A5007180466- Genomics, phytochemicals, and oxidative stress
- Glutathione Transferases and Polymorphisms
- Pharmacogenetics and Drug Metabolism
- Effects of Radiation Exposure
- Carcinogens and Genotoxicity Assessment
- Oral health in cancer treatment
- Drug Transport and Resistance Mechanisms
- Virus-based gene therapy research
- DNA Repair Mechanisms
- Eicosanoids and Hypertension Pharmacology
- Epigenetics and DNA Methylation
- Head and Neck Cancer Studies
- Nonmelanoma Skin Cancer Studies
- Peroxisome Proliferator-Activated Receptors
- Radiation Therapy and Dosimetry
- Salivary Gland Disorders and Functions
- DNA and Nucleic Acid Chemistry
- Advanced Glycation End Products research
- RNA Interference and Gene Delivery
- Organ Transplantation Techniques and Outcomes
- Cancer-related Molecular Pathways
- Chemotherapy-related skin toxicity
- Organ and Tissue Transplantation Research
- Transplantation: Methods and Outcomes
- Cancer Research and Treatments
University of Wisconsin–Madison
2014-2024
Wisconsin Institutes for Discovery
2018-2024
University of Wisconsin Carbone Cancer Center
2011-2016
ProCertus BioPharm (United States)
2000-2014
Oregon State University
1998
New Frontier
1997
Center for Cancer Research
1996
Rutgers, The State University of New Jersey
1995
Weatherford College
1992
Merck & Co., Inc., Rahway, NJ, USA (United States)
1987
Exposure of human and rodent cells to a wide variety chemoprotective compounds confers resistance against broad set carcinogens. For subset the compounds, protection is generated by an increase in abundance protective enzymes like glutathione S -transferases (GST). Antioxidant responsive elements (AREs) mediate transcriptional induction battery genes which comprise much this response system. Past studies identified necessary ARE “core” sequence RTGACnnnGC, but alone insufficient induction....
Phase II drug-metabolizing enzymes, such as glutathione <i>S</i>-transferase and quinone reductase, play an important role in the detoxification of chemical carcinogens. The induction these detoxifying enzymes by a variety agents occurs at transcriptional level is regulated <i>cis</i>-acting element, called antioxidant response element (ARE) or electrophile-response element. In this study, we identified signaling kinase pathway that negatively regulates ARE-mediated gene expression....
Methylglyoxal is an α-ketoaldehyde and dicarbonyl formed in cells as a side product of normal metabolism. Endogenously produced dicarbonyls, such methylglyoxal, are involved numerous pathogenic processes vivo , including carcinogenesis advanced glycation end-product formation; end-products contributors to the pathophysiology aging chronic diabetes. Despite recent advances understanding systemic effects full significance this compound remains unknown. Herein we provide evidence that majority...
Increased levels of glutathione S-transferase (GST; RX:glutathione R-transferase; EC 2.5.1.18) mRNA, protein, and activity in tumor biopsy samples drug-resistant cultured cells are associated with resistance to anticancer drugs. We report that each three full-length cloned GST cDNAs, for pi (acidic), Ya (basic), Yb1 (neutral), can confer drug when expressed mammalian cells. In one approach, stably transfected mouse C3H/10T1/2 express pi, Ya, or were analyzed colony-forming assays....
Several hypolipidemic drugs and certain industrial plasticizers induce proliferation of peroxisomes, enhance the activity peroxisome-associated beta-oxidation fatty acids, produce hepatocellular carcinomas in livers rodents. Because these chemicals themselves are not mutagens do covalently modify DNA, unlike majority chemical carcinogens, we proposed that persistent induction associated peroxisomal oxidases, caused a sustained increase intracellular H2O2 or other reduced oxygen species,...
Expression of PDGF-B, the gene encoding platelet-derived growth factor B chain, has been implicated as a participant in an autocrine loop human osteosarcoma cell line U2-OS. In previous work, we identified primary site PDGF-B promoter, SIS proximal element (SPE), which is critical for transcription U2-OS cells. We also Sp1 one SPE-binding proteins nuclear extracts. present have another protein to be Sp3. Gel mobility shift assays showed that both and Sp3 require CACCC motif within SPE...
The microsomal metabolism of benzo(a)pyrene and its enhancement by inducers aryl hywdrocarbon hydroxylase were studied in three C3H mouse fibroblast cell lines liver lung. examined included C3H/10T 1/2 CL8, a line that can be transformed treatment with benzo(a)pyrene; CVP3SC6, which cannot CL16, derived from 3-methylcholanthrene-treated CL8 cells. Of four polycyclic hydrocarbons examined, benz(a)anthracene was found to the most effective inducer hydrocarbon activity, while...
To identify new aminothiol radioprotectors that are active when applied topically and have fewer side effects administered systemically, a family of was designed synthesized. Three key elements in the design were, (1) small size for efficient transmembrane diffusion, (2) positive charged amines alkyl backbone strong ionic interaction with DNA backbone, (3) perpendicular, side-chain terminal thiol is projected away from to enable reactive oxygen species scavenging around DNA. Several vitro...
A family of 17 new nucleophilic-polyamine and aminothiol structures was designed synthesized to identify topical or systemic radioprotectors with acceptable mammalian toxicity profiles. design elements included: (i) Length charge the DNA-interacting, alkylamine backbone, (ii) nucleophilicity reactive oxygen species (ROS)-scavenging group, (iii) non-toxic drug concentration achievable in animal tissues.Mouse maximum tolerated doses (MTD) were determined by increasing intraperitoneal (IP)...
In a new strategy, we sought to determine whether topically applied vasoconstrictor, with its accompanying transient skin hypoxia and exclusion of systemic drug, would prevent or suppress radiotherapy chemotherapy-induced alopecia. Topical vasoconstrictor was 1-cm(2) patches on the backs 10-day-old rats minutes later they received either 7.1 gray (Gy) whole-body radiation N-nitroso-N-methylurea (MNU) Cytoxan. The degree alopecia scored 10 days by visual assessment (% coat retention) hair...
Glutathione S-transferases (EC 2.5.1.18) in mammalian cells catalyze the conjugation, and thus, detoxication of a structurally diverse group electrophilic environmental carcinogens alkylating drugs, including antineoplastic nitrogen mustards. We proposed that structural alteration nonspecific electrophile-binding site would produce mutant enzymes with increased efficiency for single drug these mutants could serve as useful somatic transgenes to protect healthy human against agents used...