multiple drug resistance

Summary

Summary: Simultaneous resistance to several structurally and functionally distinct drugs.

Top Publications

  1. 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
  2. ncbi A family of drug transporters: the multidrug resistance-associated proteins
    P Borst
    Division of Molecular Biology and Center of Biomedical Genetics, The Netherlands Cancer Institute, Amsterdam
    J Natl Cancer Inst 92:1295-302. 2000
  3. ncbi Mammalian ABC transporters in health and disease
    P Borst
    Division of Molecular Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
    Annu Rev Biochem 71:537-92. 2002
  4. 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
  5. ncbi The molecular basis of multidrug resistance in cancer: the early years of P-glycoprotein research
    Michael M Gottesman
    Laboratory of Cell Biology, The Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    FEBS Lett 580:998-1009. 2006
  6. ncbi Sonic Hedgehog promotes multiple drug resistance by regulation of drug transport
    J Sims-Mourtada
    Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
    Oncogene 26:5674-9. 2007
  7. 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
  8. pmc Differential role of sodium channels SCN1A and SCN2A gene polymorphisms with epilepsy and multiple drug resistance in the north Indian population
    Ram Lakhan
    Departments of Genetics and Neurology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
    Br J Clin Pharmacol 68:214-20. 2009
  9. 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
  10. pmc A multidrug resistance transporter from human MCF-7 breast cancer cells
    L A Doyle
    Greenebaum Cancer Center of the University of Maryland, Baltimore MD 21201, USA
    Proc Natl Acad Sci U S A 95:15665-70. 1998

Detail Information

Publications330 found, 100 shown here

  1. 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...
  2. ncbi A family of drug transporters: the multidrug resistance-associated proteins
    P Borst
    Division of Molecular Biology and Center of Biomedical Genetics, The Netherlands Cancer Institute, Amsterdam
    J Natl Cancer Inst 92:1295-302. 2000
    ..The physiologic functions of the other MRPs are not known. Whether long-term inhibition of MRPs in humans can be tolerated (assuming that suitable inhibitors will be found) remains to be determined...
  3. ncbi Mammalian ABC transporters in health and disease
    P Borst
    Division of Molecular Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
    Annu Rev Biochem 71:537-92. 2002
    ..c) A rapidly increasing number of ABC transporters are found to play a role in lipid transport. Defects in each of these transporters are involved in human inborn or acquired diseases...
  4. 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...
  5. ncbi The molecular basis of multidrug resistance in cancer: the early years of P-glycoprotein research
    Michael M Gottesman
    Laboratory of Cell Biology, The Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    FEBS Lett 580:998-1009. 2006
    ....
  6. ncbi Sonic Hedgehog promotes multiple drug resistance by regulation of drug transport
    J Sims-Mourtada
    Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
    Oncogene 26:5674-9. 2007
    ..These results suggest that the Hh pathway may be a target to overcome MDR and increase chemotherapeutic response...
  7. 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
    ....
  8. pmc Differential role of sodium channels SCN1A and SCN2A gene polymorphisms with epilepsy and multiple drug resistance in the north Indian population
    Ram Lakhan
    Departments of Genetics and Neurology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
    Br J Clin Pharmacol 68:214-20. 2009
    ..Thr 1067 Ala or c.3184 A-->G (rs2298771) and SCN2A p.Arg19Lys or c.56 G-->A (rs17183814) in north Indian epilepsy patients...
  9. 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...
  10. pmc A multidrug resistance transporter from human MCF-7 breast cancer cells
    L A Doyle
    Greenebaum Cancer Center of the University of Maryland, Baltimore MD 21201, USA
    Proc Natl Acad Sci U S A 95:15665-70. 1998
    ..BCRP is a xenobiotic transporter that appears to play a major role in the multidrug resistance phenotype of MCF-7/AdrVp human breast cancer cells...
  11. ncbi Acquired mutations in the MXR/BCRP/ABCP gene alter substrate specificity in MXR/BCRP/ABCP-overexpressing cells
    Y Honjo
    Cancer Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
    Cancer Res 61:6635-9. 2001
    ..These results suggest that amino acid 482 has a crucial role in MXR/BCRP/ABCP function and that mutation of a single amino acid residue significantly changes substrate specificity, thus altering the drug resistance phenotype...
  12. pmc Therapeutic response of multidrug-resistant Plasmodium falciparum and P. vivax to chloroquine and sulfadoxine-pyrimethamine in southern Papua, Indonesia
    A Ratcliff
    International Health Program, Menzies School of Health Research and Charles Darwin University, Darwin, NT, Australia
    Trans R Soc Trop Med Hyg 101:351-9. 2007
    ..falciparum and P. vivax exists both to first- and second-line therapies. Preliminary data indicate that amodiaquine retains superior efficacy compared with CQ for CQ-resistant P. vivax...
  13. ncbi A mechanistic study of enhanced doxorubicin uptake and retention in multidrug resistant breast cancer cells using a polymer-lipid hybrid nanoparticle system
    Ho Lun Wong
    Graduate Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, 19 Russell Street, University of Toronto, ON, Canada M5S 2S2
    J Pharmacol Exp Ther 317:1372-81. 2006
    ..The present study suggests a new mechanism for overcoming drug resistance in Pgp-overexpressing tumor cells using lipid-based nanoparticle formulations...
  14. ncbi Identification of proteins responsible for the multiple drug resistance in 5-fluorouracil-induced breast cancer cell using proteomics analysis
    Guopei Zheng
    Cancer Research Institute, Xiangya School of Medicine, Central South University, Xiangya Road 110, Changsha 410078, Hunan, People s Republic of China
    J Cancer Res Clin Oncol 136:1477-88. 2010
    ..This study aimed to explore the mechanism of multi-drug resistance (MDR) in 5-fluorouracil (5-FU)-induced breast cancer cell MCF-7...
  15. pmc Mechanism of sensitization of MDR cancer cells by Pluronic block copolymers: Selective energy depletion
    E V Batrakova
    College of Pharmacy, Department of Pharmaceutical Sciences, Nebraska Medical Center, 986025, Omaha, NE, 68198 6025, USA
    Br J Cancer 85:1987-97. 2001
    ..Therefore, the finding of the energy-depleting effects of Pluronic P85, in combination with its sensitization effects is of considerable theoretical and practical significance...
  16. ncbi Curcumin down-regulates the multidrug-resistance mdr1b gene by inhibiting the PI3K/Akt/NF kappa B pathway
    Byeong Hyeok Choi
    Department of Biomedical Science and Technology, IBST, Konkuk University, Seoul 143 701, Republic of Korea
    Cancer Lett 259:111-8. 2008
    ..Thus, curcumin can contribute to the reversal of the MDR phenotype, probably due to the suppression of P-gp expression via the inhibition of the PI3K/Akt/NF-kappa B signaling pathway...
  17. pmc Multidrug-resistant Plasmodium vivax associated with severe and fatal malaria: a prospective study in Papua, Indonesia
    Emiliana Tjitra
    National Institute of Health Research and Development, Ministry of Health, Jakarta, Indonesia
    PLoS Med 5:e128. 2008
    ..The aim of the study was to review the spectrum of disease associated with malaria due to Pv and P. falciparum (Pf) in patients presenting to a hospital in Timika, southern Papua, Indonesia...
  18. ncbi Intravenous colistin as therapy for nosocomial infections caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii
    A S Levin
    Hospital Infection Control Department, Hospital das Clinicas, Faculdade de Medicina, University of Sao Paulo, SP, Brazil
    Clin Infect Dis 28:1008-11. 1999
    ..Colistin may be a good therapeutic option for the treatment of severe infections caused by multidrug-resistant P. aeruginosa and A. baumannii...
  19. 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...
  20. ncbi A human placenta-specific ATP-binding cassette gene (ABCP) on chromosome 4q22 that is involved in multidrug resistance
    R Allikmets
    Intramural Research Support Program, Science Applications International Corporation Frederick, National Cancer Institute Frederick Cancer Research and Development Center, Maryland 21702 1201, USA
    Cancer Res 58:5337-9. 1998
    ..The abundant expression of this gene in the placenta suggests that the protein product has an important role in transport of specific molecule(s) into or out of this tissue...
  21. 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...
  22. ncbi An overview of cancer multidrug resistance: a still unsolved problem
    H Lage
    Charite, Institute of Pathology, Chariteplatz 1, 10117, Berlin, Germany
    Cell Mol Life Sci 65:3145-67. 2008
    ....
  23. ncbi The mar regulon: multiple resistance to antibiotics and other toxic chemicals
    M N Alekshun
    Center for Adaptation Genetics and Drug Resistance, Dept of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA 02111, USA
    Trends Microbiol 7:410-3. 1999
    ..The Mar phenotype is induced following exposure to a variety of chemicals with aromatic rings...
  24. pmc Decreasing pfmdr1 copy number in plasmodium falciparum malaria heightens susceptibility to mefloquine, lumefantrine, halofantrine, quinine, and artemisinin
    Amar bir Singh Sidhu
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, Bronx, NY 10461, USA
    J Infect Dis 194:528-35. 2006
    ..These results highlight the importance of pfmdr1 copy number in determining P. falciparum susceptibility to multiple agents currently being used to combat malaria caused by multidrug-resistant parasites...
  25. ncbi Targeting multidrug resistance in cancer
    Gergely Szakacs
    Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, Budapest Karolina út 29 H 1518 Hungary
    Nat Rev Drug Discov 5:219-34. 2006
    ..We describe various approaches to combating multidrug-resistant cancer, including the development of drugs that engage, evade or exploit efflux by ABC transporters...
  26. ncbi Hyaluronan: from extracellular glue to pericellular cue
    Bryan P Toole
    Department of Cell Biology and Anatomy, Medical University of South Carolina, 173 Ashley Avenue, Charleston, South Carolina 29425, USA
    Nat Rev Cancer 4:528-39. 2004
  27. ncbi Overexpression of multiple drug resistance genes in endothelial cells from patients with refractory epilepsy
    S M Dombrowski
    Department of Neurological Surgery, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    Epilepsia 42:1501-6. 2001
    ..To test this hypothesis further, we measured multiple drug resistance (MDR) gene expression in endothelial cells (ECs) isolated from temporal lobe blood vessels of 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 The vault complex
    A van Zon
    Department of Hematology, Erasmus Medical Center, Rotterdam, The Netherlands
    Cell Mol Life Sci 60:1828-37. 2003
    ..However, their distinct morphology and intracellular distribution suggest a role in intracellular transport processes. Here we review the current knowledge on the vault complex, its structure, components and possible functions...
  30. ncbi Expression of the major vault protein LRP in human non-small-cell lung cancer cells: activation by short-term exposure to antineoplastic drugs
    W Berger
    Institute of Cancer Research, Division of Applied and Experimental Oncology, Vienna University, Vienna, Austria
    Int J Cancer 88:293-300. 2000
    ..Summing up, our data suggest a role of vaults both in basic CDDP resistance and, additionally, in an short-term defensive response of NSCLC cells against several other drugs...
  31. ncbi Multiple molecular mechanisms for multidrug resistance transporters
    Christopher F Higgins
    MRC Clinical Sciences Centre, Imperial College, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK
    Nature 446:749-57. 2007
    ..Answers are emerging to questions such as how multispecificity for different drugs is achieved, why multidrug resistance arises so readily, and what chance there is of devising a clinical solution...
  32. ncbi Protecting the genome: defence against nucleotide glycation and emerging role of glyoxalase I overexpression in multidrug resistance in cancer chemotherapy
    P J Thornalley
    Department of Biological Sciences, University of Essex, Central Campus, Wivenhoe Park, Colchester, Essex CO4 3SQ, U K
    Biochem Soc Trans 31:1372-7. 2003
    ..It countered drug resistance and was a potent antitumour agent against lung and prostate carcinoma. Glyoxalase I overexpression was also found in invasive ovarian cancer and breast cancer...
  33. ncbi The application of Fe3O4 nanoparticles in cancer research: a new strategy to inhibit drug resistance
    Xuemei Wang
    State Key Lab of Bioelectronics, Chien Shiung WU Laboratory, Southeast University, Nanjing 210096, People s Republic of China
    J Biomed Mater Res A 80:852-60. 2007
    ....
  34. pmc Mrp4 confers resistance to topotecan and protects the brain from chemotherapy
    Markos Leggas
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, 332 N Lauderdale, Memphis, TN 38105 2794, USA
    Mol Cell Biol 24:7612-21. 2004
    ....
  35. 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
    ....
  36. ncbi Cellular mechanisms of multidrug resistance of tumor cells
    A A Stavrovskaya
    Institute of Carcinogenesis, Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences, Moscow, 115478, Russia
    Biochemistry (Mosc) 65:95-106. 2000
    ....
  37. ncbi AcrAB and related multidrug efflux pumps of Escherichia coli
    H Nikaido
    Department of Molecular and Cell Biology, University of California, Berkeley 94720 3206, USA
    J Mol Microbiol Biotechnol 3:215-8. 2001
    ..It forms a trimer that interacts with a monomeric AcrB, which was shown by in vitro reconstitution to be a proton antiporter. Details of interaction between the..
  38. 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...
  39. pmc Antimicrobial resistance among clinical isolates of Streptococcus pneumoniae in the United States during 1999--2000, including a comparison of resistance rates since 1994--1995
    G V Doern
    Medical Microbiology Division, Department of Pathology, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA
    Antimicrob Agents Chemother 45:1721-9. 2001
    ..1%; tetracycline, 9.0%; TMP-SMX, 9.1%; and chloramphenicol, 4.0%, the increase in multiresistance was 13.3%. Despite awareness and prevention efforts, antimicrobial resistance with S. pneumoniae continues to increase in the United States...
  40. ncbi A functional assay for detection of the mitoxantrone resistance protein, MXR (ABCG2)
    R W Robey
    Developmental Therapeutics Department, Medicine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10, Room 12N226, 9000 Rockville Pike, Bethesda, MD 20892, USA
    Biochim Biophys Acta 1512:171-82. 2001
    ..These studies show that flow cytometric measurement of FTC-inhibitable mitoxantrone or prazosin efflux is a sensitive and specific method for measuring the function of the MXR half-transporter in both selected and unselected cell lines...
  41. ncbi Mechanisms and strategies to overcome multiple drug resistance in cancer
    Tomris Ozben
    Akdeniz University, Faculty of Medicine, Department of Biochemistry, 07070 Antalya, Turkey
    FEBS Lett 580:2903-9. 2006
    ..In this review, the structure and function of ABC transporters and development of MDR inhibitors are described briefly including various approaches to suppress MDR mechanisms...
  42. pmc Gene amplification of the multidrug resistance 1 gene of Plasmodium vivax isolates from Thailand, Laos, and Myanmar
    Mallika Imwong
    Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, 420 6 Rajvithi Rd, Bangkok 10400, Thailand
    Antimicrob Agents Chemother 52:2657-9. 2008
    ..02). Five coding mutations in pvmdr1, independent of gene amplification, were also found...
  43. 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...
  44. 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
    ..The latter is due to the action of multiple drug resistance proteins capable of active CNS extrusion of drugs...
  45. pmc Deletion of TolC orthologs in Francisella tularensis identifies roles in multidrug resistance and virulence
    Horacio Gil
    Center for Infectious Diseases, Stony Brook University, Stony Brook, NY 11794 5120, USA
    Proc Natl Acad Sci U S A 103:12897-902. 2006
    ..Thus, tolC is a critical virulence factor of F. tularensis in addition to its role in multidrug resistance, which suggests the presence of a functional type I secretion system...
  46. 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
    ....
  47. pmc Drug resistance in cancer: principles of emergence and prevention
    Natalia L Komarova
    Department of Mathematics, 103 MSTB, University of California, Irvine, CA 92697, USA
    Proc Natl Acad Sci U S A 102:9714-9. 2005
    ....
  48. ncbi Nilotinib (AMN107, Tasigna) reverses multidrug resistance by inhibiting the activity of the ABCB1/Pgp and ABCG2/BCRP/MXR transporters
    Amit K Tiwari
    Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, St John s University, 8000 Utopia Parkway, Jamaica, NY 11439, USA
    Biochem Pharmacol 78:153-61. 2009
    ..Also, these findings may be useful in clinical practice for cancer combination therapy with nilotinib...
  49. ncbi Molecular modes of action of cytotoxic alkaloids: from DNA intercalation, spindle poisoning, topoisomerase inhibition to apoptosis and multiple drug resistance
    Michael Wink
    Institute of Pharmacy and Molecular Biotechnology, University of Heidelberg, 69120 Heidelberg, Germany
    Alkaloids Chem Biol 64:1-47. 2007
  50. ncbi Intensity of transmission and spread of gene mutations linked to chloroquine and sulphadoxine-pyrimethamine resistance in falciparum malaria
    Ambrose O Talisuna
    Ministry of Health, PO Box 7272, Kampala, Uganda
    Int J Parasitol 33:1051-8. 2003
    ..Our findings have important implications for malaria control because increasing drug resistance has a substantial impact on mortality...
  51. 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...
  52. ncbi Tryptanthrin inhibits MDR1 and reverses doxorubicin resistance in breast cancer cells
    Sung Tsai Yu
    Graduate Institute of Pharmaceutical Sciences, College of Medicine, National Taiwan University, Taipei 10051, Taiwan
    Biochem Biophys Res Commun 358:79-84. 2007
    ..It might contribute to negative regulation of MDR1 gene. In conclusion, tryptanthrin exhibited MDR reversing effect by down-regulation of MDR1 gene and might be a new adjuvant agent for chemotherapy...
  53. ncbi Epidemiology of drug-resistant malaria
    Chansuda Wongsrichanalai
    Armed Forces Research Institute of Medical Sciences AFRIMS, Bangkok, Thailand
    Lancet Infect Dis 2:209-18. 2002
    ..This review describes the various features of drug resistance in Plasmodium falciparum, including its determinants, current status in diverse geographical areas, molecular markers, and their implications...
  54. 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...
  55. pmc Efflux pumps, OprD porin, AmpC beta-lactamase, and multiresistance in Pseudomonas aeruginosa isolates from cystic fibrosis patients
    Maria Tomas
    Centre for Infections, Health Protection Agency, London, United Kingdom
    Antimicrob Agents Chemother 54:2219-24. 2010
    ..Overexpressed mexA or ampC and reduced oprD were associated with beta-lactam resistance. A specific combination of mexR, nalC, and nalD mutations occurred in 11 Liverpool strain isolates, including 7 with upregulated mexA...
  56. ncbi The multidrug resistance transporter ABCG2 (breast cancer resistance protein 1) effluxes Hoechst 33342 and is overexpressed in hematopoietic stem cells
    Min Kim
    Eppley Institute for Cancer Research, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA
    Clin Cancer Res 8:22-8. 2002
    ..These results suggest that Hoechst 33342 is a substrate for the ABCG2 transporter and that ABCG2/Bcrp1 expression may serve as a marker for hematopoietic stem cells in hematopoietic cells...
  57. pmc Two fixed-dose artemisinin combinations for drug-resistant falciparum and vivax malaria in Papua, Indonesia: an open-label randomised comparison
    A Ratcliff
    International Health Programme, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia
    Lancet 369:757-65. 2007
    ..Our aim was to compare the safety and efficacy of dihydroartemisinin-piperaquine with that of artemether-lumefantrine in patients with uncomplicated malaria caused by multidrug-resistant P falciparum and P vivax...
  58. ncbi Lung resistance-related protein/major vault protein and vaults in multidrug-resistant cancer
    G L Scheffer
    Department of Pathology, Free University Hospital, Amsterdam, The Netherlands
    Curr Opin Oncol 12:550-6. 2000
    ..The current clinical data on LRP/MVP detection indicate that LRP/MVP expression can be of high clinical value to predict the response to chemotherapy of several tumor types...
  59. ncbi Phase 3 study of the multidrug resistance modulator PSC-833 in previously untreated patients 60 years of age and older with acute myeloid leukemia: Cancer and Leukemia Group B Study 9720
    Maria R Baer
    Roswell Park Cancer Institute, Buffalo, NY 14263, USA
    Blood 100:1224-32. 2002
    ..Moreover, for patients with PSC-833-modulated efflux, median disease-free survival was 5 months with ADE and 14 months with ADEP (P =.07). Further modulation trials in older patients must await the design of less-toxic regimens...
  60. ncbi The functional purification of P-glycoprotein is dependent on maintenance of a lipid-protein interface
    R Callaghan
    Nuffield Department of Clinical Biochemistry, John Radcliffe Hospital, University of Oxford, UK
    Biochim Biophys Acta 1328:109-24. 1997
    ..This purification scheme yields the highest P-gp activity reported to date, and indicates a dependence of function on maintaining a lipid-protein interface...
  61. pmc Induction of the MexXY efflux pump in Pseudomonas aeruginosa is dependent on drug-ribosome interaction
    Katy Jeannot
    Laboratoire de Bacteriologie, Hopital Jean Minjoz, 25030 Besancon Cedex, France
    J Bacteriol 187:5341-6. 2005
    ..Altogether, these data demonstrate physiological interplays between MexXY and the ribosome and are suggestive of an alternative function for MexXY beyond antibiotic efflux...
  62. ncbi Toxicological relevance of the multidrug resistance protein 1, MRP1 (ABCC1) and related transporters
    E M Leslie
    Department of Pharmacology and Toxicology, Queen's University, Kingston, Ont, Canada K7L 3N6
    Toxicology 167:3-23. 2001
    ..Those isolated from the vascular plant Arabidopsis thaliana (AtMRPs) decrease the cytoplasmic concentration of conjugated toxins through sequestration in vacuoles and are implicated in providing herbicide resistance to plants...
  63. ncbi Effect of arsenic trioxide on multidrug resistant hepatocellular carcinoma cells
    Judy Yuet Wa Chan
    Department of Biochemistry, The Chinese University of Hong Kong, Shatin, N T, Hong Kong, China
    Cancer Lett 236:250-8. 2006
    ..The Western analysis showed that As2O3 was probably not the substrate to be bound and extruded by P-glycoprotein in R-HepG2 cells because it could not maintain the cellular P-glycoprotein expression...
  64. ncbi The MRP-related and BCRP/ABCG2 multidrug resistance proteins: biology, substrate specificity and regulation
    A Haimeur
    Cancer Research Laboratories, Queen s University, Kingston, Ontario, Canada K7L 3N6
    Curr Drug Metab 5:21-53. 2004
    ..Factors that regulate expression of the MRP-related proteins and ABCG2/BCRP are also reviewed...
  65. pmc Lapatinib (Tykerb, GW572016) reverses multidrug resistance in cancer cells by inhibiting the activity of ATP-binding cassette subfamily B member 1 and G member 2
    Chun Ling Dai
    State Key Laboratory for Oncology in South China, Cancer Center, Sun Yat Sen University, Guangzhou, China
    Cancer Res 68:7905-14. 2008
    ..Overall, we conclude that lapatinib reverses ABCB1- and ABCG2-mediated MDR by directly inhibiting their transport function. These findings may be useful for cancer combinational therapy with lapatinib in the clinic...
  66. ncbi Expression of multidrug resistance-related transporters in human breast carcinoma
    A Kanzaki
    Department of Pathology, Institute of Development, Aging and Cancer, Tohoku University, Aoba-ku, Sendai 980-8575, Japan
    Jpn J Cancer Res 92:452-8. 2001
    ..P-glycoprotein (P-gp) / MDR1, MRP1 and LRP may play more important roles than BCRP in chemotherapy of human breast carcinoma...
  67. ncbi Antimicrobial resistance in nosocomial bloodstream infection associated with pneumonia and the value of systematic surveillance cultures in an adult intensive care unit
    Pieter O Depuydt
    Department of Intensive Care, Ghent University Hospital, Gent, Belgium
    Crit Care Med 34:653-9. 2006
    To study the occurrence of multiple-drug-resistant pathogens in nosocomial bloodstream infection associated with pneumonia. To evaluate prediction of multiple drug resistance by systematic surveillance cultures.
  68. pmc Multigenic drug resistance among inbred malaria parasites
    C Dye
    Vector Biology and Epidemiology Unit, London School of Hygiene and Tropical Medicine, UK
    Proc Biol Sci 264:61-7. 1997
    ..We discuss some of the wider implications of these results for the evolution of multigenic resistance...
  69. ncbi Multidrug resistance mediated by the breast cancer resistance protein BCRP (ABCG2)
    L Austin Doyle
    The University of Maryland Greenebaum Cancer Center, 22 South Greene Street, Baltimore, MD 21201, USA
    Oncogene 22:7340-58. 2003
    ..More prospective studies are needed, preferably combining BCRP protein or mRNA quantification with functional assays, in order to determine the contribution of BCRP to drug resistance in human cancers...
  70. ncbi Emerging importance of multidrug-resistant Acinetobacter species and Stenotrophomonas maltophilia as pathogens in seriously ill patients: geographic patterns, epidemiological features, and trends in the SENTRY Antimicrobial Surveillance Program (1997-1999
    A C Gales
    University of Iowa College of Medicine, Iowa City, Iowa, USA, and Division of Infectious Diseases, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
    Clin Infect Dis 32:S104-13. 2001
    ..maltophilia isolates observed in this study emphasize the importance of local surveillance in determining the most adequate therapy for acinetobacter and S. maltophilia infections and the possible clonal, epidemic nature of occurrence...
  71. ncbi Vaults are up-regulated in multidrug-resistant cancer cell lines
    V A Kickhoefer
    Department of Biological Chemistry and the Jonsson Comprehensive Cancer Center, University of California, School of Medicine, Los Angeles, California 90095 1737, USA
    J Biol Chem 273:8971-4. 1998
    ..The observation that vault synthesis is linked directly to multidrug resistance supports a direct role for vaults in drug resistance...
  72. ncbi Recovery of chloroquine sensitivity and low prevalence of the Plasmodium falciparum chloroquine resistance transporter gene mutation K76T following the discontinuance of chloroquine use in Malawi
    Toshihiro Mita
    Department of International Affairs and Tropical Medicine, Tokyo Women s Medical University School of Medicine, Tokyo, Japan
    Am J Trop Med Hyg 68:413-5. 2003
    ..We assayed two genetic mutations implicated in chloroquine resistance (N86Y in the P. falciparum multiple drug resistance gene 1 and K76T in the P. falciparum chloroquine resistance transporter gene) in 82 P...
  73. ncbi Reversal of P-glycoprotein-mediated multi-drug resistance by the E3 ubiquitin ligase Cbl-b in human gastric adenocarcinoma cells
    Ye Zhang
    Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, People s Republic of China
    J Pathol 218:248-55. 2009
    ..These results demonstrate an important role for Cbl-b in reversing P-gp-mediated gastric cancer MDR through suppression of the PI3K/Akt signalling pathway and the down-regulation of P-gp expression...
  74. ncbi Reversal of multidrug resistance: lessons from clinical oncology
    Susan F Bates
    Molecular Therapeutics Section, Medicine Branch, National Cancer Institute, Bethesda, MD 20892, USA
    Novartis Found Symp 243:83-96; discussion 96-102, 180-5. 2002
    ..Using third generation Pgp antagonists and properly designed clinical trials, it should be possible to determine the contribution of modulators to the reversal of clinical drug resistance...
  75. ncbi Effects of Lewis Y antigen on the gene expression of multiple drug resistance-associated proteins in human ovarian cancer RMG-I-H cells
    Song Gao
    Department of Obstetrics and Gynecology, Shengjing Hospital, China Medical University, 110004, Shenyang, People s Republic of China
    Med Oncol 27:960-7. 2010
    The effects of Lewis Y antigen on the gene expression of multiple drug resistance-associated proteins in human ovarian cancer RMG-I-H cells were unclear by now...
  76. ncbi The drug resistance-related protein LRP is the human major vault protein
    G L Scheffer
    Department of Pathology, Free University Hospital, Amsterdam, The Netherlands
    Nat Med 1:578-82. 1995
    ..The LRP gene is located on chromosome 16, close to the genes coding for multidrug resistance-associated protein and protein kinase C-beta, and may mediate drug resistance, perhaps via a transport process...
  77. pmc Measurement of multiple drug resistance transporter activity in putative cancer stem/progenitor cells
    Vera S Donnenberg
    Hillman Cancer Center, Pittsburgh, PA, USA
    Methods Mol Biol 568:261-79. 2009
    b>Multiple drug resistance, mediated by the expression and activity of ABC-transporters, is a major obstacle to antineoplastic therapy...
  78. ncbi Predicting drug sensitivity and resistance: profiling ABC transporter genes in cancer cells
    Gergely Szakacs
    Laboratory of Cell Biology, Center for Cancer Research, NCI, NIH, Bethesda, MD, 20892, USA
    Cancer Cell 6:129-37. 2004
    ..Unexpectedly, we also found and validated compounds whose activity is potentiated, rather than antagonized, by the MDR1 multidrug transporter. Such compounds may serve as leads for development...
  79. ncbi The role of half-transporters in multidrug resistance
    S E Bates
    Medicine Branch, National Cancer Institute, Bethesda, Maryland, USA
    J Bioenerg Biomembr 33:503-11. 2001
    ..Future studies will be aimed at identifying an inhibitor, and attempting to translate recognition of this new transporter into a target for anticancer treatment...
  80. pmc Selective toxicity of NSC73306 in MDR1-positive cells as a new strategy to circumvent multidrug resistance in cancer
    Joseph A Ludwig
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
    Cancer Res 66:4808-15. 2006
    ..This article shows that NSC73306 kills cells with intrinsic or acquired P-gp-induced MDR and indirectly acts to eliminate resistance to MDR1 substrates...
  81. pmc MexR repressor of the mexAB-oprM multidrug efflux operon of Pseudomonas aeruginosa: identification of MexR binding sites in the mexA-mexR intergenic region
    K Evans
    Department of Microbiology and Immunology, Queen's University, Kingston, Ontario, Canada, K7L 3N6
    J Bacteriol 183:807-12. 2001
    ....
  82. ncbi To use MIBI or not to use MIBI? That is the question when assessing tumour cells
    Jean Luc Moretti
    UPRES 2360 Ciblage et Imagerie Fonctionnelle de la Progression Tumorale, Faculte de Medecine, Bobigny, France
    Eur J Nucl Med Mol Imaging 32:836-42. 2005
    ..Although it has been suggested that MIBI might be used to monitor tumour response to treatment, MIBI is unable to differentiate tumours with ongoing apoptosis from those developing drug resistance...
  83. ncbi Antibacterial resistance worldwide: causes, challenges and responses
    Stuart B Levy
    Center for Adaptation Genetics and Drug Resistance, Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
    Nat Med 10:S122-9. 2004
    ..Drug resistance presents an ever-increasing global public health threat that involves all major microbial pathogens and antimicrobial drugs...
  84. ncbi Reversal of multidrug resistance of cancer through inhibition of P-glycoprotein by 5-bromotetrandrine
    Jing Jin
    Department of Pharmacology, University of Cambridge, Cambridge, UK
    Cancer Chemother Pharmacol 55:179-88. 2005
    ..The present study aimed to evaluate the MDR reversal activity of bromotetrandrine (BrTet), a bromized derivative of tetrandrine (Tet), in vitro and in vivo...
  85. ncbi Systematic surveillance cultures as a tool to predict involvement of multidrug antibiotic resistant bacteria in ventilator-associated pneumonia
    P Depuydt
    Department of Intensive Care, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium
    Intensive Care Med 34:675-82. 2008
    ..To assess prediction of multidrug resistant (MDR) pathogens in ventilator-associated pneumonia (VAP) by systematic surveillance cultures (SC) and to assess the contribution of SC to initial antibiotic therapy...
  86. 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...
  87. ncbi Interactions of colistin and rifampin on multidrug-resistant Acinetobacter baumannii
    E J Giamarellos-Bourboulis
    4th Department of Internal Medicine, University of Athens, Medical School, Greece
    Diagn Microbiol Infect Dis 40:117-20. 2001
    ..baumannii is increased in the presence of rifampin, so that their administration might be proposed for nosocomial infections by these isolates...
  88. ncbi From MDR to MXR: new understanding of multidrug resistance systems, their properties and clinical significance
    T Litman
    Department of Medical Physiology, The Panum Institute, University of Copenhagen, Denmark
    Cell Mol Life Sci 58:931-59. 2001
    ..Finally, the clinical correlations, both for reversal of MDR in cancer and for drug delivery, are discussed...
  89. ncbi Occurrence of multiple drug resistance in Trypanosoma brucei rhodesiense isolated from sleeping sickness patients
    J M Kagira
    Kenya Agricultural Research Institute Trypanosomiasis Research Centre KARI TRC, P O Box 362, Kikuyu, Kenya
    Onderstepoort J Vet Res 74:17-22. 2007
    ..In conclusion, our study has revealed the existence of cross-resistance among the melarsoprol resistant isolates which could only be cured by isometamidium...
  90. ncbi Reversal of P-glycoprotein-mediated multidrug resistance by Alisol B 23-acetate
    Cheng Wang
    Department of Biology and Chemistry, Bioactive Products Research Group, City University of Hong Kong, Kowloon, Hong Kong SAR, China
    Biochem Pharmacol 68:843-55. 2004
    ..Our results suggest that ABA may be a potential MDR reversal agent and could serve as a lead compound in the development of novel drugs...
  91. ncbi Multidrug resistance and cancer: the role of the human ABC transporter ABCG2
    Karin F K Ejendal
    Department of Chemistry, Purdue University, 1393 Brown Laboratories of Chemistry, West Lafayette, IN 47907 1393, USA
    Curr Protein Pept Sci 3:503-11. 2002
    ..A complete understanding of the mechanism and biological function of ABCG2 will be important for understanding its normal physiology as well as potentially for the development of novel chemotherapeutic treatment strategies...
  92. pmc Detailed characterization of cysteine-less P-glycoprotein reveals subtle pharmacological differences in function from wild-type protein
    A M Taylor
    Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK
    Br J Pharmacol 134:1609-18. 2001
    ..The wt and cys-less P-gp isoforms display similarity in their fundamental kinetic properties thereby validating the use of cys-less P-gp as a template for future cysteine-directed structure/function analysis...
  93. ncbi Epigenetic changes to the MDR1 locus in response to chemotherapeutic drugs
    Emma K Baker
    Epigenetics in Human Health and Disease Laboratory, The Alfred Medical Research and Education Precinct, Baker Medical Research Institute, Commercial Road, Prahran, Victoria 3181, Australia
    Oncogene 24:8061-75. 2005
    ..Our results demonstrate that chemotherapeutic drugs can actively induce epigenetic changes within the MDR1 promoter, and enhance the MDR phenotype...
  94. ncbi Colistin: the re-emerging antibiotic for multidrug-resistant Gram-negative bacterial infections
    Jian Li
    Facility for Anti Infective Drug Development and Innovation, Victorian College of Pharmacy, Monash University, Parkville, Victoria, Australia
    Lancet Infect Dis 6:589-601. 2006
    ..In the battle against rapidly emerging bacterial resistance we can no longer rely entirely on the discovery of new antibiotics; we must also pursue rational approaches to the use of older antibiotics such as colistin...
  95. ncbi The role of multiple drug resistance proteins in fetal and/or placental protection against teratogen-induced orofacial clefting
    Lesli Ann Rawles
    Angel Charity for Children Wings for Genetic Research, Steele Children s Research Center, Department of Pediatrics, Section of Medical and Molecular Genetics, University of Arizona, Tucson, Arizona, USA
    Mol Reprod Dev 74:1483-9. 2007
    Previous studies have shown a role for multiple drug resistance proteins in protecting the fetus from a limited number of teratogens...
  96. pmc Need for annual surveillance of antimicrobial resistance in Streptococcus pneumoniae in the United States: 2-year longitudinal analysis
    D F Sahm
    MRL, Herndon, Virginia 20171 4603, USA
    Antimicrob Agents Chemother 45:1037-42. 2001
    ..This longitudinal surveillance study of resistance in S. pneumoniae revealed that significant changes do occur in just a single year and supports the need for surveillance at least on an annual basis, if not continuously...
  97. ncbi In vivo and in vitro multitracer analyses of P-glycoprotein expression-related multidrug resistance
    Terez Marian
    PET Center, University of Debrecen, Hungary
    Eur J Nucl Med Mol Imaging 30:1147-54. 2003
    ..Parallel administration of (18)FDG and (99m)Tc-MIBI combined with verapamil treatment seems to be a good candidate as a non-invasive marker for the diagnosis of MDR-related Pgp expression in tumours...
  98. 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...
  99. ncbi Proteome analysis of multidrug resistance in vincristine-resistant human gastric cancer cell line SGC7901/VCR
    Yi Xuan Yang
    Key Laboratory of Cancer Proteomics of Ministry of Health of China, Xiangya Hospital, Central South University, Changsha, Hunan, PR China
    Proteomics 6:2009-21. 2006
    ..These data will be valuable for further study of the mechanisms of MDR in human gastric cancer...
  100. ncbi Reversal of multidrug resistance-associated protein-mediated drug resistance in cultured human neuroblastoma cells by the quinolone antibiotic difloxacin
    M D Norris
    Children s Cancer Institute Australia for Medical Research, Sydney Children s Hospital
    Med Pediatr Oncol 36:177-80. 2001
    ..The clinical implication of these findings is that MRP modulators may prove therapeutically useful...
  101. ncbi Reversal of doxorubicin resistance in breast cancer cells by photochemical internalization
    Pei Jen Lou
    Department of Otolaryngology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan, Republic of China
    Int J Cancer 119:2692-8. 2006
    b>Multiple drug resistance (MDR) is a problem that seriously reduces the efficacy of many chemotherapy agents...

Research Grants65

  1. Molecular Basis of E. coli Adhesins in Bladder Disorders
    Scott J Hultgren; Fiscal Year: 2013
    ....
  2. 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. ..
  3. Biochemical Characterization of Cytochrome b5 Reductase in Candida albicans
    MARY JOLENE PATRICIA HOLLOWAY; Fiscal Year: 2010
    ..Hence, identification of new drug targets has particular significance to combat multiple drug resistance in opportunistic fungal pathogens...
  4. Optimization of Neoglycoside Antibiotics for Nosocomial Pathogens and Select Agen
    Arnold Louie; Fiscal Year: 2013
    ....
  5. STRUCTURE-BASED TUBERCULOSIS DRUG DESIGN TARGETED AT ACYL-COA CARBOXYLASE
    Shiou Chuan Tsai; Fiscal Year: 2010
    ..PERFORMANCE SITE(S) (organization, city, state) University of California, Irvine, CA 92697, USA REVISED ABSTRACT SECTION ..
  6. Structural mechanism of DNA segregation by the pSK41 par system
    Maria Schumacher; Fiscal Year: 2010
    ..Thus, understanding the structural basis for DNA segregation by this par system will provide several points of potential therapeutic intervention against pSK41 harboring multidrug resistant S. aureus strains. ..
  7. Eukaryotic-type STK/STP-mediated modulation of enterococcal pathogenesis
    Vijay Pancholi; Fiscal Year: 2010
    ....
  8. National surveillance of emerging MDR in pediatric Enterobacteriaceae infections
    Danielle M Zerr; Fiscal Year: 2013
    ....
  9. Deciphering of the Toxin-Antitoxin Systems in E. coli
    Masayori Inouye; Fiscal Year: 2012
    ....
  10. 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. ..
  11. Vitamin D Inhibition of HIV and M. Tuberculosis Coinfection in Macrophages
    Stephen A Spector; Fiscal Year: 2010
    ....
  12. Optimization of novel pyranopyridine efflux pump inhibitors
    Son Truong Nguyen; Fiscal Year: 2013
    ..Aim 3. Prioritize analogs using in vitro cytotoxicity and ADME assays. Aim 4. Verify the mechanism of action and identify the molecular target of the MBX-2319 series of efflux pump inhibitors. ..
  13. The population genetics of antibiotic resistance in multi-drug environments
    Roy Kishony; Fiscal Year: 2013
    ..Our goal for the application of this research is to help design drug regimes that better prevent the emergence of resistance. ..
  14. Systems Biology for Molecular Analysis of Tuberculosis in Ethiopia
    Gobena Ameni; Fiscal Year: 2013
    ..This proposal includes innovative systems biology research as well as a program training Ethiopian scientists in genomics disciplines and applications to infectious diseases. 2. ..
  15. Identification of novel HIV capsid assembly inhibitors (Hit-to-Lead development)
    OSVALDO ARIEL FLORES; Fiscal Year: 2011
    ..Molecules that target HIV Capsid assembly offer a unique promise of providing high genetic barrier to resistance as well as complement existing therapies as part of combination therapy. ..
  16. Discovering New Anti-Infective Agents from Lysobacter
    Liangcheng Du; Fiscal Year: 2013
    ..The deciphering of the biosynthetic mechanism for these structurally distinct and biologically active products will allow for designing rational strategiesin the development of the products as new anti-infectives. ..
  17. Targeted Infection Prevention (TIP) Program in Nursing Homes
    Lona Mody; Fiscal Year: 2013
    ..Our results will allow infection control practitioners, healthcare workers, clinicians, policy makers, legislatures, and consumers to better address antimicrobial resistance and infections in older adults in NHs. ..
  18. Exploring the Physiology of Leukemic Stem Cells by Mechanisms of Drug Resistance
    Robert W Storms; Fiscal Year: 2010
    ..applicant): Clinical data support the concept that both normal stem cells and leukemia stem cells exhibit multiple drug resistance. However, it is unclear how mechanisms for drug resistance might interrelate with stem cell physiology...
  19. Dissecting a novel mechanism of drug-induced death in Toxoplasma gondii
    GUSTAVO A ARRIZABALAGA; Fiscal Year: 2013
    ..The completion of these aims will elucidate the details and mechanisms of an inducible death pathway. This constitutes an innovative approach to the discovery of drug targets in this important pathogen. ..
  20. Epidemiology of multidrug-resistant tuberculosis in Peru
    Mercedes C Becerra; Fiscal Year: 2010
    ..tuberculosis strains. Results will serve to guide basic research in tuberculosis diagnostics and therapeutics. ..
  21. 2011 Multidrug Efflux Systems GRC
    Olga Lomovskaya; Fiscal Year: 2011
    ....
  22. Preserving beta-lactam utility vs pathogens producing any class of beta-lactamase
    LUIGI XERRI; Fiscal Year: 2013
    ..The Phase II application endeavors to select a pre-development candidate from these two "Finalists" and drive this compound through IND-enabling studies to an Investigational New Drug filing. ..
  23. Modulation of Inflammasome Activation by Yersinia
    Igor E Brodsky; Fiscal Year: 2013
    ..Third, we will test te hypothesis that inflammasome activation in vivo controls Yersinia infection via production of caspase-1 dependent cytokines that induce activation of specific immune cell subsets that promote bacterial clearance. ..
  24. Determinants of HIV Dynamics and Variation
    JOSE ORLANDO MALDONADO-ORTIZ; Fiscal Year: 2013
    ....
  25. Streamlined Structures of Human Integral Membrane Proteins at Atomic Resolution
    Stephen G Aller; Fiscal Year: 2011
    ..We employ a new strategy to determine structures of human IMPs at highthroughput to integrate these computational approaches and accelerate drug discovery. ..
  26. Molecular Antibiotic Resistance Arrays for clinical microbiology laboratories
    PAUL STEPHEN KEIM; Fiscal Year: 2013
    ....
  27. Development of novel small molecule drugs for the treatment of high risk B-ALL
    CATHY A SWINDLEHURST; Fiscal Year: 2013
    ..B-ALL is the most common childhood malignancy and is one of leading causes of death in children, generally due to relapse as a result of multiple drug resistance.
  28. National surveillance of emerging MDR in pediatric Enterobacteriaceae infections
    Danielle Zerr; Fiscal Year: 2009
    ..This will provide needed information for the design of future interventional studies aimed at preventing PBLR resistance. ..
  29. Computationally optimized anti-staphylococcal biotherapeutics
    Karl E Griswold; Fiscal Year: 2013
    ..aureus infections. ..
  30. Function and pharmacology of schistosome multidrug resistance proteins
    Robert M Greenberg; Fiscal Year: 2010
    ..We propose to use several approaches to determine the properties of one such schistosome molecule, P-glycoprotein, which, in vertebrates, is also involved in resistance to a broad array of drugs. ..
  31. High Throughput Screen For HIV-1 MA/CA Processing Site Inhibitors
    RONALD I SWANSTROM; Fiscal Year: 2011
    ....
  32. SPONTANEOUS AND CARCINOGEN-INDUCED MUTAGENESIS
    Jeffrey H Miller; Fiscal Year: 2010
    ..coli, and also that would complement different E. coli repair defects. We will also construct a system for studying mutagenesis in a pathogen such as B. pertussis. ..
  33. Improving Outcome in Neonatal Abstinence Syndrome
    Barry M Lester; Fiscal Year: 2013
    ....
  34. DYNAMIC NUCLEAR POLARIZATION SOLID STATE NMR SPECTROMETER FOR BIOMOLECULAR STUDIE
    Ann E McDermott; Fiscal Year: 2010
    ..and homologs), pulmonary disease (beta-2-adrenergic receptor) and infectious diseases (HIV capsid, multiple drug resistance factor from S. aureus, ATP synthase from M. tuberculosis)...
  35. Biology of the Apicomplexan Plastid
    Boris Striepen; Fiscal Year: 2013
    ..overall potency, restriction to certain life-cycle stages, unwanted side effects, and rapidly emerging multiple drug resistance. A constant stream of new drugs and potential drug targets is required to stay abreast of the threat ..
  36. Mechanism of cell polarization and asymmetric segregation of ageing determinants
    Rong Li; Fiscal Year: 2013
    ....
  37. Structure of M. tuberculosis Adenosine Kinase and Design of Antimicrobial Nucle
    Rongbao Li; Fiscal Year: 2010
    ..tuberculosis AK with a lead adenosine analog. These studies will provide molecular basis for development of anti-mycobacterial nucleoside analogs. ..
  38. Development of JS-K as an anti-leukemic agent
    Paul J Shami; Fiscal Year: 2012
    ..Work done in this project will develop a new drug called JS-K for the treatment of AML. This work will lead to great improvements in treatment of AML and other cancers. ..
  39. Molecular Imaging of Cancer and Its Response to Therapy
    Kenneth A Krohn; Fiscal Year: 2013
    ..abstract_text> ..
  40. DNA SYNTHESIS AND RECOMBINATION BY HIV DNA POLYMERASE
    Robert A Bambara; Fiscal Year: 2011
    ..This mechanism can produce viruses with increased or multi-drug resistance. Our results will help us to understand and defeat this mechanism so that anti-AIDS drugs can be more effective. ..
  41. 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. ..
  42. PSMA-based MR Imaging and Therapy of Prostate Cancer
    Sangeeta Ray; Fiscal Year: 2013
    ..Mentorship will be geared more toward biological issues to provide a well-rounded portfolio as she progresses toward independence in biomedical imaging research. ..
  43. COBRE: UID: PROJ 1: EVOLUTION OF ANTIBIOTIC RESISTANCE PLASMID HOST RANGE
    Eva M Top; Fiscal Year: 2011
    ..This may reveal attractive targets for specific drug therapy in the fight against the alarming spread of drug resistance in human pathogens. ..
  44. Mechanism of spore germination
    Philip C Hanna; Fiscal Year: 2012
    ....
  45. Function of MVFR in Pseudomonas aeruginosa virulence
    Laurence G Rahme; Fiscal Year: 2012
    ....
  46. N-Heterocycles from Azides through Rhodium-Catalyzed Nitrenoid Transfer
    TOM GREGORY DRIVER; Fiscal Year: 2012
    ..In the third specific aim, we showcase our methods in syntheses that rapidly generate multiple drug resistance (MDR) reversal agents, N-acetylardeemin, KT-5720, and coronaridine...
  47. Cellular and molecular pathways of tuberculosis progression
    Irina V Lyadova; Fiscal Year: 2012
    ..abstract_text> ..
  48. Conformational Flexibility and Antibiotic Resistance
    Jeffrey W Peng; Fiscal Year: 2012
    ..The results will advance our abilities to cope with acceleration of multi-drug resistance in MRSA and other bacterial pathogens. ..
  49. Robotic SPECT for Biological Imaging Onboard Radiation Therapy Machines
    Fang Fang Yin; Fiscal Year: 2012
    ..This work will advance SPECT in novel directions, allowing real-time biological targeting in radiation therapy, and potentially improving treatment outcome. ..
  50. Mechanisms of Staphylococcal Co-Resistance to Daptomycin and Host Defense Peptide
    Arnold S Bayer; Fiscal Year: 2013
    ..This should enable 'smart design'of future novel anti-SA agents that circumvent this adaptive response. ..
  51. Phase II SBIR: Responding to NDM-1 - Advancement of a new MBL inhibitor to IND
    LUIGI XERRI; Fiscal Year: 2013
    ..The Phase II application endeavors to drive this "first in class" MBL inhibitor candidate (VNRX-5113) through IND-enabling studies to an Investigational New Drug filing. ..
  52. Structural Analysis of Multidrug Transport
    Mark E Girvin; Fiscal Year: 2013
    ..We will determine the three dimensional structure of the protein by itself, and in complex with the compounds that it transports, in order to understand how it functions, and ultimately guide the design of inhibitors of the transporter. ..
  53. NANOTHERAPEUTIC STRATEGY FOR MULTIDRUG RESISTANT TUMORS
    Mansoor Amiji; Fiscal Year: 2009
    ..The multimodal nanocarrier strategy proposed here would provide a translatable approach to overcome MDR in cancer patients. ..
  54. 2013 Multi-Drug Efflux Systems GRC
    Olga Lomovskaya; Fiscal Year: 2013
    ....
  55. ANTITUMOR AGENTS FROM BLUE-GREEN ALGAE
    Richard Moore; Fiscal Year: 2002
    ..The last tasks are the isolation, identification and evaluation of the potent cytotoxin in Aulosira fertillisima DU-18-1 and the potent fungicidal cytotoxins in five cyanophytes. ..
  56. Molecular analysis of accurate ribosomal translocation
    KURT L FREDRICK; Fiscal Year: 2013
    ....
  57. PHARMACOPHORE INTERACTIONS WITH TUBULIN OF CRYPTOPHYCINS
    Gunda Georg; Fiscal Year: 2001
    ..that they possess tumor-selective toxicity and greatly reduced susceptibility to P-glycoprotein-mediated multiple drug resistance in comparison to vinblastine, colchicine and taxol...
  58. LAT1/Asct2 Targeted Inhibition of Efflux Pumps for the Treatment of MDR Cancers
    Andy Tsai; Fiscal Year: 2012
    ..Targeted inhibition of these pumps could resensitize the cancer to chemotherapy drugs while minimizing side effects. ..
  59. 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. ..
  60. DRUG RESISTANCE AND GENE AMPLIFICATION IN LEISHMANIA
    Stephen Beverley; Fiscal Year: 2002
    ..The H region amplification will be a major focus as this amplification encodes multiple drug resistance genes and has been observed in pathogenic species...
  61. Mechanisms of Immunological Adaptation to a Harsh Chemical Environment
    Charles Rice; Fiscal Year: 2009
    ..This model will offer novel insights into how resistance or adaptation to environmental contaminants can develop. ..
  62. The Role of Signaling Pathways in Brain Tumors in Mice
    Eric C Holland; Fiscal Year: 2013
    ..Eventually we hope to create a rational cocktail of therapy that would minimize the enhancement of stem cell character and multi-drug resistance in cells of the perivascular niche in gliomas and medulloblastomas. ..
  63. NEW DRUGS FOR RESISTANT DISEASE FROM CI/MS STUDIES
    VERONICA BIERBAUM; Fiscal Year: 2000
    ....
  64. The Evolution of Specialists and Generalists
    ANTHONY DEAN; Fiscal Year: 2004
    ..Mutational changes will be sequenced to determine the predictably of evolution at the molecular level. ..
  65. Membrane Transport Proteins Gordon Research Conference
    Lydia Aguilar Bryan; Fiscal Year: 2009
    ..Glucose Transport in the Brain, TRP Channels in Health and Disease, Trafficking of Membrane Transporters, Multiple Drug Resistance and Anti-microbial, Anti-cancer and Antiepileptic Compounds, Structure of Membrane Transporters, CNS ..