A5044894386- Pharmacogenetics and Drug Metabolism
- Glutathione Transferases and Polymorphisms
- Drug Transport and Resistance Mechanisms
- Genomics, phytochemicals, and oxidative stress
- Pharmacological Effects and Toxicity Studies
- Liver Disease Diagnosis and Treatment
- Lung Cancer Treatments and Mutations
- Cytokine Signaling Pathways and Interactions
- Synthesis and Biological Evaluation
- Epilepsy research and treatment
- Epigenetics and DNA Methylation
- Diabetes and associated disorders
- Inflammatory mediators and NSAID effects
- RNA Interference and Gene Delivery
- Drug-Induced Hepatotoxicity and Protection
- Proteoglycans and glycosaminoglycans research
- Pharmaceutical studies and practices
- Carcinogens and Genotoxicity Assessment
- Acute Lymphoblastic Leukemia research
- BRCA gene mutations in cancer
- T-cell and B-cell Immunology
- Mycotoxins in Agriculture and Food
- Pancreatic function and diabetes
- Cancer Cells and Metastasis
- Alcohol Consumption and Health Effects
Sekisui XenoTech (United States)
2002-2023
Fred Hutch Cancer Center
1997-2005
Children's Mercy Hospital
2003
University of Washington
1996-1997
Seattle University
1997
National Cancer Institute
1989-1994
Frederick National Laboratory for Cancer Research
1990
National Cancer Institute
1990
Cultured human hepatocytes are a valuable in vitro system for evaluating new molecular entities as inducers of cytochrome P450 (P450) enzymes. The present study summarizes data obtained from 62 preparations cultured that were treated with vehicles (saline or dimethylsulfoxide, 0.1%), beta-naphthoflavone (33 microM), phenobarbital (100 250 isoniazid microM) and/or rifampin (20 50 and examined the expression enzymes based on microsomal activity toward marker substrates, case CYP2C8, level...
Journal Article Expression of CYP1A1 Gene in Patients With Lung Cancer: Evidence for Cigarette Smoke-Induced Normal Tissue and Altered Regulation Primary Pulmonary Carcinomas Get access Theodore L. McLemore, McLemore * Program Development Research Group, Developmental Therapeutics Program, Division Cancer Treatment, National InstituteBethesda, Md † Correspondence to: M.D., 170 Eighth St. SE, Suite C, Paris, TX 75460 Search other works by this author on: Oxford Academic PubMed Google Scholar...
Abstract Bile acid synthesis plays a key role in regulating whole body cholesterol homeostasis. Transcriptional factor EB (TFEB) is nutrient and stress-sensing transcriptional that promotes lysosomal biogenesis. Here we report of TFEB hepatic bile synthesis. We show induces 7α-hydroxylase (CYP7A1) human hepatocytes mouse livers prevents accumulation hypercholesterolemia Western diet-fed mice. Furthermore, find cholesterol-induced stress feed-forward activates via promoting nuclear...
Busulfan is eliminated by glutathione S-transferase (GST)-catalyzed conjugation with (GSH). We have characterized the busulfan-conjugating activity of purified human liver GSTA1-1, GSTA1-2, GSTA2-2, GSTM1-1, and placental GSTP1-1. Isoforms were from cytosol GSH-affinity chromatography chromatofocusing. In addition, cDNA-expressed GTH1 GTH2, corresponding to GSTA1-1 characterized. The major product busulfan conjugation, a thiophenium ion (THT+), was assayed GC/MS after conversion...
Identification of genetic variation predictive clearance rate a wide variety prescription drugs could lead to cost-effective personalized medicine. Here we identify regulatory genes whose variable expression level among individuals may have widespread effects upon drugs. Twenty liver samples with CYP3A activity were profiled for and xenobiotic metabolism as well involved in the regulation thereof. Regulatory accounted highest degree collinearity levels identified possible master regulators...
The cytochrome P450 (CYP) systems catalyze the metabolic transformation of a wide variety xenobiotics including procarcinogens present in cigarette smoke condensate as well atmospheric pollutants. CYP1A1 isoenzyme is particular interest because it has been implicated risk factor etiology lung cancer heavy smokers. identification and expression structural gene either normal human or cells not reported. Because its potential significance cancer, we investigated 24 established cell lines 15...
Journal Article Metabolic Activation of 4-Ipomeanol in Human Lung, Primary Pulmonary Carcinomas, and Established Carcinoma Cell Lines Get access Theodore L. McLemore, McLemore * Program Development Research Group, Developmental Therapeutics Program, Division Cancer Treatment, National Institute, Frederick CenterFrederick, Md *Correspondence to : M.D., 170 Eighth St. S.E., Ste. C, Paris, TX 75460. Search for other works by this author on: Oxford Academic PubMed Google Scholar Charles...
A major obstacle to hematopoietic gene therapy is the lack of appropriate in vivo selection protocols that can raise presently low numbers gene-altered stem cells therapeutically useful levels. Overexpression glutathione-S-transferases (GST), combination with busulfan treatment, may provide an exploitable mechanism for strategies. GST provides a route detoxification variety xenobiotics, including alkylating agents used myeloablative chemotherapy. The only known clearance by GST-mediated...
Chronic ethanol overconsumption promotes alcohol-associated liver disease (ALD), characterized by hepatocyte injury, inflammation, hepatic stellate cell (HSC) activation, and fibrosis. Hyaluronan (HA) concentration is greater in livers blood from advanced ALD patients than with non-ALD. In the liver, HSCs are major HA producers. The relationship between ethanol, HA, HSC activation incompletely understood. Thus, here, we tested hypothesis that enhances a HA-dependent manner.Liver tissue...
Like most infections and certain inflammatory diseases, some therapeutic proteins cause a cytokine-mediated suppression of hepatic drug-metabolizing enzymes, which may lead to pharmacokinetic interactions with small-molecule drugs. We propose new in vitro method evaluate the whole blood–mediated effects on enzymes human hepatocytes cocultured Kupffer cells. The traditional involves treating hepatocyte cocultures protein, detects hepatocyte- macrophage-mediated cytochrome P450 (P450). blood...
Abstract Some biologics can modulate cytokines that may lead to changes in expression of drug‐metabolizing enzymes and cause drug‐drug interactions ( DDI ). potential TV ‐1106—an albumin‐fused growth hormone GH )—was investigated. In this study, human blood was exposed recombinant (rh ) or ‐1106, followed by isolation the plasma its application hepatocytes. While treatment with rh increased multiple cytokines, ‐1106 had no effect on any nine tested. The interleukin IL )‐6 concentration...
Abstract Some immunomodulatory agents stimulate the release of cytokines capable suppressing P450 enzymes and potentially affecting pharmacokinetics coadministered medications. Cytokines released in response to an immunomodulator blood ex vivo can be used screen for potential drug‐drug interactions. Tilsotolimod, investigational agonist Toll‐like receptor 9, stimulated macrophage chemoattractant protein‐1 (MCP‐1), inflammatory protein‐1α (MIP‐1α), interferon‐α2a (INF‐α2a) obtained from...
A major obstacle to hematopoietic gene therapy is the lack of appropriate in vivo selection protocols that can raise presently low numbers gene-altered stem cells therapeutically useful levels. Overexpression glutathione-S-transferases (GST), combination with busulfan treatment, may provide an exploitable mechanism for strategies. GST provides a route detoxification variety xenobiotics, including alkylating agents used myeloablative chemotherapy. The only known clearance by GST-mediated...
Clinical Pharmacology & Therapeutics (2003) 73 , P61–P61; doi: