DOCSLIB.ORG

Meo Meo C Meo US 6,794,384 B1 Page 2

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Meo Meo C Meo US 6,794,384 B1 Page 2 USOO6794384B1 (12) United States Patent (10) Patent No.: US 6,794,384 B1 Potter et al. (45) Date of Patent: Sep. 21, 2004 (54) HYDROXYLATION ACTIVATED DRUG 6,214,886 B1 4/2001 Potter et al. ................ 514/685 RELEASE 6,346,550 B2 2/2002 Potter et al. ...... ... 514/685 2002/0037296 A1 3/2002 Potter et al. ................ 424/400 (75) Inventors: Gerard Andrew Potter, Leicester (GB); Lawrence Hylton Patterson, FOREIGN PATENT DOCUMENTS Leicester (GB); Michael Danny Burke, CA 2109259 4/1994 Leicester (GB) DE 4309344 9/1949 DE 4236237 4/1994 (73) Assignee: De Montfort University, Leicester EP O322 738 A2 7/1989 EP O642799 3/1995 (GB) JP 56/O16474 A2 * 2/1981 JP 56O16474 2/1981 ......... CO7D/239/54 (*) Notice: Subject to any disclaimer, the term of this JP 61076433 4/1986 patent is extended or adjusted under 35 JP O81885.46 7/1996 U.S.C. 154(b) by 0 days. WO 971.2246 4/1997 WO WO 99/40056 8/1999 (21) Appl. No.: 09/633,697 WO WO 99/40944 8/1999 (22) Filed: Aug. 7, 2000 OTHER PUBLICATIONS Draetta, G. and Pagano, M. in “Annual Reports in Medicinal Related U.S. Application Data Chemistry, vol. 31, 1996, Academic Press, San Diego, p (63) Continuation of application No. PCT/GB99/00416, filed on 241-248. Feb. 10, 1999. Wolff, Manfred E. “Burger's Medicinal Chemistry, 5ed, Part I”, John Wiley & Sons, 1995, pp. 975–977.* (30) Foreign Application Priority Data Banker, G.S. et al., “Modern Pharmaceutics, 3ed.'', Marcel Feb. 12, 1998 (GB) ............................................. 98O2957 Dekker, New York, 1996, p. 596.* Shan, Daxian, et al., J. Pharmaceutical Sci., 1997, 86, pp. (51) Int. Cl." .................. C07C 271/14: CO7D 239/553; 765-767.* A61K 31/27; A61P 35/00 (52) U.S. Cl. .................... 514/229.8; 514/274; 514/457; (List continued on next page.) 514/481; 514/489; 514/512; 54.4/102; 54.4/313; Primary Examiner Mark L. Berch 549/399; 558/271; 560/161 ASSistant Examiner Thomas McKenzie (58) Field of Search ................................. 514/229, 274, (74) Attorney, Agent, or Firm-Baker Botts, L.L.P 514/457, 481, 489, 512; 54.4/102,313; 549/399; 558/271; 560/161 (57) ABSTRACT The present invention concerns prodrugs whose aromatic (56) References Cited oxidation, particularly their enzymatic aromatic U.S. PATENT DOCUMENTS hydroxylation, results in their activation by the release of a drug moiety. It particularly concerns anti-tumor prodrugs 5,276,058 A 1/1994 Satoh et al. ................ 514/646 5,287,386 A 2/1994 Wade et al. .................. 375/36 and those which are Specifically activated by the hydroxy 5,430,062 A 7/1995 Cushman et al. ........... 514/646 lation activity of the P-450 enzyme CYP1B1. Also provided 5,471,170 A 11/1995 Genest ....................... 330/151 are methods of detection of aromatic Oxidation activity. 5,773,435 A 6/1998 Kadow et al. .............. 514/214 5,966.032 A 10/1999 Elrabaa et al. ................ 326/84 13 Claims, 3 Drawing Sheets MeO MeO MeO MC OH °N MeO MeO c MeO US 6,794,384 B1 Page 2 OTHER PUBLICATIONS Cushman M et al., 1992, XP-000571677, “Synthesis and Evaluation of Analogues of Amble, Erik, Dale, Johannes, Acta Chem. Scand., Ser. B, (Z)-1-(4-Methoxyphenyl)-2-(3,4,5-trimethoxyphe B533(8), 584–6 (English) 1979.* nyl)ethene as Potential Cytotoxic and Antimitotic Agents' J. Pamer, Eric G.; So, Magdalene; Davis, Charles E., Mol. Med. Chem. 35(12):2293–2306. Biochem. Parasitol., 33(1), 27–32 (English) 1989.* Doehmer J et al., 1991, “Chinese Hamster Cells Genetically Buur, Anders; Bundgaard, Hans, Arch. Pharm. Chemi, Sci. Engineered for Stable Expression of Cytochromes P450” Ed., 12(2), 37–44 (English) 1984.* Meth. Enzymol. 206:117-122. Suda, Yasuo, ShimidZu, Kenji, Sumi, Masao, Kusumoto, Shoichi, Nadai, Tanekazu; Yamashita, Shinji, Biol. Pharm. Hussoin Set al., 1991, XP-002102894, “Polyhydroxylated Bull., 16(3), 322-4 (English) 1993.* Phenylacrylic Acid Derivatives as New Anti-tumor Agents' Hoang TTV et al., 2001, “Cytochrome P450 CYP1B1 J. Pharmaceut. Sci. 80(5):416–418. Expression in Human Cervical Intraepithelial Neoplasia” Barrie et al., 1989, “Inhibition of 17O-Hydroxylase/ British Journal of Cancer 85(Suppl 1):78. C17-C20 Lyase. By Bifluranol And Its Analogues' J. Steroid Stanley LA et al., 2001, “Cytochrome P450 Cyp1b1 In Biochem. 33(6):1191–1195. Colon Tumorigenesis' Drug Metabolism Reviews 33(suppl Pamer EG et al., 1989, “Identification of a developmentally 1):62. regulated cysteine protease of TrypanoSoma brucei' Mol. Suda Yet al., 2001, “Chemical and biological degradation of and Biochem. Parasitology 33:27-32. 5-fluorouracil prodrugs having high Serum albumin binding potencies”, L3 Answer 1 of 1 Chem. Abstract 119:62362. Carmichael J et al., 1987, "Evaluation of a Tetrozolium Buur Aet al., 2001, “Prodrugs of 5-fluorouracil, II. Hydroly based Semiautomated Colorimetric ASSay: ASSeSSment of Sis kinetics, bioactivation, Solubility and lipophilicity on Chemosensitivity Testing Cancer Res. 47:936-942. N-alkoxycarbonyl derivatives of 5-fluorouracil” L2 Answer Eckert H et al., 1987, “Triphosgene, a Crystalline Phosgene 1 of 1 Chen. Abstract 102:12247. Substitute” Angew, Chem. Int. Ed. Engl. 26(9):894–895. Tang YM et al., 2000, “Human CYP1B1 Leu432Val gene polymorphism: ethnic distribution in African-Americans, Burke MD et al., 1985, “Ethoxy-, pentoxy- and benzylox Caucasians and Chinese, oestradiol hydroxylase activity; yphenoxazones and homologues: a Series of Substrates to and distribution in prostate cancer cases and controls” distinguish between different induced cytochromes P-450” Pharmacogenetics 10(9):761-766. Biochem Pharmacol 34(18):3337–3345. Iyer S et al., 1998, “Induction of Apoptosis in Proliferating Amble E et al., 1979, "Formation of 2-Oxazolidinones from Human Endothelial Cells by the Tumor-specific Antiangio N-Benzyloxycarbonyl-2,2'-dichlorodiethylamine; Demon genesis Agent Combretastatin A-4 Cancer ReS. stration of Chloride Catalysis’ Acta Chem. Scand. 58:4510-4514. 33(8):584–586. Ducki Set al., 1998, “Potent Antimitotic and Cell Growth 1978, “I.26 Fractional Distillation. At Atmospheric Pressure” Inhibitory Properties of Substituted Chalcones' Bioorg. Vogels Textbook of Practical Organic Chemistry, 4th Ed. Med. Chem. Letters 8(9): 1051–1056. 878:146-155. Luch A et al., 1998, “Stable Expression of Human Cyto chrome P450 1B1 in V79 Chinese Hamster Cells and McMurray JE et al., 1974, J. Am. Chem. Soc. Metabolically Catalyzed DNA Adduct Formation of 96(14):4708-9. Dibenzo C.1 pyrene’ Chem. Res. Toxicol. 11:686-695. Wittig G, et al., 1973, “Methylenecyclohexane' Org. Synth. Murray GI et al., 1998, “Enhanced expression of cyto Col. 5:751-754. chrome P450 in stomach cancer Br J Cancer 77(7):1040–1044. Pappalardo G et al., 1968, XP-002102896, “Relation Ohsumi K et al., 1998, XP-002102895, “Novel Combret between Structure and antibacterial action of arylthioamides, astatin Analogues Effective against Murine Solid Tumors: II. Antibacterial activity, ultraViolet and infrared spectra, and Design and Structure-Activity Relationships' J. Med. acid hydrolysis of aryl- and arylvinylenethioamides' p. Chem. 41(16):3022–3032. 2014; see abstract & Farmaco, et. Sci. 22(10):808-820 Dark GG et al., 1997, “Combretastatin A-4, an Agent That (1967) Chemical Abstracts 68(5):21141r). Displays Potent and Selective Toxicity toward Vasculature” Gutsche CD et al., 1959, Chemical Abstracts, “Experiments Cancer ReS. 57:1829–1834. in the colchicine field” Am. Chem. Soc. 53(9):9122–9126. Pettit GR et al., 1995, “Antineoplastic agents 322. Synthesis “Differential Activation of Cyclophosphamide and Ifospha of combretastatin A-4 prodrugs' Anti-Cancer Drug Design mide by Cytochromes P-450 2B and 3A in Human Liver 10:299-309. Microcromes” by Chang et al. (Cancer Research 53; pp. Tully W et al., 1995, “Preparation of cyclomanganated 5629-5637, Dec. 1, 1993. chalcones and their reactions with methyl acrylate and other C.f3-unsaturated carbonyl compounds' J. Organometallic “Tumor-specific Expression of Cytochrome P450 Chem. 503(1):75–92. CYP1B1” by Murray et al. pp. 3026–3031; Cancer Klein E, 1994, Chemical Abstracts “Cosmetic compositions Research–Jul. 15, 1997. containing chalcone derivatives' Am. Chem. SOC. “Reductive Metabolism: its Application in Prodrug Activa 120(1):422 (Abstract 14,657c). tion” by Patterson et al. (XP-002106818) pp. 72-79. Won CM, 1994, “Kinetics and mechanisms of hydrolysis of tryphostins' Ind. J. Pharmaceutics 104:29-40. * cited by examiner U.S. Patent Sep. 21, 2004 Sheet 1 of 3 US 6,794,384 B1 Figure l OH OH CYP1B HO HO C. ^ Dug OH Rey U.S. Patent Sep. 21, 2004 Sheet 2 of 3 US 6,794,384 B1 Figure 2 OR PyCrOC) / CH2Cl2 OR RO RO O R = H, protecting group NaBH / EtOH OR DrugNH 7 (CCl3O)2CO OR RO RO H A 1 N Drug OH O U.S. Patent Sep. 21, 2004 Sheet 3 of 3 US 6,794,384 B1 Figure 3 O MeO C MeO MeO Cl B r O YY OH N/YC US 6,794,384 B1 1 2 HYDROXYLATION ACTIVATED DRUG The prodrugs may be designed to be activated by other RELEASE oxidising agents, for example other enzymes (e.g. other members of the cytochrome P-450 family of enzymes) which cause hydroxylation of the prodrug. For example, a This is a continuation of copending International appli prodrug activated by hydroxylation by the human CYP1A1 cation No. PCT/GB99/00416 filed Feb. 10, 1999. isoform would be useful for the treatment of stomach cancer The present invention concerns prodrugs whose aromatic Since this isoform is over expressed in this type of cancer oxidation, particularly their enzymatic aromatic (Murray et al., 1998, Br. J. Cancer, 77: 1040). Furthermore, hydroxylation, results in their activation by the release of a if the prodrug is specifically activated by a fungal P-450 drug moiety.
Load more

Recommended publications
  • WO 2018/175958 Al 27 September 2018 (27.09.2018) W !P O PCT
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2018/175958 Al 27 September 2018 (27.09.2018) W !P O PCT (51) International Patent Classification: A61K 31/53 (2006 .01) A61P 35/00 (2006 .0 1) C07D 251/40 (2006.01) (21) International Application Number: PCT/US20 18/024 134 (22) International Filing Date: 23 March 2018 (23.03.2018) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 62/476,585 24 March 2017 (24.03.2017) US (71) Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA [US/US]; 1111 Franklin Street, Twelfth Floor, Oakland, CA 94607-5200 (US). (72) Inventors: NOMURA, Daniel, K.; 4532 Devenport Av enue, Berkeley, CA 94619 (US). ANDERSON, Kimberly, E.; 8 Marchant Court, Kensington, CA 94707 (US). (74) Agent: LEE, Joohee et al; Mintz Levin Cohn Ferris Glovsky And Popeo, P.C., One Financial Center, Boston, MA 021 11 (US). (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW.
    [Show full text]
  • Recent Advances in the Management of Hormone Refractory Prostate Cancer
    Korean J Uro-Oncol 2004;2(3):147-153 Recent Advances in the Management of Hormone Refractory Prostate Cancer Mari Nakabayashi, William K. Oh Lank Center for Genitourinary Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA A typical treatment strategy after AAWD is to use secondary INTRODUCTION hormonal manipulations, although studies have not yet demonstrated a survival benefit with this class of treatment. Prostate cancer is the most common cancer in men in the Options in this category include (1) the secondary use of anti- United States and accounted for 29,900 deaths in 2003.1 androgens (e.g., high-dose bicalutamide, nilutamide), (2) thera- Although most men with advanced prostate cancer respond pies targeted against adrenal steroid synthesis (e.g., ketocona- initially to androgen deprivation therapies (ADT) by either zole, corticosteroids), and (3) estrogenic therapies (e.g. diethy- bilateral orchiectomy or leuteinizing hormone releasing hor- lstilbestrol). Symptomatic improvement and PSA responses mone (LHRH) analogues, patients eventually progress to an (defined as PSA decline ＞50% after treatment) have been androgen-independent state in which the initial ADT no longer reported in approximately 20% to 80% of patients with is adequate to control disease.2 Progression of the disease hormone-refractory prostate cancer (HRPC) with a typical manifests as an increase in serum prostate-specific antigen duration of response of 2 to 6 months. Toxicity is generally (PSA) or may be accompanied by radiographic evidence of mild for these oral therapies, although serious side effects, tumor growth. Here we report a brief summary of recent including adrenal insufficiency, liver toxicity, and thrombosis, advances in the management of hormone refractory prostate may occur (Table 1).
    [Show full text]
  • Cumulative Cross Index to Iarc Monographs
    PERSONAL HABITS AND INDOOR COMBUSTIONS volume 100 e A review of humAn cArcinogens This publication represents the views and expert opinions of an IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, which met in Lyon, 29 September-6 October 2009 LYON, FRANCE - 2012 iArc monogrAphs on the evAluAtion of cArcinogenic risks to humAns CUMULATIVE CROSS INDEX TO IARC MONOGRAPHS The volume, page and year of publication are given. References to corrigenda are given in parentheses. A A-α-C .............................................................40, 245 (1986); Suppl. 7, 56 (1987) Acenaphthene ........................................................................92, 35 (2010) Acepyrene ............................................................................92, 35 (2010) Acetaldehyde ........................36, 101 (1985) (corr. 42, 263); Suppl. 7, 77 (1987); 71, 319 (1999) Acetaldehyde associated with the consumption of alcoholic beverages ..............100E, 377 (2012) Acetaldehyde formylmethylhydrazone (see Gyromitrin) Acetamide .................................... 7, 197 (1974); Suppl. 7, 56, 389 (1987); 71, 1211 (1999) Acetaminophen (see Paracetamol) Aciclovir ..............................................................................76, 47 (2000) Acid mists (see Sulfuric acid and other strong inorganic acids, occupational exposures to mists and vapours from) Acridine orange ...................................................16, 145 (1978); Suppl. 7, 56 (1987) Acriflavinium chloride ..............................................13,
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2008/0317850 A1 Hewitt Et Al
    US 20080317850A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2008/0317850 A1 Hewitt et al. (43) Pub. Date: Dec. 25, 2008 (54) BUCCAL DELIVERY SYSTEM Publication Classification (51) Int. Cl. (76) Inventors: Ernest Alan Hewitt, New South A69/20 (2006.01) Wales (AU); Richard James A6II 47/34 (2006.01) Stenlake, New South Wales (AU) A 6LX 3/57 (2006.01) A6II 3/565 (2006.01) Correspondence Address: A6II 3/568 (2006.01) REED SMITH LLP A6II 3/66 (2006.01) P.O. BOX 488 (52) U.S. Cl. ......... 424/464; 424/486; 514/177: 514/182: PITTSBURGH, PA 15230-0488 (US) 514/178; 514/108 (57) ABSTRACT (21) Appl. No.: 11/910,902 A buccal delivery system capable of being blended in a nor 1-1. mal dry powder process and compressed using a standard (22) PCT Filed: Apr. 7, 2006 tabletting machine, said buccal delivery system comprising a matrix of: (a) an effective amount of one or more active (86). PCT No.: PCT/AU2OO6/OOO472 ingredients; (b) an amount of one or more polyethylene gly cols orderivatives thereofhaving a molecular weight between S371 (c)(1), 1000 to 8000 sufficient to provide the required hardness and (2), (4) Date: Feb. 5, 2008 time for dissolution of the matrix; (c) 0.05-2% by weight of the total matrix of one or more Suspending agents; (d) 0.05 (30) Foreign Application Priority Data 2% by weight of the total matrix of one or more flowing agents; and (e) 0.05-2% by weight of the total matrix of one or Apr.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 6,265,147 B1 Mobley Et Al
    USOO6265147B1 (12) United States Patent (10) Patent No.: US 6,265,147 B1 Mobley et al. (45) Date of Patent: Jul. 24, 2001 (54) METHOD OF SCREENING FOR Carmeci, Charles, et al., “Identification of a Gene (GPR30) NEUROPROTECTIVE AGENTS with Homology to the G-Protein-Coupled Receptor Super family ASSociated with Estrogen Receptor Expression in (75) Inventors: William C. Mobley, Palo Alto; Ronald Breast Cancer,” Genomics (1997) vol. 45:607-617. J. Weigel, Woodside; Chengbiao Wu, Owman, Christer, et al., “Cloning of Human cDNA Encod San Jose; Har Hiu Dawn Lam, ing a Novel Hepathelix Receptor Expressed in Burkitt's Stanford, all of CA (US) Lymphoma and Widely Distributed in Brain abd Peripheral Tissues,” Biochemical and Biophysical Research Cimmuni (73) Assignee: The Board of Trustees of the Leland cations (1996) vol. 228:285–292. Stanford Junior University, Palo Alto, Singh, Meharvan, et al., “Estrogen-Induced Activation of CA (US) Mitogen-Activated Protein Kinase in Cerebral Cortical Explants: Convergence of Estrogen and Neurotrophin Sig (*) Notice: Subject to any disclaimer, the term of this naling Pathways,” Journal of Neuroscience (Feb. 15, 1999) patent is extended or adjusted under 35 vol. 19(4): 1179–1188. U.S.C. 154(b) by 0 days. Toran-Allerand, C. Dominique, “The Estrogen/Neurotro phin Connection During Neural Development: Is Co-Lo (21) Appl. No.: 09/452,531 calization of Estrogen Receptors with the Neurotrophins and Their Receptors Biologically Revelant?”, Dev: Neurosci. (22) Filed: Dec. 1, 1999 (1996) vol. 18:36–48. (51) Int. Cl." ................................................... C12O 1/00 Genbank Accession Number Y08162. (52) U.S. Cl. ............................... 435/4; 435/69.1; 514/169 * cited by examiner (58) Field of Search ........................
    [Show full text]
  • Estramustine Phosphate Inhibits Germinal Vesicle Breakdown and Induces Depolymerization of Microtubules in Mouse Oocyte Hélène Rime, Catherine Jessus, R
    Estramustine phosphate inhibits germinal vesicle breakdown and induces depolymerization of microtubules in mouse oocyte Hélène Rime, Catherine Jessus, R. Ozon To cite this version: Hélène Rime, Catherine Jessus, R. Ozon. Estramustine phosphate inhibits germinal vesicle breakdown and induces depolymerization of microtubules in mouse oocyte. Reproduction Nutrition Développe- ment, 1988, 28 (2A), pp.319-334. hal-00898793 HAL Id: hal-00898793 https://hal.archives-ouvertes.fr/hal-00898793 Submitted on 1 Jan 1988 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Estramustine phosphate inhibits germinal vesicle breakdown and induces depolymerization of microtubules in mouse oocyte Hélène RIME Catherine JESSUS R. OZON Laboratoire de Physiologie de la Reproduction, Groupe Stéroides, UA-CNRS 555, Université Pierre et Marie Curie, 4, place Jussieu, 75252 Paris Cedex 05, France. Summary. The first meiotic cell division (meiotic maturation) of the dictyate stage of mouse oocytes, removed from the follicle, resumes spontaneously in vitro. This study indicates that estramustine phosphate reversibly blocks meiotic maturation by inhibiting germinal vesicle breakdown. Oocyte cryostat sections were stained with anti-tubulin and two antibodies (anti-MAP1 : JA2 and 5051) which decorated the metaphase spindle during meiotic maturation.
    [Show full text]
  • Effects of Cancer Chemotherapeutic Agents on Endocrine Organs and Serum Levels of Estrogens, Progesterone, Prolactin, and Luteinizing Hormone'
    [CANCER RESEARCH 35, 1975-1980, August 1975] Effects of Cancer Chemotherapeutic Agents on Endocrine Organs and Serum Levels of Estrogens, Progesterone, Prolactin, and Luteinizing Hormone' Eric V. H. Kuo, Henry J. Esber, D. Jane Taylor, and Arthur E. Bogden Department oflmmunobiology, Mason ResearchInstitute, Worcester,Massachusetts01608[E. Y. H. K., H. J. E., A. E. B.], and Division of Cancer Biology and Diagnosis,National CancerInstitute, Bethesda,Maryland 21.Xfl4[D.J. T.] SUMMARY INTRODUCTION The effects of the following cancer chemotherapeutic Many types ofneoplasms, both spontaneous and induced, agents on serum hormonal levels, estrous cycles, and are known to arise in the various endocrine organs as well as endocrine organs were studied in mature, normal in the target tissues of hormones. The growth of tumors Sprague-Dawley rats by radioimmunoassay, vaginal smear arising in endocrine-responsive tissues is frequently found to examination, and organ weight end point: estradiol mustard be hormone dependent or at least hormone responsive. (NSC 112259), testosterone mustard (NSC I 12260), phen Recent studies (9, 11) on gs antigen expression have estrin (NSC 104469), methotrexate (NSC 740), 5-fluo produced evidence suggesting that certain hormones may rouracil (NSC 19893), vinblastine (NSC 49842), vincristine also play a role in activating the oncogenic expression of (NSC 67574), nitrogen mustard (NSC 762), and l,3-bis(2- some RNA tumor virus genomes. While hormonal effects chloroethyl)-l-nitrosourea (NSC 409962). Following 2 are often associated with stimulation of tumor growth, an weeks of treatment, estradiol-17fi levels were markedly inhibitory effect on tumor growth may also be exerted by elevated by all compounds except testosterone mustard and hormones (14, 24).
    [Show full text]
  • Amplification of the ATP-Binding Cassette 2 Transporter Gene Is Functionally Linked with Enhanced Efflux of Estramustine in Ovarian Carcinoma Cells1
    [CANCER RESEARCH 58, 1332-1337. April 1. 1998] Advances in Brief Amplification of the ATP-Binding Cassette 2 Transporter Gene Is Functionally Linked with Enhanced Efflux of Estramustine in Ovarian Carcinoma Cells1 Naomi M. Laing, Martin G. Belinsky, Gary D. Kruh, Daphne W. Bell, Jonathan T. Boyd, Linda Barone,2 Joseph R. Testa, and Kenneth D. Tew3 Departments of Pharmacology IN. M. L.. J. T. B.. L B.. K. D. T.I and Medical Oncology ¡M.C. B.. G. D. K.. D. W. B.. J. R. T.]. Fax Chase Cancer Center, Philadelphia, Pennsylvania 19111 Abstract affinity for EM (6) suggests a mechanism by which its overexpression contributes to EM resistance. We have also detected enhanced efflux An estramustine-resistant human ovarian carcinoma cell line, SKIM, of EM in an EM-resistant cell line, suggesting that increased expres was generated to explore resistance mechanisms associated with this sion of a transporter could also contribute to EM resistance. agent. Cytogenetic analysis revealed that SKEM cells have a homoge Although EM can bind to pgp and modulate its transport activity (7, neously staining region (hsr) at chromosome 9q34. Microdissection of the 8), pgp-overexpressing cells do not display cross-resistance to EM. In hsr, followed by fluorescence in situ hybridization to SKEM and normal addition, overexpression of pgp is not detected in any EM-resistant metaphase spreads, confirmed that the amplified region was derived from sequences from 9q34. In situ hybridization with a probe specific lor .I/if?, cell lines studied to date (9). These observations suggest that a a gene located at 9q34 that encodes an ATP-binding cassette 2 (ABC2) transporter distinct from pgp may contribute to EM resistance.
    [Show full text]
  • Report Versionpdf
    THIRD EDITION 2004 Stateof the Evidence What Is the Connection Between the Environment and Breast Cancer? Edited by Nancy Evans, Health Science Consultant, Breast Cancer Fund Dedicated to our founders, pioneers in breast cancer and environmental health ANDREA RAVINETT MARTIN 1946-2003 Breast Cancer Fund ELENORE G. PRED 1933-1991 Breast Cancer Action Cover Illustration: Book of Flowers IX, by Lynda Fishbourne, 1997, “Art.Rage.Us; Art and Writing by Women with Breast Cancer” After I finished chemotherapy and started radiation treatments every day, I also found a new medium, encaustic (wax). It felt like a rebirth in a way. As a reward to myself for my daily hospitals visits, I painted in encaustic every day before leaving for my appointment. A series of these paintings resulted. The darker side has petals falling, and the background is etched with counting; it shows what I was leaving behind. The lighter, sunnier side contains written thoughts as well as flowers and leaves from my walks in nature. It reflects the more positive feelings I was having. Acknowledgments Breast Cancer Fund and Breast Cancer Action wish to thank the following scientific experts who reviewed and commented on State of the Evidence: Devra Lee Davis, Ph.D., M.P.H., Director, Center for Environmental Oncology, University of Pittsburgh Cancer Institute and Professor, Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh. Philip Randolph Lee, M.D., Professor Emeritus, University of California San Francisco School of Medicine, former Assistant Secretary of Health & Human Services, San Francisco, Calif. Annie J. Sasco, M.D., Dr P.H., Chief of the Unit of Epidemiology for Cancer Prevention, International Agency for Research on Cancer and Director of Research, Institut National de la Santé et de la Recherche Médicale, Lyon, France.
    [Show full text]
  • (12) United States Patent (Lo) Patent No.: US 8,480,637 B2
    111111111111111111111111111111111111111111111111111111111111111111111111 (12) United States Patent (lo) Patent No.: US 8,480,637 B2 Ferrari et al. (45) Date of Patent : Jul. 9, 2013 (54) NANOCHANNELED DEVICE AND RELATED USPC .................. 604/264; 907/700, 902, 904, 906 METHODS See application file for complete search history. (75) Inventors: Mauro Ferrari, Houston, TX (US); (56) References Cited Xuewu Liu, Sugar Land, TX (US); Alessandro Grattoni, Houston, TX U.S. PATENT DOCUMENTS (US); Daniel Fine, Austin, TX (US); 5,651,900 A 7/1997 Keller et al . .................... 216/56 Randy Goodall, Austin, TX (US); 5,728,396 A 3/1998 Peery et al . ................... 424/422 Sharath Hosali, Austin, TX (US); Ryan 5,770,076 A 6/1998 Chu et al ....................... 210/490 5,798,042 A 8/1998 Chu et al ....................... 210/490 Medema, Pflugerville, TX (US); Lee 5,893,974 A 4/1999 Keller et al . .................. 510/483 Hudson, Elgin, TX (US) 5,938,923 A 8/1999 Tu et al . ........................ 210/490 5,948,255 A * 9/1999 Keller et al . ............. 210/321.84 (73) Assignees: The Board of Regents of the University 5,985,164 A 11/1999 Chu et al ......................... 516/41 of Texas System, Austin, TX (US); The 5,985,328 A 11/1999 Chu et al ....................... 424/489 Ohio State University Research (Continued) Foundation, Columbus, OH (US) FOREIGN PATENT DOCUMENTS (*) Notice: Subject to any disclaimer, the term of this WO WO 2004/036623 4/2004 WO WO 2006/113860 10/2006 patent is extended or adjusted under 35 WO WO 2009/149362 12/2009 U.S.C. 154(b) by 612 days.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2002/0010208A1 Shashoua Et Al
    US 2002001 0208A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2002/0010208A1 Shashoua et al. (43) Pub. Date: Jan. 24, 2002 (54) DHA-PHARMACEUTICAL AGENT Related U.S. Application Data CONJUGATES OF TAXANES (63) Continuation of application No. 09/135,291, filed on (76) Inventors: Victor Shashoua, Brookline, MA (US); Aug. 17, 1998, now abandoned, which is a continu Charles Swindell, Merion, PA (US); ation of application No. 08/651,312, filed on May 22, Nigel Webb, Bryn Mawr, PA (US); 1996, now Pat. No. 5,795,909. Matthews Bradley, Layton, PA (US) Publication Classification Correspondence Address: Edward R. Gates, Esq. (51) Int. Cl." ............................................ A61K 31/337 Wolf, Greenfield & Sacks, P.C. (52) U.S. Cl. .............................................................. 514/449 600 Atlantic Avenue Boston, MA 02210 (US) (57) ABSTRACT The invention provides conjugates of cis-docosahexaenoic (21) Appl. No.: 09/846,838 acid and pharmaceutical agents useful in treating noncentral nervous System conditions. Methods for Selectively target 22) Filled: Mayy 1, 2001 ingg pharmaceuticalp agents9. to desired tissues are pprovided. Patent Application Publication Jan. 24, 2002 Sheet 1 of 14 US 2002/0010208A1 1 OO 5 O -5OO - 1 OO-9 -8 -7 -6 -5 -4 LOG-10 OF SAMPLE CONCENTRATION (MOLAR) CCRF-CEM-o- SR ----- RPM-8226----- K-562- - -A - - HL-60 (TB) -g- - MOLT4: ... O Fig. 1 1 OO 5 O -5OO -1 O O -8 -7 -6 -5 -4 -- 9 LOGo OF SAMPLE CONCENTRATION (MOLAR) A549/ATCC-o-NS326. NCEKVX 28. --Q-- NCI-H322M-...-a---Eidsf8::... NC-H522--O-- HOP-62---Fig. 2 a-- NC-H460.-------- Patent Application Publication Jan.
    [Show full text]
  • ADT) Plus Chemotherapy As Initial Treatment for Local Failures Or Advanced Prostate Cancer
    Phase 2 Study of Androgen Deprivation Therapy (ADT) plus Chemotherapy as Initial Treatment for Local Failures or Advanced Prostate Cancer NCT02560051 Version Date: 01/26/2016 IRB NUMBER: HSC-MS-14-0949 IRB APPROVAL DATE: 01/26/2016 Androgen Deprivation Therapy (ADT) plus Chemotherapy as Initial Treatment for Local Failures or Advanced Prostate Cancer Clinical Protocol No: GU-13-101 Principal Investigator: Robert J. Amato, D.O. Director and Professor, Department of Internal Medicine, Division of Oncology 6410 Fannin, Suite 830 Houston, TX 77030 832-725-7702 Collaborators: Varaha Tammisetti, M.D. Angel Blanco, M.D. Nwabugwu S. Ochuwa, Pharm.D., BCOP Reynolds Brobey, Ph.D. Statistician: Jessica Williams, M.S. Center: Memorial Hermann Cancer Center Version 1: February 20, 2015 Version 2: October 1, 2015 Version 3: November 20, 2015 Version 4: January 13, 2016 The study is to be conducted according to the protocol and in compliance with Good Clinical Practice (GCP) and other applicable regulatory requirements. Signature: Date: Robert J. Amato, D.O. IRB NUMBER: HSC-MS-14-0949 IRB APPROVAL DATE: 01/26/2016 Confidential Page 2 of 57 Protocol No. GU-13-101 Ver. 4, dated 01/13/2016 TABLE OF CONTENTS PROTOCOL SYNOPSIS ...........................................................................................................................................4 1.0 OBJECTIVES.................................................................................................................................................9 2.0 BACKGROUND ............................................................................................................................................9
    [Show full text]