drug resistance

Summary

Summary: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration.

Top Publications

  1. pmc Chloroquine-resistant Plasmodium vivax malaria in Debre Zeit, Ethiopia
    Hiwot Teka
    Department of Biology, Addis Ababa University, Addis Ababa, Ethiopia
    Malar J 7:220. 2008
  2. pmc A sterol-regulatory element binding protein is required for cell polarity, hypoxia adaptation, azole drug resistance, and virulence in Aspergillus fumigatus
    Sven D Willger
    Department of Veterinary Molecular Biology, Montana State University, Bozeman, MT, USA
    PLoS Pathog 4:e1000200. 2008
  3. pmc Vivax malaria: neglected and not benign
    Ric N Price
    International Health Program, Menzies School of Health Research and Charles Darwin University, Casuarina, Darwin, Northern Territory 0811, Australia
    Am J Trop Med Hyg 77:79-87. 2007
  4. pmc Chloroquine-resistant Plasmodium vivax, Brazilian Amazon
    Franklin Simoes de Santana Filho
    Emerg Infect Dis 13:1125-6. 2007
  5. pmc The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP
    Cai Hong Yun
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 105:2070-5. 2008
  6. pmc Artemisinin resistance in Plasmodium falciparum malaria
    Arjen M Dondorp
    Mahidol Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
    N Engl J Med 361:455-67. 2009
  7. pmc Emergence of artemisinin-resistant malaria on the western border of Thailand: a longitudinal study
    Aung Pyae Phyo
    Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
    Lancet 379:1960-6. 2012
  8. pmc A major genome region underlying artemisinin resistance in malaria
    Ian H Cheeseman
    Texas Biomedical Research Institute, San Antonio, TX 78245, USA
    Science 336:79-82. 2012
  9. pmc Drug resistance in leishmaniasis
    Simon L Croft
    Drugs for Neglected Diseases Initiative, 1 place Saint Gervais, CH 1201 Geneva, Switzerland
    Clin Microbiol Rev 19:111-26. 2006
  10. pmc Whole genome sequencing of multiple Leishmania donovani clinical isolates provides insights into population structure and mechanisms of drug resistance
    Tim Downing
    Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, United Kingdom
    Genome Res 21:2143-56. 2011

Detail Information

Publications337 found, 100 shown here

  1. pmc Chloroquine-resistant Plasmodium vivax malaria in Debre Zeit, Ethiopia
    Hiwot Teka
    Department of Biology, Addis Ababa University, Addis Ababa, Ethiopia
    Malar J 7:220. 2008
    ..Chloroquine (CQ) is the first line treatment for confirmed P. vivax malaria in the country. The first report of CQ treatment failure in P. vivax was from Debre Zeit, which suggested the presence of chloroquine resistance...
  2. pmc A sterol-regulatory element binding protein is required for cell polarity, hypoxia adaptation, azole drug resistance, and virulence in Aspergillus fumigatus
    Sven D Willger
    Department of Veterinary Molecular Biology, Montana State University, Bozeman, MT, USA
    PLoS Pathog 4:e1000200. 2008
    ..Thus, these findings present a new function of SREBP proteins in filamentous fungi, and demonstrate for the first time that hypoxia adaptation is likely an important virulence attribute of pathogenic molds...
  3. pmc Vivax malaria: neglected and not benign
    Ric N Price
    International Health Program, Menzies School of Health Research and Charles Darwin University, Casuarina, Darwin, Northern Territory 0811, Australia
    Am J Trop Med Hyg 77:79-87. 2007
    ..Without these, vivax malaria will continue to be neglected by ministries of health, policy makers, researchers, and funding bodies...
  4. pmc Chloroquine-resistant Plasmodium vivax, Brazilian Amazon
    Franklin Simoes de Santana Filho
    Emerg Infect Dis 13:1125-6. 2007
  5. pmc The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP
    Cai Hong Yun
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 105:2070-5. 2008
    ..kinase inhibitors (TKIs), but the efficacy of these agents is often limited because of the emergence of drug resistance conferred by a second mutation, T790M...
  6. pmc Artemisinin resistance in Plasmodium falciparum malaria
    Arjen M Dondorp
    Mahidol Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
    N Engl J Med 361:455-67. 2009
    ..There are recent concerns that the efficacy of such therapies has declined on the Thai-Cambodian border, historically a site of emerging antimalarial-drug resistance.
  7. pmc Emergence of artemisinin-resistant malaria on the western border of Thailand: a longitudinal study
    Aung Pyae Phyo
    Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
    Lancet 379:1960-6. 2012
    ..We aimed to establish whether artemisinin resistance has spread or emerged on the Thailand-Myanmar (Burma) border...
  8. pmc A major genome region underlying artemisinin resistance in malaria
    Ian H Cheeseman
    Texas Biomedical Research Institute, San Antonio, TX 78245, USA
    Science 336:79-82. 2012
    ....
  9. pmc Drug resistance in leishmaniasis
    Simon L Croft
    Drugs for Neglected Diseases Initiative, 1 place Saint Gervais, CH 1201 Geneva, Switzerland
    Clin Microbiol Rev 19:111-26. 2006
    ....
  10. pmc Whole genome sequencing of multiple Leishmania donovani clinical isolates provides insights into population structure and mechanisms of drug resistance
    Tim Downing
    Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, United Kingdom
    Genome Res 21:2143-56. 2011
    ..sequence data reveals genetic structure within these lines not shown by multilocus typing, and suggests that drug resistance has emerged multiple times in this closely related set of lines...
  11. ncbi Genetic diversity and chloroquine selective sweeps in Plasmodium falciparum
    John C Wootton
    Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894 6075, USA
    Nature 418:320-3. 2002
    ..The presence of linkage disequilibrium provides a basis for mapping genes under drug selection in P. falciparum...
  12. ncbi Artemisinin resistance: current status and scenarios for containment
    Arjen M Dondorp
    Mahidol Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok10400, Thailand
    Nat Rev Microbiol 8:272-80. 2010
    ..Mathematical modelling can be a useful tool to evaluate possible strategies for containment...
  13. pmc Changes in the treatment responses to artesunate-mefloquine on the northwestern border of Thailand during 13 years of continuous deployment
    Verena Ilona Carrara
    Shoklo Malaria Research Unit, Tak, Thailand
    PLoS ONE 4:e4551. 2009
    ....
  14. ncbi A molecular marker for chloroquine-resistant falciparum malaria
    A Djimde
    Malaria Section, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore 21201, USA
    N Engl J Med 344:257-63. 2001
    ..Chloroquine resistance has been associated in vitro with point mutations in two genes, pfcrt and pfmdr 1, which encode the P. falciparum digestive-vacuole transmembrane proteins PfCRT and Pgh1, respectively...
  15. ncbi Reemergence of chloroquine-sensitive Plasmodium falciparum malaria after cessation of chloroquine use in Malawi
    James G Kublin
    Malaria Section, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA
    J Infect Dis 187:1870-5. 2003
    ..The reintroduction of chloroquine, ideally in combination with another antimalarial drug, should be considered in areas where chloroquine resistance has declined and safe and affordable alternatives remain unavailable...
  16. pmc Spiroindolones, a potent compound class for the treatment of malaria
    Matthias Rottmann
    Swiss Tropical and Public Health Institute, Parasite Chemotherapy, CH 4002 Basel, Switzerland
    Science 329:1175-80. 2010
    ..The optimized spiroindolone NITD609 shows pharmacokinetic properties compatible with once-daily oral dosing and has single-dose efficacy in a rodent malaria model...
  17. pmc Sequence-based association and selection scans identify drug resistance loci in the Plasmodium falciparum malaria parasite
    Daniel J Park
    Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 109:13052-7. 2012
    ..and the combination of association and selection-based tests, we detected several loci associated with drug resistance. These loci included the previously known signals at pfcrt, dhfr, and pfmdr1, as well as many genes not ..
  18. ncbi Artemisinin resistance in Cambodia: a clinical trial designed to address an emerging problem in Southeast Asia
    Harald Noedl
    Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Vienna, Austria
    Clin Infect Dis 51:e82-9. 2010
    ..This article provides additional data from a clinical trial that has been published in The New England Journal of Medicine...
  19. ncbi Pgh1 modulates sensitivity and resistance to multiple antimalarials in Plasmodium falciparum
    M B Reed
    The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia
    Nature 403:906-9. 2000
    ..This has important implications for the development and efficacy of future antimalarial agents...
  20. ncbi Drug resistance in veterinary helminths
    Adrian J Wolstenholme
    Department of Biology and Biochemistry, University of Bath, Bath, BA2 7AY, UK
    Trends Parasitol 20:469-76. 2004
    ..This review summarizes some of the recent findings on resistance mechanisms, puts forward some recommendations for limiting its impact and suggests some priorities for research in this area...
  21. ncbi Intercontinental spread of pyrimethamine-resistant malaria
    Cally Roper
    London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
    Science 305:1124. 2004
    ..The resistance alleles carried by these migrants are now spreading across Africa at an alarming rate, signaling the end of affordable malaria treatment and presenting sub-Saharan Africa with a public health crisis...
  22. ncbi Increasing failure of miltefosine in the treatment of Kala-azar in Nepal and the potential role of parasite drug resistance, reinfection, or noncompliance
    Suman Rijal
    B P Koirala Institute of Health Sciences, Dharan, Nepal
    Clin Infect Dis 56:1530-8. 2013
    ..Given the paucity of anti-VL drugs and the looming threat of resistance, there is an obvious need for close monitoring of clinical efficacy of MIL...
  23. pmc Chloroquine resistance before and after its withdrawal in Kenya
    Leah Mwai
    Kenya Medical Research Institute Wellcome Trust Collaborative Research Programme, Kilifi, Kenya
    Malar J 8:106. 2009
    ..Changes to those that occurred in the dihydrofolate reductase gene (dhfr) that confers resistance to the replacement drug, pyrimethamine/sulphadoxine were also compared...
  24. pmc Artemisinin combination therapy for vivax malaria
    Nicholas M Douglas
    Menzies School of Health Research, Darwin, NT, Australia
    Lancet Infect Dis 10:405-16. 2010
    ..Analyses of the cost-effectiveness of ACTs for both Plasmodium species are needed to assess the role of these drugs in the control and elimination of vivax malaria...
  25. pmc High resistance of Plasmodium falciparum to sulphadoxine/pyrimethamine in northern Tanzania and the emergence of dhps resistance mutation at Codon 581
    Samwel Gesase
    National Institute for Medical Research, Tanga Centre, Tanga, Tanzania
    PLoS ONE 4:e4569. 2009
    ..High levels of drug resistance to SP have been reported from north-eastern Tanzania associated with mutations in parasite genes...
  26. ncbi The role of ABC transporters in drug resistance, metabolism and toxicity
    Hristos Glavinas
    SOLVO Biotechnology, Szeged, Hungary
    Curr Drug Deliv 1:27-42. 2004
    ..deal with the human ABC transporters as targets of therapeutic interventions in medicine, including cancer drug resistance, lipid and other metabolic disorders, and even gene therapy applications...
  27. ncbi In vivo parasitological measures of artemisinin susceptibility
    Kasia Stepniewska
    Mahidol Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand
    J Infect Dis 201:570-9. 2010
    ....
  28. ncbi Identification of the gene for vitamin K epoxide reductase
    Tao Li
    Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Nature 427:541-4. 2004
    ..The expressed enzyme is 163 amino acids long, with at least one transmembrane domain. Identification of the VKOR gene extends our understanding of blood clotting, and should facilitate development of new anticoagulant drugs...
  29. pmc Assessment of the molecular marker of Plasmodium falciparum chloroquine resistance (Pfcrt) in Senegal after several years of chloroquine withdrawal
    Magatte Ndiaye
    Service de Parasitologie Mycologie, Faculte de Medecine, Universite Cheikh Anta Diop, Dakar, Senegal
    Am J Trop Med Hyg 87:640-5. 2012
    As a result of widespread antimalarial drug resistance, all African countries with endemic malaria have, in recent years, changed their malaria treatment policy...
  30. pmc Detection of high levels of mutations involved in anti-malarial drug resistance in Plasmodium falciparum and Plasmodium vivax at a rural hospital in southern Ethiopia
    Patricia Mula
    National Centre for Tropical Medicine, Institute of Health Carlos III, C Sinesio Delgado 4 6, 28029, Madrid, Spain
    Malar J 10:214. 2011
    In Ethiopia, malaria is caused by Plasmodium falciparum and Plasmodium vivax, and anti-malarial drug resistance is the most pressing problem confronting control of the disease...
  31. pmc Limited geographical origin and global spread of sulfadoxine-resistant dhps alleles in Plasmodium falciparum populations
    Toshihiro Mita
    Department of International Affairs and Tropical Medicine, Tokyo Women s Medical University, Japan
    J Infect Dis 204:1980-8. 2011
    ..It remains unresolved whether P. falciparum resistance to sulfadoxine, which is conferred by mutations in dihydropteroate synthase (DHPS), evolved following a similar pattern...
  32. ncbi Antifolates in cancer therapy: structure, activity and mechanisms of drug resistance
    Nitzan Gonen
    The Fred Wyszkowski Cancer Research Laboratory, Faculty of Biology, Technion Israel Institute of Technology, Haifa 32000, Israel
    Drug Resist Updat 15:183-210. 2012
    ..g. BGC 945). Hence, targeting mechanisms of antifolate-resistance could facilitate the development of rationally-based novel antifolates and strategies that overcome chemoresistance...
  33. pmc Novel polymorphisms in Plasmodium falciparum ABC transporter genes are associated with major ACT antimalarial drug resistance
    Maria Isabel Veiga
    Malaria Research Lab, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
    PLoS ONE 6:e20212. 2011
    ..Southeast Asia is an epicenter of emerging antimalarial drug resistance, including recent resistance to the artemisinins, the core component of all recommended antimalarial ..
  34. ncbi Molecular analysis of pfatp6 and pfmdr1 polymorphisms and their association with in vitro sensitivity in Plasmodium falciparum isolates from the Thai-Myanmar border
    Papichaya Phompradit
    Thailand Center of Excellence on Drug Discovery and Development, Thammasat University, Rangsit Campus, Patumthani 12121, Thailand
    Acta Trop 120:130-5. 2011
    ..No association between mutation or amplification of pfatp6 gene and in vitro susceptibility of P. falciparum isolates was found...
  35. pmc Intermittent treatment to prevent pregnancy malaria does not confer benefit in an area of widespread drug resistance
    Whitney E Harrington
    Malaria Program, Seattle Biomedical Research Institute, Seattle, Washington, USA
    Clin Infect Dis 53:224-30. 2011
    ..However, parasites resistant to SP are widespread in parts of Africa, and IPTp may perversely exacerbate placental infections that contain SP-resistant parasites...
  36. pmc Chemical genomic profiling for antimalarial therapies, response signatures, and molecular targets
    Jing Yuan
    Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Science 333:724-9. 2011
    Malaria remains a devastating disease largely because of widespread drug resistance. New drugs and a better understanding of the mechanisms of drug action and resistance are essential for fulfilling the promise of eradicating malaria...
  37. pmc In vivo selection of Plasmodium falciparum parasites carrying the chloroquine-susceptible pfcrt K76 allele after treatment with artemether-lumefantrine in Africa
    Christin Sisowath
    Infectious Diseases Unit, Department of Medicine and Karolinska Institutet, Stockholm, Sweden
    J Infect Dis 199:750-7. 2009
    ..Identification of drug-specific parasite determinants that contribute to treatment failures will provide important tools for the detection and surveillance of AL resistance...
  38. pmc The evolution of drug resistance and the curious orthodoxy of aggressive chemotherapy
    Andrew F Read
    Center for Infectious Disease Dynamics, Department of Biology, Pennsylvania State University, University Park, PA 16802, USA
    Proc Natl Acad Sci U S A 108:10871-7. 2011
    ..An evidence-based approach to resistance management is required...
  39. ncbi In vivo selection of Plasmodium falciparum pfmdr1 86N coding alleles by artemether-lumefantrine (Coartem)
    Christin Sisowath
    Malaria Research Laboratory, Unit of Infectious Diseases, Department of Medicine, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden
    J Infect Dis 191:1014-7. 2005
    ..derivative-based combination therapy is expected to suppress the development of Plasmodium falciparum drug resistance in Africa...
  40. pmc Phenotypic evidence of emerging ivermectin resistance in Onchocerca volvulus
    Mike Y Osei-Atweneboana
    Institute of Parasitology, McGill University, Montreal, Canada
    PLoS Negl Trop Dis 5:e998. 2011
    ..In this follow up study we have investigated the reproductive response of female worms to multiple treatments with IVM...
  41. ncbi Spread and evolution of Plasmodium falciparum drug resistance
    Toshihiro Mita
    Department of International Affairs and Tropical Medicine, Tokyo Women s Medical University, School of Medicine, 9 1 Kawada cho, Shinjuku ku, Tokyo 162 8666, Japan
    Parasitol Int 58:201-9. 2009
    Worldwide spread of Plasmodium falciparum drug resistance to conventional antimalarials, chloroquine and sulfadoxine/pyrimethamine, has been imposing a serious public health problem in many endemic regions...
  42. ncbi Return of chloroquine antimalarial efficacy in Malawi
    Miriam K Laufer
    University of Maryland School of Medicine, Baltimore, MD 21201, USA
    N Engl J Med 355:1959-66. 2006
    ..The molecular marker of chloroquine-resistant falciparum malaria subsequently declined in prevalence and was undetectable by 2001, suggesting that chloroquine might once again be effective in Malawi...
  43. ncbi Praziquantel: its use in control of schistosomiasis in sub-Saharan Africa and current research needs
    M J Doenhoff
    School of Biology, University of Nottingham, University Park, Nottingham NG7 2RD, UK
    Parasitology 136:1825-35. 2009
    ....
  44. pmc Modified fixed-ratio isobologram method for studying in vitro interactions between atovaquone and proguanil or dihydroartemisinin against drug-resistant strains of Plasmodium falciparum
    Quinton L Fivelman
    ITD, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom
    Antimicrob Agents Chemother 48:4097-102. 2004
    ..The relevance of in vitro interactions to in vivo treatment is discussed...
  45. pmc Geographic patterns of Plasmodium falciparum drug resistance distinguished by differential responses to amodiaquine and chloroquine
    Juliana Martha Sá
    Laboratory of Malaria and Vector Research and Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 106:18883-9. 2009
    ..Increasing use of AQ in Africa poses the threat of a selective sweep of highly AQ-resistant, CQ-resistant parasites with pfcrt and pfmdr1 mutations that are as advantaged and persistent as in South America...
  46. ncbi Prevalence of molecular markers of Plasmodium falciparum resistance to sulfadoxine-pyrimethamine during the intermittent preventive treatment in infants coupled with the expanded program immunization in Senegal
    Babacar Faye
    Department of Parasitology, Faculty of de Medicine, Cheikh Anta Diop University of Dakar, Dakar, Senegal
    Parasitol Res 109:133-8. 2011
    ..This study reveals that despite an increase in the prevalence of individual mutations, the IPT-SP coupled with the EPI has no major impact on DHFR and DHPS combined mutations...
  47. pmc Drug resistance maps to guide intermittent preventive treatment of malaria in African infants
    Inbarani Naidoo
    London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK
    Parasitology 138:1469-79. 2011
    ..There are clear deficiencies in molecular surveillance data coverage. We discuss requirements for ongoing surveillance of SP resistance markers in support of the use of SP-IPTi...
  48. pmc Chloroquine resistance in Plasmodium falciparum malaria parasites conferred by pfcrt mutations
    Amar bir Singh Sidhu
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Science 298:210-3. 2002
    ..pfcrt mutations increased susceptibility to artemisinin and quinine and minimally affected amodiaquine activity; hence, these antimalarials warrant further investigation as agents to control chloroquine-resistant falciparum malaria...
  49. ncbi Discordance in drug resistance-associated mutation patterns in marker genes of Plasmodium falciparum and Plasmodium knowlesi during coinfections
    Rupesh K Tyagi
    Department of Biotechnology, All India Institute of Medical Sciences, New Delhi, India
    J Antimicrob Chemother 68:1081-8. 2013
    ..Human Plasmodium knowlesi infections have been reported from several South-East Asian countries, excluding India, but its drug susceptibility profile in mixed-infection cases remains unknown...
  50. ncbi Consensus and future directions on the definition of high on-treatment platelet reactivity to adenosine diphosphate
    Laurent Bonello
    Department of Cardiology, Institut National de la Santè et de la Recherche Médicale Unité Mixte de Recherche 608, Hopital Universitaire Nord, Faculte de Medecine, Marseille, France
    J Am Coll Cardiol 56:919-33. 2010
    ..This review provides a consensus opinion on the definition of high on-treatment platelet reactivity to ADP based on various methods reported in the literature and proposes how this measurement may be used in the future care of patients...
  51. pmc Benznidazole-resistance in Trypanosoma cruzi is a readily acquired trait that can arise independently in a single population
    Ana Maria Mejía
    Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, University of London, United Kingdom
    J Infect Dis 206:220-8. 2012
    ..They also demonstrate that T. cruzi has a propensity to undergo genetic changes that can lead to drug resistance, a finding that has implications for future therapeutic strategies.
  52. pmc Declining responsiveness of Plasmodium falciparum infections to artemisinin-based combination treatments on the Kenyan coast
    Steffen Borrmann
    Kenya Medical Research Institute Wellcome Trust Research Programme, Kilifi, Kenya
    PLoS ONE 6:e26005. 2011
    ..The emergence of artemisinin-resistant P. falciparum malaria in South-East Asia highlights the need for continued global surveillance of the efficacy of artemisinin-based combination therapies...
  53. ncbi The public health impact of chloroquine resistance in Africa
    J F Trape
    Laboratoire de Paludologie, Institut de recherche pour le developpement IRD, formerly ORSTOM, Dakar, Senegal
    Am J Trop Med Hyg 64:12-7. 2001
    ..Here we review published data on the public health impact of antimalarial drug resistance in Africa...
  54. pmc Pfmdr1 copy number and arteminisin derivatives combination therapy failure in falciparum malaria in Cambodia
    Pharath Lim
    Institut Pasteur in Cambodia, Phnom Penh, Cambodia
    Malar J 8:11. 2009
    ....
  55. pmc Patterns of chloroquine use and resistance in sub-Saharan Africa: a systematic review of household survey and molecular data
    Anne E P Frosch
    Center for Vaccine Development, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, MD, USA
    Malar J 10:116. 2011
    ..This observation suggests that there is continuing use of ineffective anti-malarials in Africa and that persistent chloroquine-resistant malaria is due to ongoing drug pressure despite national policy changes...
  56. pmc Artemisinin-resistant Plasmodium falciparum in Pursat province, western Cambodia: a parasite clearance rate study
    Chanaki Amaratunga
    Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20852, USA
    Lancet Infect Dis 12:851-8. 2012
    ..We investigated contributions of both parasite genetics and host factors to the artemisinin-resistance phenotype in Pursat, western Cambodia...
  57. pmc Glutathione S-transferases as antioxidant defence agents confer pyrethroid resistance in Nilaparvata lugens
    J G Vontas
    School of Biosciences, Cardiff University, Main College, Museum Avenue, P O Box 915, Cardiff CF10 3TL, Wales, UK
    Biochem J 357:65-72. 2001
    ..lugens is through protecting tissues from oxidative damage. Our study extends the GSTs' range of efficacy to pyrethroid insecticides and possibly explains the role of elevated GSTs in other pyrethroid-resistant insects...
  58. pmc Drug coverage in treatment of malaria and the consequences for resistance evolution--evidence from the use of sulphadoxine/pyrimethamine
    Allen L Malisa
    Department of Biological Sciences, Faculty of Science, Sokoine University of Agriculture, SUA, PO Box 3038, Morogoro, Tanzania
    Malar J 9:190. 2010
    ..that drug coverage is the primary determinant of drug pressure and the driving force behind the evolution of drug resistance. These models show that where the basis of resistance is multigenic, the effects of selection can be ..
  59. pmc Intrahost modeling of artemisinin resistance in Plasmodium falciparum
    Sompob Saralamba
    Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Rajthevee, Bangkok 10400, Thailand
    Proc Natl Acad Sci U S A 108:397-402. 2011
    ..This result supports the hypothesis that artemisinin resistance mainly reflects reduced ring-stage susceptibility and predicts that doubling the frequency of dosing will accelerate clearance of artemisinin-resistant parasites...
  60. pmc In vitro sensitivities of Plasmodium falciparum to different antimalarial drugs in Uganda
    Samuel L Nsobya
    Department of Medicine, Makerere University, Kampala, Uganda
    Antimicrob Agents Chemother 54:1200-6. 2010
    ..In summary, we demonstrated in parasites from Kampala a range of sensitivities to older drugs; correlation of sensitivities to CQ, MDAQ, and QN; and good activity against nearly all strains for DHA, LM, and PQ...
  61. ncbi Drug resistance in Indian visceral leishmaniasis
    S Sundar
    Kala Azar Medical Research Centre, Banaras Hindu University, Varanasi, India
    Trop Med Int Health 6:849-54. 2001
    ..Lipid associated amphotericin B has an excellent safety and efficacy profile, but remains out of reach for most patients because of its high cost...
  62. ncbi Humans as the world's greatest evolutionary force
    S R Palumbi
    Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA
    Science 293:1786-90. 2001
    ..Slowing and controlling arms races in disease and pest management have been successful in diverse ecological and economic systems, illustrating how applied evolutionary principles can help reduce the impact of humankind on evolution...
  63. pmc Identification and functional validation of the novel antimalarial resistance locus PF10_0355 in Plasmodium falciparum
    Daria Van Tyne
    Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, United States of America
    PLoS Genet 7:e1001383. 2011
    ..Our GWAS and follow-on functional validation demonstrate the potential of genome-wide studies to elucidate functionally important loci in the malaria parasite genome...
  64. ncbi Online analysis of in vitro resistance to antimalarial drugs through nonlinear regression
    Hervé Le Nagard
    INSERM Université Paris Diderot UMR 738, Paris, France
    Comput Methods Programs Biomed 104:10-8. 2011
    ..This website is used by various teams in the world and the user can do the analysis without knowing R using the GUI. This article describes version 2.1 of this website and shows illustration on five different real examples...
  65. ncbi Schistosomiasis: challenges for control, treatment and drug resistance
    Alan Fenwick
    Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College, London, UK
    Curr Opin Infect Dis 19:577-82. 2006
    ..Despite shifts in global health policy towards the implementation of mass chemotherapeutic control programmes at the national scale in sub-Saharan Africa, however, many challenges still exist...
  66. pmc In silico activity profiling reveals the mechanism of action of antimalarials discovered in a high-throughput screen
    David Plouffe
    Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA
    Proc Natl Acad Sci U S A 105:9059-64. 2008
    ..In addition, the screening method has the potential to provide the malaria community with many new starting points for the development of biological probes and drugs with novel antiparasitic activities...
  67. ncbi Susceptibility and natural resistance of Trypanosoma cruzi strains to drugs used clinically in Chagas disease
    L S Filardi
    Centro de Pesquisas Rene Rachou, FIOCRUZ, Belo Horizonte, Brazil
    Trans R Soc Trop Med Hyg 81:755-9. 1987
    ..cruzi strains was also observed. Drug resistance was identified among T...
  68. pmc High heritability of malaria parasite clearance rate indicates a genetic basis for artemisinin resistance in western Cambodia
    Tim J C Anderson
    Southwest Foundation for Biomedical Research, PO Box 760549, San Antonio, Texas 78245, USA
    J Infect Dis 201:1326-30. 2010
    ....
  69. pmc Hyperparasitaemia and low dosing are an important source of anti-malarial drug resistance
    Nicholas J White
    Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, 420 6 Rajvithi Road, Bangkok 10400, Thailand
    Malar J 8:253. 2009
    Preventing the emergence of anti-malarial drug resistance is critical for the success of current malaria elimination efforts...
  70. ncbi Diversity of the sarco/endoplasmic reticulum Ca(2+)-ATPase orthologue of Plasmodium falciparum (PfATP6)
    Sabina Dahlström
    Department of Medicine, Karolinska Institutet, Stockholm, Sweden
    Infect Genet Evol 8:340-5. 2008
    ..In conclusion our findings show that PfATP6 is a more diverse gene than previously demonstrated. This natural variation may constitute a starting ground for artemisinin-driven progressive selection of resistant parasites...
  71. pmc Antimalarial drug resistance of Plasmodium falciparum in India: changes over time and space
    Naman K Shah
    Department of Epidemiology, University of North Carolina, Chapel Hill, USA
    Lancet Infect Dis 11:57-64. 2011
    ..Strategies to reduce the emergence and spread of future drug resistance need to be proactive and supported by intensive monitoring.
  72. ncbi Unresolved issues in anthelmintic pharmacology for helminthiases of humans
    Timothy G Geary
    Institute of Parasitology, McGill University, Montreal, QC, Canada H9X 3V9
    Int J Parasitol 40:1-13. 2010
    ..and soil-transmitted helminthiases in humans increases the urgency to better understand and better monitor drug resistance, and to broaden the currently very narrow range of available anthelmintics...
  73. ncbi p38 Mitogen-activated protein kinase-induced glucocorticoid receptor phosphorylation reduces its activity: role in steroid-insensitive asthma
    Elvis Irusen
    Thoracic Medicine, Imperial College School of Medicine at the National Heart and Lung Institute, London, United Kingdom
    J Allergy Clin Immunol 109:649-57. 2002
    ..IL-2 combined with IL-4 can alter glucocorticoid receptor (GR) ligand-binding affinity and modulate glucocorticoid function...
  74. pmc Artesunate dose escalation for the treatment of uncomplicated malaria in a region of reported artemisinin resistance: a randomized clinical trial
    Delia Bethell
    Department of Immunology and Medicine, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand
    PLoS ONE 6:e19283. 2011
    ..This study investigated the impact of different AS doses on clinical and parasitological responses in malaria patients from an area of known artemisinin resistance in western Cambodia...
  75. pmc Plasmodium falciparum genome-wide scans for positive selection, recombination hot spots and resistance to antimalarial drugs
    Jianbing Mu
    Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases NIAID, National Institutes of Health NIH, Bethesda, Maryland, USA
    Nat Genet 42:268-71. 2010
    ..Parasite half-maximum inhibitory concentrations for seven antimalarial drugs were obtained and used in GWAS to identify genes associated with drug responses. This study provides valuable tools and insight into the P. falciparum genome...
  76. pmc Drug resistance in African trypanosomiasis: the melarsoprol and pentamidine story
    Nicola Baker
    London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK
    Trends Parasitol 29:110-8. 2013
    ..Here, we review these findings and consider some new questions as well as future prospects for tackling the devastating diseases caused by these parasites...
  77. pmc Prevalence of resistance associated polymorphisms in Plasmodium falciparum field isolates from southern Pakistan
    Najia Karim Ghanchi
    Malaria Research Lab, Infectious Diseases Unit, Department of Medicine, Karolinska University Hospital Karolinska Institutet, Retziusväg 10, Stockholm, Sweden
    Malar J 10:18. 2011
    Scarce data are available on Plasmodium falciparum anti-malarial drug resistance in Pakistan. The aim of this study was, therefore, to determine the prevalence of P...
  78. ncbi Evolution of Plasmodium falciparum drug resistance: implications for the development and containment of artemisinin resistance
    Toshihiro Mita
    Department of Molecular and Cellular Parasitology, Juntendo University School of Medicine, Tokyo, Japan tmita juntendo ac jp
    Jpn J Infect Dis 65:465-75. 2012
    ..Elucidation of such markers would substantially contribute to the design of an effective policy for the containment of artemisinin resistance...
  79. pmc On being the right size: the impact of population size and stochastic effects on the evolution of drug resistance in hospitals and the community
    Roger D Kouyos
    Institute of Integrative Biology, ETH Zurich, Zurich, Switzerland
    PLoS Pathog 7:e1001334. 2011
    ..the prevalence of antibiotic resistance, we use a stochastic epidemiological model describing the spread of drug resistance in a hospital setting as well as the interaction between one or several hospitals and the community...
  80. pmc Lentiviral vectors and protocols for creation of stable hESC lines for fluorescent tracking and drug resistance selection of cardiomyocytes
    Hiroko Kita-Matsuo
    Burnham Institute for Medical Research, La Jolla, California, United States of America
    PLoS ONE 4:e5046. 2009
    ....
  81. ncbi DnaE2 polymerase contributes to in vivo survival and the emergence of drug resistance in Mycobacterium tuberculosis
    Helena I M Boshoff
    Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Twinbrook II, 12441 Parklawn Drive, Rockville, MD 20852, USA
    Cell 113:183-93. 2003
    ..DNA polymerases, is the primary mediator of survival through inducible mutagenesis and can contribute directly to the emergence of drug resistance in vivo. These results may indicate a potential new target for therapeutic intervention.
  82. pmc Anthelmintic resistance: markers for resistance, or susceptibility?
    R N Beech
    Institute of Parasitology, Macdonald College, McGill University, Ste Anne de Bellevue, QC H9X3V9, Canada
    Parasitology 138:160-74. 2011
    ..Resistance may result from a loss of sensitivity as well as the appearance of resistance. A focus on the presence of anthelmintic susceptibility may be as important as the detection of resistance...
  83. ncbi Kinetoplastid membrane protein-11 DNA vaccination induces complete protection against both pentavalent antimonial-sensitive and -resistant strains of Leishmania donovani that correlates with inducible nitric oxide synthase activity and IL-4 generation: ev
    Rajatava Basu
    Department of Immunology, Indian Institute of Chemical Biology, Kolkata
    J Immunol 174:7160-71. 2005
    ..This is the first report of a vaccine conferring protection to both antimony responsive and resistant Leishmania strains reflecting several aspects of clinical visceral leishmaniasis...
  84. pmc Prospective strategies to delay the evolution of anti-malarial drug resistance: weighing the uncertainty
    David L Smith
    Emerging Pathogens Institute and Department of Biology, University of Florida, Gainesville, 32611, USA
    Malar J 9:217. 2010
    The evolution of drug resistance in malaria parasites highlights a need to identify and evaluate strategies that could extend the useful therapeutic life of anti-malarial drugs...
  85. ncbi Artemisinins and the biological basis for the PfATP6/SERCA hypothesis
    Sanjeev Krishna
    Centre for Infection, Cellular and Molecular Medicine, St George s University of London, Cranmer Terrace, London, UK, SW17 0RE
    Trends Parasitol 26:517-23. 2010
    ..Herein, evidence is discussed that relates to this hypothesis as alternative suggestions for how artemisinins might act have been reviewed elsewhere...
  86. ncbi Drug resistance in brain diseases and the role of drug efflux transporters
    Wolfgang Loscher
    Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, and Center for Systems Neuroscience, Bunteweg 17, D 30559 Hannover, Germany
    Nat Rev Neurosci 6:591-602. 2005
    ..There is increasing evidence that drug efflux transporters have an important role in drug-resistant brain disorders, and this information should allow more efficacious treatment strategies to be developed...
  87. ncbi Plasmodium sensitivity to artemisinins: magic bullets hit elusive targets
    Xavier C Ding
    Centre suisse de recherches scientifiques en Côte d Ivoire, 01 BP 1303, Abidjan 01, Cote d Ivoire
    Trends Parasitol 27:73-81. 2011
    ....
  88. ncbi Mefloquine resistance in Plasmodium falciparum and increased pfmdr1 gene copy number
    Ric N Price
    Department of Cellular and Molecular Medicine Infectious Diseases, St George s Hospital Medical School, London, UK
    Lancet 364:438-47. 2004
    ..A combination of artesunate with mefloquine now cures more than 95% of acute infections. For both treatment regimens, the underlying mechanisms of resistance are not known...
  89. pmc Assays to detect beta-tubulin codon 200 polymorphism in Trichuris trichiura and Ascaris lumbricoides
    Aissatou Diawara
    Institute of Parasitology, McGill University, Quebec, Canada
    PLoS Negl Trop Dis 3:e397. 2009
    ..We have developed pyrosequencer assays for codon 200 (TTC or TAC) in A. lumbricoides and T. trichiura to screen for this single nucleotide polymorphism (SNP)...
  90. pmc Polymorphism of PfATPase in Niger: detection of three new point mutations
    Maman Laminou Ibrahim
    Centre de Recherche Médicale et Sanitaire CERMES, BP 10887 Niamey, Niger
    Malar J 8:28. 2009
    ..The goal of this work was to describe the baseline polymorphism of PfATPase6 gene in Niger, at a time when the national implementation of the ACT policy had just begun...
  91. ncbi Monitoring of in vitro susceptibilities and molecular markers of resistance of Plasmodium falciparum isolates from Thai-Myanmar border to chloroquine, quinine, mefloquine and artesunate
    Wanna Chaijaroenkul
    Graduate Program in Biomedical Sciences, Faculty of Allied Health Sciences, Thammasat University, Rangsit, Patumthani 12121, Thailand
    Acta Trop 113:190-4. 2010
    ..Moreover, the correlation between pfmdr1 gene amplification and susceptibility of the parasite to MQ, QN and AS was observed (decreased susceptibilities to MQ, QN and AS in isolates with increased pfmdr1 copy number)...
  92. pmc A non-radioactive DAPI-based high-throughput in vitro assay to assess Plasmodium falciparum responsiveness to antimalarials--increased sensitivity of P. falciparum to chloroquine in Senegal
    Daouda Ndiaye
    Faculty of Medicine and Pharmacy, Cheikh Anta Diop University, Dakar, Senegal
    Am J Trop Med Hyg 82:228-30. 2010
    The spread of Plasmodium falciparum drug resistance is outpacing new antimalarial development and compromising effective malaria treatment...
  93. pmc Identification of a mutant PfCRT-mediated chloroquine tolerance phenotype in Plasmodium falciparum
    Stephanie G Valderramos
    Department of Microbiology and Immunology, Columbia University Medical Center, New York, New York, United States of America
    PLoS Pathog 6:e1000887. 2010
    ....
  94. ncbi Glucantime-resistant Leishmania tropica isolated from Iranian patients with cutaneous leishmaniasis are sensitive to alternative antileishmania drugs
    R Hadighi
    Department of Parasitology, Faculty of Medicine, Iran University of Medical Sciences, 14496, Tehran, Iran
    Parasitol Res 101:1319-22. 2007
    ..However, these resistant isolates were shown to be sensitive to miltefosine and paromomycin. The latter two drugs could thus be useful alternatives for the treatment of leishmaniasis in Iran even for SbV-resistant isolates...
  95. pmc Exploring the contribution of candidate genes to artemisinin resistance in Plasmodium falciparum
    Mallika Imwong
    Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
    Antimicrob Agents Chemother 54:2886-92. 2010
    ..Artemisinin resistance in western Cambodia is not linked to candidate genes, as was suggested by earlier studies...
  96. pmc Resistance to antimalarials in Southeast Asia and genetic polymorphisms in pfmdr1
    Amy L PicKard
    Department of Epidemiology, University of North Carolina School of Public Health, Chapel Hill, North Carolina, USA
    Antimicrob Agents Chemother 47:2418-23. 2003
    ..001). Thus, measurement of pfmdr1 mutations and gene copy number may be useful for surveillance of mefloquine-resistant malaria in Southeast Asia...
  97. pmc Use of high-density tiling microarrays to identify mutations globally and elucidate mechanisms of drug resistance in Plasmodium falciparum
    Neekesh V Dharia
    Department of Cell Biology, ICND 202, The Scripps Research Institute, North Torrey Pines Road, La Jolla, CA 92037, USA
    Genome Biol 10:R21. 2009
    The identification of genetic changes that confer drug resistance or other phenotypic changes in pathogens can help optimize treatment strategies, support the development of new therapeutic agents, and provide information about the ..
  98. pmc Reduced in vitro susceptibility to artemisinin derivatives associated with multi-resistance in a traveller returning from South-East Asia
    Bruno Pradines
    Unité de Recherche en Biologie et Epidémiologie Parasitaires Unité de Recherche pour les Maladies Infectieuses et Tropicales Emergentes UMR 6236, Institut de Medecine Tropicale du Service de Sante des Armees, Marseille, France
    Malar J 10:268. 2011
    ....
  99. ncbi Characterisation of antimony-resistant Leishmania donovani isolates: biochemical and biophysical studies and interaction with host cells
    Rupkatha Mukhopadhyay
    Indian Institute of Chemical Biology, Council of Scientific and Industrial Research, Kolkata, India
    Int J Parasitol 41:1311-21. 2011
    ..The above results reinforce the notion that antimony resistant parasites have undergone a number of biochemical and biophysical changes as part of their adaptation to ensure their survival in the host...
  100. pmc Aspirin "resistance" and risk of cardiovascular morbidity: systematic review and meta-analysis
    George Krasopoulos
    University Health Network, Division of Cardiovascular Surgery, Toronto General Hospital
    BMJ 336:195-8. 2008
    ..To determine if there is a relation between aspirin "resistance" and clinical outcomes in patients with cardiovascular disease...
  101. ncbi Dual action of antimonial drugs on thiol redox metabolism in the human pathogen Leishmania donovani
    Susan Wyllie
    Division of Biological Chemistry and Molecular Biology, Wellcome Trust Biocentre, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland
    J Biol Chem 279:39925-32. 2004
    ..These observations suggest ways in which current antimony therapies could be improved, overcoming the growing problem of antimony resistance...

Research Grants75

  1. Molecular Basis of E. coli Adhesins in Bladder Disorders
    Scott J Hultgren; Fiscal Year: 2013
    ..Catheter-associated UTI (CAUTI) further exacerbates this problem. Consequently, multi-drug resistance is rising rapidly...
  2. Metabolic mechanisms of antiestrogen resistance in breast cancer
    UBALDO EMILIO MARTINEZ OUTSCHOORN; Fiscal Year: 2013
    ..Summary/Abstract: My long term career goal is to become an independent physician scientist who focuses on drug resistance in breast cancer and combines laboratory based mechanistic research and clinical trial design and ..
  3. Targeting CC-Chemokine Receptor 7 for the prevention of graft-versus-host disease
    JAMES M COGHILL; Fiscal Year: 2013
    ..of healthy stem cells, very high doses of chemotherapy can be administered in an effort to overcome any drug resistance displayed by the malignancy...
  4. Drug Interactions at the Human Blood-Brain Barrier
    Jashvant D Unadkat; Fiscal Year: 2010
    ..Prominent amongst these is P-glycoprotein (P-gp), an ABC efflux transporter encoded by the multi-drug resistance 1 (MDR1) gene [2]...
  5. Molecular Mechanisms of Disease Progression in Myeloid Malignancy
    ELIZABETH ANN EKLUND; Fiscal Year: 2013
    ..of cancer/leukemia stem cells (CSC/LSC) to Fas-induced apoptosis is associated with development of drug resistance in CML, but does not correlate with decreased Fas/FasL...
  6. Biochemical Characterization of Cytochrome b5 Reductase in Candida albicans
    MARY JOLENE PATRICIA HOLLOWAY; Fiscal Year: 2010
    ..Emerging drug resistance is a major problem in Candida, contributed by enzymes involved in the detoxification of xenobiotics and ..
  7. Optimization of Neoglycoside Antibiotics for Nosocomial Pathogens and Select Agen
    Arnold Louie; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Multi-drug resistance in Gram-negative bacteria is a common problem in infected patients in the ICU environment. With Pseudomonas aeruginosa and Acinetobacter spp...
  8. A Rapid Point-of-care Diagnostic for Neisseria gonorrhoeae STDs
    Richard F Selden; Fiscal Year: 2012
    ..typing (making reliable epidemiology studies and contact tracing impossible), and incapable of determining drug resistance profiles...
  9. Analysis of the functions of axon guidance genes during vector mosquito developme
    MOLLY DUMAN SCHEEL; Fiscal Year: 2012
    ..in vaccine development, the appearance of insecticide resistance in mosquito populations, the emergence of drug resistance in parasite populations, a general lack of support in many developing countries for mosquito control programs,..
  10. Site-directed Chemotherapy for Breast Cancer using Novel Angiogenesis Inhibitor
    Shaker A Mousa; Fiscal Year: 2010
    ..to investigate whether it may also stimulate cellular response to stress and thus reverse the development of drug resistance. Our results demonstrate that tetrac impacts on drug resistance and implicate at least two pathways that play ..
  11. DRUG RESISTANCE AND PTERIDINE METABOLISM IN LEISHMANIA
    Stephen M Beverley; Fiscal Year: 2010
    ..These studies have yielded new opportunities for chemotherapeutic attack and new directions for future study of pteridine metabolism and biology. [unreadable] ..
  12. Combination therapies for chronic HBV, liver disease and cancer
    Mark A Feitelson; Fiscal Year: 2012
    ..are potent drugs, they are limited by low rates of sustained response, side effects, and the emergence of drug resistance. Hence, the objective of this proposal is to devise combination therapies, following the model of HIV ..
  13. ENZYMOLOGY OF ANTIBIOTIC RESISTANCE
    Richard Armstrong; Fiscal Year: 2009
    Over the last quarter of a century antimicrobial drug resistance has become an increasingly serious problem in the clinic and the community...
  14. STRUCTURE-BASED TUBERCULOSIS DRUG DESIGN TARGETED AT ACYL-COA CARBOXYLASE
    Shiou Chuan Tsai; Fiscal Year: 2010
    ..has a cell envelope with chemically complex lipids that are closely related with its virulence and multi-drug resistance. Acyl-CoA carboxylase (ACCase) provides the building blocks for these complex lipids, and the importance and ..
  15. Inhibitors of S. aureus bNOS for adjunctive therapy
    Donald T Moir; Fiscal Year: 2013
    ..These new drugs will prolong the duration of effective concentrations of existing antibiotics, thus reducing selection for resistance and improving therapy. ..
  16. Structural mechanism of DNA segregation by the pSK41 par system
    Maria Schumacher; Fiscal Year: 2010
    ..This proposal focuses on one such par system from Staphylococcus aureus multi-drug resistance plasmid pSK41...
  17. Centromere Structure and Function in Candida albicans
    Judith G Berman; Fiscal Year: 2012
    ..Prophylactic antifungal treatments often result in the appearance of acquired drug resistance. C...
  18. Genetic and Evolutionary Basis of Fungal Drug Resistance
    Zhenglong Gu; Fiscal Year: 2013
    ..Virulence factors for fungal pathogens, such as pathogenic fungal drug resistance, often are quantitative traits...
  19. COMBINATORIAL-DESIGNED NANO-PLATFORMS TO OVERCOME TUMOR DRUG RESISTANCE
    Zhenfeng Duan; Fiscal Year: 2013
    ..and cytotoxic drugs for maximum cell-kill effect. ..
  20. Defining evolutionary trajectories: Molecular adaptation to antibiotic resistance
    ADIL YOUSIF SHAMOO; Fiscal Year: 2012
    ..to the development of new clinical strategies that consider the molecular mechanisms of adaptation to prevent drug resistance. PUBLIC HEALTH RELEVANCE: The rise of antibiotic resistance is a clear health threat that requires immediate ..
  21. Regulation of Ovarian Cancer Multidrug Resistance by MAP Kinases
    Scott T Eblen; Fiscal Year: 2013
    ..Therefore, defining the mechanisms of drug resistance is important for existing and new cancer therapies. Alternative mRNA splicing affects 74% of the human genome...
  22. Eukaryotic-type STK/STP-mediated modulation of enterococcal pathogenesis
    Vijay Pancholi; Fiscal Year: 2010
    ..There is a clear demand to control enterococcal multi-drug resistance problems using newer approaches...
  23. Towards a vaccine against Fasciola hepatica using FhSAP2 as an antigen
    Ana M Espino; Fiscal Year: 2013
    ..is the most effective drug to control fascioliasis;however, the cost of treatment and the emergence of drug resistance in sheep infected with F...
  24. National surveillance of emerging MDR in pediatric Enterobacteriaceae infections
    Danielle M Zerr; Fiscal Year: 2013
    ..especially methicillin-resistant Staphylococcus aureus, much less is known about the epidemiology of multi-drug resistance in Gram-negative organisms, particularly in pediatrics...
  25. Rapid, Highly Multiplexed and Sensitive Blood Test for Drug-resistant Bacteria
    ARMIN H REITMAIR; Fiscal Year: 2010
    ..diagnostic test system, capable of quickly identifying specific healthcare-associated bacterial strains and drug resistance patterns among the multitude of possibilities from a single patient sample, radically pushes the limits of ..
  26. ROS, Redox Regulation and Novel Targets for Cancer Therapy
    Peng Huang; Fiscal Year: 2013
    ..dependent on the bone marrow stromal cells to alleviate the oxidative stress and promote their survival and drug resistance through enhancing GSH synthesis mediated by an intercellular metabolic communication involving cystine->..
  27. Developing a New Therapeutic for the Treatment of Invasive Aspergillosis
    Mitchell W Mutz; Fiscal Year: 2013
    ..is required for fungal stress response and small molecule or genetic inhibition of calcineurin thwarts drug resistance. The challenge of exploiting FC as an antifungal agent is due to structural and sequence homology with human ..
  28. Discovery of Critical Host Genes Enabling Resistance to HIV-1 Infection as Therap
    Leyla S Diaz; Fiscal Year: 2012
    ..HIV-1 drugs that directly target virus often fail due to rapid emergence of drug resistance. Functional Genetics (FGI) used a proprietary technology, Random Homozygous Gene Perturbation (RHGP) and ..
  29. FUNCTION OF THE RAS RELATED RAL PROTEINS
    LARRY FEIG; Fiscal Year: 2009
    ..Ral signaling cascade in genetically stable dermal fibroblasts, which have a low probability of developing drug resistance, as a novel mode of anti-cancer therapy...
  30. Antisense Mediated Treatment of Hepatitis B Virus Infection
    STEFAN FRANK WIELAND; Fiscal Year: 2013
    ..In specific aim 3 the antiviral efficacy of the leads and the potential for emergence of drug resistance will be tested in the context of a bonefide HBV infection initiated with a monoclonal viral isolate using ..
  31. Development of Transdermal Films for the the Delivery of HIV Therapeutics
    Anthony Sang Won Ham; Fiscal Year: 2010
    ..HAART therapies have resulted in reduced patient adherence to the drug regimens, fueling the development of drug resistance. Thus, a continuing need for new and improved antiretroviral agents exists...
  32. Defining the role of proteostasis pathways in cancer drug resistance
    ERICA LYNN CAIN; Fiscal Year: 2013
    ..In most cases the molecular components that drive the evolution and maintenance of drug resistance are not well defined, but are likely to be conserved amongst cancer subtypes...
  33. The role of ICSBP in the pathogenesis of chronic myeloid leukemia
    ELIZABETH ANN EKLUND; Fiscal Year: 2013
    ..Insensitivity of leukemia stem cells (LSC) to Fas-induced apoptosis is associated with development of drug resistance in CML, but does not correlate with decreased expression of Fas or FasL...
  34. Understanding the biology of schistosomes in response to praziquantel
    Charles Cunningham; Fiscal Year: 2013
    ..A second potential problem is the presence of drug resistance traits in natural populations of worms...
  35. Regulatory Functions of APE1 acetylation
    KISHOR KUMAR BHAKAT; Fiscal Year: 2013
    ..DNA repair and transcriptional regulatory functions, and thus play a critical role in cell survival and drug resistance of tumor cells. This hypothesis will be tested in three specific aims...
  36. Transport ATPases: From Molecules to Maladies
    Rajini Rao; Fiscal Year: 2010
    ..is the rapidly growing number of diseases associated with Transport ATPases, among them: cancer and drug resistance, heart disease, immune and infectious diseases, ulcers, diabetes, vision and hearing loss, neurodegeneration ..
  37. Genetic Interactions and Synthetic Population Biology
    Michael B Elowitz; Fiscal Year: 2013
    ..These interactions can, and do, have large effects on phenotypes ranging from acquisition of drug resistance by viruses to autism and other complex disorders...
  38. Control of HIV drug resistance in older patients
    Alonso Heredia; Fiscal Year: 2010
    ..For those patients failing HAART due to HIV drug resistance, the recently developed antiretroviral class of CCR5 antagonists represents an alternative treatment option...
  39. AID-mediated genetic instability in BCR-ABL1-transformed B cell lineage leukemia
    MARKUS MUSCHEN; Fiscal Year: 2013
    ..abstract_text> ..
  40. Deciphering of the Toxin-Antitoxin Systems in E. coli
    Masayori Inouye; Fiscal Year: 2012
    ..The prolonged dormancy of M. tuberculosis in human tissues, biofilm formation, and persistent multi-drug resistance of various other human pathogens are presumed to be closely associated with toxin expression in these ..
  41. Targeting Akt Activation in CLL
    Wei Ding; Fiscal Year: 2013
    ..microenvironment components and this interaction is critical for maintaining their survival and mediates drug resistance. There is now significant and growing data supporting the key role of phosphoinositide 3- kinase (PI3K)/Akt ..
  42. Metabolic reprogramming: A new paradigm for targeting cisplatin resistant cells
    Medhi Wangpaichitr; Fiscal Year: 2013
    ..The majority of lung cancer patients will respond initially to cisplatin treatment;however, development of drug resistance is inevitable which results in disease progression...
  43. Rational Development of Anti-Trypanosoma Cruzi Drugs
    Michael H Gelb; Fiscal Year: 2013
    ..drug regimen that is shorter than current treatment courses of 60-90 days and stems development of potential drug resistance. PUBLIC HEALTH RELEVANCE: The proposed research will help develop new treatments for Chagas disease, a ..
  44. Molecular epidemiology of drug resistance and population genetic structure of Pla
    Fangli Lu; Fiscal Year: 2013
    ..2. Determine the point mutation prevalence in the dhfr (pyrimethamine drug resistance) and dhps (sulfadoxine drug resistance) genes associated with SP resistance in P...
  45. Genome Sequencer FLX Instrument
    ANNE VIRGINIA KANE; Fiscal Year: 2010
    ..In addition, deep sequencing will be used to achieve full length HIV sequencing to assess HIV drug resistance mutations and regions of HIV-1 envelope protein related to long term non-progression...
  46. Immune-based detection of rifampicin-resistance in HIV/TB
    Gregory P Bisson; Fiscal Year: 2013
    ..A major barrier to TB control is that detection of Mtb drug resistance requires collection of microbiological samples, which are not available in many cases of active disease in ..
  47. Mechanisms and regulation of serine resolvases
    Phoebe A Rice; Fiscal Year: 2012
    ..the mechanism and regulation of a DNA recombination reaction that is important for stable maintenance of many drug resistance-carrying plasmids found in Staphylococcus aureus, a common cause of opportunistic infections...
  48. Role of ABC efflux transporters in ALS
    Davide Trotti; Fiscal Year: 2013
    ..e. P-glycoprotein or P-gp, Multi-drug resistance proteins or MRPs, breast cancer resistance protein or BCRP, a.k.a...
  49. Lung Cancer Chemoradiation: Predictors of Survival
    Xifeng Wu; Fiscal Year: 2009
    ..b>Drug resistance presents a major obstacle in NSCLC treatment...
  50. Evo-epidemiology of Scistosoma mansoni in children in Kenya
    ERIC SAMUEL LOKER; Fiscal Year: 2010
    ..and presence of clonal genotypes as well as monitor the recruitment process of new worms and the evolution of drug resistance. This information will be valuable for understanding transmission dynamics, spread of novel traits such as ..
  51. A novel assay for inhibitors of influenza A virus polymerase complex assembly
    Feng Li; Fiscal Year: 2009
    ..To better prepare us to cope with an emerging influenza pandemic and combat the rising problem of antiviral drug resistance, new classes of antiviral drugs targeted to conserved viral functions are urgently needed...
  52. Phenotype MicroArray Analysis of Fastidious Pathogens
    Barry Bochner; Fiscal Year: 2009
    ..use knockout strains with PM technology to study the function of genes that are unique to the metabolism and drug resistance of this genus...
  53. The role of a histone H4 phosphorylation in drug resistance
    Zhiguo Zhang; Fiscal Year: 2013
    ..Together, these studies will reveal a novel epigenetic mechanism by which acquired TMZ resistance is regulated and validate Pak2 as a potential therapeutic target for overcoming TMZ resistance. ..
  54. In Vivo Imaging of bcl-2 Expression in Lymphoma
    Michael R Lewis; Fiscal Year: 2012
    ..chemotherapy is inevitable, with transformation to a more aggressive histologic type and development of drug resistance. High bcl-2 expression was more frequently associated with stage III-IV disease and correlated strongly with ..
  55. The new biology of estrogen action in aromatase resistance breast cancer cells
    JOAN SUEDEE LEWIS-WAMBI; Fiscal Year: 2011
    ..e., aromatase inhibition), however, is the development of acquired drug resistance. To further study the development of acquired resistance to Als, I have developed a panel of long-term ..
  56. The Environment as a Variable to Calibrate Mouse Models of Human Disease
    John M Essigmann; Fiscal Year: 2013
    ..Our animal model is well suited to study the time of onset of a mutator phenotype and, of equal importance, for additional studies to investigate interventions that could delay tumor development and drug resistance.
  57. Endoplasmic reticulum structure and dynamics in breast cancer cell metastasis and
    JASON EDWARD LEE; Fiscal Year: 2013
    ..Poor prognosis has been correlated to tumor metastasis and drug resistance. Therefore, there is a need to build on the present understanding of the mechanisms underlying cell migration ..
  58. Novel small-molecule inhibitors of Wee1 kinase for medulloblastoma treatment
    Philip Reigan; Fiscal Year: 2013
    ..to therapy has improved survival rates, high doses of cytotoxic chemotherapy are required to circumvent drug resistance mechanisms and to confer clinical efficacy, and unfortunately this often results in lasting neurocognitive ..
  59. Longitudinal Studies of HIV-Associated Bacterial Pneumonia
    William N Rom; Fiscal Year: 2013
    ..increasing HIV- 1 RNA viral load, RT-PCR in macrophages and increased envelope V3 loop mutations and drug resistance mutations in involved lobes...
  60. MicroRNA Signature of Tamoxifen Resistance in Breast Cancer
    Sarmila Majumder; Fiscal Year: 2010
    ..the role of microRNAs (miRs) in cellular processes linked to human diseases such as cancer, in development of drug resistance and to identify the miRs that can be used as diagnostic/prognostic markers...
  61. Novel Antifungal Therapeutic Approaches
    Joseph Heitman; Fiscal Year: 2012
    ..in delivering parenteral agents, consistent efficacy, need for rapid, short courses of therapy, and emerging drug resistance, therapeutic advances remain to be achieved...
  62. Vitamin D Inhibition of HIV and M. Tuberculosis Coinfection in Macrophages
    Stephen A Spector; Fiscal Year: 2010
    ..with coinfection associated with increased mortality and greater likelihood of selection for Mtb multi-drug resistance. Treatment of Mtb in the presence of HIV/AIDS is complicated by the immunosuppression associated with HIV ..
  63. Inhibition of glutathione reductase and ovarian cancer drug resistance reversal
    Xiangming Guan; Fiscal Year: 2006
    ..b>Drug resistance is a major cause of failure in ovarian cancer treatment...
  64. DETECTION & REVERSAL OF OVARIAN CANCER DRUG RESISTANCE
    Robert Ozols; Fiscal Year: 1992
    Acquired drug resistance and cross resistance is the major cause of chemotherapy failure...
  65. DRUG RESISTANCE AND GENE TRANSFER IN H PYLORI
    Douglas Berg; Fiscal Year: 2003
    ..sets of experiments are proposed: First, we will seek to better understand the emergence and persistence of drug resistance in HP populations...
  66. ADVANCED TECHNOLOGY FOR ASSAYING CANCER-DRUG RESISTANCE
    Mark Lim; Fiscal Year: 2010
    ..This problem is exemplified by drug resistance developed in patients treated for chronic myeloid leukemia (CML) with the small molecule drug Imatinib (..
  67. Biology and Drug Resistance of Candida Biofilms
    Mahmoud Ghannoum; Fiscal Year: 2005
    ..have received much less attention than bacterial biofilms, and our present knowledge of their biology and drug resistance is at a rudimentary stage...
  68. Chemical Glycobiology on Anthracyclines
    Peng Wang; Fiscal Year: 2009
    ..Despite the widespread use in cancer therapy, drug resistance and cardiotoxicity are the two major limitations for anthracycline drugs...
  69. GLUTATHIONE BIOSYSTHESIS AND DRUG RESISTANCE
    R Mulcahy; Fiscal Year: 1999
    ..Despite a long-standing association between elevated GSH and drug resistance, details of the molecular mechanisms responsible for alterations of GSH homeostasis in resistant tumor cells ..
  70. Dual Function Acridones as A New Antimalarial Chemotype
    Jane X Kelly; Fiscal Year: 2010
    ..Affordability, safety in the most vulnerable, and low susceptibility to drug resistance adaptations each represent unmet needs. In contrast to other drug classes (e.g...
  71. Imaging of O6-Alkylguanine-DNA Alkyltransferase
    Ganesan Vaidyanathan; Fiscal Year: 2005
    ..A major reason for poor prognosis in many patients is the development of drug resistance, resulting in tumor regrowth and eventual patient death...
  72. MOLECULAR GENETICS OF DRUG RESISTANCE IN E HISTOLYICA
    John Samuelson; Fiscal Year: 1993
    The goal of the proposed work is to investigate mechanism of drug resistance in Entamoeba histolytica, the protozoan parasite that causes human amoebiasis. Drug treatment is presently the major means of controlling E...
  73. Role of Proteinase-3 in Apoptosis and Drug Resistance
    AHMAD SAFA; Fiscal Year: 2007
    ..recently discovered that decreased expression of proteinase-3 (PR3), a serine protease, is associated with drug resistance. Inhibition of cellular PR3 expression by an antisense PR3 oligodeoxynucleotide resulted in a significant ..
  74. DRUG RESISTANCE AND GENE AMPLIFICATION IN LEISHMANIA
    Stephen Beverley; Fiscal Year: 2002
    Gene amplification and drug resistance is an important phenomenon in the biology and chemotherapy of Leishmania, as both laboratory and clinical isolates can often develop resistance to drugs in clinical usage (pentavalent antimonials) ..
  75. Nanoparticle targeting of cathepsin-L inhibitor and doxorubicin in breast cancer
    Shaker Mousa; Fiscal Year: 2007
    ..provide a persuasive rationale for studying the role of cathepsin L in the process of chemotherapeutic drug resistance. We showed that specific targeting of cathepsin L using chemical inhibitors or siRNA to this molecule forced ..