1,564 results match your criteria: "National Cancer Institute - Frederick[Affiliation]"
Mol Immunol
January 2010
Protein Interactions Group, Center for Cancer Research Nanobiology Program, National Cancer Institute-Frederick, National Institutes of Health, Frederick, MD 21702-1201, USA.
Domain antibodies (dAbs) are promising candidate therapeutics and diagnostics. Efficient selection of novel potent dAbs with potential for clinical utility is critically dependent on the library diversity and size, and the scaffold stability. We have previously constructed a large (size approximately 2.
View Article and Find Full Text PDFJ Immunol
October 2009
Tumor Immunity and Tolerance Section, Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, National Cancer Institute-Frederick, Frederick, MD 21702, USA.
We previously reported that naive, tumor-specific CD8(+) (TcR-I) T cells transferred into prostate tumor-bearing mice traffic to the prostate where they become tolerized. We now report that TcR-I cells suppress the proliferation of naive T cells. This suppression is mediated at least in part by secreted factors, and the suppressive activity can be blocked by Abs directed against TGF-beta.
View Article and Find Full Text PDFNucleic Acids Res
November 2009
Human Retrovirus Pathogenesis Section, National Cancer Institute-Frederick, Frederick, MD 21702-1201, USA.
The conserved mRNA export receptor NXF1 (Mex67 in yeast) assembles with messenger ribonucleoproteins (mRNP) in the nucleus and guides them through the nuclear pore complex into the cytoplasm. The DEAD family RNA helicase Dbp5 is essential for nuclear export of mRNA and is thought to dissociate Mex67 from mRNP upon translocation, thereby generating directional passage. However, the molecular mechanism by which Dbp5 recognizes Mex67-containing mRNP is not clear.
View Article and Find Full Text PDFVet J
October 2010
Laboratory of Genomic Diversity, National Cancer Institute-Frederick, Frederick, MD 21702, USA.
The recent discovery of a mutational variant in the CEP290 gene (CEP290: IVS50+9T>G), conferring recessive retinal degeneration in Abyssinian and Somali (long-haired Abyssinian) cats (rdAc) prompted a survey among 41 cat breeds (846 individuals) to assess the incidence, frequency and clinical consequence of rdAc. The rdAc allele displayed widespread distribution, observed in 16/43 (37%) breeds, exhibiting a high allele frequency (∼33%) in North American and European Siamese populations. Clinical evaluations demonstrated high concordance between rdAc pathology and the CEP290 (IVS50+9T>G) homozygous genotype (P=1.
View Article and Find Full Text PDFJ Infect Dis
October 2009
Laboratory of Genomic Diversity, SAIC-Frederick, National Cancer Institute-Frederick, Frederick, MD 21702, USA.
The human APOBEC3 family of cytidine deaminases provides intrinsic immunity to retroviral infection. A naturally occurring 29.5-kb deletion removes the entire APOBEC3B gene.
View Article and Find Full Text PDFBiophys J
August 2009
Center for Cancer Research Nanobiology Program, National Cancer Institute-Frederick, Frederick, Maryland, USA.
Abeta(17-42) (so-called p3) amyloid is detected in vivo in the brains of individuals with Alzheimer's disease or Down's syndrome. We investigated the polymorphism of Abeta(17-42) oligomers based on experimental data from steady-state NMR measurements, electron microscopy, two-dimensional hydrogen exchange, and mutational studies, using all-atom molecular-dynamics simulation with explicit solvent. We assessed the structural stability and the populations.
View Article and Find Full Text PDFAnn Clin Lab Sci
December 2009
Laboratory of Comparative Carcinogenesis, National Cancer Institute-Frederick, Frederick, MD 21702, USA.
Nickel(II), capable of transforming cells and causing tumors in humans and animals, has been previously shown by us to mediate hydrolytic truncation of histone H2A's C-terminal tail by 8 amino acids in both cell-free and cell culture systems. Since H2A's C-tail is involved in maintaining chromatin structure, such truncation might alter this structure and affect gene expression. To test the latter possibility, we transfected cultured T-REx 293 human embryonic kidney cells with plasmids expressing either wild type (wt) or truncated (q) histone H2A proteins, which were either untagged or N-terminally tagged with fluorescent proteins.
View Article and Find Full Text PDFCancer Res
August 2009
Laboratory of Experimental Immunology, Cancer and Inflammation Program, National Cancer Institute-Frederick, Maryland 21702, USA.
The biological relevance of the perforin and Fas ligand (FasL) cytolytic pathways of CD8(+) T lymphocytes (CTL) for cancer immunotherapy is controversial. We investigated the importance of these pathways in a murine renal cell carcinoma expressing influenza viral hemagglutinin as a defined surrogate antigen (Renca-HA). Following Renca-HA injection, all FasL-dysfunctional FasL(gld/gld) mice (n = 54) died from Renca-HA tumors by day 62.
View Article and Find Full Text PDFCancer Res
August 2009
Tumor Angiogenesis Section, Mouse Cancer Genetics Program, Science Applications International Corporation, National Cancer Institute-Frederick, Frederick, Maryland 21702-1201, USA.
Tumor endothelial marker 8 (TEM8) was initially identified as a gene overexpressed in the vasculature of human tumors and was subsequently identified as an anthrax toxin receptor. To assess the functional role of TEM8, we disrupted the TEM8 gene in mice by targeted homologous recombination. TEM8(-/-) mice were viable and reached adulthood without defects in physiologic angiogenesis.
View Article and Find Full Text PDFMol Cancer Ther
July 2009
Laboratory of Human Toxicology and Pharmacology, Applied/Developmental Research Support Directorate, Science Applications International Corporation-Frederick Inc, National Cancer Institute-Frederick, Frederick, MD 21702, USA.
Topoisomerase I (Top1) is a proven target for cancer therapeutics, and the level of Top1 in tumors has been used as a biomarker for chemotherapeutic efficacy. In this study, we report the development and validation of a two-site enzyme chemiluminescent immunoassay for Top1, which we used to measure Top1 levels in the NCI-60 cancer cell line panel. Top1 levels ranged from 0.
View Article and Find Full Text PDFOncogene
August 2009
Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute-Frederick, Frederick, MD 21702-1201, USA.
After a decade of extensive work on gene knockout mouse models of cell-cycle regulators, the classical model of cell-cycle regulation was seriously challenged. Several unexpected compensatory mechanisms were uncovered among cyclins and Cdks in these studies. The most astonishing observation is that Cdk2 is dispensable for the regulation of the mitotic cell cycle with both Cdk4 and Cdk1 covering for Cdk2's functions.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
July 2009
Laboratory of Cell and Developmental Signaling, Center for Cancer Research, National Cancer Institute-Frederick, P. O. Box B, Frederick, MD 21702, USA.
Scaffold proteins contribute to the spatiotemporal control of MAPK signaling and KSR1 is an ERK cascade scaffold that localizes to the plasma membrane in response to growth factor treatment. To better understand the molecular mechanisms of KSR1 function, we examined the interaction of KSR1 with each of the ERK cascade components, Raf, MEK, and ERK. Here, we identify a hydrophobic motif within the proline-rich sequence (PRS) of MEK1 and MEK2 that is required for constitutive binding to KSR1 and find that MEK binding and residues in the KSR1 CA1 region enable KSR1 to form a ternary complex with B-Raf and MEK following growth factor treatment that enhances MEK activation.
View Article and Find Full Text PDFJ Hered
September 2009
Laboratory of Genomic Diversity, Basic Research Program, Science Applications International Corporation-Frederick, Inc., National Cancer Institute-Frederick, Frederick, MD 21702, USA.
Bioorg Med Chem
July 2009
Laboratory of Medicinal, Center for Cancer Research, National Cancer Institute-Frederick, National Institutes of Health, Frederick, MD 21702, United States.
Using our recently disclosed 2,3-dihydro-6,7-dihydroxy-1H-isoindol-1-one and 4,5-dihydroxy-1H-isoindole-1,3(2H)-dione integrase inhibitors, we report differential effects on inhibitory potency induced by introduction of an alpha-chiral center into a key aryl substituent. We show that introduction of the chiral center is uniformly deleterious to binding, with the (R)-enantiomer being more deleterious than the (S)-enantiomer. A greater enantiomeric difference in potency is shown by inhibitors that have restricted rotation of the aryl ring, with the larger difference being due to poorer potency of the (R)-enantiomer rather than higher potency of the (S)-enantiomer.
View Article and Find Full Text PDFRetrovirology
June 2009
HIV Drug Resistance Program, National Cancer Institute-Frederick, Frederick, Maryland 21702-1201, USA.
Background: Host restriction factor APOBEC3G (A3G) blocks human immunodeficiency virus type 1 (HIV-1) replication by G-to-A hypermutation, and by inhibiting DNA synthesis and provirus formation. Previous reports have suggested that A3G is a dimer and its virion incorporation is mediated through interactions with viral or nonviral RNAs and/or HIV-1 Gag. We have now employed a bimolecular fluorescence complementation assay (BiFC) to analyze the intracellular A3G-A3G, A3G-RNA, and A3G-Gag interactions in living cells by reconstitution of yellow fluorescent protein (YFP) from its N- or C-terminal fragments.
View Article and Find Full Text PDFBlood
August 2009
Basic Research Program, SAIC-Frederick Inc, Center For Cancer Research, National Cancer Institute-Frederick, Frederick, MD 21702-1201, USA.
Development of hematopoietic stem cells (HSCs) and their immediate progeny is maintained by the interaction with cells in the microenvironment. We found that hematopoiesis was dysregulated in Id1(-/-) mice. Although the frequency of HSCs in Id1(-/-) bone marrow was increased, their total numbers remained unchanged as the result of decreased bone marrow cellularity.
View Article and Find Full Text PDFInt J Cancer
September 2009
Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute-Frederick, MD 21702-1201, USA.
Flavonoids and proanthocyanidins are bioactive polyphenolic components of fruits and vegetables that may account for part of the protective effect of raw fruit and vegetable consumption in esophageal cancer. We studied the relationship between esophageal cancer and dietary proanthocyanidins, flavonoids and flavonoid subclasses (anthocyanidins, flavan-3-ols, flavanones, flavones, flavonols and isoflavonoids) using recently developed USDA and Tufts flavonoid and proanthocyanidin databases. The study was a population-based, case-control analysis of 161 white men with esophageal adenocarcinoma (EAC), 114 white and 218 black men with esophageal squamous cell carcinoma (ESCC) and 678 white and 557 black male controls who lived in 3 areas of the United States.
View Article and Find Full Text PDFMol Cancer Ther
May 2009
Protein Interactions Group, Center for Cancer Research Nanobiology Program, National Cancer Institute-Frederick, NIH, Frederick, Maryland 21702-1201, USA.
Mesothelin is a potential new target for cancer immunotherapy because it is present at relatively low levels only in mesothelial cells of pleura, peritoneum, and pericardium of healthy people, but is significantly elevated in a number of tumors, including mesothelioma, ovarian, pancreatic, and lung cancers. However, all currently available antibodies against mesothelin are either murine or chimeric, which could limit their use because of increased likelihood of immunogenicity compared with fully human antibodies. Here, we report the identification and characterization of a novel fully human monoclonal antibody, m912, which was isolated from a human Fab library by panning against recombinant mesothelin.
View Article and Find Full Text PDFJ Hered
September 2009
Laboratory of Genomic Diversity, National Cancer Institute-Frederick, Frederick, MD 21702, USA.
The SILVER locus has been mapped in the domestic cat, identifying a unique genomic location distinct from that of any known reported gene associated with silver or hypopigmentation in mammals. A demonstrated lack of linkage to SILV, the strong candidate gene for silver, led to the initiation of a genome scan utilizing 2 pedigrees segregating for silver coat color. Linkage mapping defined a genomic region for SILVER as a 3.
View Article and Find Full Text PDFMethods
August 2009
Gene Regulation and Chromosome Biology Laboratory, National Cancer Institute-Frederick, Bldg. 539, Room 222, Frederick, MD 21702-1201, USA.
Strategies for assembly and analysis of human, yeast, and bacterial RNA polymerase elongation complexes are described, and methods are shown for millisecond phase kinetic analyses of elongation using rapid chemical quench flow. Human, yeast, and bacterial RNA polymerases function very similarly in NTP-Mg2+ commitment and phosphodiester bond formation. A "running start, two-bond, double-quench" protocol is described and its advantages discussed.
View Article and Find Full Text PDFJ Bacteriol
July 2009
Transcription Control Section, Gene Regulation and Chromosome Biology Laboratory, National Cancer Institute-Frederick, National Institutes of Health, Frederick, Maryland 21702, USA.
In Escherichia coli the genome must be compacted approximately 1,000-fold to be contained in a cellular structure termed the nucleoid. It is proposed that the structure of the nucleoid is determined by a balance of multiple compaction forces and one major expansion force. The latter is mediated by transertion, a coupling of transcription, translation, and translocation of nascent membrane proteins and/or exported proteins.
View Article and Find Full Text PDFJ Med Chem
May 2009
Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute-Frederick, National Institutes of Health, 376 Boyles Street, Frederick, Maryland 21702, USA.
Diacylglycerol lactones built with a rigid 4-[(methylphenyl)ethynyl]phenyl rod that is separated from the exocyclic acylcarbonyl of the DAG-lactone core by a spacer unit of variable length were synthesized and studied. Binding affinities for a panel of classical and novel PKC isozymes in two different phospholipid environments, one corresponding to the plasma membrane of cells, were determined. The kinetics and site of translocation for the PKC isozymes alpha and delta upon treatment with the compounds were also studied as well as the early response of ERK phosphorylation and the late response of induction of apoptosis in the human prostatic carcinoma cell line LNCaP.
View Article and Find Full Text PDFCancer Res
May 2009
Laboratory of Experimental Immunology, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute-Frederick, and SAIC Frederick, Frederick, Maryland 21702-1201, USA.
Large granular lymphocyte (LGL) leukemia is a clonal proliferative disease of T and natural killer (NK) cells. Interleukin (IL)-15 is important for the development and progression of LGL leukemia and is a survival factor for normal NK and T memory cells. IL-15 alters expression of Bcl-2 family members, Bcl-2, Bcl-XL, Bim, Noxa, and Mcl-1; however, effects on Bid have not been shown.
View Article and Find Full Text PDFBioorg Med Chem Lett
May 2009
Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute-Frederick, National Institutes of Health, MD 21702, United States.
Using 2,3-dihydro-6,7-dihydroxy-1H-isoindol-1-one and 4,5-dihydroxy-1H-isoindole-1,3(2H)-dione based HIV-1 integrase inhibitors as display platforms, we undertook a thorough examination of the effects of modifying the halogen substituents on a key benzyl ring that is hypothesized to bind in a hydrophobic pocket of the integrase.DNA complex. Data from this study suggest that in general dihalo-substituted analogues have higher potency than monohalo-substituted compounds, but that further addition of halogens is not beneficial.
View Article and Find Full Text PDFKansenshogaku Zasshi
March 2009
HIV Drug Resistance Program, National Cancer Institute-Frederick, NIH, U.S.A.
It is estimated that one million people are dually infected with Human Immunodeficiency Virus type-I (HIV-1) and type-II (HIV-2) in West Africa and parts of India. HIV-1 and HIV-2 use the same receptor and coreceptors for entry into cells, and thus target the same cell populations in the host. Additionally, we first examined whether RNAs from HIV-1 and HIV-2 can be copackaged into the same virion.
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