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Find video protocols related to scientific articles indexed in Pubmed.
HES6 drives a critical AR transcriptional programme to induce castration-resistant prostate cancer through activation of an E2F1-mediated cell cycle network.
EMBO Mol Med
PUBLISHED: 04-17-2014
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Castrate-resistant prostate cancer (CRPC) is poorly characterized and heterogeneous and while the androgen receptor (AR) is of singular importance, other factors such as c-Myc and the E2F family also play a role in later stage disease. HES6 is a transcription co-factor associated with stem cell characteristics in neural tissue. Here we show that HES6 is up-regulated in aggressive human prostate cancer and drives castration-resistant tumour growth in the absence of ligand binding by enhancing the transcriptional activity of the AR, which is preferentially directed to a regulatory network enriched for transcription factors such as E2F1. In the clinical setting, we have uncovered a HES6-associated signature that predicts poor outcome in prostate cancer, which can be pharmacologically targeted by inhibition of PLK1 with restoration of sensitivity to castration. We have therefore shown for the first time the critical role of HES6 in the development of CRPC and identified its potential in patient-specific therapeutic strategies.
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Extraocular sebaceous carcinoma mimicking benign sebaceous cyst.
BMJ Case Rep
PUBLISHED: 02-01-2013
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Extraocular sebaceous carcinoma (SC) is an exceptionally rare neoplasm and has been confused in the past with basal cell carcinoma showing sebaceous differentiation. However, in contrast to the latter tumour, SC can be an aggressive cancer. We describe the case of a 55-year-old man with a 3-year history of a 5 × 2 cm lesion on the posterior thoracic wall. It had increased in size during this period but was otherwise asymptomatic. There was no significant past medical history or lymphadenopathy. Nor was there a family history of malignancy. The lesion was totally excised. The histopathological report revealed SC. As this neoplasm may be associated with Muir-Torre syndrome, the patient was screened for underlying internal neoplasia. All haematological, biochemical and tumour markers, imaging and endoscopic examinations were normal. Since SC may appear before the development of internal malignancy, our patient was scheduled for follow-up visits every 3 months.
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Endogenous purification reveals GREB1 as a key estrogen receptor regulatory factor.
Cell Rep
PUBLISHED: 01-14-2013
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Estrogen receptor-? (ER) is the driving transcription factor in most breast cancers, and its associated proteins can influence drug response, but direct methods for identifying interacting proteins have been limited. We purified endogenous ER using an approach termed RIME (rapid immunoprecipitation mass spectrometry of endogenous proteins) and discovered the interactome under agonist- and antagonist-liganded conditions in breast cancer cells, revealing transcriptional networks in breast cancer. The most estrogen-enriched ER interactor is GREB1, a potential clinical biomarker with no known function. GREB1 is shown to be a chromatin-bound ER coactivator and is essential for ER-mediated transcription, because it stabilizes interactions between ER and additional cofactors. We show a GREB1-ER interaction in three xenograft tumors, and using a directed protein-protein approach, we find GREB1-ER interactions in half of ER(+) primary breast cancers. This finding is supported by histological expression of GREB1, which shows that GREB1 is expressed in half of ER(+) cancers, and predicts good clinical outcome. These findings reveal an unexpected role for GREB1 as an estrogen-specific ER cofactor that is expressed in drug-sensitive contexts.
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Oestrogen receptor-co-factor-chromatin specificity in the transcriptional regulation of breast cancer.
EMBO J.
PUBLISHED: 06-20-2011
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The complexity of oestrogen receptor ? (ER?)-mediated transcription is becoming apparent, but global insight into the co-regulatory proteins that assist ER? transcription is incomplete. Here, we present the most comprehensive chromatin-binding landscape of ER? co-regulatory proteins to date. We map by ChIP-seq the essential p160 co-regulators (SRC1, SRC2 and SRC3), and the histone acetyl transferases p300 and CBP in MCF-7 breast cancer cells. We find a complex network of co-regulator binding, with preferential binding sites for each co-regulator. Unlike previous suggestions, we find SRC recruitment almost exclusively following ligand treatment. Interestingly, we find specific subsets of genes regulated by ligand-dependent and -independent co-regulator recruitment. Co-factor-binding profiles were integrated with expression data from cell lines and primary tumour cohorts, to reveal specific transcriptional networks that influence clinical outcome. Genes that are bound by SRC3, but not other p160 proteins, have predictive value in cohorts of breast cancer patients. By generating a robust and global view of co-factor-binding properties, we discover new levels of co-regulator complexity, but also reveal specific gene networks that may influence endocrine response.
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Estrogen receptor-positive breast cancer: a multidisciplinary challenge.
Wiley Interdiscip Rev Syst Biol Med
PUBLISHED: 02-10-2011
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Estrogen receptor (ER)-positive breast cancer research is an ideal example of how systems biology can be applied to better understand a specific clinical issue. By integrating vast data sets from tumor-derived expression arrays, genome-wide transcription factor/chromatin interactions, proteomics and computational analyses, we may better understand the concept of breast cancer development, heterogeneity, and its treatment. Resistance to endocrine treatment, such as anti-estrogens, often occurs and systems biology may prove to be a valuable asset in tailoring treatment for each patient. In such a multidisciplinary setup, it is essential to try and connect these massive data streams with the known pathological background and cell biology. In this review, we describe the current status of such studies and the challenges that are to be met in order to fully understand the concept of anti-estrogen resistance from a holistic perspective.
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Estrogen receptor action in three dimensions - looping the loop.
Breast Cancer Res.
PUBLISHED: 02-08-2010
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Due to advances in genomic technologies, our understanding of estrogen receptor (ER)-mediated transcription in breast cancer cells has evolved significantly in recent years. Genome-wide mapping experiments revealed thousands of ER-binding events, but linking them to the target genes has been an ongoing struggle. A recent paper describes a new technique, called ChIA-PET (chromatin interaction analysis using paired-end tag sequencing), that can directly address these questions. ChIA-PET is an unbiased approach for simultaneously identifying all genome-wide binding events of a transcription factor and those involved in long-range chromatin loops.
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Relation of heart rate variability to serum levels of C-reactive protein, interleukin 6, and 10 in patients with sepsis and septic shock.
J Crit Care
PUBLISHED: 02-12-2009
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The aim of the study was to investigate possible associations between different heart rate variability (HRV) indices and various biomarkers of inflammation in 45 septic patients.
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GATA3 acts upstream of FOXA1 in mediating ESR1 binding by shaping enhancer accessibility.
Genome Res.
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Estrogen receptor (ESR1) drives growth in the majority of human breast cancers by binding to regulatory elements and inducing transcription events that promote tumor growth. Differences in enhancer occupancy by ESR1 contribute to the diverse expression profiles and clinical outcome observed in breast cancer patients. GATA3 is an ESR1-cooperating transcription factor mutated in breast tumors; however, its genomic properties are not fully defined. In order to investigate the composition of enhancers involved in estrogen-induced transcription and the potential role of GATA3, we performed extensive ChIP-sequencing in unstimulated breast cancer cells and following estrogen treatment. We find that GATA3 is pivotal in mediating enhancer accessibility at regulatory regions involved in ESR1-mediated transcription. GATA3 silencing resulted in a global redistribution of cofactors and active histone marks prior to estrogen stimulation. These global genomic changes altered the ESR1-binding profile that subsequently occurred following estrogen, with events exhibiting both loss and gain in binding affinity, implying a GATA3-mediated redistribution of ESR1 binding. The GATA3-mediated redistributed ESR1 profile correlated with changes in gene expression, suggestive of its functionality. Chromatin loops at the TFF locus involving ESR1-bound enhancers occurred independently of ESR1 when GATA3 was silenced, indicating that GATA3, when present on the chromatin, may serve as a licensing factor for estrogen-ESR1-mediated interactions between cis-regulatory elements. Together, these experiments suggest that GATA3 directly impacts ESR1 enhancer accessibility, and may potentially explain the contribution of mutant-GATA3 in the heterogeneity of ESR1+ breast cancer.
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Procalcitonin and procalcitonin kinetics for diagnosis and prognosis of intravascular catheter-related bloodstream infections in selected critically ill patients: a prospective observational study.
BMC Infect. Dis.
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Procalcitonin (PCT) has emerged as a valuable marker of sepsis. The potential role of PCT in diagnosis and therapy monitoring of intravascular catheter-related bloodstream infections (CRBSI) in intensive care unit (ICU) is still unclear and was evaluated.
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Traumatic asphyxia due to blunt chest trauma: a case report and literature review.
J Med Case Rep
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Crush asphyxia is different from positional asphyxia, as respiratory compromise in the latter is caused by splinting of the chest and/or diaphragm, thus preventing normal chest expansion. There are only a few cases or small case series of crush asphyxia in the literature, reporting usually poor outcomes.
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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.

How does it work?

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

Video X seems to be unrelated to Abstract Y...

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.