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+
Functional characterization of cancer-associated Gab1 mutations.
Grb2-associated binder 1 (Gab1) is a docking protein that transduces signals from a variety of tyrosine kinases, including Met and the epidermal growth factor receptor (EGFR). Although the related protein Gab2 is strongly implicated in human cancer, a role for Gab1 has been less clear. However, a screen for gene mutations in breast cancer identified two somatic mutations in Gab1, Y83C and T387N. In this paper we describe the functional characterization of these Gab1 mutants. MCF-10A immortalized mammary epi...
Role of AMPK in UVB-induced DNA damage repair and growth control.
Skin cancer is the most common cancer in the United States, while DNA-damaging ultraviolet B (UVB) radiation from the sun remains the major environmental risk factor. Reducing skin cancer incidence is becoming an urgent issue. The energy-sensing enzyme 5'-AMP-activated protein kinase (AMPK) has a key role in the regulation of cellular lipid and protein metabolism in response to stimuli such as exercise and changes in fuel availability. However, the role of AMPK in the response of skin cells to UVB damage an...
Pancreatic carcinoma, a leading cause of cancer death, is thought to develop out of pancreatic intraepithelial neoplasia (PanIN). PanIN lesions have not yet attained the fully malignant phenotype, but show increased proliferation and dysplasia, and frequently bear an oncogenic KRAS mutation. Pancreatic cancer development is associated with increased activity of the transcription factor NF-κB. NEMO (IKKγ) is a subunit of the IKK complex essential for the activation of canonical NF-κB signaling and has bee...
Cell fusion promotes chemoresistance in metastatic colon carcinoma.
Chemoresistance is an important concern in the treatment of metastatic colon cancer. It may emerge through selection of clones that are inherently resistant from the outset or through mechanisms acquired during treatment. Cell fusion represents an efficient means of rapid phenotypic evolution that make cells with new properties at a rate exceeding that achievable by random mutagenesis. Here, we first identified a number of proteins involved in cell fusion using a shotgun proteomics approach, then we investi...
Epigenetic regulation of the neuroblastoma genes, Arid3b and Mycn.
AT-rich interaction domain molecule 3B (ARID3B) and MYCN are expressed in a portion of neuroblastoma, and form a combination that has strong oncogenic activity in mouse embryonic fibroblasts (MEFs). Here, we show that this combination can also convert neural stem cells to neuroblastoma-like tumor. To address whether there are common mechanisms regulating the expression of this combination of genes, we examined public repositories of gene expression data and found that although these genes are rarely express...
Arg/Abl2 promotes invasion and attenuates proliferation of breast cancer in vivo.
Tumor progression is a complex, multistep process involving accumulation of genetic aberrations and alterations in gene expression patterns leading to uncontrolled cell division, invasion into surrounding tissue and finally dissemination and metastasis. We have previously shown that the Arg/Abl2 non-receptor tyrosine kinase acts downstream of the EGF receptor and Src tyrosine kinases to promote invadopodium function in breast cancer cells, thereby promoting their invasiveness. However, whether and how Arg c...
Regulation of DCIS to invasive breast cancer progression by Singleminded-2s (SIM2s).
Singleminded-2s (SIM2s) is a member of the bHLH/PAS family of transcription factors and a key regulator of mammary epithelial cell differentiation. SIM2s is highly expressed in mammary epithelial cells and downregulated in human breast cancer. Loss of Sim2s causes aberrant mouse mammary ductal development, with features suggestive of malignant transformation, whereas overexpression of SIM2s promotes precocious alveolar differentiation in nulliparous mouse mammary glands, suggesting that SIM2s is required fo...
RelB inhibits cell proliferation and tumor growth through p53 transcriptional activation.
The alternative nuclear factor-kappaB (NF-κB) -activation pathway proceeds via inducible p100 processing, leading to the activation of RelB-containing dimers. This pathway is aberrantly activated in several types of tumors; however, a direct role for RelB in the control of cell proliferation is still largely unexplored. Here, we demonstrate that RelB provides cell proliferation-inhibitory signals in murine fibroblasts. In agreement with these results, RelB ectopic expression inhibits xenograft tumor growth...
Amplification and rearrangements of the epidermal growth factor receptor (EGFR) gene are frequently found in glioblastoma multiforme (GBM). The most common variant is EGFR variant III (EGFRvIII). Research suggests that EGFRvIII could be a marker for a cancer stem cell or tumor-initiating population. If amplification and rearrangement are early events in tumorigenesis, this implies that they should be preserved throughout the tumor. However, in primary GBM, EGFRvIII expression is focal and sporadic. Unexpect...
Vertebrate Tob/BTG proteins inhibit cell proliferation when overexpressed in tissue-culture cells, and they can function as tumor suppressors in mice. The single Caenorhabditis elegans Tob/BTG ortholog, FOG-3, by contrast, was identified from its loss-of-function phenotype as a regulator of sperm fate specification. Here we report that FOG-3 also regulates proliferation in the germline tissue. We first demonstrate that FOG-3 is a positive regulator of germline proliferation. Thus, fog-3 null mutants possess...
JAK/STAT signaling in hematological malignancies.
The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is central to signaling by cytokine receptors, a superfamily of more than 30 transmembrane proteins that recognize specific cytokines, and is critical in blood formation and immune response. Many of those receptors transmit anti-apoptotic, proliferative and differentiation signals, and their expression and functions are critical for the formation of blood lineages. Several cancers, including blood malignancies, have been...
N-(2-Chlorobenzyl)-substituted hydroxamate, readily produced by hydrolysis of ketoclomazone, was identified as an inhibitor of 1-deoxy-d-xylulose 5-phosphate synthase (DXS), with an IC50 value of 1.0 μM. The compound inhibited the growth of Haemophilus influenzae. A convenient spectroscopic method for assaying DXS using NADPH-lactate dehydrogenase (LDH) is also reported.
Recognizing acetyllysine of histone is a vital process of epigenetic regulation that is mediated by a protein module called bromodomain. To contribute novel scaffolds for developing into bromodomain inhibitors, we utilize a fragment-based drug discovery approach. By successively applying docking and X-ray crystallography, we were able to identify 9 fragment hits from diffracting more than 60 crystals. In the present work, we described four of them and carried out the integrated lead optimization for fragmen...
Phasing Out Fee-for-Service Payment.
The National Commission on Physician Payment Reform recommends phasing out fee-for-service and outlines strategies to change the model during the transition. The commission advises revision of fee schedules so that evaluation and management are valued as highly as procedures.
Cooperative aggregation of monomers into one-dimensional nanostructures typically results in elongated objects. Here we analyse in depth the self-assembly of an N-monoarylated perylene bisimide which shows characteristics of a cooperative growth mechanism but unexpectedly yields objects of small size, due to anti-cooperativity by attenuated growth.
Oxadiazole-isopropylamides as Potent and Noncovalent Proteasome Inhibitors.
Screening of the 50 000 ChemBridge compound library led to the identification of the oxadiazole-isopropylamide 1 (PI-1833) which inhibited chymotrypsin-like (CT-L) activity (IC50 = 0.60 μM) with little effects on the other two major proteasome proteolytic activities, trypsin-like (T-L) and postglutamyl-peptide-hydrolysis-like (PGPH-L). LC-MS/MS and dialysis show that 1 is a noncovalent and rapidly reversible CT-L inhibitor. Focused library synthesis provided 11ad (PI-1840) with CT-L activity (IC50 = 27 n...
The two inner lines of the EPR quartet of methyl radicals trapped in cryogenic gas matrices are superpositions of the inner transitions of an A-proton-spin quartet and an E-proton-spin doublet. Their intensity relative to the outer lines provides information on the population of the methyl-rotation quantum states. The above intensity ratio for the CH3 in solids is a challenging problem of the quantum dynamics and statistical thermodynamics. The influence of the quantum-mechanical/inertial rotation on the in...
The third sequential binding energies of the late first-row divalent transition metal cations to 1,10-phenanthroline (Phen) are determined by energy-resolved collision-induced dissociation (CID) techniques using a guided ion beam tandem mass spectrometer. Five late first-row transition metal cations in their +2 oxidation states are examined including: Fe(2+), Co(2+), Ni(2+), Cu(2+), and Zn(2+). The kinetic energy dependent CID cross sections for loss of an intact Phen ligand from the M(2+)(Phen)3 complexes...
Diastereotopic and Deuterium Effects in Gemini.
Changing the geminal methyl groups on 1α,25-dihydroxyvitamin D3 and its analogues to the deuterio versions generally improves the bioactivity. Derivatives of 1α,25-dihydroxyvitamin D3 with two chains emanating at C20, commonly referred to as gemini, are subject to the same phenomenon. Additionally, gemini with different side chains are susceptible to bioactivity differentials where the C17-C20 threo configuration usually imparts higher activity than the corresponding erythro arrangement. In an effort to a...
A series of 7-amino- and 7-acetamidoquinoline-5,8-diones with aryl substituents at the 2-position were synthesized, characterized, and evaluated as potential NAD(P)H:quinone oxidoreductase (NQO1) -directed antitumor agents. The synthesis of lavendamycin analogues is illustrated. Metabolism studies demonstrated that 7-amino analogues were generally better substrates for NQO1 than 7-amido analogues, as were compounds with smaller heteroaromatic substituents at the C-2 position. Surprisingly, only two compound...
Public Health Approach to the Prevention of Gun Violence.
Public health interventions have reduced motor vehicle fatalities by 80%. The authors argue for a public health approach to prevent gun violence, including designing and manufacturing safer guns.
Due to its production of potent antimicrobial oxidants including hypochlorous acid, human myeloperoxidase (MPO) plays a critical role in innate immunity and inflammatory diseases. Thus MPO is an attractive target in drug design. (Aminoalkyl)fluoroindole derivatives were detected to be very potent MPO inhibitors; however, they also promote inhibition of the serotonin reuptake transporter (SERT) at the same concentration range. Via structure-based drug design, a new series of MPO inhibitors derived from 3-alk...
The synthesis, characterization, and functional in vitro assay in cardiac and smooth muscle (vascular and nonvascular) of a series of 4-imidazo[2,1-b]thiazole-1,4-dihydropyridines are reported. To define the calcium blocker nature of the imidazo[2,1-b]thiazole-1,4-DHPs and their selectivity on Cav1.2 and Cav1.3 isoforms, we performed binding studies on guinea pig atrial and ventricular membranes on intact cells expressing the cloned Cav1.2a subunit and on rat brain cortex. To get major insights into the rea...
Glycolaldehyde (GA, 2-hydroxyethanal, C2H4O2) is a semivolatile molecule of atmospheric importance, recently proposed as a precursor in the formation of aqueous-phase secondary organic aerosol (SOA). There are few methods to measure GA vapor, but infrared spectroscopy has been used successfully. Using vetted protocols we have completed the first assignment of all fundamental vibrational modes and also derived quantitative IR absorption band strengths using both neat and pressure-broadened GA vapor. Even tho...
Extreme drug resistant mutant of HIV-1 protease (PR) bearing 20 mutations (PR20) has been studied with the clinical inhibitor amprenavir (1) and two potent antiviral investigational inhibitors GRL-02031 (2) and GRL-0519 (3). Clinical inhibitors are >1000-fold less active on PR20 than on wild-type enzyme, which is consistent with dissociation constants (KL) from isothermal titration calorimetry of 40 nM for 3, 178 nM for amprenavir, and 960 nM for 2. High resolution crystal structures of PR20-inhibitor compl...
