GLORIA

GEOMAR Library Ocean Research Information Access

X
feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    facet.materialart.
    Unknown
    Identification and Validation of an Anthracycline/Cyclophosphamide-Based Chemotherapy Response Assay in Breast Cancer (2014)
    Oxford University Press
    Details
    Publication Date: 2014-01-09
    Description: Background There is no method routinely used to predict response to anthracycline and cyclophosphamide–based chemotherapy in the clinic; therefore patients often receive treatment for breast cancer with no benefit. Loss of the Fanconi anemia/BRCA (FA/BRCA) DNA damage response (DDR) pathway occurs in approximately 25% of breast cancer patients through several mechanisms and results in sensitization to DNA-damaging agents. The aim of this study was to develop an assay to detect DDR-deficient tumors associated with loss of the FA/BRCA pathway, for the purpose of treatment selection. Methods DNA microarray data from 21 FA patients and 11 control subjects were analyzed to identify genetic processes associated with a deficiency in DDR. Unsupervised hierarchical clustering was then performed using 60 BRCA1/2 mutant and 47 sporadic tumor samples, and a molecular subgroup was identified that was defined by the molecular processes represented within FA patients. A 44-gene microarray-based assay (the DDR deficiency assay) was developed to prospectively identify this subgroup from formalin-fixed, paraffin-embedded samples. All statistical tests were two-sided. Results In a publicly available independent cohort of 203 patients, the assay predicted complete pathologic response vs residual disease after neoadjuvant DNA-damaging chemotherapy (5-fluorouracil, anthracycline, and cyclophosphamide) with an odds ratio of 3.96 (95% confidence interval [Cl] =1.67 to 9.41; P = .002). In a new independent cohort of 191 breast cancer patients treated with adjuvant 5-fluorouracil, epirubicin, and cyclophosphamide, a positive assay result predicted 5-year relapse-free survival with a hazard ratio of 0.37 (95% Cl = 0.15 to 0.88; P = .03) compared with the assay negative population. Conclusions A formalin-fixed, paraffin-embedded tissue-based assay has been developed and independently validated as a predictor of response and prognosis after anthracycline/cyclophosphamide–based chemotherapy in the neoadjuvant and adjuvant settings. These findings warrant further validation in a prospective clinical study.
    Electronic ISSN: 1460-2105
    Topics: Medicine
    Published by Oxford University Press
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 2
    facet.materialart.
    Unknown
    Heme oxygenase-1 regulates the immune response to influenza virus infection and vaccination in aged mice [Research Communications] (2012)
    The Federation of American Societies for Experimental Biology (FASEB)
    Details
    Publication Date: 2012-06-29
    Description: Underlying mechanisms of individual variation in severity of influenza infection and response to vaccination are poorly understood. We investigated the effect of reduced heme oxygenase-1 (HO-1) expression on vaccine response and outcome of influenza infection. HO-1-deficient and wild-type (WT) mice (kingdom, Animalia; phylum, Chordata; genus/species, Mus musculus ) were infected with influenza virus A/PR/8/34 with or without prior vaccination with an adenoviral-based influenza vaccine. A genome-wide association study evaluated the expression of single-nucleotide polymorphisms (SNPs) in the HO-1 gene and the response to influenza vaccination in healthy humans. HO-1-deficient mice had decreased survival after influenza infection compared to WT mice (median survival 5.5 vs. 6.5 d, P =0.016). HO-1-deficient mice had impaired production of antibody following influenza vaccination compared to WT mice (mean antibody titer 869 vs. 1698, P =0.02). One SNP in HO-1 and one SNP in the constitutively expressed isoform HO-2 were independently associated with decreased antibody production after influenza vaccination in healthy human volunteers ( P =0.017 and 0.014, respectively). HO-1 deficient mice were paired with sex- and age-matched WT controls. HO-1 affects the immune response to both influenza infection and vaccination, suggesting that therapeutic induction of HO-1 expression may represent a novel adjuvant to enhance influenza vaccine effectiveness.—Cummins, N. W., Weaver, E. A., May, S. M., Croatt, A. J., Foreman, O., Kennedy, R. B., Poland, G. A., Barry, M. A., Nath, K. A., Badley, A. D. Heme oxygenase-1 regulates the immune response to influenza virus infection and vaccination in aged mice.
    Print ISSN: 0892-6638
    Electronic ISSN: 1530-6860
    Topics: Biology
    Published by The Federation of American Societies for Experimental Biology (FASEB)
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 3
    facet.materialart.
    Unknown
    High-Dimensional Gene Expression Profiling Studies in High and Low Responders to Primary Smallpox Vaccination (2012)
    Oxford University Press
    Details
    Publication Date: 2012-10-19
    Description: Background.  The mechanisms underlying smallpox vaccine-induced variations in immune responses are not well understood, but are of considerable interest to a deeper understanding of poxvirus immunity and correlates of protection. Methods.  We assessed transcriptional messenger RNA expression changes in 197 recipients of primary smallpox vaccination representing the extremes of humoral and cellular immune responses. Results.  The 20 most significant differentially expressed genes include a tumor necrosis factor–receptor superfamily member, an interferon (IFN) gene, a chemokine gene, zinc finger protein genes, nuclear factors, and histones ( P  ≤ 1.06E –20 , q  ≤ 2.64E –17 ). A pathway analysis identified 4 enriched pathways with cytokine production by the T-helper 17 subset of CD4+ T cells being the most significant pathway ( P  = 3.42E –05 ). Two pathways (antiviral actions of IFNs, P  = 8.95E –05 ; and IFN-α/β signaling pathway, P  = 2.92E –04 ), integral to innate immunity, were enriched when comparing high with low antibody responders (false discovery rate, 〈 0.05). Genes related to immune function and transcription ( TLR8 , P  = .0002; DAPP1 , P  = .0003; LAMP3 , P  = 9.96E –05 ; NR4A2 , P  ≤ .0002; EGR3 , P  = 4.52E –05 ), and other genes with a possible impact on immunity ( LNPEP , P  = 3.72E –05 ; CAPRIN1 , P  = .0001; XRN1 , P  = .0001), were found to be expressed differentially in high versus low antibody responders. Conclusion.  We identified novel and known immunity-related genes and pathways that may account for differences in immune response to smallpox vaccination.
    Print ISSN: 0022-1899
    Electronic ISSN: 1537-6613
    Topics: Medicine
    Published by Oxford University Press on behalf of The Infectious Diseases Society of America (IDSA).
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 4
    facet.materialart.
    Unknown
    Secondhand smoke emission levels in enclosed public places during Ramadan (2013)
    Oxford University Press
    Details
    Publication Date: 2013-09-28
    Description: Secondhand smoke levels were assessed among a convenience sample of 15 public venues in Amman, Jordan, during Ramadan. PM 2.5 measurements were taken inside each venue pre- and post-‘iftar’, when daily smoking abstinence can be broken at sundown. Cigarette smoking was observed in all venues post-iftar, and the median PM 2.5 level among the 15 venues (285 µg/m 3 ) was significantly higher than the pre-iftar level (11 µg/m 3 ; P 〈 0.001). Post-iftar PM 2.5 levels exceeded the World Health Organization standard for particulate pollution by 5–20-fold. To protect public health in Jordan, smoke-free legislation should be enforced at all times of day, and all days of the year.
    Print ISSN: 1101-1262
    Electronic ISSN: 1464-360X
    Topics: Medicine
    Published by Oxford University Press
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 5
    facet.materialart.
    Unknown
    Genetic Variation in IL18R1 and IL18 Genes and Inteferon {gamma} ELISPOT Response to Smallpox Vaccination: An Unexpected Relationship (2013)
    Oxford University Press
    Details
    Publication Date: 2013-10-04
    Description: Background.  Genetic association studies demonstrated a role for cytokine proteins and cytokine or cytokine receptor gene polymorphisms in smallpox vaccine–induced adaptive immunity. Methods.  We examined the association of genetic polymorphisms with cellular (interferon [IFN] enzyme-linked immunospot assay [ELISPOT]) immune response to smallpox vaccine in 1076 immunized individuals. Results.  The majority of significant associations were discovered between single-nucleotide polymorphisms/haplotypes in IL18R1 and IL18 genes, in which we previously reported an association with vaccinia virus–induced neutralizing antibody titers in this study cohort. A functional coding IL18R1 polymorphism (rs1035130/Phe251Phe; P = .01) was significantly associated with an allele dose-related increase in IFN- production and was also associated with vaccinia-specific neutralizing antibody titers. Significant associations were also found between IL18R1 haplotypes and variations in IFN- ELISPOT responses (global P 〈 .0001). Conclusions.  Our data suggest the importance of variants in the IL18R1 and IL18 genetic loci for broad-based smallpox vaccine–induced adaptive immunity.
    Print ISSN: 0022-1899
    Electronic ISSN: 1537-6613
    Topics: Medicine
    Published by Oxford University Press on behalf of The Infectious Diseases Society of America (IDSA).
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 6
    facet.materialart.
    Unknown
    BRCA1 is a key regulator of breast differentiation through activation of Notch signalling with implications for anti-endocrine treatment of breast cancers (2013)
    Oxford University Press
    Details
    Publication Date: 2013-10-08
    Description: Here, we show for the first time, that the familial breast/ovarian cancer susceptibility gene BRCA1 activates the Notch pathway in breast cells by transcriptional upregulation of Notch ligands and receptors in both normal and cancer cells. We demonstrate through chromatin immunoprecipitation assays that BRCA1 is localized to a conserved intronic enhancer region within the Notch ligand Jagged-1 (JAG1) gene, an event requiring Np63. We propose that this BRCA1/Np63-mediated induction of JAG1 may be important the regulation of breast stem/precursor cells, as knockdown of all three proteins resulted in increased tumoursphere growth and increased activity of stem cell markers such as Aldehyde Dehydrogenase 1 (ALDH1). Knockdown of Notch1 and JAG1 phenocopied BRCA1 knockdown resulting in the loss of Estrogen Receptor-α (ER-α) expression and other luminal markers. A Notch mimetic peptide could activate an ER-α promoter reporter in a BRCA1-dependent manner, whereas Notch inhibition using a -secretase inhibitor reversed this process. We demonstrate that inhibition of Notch signalling resulted in decreased sensitivity to the anti-estrogen drug Tamoxifen but increased expression of markers associated with basal-like breast cancer. Together, these findings suggest that BRCA1 transcriptional upregulation of Notch signalling is a key event in the normal differentiation process in breast tissue.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 7
    facet.materialart.
    Unknown
    Constraining the warm dark matter particle mass with Milky Way satellites (2014)
    Oxford University Press
    Details
    Publication Date: 2014-06-26
    Description: Particle physics theories predict the existence of particles (such as keV mass sterile neutrinos) which could behave as warm dark matter (WDM), producing a cutoff in the linear density power spectrum on the scale of dwarf galaxies. Thus, the abundance of Milky Way satellite galaxies depends on the mass of the warm particle and also scales with the mass of the host galactic halo. We use the galform semi-analytic model of galaxy formation to compare predicted satellite luminosity functions to Milky Way data and determine a lower bound on the thermally produced WDM particle mass. This depends strongly on the Milky Way halo mass and, to some extent, on the baryonic physics assumed. For our fiducial model, we find that for a particle mass of 3.3 keV (the 2 lower limit from an analysis of the Lyman α forest by Viel et al.) the Milky Way halo mass is required to be 〉1.4 10 12 M . For this same fiducial model, we also find that all WDM particle masses are ruled out (at 95 per cent confidence) if the Milky Way halo mass is smaller than 1.1 10 12 M , while if the mass of the Galactic halo is greater than 1.8 10 12 M , only WDM particle masses larger than 2 keV are allowed.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 8
    facet.materialart.
    Unknown
    Combination of bendamustine, lenalidomide, and dexamethasone (BLD) in patients with relapsed or refractory multiple myeloma is feasible and highly effective: results of phase 1/2 open-label, dose escalation study (2012)
    American Society of Hematology (ASH)
    In: Blood
    Details
    Publication Date: 2012-05-18
    Description: This multicenter phase 1/2 trial investigated the combination of bendamustine, lenalidomide, and dexamethasone in repeating 4-week cycles as treatment for relapsed refractory multiple myeloma (MM). Phase 1 established maximum tolerated dose (MTD). Phase 2 assessed overall response rate at the MTD. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). A total of 29 evaluable patients were enrolled. Median age was 63 years (range, 38-80 years). Median number of prior therapies was 3 (range, 1-6). MTD was bendamustine 75 mg/m 2 (days 1 and 2), lenalidomide 10 mg (days 1-21), and dexamethasone 40 mg (weekly) of a 28-day cycle. Partial response rate was 52%, with very good partial response achieved in 24%, and minimal response in an additional 24% of patients. Median follow-up was 13 months; median OS has not been reached. One-year OS is 93% (95% confidence interval [CI], 59%-99%). Median PFS is 6.1 months (95% CI, 3.7-9.4 months) with one-year PFS of 20% (95% CI, 6%-41%). Grade 3/4 adverse events included neutropenia, thrombocytopenia, anemia, hyperglycemia, and fatigue. This first phase 1/2 trial testing bendamustine, lenalidomide, and dexamethasone as treatment of relapsed refractory MM was feasible and highly active. This study is registered at www.clinicaltrials.gov as #NCT01042704.
    Keywords: Free Research Articles, Lymphoid Neoplasia, Clinical Trials and Observations
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology (ASH)
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 9
    facet.materialart.
    Unknown
    Enhanced GLP-1- and Sulfonylurea-Induced Insulin Secretion in Islets Lacking Leptin Signaling (2012)
    The Endocrine Society
    Details
    Publication Date: 2012-06-20
    Description: We have previously reported that the absence of leptin signaling in β-cells enhances glucose-stimulated insulin secretion and improves glucose tolerance in vivo. To investigate the relevance of β-cell leptin signaling in the context of postprandial or therapeutic insulin secretion, we examined the cross talk between leptin and glucagon-like peptide (GLP)-1 and sulfonylurea actions. Single and size-matched islets isolated from control or pancreas-specific leptin receptor knockout (pancreas-ObR-KO) mice were treated either with GLP-1 or with glibenclamide. Leptin suppressed GLP-1-stimulated intracellular Ca2+ concentrations ([Ca2+]i) increase that paralleled the decrease in insulin secretion in controls. In contrast, and as expected, the ObR-KO islets were nonresponsive to leptin, and instead, showed a 2.8-fold greater GLP-1-stimulated [Ca2+]i increase and a 1.7-fold greater insulin secretion. Phosphorylation of cAMP-responsive element binding protein was enhanced, and phosphodiesterase enzymatic activity was suppressed in MIN6 β-cells with ObR knockdown compared with controls. The ObR-KO islets also showed significantly higher glibenclamide-induced insulin secretion compared with control islets, whereas [Ca2+]i was similar to the controls. These data support enhanced insulinotropic effects of glucose, GLP-1, and sulfonylureas in the islets lacking leptin signaling with potential therapeutic implications.
    Keywords: TRANSLATIONAL RESEARCH IN ENDOCRINOLOGY AND METABOLISM, Translational Highlights from MEND
    Print ISSN: 0888-8809
    Electronic ISSN: 1944-9917
    Topics: Biology , Medicine
    Published by The Endocrine Society
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 10
    facet.materialart.
    Unknown
    {beta}-Cell Metabolomics [Cell Biology] (2013)
    The American Society for Biochemistry and Molecular Biology (ASBMB)
    Details
    Publication Date: 2013-04-13
    Description: Glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells is triggered by metabolism of the sugar to increase ATP/ADP ratio that blocks the KATP channel leading to membrane depolarization and insulin exocytosis. Other metabolic pathways believed to augment insulin secretion have yet to be fully elucidated. To study metabolic changes during GSIS, liquid chromatography with mass spectrometry was used to determine levels of 87 metabolites temporally following a change in glucose from 3 to 10 mm glucose and in response to increasing concentrations of glucose in the INS-1 832/13 β-cell line. U-[13C]Glucose was used to probe flux in specific metabolic pathways. Results include a rapid increase in ATP/ADP, anaplerotic tricarboxylic acid cycle flux, and increases in the malonyl CoA pathway, support prevailing theories of GSIS. Novel findings include that aspartate used for anaplerosis does not derive from the glucose fuel added to stimulate insulin secretion, glucose flux into glycerol-3-phosphate, and esterification of long chain CoAs resulting in rapid consumption of long chain CoAs and de novo generation of phosphatidic acid and diacylglycerol. Further, novel metabolites with potential roles in GSIS such as 5-aminoimidazole-4-carboxamide ribotide (ZMP), GDP-mannose, and farnesyl pyrophosphate were found to be rapidly altered following glucose exposure.
    Print ISSN: 0021-9258
    Electronic ISSN: 1083-351X
    Topics: Biology , Chemistry and Pharmacology
    Published by The American Society for Biochemistry and Molecular Biology (ASBMB)
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...