PubMed Journal Database 
The US National Library of Medicine and National Institutes of Health manage PubMed.gov which comprises of more than 21 million records, papers, reports for biomedical literature, including MEDLINE, life science and medical journals, articles, reviews, reports and books. BioPortfolio aims to publish relevant information on published papers, clinical trials and news associated with users selected topics.
For example view all recent relevant publications on Epigenetics and associated publications and clincial trials.
Showing PubMed Articles 1–25 of 430,000+
Revision of the Biodistribution of Uranyl in Serum: Is Fetuin-A the Major Protein Target?
Uranium is a natural actinide present as uranyl U(VI) species in aqueous environments. Its toxicity is considered to be chemical rather than radiotoxicological. Whatever the route of entry, uranyl reaches the blood, is partly eliminated via the kidneys, and accumulated in the bones. In serum, its speciation mainly involves carbonate and proteins. Direct identification of labile uranyl-protein complexes is extremely difficult because of the complexity of this matrix. Thus, until now the biodistribution of th...
Does Dietary Copper Supplementation Enhance or Diminish PCB126 Toxicity in the Rodent Liver?
Copper is essential for the function of the mitochondrial electron transport chain and several antioxidant proteins. However, in its free form copper can participate in Fenton-like reactions that produce reactive hydroxyl radicals. Aryl-hydrocarbon receptor (AhR) agonists, including the most potent polychlorinated biphenyl (PCB) congener, 3,3',4,4',5-pentachlorobiphenyl (PCB126), increase copper levels in rodent livers. This is accompanied by biochemical and toxic changes. To assess the involvement of coppe...
The antithrombotics of the tetrahydrothienopyridine series, clopidogrel and prasugrel, are prodrugs that must be metabolized in two steps to become pharmacologically active. The first step is the formation of a thiolactone metabolite. The second step is a cytochrome P450 (P450)-dependent oxidation of this thiolactone resulting in the formation of a sulfenic acid that is eventually reduced into the corresponding active thiol. It has been postulated that the sulfenic acid metabolite resulted from a nucleophil...
Skin Sensitization of Epoxyaldehydes: Importance of Conjugation.
Structure-activity relationship (SAR) models are important tools for predicting the skin sensitization potential of new compounds without animal testing. In compounds possessing a structural alert (aldehyde) and an activation alert (double bond), it is important to consider bioactivation/autoxidation (e.g., epoxidation). In the present study, we have explored a series of aldehydes with regard to contact allergy. The chemical reactivity of these 6 aldehydes toward a model hexapeptide was investigated, and th...
Isoamyl nitrite has previously been considered acceptable as an inhaled cyanide antidote; therefore, the antidotal utility of this organic nitrite compared with sodium nitrite was investigated. To facilitate a quantitative comparison, doses of both sodium nitrite and isoamyl nitrite were given intraperitoneally in equimolar amounts to sublethally cyanide-challenged mice. Righting recovery from the knockdown state was clearly compromised in the isoamyl nitrite-treated animals, the effect being attributable t...
Polybrominated diphenyl ethers (PBDEs) were widely used flame retardants that have become persistent environmental pollutants. In the present study, we investigated the in vitro oxidative metabolism of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), a major PBDE detected in human tissue and environmental samples. Biotransformation of BDE-47 by pooled and individual human liver microsomes and by human recombinant cytochrome P450 (P450) enzymes was assessed using a liquid chromatography/tandem mass spectrometry-...
Experimental Testing of Quantum Mechanical Predictions of Mutagenicity: Aminopyrazoles.
A computational method for predicting the likelihood of aromatic amines being active in the Ames test for mutagenicity was trialed on a set of aminopyrazoles. A virtual array of compounds was generated from the available sets of hydrazines and α-cyanoaldehydes (or ketones) and quantum mechanical calculations used to compute a probability of being active in the Ames test. The compounds selected for synthesis and testing were not based on the predictions and so spanned the range of predicted probabilities. T...
Susceptibility to abacavir hypersensitivity has been attributed to possession of the specific human leukocyte antigen allele HLA-B*57:01. HLA-B*57:01-restricted activation of CD8+ T-cells provides a link between the genetic association and the iatrogenic disease. The objectives of this study were to characterize the functionality of drug-responsive CD8+ T-cell clones generated from HLA-B*57:01+ drug-naive subjects and to explore the relationship between abacavir accumulation in antigen presenting cells and...
The conformational flexibility of the C8-linked guanine adduct formed from attachment of ochratoxin A (OTA) was analyzed using a systematic computational approach and models ranging from the nucleobase to the adducted DNA helix. A focus was placed on the influence of the C8-modification of 2'-deoxyguanosine (dG) on the preferred relative arrangement of the nucleobase and the C8-substituent and, more importantly, the anti/syn conformational preference with respect to the glycosidic bond. Although OTA is twis...
Idiosyncratic drug-induced liver injury (IDILI) is a major problem during drug development and has caused drug withdrawal and black-box warnings. Because of the low concordance of the hepatotoxicity of drugs in animals and humans, robust screening methods using human tissue are needed to predict IDILI in humans. According to the inflammatory stress hypothesis, the effects of inflammation interact with the effects of a drug or its reactive metabolite, precipitating toxic reactions in the liver. As a follow-u...
Carcinogenicity Prediction of Noncongeneric Chemicals by a Support Vector Machine.
The ability to identify carcinogenic compounds is of fundamental importance to the safe application of chemicals. In this study, we generated an array of in silico models allowing the classification of compounds into carcinogenic and noncarcinogenic agents based on a data set of 852 noncongeneric chemicals collected from the Carcinogenic Potency Database (CPDBAS). Twenty-four molecular descriptors were selected by Pearson correlation, F-score, and stepwise regression analysis. These descriptors cover a rang...
Identification of Stable Benzoapyrene-7,8-dione-DNA Adducts in Human Lung Cells.
Metabolic activation of the proximate carcinogen benzo[a]pyrene-7,8-trans-dihydrodiol (B[a]P-7,8-trans-dihydrodiol) by aldo-keto reductases (AKRs) leads to B[a]P-7,8-dione that is both electrophilic and redox-active. B[a]P-7,8-dione generates reactive oxygen species resulting in oxidative DNA damage in human lung cells. However, information on the formation of stable B[a]P-7,8-dione-DNA adducts in these cells is lacking. We studied stable DNA adduct formation of B[a]P-7,8-dione in human lung adenocarcinoma...
3-Hydroperoxy-N-nitrosomorpholine in buffered aqueous media in the presence of calf thymus DNA was treated with a phosphine reductant to generate the transient α-hydroxynitrosamine and subsequent diazonium ion that alkylated the DNA, as previously reported. Subsequent addition of hydride donors, for 30 min, followed by acid hydrolysis of the mixture allowed detection and quantification of 6-(2-{2-[(9H-purin-6-yl)amino]ethoxy}ethoxy)-9H-purin-2-amine, the reduced cross-link formed from deposition, via the d...
The advent of novel therapeutics that specifically target signaling pathways activated by genetic alterations has revolutionized the way patients with lung cancer are treated. Although only few and largely ineffective chemotherapeutic regimens were available 10 years ago, a lung tumor diagnosed today requires extensive pathologic subtyping and diagnosis of genome alterations to afford more effective treatment (eg, in EGFR-mutant adenocarcinoma). This change of paradigm has several profound implications, ran...
Precision Oncology: An Overview.
Existing and Emerging Technologies for Tumor Genomic Profiling.
Ongoing global genome characterization efforts are revolutionizing our knowledge of cancer genomics and tumor biology. In parallel, information gleaned from these studies on driver cancer gene alterations-mutations, copy number alterations, translocations, and/or chromosomal rearrangements-can be leveraged, in principle, to develop a cohesive framework for individualized cancer treatment. These possibilities have been enabled, to a large degree, by revolutionary advances in genomic technologies that facilit...
Personalizing Oncology: Perspectives and Prospects.
This article provides an overview of the research, beginning a century ago, that has led to the current use of genomically informed methods for selection of targeted therapies to treat individual patients with cancer-so-called precision cancer medicine. Until 1980, most research on cancer therapy was not targeted in the sense we use the word today. Since then, there has been an acceleration in research identifying genetic and molecular targets and in clinical trials using biomarkers that identify the presen...
Building a Personalized Medicine Infrastructure at a Major Cancer Center.
Our understanding of cancer biology is rapidly increasing, as is the availability and affordability of high throughput technologies for comprehensive molecular characterization of tumors and the individual's own genetic makeup. Thus, the time is right to implement personalized molecular medicine for all patients with cancer. Personalized approaches span the full cancer care spectrum from risk stratification to prevention, screening, therapy, and survivorship programs. Several molecular therapeutics have ent...
Clinical Analysis and Interpretation of Cancer Genome Data.
The scale of tumor genomic profiling is rapidly outpacing human cognitive capacity to make clinical decisions without the aid of tools. New frameworks are needed to help researchers and clinicians process the information emerging from the explosive growth in both the number of tumor genetic variants routinely tested and the respective knowledge to interpret their clinical significance. We review the current state, limitations, and future trends in methods to support the clinical analysis and interpretation...
Advancing Precision Medicine for Prostate Cancer Through Genomics.
Prostate cancer is the most common type of cancer in men and the second leading cause of cancer death in men in the United States. The recent surge of high-throughput sequencing of cancer genomes has supported an expanding molecular classification of prostate cancer. Translation of these basic science studies into clinically valuable biomarkers for diagnosis and prognosis and biomarkers that are predictive for therapy is critical to the development of precision medicine in prostate cancer. We review potenti...
Genomic Medicine Frontier in Human Solid Tumors: Prospects and Challenges.
Recent discoveries of genomic alterations that underlie and promote the malignant phenotype, together with an expanded repertoire of targeted agents, have provided many opportunities to conduct hypothesis-driven clinical trials. The ability to profile each unique cancer for actionable aberrations by using high-throughput technologies in a cost-effective way provides unprecedented opportunities for using matched therapies in a selected patient population. The major challenges are to integrate and make biolog...
Ethical, Legal, and Counseling Challenges Surrounding the Return of Genetic Results in Oncology.
In the last decade, an overwhelming number of genetic aberrations have been discovered and linked to the development of treatment for cancer. With the rapid advancement of next-generation sequencing (NGS) techniques, it is expected that large-scale DNA analyses will increasingly be used to select patients for treatment with specific anticancer agents. Personalizing cancer treatment has many advantages, but sequencing germline DNA as reference material for interpreting cancer genetics may have consequences t...
Leveraging Cancer Genome Information in Hematologic Malignancies.
The use of candidate gene and genome-wide discovery studies in the last several years has led to an expansion of our knowledge of the spectrum of recurrent, somatic disease alleles, which contribute to the pathogenesis of hematologic malignancies. Notably, these studies have also begun to fundamentally change our ability to develop informative prognostic schema that inform outcome and therapeutic response, yielding substantive insights into mechanisms of hematopoietic transformation in different tissue comp...
Designing Transformative Clinical Trials in the Cancer Genome Era.
The incorporation of molecular profiling into routine clinical practice has already been adopted in some tumor types, such as human epidermal growth factor receptor 2 (HER2) testing in breast cancer and KRAS genotyping in colorectal cancer, providing a guide to treatment selection that is not afforded by histopathologic diagnosis alone. It is inevitable that over time, with rapid advances in scientific knowledge, bioinformatics, and technology to identify oncogenic drivers, molecular profiling will compleme...
Genomics-Driven Oncology: Framework for an Emerging Paradigm.
A majority of cancers are driven by genomic alterations that dysregulate key oncogenic pathways influencing cell growth and survival. However, the ability to harness tumor genetic information for its full clinical potential has only recently become manifest. Over the past several years, the convergence of discovery, technology, and therapeutic development has created an unparalleled opportunity to test the hypothesis that systematic knowledge of genomic information from individual tumors can improve clinica...
