Pure Oestrogen Antagonists for the Treatment of Advanced Breast Cancer

Total Page:16

File Type:pdf, Size:1020Kb

Pure Oestrogen Antagonists for the Treatment of Advanced Breast Cancer Endocrine-Related Cancer (2006) 13 689–706 REVIEW Pure oestrogen antagonists for the treatment of advanced breast cancer Anthony Howell CRUK Department of Medical Oncology, University of Manchester, Christie Hospital NHS Trust, Manchester M20 4BX, UK (Requests for offprints should be addressed to A Howell; Email: [email protected]) Abstract For more than 30 years, tamoxifen has been the drug of choice in treating patients with oestrogen receptor (ER)-positive breast tumours. However, research has endeavoured to develop agents that match and improve the clinical efficacy of tamoxifen, but lack its partial agonist effects. The first ‘pure’ oestrogen antagonist was developed in 1987; from this, an even more potent derivative was developed for clinical use, known as fulvestrant (ICI 182,780, ‘Faslodex’). Mechanistic studies have shown that fulvestrant possesses high ER-binding affinity and has multiple effects on ER signalling: it blocks dimerisation and nuclear localisation of the ER, reduces cellular levels of ER and blocks ER-mediated gene transcription. Unlike anti-oestrogens chemically related to tamoxifen, fulvestrant also helps circumvent resistance to tamoxifen. There are extensive data to support the lack of partial agonist effects of fulvestrant and, importantly, its lack of cross-resistance with tamoxifen. In phase III studies in patients with locally advanced or metastatic breast cancer, fulvestrant was at least as effective as anastrozole in patients with tamoxifen-resistant tumours, was effective in the first-line setting and was also well tolerated. These data are supported by experience from the compassionate use of fulvestrant in more heavily pretreated patients. Further studies are now underway to determine the best strategy for sequencing oestrogen endocrine therapies and to optimise dosing regimens offulvestrant. At present, and for the foreseeable future, fulvestrant is the only oestrogen antagonist with no agonistic effects licensed for the treatment of advanced breast cancer in postmenopausal women. Other similar oestrogen antagonists are undergoing research and development, with a few currently being evaluated in phase II trials. Endocrine-Related Cancer (2006) 13 689–706 Background use. As such, research has endeavoured to develop The critical role played by oestrogen in breast cancer agents that are at least as effective as tamoxifen but has driven a huge amount of research into the which lack its partial agonist effects. development of hormonal therapies that are able to First-generation selective ER modulators (SERMs, block oestrogen-mediated cell signalling. For more e.g. toremifene, droloxifene and idoxifene) were based than 30 years, tamoxifen, a non-steroidal triphenyl- on the non-steroidal triphenylethylene structure of ethylene derivative (Fig. 1), has been the drug of tamoxifen (Wakeling 2000). These agents have no choice in treating patients with oestrogen receptor efficacy benefits over tamoxifen and also show partial (ER)-positive and/or progesterone receptor (PgR)- agonist activity (Pyrhonen et al. 1994, Lee et al. 2000, positive tumours. Not only is tamoxifen effective in Buzdar et al. 2002), with some studies suggesting there patients with breast cancer, it also reduces the is cross-resistance ‘between’ first-generation SERMs incidence of disease in healthy women at high risk of and tamoxifen (Haarstad et al. 1992, Stenbygaard et al. developing breast cancer (Cuzick et al. 2003). The 1993, Pyrhonen et al. 1994, 1997, 1999, Hayes et al. success of tamoxifen has been achieved despite its 1995, Gershanovich et al. 1997, Lee et al. 2000, partial agonist activity, which is associated with Johnston et al. 2001, MillaSantos et al. 2001). increased risk of endometrial cancer, thromboembolic Disappointing efficacy data for both droloxifene and events and tumour flare, particularly with long-term idoxifene when compared with tamoxifen or when Endocrine-Related Cancer (2006) 13 689–706 Downloaded from Bioscientifica.comDOI: 10.1677/erc.1.00846 at 09/27/2021 10:26:15PM 1351-0088/06/013–689 q 2006 Society for Endocrinology Printed in Great Britain Online version via http://www.endocrinology-journals.orgvia free access A Howell: Pure anti-oestrogens in advanced breast cancer Figure 1 Chemical structures of oestradiol, tamoxifen, fulvestrant and raloxifene. used in tamoxifen-resistant disease have led to their of steroidal 7a-alkylamide analogues of oestradiol. development being halted. Toremifene (chloro-tamox- Of these, ICI 164,384 was the first pure oestrogen ifen), which has similar efficacy but fewer agonist antagonist to be described, completely blocking the properties compared with tamoxifen (Marttunen et al. uterotrophic action of both oestradiol and tamoxifen in 1998, 2001), remains in clinical development in the rats (Wakeling & Bowler 1987). Following this, a far breast cancer prevention setting. more potent pure oestrogen antagonist was developed, Structurally distinct second- and third-generation ICI 182,780, which is now known as fulvestrant SERMs (‘fixed-ring’ benzothiophene derivatives (‘Faslodex’) (Fig. 1)(Wakeling et al. 1991). At present (Fig. 1)) such as raloxifene, arzoxifene and ERA- (and for the foreseeable future), fulvestrant, an 923 were then developed. Most of these have oestrogen antagonist with no agonist effects, is licensed demonstrated anti-tumour activity in breast cancer for the treatment of advanced breast cancer in but also have some partial agonist activity (Buzdar postmenopausal women. Therefore, this paper will et al. 1988, Gradishar et al. 2000, Munster et al. 2001, describe in detail the mode of action of fulvestrant, Buzdar et al. 2003). Results from the Study of and explore how this underlies its clinical efficacy, Tamoxifen and Raloxifene (STAR) trial, one of the tolerability and safety profile in the treatment of largest breast cancer prevention studies, which has advanced breast cancer. In considering the future recruited 19 000 postmenopausal women at risk of directions for oestrogen-antagonistic agents, ongoing breast cancer, are expected in 2006. Based on its clinical trials with fulvestrant will be reviewed. The partial oestrogen agonist effects (Delmas et al. 1997), current status of other ‘pure’ oestrogen antagonists in raloxifene is also currently being used for the preclinical and clinical development will also be prevention and treatment of osteoporosis and breast described. cancer. Arzoxifene showed promising initial results in a phase II study in advanced breast cancer, although its efficacy was greater in tamoxifen-sensitive than Mode of action tamoxifen-resistant disease (Buzdar et al. 2003). Results from a phase I study suggest that ERA-923 ER-mediated signalling has no trophic effects on the uterus (Cotreau et al. The biological actions of oestrogen are mediated by 2002), and its role in patients with breast cancer is two subtypes of ER, ERa and ERb. Both receptors currently being investigated. belong to a family of ligand-activated nuclear The search for novel agents that would completely transcription factors (Evans 1988) and share a high block all ER signalling led to the synthesis of a series degree of homology in their DNA binding domains Downloaded from Bioscientifica.com at 09/27/2021 10:26:15PM via free access 690 www.endocrinology-journals.org Endocrine-Related Cancer (2006) 13 689–706 (Kuiper et al. 1996). However, they differ considerably to promoters of responsive genes. Genes that are in their N-terminal regions, which contain the ligand- regulated by oestrogen but do not have an ERE include independent transcription activation function, AF1 cyclin D1, p21 and the PgR (Shupnik 2004). Many (Kuiper et al. 1996). These differences suggest that such genes are regulated via ER interactions with ERa and ERb could have distinct functions in terms of stimulating protein 1 (Sp1), the signal transducers and gene regulation and may contribute to the selec- activators of transcription (STAT) family of transcrip- tive action of oestradiol in different target tissues tion factors and transcription factors associated with (Gustafsson & Warner 2000). There is evidence from activating protein 1 (AP1) sites. The AP1 transcription in vitro studies to suggest that imbalanced ERa/ERb factors are a family of homo- and heterodimers expression may be a feature of oestrogen-dependent composed of proteins that belong to the Jun, Fos, tumour progression and that ERb has a key role in Maf and ATF subfamilies that bind to 12-0-tetra- providing protection against ERa-induced hyperproli- decanoylphorbol-13-acetate (TPA) response elements feration (Bardin et al. 2004). It has also been suggested (TRE) or cAMP response elements (CRE) in target that ERb may be a dominant regulator of oestrogen genes (Chinenov & Kerppola 2001). The c-Jun signalling as it causes a dose-dependent reduction homodimer is the most potent transcriptional activator in ERa-mediated transcription when coexpressed with in the AP1 family (Matthews et al. 2006). ERa (Lindberg et al. 2003). While both ERa and ERb can bind oestradiol and activate transcription through an ERE, they have Classical pathway of ER signalling differential transcriptional activities at Sp1 and AP1 sites. Only ERa can stimulate genes via the Sp1 In classical ER signalling, unbound ER can be nuclear pathway and the two isoforms are differentially localised and bound loosely to the oestrogen response regulated by oestrogens and antioestrogens at AP1 elements (ERE) (Kumar & Chambon 1988, Reese & sites (Shupnik
Recommended publications
  • 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]
  • Cytoplasmic Localization of RXR Determines Outcome in Breast
    cancers Article Cytoplasmic Localization of RXRα Determines Outcome in Breast Cancer Alaleh Zati zehni 1,†, Falk Batz 1,†, Vincent Cavaillès 2 , Sophie Sixou 3,4, Till Kaltofen 1 , Simon Keckstein 1, Helene Hildegard Heidegger 1, Nina Ditsch 5, Sven Mahner 1, Udo Jeschke 1,5,* and Theresa Vilsmaier 1 1 Department of Obstetrics and Gynecology, University Hospital Munich LMU, 81377 Munich, Germany; [email protected] (A.Z.z.); [email protected] (F.B.); [email protected] (T.K.); [email protected] (S.K.); [email protected] (H.H.H.); [email protected] (S.M.); [email protected] (T.V.) 2 IRCM—Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université Montpellier, Parc Euromédecine, 208 rue des Apothicaires, CEDEX 5, F-34298 Montpellier, France; [email protected] 3 Faculté des Sciences Pharmaceutiques, Université Paul Sabatier Toulouse III, CEDEX 09, 31062 Toulouse, France; [email protected] 4 Cholesterol Metabolism and Therapeutic Innovations, Cancer Research Center of Toulouse (CRCT), UMR 1037, Université de Toulouse, CNRS, Inserm, UPS, 31037 Toulouse, France 5 Department of Obstetrics and Gynecology, University Hospital, 86156 Augsburg, Germany; [email protected] * Correspondence: [email protected]; Tel.: +49-8214-0016-5505 † These authors equally contributed to this work. Citation: Zati zehni, A.; Batz, F.; Cavaillès, V.; Sixou, S.; Kaltofen, T.; Simple Summary: Considering the immense development of today’s therapeutic approaches in on- Keckstein, S.; Heidegger, H.H.; Ditsch, cology towards customized therapy, this study aimed to assess the prognostic value of nuclear versus N.; Mahner, S.; Jeschke, U.; et al.
    [Show full text]
  • In Vitro and in Silico Analyses of the Inhibition of Human Aldehyde Oxidase By
    JPET Fast Forward. Published on July 9, 2019 as DOI: 10.1124/jpet.119.259267 This article has not been copyedited and formatted. The final version may differ from this version. JPET #259267 In Vitro and In Silico Analyses of the Inhibition of Human Aldehyde Oxidase by Bazedoxifene, Lasofoxifene, and Structural Analogues Shiyan Chen, Karl Austin-Muttitt, Linghua Harris Zhang, Jonathan G.L. Mullins, and Aik Jiang Lau Downloaded from Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore jpet.aspetjournals.org (S.C., A.J.L.); Institute of Life Science, Swansea University Medical School, United Kingdom (K.A-M, J.G.L.M.); NanoBioTec, LLC., Whippany, New Jersey, U.S.A. (L.H.Z.); at ASPET Journals on September 29, 2021 Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore (A.J.L.) 1 JPET Fast Forward. Published on July 9, 2019 as DOI: 10.1124/jpet.119.259267 This article has not been copyedited and formatted. The final version may differ from this version. JPET #259267 Running Title In Vitro and In Silico Analyses of AOX Inhibition by SERMs Corresponding author: Dr. Aik Jiang Lau Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, Singapore 117543. Downloaded from Tel.: 65-6601 3470, Fax: 65-6779 1554; E-mail: [email protected] jpet.aspetjournals.org Number of text pages: 35 Number of tables: 4 Number of figures: 8 at ASPET Journals on September 29, 2021 Number of references 60 Number of words in Abstract (maximum
    [Show full text]
  • Pharmaceutical Appendix to the Tariff Schedule 2
    Harmonized Tariff Schedule of the United States (2007) (Rev. 2) Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States (2007) (Rev. 2) 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. ABACAVIR 136470-78-5 ACIDUM LIDADRONICUM 63132-38-7 ABAFUNGIN 129639-79-8 ACIDUM SALCAPROZICUM 183990-46-7 ABAMECTIN 65195-55-3 ACIDUM SALCLOBUZICUM 387825-03-8 ABANOQUIL 90402-40-7 ACIFRAN 72420-38-3 ABAPERIDONUM 183849-43-6 ACIPIMOX 51037-30-0 ABARELIX 183552-38-7 ACITAZANOLAST 114607-46-4 ABATACEPTUM 332348-12-6 ACITEMATE 101197-99-3 ABCIXIMAB 143653-53-6 ACITRETIN 55079-83-9 ABECARNIL 111841-85-1 ACIVICIN 42228-92-2 ABETIMUSUM 167362-48-3 ACLANTATE 39633-62-0 ABIRATERONE 154229-19-3 ACLARUBICIN 57576-44-0 ABITESARTAN 137882-98-5 ACLATONIUM NAPADISILATE 55077-30-0 ABLUKAST 96566-25-5 ACODAZOLE 79152-85-5 ABRINEURINUM 178535-93-8 ACOLBIFENUM 182167-02-8 ABUNIDAZOLE 91017-58-2 ACONIAZIDE 13410-86-1 ACADESINE 2627-69-2 ACOTIAMIDUM 185106-16-5 ACAMPROSATE 77337-76-9
    [Show full text]
  • 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 .
    [Show full text]
  • Treatment of Moderate to Severe Dyspareunia with Intravaginal Prasterone Therapy: a Review
    Climacteric ISSN: 1369-7137 (Print) 1473-0804 (Online) Journal homepage: https://www.tandfonline.com/loi/icmt20 Treatment of moderate to severe dyspareunia with intravaginal prasterone therapy: a review D. J. Portman, S. R. Goldstein & R. Kagan To cite this article: D. J. Portman, S. R. Goldstein & R. Kagan (2019) Treatment of moderate to severe dyspareunia with intravaginal prasterone therapy: a review, Climacteric, 22:1, 65-72, DOI: 10.1080/13697137.2018.1535583 To link to this article: https://doi.org/10.1080/13697137.2018.1535583 © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group View supplementary material Published online: 17 Dec 2018. Submit your article to this journal Article views: 575 View Crossmark data Full Terms & Conditions of access and use can be found at https://www.tandfonline.com/action/journalInformation?journalCode=icmt20 CLIMACTERIC 2019, VOL. 22, NO. 1, 65–72 https://doi.org/10.1080/13697137.2018.1535583 REVIEW Treatment of moderate to severe dyspareunia with intravaginal prasterone therapy: a review D. J. Portmana,b, S. R. Goldsteinc and R. Kagand,e aColumbus Center for Women’s Health Research, Columbus, OH, USA; bSermonix Pharmaceuticals, Columbus, OH, USA; cDepartment of Obstetrics and Gynecology, New York University School of Medicine, New York, NY, USA; dDepartment of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, CA, USA; eSutter East Bay Medical Foundation, Berkeley, CA, USA ABSTRACT ARTICLE HISTORY The loss of sex steroids (e.g. estradiol, dehydroepiandrosterone [DHEA], progesterone) that causes Received 11 May 2018 menopause commonly affects a woman’s general health and produces bothersome physical changes Revised 25 September 2018 that may interfere with normal sexual and genitourinary functioning.
    [Show full text]
  • Abnormal Uterine Bleeding, 108, 113 Acupuncture, 159-160
    Cambridge University Press 978-1-107-45182-7 - Managing the Menopause: 21st Century Solutions Edited by Nick Panay, Paula Briggs and Gab Kovacs Index More information Index abnormal uterine bleeding, 108, American Society of Clinical potential role as reproductive 113 Oncology (ASCO) biomarker, 6 acupuncture, 159–160 guidelines, 143 predicting the menopause, adenomyosis American Society of 14–17 effects of the menopause, 108 Reproductive Medicine, anti-ovarian antibodies, 16 management, 115 198 antral follicle count (AFC), 16 pathophysiology, 109 androgen therapy antral follicles, 2 aging adverse events in women, anxiety and risk of VTE, 185 139–140 cognitive behavior therapy and sexual decline, 104 androgen physiology in (CBT), 88 risk factor for CVD, 36 women, 137 Aristotle, 20 Albright, Fuller, 58 causes of androgen asoprisnil, 125 alendronate, 76–77 insufficiency in women, assisted reproduction, 13–14, alternative therapies 137–138 16 claims made by proponents, considerations when oocyte vitrification, 17–18 158 prescribing for FSD, atherosclerosis, 38 common misunderstandings 140–141 atractylodes in herbal medicine, about, 161 description, 136–137 22 definition, 157 DHEA, 136 atrophic vaginitis direct risks, 159 effectiveness in treating FSD, definition, 52 evidence for effectiveness, 138–139 local estrogen therapies, 48 158–159 for female sexual dysfunction See also vulvo-vaginal expectations of users, (FSD), 137 atrophy. 157–158 indications for, 137 autoimmune disease extent of use for menopausal postmenopausal therapies, and premature
    [Show full text]
  • Lääkeaineiden Yleisnimet (INN-Nimet) 21.6.2021
    Lääkealan turvallisuus- ja kehittämiskeskus Säkerhets- och utvecklingscentret för läkemedelsområdet Finnish Medicines Agency Lääkeaineiden yleisnimet (INN-nimet) 21.6.
    [Show full text]
  • Nontargeted Discovery of Xenobiotics in Human Urine by Maldi-Tof/Tof-Ms
    NONTARGETED DISCOVERY OF XENOBIOTICS IN HUMAN URINE BY MALDI-TOF/TOF-MS Dissertation Presented by Yuanyuan Yao To The Bouve’ Graduate School of Health Sciences in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy in Pharmaceutical Sciences with specialization in Biomedical Sciences NORTHEASTERN UNIVERSITY BOSTON, MASSACHUSETTS April 2018 ABSTRACT In this dissertation research, nontargeted analysis of the urine metabolome, including xenobiotics, was studied using LC (Liquid Chromatography)-MALDI (Matrix Assisted Laser Desorption Ionization) MS (Mass Spectrometry) techniques. MALDI is a sensitive soft ionization MS technique that has been mainly used to analyze large molecules such as peptides, proteins, and nucleic acids. Here, MALDI MS methods were employed for detection of urine metabolites. To increase the recovery of nonpolar metabolites, a novel porous extraction paddle (PEP) was validated with co-workers and used for urine extraction. A method for sample preparation including UHPLC (Ultra High-Performance Liquid Chromatography) was optimized to facilitate detection of nonpolar urine sulfate metabolites by MALDI MS. Using this approach, the detection coverage of such compounds was greatly expanded as compared to prior methods. Detection of 1129 MS precursor ions corresponding to putative sulfate and glucuronide metabolites was achieved. Combining MS and MS/MS experiments, a strategy was developed for tentative identification of the detected metabolites. This led to the first nontargeted analysis of environmental contaminants in urine. It was shown that the detection sensitivity of positive-mode MALDI MS can be enhanced using enzymatic deconjugation and cationic tagging methods. Also, an evaporative derivatization method was developed to increase the sensitivity of negative-mode MALDI MS for detection of phenolic compounds.
    [Show full text]
  • Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DIX to the HTSUS—Continued
    20558 Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DEPARMENT OF THE TREASURY Services, U.S. Customs Service, 1301 TABLE 1.ÐPHARMACEUTICAL APPEN- Constitution Avenue NW, Washington, DIX TO THE HTSUSÐContinued Customs Service D.C. 20229 at (202) 927±1060. CAS No. Pharmaceutical [T.D. 95±33] Dated: April 14, 1995. 52±78±8 ..................... NORETHANDROLONE. A. W. Tennant, 52±86±8 ..................... HALOPERIDOL. Pharmaceutical Tables 1 and 3 of the Director, Office of Laboratories and Scientific 52±88±0 ..................... ATROPINE METHONITRATE. HTSUS 52±90±4 ..................... CYSTEINE. Services. 53±03±2 ..................... PREDNISONE. 53±06±5 ..................... CORTISONE. AGENCY: Customs Service, Department TABLE 1.ÐPHARMACEUTICAL 53±10±1 ..................... HYDROXYDIONE SODIUM SUCCI- of the Treasury. NATE. APPENDIX TO THE HTSUS 53±16±7 ..................... ESTRONE. ACTION: Listing of the products found in 53±18±9 ..................... BIETASERPINE. Table 1 and Table 3 of the CAS No. Pharmaceutical 53±19±0 ..................... MITOTANE. 53±31±6 ..................... MEDIBAZINE. Pharmaceutical Appendix to the N/A ............................. ACTAGARDIN. 53±33±8 ..................... PARAMETHASONE. Harmonized Tariff Schedule of the N/A ............................. ARDACIN. 53±34±9 ..................... FLUPREDNISOLONE. N/A ............................. BICIROMAB. 53±39±4 ..................... OXANDROLONE. United States of America in Chemical N/A ............................. CELUCLORAL. 53±43±0
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2001/0047033 A1 Taylor Et Al
    US 20010047033A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2001/0047033 A1 Taylor et al. (43) Pub. Date: Nov. 29, 2001 (54) COMPOSITION FOR AND METHOD OF Publication Classification PREVENTING OR TREATING BREAST CANCER (51) Int. Cl." ........................ A61K 31/35; A61K 31/138 (52) U.S. Cl. ............................................ 514/456; 514/651 (75) Inventors: Richard B. Taylor, Valley Park, MO (US); Edna C. Henley, Athens, GA (57) ABSTRACT (US) The present invention is a composition for preventing, Correspondence Address: minimizing, or reversing the development or growth of Richard B. Taylor breast cancer. The composition contains a combination of a Protein Technologies International, Inc. Selective estrogen receptor modulator Selected from at least P.O. BOX 88940 one of raloxifene, droloxifene, toremifene, 4'-iodotamox St. Louis, MO 63188 (US) ifen, and idoxifene and at least one isoflavone Selected from genistein, daidzein, biochanin A, formononetin, and their (73) Assignee: Protein Technologies International, respective naturally occurring glucosides and glucoside con Inc., St. Louis, MO jugates. The present invention also provides a method of (21) Appl. No.: 09/900,573 preventing, minimizing, or reversing the development or growth of breast cancer in which a Selective estrogen (22) Filed: Jul. 6, 2001 receptor modulator Selected from at least one of raloxifene, droloxifene, toremifene, 4'-iodotamoxifen, and idoxifene is Related U.S. Application Data co-administered with at least one isoflavone Selected from genistein, daidzein, biochanin A, formononetin, and their (62) Division of application No. 09/294,519, filed on Apr. naturally occuring glucosides and glucoside conjugates to a 20, 1999. woman having or predisposed to having breast cancer.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 8,158,152 B2 Palepu (45) Date of Patent: Apr
    US008158152B2 (12) United States Patent (10) Patent No.: US 8,158,152 B2 Palepu (45) Date of Patent: Apr. 17, 2012 (54) LYOPHILIZATION PROCESS AND 6,884,422 B1 4/2005 Liu et al. PRODUCTS OBTANED THEREBY 6,900, 184 B2 5/2005 Cohen et al. 2002fOO 10357 A1 1/2002 Stogniew etal. 2002/009 1270 A1 7, 2002 Wu et al. (75) Inventor: Nageswara R. Palepu. Mill Creek, WA 2002/0143038 A1 10/2002 Bandyopadhyay et al. (US) 2002fO155097 A1 10, 2002 Te 2003, OO68416 A1 4/2003 Burgess et al. 2003/0077321 A1 4/2003 Kiel et al. (73) Assignee: SciDose LLC, Amherst, MA (US) 2003, OO82236 A1 5/2003 Mathiowitz et al. 2003/0096378 A1 5/2003 Qiu et al. (*) Notice: Subject to any disclaimer, the term of this 2003/OO96797 A1 5/2003 Stogniew et al. patent is extended or adjusted under 35 2003.01.1331.6 A1 6/2003 Kaisheva et al. U.S.C. 154(b) by 1560 days. 2003. O191157 A1 10, 2003 Doen 2003/0202978 A1 10, 2003 Maa et al. 2003/0211042 A1 11/2003 Evans (21) Appl. No.: 11/282,507 2003/0229027 A1 12/2003 Eissens et al. 2004.0005351 A1 1/2004 Kwon (22) Filed: Nov. 18, 2005 2004/0042971 A1 3/2004 Truong-Le et al. 2004/0042972 A1 3/2004 Truong-Le et al. (65) Prior Publication Data 2004.0043042 A1 3/2004 Johnson et al. 2004/OO57927 A1 3/2004 Warne et al. US 2007/O116729 A1 May 24, 2007 2004, OO63792 A1 4/2004 Khera et al.
    [Show full text]