Research Topics
Species | Thomas KenslerSummaryAffiliation: Johns Hopkins Bloomberg School of Public Health Country: USA Publications
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Publications
Nrf2: friend or foe for chemoprevention?Thomas W Kensler
Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, 615 North Wolfe Street, Baltimore, MD 21205, USA
Carcinogenesis 31:90-9. 2010..This review provides a synopsis of KEAP1-NRF2 signaling, compares the impact of genetic versus pharmacologic activation and considers both the attributes and concerns of targeting the pathway in chemoprevention...- Keap1-nrf2 signaling: a target for cancer prevention by sulforaphaneThomas W Kensler
Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA
Top Curr Chem 329:163-77. 2013.... - Modulation of the metabolism of airborne pollutants by glucoraphanin-rich and sulforaphane-rich broccoli sprout beverages in Qidong, ChinaThomas W Kensler
Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
Carcinogenesis 33:101-7. 2012..No significant differences were seen between the effects of SFR versus GRR. Intervention with broccoli sprouts may enhance detoxication of airborne pollutants and attenuate their associated health risks... 
Translational strategies for cancer prevention in liverThomas W Kensler
Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA
Nat Rev Cancer 3:321-9. 2003..In the developing world--where the burden of liver cancer is highest--immediate, practical and economical approaches are essential. So, targeted chemoprevention might be most appropriate for the present generation of individuals at risk...- Strategies for chemoprevention of liver cancerThomas W Kensler
Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA
Eur J Cancer Prev 11:S58-64. 2002..Both chemopreventive agents modulated levels of aflatoxin biomarkers in the study participants in manners consonant with protection... 
Is it time to advance the chemoprevention of environmental carcinogenesis with microdosing trials?Thomas W Kensler
Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA
Cancer Prev Res (Phila) 2:1003-7. 2009..We also reflect on what microdosing studies have taught us to date...- Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathwayThomas W Kensler
Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
Annu Rev Pharmacol Toxicol 47:89-116. 2007..This review highlights the key elements in this adaptive response to protection against acute and chronic cell injury provoked by environmental stresses... - Chemoprevention of hepatocellular carcinoma in aflatoxin endemic areasThomas W Kensler
Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe Street, Baltimore, Maryland 21205, USA
Gastroenterology 127:S310-8. 2004.... - Oltipraz chemoprevention trial in Qidong, People's Republic of China: modulation of serum aflatoxin albumin adduct biomarkersT W Kensler
Department of Environmental Health Sciences, Johns Hopkins School of Hygiene and Public Health, Baltimore, Maryland 21205, USA
Cancer Epidemiol Biomarkers Prev 7:127-34. 1998..A follow-up Phase IIb trial with a longer intervention period will be necessary to determine the full extent to which aflatoxin biomarker burden can be reduced and whether diminution of biomarkers can be sustained over the long term... - Use of aflatoxin adducts as intermediate endpoints to assess the efficacy of chemopreventive interventions in animals and manT W Kensler
Department of Environmental Health Sciences, Johns Hopkins School of Hygiene and Public Health, Baltimore, MD 21205, USA
Mutat Res 402:165-72. 1998..The general approach that has been utilized for the development, validation and application of aflatoxin-DNA and protein adduct biomarkers to cancer chemoprevention trials is summarized... - Conceptually new deltanoids (vitamin D analogs) inhibit multistage skin tumorigenesisT W Kensler
Department of Environmental Health Sciences and Department of Epidemiology, School of Hygiene and Public Health, The Johns Hopkins University, Baltimore, MD 21205, USA
Carcinogenesis 21:1341-5. 2000.... - Chemoprotection by organosulfur inducers of phase 2 enzymes: dithiolethiones and dithiinsT W Kensler
Department of Environmental Health Sciences, Johns Hopkins School of Hygiene and Public Health, Baltimore, MD 21205, USA
Drug Metabol Drug Interact 17:3-22. 2000..Thus, identification and utilization of naturally-occurring organosulfur chemoprotectors including dithiins should be a high priority... - Effects of glucosinolate-rich broccoli sprouts on urinary levels of aflatoxin-DNA adducts and phenanthrene tetraols in a randomized clinical trial in He Zuo township, Qidong, People's Republic of ChinaThomas W Kensler
Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Room E7541, 615 North Wolfe Street, Baltimore, MD 21205, USA
Cancer Epidemiol Biomarkers Prev 14:2605-13. 2005..29). Understanding factors influencing glucosinolate hydrolysis and bioavailability will be required for optimal use of broccoli sprouts in human interventions... - Genetic ablation of Nrf2 enhances susceptibility to cigarette smoke-induced emphysema in miceTirumalai Rangasamy
Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA
J Clin Invest 114:1248-59. 2004..The responsiveness of the Nrf2 pathway may act as a major determinant of susceptibility to tobacco smoke-induced emphysema by upregulating antioxidant defenses and decreasing lung inflammation and alveolar cell apoptosis... - Modulation of gene expression by cancer chemopreventive dithiolethiones through the Keap1-Nrf2 pathway. Identification of novel gene clusters for cell survivalMi Kyoung Kwak
Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205, USA
J Biol Chem 278:8135-45. 2003.... - Protection against electrophile and oxidant stress by induction of the phase 2 response: fate of cysteines of the Keap1 sensor modified by inducersNobunao Wakabayashi
The Lewis B and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, School of Medicine, The Johns Hopkins University, Baltimore, MD 21205, USA
Proc Natl Acad Sci U S A 101:2040-5. 2004.... - Glutathione peroxidase 2, the major cigarette smoke-inducible isoform of GPX in lungs, is regulated by Nrf2Anju Singh
Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
Am J Respir Cell Mol Biol 35:639-50. 2006..This study shows that GPX2 is the major oxidative stress-inducible cellular GPX isoform in the lungs, and that its basal as well as inducible expression is dependent on Nrf2... - Antioxidants enhance mammalian proteasome expression through the Keap1-Nrf2 signaling pathwayMi Kyoung Kwak
Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205, USA
Mol Cell Biol 23:8786-94. 2003..We propose that induction of the 26S proteasome through the Nrf2 pathway represents an important indirect action of these antioxidants that can contribute to their protective effects against chronic diseases... - Disruption of Nrf2 enhances susceptibility to severe airway inflammation and asthma in miceTirumalai Rangasamy
Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
J Exp Med 202:47-59. 2005..Our studies suggest that the responsiveness of Nrf2-directed antioxidant pathways may act as a major determinant of susceptibility to allergen-mediated asthma... - Chemoprevention through the Keap1-Nrf2 signaling pathway by phase 2 enzyme inducersMi-Kyoung Kwak
Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, 615 N. Wolfe St, Baltimore, MD 21205, USA
Mutat Res 555:133-48. 2004..Rapidly accumulating data on this pathway is providing insight into the coordinated mammalian defense systems against electrophiles and oxidative stresses and the means by which it may be targeted by small molecules... - Role of NRF2 in protection against hyperoxic lung injury in miceHye-Youn Cho
Department of Environmental Health Sciences, The Bloomberg School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland, USA
Am J Respir Cell Mol Biol 26:175-82. 2002..Results demonstrated that NRF2 has a significant protective role against pulmonary hyperoxic injury in mice, possibly through transcriptional activation of lung antioxidant defense enzymes... - Linkage analysis of susceptibility to hyperoxia. Nrf2 is a candidate geneHye Youn Cho
Department of Environmental Health Sciences, Johns Hopkins University, School of Public Health, Baltimore, Maryland, USA
Am J Respir Cell Mol Biol 26:42-51. 2002..Results from this study have important implications for understanding the mechanisms through which oxidants mediate the pathogenesis of lung disease... - Disruption of Nrf2 impairs the resolution of hyperoxia-induced acute lung injury and inflammation in miceNarsa M Reddy
Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
J Immunol 182:7264-71. 2009.... - Enhanced expression of the transcription factor Nrf2 by cancer chemopreventive agents: role of antioxidant response element-like sequences in the nrf2 promoterMi Kyoung Kwak
Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA
Mol Cell Biol 22:2883-92. 2002.... - Global mapping of binding sites for Nrf2 identifies novel targets in cell survival response through ChIP-Seq profiling and network analysisDeepti Malhotra
Department of Environmental Health Sciences Department, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
Nucleic Acids Res 38:5718-34. 2010..Results were confirmed in an in vivo stress model of cigarette smoke-exposed mice. This study reveals global circuitry of the Nrf2 stress response emphasizing Nrf2 as a central node in cell survival response... - Identification of Nrf2-regulated genes induced by the chemopreventive agent sulforaphane by oligonucleotide microarrayRajesh K Thimmulappa
Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MA 21205-2179, USA
Cancer Res 62:5196-203. 2002.... - Nrf2-dependent sulfiredoxin-1 expression protects against cigarette smoke-induced oxidative stress in lungsAnju Singh
Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 212045, USA
Free Radic Biol Med 46:376-86. 2009..Thus, Srx1, a key Nrf2-regulated gene, contributes to protection against oxidative injury in the lung... - Genetic versus chemoprotective activation of Nrf2 signaling: overlapping yet distinct gene expression profiles between Keap1 knockout and triterpenoid-treated miceMelinda S Yates
Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA
Carcinogenesis 30:1024-31. 2009..Additionally, analysis of pharmacologic activation suggests that Nrf2 is the primary mediator of CDDO-Im activity, though other cell-signaling targets are also modulated following an oral dose of 30 micromol/kg... - Nrf2 regulates an adaptive response protecting against oxidative damage following diquat-mediated formation of superoxide anionWilliam O Osburn
Johns Hopkins University Bloomberg School of Public Health, Department of Environmental Health Sciences, Baltimore, MD, USA
Arch Biochem Biophys 454:7-15. 2006..Thus the enhanced sensitivity of N0 cells does not reflect basal differences in antioxidative capacity, but rather an impaired ability to mount an adaptive response to sustained oxidative stress... - Nrf2-dependent protection from LPS induced inflammatory response and mortality by CDDO-ImidazolideRajesh K Thimmulappa
Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA
Biochem Biophys Res Commun 351:883-9. 2006..Activation of Nrf2-dependent compensatory antioxidative pathways by CDDO-Im protects from LPS induced inflammatory response and mortality... - Pharmacodynamic characterization of chemopreventive triterpenoids as exceptionally potent inducers of Nrf2-regulated genesMelinda S Yates
Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Room E7541, 615 North Wolfe Street, Baltimore, MD 21205, USA
Mol Cancer Ther 6:154-62. 2007..This pharmacodynamic characterization highlights the chemopreventive promise of several synthetic triterpenoids in multiple target organs... - The triterpenoid CDDO-imidazolide confers potent protection against hyperoxic acute lung injury in miceNarsa M Reddy
Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA
Am J Respir Crit Care Med 180:867-74. 2009..Moreover, we have recently demonstrated that Nrf2-deficiency impairs the resolution of lung injury and inflammation after nonlethal hyperoxia exposure... - Genetic and pharmacologic evidence links oxidative stress to ventilator-induced lung injury in miceSrinivas Papaiahgari
Department of Environmental Health Sciences Division of Physiology, Room E7547, 615 North Wolfe Street, Baltimore, MD 21205, USA
Am J Respir Crit Care Med 176:1222-35. 2007..Mechanical ventilation (MV) is an indispensable therapy for critically ill patients with acute lung injury and the adult respiratory distress syndrome. However, the mechanisms by which conventional MV induces lung injury remain unclear... - Genetic or pharmacologic amplification of nrf2 signaling inhibits acute inflammatory liver injury in miceWilliam O Osburn
Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA
Toxicol Sci 104:218-27. 2008..Taken together, these results clearly illustrate that targeted cytoprotection of hepatocytes through Nrf2 signaling during inflammation prevents the amplification of inflammatory responses in the liver... - Chemoprevention with chlorophyllin in individuals exposed to dietary aflatoxinPatricia A Egner
Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA
Mutat Res 523:209-16. 2003..Compliance in the intervention was outstanding and no toxicities were observed. Thus, CHL has been found to be a safe and effective agent suitable for use in individuals unavoidably exposed to aflatoxins... - Chlorophyll, chlorophyllin and related tetrapyrroles are significant inducers of mammalian phase 2 cytoprotective genesJed W Fahey
Lewis B and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD 21205 2185, USA
Carcinogenesis 26:1247-55. 2005.... - Interactive effects of nrf2 genotype and oltipraz on benzo[a]pyrene-DNA adducts and tumor yield in miceMinerva Ramos-Gomez
Department of Environmental Health Sciences, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD 21202, USA
Carcinogenesis 24:461-7. 2003..g. P450 inhibition) for oltipraz can also occur in vivo in some tissues... - Nrf2 as a target for cancer chemopreventionXiang Yu
Department of Pharmacology and Molecular Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA
Mutat Res 591:93-102. 2005..Observations that nrf2-deficient mice are refractory to the protective actions of some chemopreventive agents highlight the importance of the Keap1-Nrf2-ARE signaling pathway as a molecular target for prevention... - Quantification of urinary aflatoxin B1 dialdehyde metabolites formed by aflatoxin aldehyde reductase using isotope dilution tandem mass spectrometryDenise N Johnson
Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA
Chem Res Toxicol 21:752-60. 2008..This urinary detection of the alcohol products directly contributes to the goal of mass balancing the fate of the bioreactive 8,9-epoxides of AFB 1 in vivo... - Phase 2 enzyme induction by the major metabolite of oltiprazJacobus P Petzer
Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, 1000 Hilltop Circle, Baltimore, Maryland 21250, USA
Chem Res Toxicol 16:1463-9. 2003..From this study, it is concluded that the major metabolite of the cancer chemopreventive oltipraz is a phase 2 enzyme inducer of comparable potency that activates the ARE and initiates nuclear translocation of transcription factor Nrf 2... - Genetic dissection of the Nrf2-dependent redox signaling-regulated transcriptional programs of cell proliferation and cytoprotectionNarsa M Reddy
Department of Environmental Health Sciences, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
Physiol Genomics 32:74-81. 2007..Collectively, these findings uncover an important insight into the nature of genes regulated by Nrf2-dependent redox signaling through GSH that are involved in cellular detoxification and proliferation... - Quantification of sulforaphane mercapturic acid pathway conjugates in human urine by high-performance liquid chromatography and isotope-dilution tandem mass spectrometryPatricia A Egner
Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA
Chem Res Toxicol 21:1991-6. 2008..This method determines SFN and all four SFN glutathione-derived metabolites with minimal sample preparation and will be extremely useful in understanding the role of SFN-rich foods in preventing cancer and other chronic diseases... - Prospective detection of codon 249 mutations in plasma of hepatocellular carcinoma patientsPeta E Jackson
Johns Hopkins University, Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA
Carcinogenesis 24:1657-63. 2003..We have therefore found that pre-diagnosis biomarkers of specific p53 mutations can be measured in plasma and this suggests a paradigm for developing these markers for use in prevention and intervention trials... - NRF2 modulates aryl hydrocarbon receptor signaling: influence on adipogenesisSoona Shin
Department of Pharmacology and Molecular Sciences, School of Medicine, The Johns Hopkins University, Baltimore, MD 21205, USA
Mol Cell Biol 27:7188-97. 2007..Ectopic expression of Ahr and dominant-positive Nrf2 in Nrf2-/- MEFs also substantially delayed differentiation. Thus, NRF2 directly modulates AHR signaling, highlighting bidirectional interactions of these pathways... - Identification of aflatoxin M1-N7-guanine in liver and urine of tree shrews and rats following administration of aflatoxin B1Patricia A Egner
Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA
Chem Res Toxicol 16:1174-80. 2003..Bioassays indicated that the tree shrew was considerably more resistant than the rat to AFB(1) hepatocarcinogenesis, which may reflect the significant differences in metabolic profiles of the two species... - Cell stiffness, contractile stress and the role of extracellular matrixSteven S An
Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
Biochem Biophys Res Commun 382:697-703. 2009..These findings provide biophysical evidence that ECM differentially modulates muscle contractility and, for the first time, demonstrate a link between muscle contractility and Nrf2-directed responses... - Potent protection against aflatoxin-induced tumorigenesis through induction of Nrf2-regulated pathways by the triterpenoid 1-[2-cyano-3-,12-dioxooleana-1,9(11)-dien-28-oyl]imidazoleMelinda S Yates
Johns Hopkins University, Baltimore, Maryland, USA
Cancer Res 66:2488-94. 2006..The unparalleled potency of CDDO-Im in vivo highlights the chemopreventive promise of targeting Nrf2 pathways with triterpenoids... - Induction of phase 2 enzymes by serum oxidized polyamines through activation of Nrf2: effect of the polyamine metabolite acroleinMi Kyoung Kwak
Department of Environmental Health Sciences, Johns Hopkins University, Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD 21205, USA
Biochem Biophys Res Commun 305:662-70. 2003..These results indicate that spermidine and spermine increase the expression of phase 2 genes in cells grown in culture through activation of the Nrf2-ARE pathway by generating the sulfhydryl reactive aldehyde, acrolein... - Innate immunity against bacterial infection following hyperoxia exposure is impaired in NRF2-deficient miceNarsa M Reddy
Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Room E7610, 615 North Wolfe Street, Baltimore, Maryland 21205, USA
J Immunol 183:4601-8. 2009..Thus, loss of Nrf2 impairs lung innate immunity and promotes susceptibility to bacterial infection after hyperoxia exposure, ultimately leading to death of the host... - Protective interventions to prevent aflatoxin-induced carcinogenesis in developing countriesJohn D Groopman
Department of Environmental Health Sciences, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD 21205, USA
Annu Rev Public Health 29:187-203. 2008..Therefore, many diverse and appropriate strategies for disease prevention are needed to decrease the incidence of aflatoxin carcinogenesis in developing countries... - Prevention of liver cancerKathryn Z Guyton
Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, 615 North Wolfe Street, Baltimore, MD 21205-2179, USA
Curr Oncol Rep 4:464-70. 2002..These include genes and gene products controlling viral replication, carcinogen metabolism, signal transduction, cell-cycle arrest, apoptosis, proliferation, and oxidative stress... - Regulation of notch1 signaling by nrf2: implications for tissue regenerationNobunao Wakabayashi
Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
Sci Signal 3:ra52. 2010..We report a functional role for this cross talk between the two pathways and show that disruption of Nrf2 impeded liver regeneration after partial hepatectomy and was rescued by reestablishment of Notch1 signaling... - Conceptually new low-calcemic oxime analogues of the hormone 1 alpha,25-dihydroxyvitamin D(3): synthesis and biological testingGary H Posner
Department of Chemistry, School of Arts and Sciences, The Johns Hopkins University, Baltimore, Maryland 21218, USA
J Med Chem 45:1723-30. 2002..In terms of in vivo toxicity (hypercalcemia), ketone 2b is strongly calcemic in rats, whereas oxime 3b and oxime ether 4b are considerably less calcemic (i.e., safer) than calcitriol (1)... - Deficiency in Nrf2-GSH signaling impairs type II cell growth and enhances sensitivity to oxidantsNarsa M Reddy
The Johns Hopkins Bloomberg School of Public Health, Department of Environmental Health Sciences, 615 North Wolfe Street, Baltimore, MD 21205, USA
Am J Respir Cell Mol Biol 37:3-8. 2007..Our data suggest that dysfunctional Nrf2-regulated GSH-induced signaling is associated with deregulation of type II cell proliferation, which contributes to abnormal injury and repair and leads to respiratory impairment... - Aflatoxin and hepatitis B virus biomarkers: a paradigm for complex environmental exposures and cancer riskJohn D Groopman
Johns Hopkins University, Bloomberg School of Public Health, Department of Environmental Health Sciences, 615 North Wolfe Street, Baltimore, MD 21205, USA
Cancer Biomark 1:5-14. 2005..This systematic approach provides encouragement for preventive interventions and should serve as a template for the development, validation and application of other chemical-specific biomarkers to cancer or other chronic diseases... - Divergent responses of chondrocytes and endothelial cells to shear stress: cross-talk among COX-2, the phase 2 response, and apoptosisZachary R Healy
Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD 21218, USA
Proc Natl Acad Sci U S A 102:14010-5. 2005.... - Role of metabolism and viruses in aflatoxin-induced liver cancerJohn D Groopman
Department of Environmental Health Sciences, The Johns Hopkins University, Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA
Toxicol Appl Pharmacol 206:131-7. 2005..This systematic approach provides encouragement for preventive interventions and should serve as a template for the development, validation and application of other chemical-specific biomarkers to cancer or other chronic diseases... - Quantification of aflatoxin-B1-N7-Guanine in human urine by high-performance liquid chromatography and isotope dilution tandem mass spectrometryPatricia A Egner
Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA
Chem Res Toxicol 19:1191-5. 2006.... - Specific mutations of hepatitis B virus in plasma predict liver cancer developmentShuang-Yuan Kuang
Bloomberg School of Public Health, Johns Hopkins University, 615 North Wolfe Street, Baltimore, MD 21205, USA
Proc Natl Acad Sci U S A 101:3575-80. 2004..022, two-tailed). We therefore found that a prediagnosis biomarker of specific HBV mutations can be measured in plasma and suggest this marker for use as an intermediate endpoint in prevention and intervention trials... - Quantitative analysis and chronic dosimetry of the aflatoxin B1 plasma albumin adduct Lys-AFB1 in rats by isotope dilution mass spectrometryPeter F Scholl
Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, 615 North Wolfe Street, Baltimore, Maryland 21205 2103, USA
Chem Res Toxicol 19:44-9. 2006.... - Assessing the effect of interventions in the context of mixture distributions with detection limitsHaitao Chu
Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, 615 N Wolfe Street, Baltimore, MD 21205, U S A
Stat Med 24:2053-67. 2005..We illustrate our methods using data from a randomized clinical trial conducted in Qidong, People's Republic of China... - Nrf2 signaling: an adaptive response pathway for protection against environmental toxic insultsWilliam O Osburn
Johns Hopkins University Bloomberg School of Public Health, Department of Environmental Health Sciences, 615 North Wolfe Street, Baltimore, MD 21205, USA
Mutat Res 659:31-9. 2008.... - Formation of two novel estrogen guanine adducts and HPLC/MS detection of 4-hydroxyestradiol-N7-guanine in human urineLeslie A Bransfield
Department of Chemistry, Zanvyl Krieger School of Arts and Sciences, Johns Hopkins University, Baltimore, Maryland 21218, USA
Chem Res Toxicol 21:1622-30. 2008.... - Chemoprevention by 1,2-dithiole-3-thiones through induction of NQO1 and other phase 2 enzymesMi-Kyoung Kwak
Department of Environmental Health Sciences, School of Public Health Sciences, Johns Hopkins University Bloomberg, Baltimore, Maryland 21205, USA
Methods Enzymol 382:414-23. 2004 - Increased colonic inflammatory injury and formation of aberrant crypt foci in Nrf2-deficient mice upon dextran sulfate treatmentWilliam O Osburn
Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
Int J Cancer 121:1883-91. 2007..Taken together, these results clearly illustrate the role of Nrf2 in regulating an adaptive response that protects against early-phase inflammation-mediated tumorigenesis... - In vivo modulation of the Parkinsonian phenotype by Nrf2Neal C Burton
Department of Environmental Health Sciences, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD 21205, USA
Neurotoxicology 27:1094-100. 2006..The in vivo activation of the Nrf2 pathway in the brain may be an important strategy to mitigate the effects of oxidative stress in neurodegenerative disorders and neurological disease... - Role of dietary supplements/nutraceuticals in chemoprevention through induction of cytoprotective enzymesJed W Fahey
Department of Pharmacology, International Health, and Environmental Health Sciences, Johns Hopkins University, Baltimore, Maryland 21205, USA
Chem Res Toxicol 20:572-6. 2007 - Targeting Nrf2 with the triterpenoid CDDO-imidazolide attenuates cigarette smoke-induced emphysema and cardiac dysfunction in miceThomas E Sussan
Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
Proc Natl Acad Sci U S A 106:250-5. 2009..These results suggest that targeting the Nrf2 pathway during the etiopathogenesis of emphysema may represent an important approach for prophylaxis against COPD... - Nrf2 is a critical regulator of the innate immune response and survival during experimental sepsisRajesh K Thimmulappa
Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA
J Clin Invest 116:984-95. 2006..Our study reveals Nrf2 as a novel modifier gene of sepsis that determines survival by mounting an appropriate innate immune response... - Bioavailability of Sulforaphane from two broccoli sprout beverages: results of a short-term, cross-over clinical trial in Qidong, ChinaPatricia A Egner
Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA
Cancer Prev Res (Phila) 4:384-95. 2011..Cancer Prev Res; 4(3); 384-95. ©2011 AACR... - A novel acetylenic tricyclic bis-(cyano enone) potently induces phase 2 cytoprotective pathways and blocks liver carcinogenesis induced by aflatoxinKaren Liby
Dartmouth Medical School, Hanover, NH 03755, USA
Cancer Res 68:6727-33. 2008.... - Induction of NAD(P)H quinone oxidoreductase by vegetables widely consumed in Catalonia, SpainNuria Laso
, IDIBAPS, Facultad de Medicina, Universidad de Barcelona, Spain
Nutr Cancer 52:49-58. 2005..These results are very similar to those described for vegetables consumed in the United States, with the exception of calcot, which is common in Catalonia but is not grown or consumed widely in the United States... - Natural chlorophyll inhibits aflatoxin B1-induced multi-organ carcinogenesis in the ratMichael T Simonich
Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA
Carcinogenesis 28:1294-302. 2007..0026) and 75% (P = 0.0004), respectively. These results show Chl and CHL provide potent chemoprotection against early biochemical and late pathophysiological biomarkers of AFB(1) carcinogenesis in the rat liver and colon... - Acceleration to death from liver cancer in people with hepatitis B viral mutations detected in plasma by mass spectrometryJian Guo Chen
Qidong Liver Cancer Institute, Qidong, Jiangsu Province, People s Republic of China
Cancer Epidemiol Biomarkers Prev 16:1213-8. 2007..04 for age 35 years to 1.0 for age 65 years with the 90% confidence band being above 1 for ages < 50 years. These findings provide a conceptual framework to explain the acceleration of mortality in individuals infected with HBV... - Multiple comparisons model-based clustering and ternary pattern tree numerical display of gene response to treatment: procedure and application to the preclinical evaluation of chemopreventive agentsThomas R Sutter
W Harry Feinstone Center for Genomic Research, University of Memphis, Memphis, Tennessee 38152, USA
Mol Cancer Ther 1:1283-92. 2002..Also, small treatment-specific subsets of genes were identified that may be indicative of additional pharmacophores present in the test compounds... - Hepatocyte-specific deletion of the keap1 gene activates Nrf2 and confers potent resistance against acute drug toxicityHiromi Okawa
Graduate School of Comprehensive Human Sciences, Center for Tsukuba Advanced Research Alliance, University of Tsukuba, 1 1 1 Tennoudai, Tsukuba 305 8577, Japan
Biochem Biophys Res Commun 339:79-88. 2006..These results demonstrate that chronic activation of Nrf2 confers animals with resistance to xenobiotics without affecting the morphological and physiological integrity of hepatocytes... - Identification of novel transcriptional networks in response to treatment with the anticarcinogen 3H-1,2-dithiole-3-thioneYong Huang
W. Harry Feinstone Center for Genomic Research, University of Memphis, Memphis, Tennessee 38152, USA
Physiol Genomics 24:144-53. 2006..000331) pathways. These findings showed a profound impact of D3T on lipid metabolism and anti-inflammatory/immune-suppressive response, indicating a broader cytoprotective effect of this compound than previously expected... - Induction of Nrf2-regulated genes by 3H-1, 2-dithiole-3-thione through the ERK signaling pathway in murine keratinocytesSarala Manandhar
College of Pharmacy, Yeungnam University, 214 1 Dae Dong, Gyeongsan si, Gyeongsangbuk do 712 749, South Korea
Eur J Pharmacol 577:17-27. 2007.... - Evaluation of the cancer chemopreventive potency of dithiolethione analogs of oltiprazB D Roebuck
Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, NH 03755, USA
Carcinogenesis 24:1919-28. 2003..While efficacy in humans has yet to be tested, D3T is clearly more potent than oltipraz and serves as a useful molecular probe for determining the key events associated with protection by this class of agents... - Oltipraz chemoprevention trial in Qidong, People's Republic of China: unaltered oxidative biomarkersBente Glintborg
Department of Clinical Pharmacology Q7642, H:S Rigshospitalet, Tagensvej 20, Copenhagen, Denmark
Free Radic Biol Med 41:1010-4. 2006..Mechanisms other than prevention of oxidative DNA damage may be of higher importance when oltipraz is used as a chemopreventive agent in humans... - The importance of carcinogen dose in chemoprevention studies: quantitative interrelationships between, dibenzo[a,l]pyrene dose, chlorophyllin dose, target organ DNA adduct biomarkers and final tumor outcomeM Margaret Pratt
Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97339, USA
Carcinogenesis 28:611-24. 2007.... - The transcriptional response to a peroxisome proliferator-activated receptor alpha agonist includes increased expression of proteome maintenance genesSteven P Anderson
Investigative Toxicology and Pathology Group, Safety Assessment, GlaxoSmithKline Research and Development, Research Triangle Park, North Carolina 27709, USA
J Biol Chem 279:52390-8. 2004.... - Mimetics of caloric restriction include agonists of lipid-activated nuclear receptorsJ Christopher Corton
Toxicogenomics, Chapel Hill, North Carolina 27514, USA
J Biol Chem 279:46204-12. 2004..These results demonstrate that PPARalpha mediates some of the effects of CR and indicate that a pharmacological approach to mimicking many of the beneficial effects of CR may be possible...
Research Grants
- MOLECULAR MECHANISMS OF CHEMOPREVENTION--DITHIOLETHIONESThomas Kensler; Fiscal Year: 2003..The long-term goal of this project is to facilitate the most efficient and effective use dithiolethiones as protective agents in human populations exposed to environmental toxicants. ..
- Chemopreventive Efficacy of Broccoli Sprouts in HumansThomas Kensler; Fiscal Year: 2004..abstract_text> ..
- Protection by Induction of Ubiquitin-Proteasome SystemsThomas Kensler; Fiscal Year: 2005....
- Role of Enzyme Induction in Cancer ChemopreventionThomas Kensler; Fiscal Year: 2006....
- Molecular Mechanisms of Chemoprevention: DithiolethionesThomas Kensler; Fiscal Year: 2007..Collectively, these studies will further the goal of effectively using dithiolethiones as protective agents in human populations exposed to environmental toxicants. ..
- Role of Enzyme Induction in Cancer ChemopreventionThomas Kensler; Fiscal Year: 2007....
- Role of Enzyme Induction in Cancer ChemopreventionThomas Kensler; Fiscal Year: 2009..abstract_text> ..
- MECHANISMS OF ANTICARCINOGENESIS BY DITHIOLTHIONESThomas Kensler; Fiscal Year: 1993..The long term goal of this work is to facilitate our understanding of how dietary constituents may modulate the target organ risk in human populations exposed to naturally-occurring carcinogens...
- Molecular Mechanisms of Chemoprevention: NRF2 SignalingThomas Kensler; Fiscal Year: 2009....