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Find video protocols related to scientific articles indexed in Pubmed.
Impact of RANK signalling on survival and chemotherapy response in osteosarcoma.
Pathology
PUBLISHED: 05-21-2014
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The receptor activator of NF-?B (RANK) signalling pathway represents a promising target for the therapy of bone-related tumours. In the present study we evaluated the impact of the expression of RANK and its ligand (RANKL) on survival and response to chemotherapy in osteosarcoma patients.Expression of RANK and RANKL was examined in 91 human osteosarcomas by immunohistochemistry using formalin fixed, paraffin embedded (FFPE) tumour samples. Results of the stainings were correlated with clinicopathological parameters and patient survival.Sixty-three osteosarcomas (69.2%) expressed RANK, whereas only eight cases (8.8%) showed expression of RANKL. Expression of RANK was significantly associated with shorter disease-free survival by Kaplan-Meier analysis (p=0.031). We further observed worse response to chemotherapy in RANK expressing tumours, which was statistically not significant (p=0.099). RANKL expression was significantly more frequent in osteosarcoma of the lower extremity than in any other location. Analysis of RANKL expression did not reveal any statistically significant correlation with disease-free or osteosarcoma-specific survival.In our study, we identified RANK expression as a negative prognostic factor regarding disease-free survival in osteosarcoma. Moreover, RANK might modulate response of human osteosarcoma to chemotherapy. Therefore, RANK signalling cascade is likely to provide a novel alternative to targeted therapy of osteosarcoma and deserves further investigation.
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SIAH2 antagonizes TYK2-STAT3 signaling in lung carcinoma cells.
Oncotarget
PUBLISHED: 05-17-2014
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The Janus tyrosine kinases JAK1-3 and tyrosine kinase-2 (TYK2) are frequently hyperactivated in tumors. In lung cancers JAK1 and JAK2 induce oncogenic signaling through STAT3. A putative role of TYK2 in these tumors has not been reported. Here, we show a previously not recognized TYK2-STAT3 signaling node in lung cancer cells. We reveal that the E3 ubiquitin ligase seven-in-absentia-2 (SIAH2) accelerates the proteasomal degradation of TYK2. This mechanism consequently suppresses the activation of STAT3. In agreement with these data the analysis of primary non-small-cell lung cancer (NSCLC) samples from three patient cohorts revealed that compared to lung adenocarcinoma (ADC), lung squamous cell carcinoma (SCC) show significantly higher levels of SIAH2 and reduced STAT3 phosphorylation levels. Thus, SIAH2 is a novel molecular marker for SCC. We further demonstrate that an activation of the oncologically relevant transcription factor p53 in lung cancer cells induces SIAH2, depletes TYK2, and abrogates the tyrosine phosphorylation of STAT1 and STAT3. This mechanism appears to be different from the inhibition of phosphorylated JAKs through the suppressor of cytokine signaling (SOCS) proteins. Our study may help to identify molecular mechanisms affecting lung carcinogenesis and potential therapeutic targets.
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The safety and clinical usefulness of dobutamine stress echocardiography among octogenarians.
Heart
PUBLISHED: 04-23-2014
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Increasing numbers of octogenarians are being referred for investigation of chest pain. While dobutamine stress echocardiography (DSE) has been shown to be useful in younger patients, its role among octogenarians remains unclear. This investigation aimed to investigate the safety and prognostic benefits of DSE on cardiac events and total mortality in octogenarians.
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Why are all the White (Asian) kids sitting together in the cafeteria? Resegregation and the role of intergroup attributions and norms.
Br J Soc Psychol
PUBLISHED: 03-07-2014
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Over three studies, we identified the phenomenon of ethnic 'resegregation' and assessed the extent to which it was predicted by attributions and norms, among other variables. Study 1, an observational study, showed extensive resegregation between White and Asian students in the cafeteria of a highly mixed school. In Study 2, we found evidence of attributional correspondence for White students, who attributed both their own and the outgroup's contact avoidance more to a lack of interest than fear of rejection, whereas Asian students attributed the outgroup's contact avoidance more to lack of interest, but preferred neither explanation of their own avoidance. In Study 3, we observed a pattern of attributional correspondence among both White and Asian students who attributed both their own and the outgroup's inaction in a hypothetical intergroup cafeteria scenario more to a lack of interest than fear of rejection. Study 3 also demonstrated longitudinally, for both groups, that own lack of interest in the outgroup reduced likelihood of cafeteria contact, whereas having outgroup friends and perceiving positive ingroup norms promoted it. In addition, positive outgroup norms promoted likelihood of cafeteria contact only for Asian students. We discuss how an understanding of the factors driving resegregation is critical to effectively realizing the potential of desegregated settings.
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Contextual effect of positive intergroup contact on outgroup prejudice.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 03-03-2014
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We assessed evidence for a contextual effect of positive intergroup contact, whereby the effect of intergroup contact between social contexts (the between-level effect) on outgroup prejudice is greater than the effect of individual-level contact within contexts (the within-level effect). Across seven large-scale surveys (five cross-sectional and two longitudinal), using multilevel analyses, we found a reliable contextual effect. This effect was found in multiple countries, operationalizing context at multiple levels (regions, districts, and neighborhoods), and with and without controlling for a range of demographic and context variables. In four studies (three cross-sectional and one longitudinal) we showed that the association between context-level contact and prejudice was largely mediated by more tolerant norms. In social contexts where positive contact with outgroups was more commonplace, norms supported such positive interactions between members of different groups. Thus, positive contact reduces prejudice on a macrolevel, whereby people are influenced by the behavior of others in their social context, not merely on a microscale, via individuals' direct experience of positive contact with outgroup members. These findings reinforce the view that contact has a significant role to play in prejudice reduction, and has great policy potential as a means to improve intergroup relations, because it can simultaneously impact large numbers of people.
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Neighborhood ethnic diversity and trust: the role of intergroup contact and perceived threat.
Psychol Sci
PUBLISHED: 01-16-2014
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This research reported here speaks to a contentious debate concerning the potential negative consequences of diversity for trust. We tested the relationship between neighborhood diversity and out-group, in-group, and neighborhood trust, taking into consideration previously untested indirect effects via intergroup contact and perceived intergroup threat. A large-scale national survey in England sampled White British majority (N = 868) and ethnic minority (N = 798) respondents from neighborhoods of varying degrees of diversity. Multilevel path analyses showed some negative direct effects of diversity for the majority group but also confirmed predictions that diversity was associated indirectly with increased trust via positive contact and lower threat. These indirect effects had positive implications for total effects of diversity, cancelling out most negative direct effects. Our findings have relevance for a growing body of research seeking to disentangle effects of diversity on trust that has so far largely ignored the key role of intergroup contact.
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Selectins mediate small cell lung cancer systemic metastasis.
PLoS ONE
PUBLISHED: 01-01-2014
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Metastasis formation is the major reason for the extremely poor prognosis in small cell lung cancer (SCLC) patients. The molecular interaction partners regulating metastasis formation in SCLC are largely unidentified, however, from other tumor entities it is known that tumor cells use the adhesion molecules of the leukocyte adhesion cascade to attach to the endothelium at the site of the future metastasis. Using the human OH-1 SCLC line as a model, we found that these cells expressed E- and P-selectin binding sites, which could be in part attributed to the selectin binding carbohydrate motif sialyl Lewis A. In addition, protein backbones known to carry these glycotopes in other cell lines including PSGL-1, CD44 and CEA could be detected in in vitro and in vivo grown OH1 SCLC cells. By intravital microscopy of murine mesenterial vasculature we could capture SCLC cells while rolling along vessel walls demonstrating that SCLC cells mimic leukocyte rolling behavior in terms of selectin and selectin ligand interaction in vivo indicating that this mechanism might indeed be important for SCLC cells to seed distant metastases. Accordingly, formation of spontaneous distant metastases was reduced by 50% when OH-1 cells were xenografted into E-/P-selectin-deficient mice compared with wild type mice (p = 0.0181). However, as metastasis formation was not completely abrogated in selectin deficient mice, we concluded that this adhesion cascade is redundant and that other molecules of this cascade mediate metastasis formation as well. Using several of these adhesion molecules as interaction partners presumably make SCLC cells so highly metastatic.
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Prognostic relevance of ubiquitin C-terminal hydrolase L1 (UCH-L1) mRNA and protein expression in breast cancer patients.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 08-01-2013
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The ubiquitin C-terminal hydrolase L1 (UCH-L1) belongs to the family of deubiquitinating enzymes. It is overexpressed in various tumour entities and associated with metastases formation in some solid tumours. However, only limited information about its role in breast cancer is available. The aim of this study was to examine the UCH-L1 expression in primary breast cancer and to determine its relevance as a potential prognostic marker.
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Reducing aggressive intergroup action tendencies: Effects of intergroup contact via perceived intergroup threat.
Aggress Behav
PUBLISHED: 06-21-2013
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Two studies tested the prediction that more positive intergroup contact would be associated with reduced aggressive intergroup action tendencies, an effect predicted to occur indirectly via reduced intergroup threat perceptions, and over and above well-established effects of contact on intergroup attitudes. Study 1, using data based on a cross-section of the general population of eight European countries (France, Germany, Hungary, Italy, the Netherlands, Poland, Portugal, and the UK; N?=?7,042), examined this hypothesis in the context of aggressive action tendencies towards immigrants. Study 2, using longitudinal data obtained from a general population sample in Northern Ireland, considered effects on aggressive action tendencies between ethno-religious groups in conflict. Both studies confirmed our predictions, showing that while perceived threat was associated with greater intergroup aggressive tendencies, positive intergroup contact was indirectly associated with reduced aggressive action tendencies, via reduced intergroup threat. Findings are discussed in terms of the theoretical contributions of this research for understanding the relationship between intergroup contact and intergroup aggression. Aggr. Behav. 9999:XX-XX, 2013. © 2013 Wiley Periodicals, Inc.
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Secondary transfer effects of intergroup contact via social identity complexity.
Br J Soc Psychol
PUBLISHED: 06-12-2013
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Secondary transfer effects (STEs) of intergroup contact refer to the generalization of contact effects from a primary encountered outgroup to attitudes towards secondary outgroups (Pettigrew, 2009). Using two large, cross-sectional data sets from Germany (N = 1,381) and Northern Ireland (N = 1,948), this article examined the extent to which STEs of intergroup contact on attitudes towards a range of secondary outgroups occur via a previously unexplored psychological construct, social identity complexity (operationalized as similarity complexity and overlap complexity). Study 1 found primary outgroup contact to be associated with greater similarity complexity, but no indirect effects on secondary outgroup attitudes via complexity emerged. Study 2, however, revealed indirect positive relationships between primary outgroup contact and secondary outgroup attitudes via increased similarity complexity and overlap complexity. These relationships were obtained while controlling for two previously tested mediating mechanisms, attitude generalization (operationalized as primary outgroup attitude) and deprovincialization (operationalized as ingroup attitude and identification). We discuss the theoretical implications of these findings and the contribution of social identity complexity to understanding processes underlying STEs of contact.
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Comparing treatment of neovascular age-related macular degeneration with sequential intravitreal Avastin and Macugen versus intravitreal mono-therapy--a pilot study.
Curr. Eye Res.
PUBLISHED: 09-29-2011
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To examine if the sequential treatment of Avastin and Macugen is safe and more efficient than the mono-therapies in a prospective randomized masked pilot study.
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High expression of Dicer reveals a negative prognostic influence in certain subtypes of primary cutaneous T cell lymphomas.
J. Dermatol. Sci.
PUBLISHED: 03-06-2011
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Aberrant expression of microRNAs (miRNAs) has been implicated in oncogenesis of various tumors and primary cutaneous T cell lymphomas. Dicer, a ribonuclease III-like enzyme is essential for miRNA processing.
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Localization of gentamicin uptake in the acutely isolated inner ear of the rat.
Int J Physiol Pathophysiol Pharmacol
PUBLISHED: 02-25-2011
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The quantitative analysis of fluorescence in frozen sections of rat inner ears exposed to Texas Red conjugated gentamicin revealed distinct gradients of gentamicin fluorescence. At 500 µg/ml gentamicin fluorescence occurred in inner and outer hair cells, the interdental cell region, the spiral limbus below the interdental cells, the nerve fiber bundle in the spiral lamina, the inner sulcus cells and the dorsal region of the spiral ligament. No gentamicin fluorescence was observed in the Hensen / Claudius cells, the ventral region of the spiral ligament, the stria vascularis and the spiral ganglion. In the vestibule only the hair cell epithelium and the transitional cells of the saccule showed gentamicin fluorescence while no gentamicin fluorescence was found in hair cell epithelia and transitional cells of utricle and ampule, nerve fibers below hair cell epithelia of saccule, utricle and ampule and in dark cells. The gentamicin flurescence increased at higher concentrations. Gentamicin exposure led to more pronounced gentamicin fluorescence in the cochlea compared to the vestibule. Based on the predominant gentamicin fluorescence in the hair cell - limbus region of the cochlea at a low dose we propose that gentamicin may interact with the K(+)-flow from the inner hair cells back to the scala media.
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Functional role of inositol-1,4,5-trisphosphate-3-kinase-A for motility of malignant transformed cells.
Int. J. Cancer
PUBLISHED: 01-06-2011
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Cell migration is one of the hallmarks of metastatic disease and thus identification of migration promoting proteins is crucial for the understanding of metastasis formation. Here we show that the neuron-specific, F-actin bundling inositol-1,4,5-trisphosphate-3-kinase-A (ITPKA) is ectopically expressed in tumor cells and critically involved in migration. Down-regulation of ITPKA expression in transformed cell-lines with ectopic expression of ITPKA significantly decreased migration and the number of linear and branched cell protrusion. Conversely, up-regulation of ITPKA in tumor cell lines with low endogenous ITPKA expression increased migration and formation of cell processes. In vitro, ITPKA alone induced the formation of linear actin filaments, whereas ITPKA mediated formation of branched protrusions seems to result from interaction between ITPKA and the F-actin cross-linking protein filamin C. Based on these actin-modulating and migration-promoting effects of ITPKA we examined its expression in clinical samples of different tumor entities, starting with the analysis of multiple tumor tissue arrays. As in lung adenocarcinoma specimens, the highest ITPKA expression rate was found, this tumor entity was examined in more detail. ITPKA was expressed early in adenocarcinoma progression (pN0) and was largely maintained in invasive and metastatic tumor cell populations (pN1/2, lymph node metastases). Together with our result that high expression of ITPKA increases motility of tumor cells we conclude that the observed expression of ITPKA early in tumor development increases the metastatic potential of lung adenocarcinoma cells. Therefore, we suggest that ITPKA may be a promising therapeutic molecular target for anti metastatic therapy of lung cancer.
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Circulating angiopoietic cells and diabetic retinopathy in type 2 diabetes mellitus, with or without macrovascular disease.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 01-01-2011
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To investigate different types of circulating angiopoietic cells, such as vasculogenic circulating progenitor cells (CPCs), endothelial progenitor cells (EPCs), and mature EPCs (matEPCs) in patients with type 2 diabetes mellitus (T2DM), with or without diabetic retinopathy (DR) and with or without macrovascular disease (MVD).
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Serum VEGF and CFH in exudative age-related macular degeneration.
Curr. Eye Res.
PUBLISHED: 12-15-2010
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To determine serum vascular endothelial growth factor 165 (VEGF165) levels and the association of the complement factor H gene (CFH) Y402H polymorphism in patients with exudative age-related macular degeneration (AMD) in comparison to unaffected control subjects.
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E2-2 protein and Fuchss corneal dystrophy.
N. Engl. J. Med.
PUBLISHED: 09-10-2010
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Fuchss corneal dystrophy (FCD) is a leading cause of corneal transplantation and affects 5% of persons in the United States who are over the age of 40 years. Clinically visible deposits called guttae develop under the corneal endothelium in patients with FCD. A loss of endothelial cells and deposition of an abnormal extracellular matrix are observed microscopically. In advanced disease, the cornea swells and becomes cloudy because the remaining endothelial cells are not sufficient to keep the cornea dehydrated and clear. Although rare genetic variation that contributes to both early-onset and typical late-onset forms of FCD has been identified, to our knowledge, no common variants have been reported.
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Secondary transfer effects of intergroup contact: Alternative accounts and underlying processes.
J Pers Soc Psychol
PUBLISHED: 07-28-2010
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Although intergroup contact is one of the most prominent interventions to reduce prejudice, the generalization of contact effects is still a contentious issue. This research further examined the rarely studied secondary transfer effect (STE; Pettigrew, 2009), by which contact with a primary outgroup reduces prejudice toward secondary groups that are not directly involved in the contact. Across 3 cross-sectional studies conducted in Cyprus (N = 1,653), Northern Ireland (N = 1,973), and Texas (N = 275) and 1 longitudinal study conducted in Northern Ireland (N = 411), the present research sought to systematically rule out alternative accounts of the STE and to investigate 2 potential mediating mechanisms (ingroup reappraisal and attitude generalization). Results indicated that, consistent with the STE, contact with a primary outgroup predicts attitudes toward secondary outgroups, over and above contact with the secondary outgroup, socially desirable responding, and prior attitudes. Mediation analyses found strong evidence for attitude generalization but only limited evidence for ingroup reappraisal as an underlying process. Two out of 3 tests of a reverse model, where contact with the secondary outgroup predicts attitudes toward the primary outgroup, provide further evidence for an indirect effect through attitude generalization. Theoretical and practical implications of these results are discussed, and directions for future research are identified.
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Osteopontin expression predicts overall survival after liver transplantation for hepatocellular carcinoma in patients beyond the Milan criteria.
J. Hepatol.
PUBLISHED: 06-16-2010
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Microarray data showed that osteopontin overexpression predicts early HCC-recurrence after liver resection. Osteopontin (OPN) expression could serve as a predictor of HCC-recurrence after OLT.
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A plasmid-based multigene expression system for mammalian cells.
Nat Commun
PUBLISHED: 06-15-2010
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The introduction of heterologous genetic information, particularly of multiple genes, into mammalian cells is a key technology in contemporary experimental biological research. The coexpression of fluorescently tagged sensors is required to simultaneously analyse multiple parameters in living cells and the coexpression of several proteins is necessary to manipulate cell fate in stem cell biology. Current technologies for multigene expression in mammalian cells are inefficient, inflexible and time-consuming. In this paper we describe MultiLabel, a novel and highly efficient modular plasmid-based eukaryotic expression system. Independent expression vectors are assembled by a Cre/LoxP reaction into a plasmid with multiple expression cassettes. MultiLabel enables rapid construction of multigene expression vectors for the single-step creation of transiently or stably transfected mammalian cells.
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TREM-1 activation alters the dynamics of pulmonary IRAK-M expression in vivo and improves host defense during pneumococcal pneumonia.
J. Immunol.
PUBLISHED: 07-13-2009
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Triggering receptor expressed on myeloid cells-1 (TREM-1) is an amplifier of TLR-mediated inflammation during bacterial infections. Thus far, TREM-1 is primarily associated with unwanted signs of overwhelming inflammation, rendering it an attractive target for conditions such as sepsis. Respiratory tract infections are the leading cause of sepsis, but the biological role of TREM-1 therein is poorly understood. To determine the function of TREM-1 in pneumococcal pneumonia, we first established TREM-1 up-regulation in infected lungs and human plasma together with augmented alveolar macrophage responsiveness toward Streptococcus pneumoniae. Mice treated with an agonistic TREM-1 Ab and infected with S. pneumoniae exhibited an enhanced early induction of the inflammatory response that was indirectly associated with lower levels of negative regulators of TLR signaling in lung tissue in vivo. Later in infection, TREM-1 engagement altered S. pneumoniae-induced IRAK-M (IL-1R-associated kinase-M) kinetics so as to promote the resolution of pneumonia and remarkably led to an accelerated elimination of bacteria and consequently improved survival. These data show that TREM-1 exerts a protective role in the innate immune response to a common bacterial infection and suggest that caution should be exerted in modulating TREM-1 activity during certain clinically relevant bacterial infections.
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EGFR/KRAS/BRAF mutations in primary lung adenocarcinomas and corresponding locoregional lymph node metastases.
Clin. Cancer Res.
PUBLISHED: 07-07-2009
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The epidermal growth factor receptor (EGFR) and its downstream factors KRAS and BRAF are mutated with different frequencies in non-small cell lung cancer and mutations predict clinical response to EGFR inhibitors. The present study compared the mutational status of EGFR, KRAS, and BRAF in primary tumors with the one in corresponding lymph node metastases.
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Contribution of copy number variation in the regulation of complement activation locus to development of age-related macular degeneration.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 06-24-2009
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To develop an assay for determining the number of copies of the genes encoding complement factor H related 3 (CFHR3) and 1 (CFHR1) and determine the contribution of copy number variation (CNV) at CFHR3 and CFHR1 to the development of age-related macular degeneration (AMD).
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Simultaneous blockade of the epidermal growth factor receptor/mammalian target of rapamycin pathway by epidermal growth factor receptor inhibitors and rapamycin results in reduced cell growth and survival in biliary tract cancer cells.
Mol. Cancer Ther.
PUBLISHED: 06-09-2009
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The prognosis of patients with biliary tract adenocarcinomas (BTA) is still poor due to lack of effective systemic treatment options. Knowledge of the molecular mechanisms involved in the pathogenesis of this disease is of importance for the development of new treatment strategies. We determined the expression of epidermal growth factor receptor (EGFR) and activated mammalian target of rapamycin (p-mTOR) in paraffin-embedded surgical specimens of BTA (n = 89) by immunohistochemistry. Overall survival was analyzed with Cox models adjusted for clinical and pathologic factors. Combined EGFR/p-mTOR expression was significantly associated with relapse-free survival [adjusted hazard ratio for relapse, 2.20; 95% confidence interval (95% CI), 1.45-3.33; P < 0.001] and overall survival (adjusted hazard ratio for death, 2.32; 95% CI, 1.50-3.58; P < 0.001) of the patients. The effect of the EGFR inhibitors erlotinib or cetuximab and the mTOR inhibitor rapamycin on growth and survival of five BTA cell lines was tested in short-term 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays and long-term colony formation assays. Simultaneous blockade of EGFR and mTOR in biliary tract cancer cell lines results in a synergistic inhibition of both phosphatidylinositol-3-kinase and mitogen-activated protein kinase pathways, leading to reduced cell growth and survival. These results suggest that combined targeted therapy with EGFR and mTOR inhibitors may potentially benefit patients with BTAs and should be further evaluated in clinical trials.
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Antecedents and consequences of social identity complexity: intergroup contact, distinctiveness threat, and outgroup attitudes.
Pers Soc Psychol Bull
PUBLISHED: 06-08-2009
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Social identity complexity defines peoples more or less complex cognitive representations of the interrelationships among their multiple ingroup identities. Being high in complexity is contingent on situational, cognitive, or motivational factors, and has positive consequences for intergroup relations. Two survey studies conducted in Northern Ireland examined the extent to which intergroup contact and distinctiveness threat act as antecedents, and outgroup attitudes as consequences, of social identity complexity. In both studies, contact was positively, and distinctiveness threat negatively, associated with complex multiple ingroup perceptions, whereas respondents with more complex identity structures also reported more favorable outgroup attitudes. Social identity complexity also mediated the effects of contact and distinctiveness threat on attitudes. This research highlights that the extent to which individuals perceive their multiple ingroups in more or less complex and differentiated ways is of central importance to understanding intergroup phenomena.
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Daytime levels of melatonin in patients with age-related macular degeneration.
Acta Ophthalmol
PUBLISHED: 05-05-2009
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Melatonin (N-acetyl-5-methoxytryptamine) (MT) is a hormone that acts as an antioxidant. It is produced by the pineal gland and within the retina; its release is blocked by light entering the eye. We examined whether MT daytime levels differ between pseudophakic patients with age-related macular degeneration (ARMD) and pseudophakic subjects without any ocular pathology of the same age.
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Correlation of different circulating endothelial progenitor cells to stages of diabetic retinopathy: first in vivo data.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 01-17-2009
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To investigate vasculogenic circulating progenitor cells (CPCs), endothelial progenitor cells (EPCs), and mature EPCs in patients with type 1 diabetes mellitus (T1DM) with or without diabetic retinopathy (DR).
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Synergistic effects of erlotinib and everolimus on bronchial carcinoids and large-cell neuroendocrine carcinomas with activated EGFR/AKT/mTOR pathway.
Neuroendocrinology
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Epidermal growth factor receptor (EGFR) and mammalian target of rapamycin (mTOR) are crucial targets in cancer therapy. Combined inhibition of both targets yielded synergistic effects in vitro and in vivo in several cancer entities. However, the impact of EGFR and mTOR expression and combined inhibition in neuroendocrine lung tumors other than small-cell lung cancer remains unclear.
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The major vault protein mediates resistance to epidermal growth factor receptor inhibition in human hepatoma cells.
Cancer Lett.
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To better understand the response of HCC to EGFR inhibition, we analyzed factors connected to the resistance of HCC cells against gefitinib. Sensitive HCC3 cells co-expressed EGFR and ErbB3 but lacked kinase-domain mutations in EGFR. Interestingly, expression of MVP was restricted to resistant cell lines, whereas ABCB1 and ABCC1 showed no association with gefitinib resistance. Moreover, ectopic MVP expression in HCC3 cells decreased gefitinib sensitivity, increased AKT phosphorylation and reduced the expression of inflammatory pathway-associated genes, whereas silencing of MVP in Hep3B and HepG2 cells increased sensitivity. These findings suggest MVP as a novel player in resistance against EGFR inhibition.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.