A5079384190- Cancer, Lipids, and Metabolism
- Eicosanoids and Hypertension Pharmacology
- Metabolomics and Mass Spectrometry Studies
- Cancer, Hypoxia, and Metabolism
- Inflammatory mediators and NSAID effects
- Mass Spectrometry Techniques and Applications
- Ferroptosis and cancer prognosis
- Analytical Chemistry and Chromatography
- Drug Transport and Resistance Mechanisms
- Pharmacogenetics and Drug Metabolism
- Peroxisome Proliferator-Activated Receptors
- Mitochondrial Function and Pathology
- Hormonal and reproductive studies
- Pancreatic and Hepatic Oncology Research
- Advanced Proteomics Techniques and Applications
- Metabolism and Genetic Disorders
- Free Radicals and Antioxidants
- Carcinogens and Genotoxicity Assessment
- Estrogen and related hormone effects
- Phagocytosis and Immune Regulation
- Aldose Reductase and Taurine
- Genetic Neurodegenerative Diseases
- Antioxidant Activity and Oxidative Stress
- Genomics, phytochemicals, and oxidative stress
- Receptor Mechanisms and Signaling
University of Pennsylvania
2015-2024
Translational Therapeutics (United States)
2015-2024
California University of Pennsylvania
2017-2024
Philadelphia University
2000-2023
Friedreich's Ataxia Research Alliance
2017-2023
University of Pennsylvania Health System
2020
Children's Hospital of Philadelphia
1998-2018
Center for Excellence in Education
2017
Abramson Cancer Center
2017
Drexel University
2016
We recently reported the discovery of a series bioactive prostaglandin F2-like compounds (F2-isoprostanes) that are produced in vivo by free radical-catalyzed peroxidation arachidonic acid independent cyclooxygenase enzyme. Inasmuch as phospholipids readily undergo peroxidation, we examined possibility F2-isoprostanes may be formed situ on phospholipids. Initial support for this hypothesis was obtained finding levels measured after hydrolysis lipids extracted from livers rats treated with...
Background— The failing human heart is characterized by metabolic abnormalities, but these defects remains incompletely understood. In animal models of failure there a switch from predominance fatty acid utilization to the more oxygen-sparing carbohydrate metabolism. Recent studies have reported decreases in myocardial lipid content, inclusion diabetic and nondiabetic patients obscures distinction adaptations derangements per se. Methods Results— We performed both unbiased targeted surveys...
Epidemiological data suggest that dietary antioxidants play a protective role against cancer. This has led to the proposal supplementation with such as vitamin C (vit C) may be useful in disease prevention. However, vit proved ineffective cancer chemoprevention studies. In addition, concerns have been raised over potentially deleterious transition metal ion–mediated pro-oxidant effects. We now determined induces lipid hydroperoxide decomposition DNA-reactive bifunctional electrophiles...
Macrophage activation/polarization to distinct functional states is critically supported by metabolic shifts. How polarizing signals coordinate and reprogramming, the potential implications for control of macrophage activation, remains poorly understood. Here we show that IL-4 signaling co-opts Akt-mTORC1 pathway regulate Acly, a key enzyme in Ac-CoA synthesis, leading increased histone acetylation M2 gene induction. Only subset genes controlled this way, including those regulating cellular...
Mechanisms of metabolic flexibility enable cells to survive under stressful conditions and can thwart therapeutic responses. Acetyl-coenzyme A (CoA) plays central roles in energy production, lipid metabolism, epigenomic modifications. Here, we show that, upon genetic deletion Acly, the gene coding for ATP-citrate lyase (ACLY), remain viable proliferate, although at an impaired rate. In absence ACLY, upregulate ACSS2 utilize exogenous acetate provide acetyl-CoA de novo lipogenesis (DNL)...
Alterations in gut microbiota impact the pathophysiology of several diseases, including cancer. Radiotherapy (RT), an established curative and palliative cancer treatment, exerts potent immune modulatory effects, inducing tumor-associated antigen (TAA) cross-priming with antitumor CD8+ T cell elicitation abscopal effects. We tested whether modulates response following RT distal to gut. Vancomycin, antibiotic that acts mainly on gram-positive bacteria is restricted gut, potentiated RT-induced...
Significance It is generally thought that the gut microbes consume oxygen and maintain lumen in a deeply anaerobic state. However, we found of germ-free mice also anaerobic, suggesting there exist other mechanisms responsible for consumption addition to microbes’ respiration. These comprise oxidative reactions, such as oxidation lipids organic substrates. Both microbiota chemistry regulate luminal levels turn influence composition microbial communities throughout intestinal tract.
Immune cell function is influenced by metabolic conditions. Low-glucose, high-lactate environments, such as the placenta, gastrointestinal tract, and tumor microenvironment, are immunosuppressive, especially for glycolysis-dependent effector T cells. We report that nicotinamide adenine dinucleotide (NAD+), which reduced to NADH lactate dehydrogenase in lactate-rich conditions, a key point of control Reduced not available NAD+-dependent enzymatic reactions involving glyceraldehyde 3-phosphate...
Recently, many new approaches, study designs, and statistical analytical methods have emerged for studying gene-environment interactions (G×Es) in large-scale studies of human populations. There are opportunities this field, particularly with respect to the incorporation -omics next-generation sequencing data continual improvement measures environmental exposures implicated complex disease outcomes. In a workshop called "Current Challenges New Opportunities Gene-Environment Interaction...
Epipodophyllotoxins are associated with leukemias characterized by translocations of the MLL gene at chromosome band 11q23 and other translocations. Cytochrome P450 (CYP) 3A metabolizes epipodophyllotoxins chemotherapeutic agents. CYP3A metabolism generates epipodophyllotoxin catechol quinone metabolites, which could damage DNA. There is a polymorphism in 5′ promoter region CYP3A4 ( CYP3A4-V ) that might alter anticancer drugs. We examined 99 de novo 30 treatment-related...
Abstract We recently reported the discovery that a series of novel prostaglandin (PG)F2-like compounds (F2-isoprostanes) are produced in vivo independent cyclooxygenase as products free radical-catalyzed lipid peroxidation. F2-isoprostanes initially formed situ from arachidonic acid esterified to phospholipids and then released preformed. have now investigated whether PGD2/E2-like isoprostanes also by rearrangement PGG2-like intermediates involved isoprostane formation. Using variety...
The anti-arrhythmic quinidine has been reported to be a competitive inhibitor of the catalytic activities human liver P-450DB, including sparteine delta 2-oxidation and bufuralol 1'-hydroxylation, we confirmed observation that submicromolar concentrations are strongly inhibitory. Human microsomes oxidize 3-hydroxy (Km 4 microM) N-oxide 33 products, consonant with in vivo observations. Both inhibited microsomal 3-hydroxylation. Liver prepared from DA strain rats showed relative deficiency...
Chromosomal translocations leading to chimeric oncoproteins are important in leukemogenesis, but how they form is unclear. We studied acute promyelocytic leukemia (APL) with the t(15;17) translocation that developed after treatment of breast or laryngeal cancer chemotherapeutic agents poison topoisomerase II.We used long-range polymerase chain reaction and sequence analysis characterize genomic breakpoints therapy-related APL. To determine whether II was directly involved mediating breaks...
FeII-mediated decomposition of 13-[S-(Z,E)]-9,11-hydroperoxyoctadecadienoic (hydroperoxylinoleic) acid resulted in the formation three α,β-unsaturated aldehydes. At low FeII concentrations or at early time points after addition FeII, two major products were observed. The least polar product had chromatographic properties that identical with those 4-oxo-2-nonenal. Conversion this to its bis-oxime derivative hydroxylamine hydrochloride syn- and anti-oxime isomers mass spectral derived from an...
We have measured the excretion of a major urinary metabolite thromboxane B2 (TxB2), i.e., 2,3-dinor-TxB2, during infusion exogenous TxB2 over 50-fold dose range to enable estimation rate entry endogenous into bloodstream. Four healthy male volunteers received 6-h i.v. infusions venhicle alone and at 0.1, 1.0, 5.0 ng/kg X min in random order. They were pretreated with aspirin 325 mg/d order suppress production. Urinary 2,3-dinor-TxB2 was before, during, up 24 h after aspirin-free periods, by...
Polycyclic aromatic hydrocarbons (PAH) are environmental pollutants and suspected human lung carcinogens. In patients with non-small cell carcinoma, differential display shows that aldo-keto reductase (AKR1C) transcripts dramatically overexpressed. However, whether AKR1C isoforms contribute to the carcinogenic process oxidize potent PAH<i>trans</i>-dihydrodiols (proximate carcinogens) reactive redox active <i>o</i>-quinones is unknown; nor it known these reactions occur in lungs. We now show...