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| 2. |
- Aaron, F. D., et al.
(author)
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Multi-leptons with high transverse momentum at HERA
- 2009
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In: Journal of High Energy Physics. - : Springer Science and Business Media LLC. - 1029-8479. ; :10
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Journal article (peer-reviewed)abstract
- Events with at least two high transverse momentum leptons (electrons or muons) are studied using the H1 and ZEUS detectors at HERA with an integrated luminosity of 0.94 fb(-1). The observed numbers of events are in general agreement with the Standard Model predictions. Seven di- and tri-lepton events are observed in e(+)p collision data with a scalar sum of the lepton transverse momenta above 100 GeV while 1.94 +/- 0.17 events are expected. Such events are not observed in e(-)p collisions for which 1.19 +/- 0.12 are predicted. Total visible and differential di-electron and di-muon photoproduction cross sections are extracted in a restricted phase space dominated by photon-photon collisions.
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| 3. |
- McSherry, Elaine A., et al.
(author)
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JAM-A expression positively correlates with poor prognosis in breast cancer patients
- 2009
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 125:6, s. 1343-1351
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Journal article (peer-reviewed)abstract
- The cell-cell adhesion protein junctional adhesion molecule-A (JAM-A) influences; epithelial cell morphology and migration. As migration is required for tumor cell invasion and metastasis, we sought to elucidate the role of JAM-A in invasive breast cancer. A breast cancer tissue microarray was analyzed for JAM-A protein expression, in parallel with analysis of JAM-A gene expression data from a breast cancer clinical dataset. Our data demonstrate a novel association between JAM-A gene and protein upregulation and poor prognosis in breast cancer. To mechanistically dissect this process, we used lentiviral technology to stably knock down JAM-A gene expression by shRNA in MCF7 breast cancer cells, which express high-endogenous levels of JAM-A. We also antagonized JAM-A function in wild-type MCF7 cells using an inhibitory antibody that blocks JAM-A dimerization. Knockdown or functional antagonism of JAM-A decreased breast cancer cell migration in scratch-wound assays. Reductions in beta 1-integrin protein levels were observed after JAM-A-knockdown in MCF7 cells, suggesting a mechanism for reduced motility after loss of JAM-A. Consistent with this hypothesis, tissue microarray analysis of beta 1-integrin protein expression in invasive breast cancer tissues revealed a trend toward high beta 1-integrin protein levels being indicative of poor prognosis. Twenty-two percent of patients were observed to coexpress high levels of JAM-A and beta 1-integrin protein, and MDA-MB-231 breast cells stably overexpressing JAM-A showed an increase in beta 1-integrin protein expression. Our results are consistent with a previously unreported role for JAM-A overexpression as a possible mechanism contributing to progression in primary breast cancer; and a potential therapeutic target. (C) 2009 UICC
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| 7. |
- Shaffer, David R, et al.
(author)
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Circulating tumor cell analysis in patients with progressive castration-resistant prostate cancer
- 2007
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In: Clinical Cancer Research. - 1078-0432. ; 13:7, s. 2023-2029
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Journal article (peer-reviewed)abstract
- PURPOSE: To better direct targeted therapies to the patients with tumors that express the target, there is an urgent need for blood-based assays that provide expression information on a consistent basis in real time with minimal patient discomfort. We aimed to use immunomagnetic-capture technology to isolate and analyze circulating tumor cells (CTC) from small volumes of peripheral blood of patients with advanced prostate cancer. EXPERIMENTAL DESIGN: Blood was collected from 63 patients with metastatic prostate cancer. CTCs were isolated by the Cell Search system, which uses antibodies to epithelial cell adhesion marker and immunomagnetic capture. CTCs were defined as nucleated cells positive for cytokeratins and negative for CD45. Captured cells were analyzed by immunofluorescence, Papanicolau staining, and fluorescence in situ hybridization. RESULTS: Most patients (65%) had 5 or more CTCs per 7.5 mL blood sample. Cell counts were consistent between laboratories (c = 0.99) and did not change significantly over 72 or 96 h of storage before processing (c = 0.99). Their identity as prostate cancer cells was confirmed by conventional cytologic analysis. Molecular profiling, including analysis of epidermal growth factor receptor (EGFR) expression, chromosome ploidy, and androgen receptor (AR) gene amplification, was possible for all prostate cancer patients with >or=5 CTCs. CONCLUSIONS: The analysis of cancer-related alterations at the DNA and protein level from CTCs is feasible in a hospital-based clinical laboratory. The alterations observed in EGFR and AR suggest that the methodology may have a role in clinical decision making.
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| 9. |
- Brennan, Donal, et al.
(author)
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The transcription factor Sox11 is a prognostic factor for improved recurrence-free survival in epithelial ovarian cancer
- 2009
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In: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 45:8, s. 1510-1517
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Journal article (peer-reviewed)abstract
- Abstract Background: Current prognostic molecular markers for epithelial ovarian cancer (EOC) are insufficient. The aim of the current study was to investigate the role of Sox11 in EOC Methods: Using an in silico transcriptomic screen Sox11 was identified as a potential EOC biomarker. Sox11 protein expression was evaluated using immunohistochemistry (IHC) in 76 EOC cases, which were analyzed using automated algorithms to develop a quantitative scoring model. Results: Sox11 mRNA expression was up-regulated in EOC compared to normal tissues. Automated analysis of Sox11 in the EOC cohort revealed high expression of Sox11, in 40% of tumours, who had an improved recurrence free survival (RFS) (p= 0.002). Multivariate analysis confirmed Sox11 was an independent predictor of improved RFS after controlling for stage and grade. Conclusions: These data suggest that Sox11 is a new prognostic marker in EOC. Loss of SOX 11 is associated with a decreased RFS and a more aggressive phenotype.
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| 11. |
- Leung, Kin-Chuen, et al.
(author)
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Regulation of growth hormone signaling by selective estrogen receptor modulators occurs through suppression of protein tyrosine phosphatases.
- 2007
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In: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 148:5, s. 2417-23
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Journal article (peer-reviewed)abstract
- Activation of the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 5 (STAT5) pathway by GH is terminated by the suppressors of cytokine signaling (SOCSs) and protein tyrosine phosphatases, Src homology 2 domain-containing protein tyrosine phosphatase (SHP)-1 and SHP-2. Based on our recent report that estrogen inhibits GH signaling by stimulating SOCS-2 expression, we investigated the effects of selective estrogen receptor modulators (SERMs) on GH signaling in human embryonic kidney (HEK293) and breast cancer (MDA-MB-231) cells expressing human GH receptor and estrogen receptor-alpha. 17beta-estradiol (E(2)) suppressed GH activation of a STAT5-responsive luciferase reporter and JAK2 phosphorylation in both cell models. 4-hydroxytamoxifen and raloxifene augmented these actions of GH in HEK293 cells but not breast cancer cells. SOCS-2 expression in both cell types was stimulated by E(2) but unaffected by SERMs. In HEK293 cells, SHP-1 was inhibited by raloxifene and 4-hydroxytamoxifen, whereas the latter additionally inhibited SHP-2. The phosphatases were unaffected by E(2). In breast cancer cells, phosphatase activity was not altered by SERMs or E(2). In summary, estrogen inhibited the JAK2/STAT5 signaling of GH and stimulated SOCS-2 expression in both HEK293 and breast cancer cells. By contrast, SERMs augmented GH signaling by reducing SHP activities in HEK293 cells and had no effect on both in breast cancer cells. We provide the first evidence for a novel mechanism regulating GH signaling, in which SERMs enhance GH activation of the JAK2/STAT5 pathway in a cell-type-dependent manner by attenuating protein tyrosine phosphatase activities.
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| 12. |
- Rossi, P, et al.
(author)
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Performance of an alpha-IPEM
- 2006
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In: Ion Beam Analysis - Proceedings of the Seventeenth International Conference on Ion Beam Analysis (Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms). - : Elsevier BV. - 0168-583X. ; 249, s. 242-245
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Conference paper (peer-reviewed)abstract
- The ion photon emission microscope, or IPEM, is the first device that allows scientists to microscopically study the effects of single ions in air on semiconductors, microchips and even biological cells without having to focus the beam. Reported here is a prototype, the size of a conventional optical microscope, developed at Sandia. The alpha-IPEM, that employs alpha particles from a radioactive source, represents the first example of IBA imaging without an accelerator. The IPEM resolution is currently limited to similar to 10 mu m, but we also report a gridded-phosphor approach that could improve this resolution to that of the optical microscope, or similar to 1 mu m. Finally, we propose that a simple adaptation of the alpha-IPEM could be the only way to maintain the high utility of radiation effects microscopy into the future.
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| 13. |
- von Uexull, O, et al.
(author)
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Antimony in brake pads - a carcinogenic component?
- 2005
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In: Journal of Cleaner Production. - : Elsevier BV. - 0959-6526. ; 13:1, s. 19-31
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Journal article (peer-reviewed)abstract
- Antimony trisulfide (Sb2S3) is used as a lubricant in friction material. X-ray diffraction analysis revealed Sb in 3/3 disc brake pads (range 41,000-46,000 mg/kg) and in 2/2 disc brake dust samples (21,000 and 17,000 mg/kg) from trucks. Considerably lower concentrations were found in drum brake pads (3/5, 59-6400 mg/kg) and in drum brake dust (4/18, 78-2800 mg/kg). Other toxic metals were also detected in pads and dust. The health risk of Sb in particulate brake emissions should be dependent on particle size and chemical entity, in particular solubility. A significant amount of the emitted dust was shown by size-fractionated optical particle counting to be inhalable in environmental ( > 90% mass) and occupational ( > 50% mass) exposure situations. Differentiation via selective solubility showed a considerable amount of Sb2S3 to oxidize during the braking process, likely leading to the formation of Sb2O3, a suspected human carcinogen. Sb in brake dust was soluble in calf serum (8.5 +/- 1.2%, 8.9 +/- 1.7 mg/l at 37degreesC for 3 d). Hence, the use of Sb in friction material should be suspected to pose a human cancer risk and be deterred. To design healthy and environmentally sound alternatives, we propose to apply the Intelligent Product System that distinguishes products of consumption and products of service. Brake pads are true products of consumption, because they are released to biological cycles, and should thus consist of materials with positively defined health and environmental properties.
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