p glycoprotein

Summary

Summary: A 170-kDa transmembrane glycoprotein from the superfamily of ATP-BINDING CASSETTE TRANSPORTERS. It serves as an ATP-dependent efflux pump for a variety of chemicals, including many ANTINEOPLASTIC AGENTS. Overexpression of this glycoprotein is associated with multidrug resistance (see DRUG RESISTANCE, MULTIPLE).

Top Publications

  1. ncbi A "silent" polymorphism in the MDR1 gene changes substrate specificity
    Chava Kimchi-Sarfaty
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
    Science 315:525-8. 2007
  2. ncbi P-glycoprotein: from genomics to mechanism
    Suresh V Ambudkar
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute NIH, 37 Convent Drive, Building 37, Room 1A 09, Bethesda, MD 20892 4254, USA
    Oncogene 22:7468-85. 2003
  3. ncbi The role of ABC transporters in clinical practice
    Gregory D Leonard
    Cancer Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Oncologist 8:411-24. 2003
  4. ncbi Pharmacogenomics--drug disposition, drug targets, and side effects
    William E Evans
    St Jude Children s Research Hospital and the University of Tennessee Colleges of Pharmacy and Medicine, Memphis 38101 0318, USA
    N Engl J Med 348:538-49. 2003
  5. ncbi Multidrug resistance in cancer: role of ATP-dependent transporters
    Michael M Gottesman
    Laboratory of Cell Biology and Cancer Therapeutics Branch, The Center for Cancer Research, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Rev Cancer 2:48-58. 2002
  6. pmc Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo
    S Hoffmeyer
    Epidauros Biotechnology, Pharmacogenetics Laboratory, Am Neuland 1, D 82347 Bernried, Germany
    Proc Natl Acad Sci U S A 97:3473-8. 2000
  7. ncbi Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line
    S P Cole
    Cancer Research Laboratories, Queen s University, Kingston, Ontario, Canada
    Science 258:1650-4. 1992
  8. ncbi Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs
    A H Schinkel
    Division of Molecular Biology, The Netherlands Cancer Institute, Amsterdam
    Cell 77:491-502. 1994
  9. ncbi Multidrug resistance proteins: role of P-glycoprotein, MRP1, MRP2, and BCRP (ABCG2) in tissue defense
    Elaine M Leslie
    Division of Drug Delivery and Disposition, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Toxicol Appl Pharmacol 204:216-37. 2005
  10. ncbi Multidrug resistance (MDR) in cancer. Mechanisms, reversal using modulators of MDR and the role of MDR modulators in influencing the pharmacokinetics of anticancer drugs
    R Krishna
    Department of Advanced Therapeutics, British Columbia Cancer Agency, BC V5Z 4E6, Vancouver, Canada
    Eur J Pharm Sci 11:265-83. 2000

Detail Information

Publications271 found, 100 shown here

  1. ncbi A "silent" polymorphism in the MDR1 gene changes substrate specificity
    Chava Kimchi-Sarfaty
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
    Science 315:525-8. 2007
    ....
  2. ncbi P-glycoprotein: from genomics to mechanism
    Suresh V Ambudkar
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute NIH, 37 Convent Drive, Building 37, Room 1A 09, Bethesda, MD 20892 4254, USA
    Oncogene 22:7468-85. 2003
    ..Understanding of the biology, genetics, and biochemistry of P-gp promises to improve the treatment of cancer and explain the pharmacokinetics of many commonly used drugs...
  3. ncbi The role of ABC transporters in clinical practice
    Gregory D Leonard
    Cancer Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Oncologist 8:411-24. 2003
    ..Further optimism is warranted with the advent of potent, nontoxic inhibitors and new treatment strategies, including the combination of new targeted therapies with therapies aimed at the prevention of drug resistance...
  4. ncbi Pharmacogenomics--drug disposition, drug targets, and side effects
    William E Evans
    St Jude Children s Research Hospital and the University of Tennessee Colleges of Pharmacy and Medicine, Memphis 38101 0318, USA
    N Engl J Med 348:538-49. 2003
  5. ncbi Multidrug resistance in cancer: role of ATP-dependent transporters
    Michael M Gottesman
    Laboratory of Cell Biology and Cancer Therapeutics Branch, The Center for Cancer Research, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Rev Cancer 2:48-58. 2002
    ..Therefore, the ability to predict and circumvent drug resistance is likely to improve chemotherapy...
  6. pmc Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo
    S Hoffmeyer
    Epidauros Biotechnology, Pharmacogenetics Laboratory, Am Neuland 1, D 82347 Bernried, Germany
    Proc Natl Acad Sci U S A 97:3473-8. 2000
    ..Homozygosity for this variant was observed in 24% of our sample population (n = 188). This polymorphism is expected to affect the absorption and tissue concentrations of numerous other substrates of MDR-1...
  7. ncbi Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line
    S P Cole
    Cancer Research Laboratories, Queen s University, Kingston, Ontario, Canada
    Science 258:1650-4. 1992
    ..1. Reversion to drug sensitivity was associated with loss of gene amplification and a marked decrease in mRNA expression. The mRNA encodes a member of the ATP-binding cassette transmembrane transporter superfamily...
  8. ncbi Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs
    A H Schinkel
    Division of Molecular Biology, The Netherlands Cancer Institute, Amsterdam
    Cell 77:491-502. 1994
    ....
  9. ncbi Multidrug resistance proteins: role of P-glycoprotein, MRP1, MRP2, and BCRP (ABCG2) in tissue defense
    Elaine M Leslie
    Division of Drug Delivery and Disposition, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Toxicol Appl Pharmacol 204:216-37. 2005
    ..Species variations in substrate specificity and tissue distribution of these transporters are also addressed since these properties have implications for in vivo models of toxicity used for drug discovery and development...
  10. ncbi Multidrug resistance (MDR) in cancer. Mechanisms, reversal using modulators of MDR and the role of MDR modulators in influencing the pharmacokinetics of anticancer drugs
    R Krishna
    Department of Advanced Therapeutics, British Columbia Cancer Agency, BC V5Z 4E6, Vancouver, Canada
    Eur J Pharm Sci 11:265-83. 2000
    ....
  11. pmc Normal viability and altered pharmacokinetics in mice lacking mdr1-type (drug-transporting) P-glycoproteins
    A H Schinkel
    Division of Molecular Biology, The Netherlands Cancer Institute, Amsterdam
    Proc Natl Acad Sci U S A 94:4028-33. 1997
    ..mdr1a/1b (-/-) mice should provide a useful model system to further test the pharmacological roles of the drug-transporting P-gps and to analyze the specificity and effectivity of P-gp-blocking drugs...
  12. ncbi Biochemical, cellular, and pharmacological aspects of the multidrug transporter
    S V Ambudkar
    Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Annu Rev Pharmacol Toxicol 39:361-98. 1999
    ..This review summarizes current research on the structure-function analysis of P-glycoprotein, its mechanism of action, and facts and speculations about its normal physiological role...
  13. ncbi P-glycoprotein (MDR1) expression in leukemic cells is regulated at two distinct steps, mRNA stabilization and translational initiation
    Ernesto Yague
    Medical Research Council Clinical Sciences Centre, Imperial College Faculty of Medicine, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, United Kingdom
    J Biol Chem 278:10344-52. 2003
    ..These findings have implications for the avoidance or reversal of multidrug resistance in the clinic...
  14. pmc P-glycoprotein in the blood-brain barrier of mice influences the brain penetration and pharmacological activity of many drugs
    A H Schinkel
    The Netherlands Cancer Institute, Division of Molecular Biology, 1066 CX Amsterdam, The Netherlands
    J Clin Invest 97:2517-24. 1996
    ..These results point to the possible role that the drug-transporting P-GP(s) may play in the clinical use of many drugs, especially those with potential targets in the central nervous system...
  15. ncbi Structure, function and regulation of P-glycoprotein and its clinical relevance in drug disposition
    S F Zhou
    Division of Chinese Medicine, School of Health Science, WHO Collaborating Centre for Traditional Medicine, RMIT University, Bundoora, Vic, Australia
    Xenobiotica 38:802-32. 2008
    ..8. Further studies are warranted to explore the physiological function and pharmacological role of P-gp/MDR1...
  16. ncbi Clinical management of recurrent breast cancer: development of multidrug resistance (MDR) and strategies to circumvent it
    William N Hait
    University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, and The Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA
    Semin Oncol 32:S16-21. 2005
    ..Despite successful proof of concept in the laboratory, to date none of these agents has had a major impact in the clinic...
  17. ncbi Functional expression of P-glycoprotein and multidrug resistance-associated protein (Mrp1) in primary cultures of rat astrocytes
    X Declèves
    INSERM U26, Hopital Fernand Widal, Paris, France
    J Neurosci Res 60:594-601. 2000
    ..Taken together, our results provide the first biochemical and functional evidence supporting the expression of P-gp and Mrp1 in rat cultured astrocytes...
  18. ncbi Frequency of single nucleotide polymorphisms in the P-glycoprotein drug transporter MDR1 gene in white subjects
    I Cascorbi
    Institute of Clinical Pharmacology, University Medical Center Charite, Humboldt University Berlin
    Clin Pharmacol Ther 69:169-74. 2001
    ..Various polymorphisms in the MDR1 gene were recently identified. A silent mutation in exon 26 (C3435T) was correlated with intestinal P-glycoprotein expression and oral bioavailability of digoxin...
  19. ncbi Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance
    Catia Marzolini
    Division of Clinical Pharmacology, Vanderbilt University, Nashville, TN 37232, USA
    Clin Pharmacol Ther 75:13-33. 2004
    ..In addition, issues relating to MDR1 haplotypes, environmental factors, and study design, as potential confounding factors of the observed MDR1 polymorphism effect in vivo, are also discussed...
  20. ncbi Multidrug resistance in small cell lung cancer: expression of P-glycoprotein, multidrug resistance protein 1 and lung resistance protein in chemo-naive patients and in relapsed disease
    Nadja Triller
    University Clinic of Respiratory and Allergic Diseases, 4204 Golnik, Slovenia
    Lung Cancer 54:235-40. 2006
    ....
  21. ncbi In vitro and in vivo reversal of P-glycoprotein-mediated multidrug resistance by a novel potent modulator, XR9576
    P Mistry
    Xenova Limited, Slough, Berkshire, United Kingdom
    Cancer Res 61:749-58. 2001
    ..It exhibits potent i.v. and p.o. activity without apparently enhancing the plasma pharmacokinetics of paclitaxel or the toxicity of coadministered drugs. Hence, XR9576 holds great promise for the treatment of P-gp-mediated MDR cancers...
  22. ncbi YB-1 is upregulated during prostate cancer tumor progression and increases P-glycoprotein activity
    Pepita Gimenez-Bonafe
    The Prostate Centre at Vancouver General Hospital, University of British Columbia, Vancouver, British Columbia, Canada
    Prostate 59:337-49. 2004
    ..We focused on increased YB-1 expression during progression in clinical specimens, and further examined one of its downstream targets, P-glycoprotein (P-gp)...
  23. ncbi Inhibition of P-glycoprotein by newer antidepressants
    Johanna Weiss
    Department of Internal Medicine VI, Clinical Pharmacology, and Pharmacoepidemiology, University of Heidelberg, Heidelberg, Germany
    J Pharmacol Exp Ther 305:197-204. 2003
    ....
  24. ncbi Flavonoid permeability across an in situ model of the blood-brain barrier
    Kuresh A Youdim
    Antioxidant Research Group, Wolfson Centre for Age Related Diseases, Centre for Neuroscience Research, Guy s King s and St Thomas s School of Biomedical Sciences, King s College, London SE1 1UL, UK
    Free Radic Biol Med 36:592-604. 2004
    ..In conclusion, the results demonstrate that flavonoids are able to traverse the BBB in vivo. However, the permeability of certain flavonoids in vivo is influenced by their lipophilicity and interactions with efflux transporters...
  25. ncbi Molecular targeting therapy of cancer: drug resistance, apoptosis and survival signal
    Takashi Tsuruo
    Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1 1 1 Yayoi, Bunkyo ku, Tokyo 113 0032
    Cancer Sci 94:15-21. 2003
    ..Our present studies provide novel targets for future effective molecular cancer therapeutics...
  26. ncbi Induction of human MDR1 gene expression by 2-acetylaminofluorene is mediated by effectors of the phosphoinositide 3-kinase pathway that activate NF-kappaB signaling
    Macus Tien Kuo
    Department of Molecular Pathology, The University of Texas M D Anderson Cancer Center, Houston, Texas, TX 77030, USA
    Oncogene 21:1945-54. 2002
    ..These results demonstrated that 2-AAF up-regulates MDR1 expression is mediated by the multiple effectors of the PI3K signaling pathway...
  27. pmc Absence of the mdr1a P-Glycoprotein in mice affects tissue distribution and pharmacokinetics of dexamethasone, digoxin, and cyclosporin A
    A H Schinkel
    The Netherlands Cancer Institute, Division of Molecular Biology, Amsterdam, The Netherlands
    J Clin Invest 96:1698-705. 1995
    ..These results may explain a range of pharmacological interactions observed between various drugs in patients...
  28. ncbi Multidrug resistance: molecular mechanisms and clinical relevance
    V Ling
    BC Cancer Research Centre, Vancouver, Canada
    Cancer Chemother Pharmacol 40:S3-8. 1997
    ..Despite the potential of tumor cells to protect themselves, a variety of malignancies can be successfully treated with chemotherapy. This may provide unique insights...
  29. ncbi Effect of the mutation (C3435T) at exon 26 of the MDR1 gene on expression level of MDR1 messenger ribonucleic acid in duodenal enterocytes of healthy Japanese subjects
    Tsutomu Nakamura
    Department of Hospital Pharmacy, School of Medicine, Kobe University, Japan
    Clin Pharmacol Ther 71:297-303. 2002
    ..This finding suggested a lower plasma concentration of the substrates for CYP3A4 in subjects harboring the C3435T mutation of the MDR1 gene...
  30. pmc Interaction of common azole antifungals with P glycoprotein
    Er jia Wang
    Drug Metabolism and Pharmacokinetics, Schering Plough Research Institute, Lafayette, New Jersey 07848, USA
    Antimicrob Agents Chemother 46:160-5. 2002
    ..The most studied transporter in the mammalian ATP-binding cassette transporter superfamily, P glycoprotein (P-gp), ejects many structurally unrelated amphiphilic and lipophilic xenobiotics...
  31. ncbi RNA expression of breast cancer resistance protein, lung resistance-related protein, multidrug resistance-associated proteins 1 and 2, and multidrug resistance gene 1 in breast cancer: correlation with chemotherapeutic response
    Herman Burger
    Department of Medical Oncology, Erasmus Medical Center Rotterdam Daniel den Hoed Kliniek Josephine Nefkens Institute, 3000 DR Rotterdam, The Netherlands
    Clin Cancer Res 9:827-36. 2003
    ..The aim of this study was to investigate whether expression of particular drug resistance genes in primary operable breast cancer correlates with response to first-line chemotherapy in advanced disease...
  32. ncbi Sequential gene disruption in Candida albicans by FLP-mediated site-specific recombination
    J Morschhäuser
    Zentrum für Infektionsforschung, Universitat Wurzburg, Rontgenring 11, D 97070 Wurzburg, Germany
    Mol Microbiol 32:547-56. 1999
    ..albicans mutants as it eliminates the need for a negative selection scheme for marker deletion and minimizes the risk of mitotic recombination in sequential disruption experiments...
  33. ncbi Expression of P-glycoprotein in human placenta: relation to genetic polymorphism of the multidrug resistance (MDR)-1 gene
    M Tanabe
    Department of Clinical Pharmacokinetics, Division of Pharmaceutical Sciences, Graduate School, Kyushu University, Fukuoka, Japan
    J Pharmacol Exp Ther 297:1137-43. 2001
    ....
  34. ncbi P-glycoprotein models of the apo and ATP-bound states based on homology with Sav1866 and MalK
    Megan L O'Mara
    Department of Biological Sciences, University of Calgary, 2500 University Drive NW, Calgary, Alberta, Canada
    FEBS Lett 581:4217-22. 2007
    ..These conformations (see supplementary material) may characterize some of the major steps in the nucleotide catalytic cycle...
  35. pmc Comparison of gene expression profiles of Candida albicans azole-resistant clinical isolates and laboratory strains exposed to drugs inducing multidrug transporters
    Mahir Karababa
    Institut de Microbiologie, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland
    Antimicrob Agents Chemother 48:3064-79. 2004
    ..Upregulated genes in both drug-exposed conditions and clinical strains are drug resistance genes but also genes that could be activated under cell damage conditions...
  36. ncbi Tariquidar (XR9576): a P-glycoprotein drug efflux pump inhibitor
    Elizabeth Fox
    National Cancer Institute, Pediatric Oncology Branch, Bethesda, MD 20892, USA
    Expert Rev Anticancer Ther 7:447-59. 2007
    ..Tariquidar can be considered an ideal agent for testing the role of P-glycoprotein inhibition in cancer...
  37. ncbi P-glycoprotein protects leukemia cells against caspase-dependent, but not caspase-independent, cell death
    R W Johnstone
    The Austin Research Institute, Austin Hospital, Heidelberg, Victoria, Australia
    Blood 93:1075-85. 1999
    ..This study has confirmed a potential novel physiological function for P-glycoprotein and it now remains to dissect the molecular mechanisms involved in the inhibition of capsase-dependent cell death by P-glycoprotein...
  38. ncbi Regulation of the multidrug resistance transporter P-glycoprotein in multicellular tumor spheroids by hypoxia-inducible factor (HIF-1) and reactive oxygen species
    Maria Wartenberg
    Department of Neurophysiology, University of Cologne, D 50931 Cologne, Germany
    FASEB J 17:503-5. 2003
    ..Hence, our data demonstrate that expression of P-gp in multicellular tumor spheroids is under the control of HIF-1...
  39. ncbi MDR1 pharmacogenetics: frequency of the C3435T mutation in exon 26 is significantly influenced by ethnicity
    M M Ameyaw
    University of Aberdeen, Department of Medicine and Therapeutics, Institute of Medical Sciences, Foresterhill, Aberdeen, UK
    Pharmacogenetics 11:217-21. 2001
    ..The high frequency of the C allele in the African group implies overexpression of PGP and may have important therapeutic and prognostic implications for use of PGP dependent drugs in individuals of African origin...
  40. ncbi Response to antiretroviral treatment in HIV-1-infected individuals with allelic variants of the multidrug resistance transporter 1: a pharmacogenetics study
    Jacques Fellay
    Division of Infectious Diseases, University Hospital of Lausanne, Lausanne, Switzerland
    Lancet 359:30-6. 2002
    ..This variability could have a genetic basis. We did a pharmacogenetics study to analyse the association between response to antiretroviral treatment and allelic variants of several genes...
  41. ncbi Brain penetration of methadone (R)- and (S)-enantiomers is greatly increased by P-glycoprotein deficiency in the blood-brain barrier of Abcb1a gene knockout mice
    Jun Sheng Wang
    Laboratory of Drug Disposition and Pharmacogenetics, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, 67 President Street, Charleston, SC 29425, USA
    Psychopharmacology (Berl) 173:132-8. 2004
    ..Therefore, the function of P-gp in blood-brain barrier (BBB) may affect the concentration of methadone at its site(s) of action in the central nervous system, thereby contributing to its therapeutic efficacy and/or adverse events...
  42. ncbi Identification of putative binding sites of P-glycoprotein based on its homology model
    Christoph Globisch
    Pharmaceutical Institute, University of Bonn, 53121 Bonn, Germany
    ChemMedChem 3:280-95. 2008
    ..The pockets are analyzed in relation to amino acids shown experimentally to influence the protein function. The results suggest that the protein has multiple binding sites and may bind and/or release substrates in multiple pathways...
  43. ncbi Identification of functionally variant MDR1 alleles among European Americans and African Americans
    R B Kim
    Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA
    Clin Pharmacol Ther 70:189-99. 2001
    ..Thus allelic variation in MDR1 is more common than previously recognized and involves multiple SNPs whose allelic frequencies vary between populations, and some of these SNPs are associated with altered P-glycoprotein function...
  44. ncbi Classification analysis of P-glycoprotein substrate specificity
    Remigijus Didziapetris
    Pharma Algorithms, Inc, Mickeviciaus 29, Vilnius 2001, Lithuania
    J Drug Target 11:391-406. 2003
    ..The definition of class-specific effects entails construction of the knowledge base that can be very useful in ADME profiling of new drugs...
  45. ncbi Rational use of in vitro P-glycoprotein assays in drug discovery
    J W Polli
    Preclinical Drug Metabolism and Pharmacokinetics, GlaxoSmithKline, Inc, Research Triangle Park, North Carolina 27709, USA
    J Pharmacol Exp Ther 299:620-8. 2001
    ..The efflux assay is more reliable at low/moderate P(app) and is the method of choice for evaluating drug candidates despite low throughput and reliance on liquid chromatography with tandem mass spectrometry...
  46. ncbi Mammalian drug efflux transporters of the ATP binding cassette (ABC) family: an overview
    Alfred H Schinkel
    Division of Experimental Therapy, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Adv Drug Deliv Rev 55:3-29. 2003
    ..We aim to provide an overview of properties of the mammalian ABC transporters known to mediate significant transport of clinically relevant drugs...
  47. ncbi P-glycoprotein increases from proximal to distal regions of human small intestine
    Stephane Mouly
    Hopital Lariboisiere, Service de Medecine Interne A, 75475 Paris Cedex 10, France
    Pharm Res 20:1595-9. 2003
    ..Accordingly, the distribution of P-gp was examined along the entire length of the human small intestine...
  48. ncbi beta-Amyloid efflux mediated by p-glycoprotein
    F C Lam
    Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, British Columbia, Canada
    J Neurochem 76:1121-8. 2001
    ..Taken together, our study suggests a novel mechanism of Abeta detachment from cellular membranes, and represents an obvious route towards identification of such a mechanism in the brain...
  49. ncbi Genetic polymorphisms of the human MDR1 drug transporter
    Matthias Schwab
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Auerbachstrasse 112, D 70376 Stuttgart, Germany
    Annu Rev Pharmacol Toxicol 43:285-307. 2003
    ..Potential implications of MDR1 polymorphisms for drug disposition, drug effects, and disease risk are discussed...
  50. ncbi Benefit of cyclosporine modulation of drug resistance in patients with poor-risk acute myeloid leukemia: a Southwest Oncology Group study
    A F List
    Southwest Oncology Group, Operations Office, 14980 Omicron Dr, San Antonio, TX, USA
    Blood 98:3212-20. 2001
    ....
  51. ncbi LY294,002, a specific inhibitor of PI3K/Akt kinase pathway, antagonizes P-glycoprotein-mediated multidrug resistance
    Miroslav Barancik
    Institute for Heart Research, Slovak Academy of Sciences, Dubravska cesta 9, PO Box 104, 840 05, Bratislava 45, Slovak Republic
    Eur J Pharm Sci 29:426-34. 2006
    ..MDR reversal effect of LY294,002 is accompanied with this compound's influence on vincristine-induced apoptosis...
  52. ncbi Inhibition of ABCB1 (MDR1) and ABCB4 (MDR3) expression by small interfering RNA and reversal of paclitaxel resistance in human ovarian cancer cells
    Zhenfeng Duan
    Department of Hematology Oncology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    Mol Cancer Ther 3:833-8. 2004
    ..These results indicate that siRNA targeted to ABCB1 can sensitize paclitaxel-resistant ovarian cancer cells in vitro and suggest that siRNA treatment may represent a new approach for the treatment of ABCB1-mediated drug resistance...
  53. ncbi Expression and cellular distribution of multidrug resistance-related proteins in the hippocampus of patients with mesial temporal lobe epilepsy
    Eleonora Aronica
    Department of Neuro Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    Epilepsia 45:441-51. 2004
    ....
  54. ncbi Chemotherapy and P-glycoprotein expression in chondrosarcoma
    R M Terek
    Department of Orthopaedics, Brown University and Rhode Island Hospital, Providence, USA
    J Orthop Res 16:585-90. 1998
    ..P-glycoprotein expression is common in benign and malignant cartilage lesions. The lack of response to chemotherapy may be related to the expression of P-glycoprotein...
  55. ncbi Cyclosporin A is a broad-spectrum multidrug resistance modulator
    Misbah Qadir
    Leukemia Section, Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA
    Clin Cancer Res 11:2320-6. 2005
    ..Cyclosporin A is known to also modulate MRP-1, and we hypothesized that broad-spectrum multidrug resistance modulation might contribute to its clinical efficacy...
  56. ncbi Reversal of P-glycoprotein-mediated multidrug resistance in cancer cells by the c-Jun NH2-terminal kinase
    Jun Zhou
    Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, Tianjin, China
    Cancer Res 66:445-52. 2006
    ..Our study provides the first direct evidence that enhancement of the JNK pathway down-regulates P-glycoprotein and reverses P-glycoprotein-mediated MDR in cancer cells...
  57. ncbi MDR1 promoter hypermethylation in MCF-7 human breast cancer cells: changes in chromatin structure induced by treatment with 5-Aza-cytidine
    Gloria L David
    The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231 1000, USA
    Cancer Biol Ther 3:540-8. 2004
    ..In this state, MDR1 expression was markedly sensitive to treatment with the histone deacetylase inhibitor trichostatin A...
  58. ncbi Evaluation of in vivo P-glycoprotein function at the blood-brain barrier among MDR1 gene polymorphisms by using 11C-verapamil
    Akihiro Takano
    Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan
    J Nucl Med 47:1427-33. 2006
    ..In the present study, we investigated the P-gp functional differences at the BBB between the haplotypes (1236TT, 2677TT, 3435TT vs. 1236CC, 2677GG, 3435CC) of the MDR1 gene with different quantitative analyses of (11)C-verapamil...
  59. pmc Identification of Nile red as a fluorescent substrate of the Candida albicans ATP-binding cassette transporters Cdr1p and Cdr2p and the major facilitator superfamily transporter Mdr1p
    Irena Ivnitski-Steele
    New Mexico Center for Molecular Discovery, University of New Mexico, Albuquerque, NM 87131, USA
    Anal Biochem 394:87-91. 2009
    ..This indicates that Nile red can be used for the identification of inhibitors specific for particular transporters mediating antifungal resistance in pathogenic yeast...
  60. ncbi Vascular and parenchymal mechanisms in multiple drug resistance: a lesson from human epilepsy
    Matteo Marroni
    Cerebrovascular Research, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    Curr Drug Targets 4:297-304. 2003
    ..This second line of defense for xenobiotics may have profound implications for the pharmacokinetic properties of antiepileptic drugs and their capacity to reach neuronal targets...
  61. ncbi Strategies for inhibition of MDR1 gene expression
    Dong Xu
    Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA
    Mol Pharmacol 66:268-75. 2004
    ..These studies suggest that there are several comparably effective strategies for inhibiting MDR1 expression...
  62. ncbi Inhibition of P-glycoprotein function by XR9576 in a solid tumour model can restore anticancer drug efficacy
    J Walker
    Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, University of Oxford, Oxford OX3 8PA, UK
    Eur J Cancer 40:594-605. 2004
    ..The results suggest that inhibition of P-gp in solid tumours is achievable and that generation of potent inhibitors will provide a significant benefit towards restoration of chemotherapy in solid tissues...
  63. pmc Role of P-glycoprotein in transplacental transfer of methadone
    Tatiana Nanovskaya
    Department of Obstetrics and Gynecology, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555 0587, USA
    Biochem Pharmacol 69:1869-78. 2005
    ..It is reasonable to speculate that placental disposition of methadone affects its concentration in the fetal circulation. If true, this may also be directly related to the incidence and intensity of neonatal abstinence syndrome (NAS)...
  64. ncbi Interaction of cytochrome P450 3A inhibitors with P-glycoprotein
    Kazuto Yasuda
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    J Pharmacol Exp Ther 303:323-32. 2002
    ..Simultaneous inhibition of Pgp by many CYP3A inhibitors contributes to human variation in the extent of drug-drug interactions...
  65. ncbi Suppressor mutations in the transmembrane segments of P-glycoprotein promote maturation of processing mutants and disrupt a subset of drug-binding sites
    Tip W Loo
    Department of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada
    J Biol Chem 282:32043-52. 2007
    ..These results show that the arginine mutations affect a subset of drug-binding sites and suggest that they rescue processing mutants by mimicking drug substrate interactions with P-gp...
  66. pmc Doxycycline induces expression of P glycoprotein in MCF-7 breast carcinoma cells
    Katrina L Mealey
    Department of Veterinary Physiology and Pharmacology, Texas A and M University College of Veterinary Medicine, College Station, Texas 77843 4466, USA
    Antimicrob Agents Chemother 46:755-61. 2002
    ..Doxycycline, a drug that has been used for treatment of bacterial infections in cancer patients, can induce functional P-gp expression in cancer cells, resulting in multidrug resistance...
  67. ncbi Interaction of omeprazole, lansoprazole and pantoprazole with P-glycoprotein
    C Pauli-Magnus
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Stuttgart, Germany
    Naunyn Schmiedebergs Arch Pharmacol 364:551-7. 2001
    ..In summary, our data provide evidence that proton pump inhibitors are substrates and inhibitors of P-glycoprotein. These findings might explain some of the drug interactions with proton pump inhibitors observed in vivo...
  68. ncbi Expression of COX-2, mPGE-synthase1, MDR-1 (P-gp), and Bcl-xL: a molecular pathway of H pylori-related gastric carcinogenesis
    Gerardo Nardone
    Department of Clinical and Experimental Medicine, Gastroenterology Unit, University Federico II, Naples, Italy
    J Pathol 202:305-12. 2004
    ..In conclusion, H pylori-dependent induction of COX-2 and mPGES1 is associated with enhanced production of P-gp and Bcl-xL that may contribute to gastric tumourigenesis and resistance to therapy...
  69. ncbi Isolation and sequence of the promoter region of the human multidrug-resistance (P-glycoprotein) gene
    K Ueda
    Laboratory of Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892
    J Biol Chem 262:17432-6. 1987
    ..This identification and isolation of promoter sequences for the MDR 1 gene will permit studies on how expression of this gene is regulated in normal human tissues and cancers...
  70. ncbi Ivermectin sensitivity in collies is associated with a deletion mutation of the mdr1 gene
    K L Mealey
    Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, Washington 99164 6610, USA
    Pharmacogenetics 11:727-33. 2001
    ..Dogs that are homozygous for the deletion mutation display the ivermectin-sensitive phenotype, while those that are homozygous normal or heterozygous do not display increased sensitivity to ivermectin...
  71. ncbi Small interfering RNA-induced suppression of MDR1 (P-glycoprotein) restores sensitivity to multidrug-resistant cancer cells
    Hao Wu
    Department of Pharmacology, University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901, USA
    Cancer Res 63:1515-9. 2003
    ..These studies indicate that RNA interference can modulate MDR in preclinical models...
  72. ncbi The gut as a barrier to drug absorption: combined role of cytochrome P450 3A and P-glycoprotein
    Y Zhang
    Department of Pharmacokinetics, Dynamics and Metabolism, Pfizer Global Research and Development, Groton, Connecticut, 06340, USA
    Clin Pharmacokinet 40:159-68. 2001
    ....
  73. pmc Transport of paclitaxel (Taxol) across the blood-brain barrier in vitro and in vivo
    Stephan Fellner
    Institute of Pharmacy, University of Regensburg, Regensburg, Germany
    J Clin Invest 110:1309-18. 2002
    ..Thus, p-gp is an important obstacle preventing paclitaxel entry into the brain, and inhibition of this transporter allows the drug to reach sensitive tumors within the CNS...
  74. ncbi Methanethiosulfonate derivatives of rhodamine and verapamil activate human P-glycoprotein at different sites
    Tip W Loo
    Canadian Institutes of Health Research Group in Membrane Biology, Departments of Medicine and Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada
    J Biol Chem 278:50136-41. 2003
    ..These results indicate that the MTS-rhodamine binding site overlaps that of colchicine and calcein-AM but not that of verapamil and Hoechst 33342 within the common drug-binding pocket...
  75. ncbi Correlation between steady-state ATP hydrolysis and vanadate-induced ADP trapping in Human P-glycoprotein. Evidence for ADP release as the rate-limiting step in the catalytic cycle and its modulation by substrates
    K M Kerr
    Laboratory of Cell Biology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 276:8657-64. 2001
    ..We suggest that substrates modulate the rate of ATPase activity of Pgp by controlling the rate of dissociation of ADP following ATP hydrolysis and that ADP release is the rate-limiting step in the normal catalytic cycle of Pgp...
  76. ncbi Cyclooxygenase-2, P-glycoprotein-170 and drug resistance; is chemoprevention against multidrug resistance possible?
    D Ratnasinghe
    Cancer Prevention Studies Branch, Division of Clinical Sciences, National Cancer Institute, NIH, Bethesda, MD 20892 7058, USA
    Anticancer Res 21:2141-7. 2001
    ..In this study we investigated whether expression of the inducible isoform of Cox (Cox-2) is linked with the multidrug resistance phenotype in breast cancer...
  77. ncbi Regulation of the stability of P-glycoprotein by ubiquitination
    Zhigang Zhang
    The Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, 195 Little Albany Street, New Brunswick, NJ 08901, USA
    Mol Pharmacol 66:395-403. 2004
    ....
  78. ncbi Pharmacokinetic and pharmacodynamic implications of P-glycoprotein modulation
    C J Matheny
    Division of Drug Delivery and Disposition, School of Pharmacy, University of North Carolina at Chapel Hill, 27599-7360, USA
    Pharmacotherapy 21:778-96. 2001
    ..Clinicians should recognize that P-gp induction or inhibition may have a substantial effect on the pharmacokinetics and pharmacodynamics of concomitantly administered drugs that are substrates for this transporter...
  79. ncbi ABCB1 (MDR 1) polymorphisms and progression-free survival among women with ovarian cancer following paclitaxel/carboplatin chemotherapy
    Sharon E Johnatty
    Queensland Institute of Medical Research, Brisbane, Queensland, Australia
    Clin Cancer Res 14:5594-601. 2008
    ..Although the functional consequences of ABCB1 polymorphisms have been the subject of numerous studies, few have assessed the association with clinical outcome...
  80. ncbi How can we best use structural information on P-glycoprotein to design inhibitors?
    Christopher A McDevitt
    Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK
    Pharmacol Ther 113:429-41. 2007
    ..In particular, the plethora of functional data can provide important regions on the protein that could conceivably be exploited as inhibitor targets...
  81. ncbi Recent progress in understanding the mechanism of P-glycoprotein-mediated drug efflux
    T W Loo
    Department of Medicine and Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada
    J Membr Biol 206:173-85. 2005
    ..In this mini-review, we discuss recent progress in determining the structure and mechanism of human P-glycoprotein...
  82. ncbi P-glycoprotein--implications of metabolism of neoplastic cells and cancer therapy
    Albert Breier
    Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Vlarska 5, 833 34 Bratislava, Slovak Republic
    Curr Cancer Drug Targets 5:457-68. 2005
    ..Effects of MDR reversal agents on the P-gp expression have also been reported. Function and expression of P-gp can be affected indirectly as well, e.g. through cyclooxygenase-2 or carbonic anhydrase-IX expression and effects...
  83. ncbi Effect of P-glycoprotein inhibition on methadone analgesia and brain distribution in the rat
    Monica Rodriguez
    Department of Pharmacology, Faculty of Medicine, University of the Basque Country, Barrio Sarriena s n 48940, Leioa, Vizcaya, Spain
    J Pharm Pharmacol 56:367-74. 2004
    ..P-gp, and hence substrate comedication, plays a critical role in the evolution of the methadone analgesic effect and in its brain uptake, independent of the administration route...
  84. ncbi Blood-brain barrier dysfunction in parkinsonian midbrain in vivo
    Rudie Kortekaas
    Department of Neurology, Groningen University Hospital, Groningen, The Netherlands
    Ann Neurol 57:176-9. 2005
    ..Here, we show significantly elevated uptake of [(11)C]-verapamil (18%) in the midbrain of PD patients relative to controls. This is the first evidence supporting a dysfunctional blood-brain barrier as a causative mechanism in PD...
  85. ncbi Differential interaction of 3-hydroxy-3-methylglutaryl-coa reductase inhibitors with ABCB1, ABCC2, and OATP1B1
    Cuiping Chen
    Pharmacokinetics, Dynamics and Metabolism, Pfizer Global Research and Development, MS4044, Eastern Point Rd, Groton, CT 06340, USA
    Drug Metab Dispos 33:537-46. 2005
    ....
  86. ncbi BCRP/MXR/ABCP expression in topotecan-resistant human breast carcinoma cells
    C H Yang
    Department of Oncology, National Taiwan University Hospital and the Graduate Institute of Medicine, Medical College, National Taiwan University, Taipei
    Biochem Pharmacol 60:831-7. 2000
    ..Our data suggest that enhanced topotecan efflux contributes partly to topotecan resistance in MCF7/TPT300 cells, possibly mediated by BCRP/MXR/ABCP...
  87. ncbi P-Glycoprotein-mediated efflux of phenobarbital, lamotrigine, and felbamate at the blood-brain barrier: evidence from microdialysis experiments in rats
    Heidrun Potschka
    Department of Pharmacology, Toxicology, and Pharmacy, School of Veterinary Medicine, Bunteweg 17, D 30559, Hannover, Germany
    Neurosci Lett 327:173-6. 2002
    ....
  88. pmc Prevalence of molecular mechanisms of resistance to azole antifungal agents in Candida albicans strains displaying high-level fluconazole resistance isolated from human immunodeficiency virus-infected patients
    S Perea
    Department of Medicine, Division of Infectious Diseases, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78245, USA
    Antimicrob Agents Chemother 45:2676-84. 2001
    ..These results may help in the development of new strategies to overcome the problem of resistance as well as new treatments for this condition...
  89. pmc HMG-CoA reductase inhibitors and P-glycoprotein modulation
    K Bogman
    Department of Clinical Pharmacology and Toxicology, University Hospital/Kantonsspital, Basel, Switzerland
    Br J Pharmacol 132:1183-92. 2001
    ....
  90. pmc Multidrug resistance protein 1 protects the oropharyngeal mucosal layer and the testicular tubules against drug-induced damage
    J Wijnholds
    Division of Molecular Biology, The Netherlands Cancer Institute, Amsterdam
    J Exp Med 188:797-808. 1998
    ..Our results indicate that specific inhibitors of MRP1 used to reverse MDR, in combination with carcinostatic drugs transported by MRP1, might lead to drug-induced mucositis, (temporary) infertility, and diabetes insipidus...
  91. ncbi An inventory of the human ABC proteins
    I Klein
    Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, H 1502, Budapest, Hungary
    Biochim Biophys Acta 1461:237-62. 1999
    ..Mutations of many human ABC proteins are known to be causative in inherited diseases, and a short description of the molecular pathology of these ABC gene-related genetic diseases is also provided...
  92. pmc Cortisol is transported by the multidrug resistance gene product P-glycoprotein
    C K van Kalken
    Department of Medical Oncology, Free University Hospital, Amsterdam, The Netherlands
    Br J Cancer 67:284-9. 1993
    ..These results demonstrate that Pgp may function as a transporter for cortisol and suggest a physiological role of the protein in steroid handling by organs such as the adrenal...
  93. pmc The three mouse multidrug resistance (mdr) genes are expressed in a tissue-specific manner in normal mouse tissues
    J M Croop
    Department of Pediatric Hematology and Oncology, Childrens Hospital, Boston, Massachusetts
    Mol Cell Biol 9:1346-50. 1989
    ..5, 5, and 6 kilobases have been detected. Each of the mdr genes has a specific RNA transcript pattern. These results should be considered in relation to understanding the normal physiological function of the mdr multigene family...
  94. ncbi P-glycoprotein and multidrug resistance-associated protein are involved in the regulation of extracellular levels of the major antiepileptic drug carbamazepine in the brain
    H Potschka
    Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, , D-30559 Hannover, Germany
    Neuroreport 12:3557-60. 2001
    ..The data indicate that both PGP and MRP participate in the regulation of extracellular brain concentrations of the major AED carbamazepine...
  95. ncbi Tumor necrosis factor alpha and endothelin-1 increase P-glycoprotein expression and transport activity at the blood-brain barrier
    Bjorn Bauer
    Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Mol Pharmacol 71:667-75. 2007
    ..Moreover, involvement of NF-kappaB raises the possibility that other effectors acting through this transcription factor may have similar effects on this key blood-brain barrier transporter...
  96. ncbi Nucleotide-induced structural changes in P-glycoprotein observed by electron microscopy
    Jyh Yeuan Lee
    Department of Biochemistry, University of California, Riverside, California 92521, USA
    J Biol Chem 283:5769-79. 2008
    ..The structural analysis presented here adds to the emerging picture that multidrug ABC transporters function by switching between two major conformations in a nucleotide-dependent manner...
  97. ncbi Limbic seizures induce P-glycoprotein in rodent brain: functional implications for pharmacoresistance
    Massimo Rizzi
    Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri, 20157 Milano, Italy
    J Neurosci 22:5833-9. 2002
    ..P-gp alterations significantly affect antiepileptic drugs concentrations in the brain, suggesting that seizure-induced mdr mRNA expression contributes to MDR in epilepsy...
  98. pmc Multidrug resistance protein 1 protects the choroid plexus epithelium and contributes to the blood-cerebrospinal fluid barrier
    J Wijnholds
    Division of Molecular Biology and Center for Biomedical Genetics, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
    J Clin Invest 105:279-85. 2000
    ..Our results indicate that Mrp1 helps to limit tissue distribution of certain drugs and contributes to the blood-CSF drug-permeability barrier...
  99. ncbi ABCB1 gene polymorphisms and expression of P-glycoprotein and long-term prognosis in colorectal cancer
    Sara De Iudicibus
    Department of Life Sciences, University of Trieste, Italy
    Anticancer Res 28:3921-8. 2008
    ..The association of two ABCB1 polymorphisms with the occurrence of colon cancer and long-term prognosis was evaluated in a selected patient population. The expression of Pgp in neoplastic and normal intestinal mucosa was also studied...
  100. ncbi Ceramide glycosylation potentiates cellular multidrug resistance
    Y Y Liu
    John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, CA 90404, USA
    FASEB J 15:719-30. 2001
    ..This study reveals that GCS is a novel mechanism of multidrug resistance and positions GCS antisense as an innovative force to overcome multidrug resistance in cancer chemotherapy...
  101. ncbi ABCB1 gene polymorphisms and haplotype analysis in colorectal cancer
    Mariusz Panczyk
    Department of Pharmaceutical Biochemistry, Laboratory of Molecular Biology and Pharmacogenomics, Medical University of Lodz, Lodz, Poland
    Int J Colorectal Dis 24:895-905. 2009
    ..Haplotype structure of ABCB1 was analysed, and degree of linkage disequilibrium (LD) between SNPs of ABCB1 was estimated...

Research Grants62

  1. Drug Interactions at the Human Blood-Brain Barrier
    Jashvant D Unadkat; Fiscal Year: 2010
    ..In addition, our studies will measure the magnitude of such interactions. The results of our study should lead to better management of drug therapy and improvement of the drug development process. ..
  2. NOVEL PET AGENT FOR MYOCARDIAL PERFUSION IMAGING
    Vijay Sharma; Fiscal Year: 2013
    ..Successful execution of the outlined objectives should provide a molecular-targeted 68Ga-PET agent for MPI and management of CAD. ..
  3. Control of Drug Delivery to the CNS: Modulating P-glycoprotein Activity
    William A Banks; Fiscal Year: 2013
    ..abstract_text> ..
  4. Genetic Determinants of the Response to Thienopyridine Therapy
    Jessica L Mega; Fiscal Year: 2013
    ..The TIMI Study Group also offers the appropriate training environment to provide Dr. Mega with the skills needed to lead the multicenter clinical trial described in Aim 3. ..
  5. Impact of genetic variation on response to GO therapy in COG-AML clinical trials
    ROLAND BRUNO WALTER; Fiscal Year: 2013
    ..Moreover, this research will provide novel insights into the impact of genetic polymorphisms on efficacy of standard therapeutics with broad implications for the treatment of AML. ..
  6. Role of ABC efflux transporters in ALS
    Davide Trotti; Fiscal Year: 2013
    ..In this application we propose to study the regulation and role of these ABC transporters in ALS. Our ultimate goal is to understand the pathogenic mechanisms of ALS to improve the chances of success of pharmacotherapy for this disease. ..
  7. Functions of MRP2 and MRP3 in Drug Disposition
    James M Gallo; Fiscal Year: 2011
    ..These improvements could potentially allow the drugs to be given by mouth instead of intravenously, and also reduce the side effects that are associated with the way the body disposes of anticancer agents. ..
  8. Medications Development for the Pregnant Opiate Addict
    Mahmoud S Ahmed; Fiscal Year: 2010
    ..two opioids is affected by their metabolism by Cytochrome P450 19 (CYP19) and their efflux by the transporter P glycoprotein (P-gp)...
  9. Novel mycobacterial translocase I inhibitors - a new class of anti-TB drugs
    Venkata M Reddy; Fiscal Year: 2010
    ..abstract_text> ..
  10. Identification of Lactobacillus Secreted Factors in Regulation of Pgp
    Seema Saksena; Fiscal Year: 2013
    ..Since using live bacteria could be a potential risk in the treatment of gut disorders, using secreted bioactive factor (s) instead of live bacteria would lead to an innovative approach for their therapeutic usage. ..
  11. Designing HIV Protease Inhibitors with Lower Dosing Requirements and Lower Toxici
    Mitchell W Mutz; Fiscal Year: 2013
    ..By reducing the toxicity of HIV protease inhibitors, we hope to improve compliance with HAART and therapeutic outcomes. ..
  12. Brain endothelial cell function under adenosine receptor signaling directive
    Margaret S Bynoe; Fiscal Year: 2013
    ....
  13. Diffraction Methods in Molecular Biology Gordon Research Conference
    NANCY RYAN GRAY; Fiscal Year: 2010
    ..These include ABC transporters that mediate resistance to anticancer drugs (P glycoprotein) and most recently the structures of a number of G Protein Coupled Receptors...
  14. Blood-to-CNS Drug Uptake in Pain
    THOMAS PAUL DAVIS; Fiscal Year: 2013
    ..This study may point to novel ways to improve CNS opioid delivery and to avoid unwanted opioid side effects during the treatment of pain. ..
  15. Herb-Drug Glucuronidation Interactions
    Reginald F Frye; Fiscal Year: 2011
    ....
  16. Bupropion for smoking cessation during pregnancy
    Tatiana Nanovskaya; Fiscal Year: 2013
    ..In summary, The information obtained is necessary for evaluating bupropion as a potential medication for aiding in smoking cessation during pregnancy. ..
  17. St. John's wort for Drug Abuse Treatment During Pregnancy
    C LINDSAY LINDSAY DEVANE; Fiscal Year: 2012
    ..The results will be a test of a novel pharmacological strategy for treatment of pregnant women with opioid dependence/addiction. ..
  18. Improving Delivery of Molecularly-Targeted Therapy to Invasive Glioma Cells
    John R Ohlfest; Fiscal Year: 2013
    ..Improving drug delivery could lead to improved patient outcomes, including longer progression free survival and possible cure. ..
  19. Targeted Sphingolipid Metabolism for Treatment of AML
    THOMAS PATRICK LOUGHRAN; Fiscal Year: 2013
    ..Importantly, we have documented engraftment in NSG mice of AML subsets defined by integrated genetic profiling. ..
  20. Genomic and Cellular Markers and Chronic Renal Allograft Function
    Kathleen M Tornatore; Fiscal Year: 2010
    ....
  21. Studies on a Novel Taxane Pump
    Elizabeth Hopper-Borge; Fiscal Year: 2011
    ..The goal of this proposal is aimed is to obtain information about one of these recently identified proteins. ..
  22. The Role of P-glycoprotein in Sitagliptin Clinical Pharmacology
    Christina L Aquilante; Fiscal Year: 2010
    ..e., clinical pharmacology). The aims of this application are to investigate the clinical pharmacology of sitagliptin in order to promote its safe and effective use in patients with type 2 diabetes. ..
  23. Cellular Efflux and Metabolism of Protease Inhibitors
    Ashim Mitra; Fiscal Year: 2004
    ..The brain parenchymal and alveolar lining - two sanctuary sites that are 'protected' from optimal antiretroviral drug access. 4) to study the effect of protein binding on the influx and efflux of model compounds, and anti-HIV drugs. ..
  24. Molecular Imaging of Cancer and Its Response to Therapy
    Kenneth A Krohn; Fiscal Year: 2013
    ..abstract_text> ..
  25. CHEMICAL SYNTHESIS OF NOVEL NATURAL PRODUCTS
    David Williams; Fiscal Year: 2009
    ..Daphnicyclidin A. This recent discovery has revealed a new molecular architecture which exhibits significant antitumor activity. Our research will investigate strategies for chemical synthesis of these complex polycyclic systems. ..
  26. Water Soluble Antimitotics That Circumvent Rumor Resistance
    Susan L Mooberry; Fiscal Year: 2013
    ....
  27. Blood-brain barrier P-glycoprotein: a new target for Alzheimer's disease
    Anika M S Hartz; Fiscal Year: 2013
    ....
  28. Molecular Mechanisms of P-Glycoprotein
    William M Atkins; Fiscal Year: 2013
    ..Such studies could lead to conformation-specific inhibitors of P-gp with utility in the modulation of pharmacokinetic properties of existing drugs. ..
  29. Discovery of Novel Thiazole Analogs for Treating Malignant Melanoma
    Wei Li; Fiscal Year: 2013
    ....
  30. Development of Dual GABAA and alpah7 Nicotinic Receptor Modulators for AD
    Kelvin W Gee; Fiscal Year: 2013
    ..abstract_text> ..
  31. IMAGING FUNCTIONAL P-GLYCOPROTEIN TRANSPORT AT THE BBB IN ALZHEIMER'S DISEASE
    Vijay Sharma; Fiscal Year: 2011
    ....
  32. Drug Transporters and the Disposition of ADHD Therapeutic Agents
    John S Markowitz; Fiscal Year: 2010
    ....
  33. DRUG INTERACTIONS
    ALLAN EDWARD RETTIE; Fiscal Year: 2012
    ..abstract_text> ..
  34. BLOOD BRAIN BARRIER CHANGES INDUCED BY PAIN
    THOMAS PAUL DAVIS; Fiscal Year: 2013
    ....
  35. Synthesis and pharmacology of novel opiates and their modulatory systems
    Gavril W Pasternak; Fiscal Year: 2012
    ..abstract_text> ..
  36. Gestational Age Variation in Human Placental Transport Mechanisms
    Sammanda Ramamoorthy; Fiscal Year: 2013
    ..This translational research will promote more informed decisions regarding fetal risk from psychoactive drug use during pregnancy. ..
  37. Effects of Anthocyanins on Cytochrome P450 Enzymes and P-glycoprotein
    MICHAEL JOHN HANLEY; Fiscal Year: 2012
    ....
  38. Curcumin and Piperine in Breast Cancer Prevention
    Madhuri Kakarala; Fiscal Year: 2011
    ..I propose to enhance curcumin bioavailability by using piperine to modulate P glycoprotein, CYP 3A4 and phase II conjugation enzymes. Piperine may also have synergistic cancer preventive effect alone...
  39. HIV-1 and amyloid beta interactions at the blood-brain barrier
    Michal Toborek; Fiscal Year: 2013
    ....
  40. Structural biology and high resolution studies of P-glycoprotein
    GEOFFREY A CHANG; Fiscal Year: 2013
    ..The structures of Pgp should greatly facilitate the development of new drugs to circumvent multidrug resistance in the future. ..
  41. MODULATION OF MULTIDRUG RESISTANCE BY CYCLOSPORIN A
    Charles Erlichman; Fiscal Year: 1992
    ..The proposed studies will evaluate the importance of P-glycoprotein in clinical resistance to MDR and determine whether cyclosporin A can reverse the MDR phenotype in patients...
  42. Mechanisms of Anticancer Agents Selective against Drug Resistant Leukemia
    Chengguo Xing; Fiscal Year: 2013
    ..Aim 3. To validate the anticancer selectivity and mechanism of action for CXL positive lead against drug resistant AML in engraftment models. ..
  43. Taxol: Mechanisms of Action and Resistance
    HAYLEY MARIA MCDAID; Fiscal Year: 2013
    ..The mechansim of action of another Taxol-like drug, discodermolide will be determined and different structural analogs will be tested for improved chemotherapeutic activity. ..
  44. P-glycoprotein and Alzheimer's Disease
    Jashvant D Unadkat; Fiscal Year: 2010
    ..These proposed studies have the potential to result in identification of P-gp as a novel therapeutic target for the treatment of AD, a disease for which no effective therapy exists. ..
  45. Understanding polyspecific drug binding in P-glycoprotein
    Ina L Urbatsch; Fiscal Year: 2012
    ..By learning more about how Pgp recognizes the chemicals that it carries out of the cell, scientists may devise new drugs to prevent Pgp from interfering with the valuable effects of anticancer drugs. ..
  46. Therapeutic Interventions for HIV-1 CNS Sequestration.
    Natalie Eddington; Fiscal Year: 2005
    ..Obtaining therapeutic CNS levels of anti-retroviral agents is essential to minimizing HIV-1 in the CNS. As such, this proposal offers a viable approach to address this complication of HIV/AIDS. ..
  47. NEONATAL BILIRUBIN NEUROTOXICITY AND P-GLYCOPROTEIN
    Jon Watchko; Fiscal Year: 2007
    ..abstract_text> ..
  48. BIOCHEMICAL CHARACTERIZATION OF P-GLYCOPROTEIN
    AHMAD SAFA; Fiscal Year: 1999
    ..parent drugs, and (3) molecular modeling analysis of the drug binding sites will be performed. ..
  49. HUMAN MULTIDRUG RESISTANCE--PGLYCOPROTEIN GENES
    IGOR RONINSON; Fiscal Year: 1992
    ..Finally, protocols for detection of mdrl expression in clinical tumor samples, based on in situ RNA hybridization, will be developed and optimized for clinical studies...
  50. AIDS Neurotherapeutics and BBB Drug Efflux
    William Pardridge; Fiscal Year: 2007
    ..This work provides the basis for future drug discovery of AET blockers, which can be used as co-drugs to increase CNS penetration of HAART drugs. ..
  51. P-GLYCOPROTEIN MEDIATED CHEMORESISTANCE IN ALS THERAPY
    Davide Trotti; Fiscal Year: 2010
    ....
  52. CELLULAR CONCOMITANTS OF VINCRISTINE RESISTANCE
    JUNE BIEDLER; Fiscal Year: 1992
    ..In situ hybridization and cytogenetic methods with P-glycoprotein, sorcin, and N-myc probes will be used to being this study. Identification of parameters related to resistance development in the drug-treated patient is a long term goal...
  53. MEMBRANES AND ACTIVE TRANSPORT OF AMINO ACIDS
    GIOVANNA AMES; Fiscal Year: 2001
    ....
  54. TG RICH LIPOPROTEIN SYNTHESIS/SECRETION IN CACO 2 CELLS
    F Field; Fiscal Year: 2000
    ....
  55. NEW MECHANISMS OF MULTIDRUG RESISTANCE IN CANCER CELLS
    Erasmus Schneider; Fiscal Year: 2001
    ..In addition, since bone marrow Toxicity appears to be a major dose limiting factor in chemotherapy with camptothecin analogs, the MTPR gene may also provide a new gene for bone marrow stem cell protective gene therapy. ..
  56. Rapid in vitro substrate assay for the multi-drug resistance p-glycoprotein
    DONALD MELCHIOR; Fiscal Year: 2009
    ..The test thereby allows the pharmaceutical industry to evaluate, at an early stage, the suitability of drug candidates for continued development. The test is reliable, simple, rapid, inexpensive and amenable to robotics. ..
  57. NEW ANTIMICROTUBULE AGENTS FROM MARINE ORGANISMS
    Bradley Davidson; Fiscal Year: 2001
    ....
  58. ROLE OF ATP-BINDING CASSETTE TRANSPORTERS IN INNATE INTESTINAL DEFENSE
    Brien Neudeck; Fiscal Year: 2007
    ..Once this is accomplished, we can use this information to develop protective strategies that exploit these preexisting barriers to L. monocytogenes and potentially other pathogens. [unreadable] [unreadable] [unreadable]..
  59. Targeting MRP7 to Overcome Drug Resistance for Ovarian Cancer Therapy by Taxanes
    Zhe Sheng Chen; Fiscal Year: 2010
    ..Finally, the knowledge obtained from this research could assist physicians in improving survival rate of ovarian cancer patients. ..
  60. MECHANISM TO LIMIT CNS BILIRUBIN INFLUX: P-GLYCOPROTEIN
    Jon Watchko; Fiscal Year: 1999
    ....
  61. Vaginal Drug Delivery of P-glycoprotein Substrates
    Giovanni Pauletti; Fiscal Year: 2003
    ..From the drug delivery point of view, the results may be applicable to determine an optimum time window during the menstrual cycle for effective vaginal delivery of P-gp substrates in order to maximize systemic bioavailability. ..
  62. Cancer Targeting with Multi-Responsive Core/Shell Microgels
    LOUIS LYON; Fiscal Year: 2007
    ..We will also gain a detailed understanding of the fundamental issues involved in receptor-mediated endosomal uptake of polymeric nanoparticles. [unreadable] [unreadable] [unreadable]..