt Definition: A fully human monoclonal antibody targeting the vascular endothelial growth factor receptor 2 (VEGFR2), with potential antiangiogenic activity. Upon administration, tanibirumab specifically binds to VEGFR2, thereby preventing the binding of its ligand VEGF. This may result in the inhibition of tumor angiogenesis and a decrease in tumor nutrient supply. VEGFR2 is a pro-angiogenic growth factor receptor tyrosine kinase expressed by endothelial cells, while VEGF is overexpressed in many tumors and is correlated to tumor progression. PDQ Definition: A fully human monoclonal antibody targeting the vascular endothelial growth factor receptor 2 (VEGFR2), with potential antiangiogenic activity. Upon administration, tanibirumab specifically binds to VEGFR2, thereby preventing the binding of its ligand VEGF. This may result in the inhibition of tumor angiogenesis and a decrease in tumor nutrient supply. VEGFR2 is a pro-angiogenic growth factor receptor
    [Show full text]
  • PHARMACEUTICAL APPENDIX to the TARIFF SCHEDULE 2 Table 1
    Harmonized Tariff Schedule of the United States (2020) Revision 19 Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States (2020) Revision 19 Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 2 Table 1. This table enumerates products described by International Non-proprietary Names INN which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service CAS registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known.
    [Show full text]
  • TE INI (19 ) United States (12 ) Patent Application Publication ( 10) Pub
    US 20200187851A1TE INI (19 ) United States (12 ) Patent Application Publication ( 10) Pub . No .: US 2020/0187851 A1 Offenbacher et al. (43 ) Pub . Date : Jun . 18 , 2020 ( 54 ) PERIODONTAL DISEASE STRATIFICATION (52 ) U.S. CI. AND USES THEREOF CPC A61B 5/4552 (2013.01 ) ; G16H 20/10 ( 71) Applicant: The University of North Carolina at ( 2018.01) ; A61B 5/7275 ( 2013.01) ; A61B Chapel Hill , Chapel Hill , NC (US ) 5/7264 ( 2013.01 ) ( 72 ) Inventors: Steven Offenbacher, Chapel Hill , NC (US ) ; Thiago Morelli , Durham , NC ( 57 ) ABSTRACT (US ) ; Kevin Lee Moss, Graham , NC ( US ) ; James Douglas Beck , Chapel Described herein are methods of classifying periodontal Hill , NC (US ) patients and individual teeth . For example , disclosed is a method of diagnosing periodontal disease and / or risk of ( 21) Appl. No .: 16 /713,874 tooth loss in a subject that involves classifying teeth into one of 7 classes of periodontal disease. The method can include ( 22 ) Filed : Dec. 13 , 2019 the step of performing a dental examination on a patient and Related U.S. Application Data determining a periodontal profile class ( PPC ) . The method can further include the step of determining for each tooth a ( 60 ) Provisional application No.62 / 780,675 , filed on Dec. Tooth Profile Class ( TPC ) . The PPC and TPC can be used 17 , 2018 together to generate a composite risk score for an individual, which is referred to herein as the Index of Periodontal Risk Publication Classification ( IPR ) . In some embodiments , each stage of the disclosed (51 ) Int. Cl. PPC system is characterized by unique single nucleotide A61B 5/00 ( 2006.01 ) polymorphisms (SNPs ) associated with unique pathways , G16H 20/10 ( 2006.01 ) identifying unique druggable targets for each stage .
    [Show full text]
  • Nci 2017-09-01 Phase I Trial of Endoxifen Gel Versus
    NWU2017-09-01 Protocol Version 6.5, May 11, 2020 COVER PAGE DCP Protocol #: NWU2017-09-01 Local Protocol #: NCI 2017-09-01 PHASE I TRIAL OF ENDOXIFEN GEL VERSUS PLACEBO GEL IN WOMEN UNDERGOING BREAST SURGERY Consortium Name: Northwestern Cancer Prevention Consortium Organization Name: Northwestern University Name of Consortium Principal Seema A. Khan, M.D. Investigator: 303 E. Superior, Suite 4-111 Chicago, IL 60611 Tel: (312) 503-4236 Fax: (312) 503-2555 E-mail: [email protected] Organization Name: Northwestern University Protocol Principal Seema A. Khan, M.D. Investigator and Protocol Chair: Professor of Surgery 303 E. Superior, Suite 4-111 Chicago, IL 60611 Tel: (312) 503-4236 Fax: (312) 503-2555 E-mail: [email protected] Organization: Memorial Sloan-Kettering Cancer Center Investigator: Melissa Pilewskie, M.D. Evelyn H. Lauder Breast Center 300 East 66th Street New York, NY 10065 Tel: 646-888-4590 Fax: 646-888-4921 E-mail: [email protected] Organization: Cedars-Sinai Medical Center Investigator: Scott Karlan, M.D. Saul and Joyce Brandman Breast Center in the Samuel Oschin Cancer Center 310 N. San Vicente Blvd., Room 314 West Hollywood, CA 90048-1810 Tel: (310) 423-9331 Fax: (310) 423-9339 E-mail: [email protected] Organization: Northwestern University Statistician: Masha Kocherginsky, Ph.D. 680 N. Lake Shore Dr., Suite 1400 –1– NWU2017-09-01 Protocol Version 6.5, May 11, 2020 Chicago, IL 60611 Telephone: (312) 503- 4224 Fax: (312) 908- 9588 Email: [email protected] IND Sponsor: NCI/Division of Cancer Prevention IND# Agent(s)/Supplier: National Cancer Institute NCI Contract # HHSN2612201200035I Protocol Template: Version 8.5 08/31/2016 Protocol Version Date: May 11, 2020 Protocol Revision or Amendment # Version 6.5 –2– NWU2017-09-01 Protocol Version 6.5, May 11, 2020 SCHEMA NWU2017-09-01: Phase I trial of endoxifen gel versus placebo gel in women undergoing breast surgery Women scheduled for mastectomy1 Screening Visit 1 – consent, baseline tests, BESS Q, skin photos 2:1 Randomization in Cohorts 1 and 2.
    [Show full text]
  • Molecular Mechanisms Involved in the Protective Actions of Selective Estrogen Receptor Modulators in Brain Cells
    Molecular mechanisms involved in the protective actions of Selective Estrogen Receptor Modulators in brain cells Baez-Jurado E. Rincón-Benavides M.A. Hidalgo-Lanussa O. Guio-Vega G. Ashraf G.M. Sahebkar A. Echeverria V. Garcia-Segura L.M. Barreto G.E. Synthetic selective modulators of the estrogen receptors (SERMs) have shown to protect neurons and glial cells against toxic insults. Among the most relevant beneficial effects attributed to these compounds are the regulation of inflammation, attenuation of astrogliosis and microglial activation, prevention of excitotoxicity and as a consequence the reduction of neuronal cell death. Under pathological conditions, the mechanism of action of the SERMs involves the activation of estrogen receptors (ERs) and G protein-coupled receptor for estrogens (GRP30). These receptors trigger neuroprotective responses such as increasing the expression of antioxidants and the activation of kinase-mediated survival signaling pathways. Despite the advances in the knowledge of the pathways activated by the SERMs, their mechanism of action is still not entirely clear, and there are several controversies. In this review, we focused on the molecular pathways activated by SERMs in brain cells, mainly astrocytes, as a response to treatment with raloxifene and tamoxifen. © 2018 Elsevier Inc. Astrocytes Brain pathologies Estrogen receptors GRP30 SERMs Tamoxifen afimoxifene cre recombinase droloxifene drug metabolite endoxifen estrogen receptor G protein coupled receptor 30 hydroxytamoxifen inositol 1,4,5 trisphosphate
    [Show full text]
  • Elucidating Binding Sites and Affinities of Erα Agonist and Antagonist to Human Alpha-Fetoprotein by in Silico Modeling and Point Mutagenesis Nurbubu T
    Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 29 December 2019 doi:10.20944/preprints201912.0374.v1 Peer-reviewed version available at Int. J. Mol. Sci. 2020, 21, 893; doi:10.3390/ijms21030893 Elucidating Binding Sites and Affinities of ERα Agonist and Antagonist to Human Alpha-Fetoprotein by in silico Modeling and Point Mutagenesis Nurbubu T. Moldogazieva1*, Daria S. Ostroverkhova1,2, Nikolai N. Kuzmich1,3, Vladimir V. Kadochnikov4, Alexander A. Terentiev5, Yuri B. Porozov1,4 1 Laboratory of Bioinformatics, I.M. Sechenov First Moscow State Medical University (Sechenov University); Moscow, Russia; 2Department of Bioengineering, M.V. Lomonosov Moscow State University; Moscow, Russia; 3Department of Drug Safety, I.M. Smorodintsev Research Institute of Influenza, WHO National Influenza Centre of Russia; Saint Petersburg, Russia 4Department of Information and Communication Technologies, Saint Petersburg National Research University of Information Technologies, Mechanics and Optics; Saint Petersburg, Russia 5Deparment of Biochemistry and Molecular Biology, N.I. Pirogov Russian National Research Medical University; Moscow Russia *Corresponding author: Nurbubu T. Moldogazieva, e-mail: [email protected] (NM) ¶ These authors contributed equally to this work Short title: Binding of ERα ligands to human alpha-fetoprotein Key words: alpha-fetoprotein, estrogens, selective estrogen receptor modulators, homology-based modeling, molecular docking, protein-ligand interaction, amino acid substitutions. Abbreviations: HAFP, human alpha-fetoprotein; HSA, human serum albumin; E2, 17β-estradiol; DES, diethylstilbestrol. Author contribution: Conceptualization, Nurbubu T. Moldogazieva, Alexander A. Terentiev and Yuri B. Porozov; Data curation, Nurbubu T. Moldogazieva; Formal analysis, Nurbubu T. Moldogazieva and Nikolai N. Kuzmich; Investigation, Daria S. Ostroverkhova and Vladimir V. Kadochnikov; Methodology, Nikolai N. Kuzmich; Supervision, Alexander A.
    [Show full text]
  • In Vitro Targeting of Transcription Factors to Control the Cytokine Release Syndrome in 2 COVID-19 3
    bioRxiv preprint doi: https://doi.org/10.1101/2020.12.29.424728; this version posted December 30, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. 1 In vitro Targeting of Transcription Factors to Control the Cytokine Release Syndrome in 2 COVID-19 3 4 Clarissa S. Santoso1, Zhaorong Li2, Jaice T. Rottenberg1, Xing Liu1, Vivian X. Shen1, Juan I. 5 Fuxman Bass1,2 6 7 1Department of Biology, Boston University, Boston, MA 02215, USA; 2Bioinformatics Program, 8 Boston University, Boston, MA 02215, USA 9 10 Corresponding author: 11 Juan I. Fuxman Bass 12 Boston University 13 5 Cummington Mall 14 Boston, MA 02215 15 Email: [email protected] 16 Phone: 617-353-2448 17 18 Classification: Biological Sciences 19 20 Keywords: COVID-19, cytokine release syndrome, cytokine storm, drug repurposing, 21 transcriptional regulators 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.12.29.424728; this version posted December 30, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. 22 Abstract 23 Treatment of the cytokine release syndrome (CRS) has become an important part of rescuing 24 hospitalized COVID-19 patients. Here, we systematically explored the transcriptional regulators 25 of inflammatory cytokines involved in the COVID-19 CRS to identify candidate transcription 26 factors (TFs) for therapeutic targeting using approved drugs.
    [Show full text]
  • Toremifene in Premenstrual Mastalgia
    SINIKKA OKSA Toremifene in Premenstrual Mastalgia ACADEMIC DISSERTATION To be presented, with the permission of the Board of the School of Medicine of the University of Tampere, for public discussion in the Small Auditorium of Building M, Pirkanmaa Hospital District, Teiskontie 35, Tampere, on June 14th, 2013, at 12 o’clock. UNIVERSITY OF TAMPERE ACADEMIC DISSERTATION University of Tampere, School of Medicine Tampere University Hospital, Department of Obstetrics and Gynecology Satakunta Central Hospital, Department of Obstetrics and Gynecology Finland Supervised by Reviewed by Professor Johanna Mäenpää Docent Tiina Saarto University of Tampere University of Helsinki Finland Finland Professor Aila Tiitinen University of Helsinki Finland Copyright ©2013 Tampere University Press and the author Cover design by Mikko Reinikka Layout Marita Alanko Acta Universitatis Tamperensis 1832 Acta Electronica Universitatis Tamperensis 1310 ISBN 978-951-44-9144-3 (print) ISBN 978-951-44-9145-0 (pdf) ISSN-L 1455-1616 ISSN 1456-954X ISSN 1455-1616 http://tampub.uta.fi Suomen Yliopistopaino Oy – Juvenes Print Tampere 2013 To Janne, Siiri, and Jenni CONTENTS LIST OF ORIGINAL COMMUNICATIONS 9 ABBREVIATIONS 11 ABSTRACT 13 TIIVISTELMÄ 15 1 INTRODUCTION 17 2 REVIEW OF THE LITERATURE 19 2.1 Development and anatomy of the breast 19 2.1.1 Arterial supply and venous drainage 21 2.1.2 Lymphatic drainage 21 2.1.3 Innervation 21 2.2 Mastalgia 22 2.2.1 Classification 22 2.2.1.1 Cyclic pain 22 2.2.1.2 Noncyclical pain 22 2.2.1.3 Extramammary pain 22 2.3 Prevalence and
    [Show full text]
  • Atossa Genetics Clinical Update
    Atossa Genetics Clinical update Endoxifen to start Phase II studies shortly Pharma & biotech 26 April 2018 Atossa Genetics is preparing to start Phase II studies of both its oral and topical endoxifen formulations in Q218. Endoxifen, an estrogen receptor Price US$3.72 (ER) antagonist, is being advanced in topical form to treat high Market cap US$10m mammographic breast density (MBD), and also as an oral drug to prevent cancer recurrence in women refractory to tamoxifen. The company plans Estimated net cash ($m) at Q118 5.2 to raise $20m in equity through a rights offering in May 2018, which we Shares in issue 2.65m believe should fund the Phase II endoxifen trials through completion. Free float 99% Code ATOS Revenue PBT* EPS* DPS P/E Yield Year end ($m) ($m) ($) ($) (x) (%) Primary exchange NASDAQ 12/16 0.0 (7.2) (29.52) 0.0 N/A N/A 12/17 0.0 (7.2) (10.01) 0.0 N/A N/A Secondary exchange N/A 12/18e 0.0 (11.2) (4.23) 0.0 N/A N/A 12/19e 0.0 (7.2) (2.70) 0.0 N/A N/A Share price performance Note: *PBT and EPS are normalised, excluding amortisation of acquired intangibles, exceptional items and share-based payments. More rapid steady-state levels with oral endoxifen In February 2018, Atossa reported new data from its prior Phase I study, suggesting that the median time for patients to reach the steady-state serum levels of endoxifen while taking daily oral doses was seven days vs 50-200 days for patients taking oral tamoxifen daily.
    [Show full text]
  • Screen of FDA-Approved Drug Library Reveals Compounds That Protect Hair Cells from Aminoglycosides and Cisplatin
    Hearing Research 294 (2012) 153e165 Contents lists available at SciVerse ScienceDirect Hearing Research journal homepage: www.elsevier.com/locate/heares Research paper Screen of FDA-approved drug library reveals compounds that protect hair cells from aminoglycosides and cisplatin Anna L. Vlasits a,b,1, Julian A. Simon d, David W. Raible a,c, Edwin W. Rubel a,b, Kelly N. Owens a,b,* a Virginia Merrill Bloedel Hearing Research Center, University of Washington, Box 357923, Seattle, WA 98195-7923, USA b Department of Otolaryngology Head & Neck Surgery, University of Washington, Box 356161, Seattle, WA 98195, USA c Department of Biological Structure, University of Washington, Box 357420, Seattle, WA 98195, USA d Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA article info abstract Article history: Loss of mechanosensory hair cells in the inner ear accounts for many hearing loss and balance disorders. Received 23 April 2012 Several beneficial pharmaceutical drugs cause hair cell death as a side effect. These include amino- Received in revised form glycoside antibiotics, such as neomycin, kanamycin and gentamicin, and several cancer chemotherapy 17 July 2012 drugs, such as cisplatin. Discovering new compounds that protect mammalian hair cells from toxic Accepted 9 August 2012 insults is experimentally difficult because of the inaccessibility of the inner ear. We used the zebrafish Available online 31 August 2012 lateral line sensory system as an in vivo screening platform to survey a library of FDA-approved phar- maceuticals for compounds that protect hair cells from neomycin, gentamicin, kanamycin and cisplatin. Ten compounds were identified that provide protection from at least two of the four toxins.
    [Show full text]