- Switch from antagonist to agonist of the androgen receptor bicalutamide is associated with prostate tumour progression in a new model system
Department of Urology, University of Innsbruck, Austria
Br J Cancer 81:242-51. 1999
..These findings may have repercussions on the natural course of prostate cancer with androgen deprivation and on strategies of therapeutic intervention...
- Inhibition of the hedgehog pathway in advanced basal-cell carcinoma
Daniel D Von Hoff
Translational Genomics Research Institute and Scottsdale Healthcare, Scottsdale, AZ, USA
N Engl J Med 361:1164-72. 2009
..In a phase 1 clinical trial, we assessed the safety and pharmacokinetics of GDC-0449, a small-molecule inhibitor of SMO, and responses of metastatic or locally advanced basal-cell carcinoma to the drug...
- Smoothened mutation confers resistance to a Hedgehog pathway inhibitor in medulloblastoma
Robert L Yauch
Genentech, South San Francisco, CA 94080, USA
Science 326:572-4. 2009
..These findings show that acquired mutations in a serpentine receptor with features of a G protein-coupled receptor can serve as a mechanism of drug resistance in human cancer...
- Efficacy and safety of vismodegib in advanced basal-cell carcinoma
Mayo Clinic, Scottsdale, AZ 85259, USA
N Engl J Med 366:2171-9. 2012
..A phase 1 study of vismodegib (GDC-0449), a first-in-class, small-molecule inhibitor of the hedgehog pathway, showed a 58% response rate among patients with advanced basal-cell carcinoma...
- Phase I trial of hedgehog pathway inhibitor vismodegib (GDC-0449) in patients with refractory, locally advanced or metastatic solid tumors
Patricia M LoRusso
Karmanos Cancer Institute, Detroit, Michigan Johns Hopkins University, Baltimore, Maryland, USA
Clin Cancer Res 17:2502-11. 2011
..This phase I trial assessed GDC-0449 treatment in patients with solid tumors refractory to current therapies or for which no standard therapy existed...
- VEGF and c-Met blockade amplify angiogenesis inhibition in pancreatic islet cancer
Weon Kyoo You
Cardiovascular Research Institute, Comprehensive Cancer Center, and Department of Anatomy, University of California, San Francisco, CA 94143, USA
Cancer Res 71:4758-68. 2011
- Coregulator recruitment and histone modifications in transcriptional regulation by the androgen receptor
Biomedicum Helsinki, Institute of Biomedicine, University of Helsinki, FI 00014, Finland
Mol Endocrinol 18:2633-48. 2004
- Androgen receptor or estrogen receptor-beta blockade alters DHEA-, DHT-, and E(2)-induced proliferation and PSA production in human prostate cancer cells
Julia T Arnold
Endocrine Section, Laboratory of Clinical Investigation, Division of Intramural Research, National Center for Complementary and Alternative Medicine, National Institutes of Health, Bethesda, Maryland 20892 0933, USA
Prostate 67:1152-62. 2007
..LNCaP and LAPC-4 prostate cancer cells were used to determine whether DHEA-modulated proliferation and prostate specific antigen (PSA) production were mediated via the androgen receptor (AR) and/or ERbeta...
- Inhibition of tumor cell growth, invasion, and metastasis by EXEL-2880 (XL880, GSK1363089), a novel inhibitor of HGF and VEGF receptor tyrosine kinases
Exelixis, Inc, South San Francisco, California 94083, USA
Cancer Res 69:8009-16. 2009
..Collectively, these data indicate that EXEL-2880 may prevent tumor growth through a direct effect on tumor cell proliferation and by inhibition of invasion and angiogenesis mediated by HGF and VEGF receptors...
- A phase I study of foretinib, a multi-targeted inhibitor of c-Met and vascular endothelial growth factor receptor 2
Joseph Paul Eder
Early Drug Development Center, Department of Medical Oncology, Dana Farber Cancer Institute and Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts, USA
Clin Cancer Res 16:3507-16. 2010
..Secondary objectives included evaluation of plasma pharmacokinetics, long-term safety after repeated administration, preliminary antitumor activity, and pharmacodynamic activity...
- Androgen receptor regulates Cdc6 in synchronized LNCaP cells progressing from G1 to S phase
V Uma Bai
Vattikuti Urology Institute, Henry Ford Health Sciences Center, Detroit, Michigan, USA
J Cell Physiol 204:381-7. 2005
..AR may play an important role in the onset of DNA synthesis in prostate cancer cells by regulating the expression and stability of Cdc6, which is critically required for the assembly of the pre-replication complex(pre-RC)...
- Mechanisms underlying pioglitazone-mediated relaxation in isolated blood vessel
Department of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Aomori, Japan
J Pharmacol Sci 108:258-65. 2008
..While endothelium-dependent relaxation is mediated via nitric oxide, the endothelium-independent one is responsible for smooth muscle K+ (K(V), K(IR))-channel opening...
- Combined androgen blockade for prostate cancer: review of efficacy, safety and cost-effectiveness
Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan
Cancer Sci 102:51-6. 2011
- GDC-0449-a potent inhibitor of the hedgehog pathway
Kirk D Robarge
Genentech, Small Molecule Drug Discovery 1 DNA Way, South San Francisco, CA 94080, United States
Bioorg Med Chem Lett 19:5576-81. 2009
..5mg/kg BID in a medulloblastoma allograft mouse model that is wholly dependent on the Hh pathway for growth and is currently in human clinical trials, where it is initially being evaluated for the treatment of BCC...
- Small-molecule modulators of the Sonic Hedgehog signaling pathway
Benjamin Z Stanton
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA
Mol Biosyst 6:44-54. 2010
..Several Shh inhibitors have not succeeded in the clinic for unknown reasons, but clinical trials in BCC and pancreatic cancer with the promising Smo antagonists GDC-0449 and IPI-926 are currently underway...
- Attenuation of early liver fibrosis by pharmacological inhibition of smoothened receptor signaling
Division of Solid Organ Transplantation, Methodist University Hospital, Memphis, TN, USA
J Drug Target 20:770-82. 2012
..Thus, GDC has the potential to serve as a new therapeutic agent for treating early liver fibrosis...
- Itraconazole and arsenic trioxide inhibit Hedgehog pathway activation and tumor growth associated with acquired resistance to smoothened antagonists
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305, USA
Cancer Cell 23:23-34. 2013
..Itraconazole and arsenic trioxide, alone or in combination, inhibit the growth of medulloblastoma and basal cell carcinoma in vivo, and prolong survival of mice with intracranial drug-resistant SMO(D477G) medulloblastoma...
- Rosiglitazone treatment prevents mitochondrial dysfunction in mutant huntingtin-expressing cells: possible role of peroxisome proliferator-activated receptor-gamma (PPARgamma) in the pathogenesis of Huntington disease
Rodrigo A Quintanilla
Department of Anesthesiology, University of Rochester, University Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA
J Biol Chem 283:25628-37. 2008
- PPARgamma agonist rosiglitazone is neuroprotective after traumatic brain injury via anti-inflammatory and anti-oxidative mechanisms
Jae Hyuk Yi
Department of Neurological Surgery, University of Wisconsin, K4 8 Mail code CSC 8660, 600 Highland Avenue, Madison, WI 53792, USA
Brain Res 1244:164-72. 2008
..Treatment with GW9662 (a specific PPARgamma antagonist) prevented all the above PPARgamma-mediated actions. Thus, PPARgamma activation confers neuroprotection after TBI by anti-inflammatory, anti-apoptotic and anti-oxidative mechanisms...
- Androgens up-regulate the insulin-like growth factor-I receptor in prostate cancer cells
Dipartimento di Medicina Interna e di Medicina Specialistica, Cattedra di Endocrinologia, University of Catania, Ospedale Garibaldi, Catania, Italy
Cancer Res 65:1849-57. 2005
..Anti-androgen therapy may be only partially effective, or almost ineffective, in blocking important biological effects of androgens, such as activation of the IGF system...
- Hedgehog signaling antagonist promotes regression of both liver fibrosis and hepatocellular carcinoma in a murine model of primary liver cancer
George M Philips
Division of Gastroenterology, Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America
PLoS ONE 6:e23943. 2011
..We used Mdr2(-/-) mice to investigate the hypothesis that activation of the hedgehog (Hh) signaling pathway promotes development of both liver fibrosis and HCC...
- Activation of TRPV1 contributes to morphine tolerance: involvement of the mitogen-activated protein kinase signaling pathway
Department of Neurology, University of Wurzburg, 97080 Wurzburg, Germany
J Neurosci 28:5836-45. 2008
..Thus, blocking TRPV1 might be a way to reduce morphine tolerance...
- Small molecule inhibition of GDC-0449 refractory smoothened mutants and downstream mechanisms of drug resistance
Gerrit J P Dijkgraaf
Department of Molecular Biology, Genentech Inc, South San Francisco, California 94080, USA
Cancer Res 71:435-44. 2011
..Importantly, these HPI resistant MB allografts retained their sensitivity to PI3K inhibition, presenting additional opportunities for the treatment of such tumors...
- Role of androgen receptor in the progression of human prostate tumor cells to androgen independence and insensitivity
John M Kokontis
Ben May Institute for Cancer Research and the Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, Illinois 60637, USA
Prostate 65:287-98. 2005
..Various studies have implicated the androgen receptor (AR) in the progression of androgen-dependent human prostate cancer cells to androgen-independent and androgen-insensitive phenotypes, but the exact role of AR in progression is unclear...
- Antagonism of peroxisome proliferator-activated receptor gamma prevents high-fat diet-induced obesity in vivo
Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc, 5 2 3 Toukoudai, Tsukuba shi, Ibaraki 300 2698, Japan
Biochem Pharmacol 72:42-52. 2006
..These data indicate that antagonism of PPARgamma using a synthetic ligand suppresses the increased adiposity observed in HF diet-induced obesity, and that a PPARgamma antagonist could possibly be developed as an anti-obesity drug...
- Prolonged treatment with bicalutamide induces androgen receptor overexpression and androgen hypersensitivity
Pharmaceutical Research Department 2, Kamakura Research Laboratories, Chugai Pharmaceutical Co, Ltd, Kamakura, Kanagawa, Japan
Prostate 70:745-54. 2010
..However, the mechanism of bicalutamide resistance remains unclear because few cell models have been generated...
- Hedgehog pathway inhibition radiosensitizes non-small cell lung cancers
Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231 2410, USA
Int J Radiat Oncol Biol Phys 86:143-9. 2013
..Whether Hedgehog inhibition can affect radiation efficacy in vivo has not been reported...
- Bicalutamide functions as an androgen receptor antagonist by assembly of a transcriptionally inactive receptor
Cancer Biology Program, Hematology Oncology Division, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
J Biol Chem 277:26321-6. 2002
..These results demonstrate that bicalutamide stimulates the assembly of a transcriptionally inactive AR on DNA and support altered coactivator (or corepressor) expression as a mechanism of bicalutamide-resistant androgen-independent PCa...
- Bicalutamide as immediate therapy either alone or as adjuvant to standard care of patients with localized or locally advanced prostate cancer: first analysis of the early prostate cancer program
William A See
Medical College of Wisconsin, Milwaukee, Wisconsin, USA
J Urol 168:429-35. 2002
..We determine the efficacy and tolerability of bicalutamide as immediate therapy, either alone or as adjuvant to treatment of curative intent, in patients with clinically localized or locally advanced prostate cancer...
- The androgen receptor pathway is by-passed in prostate cancer cells generated after prolonged treatment with bicalutamide
Department of Urology, General Hospital Feldkirch, Feldkirch, Austria
Prostate 66:413-20. 2006
..However, little attention has been paid to the androgen receptor-signaling pathway in the development of therapy resistance in patients who receive chronic treatment with a non-steroidal anti-androgen...
- Hedgehog signaling inhibition by the small molecule smoothened inhibitor GDC-0449 in the bone forming prostate cancer xenograft MDA PCa 118b
Department of Genitourinary Medical Oncology, The David Koch Center for Applied Research of Genitourinary Cancers, The Stanford Alexander Tissue Derivatives Laboratory, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030 4009, USA
Prostate 72:1638-47. 2012
- Store-operated Ca(2+) entry (SOCE) contributes to normal skeletal muscle contractility in young but not in aged skeletal muscle
Angela M Thornton
Department of Physiology and Biophysics, Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA
Aging (Albany NY) 3:621-34. 2011
- Multidimensional chemical genetic analysis of diversity-oriented synthesis-derived deacetylase inhibitors using cell-based assays
Stephen J Haggarty
Departments of Molecular and Cellular Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA
Chem Biol 10:383-96. 2003
..These small molecules will facilitate dissecting the role of acetylation in a variety of cell biological processes...
- Prosaposin upregulates AR and PSA expression and activity in prostate cancer cells (LNCaP)
Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA
Prostate 67:178-89. 2007
..Here, we explored the possibility for a functional relationship between prosaposin and androgen receptor (AR) in LNCaP cells...
- Structural biasing elements for in-cell histone deacetylase paralog selectivity
Jason C Wong
Department of Chemistry and Chemical Biology, Harvard Institute of Chemistry and Cell Biology, and the Howard Hughes Medical Institute, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA
J Am Chem Soc 125:5586-7. 2003
..We also show that suberoylanilide hydroxamic acid (SAHA) alone is a nonparalog-selective HDAC inhibitor and that the 1,3-dioxane diversity appended to SAHA is essential for HDAC6 paralog selectivity...
- c-Met is a marker of pancreatic cancer stem cells and therapeutic target
Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA
Gastroenterology 141:2218-2227.e5. 2011
..c-Met is a marker of normal mouse pancreatic stem and progenitor cells; we investigated whether it is also a marker of human pancreatic CSCs that might be developed as a therapeutic target...
- Inhibition of cell proliferation by potential peroxisome proliferator-activated receptor (PPAR) gamma agonists and antagonists
Michael A Lea
Department of Biochemistry and Molecular Biology, UMDNJ New Jersey Medical School, Newark, New Jersey 07103, USA
Anticancer Res 24:2765-71. 2004
..We conclude that potential PPAR gamma antagonists may fail to reverse the growth inhibitory effect of PPAR gamma ligands and may themselves act as growth inhibitory agents...
- Additive antitumor effects of the epidermal growth factor receptor tyrosine kinase inhibitor, gefitinib (Iressa), and the nonsteroidal antiandrogen, bicalutamide (Casodex), in prostate cancer cells in vitro
Department of Experimental Medicine, University of L Aquila, L Aquila, Italy
Int J Cancer 115:630-40. 2005
..This causes a significant delay in the onset of EGFR-driven androgen independence...
- Quantifying effects of ligands on androgen receptor nuclear translocation, intranuclear dynamics, and solubility
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
J Cell Biochem 98:770-88. 2006
..These results further support the notion that ligand specific interactions rapidly affect receptor and co-factor organization, solubility, and molecular dynamics, and each can be aberrantly affected by mutation and overexpression...
- A 90 kDa fragment of filamin A promotes Casodex-induced growth inhibition in Casodex-resistant androgen receptor positive C4-2 prostate cancer cells
Department of Urology, School of Medicine, University of California Davis, Sacramento, CA, USA
Oncogene 26:6061-70. 2007
..Our results demonstrate that expression of nuclear FlnA is necessary for androgen dependence in these cells...
- Histone deacetylase inhibitors reverse gene silencing in Friedreich's ataxia
Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
Nat Chem Biol 2:551-8. 2006
..This class of HDAC inhibitors may yield therapeutics for Friedreich's ataxia...
- Ca2+-independent phospholipase A2 enhances store-operated Ca2+ entry in dystrophic skeletal muscle fibers
François Xavier Boittin
Laboratory of Pharmacology, Geneva Lausanne School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 1211 Geneva 4, Switzerland
J Cell Sci 119:3733-42. 2006
..The Ca2+-independent phospholipase A2 pathway therefore appears as an attractive target to reduce excessive Ca2+ influx and subsequent degeneration occurring in dystrophic fibers...
- S32826, a nanomolar inhibitor of autotaxin: discovery, synthesis and applications as a pharmacological tool
Pharmacologie Moléculaire et Cellulaire, Institut de Recherches Servier, Croissy sur Seine, France
J Pharmacol Exp Ther 327:809-19. 2008
..S32826 is the first reported inhibitor of autotaxin with an IC(50) in the nanomolar range that can be used to validate the role of autotaxin in various pathologies in cellular models...
- Hedgehog pathway inhibitor HhAntag691 is a potent inhibitor of ABCG2/BCRP and ABCB1/Pgp
Russell H Morgan Department of Radiology and Radiological Sciences, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA
Neoplasia 11:96-101. 2009
..In addition to its effect on Hh signaling, the ability of HhAntag691 and related compounds to inhibit two key ABC transporters could contribute to their effectiveness in treating malignancies...
- Establishment and characterization of an androgen receptor-dependent, androgen-independent human prostate cancer cell line, LNCaP-CS10
Research Division, Kamakura Research Laboratories, Pharmaceutical Research Department 2, Chugai Pharmaceutical Co Ltd, Kamakura, Kanagawa, Japan
Prostate 70:457-66. 2010
- Platensimycin is a selective FabF inhibitor with potent antibiotic properties
Merck Research Laboratories, Rahway, New Jersey 07065, USA
Nature 441:358-61. 2006
..Platensimycin is the most potent inhibitor reported for the FabF/B condensing enzymes, and is the only inhibitor of these targets that shows broad-spectrum activity, in vivo efficacy and no observed toxicity...
- Antiandrogen-induced cell death in LNCaP human prostate cancer cells
E C Y Lee
Department of Biological Science, University of Notre Dame, Notre Dame, IN 46556, USA
Cell Death Differ 10:761-71. 2003
- Acyl substitution at the ortho position of anilides enhances oral bioavailability of thiophene sulfonamides: TBC3214, an ETA selective endothelin antagonist
Department of Chemistry, Texas Biotechnology Corporation, 7000 Fannin, Suite 1920, Houston, Texas 77030, USA
J Med Chem 44:1211-6. 2001
..It is very potent (IC(50) for ET(A) = 40 pM) and highly selective for ET(A) vs ET(B) receptors (400 000-fold), with a half-life of >4 h and oral bioavailability of 25% in rats, 42% in cats, and 70% in dogs...
- Synergistic effects of foretinib with HER-targeted agents in MET and HER1- or HER2-coactivated tumor cells
GlaxoSmithKline, 17 1356I, 5 Moore Drive, Research Triangle Park, NC 27709 3398, USA
Mol Cancer Ther 10:518-30. 2011
..0225). These data suggest that combination therapy with foretinib and HER-targeted agents should be tested as a treatment option for HER1- or HER2-positive patients with MET-amplified or -overexpressing tumors...
- Pathological changes of high-grade prostatic intraepithelial neoplasia and prostate cancer after monotherapy with bicalutamide 150 mg
Department of Urology, University Vita Salute, Scientific Institute H San Raffaele, Milan, Italy
BJU Int 98:54-8. 2006
..To evaluate the morphological changes induced by a 3-month course of neoadjuvant bicalutamide 150 mg/day before radical prostatectomy (RP) on prostatic adenocarcinoma and high-grade prostatic intraepithelial neoplasia (HGPIN)...
- Induction of invasive phenotype by Casodex in hormone-sensitive prostate cancer cells
Department of Biological Science, University of Notre Dame, Notre Dame, IN 46556, USA
J Steroid Biochem Mol Biol 83:101-11. 2002
..These observations have significant implications in the treatment of prostate cancer, since the appearance of a more aggressive phenotype following treatment is clearly undesirable...
- Transgenic mouse model for rapid pharmacodynamic evaluation of antiandrogens
Department of Medicine, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California at Los Angeles, California, USA
Cancer Res 66:10513-6. 2006
..ARR2 Pb-Lux mice provide a novel method for rapid pharmacodynamic evaluation of novel pharmacologic compounds designed to inhibit androgen receptor signaling...
- Rosiglitazone, a peroxisome proliferator-activated receptor-gamma agonist, reduces acute lung injury in endotoxemic rats
Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Crit Care Med 33:2309-16. 2005
..This study was designated to determine the effects of rosiglitazone on endotoxin-induced acute lung injury in rats...
Charles M Rudin
The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
Clin Cancer Res 18:3218-22. 2012
..The mechanism of action, preclinical and clinical data, and potential utility in other disease contexts are reviewed here...
- Drug-targeted inhibition of peroxisome proliferator-activated receptor-gamma enhances the chemopreventive effect of anti-estrogen therapy
Department of Oncology, Georgetown University School of Medicine, and Lombardi Comprehensive Cancer Center, Washington, DC, USA
Oncotarget 3:345-56. 2012
..These findings suggest that it may be possible to pharmacologically influence the responsiveness of tumors to anti-estrogen therapy...
- Androgen receptor as a target in androgen-independent prostate cancer
Steven P Balk
Cancer Biology Program, Division of Hematology Oncology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
Urology 60:132-8; discussion 138-9. 2002
..Understanding the mechanisms responsible for AR function in androgen-independent prostate cancer should allow the more rational development of antagonists that can enhance the efficacy of androgen ablation therapies...
- Ethanol modulates the VR-1 variant amiloride-insensitive salt taste receptor. II. Effect on chorda tympani salt responses
Department of Physiology, Division of Nephrology, Virginia Commonwealth University, Richmond, VA 23298, USA
J Gen Physiol 125:587-600. 2005
..VR-1 KO mice demonstrated no Bz-insensitive CT response to NaCl and no sensitivity to ethanol. We conclude that ethanol increases salt taste sensitivity by its direct action on the Bz-insensitive VR-1 variant salt taste receptor...
- Differential androgen deprivation therapies with anti-androgens casodex/bicalutamide or MDV3100/Enzalutamide versus anti-androgen receptor ASC-J9(R) Lead to promotion versus suppression of prostate cancer metastasis
Tzu Hua Lin
George Whipple Laboratory for Cancer Research, Department of Pathology, Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York 14642, USA
J Biol Chem 288:19359-69. 2013
..These findings suggest the potential risks of using anti-androgens and provide a potential new therapy using ASC-J9® to battle PCa metastasis at the castration-resistant stage. ..
- Selection for androgen receptor mutations in prostate cancers treated with androgen antagonist
M E Taplin
University of Massachusetts Cancer Center, Worcester 01655, USA
Cancer Res 59:2511-5. 1999
..These findings demonstrate that AR mutations occur in response to strong selective pressure from flutamide treatment...
- Estrogen improves vascular function via peroxisome-proliferator-activated-receptor-γ
Medizinische Klinik und Poliklinik II, Innere Medizin, Universitatsklinikum Bonn, Sigmund Freud Str 25, 53105 Bonn, Germany
J Mol Cell Cardiol 53:268-76. 2012
- Apoptosis induced in HepG2 cells by the synthetic cannabinoid WIN: involvement of the transcription factor PPARgamma
Dipartimento di Scienze Biochimiche, Universita di Palermo, Via del Vespro 129, 90127 Palermo, Italy
Biochimie 91:457-65. 2009
..Altogether, the results seem to indicate a potential therapeutic role of WIN in hepatic cancer treatment...
- PPARgamma agonists inhibit TGF-beta induced pulmonary myofibroblast differentiation and collagen production: implications for therapy of lung fibrosis
Heather A Burgess
Department of Environmental Medicine, Univ of Rochester School of Medicine, 601 Elmwood Ave, Rochester, NY 14642, USA
Am J Physiol Lung Cell Mol Physiol 288:L1146-53. 2005
..Thus PPARgamma agonists have novel and potent antifibrotic effects in human lung fibroblasts and may have potential for therapy of fibrotic diseases in the lung and other tissues...
- Antagonistic interaction between bicalutamide (Casodex) and radiation in androgen-positive prostate cancer LNCaP cells
Institut Curie, Bât 110 112, Centre Universitaire, Orsay, France
Prostate 70:401-11. 2010
..However, biological data for the interaction between bicalutamide and ionizing radiation in concomitant association are lacking...
- Novel mechanism of lapatinib resistance in HER2-positive breast tumor cells: activation of AXL
Department of Translational Research, GlaxoSmithKline, King of Prussia, Pennsylvania, USA
Cancer Res 69:6871-8. 2009
- Telmisartan ameliorates insulin sensitivity by activating the AMPK/SIRT1 pathway in skeletal muscle of obese db/db mice
Department of Cardio Diabetes Medicine, University of Tokushima Graduate School of Health Biosciences, 3 18 15 Kuramoto, Tokushima 770 8503, Japan
Cardiovasc Diabetol 11:139. 2012
..Here, we investigated the pathways through which telmisartan acts on skeletal muscle, in vitro as well as in vivo...
- Capsaicin, a component of red peppers, induces expression of androgen receptor via PI3K and MAPK pathways in prostate LNCaP cells
Department of Biochemistry and Molecular Biology, School of Medicine, University of Alcala, Madrid, Spain
FEBS Lett 583:141-7. 2009
..AR silencing by the use of siRNA, as well as blocking the AR receptor with bicalutamide, inhibited the proliferative effect of capsaicin...
- Functional consequences of cysteine modification in the ligand binding sites of peroxisome proliferator activated receptors by GW9662
Lisa M Leesnitzer
Systems Research, GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27709, USA
Biochemistry 41:6640-50. 2002
- Sulfonamide anilides, a novel class of histone deacetylase inhibitors, are antiproliferative against human tumors
MethylGene, Inc, St Laurent, Quebec, H4S 2A1 Canada
Cancer Res 62:4325-30. 2002
..We have designed and synthesized novel nonhydroxamate sulfonamide anilides that can inhibit human HDAC enzymes and can induce hyperacetylation of histones in human cancer cells...
- Non-steroidal antiandrogens act as AF-1 agonists under conditions of high androgen-receptor expression
Pharmacological Research Department, ASKA Pharmaceutical Co Ltd, Takatsu ku, Kawasaki, Kanagawa, Japan
Prostate 67:630-7. 2007
- The novel histone deacetylase inhibitor BML-210 exerts growth inhibitory, proapoptotic and differentiation stimulating effects on the human leukemia cell lines
Department of Developmental Biology, Institute of Biochemistry, LT 08662 Vilnius, Lithuania
Eur J Pharmacol 549:9-18. 2006
..These findings suggest that BML-210 could be a promising antileukemic agent to induce apoptosis and to modulate differentiation through the modulation of histone acetylation and gene expression...
- Androgen receptor interacts with telomeric proteins in prostate cancer cells
Sahn Ho Kim
Vattikuti Urology Institute, Henry Ford Hospital, Detroit, Michigan 48202, USA
J Biol Chem 285:10472-6. 2010
..Together, these observations suggest an allosteric role of AR in telomere complex stability in prostate cancer cells and suggest that AR-antagonist Casodex-mediated cell death may be due to telomere complex disruption...
- Domain-selective small-molecule inhibitor of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation
Stephen J Haggarty
Department of Molecular and Cellular Biology, and Harvard Institute of Chemistry and Cell Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA
Proc Natl Acad Sci U S A 100:4389-94. 2003
..They also suggest that small molecules that selectively inhibit HDAC6-mediated alpha-tubulin deacetylation, a first example of which is tubacin, might have therapeutic applications as antimetastatic and antiangiogenic agents...
- Activation of the androgen receptor N-terminal domain by interleukin-6 via MAPK and STAT3 signal transduction pathways
Department of Cancer Endocrinology, British Columbia Cancer Agency, 600 West 10th Avenue, Vancouver, British Columbia V5Z 4E6, Canada
J Biol Chem 277:7076-85. 2002
..These results demonstrate that activation of the human AR NTD by IL-6 was mediated through MAPK and STAT3 signal transduction pathways in LNCaP prostate cancer cells...
- Neuroprotection against focal ischemic brain injury by the peroxisome proliferator-activated receptor-gamma agonist rosiglitazone
Department of Neurology, University of Pittsburgh School of Medicine, PA 15213, USA
J Neurochem 97:435-48. 2006
..These results suggest that the PPAR-gamma agonist rosiglitazone has neuroprotective properties that are at least partially mediated via anti-inflammatory actions, and is thus a potential novel therapeutic agent for stroke...
- The role of antiandrogen monotherapy in the treatment of prostate cancer
Department of Urology, The Royal Hallamshire Hospital, Sheffield, UK
BJU Int 91:455-61. 2003
..Bicalutamide has a more favourable side-effect profile than the other antiandrogens and is more likely to promote compliance...
- Antagonist of peroxisome proliferator-activated receptor gamma induces cerebellar amyloid-beta levels and motor dysfunction in APP/PS1 transgenic mice
Protein Science Key Laboratory of the Ministry of Education, Department of Biological Sciences and Biotechnology, School of Medicine, Tsinghua University, Beijing 100084, PR China
Biochem Biophys Res Commun 384:357-61. 2009
..Since cerebellum is spared from significant Abeta accumulation and neurotoxicity in AD patients and animal models, these findings suggest a crucial role of PPARgamma steady-state activity in protection of cerebellum against AD pathology...
- Highly favorable antiviral activity and resistance profile of the novel thiocarboxanilide pentenyloxy ether derivatives UC-781 and UC-82 as inhibitors of human immunodeficiency virus type 1 replication
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium
Mol Pharmacol 50:394-401. 1996
- Peroxisome proliferator-activated receptor-gamma antagonists exhibit potent antiproliferative effects versus many hematopoietic and epithelial cancer cell lines
Jack D Burton
Center for Molecular Medicine and Immunology, Belleville, New Jersey 07109, USA
Anticancer Drugs 18:525-34. 2007
..These findings support further translational studies to explore the mechanism of action and therapeutic potential of this class of agents...
- Novel mutations of androgen receptor: a possible mechanism of bicalutamide withdrawal syndrome
Pharmaceutical Research Laboratories, Takeda Chemical Industries, Ltd, Osaka 532 8686, Japan
Cancer Res 63:149-53. 2003
..Our data strongly support the hypothesis that AR mutation is one possible mechanism of the AWS and suggest that flutamide might be effective as a second-line therapy for refractory PC previously treated with bicalutamide...
- A novel androgen receptor-binding element modulates Cdc6 transcription in prostate cancer cells during cell-cycle progression
Department of Physiology and Biophysics, Robert Wood Johnson Medical School, UMDNJ, Piscataway, NJ 08854, USA
Nucleic Acids Res 37:4826-38. 2009
..Collectively, our results suggest that Cdc6 is a key regulatory target for AR and provide new insights into the mechanisms of prostate cancer cell proliferation...
- Development of a comprehensive human immunodeficiency virus type 1 screening algorithm for discovery and preclinical testing of topical microbicides
Southern Research Institute, 431 Aviation Way, Frederick, Maryland 21701, USA
Antimicrob Agents Chemother 52:1768-81. 2008
- Acceptability of UC781 gel as a rectal microbicide among HIV-uninfected women and men
HIV Center for Clinical and Behavioral Studies, New York State Psychiatric Institute and Columbia University, 1051 Riverside Drive, Unit 15, New York, NY 10032, USA
AIDS Behav 14:618-28. 2010
..Acceptability research is essential in early phases of microbicide development to identify potential problems, understand user preferences, and introduce changes if needed...
- Pronociceptive response elicited by TRPA1 receptor activation in mice
E L Andrade
Department of Pharmacology, Federal University of Santa Catarina, CCB, Campus Universitario Trindade, 88049 900, Florianopolis, SC, Brazil
Neuroscience 152:511-20. 2008
..Thus, the TRPA1 receptor has an apparently relevant role in nociceptive processes and the selective TRPA1 antagonist might possess a potential antinociceptive property...
- Peroxisome proliferator-activated receptor gamma is a target of progesterone regulation in the preovulatory follicles and controls ovulation in mice
University of Illinois, MC 114, 534 Burrill Hall, 407 S Goodwin, Urbana, IL 61801, USA
Mol Cell Biol 28:1770-82. 2008
..Collectively, these studies revealed that PPARgamma is a key mediator of the biological actions of PR in the granulosa cells and activation of its downstream pathways critically controls ovulation...
- Androgen receptor mediates non-genomic activation of phosphatidylinositol 3-OH kinase in androgen-sensitive epithelial cells
Génétique des Eucaryotes et Endocrinologie Moléculaire, UMR 6547 CNRS Université Blaise Pascal, Campus Universitaire des Cezeaux, 24 avenue des Landais, 63177 Aubiere Cedex, France
J Biol Chem 279:14579-86. 2004
..Together, these novel findings point out an important and physiologically relevant link between androgens and the PI3-K/AKT signaling pathway in governing cell survival...
- Inhibition of a Golgi complex lysophospholipid acyltransferase induces membrane tubule formation and retrograde trafficking
Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA
Mol Biol Cell 14:3459-69. 2003
..These two opposing enzyme activities may help to coordinately regulate Golgi membrane shape and tubule formation...
- Isolation, structure, and absolute stereochemistry of platensimycin, a broad spectrum antibiotic discovered using an antisense differential sensitivity strategy
Sheo B Singh
Merck Research Laboratories, P O Box 2000, Rahway, New Jersey 07065, USA
J Am Chem Soc 128:11916-20. 2006
..However, cyclohexenone ring conformation renders for the stronger binding interaction with the enzyme. The isolation, structure elucidation, derivatization, and biological activity of 6,7-dihydroplatensimycin are described...
- A randomized six-day safety study of an antiretroviral microbicide candidate UC781, a non-nucleoside reverse transcriptase inhibitor
Jill L Schwartz
CONRAD, Eastern Virginia Medical School, Arlington, Virginia 22209, USA
Sex Transm Dis 35:414-9. 2008
..This study evaluated the effect of a single dose and 5 additional consecutive daily doses of UC781 gel at concentrations of 0.1%, 0.25%, 1.0%, and 0% on urogenital irritation...
- The lysophospholipid acyltransferase antagonist CI-976 inhibits a late step in COPII vesicle budding
William J Brown
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA
Traffic 9:786-97. 2008
..These results identify a small molecule inhibitor of a very late step in COPII vesicle formation, consistent with fission inhibition, and demonstrate that this step is likely facilitated by an ER-associated LPAT...
- PPARgamma inhibitors reduce tubulin protein levels by a PPARgamma, PPARdelta and proteasome-independent mechanism, resulting in cell cycle arrest, apoptosis and reduced metastasis of colorectal carcinoma cells
Katherine L Schaefer
Section of Gastroenterology and Hepatology, University of Rochester Medical Center, Rochester, NY 14642, USA
Int J Cancer 120:702-13. 2007
..These results suggest that PPARgamma inhibitors are a novel potential antimicrotubule therapy for CRC that acts by directly reducing microtubule precursors...
- A novel vanilloid receptor-1 (VR-1) variant mammalian salt taste receptor
Department of Physiology, Virginia Commonwealth University, Richmond, VA 23298 0551, USA
Chem Senses 30:i42-3. 2005
- Ethanol modulates the VR-1 variant amiloride-insensitive salt taste receptor. I. Effect on TRC volume and Na+ flux
Department of Physiology, Division of Nephrology, Virginia Commonwealth University, Richmond, VA 23298, USA
J Gen Physiol 125:569-85. 2005
..We conclude that in the presence of mineral salts, ethanol modulates the Bz-insensitive VR-1 variant salt taste receptor...
- GW9662, a potent antagonist of PPARgamma, inhibits growth of breast tumour cells and promotes the anticancer effects of the PPARgamma agonist rosiglitazone, independently of PPARgamma activation
Jill M Seargent
Cancer Research Unit, Tom Connor s Cancer Research Centre, University of Bradford, All Saints Road, Bradford BD7 1DP, UK
Br J Pharmacol 143:933-7. 2004
..As such, these data support the existence of PPARgamma-independent pathways and question the central belief that PPARgamma ligands mediate their anticancer effects via activation of PPARgamma...
- Dynamics of intracellular movement and nucleocytoplasmic recycling of the ligand-activated androgen receptor in living cells
R K Tyagi
Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, 78284, USA
Mol Endocrinol 14:1162-74. 2000
- A unique lysophospholipid acyltransferase (LPAT) antagonist, CI-976, affects secretory and endocytic membrane trafficking pathways
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA
J Cell Sci 118:3061-71. 2005
- Androgen receptor alterations in prostate cancer relapsed during a combined androgen blockade by orchiectomy and bicalutamide
Department of Clinical Genetics, Tampere University Hospital, Tampere, Finland
Lab Invest 81:1647-51. 2001
..These data suggest that different AR variants are developed and selected for during various types of hormonal treatments, and also, that CAB achieved by orchiectomy and bicalutamide does not act as a selective force for AR amplification...
- Androgen receptor-mediated repression of novel target genes
Department of Preventive Medicine, Norris Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
Prostate 67:1371-83. 2007
- Peroxisome proliferator-activated receptor gamma inhibition prevents adhesion to the extracellular matrix and induces anoikis in hepatocellular carcinoma cells
Katherine L Schaefer
Section of Gastroenterology, Boston Medical Center, Boston, MA 02118, USA
Cancer Res 65:2251-9. 2005
..Inhibition of PPARgamma function causes HCC cell death by preventing adhesion and inducing anoikis-mediated apoptosis. PPARgamma inhibitors represent a potential novel treatment approach to HCC...
- Anilides of (R)-trifluoro-2-hydroxy-2-methylpropionic acid as inhibitors of pyruvate dehydrogenase kinase
G R Bebernitz
Metabolic and Cardiovascular Disease Research, Novartis Institute for Biomedical Research, Summit, New Jersey 07901, USA
J Med Chem 43:2248-57. 2000
..Nevertheless, they are effective at increasing the utilization and disposal of lactate and could be of utility to ameliorate conditions of inappropriate blood lactate elevation...
- Stress kinase signaling regulates androgen receptor phosphorylation, transcription, and localization
Department of Microbiology, P O Box 800734, University of Virginia Health System, Charlottesville, Virginia 22908, USA
Mol Endocrinol 20:503-15. 2006
..Our data suggest that stress kinase signaling and nuclear export regulate AR transcriptional activity...
- Characterization of a novel CI-976-sensitive lysophospholipid acyltransferase that is associated with the Golgi complex
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA
Biochem Biophys Res Commun 313:681-6. 2004
..0 and 8.0. These studies further define a unique LPC/LPE-specific LPAT from Golgi membranes that likely has a novel function in membrane trafficking...