Posttranslational knockdown of a specific protein is an attractive approach for examining its function within a system. Here we introduce phospho-dependent proteolysis targeting chimeras (phosphoPROTACs), a method to couple the conditional degradation of targeted proteins to the activation state of particular kinase-signaling pathways. We generated two phosphoPROTACs that couple the ...

Molecular markers reliably predicting the aggressiveness of prostate cancer are currently lacking. Death-domain-associated protein (DAXX) has been implicated in the regulation of chromatin remodeling, transcription, and apoptosis that are integral to oncogenesis and cancer progression. DAXX expression was analyzed by immunohistochemistry on a tissue microarray containing 7478 prostate cancer specimens. ...

It is well recognized that there is sex-dimorphic expression of mRNA and protein in the heart; however the underlying mechanism is poorly understood. Endothelial nitric oxide synthase (eNOS) is an important regulator of cardiac function, and the expression levels of eNOS differ between male and female hearts. The aim of ...

In mammals, the main component of the circadian system is the suprachiasmatic nucleus in the hypothalamus. However, circadian clocks are also present in most peripheral tissues, such as adipose tissue. The aim of the present study was to analyse the potential effects of resveratrol on changes induced by high-fat feeding ...

BACKGROUND: Emaciation, depression and lethargy were observed in two flocks of Chinese local breed and one flock of commercial layer chicken infected naturally from 2010 to 2011. The aims of this study were to diagnose.Methods and results: Gross observation showed that severe enlargement of liver, spleen and kidney, and hemorrhage ...

Drug addicts have severe disruptions in many physiological and behavioral rhythms, such as the sleep/wake cycle. Interestingly, amphetamine, a psychostimulant, is able to alter many circadian patterns, which are independent of the master biological clock located in the suprachiasmatic nucleus. To increase our understanding of the circadian regulation of amphetamine ...

Bladder cancer is one of the most prevalent cancers worldwide, but the treatment and management of this disease can be very successful if the disease is detected early. The development of molecular assays that could diagnose bladder cancer accurately, and at an early stage, would be a significant advance. Ideally, ...

BACKGROUND: The molecular basis of the clinical heterogeneity of prostate cancer (PCa) is not well understood. OBJECTIVE: The purpose of our study was to identify and characterize genes in a clinically relevant gene expression signature in a subgroup of primary PCa positive for transmembrane protease, serine 2 (TMPRSS2)-v-ets erythroblastosis virus ...

CD8+ T cells are key factors mediating hepatitis B virus (HBV) clearance. However, these cells are killed through HBV-induced apoptosis during the antigen-presenting period in HBV-induced chronic liver disease (CLD) patients. Interferon-inducible protein 6 (IFI6) delays type I interferon-induced apoptosis in cells. We hypothesized that single nucleotide polymorphisms (SNPs) in ...

ERK1/2 (extracellular-signal-regulated kinase 1/2) and their substrates RSKs (p90 ribosomal S6 kinases) phosphorylate different transcription factors, contributing differentially to transcriptomic profiles. In cardiomyocytes ERK1/2 are required for >70% of the transcriptomic response to endothelin-1. In the present study we investigated the role of RSKs in the transcriptomic responses to the ...

ABSTRACT: BACKGROUND: A number of studies have established that stochasticity in gene expression may play an important role in many biological phenomena. This therefore calls for further investigations to identify the molecular mechanisms at stake, in order to understand and manipulate cell-to-cell variability. In this work, we explored the role ...

Giuseppe Macciotta directed the Pediatric Clinic of Cagliari in Sardinia. He dedicated his work to the study of pathology present in Sardinia and the Mediteranean basin area, He identified a variant of the β thalassemia major (homozygote Cooley's disease). He defined this variant as subchronic erythroblastosis, referred to by many ...

ABSTRACT: BACKGROUND: Alzheimer's disease (AD) is intimately tied to amyloid-beta (Abeta) peptide. Extraneuronal brain plaques consisting primarily of Abeta aggregates are a hallmark of AD. Intraneuronal Abeta subunits are strongly implicated in disease progression. Protein sequence mutations of the Abeta precursor protein (APP) account for a small proportion of AD ...

Recent evidence shows that altered microRNA-9 (miR-9) expression is implicated in the progression of gastric cancer. However, the exact roles and underlying mechanisms of miR-9 in the proliferation, invasion and metastasis of gastric cancer still remain unknown. In this study, miR-9 was found to be down-regulated and inversely correlated with ...

Special attention has recently been drawn to the molecular network of different genes that are responsible for the development of erythroid cells. The aim of the present study was to establish in detail the immunophenotype of early erythroid cells and to compare the gene expression profile of freshly isolated early ...

Neuroblastoma is the most common extra cranial solid tumor in childhood and the most frequently diagnosed neoplasm during the infancy. MYCN amplification and overexpression occur in about 25% of total neuroblastoma cases and this percentage increases at 30% in advanced stage neuroblastoma. So far, MYCN expression profile is still one ...

The identification of reliable transcriptome biomarkers requires the simultaneous consideration of regulatory and target elements including microRNAs (miRNAs), transcription factors (TFs), and target genes. A novel approach that integrates multivariate survival analysis, feature selection, and regulatory network visualization was used to identify reliable biomarkers of ovarian cancer survival and recurrence. ...

Rhabdomyosarcoma (RMS) is the most common type of pediatric soft tissue sarcoma. The MET receptor has an important role in the biology of RMS, and its overexpression and hyperactivation correlate with the metastatic ability of RMS. Consequently, interfering with MET expression or functionality may constitute a sound strategy for reducing ...

ERG gene rearrangements are found in about one half of all prostate cancers. Functional analyses do not fully explain the selective pressure causing ERG rearrangement during the development of prostate cancer. To identify transcriptional changes in prostate cancer, including tumors with ERG gene rearrangements, we performed a meta-analysis on published ...

Proper expression and functioning of transcription factors (TFs) are essential for regulation of different traits and thus could be crucial for the development of complex diseases. Subjects with Down syndrome (DS) have a higher incidence of acute lymphoblastic leukemia (ALL) while solid tumors, like breast cancer (BC) and oral cancer ...

Molecular mechanisms associated with pathophysiological changes in ventricular remodelling due to myocardial infarction (MI) remain poorly understood. We analyzed changes in gene expression by microarray technology in porcine myocardial tissue at 1, 4, and 6 weeks post-MI.MI was induced by coronary artery ligation in 9 female pigs (30-40 kg). Animals ...

Recent evidence suggested that muscle degeneration might lead and/or contribute to neurodegeneration, thus it possibly play a key role in the etiopathogenesis and progression of amyotrophic lateral sclerosis (ALS). To test this hypothesis, this study attempted to categorize functionally relevant genes within the genome-wide expression profile of human ALS skeletal ...

During pregnancy, a Rhesus-negative (Rh-negative) woman may develop antibodies if her fetus is Rh-positive, which can cause fetal morbidity or mortality in following pregnancies, if untreated. To assess the effects of administering anti-D immunoglobulin (Ig) after spontaneous miscarriage in a Rh-negative woman, with no anti-D antibodies. We searched the Cochrane ...

ABSTRACT: BACKGROUND: It has recently emerged that common epithelial cancers such as breast cancers have fusion genes like those in leukaemias. In a representative breast cancer cell line, ZR-75-30, we searched for fusion genes, by analysing genome rearrangements. RESULTS: We first analysed rearrangements of the ZR-75-30 genome, to around 10kb ...

Recent evidence shows that v-ets erythroblastosis virus E26 oncogene homolog 1 (Ets1) is implicated in tumor development and progression. However, the clinical potentials and underlying mechanisms of Ets1 in gastric cancer progression and metastasis remain largely unknown. In this study, Ets1 immunostaining was identified in 56/84 (66.7%) gastric cancer tissues, ...

Thrombotic microangiopathy (TMA) in patients with sickle cell disease (SCD) is a rare complication. These patients manifest microangiopathic hemolytic anemia (MAHA) with laboratory evidence of hemolytic anemia, schistocytosis, and thrombocytopenia. This is the first report of the syndrome in a group of these patients. A retrospective chart analysis of 10 ...

BACKGROUND: We compared urinary prostate cancer antigen 3 (PCA3), transmembrane protease, serine 2 (TMPRSS2):v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG) gene fusion (T2:ERG), and the serum [-2]proprostate-specific antigen ([-2]proPSA)-based prostate health index (Phi) for predicting biopsy outcome.METHODS: Serum samples and first-catch urine samples were collected after digital rectal examination ...

Avian v-ets erythroblastosis virus E26 oncogene homolog (ERG) is highly sensitive and specific for endothelial neoplasms and specific for prostate carcinoma. We characterized a rabbit anti-ERG antibody as an immunohistochemical agent to detect ERG expression in various tumors using tissue microarrays with a wide array of epithelial and mesenchymal tumors. ...

Vascular calcification resembles bone formation and involves vascular smooth muscle cell (SMC) transition to an osteoblast-like phenotype to express Runx2, a master osteoblast transcription factor. One possible mechanism by which Runx2 protein expression is induced is downregulation of inhibitory microRNAs (miR). Human coronary artery SMCs (CASMCs) treated with bone morphogenetic ...

OBJECTIVE: To investigate gross and microscopic placental lesions associated with pre-eclampsia and to determine which lesions are most strongly linked to serious pregnancy complications. METHODS: A retrospective case-control study of 173 placentas from women with pre-eclampsia and 173 placentas from healthy normotensive women was conducted. RESULTS: The mean placental weight ...

The activation of the epidermal growth factor receptor (EGFR) kinase requires ligand binding to the extracellular domain (ECD). Previous reports demonstrate that the EGFR-ECD can be crystallized in two conformations - a tethered monomer or, in the presence of ligand, an untethered back-to-back dimer. We use Biosensor analysis to demonstrate ...

BACKGROUND: Prostate cancer antigen 3 (PCA3) and v-ets erythroblastosis virus E26 oncogene homolog (TMPRSS2-ERG) gene fusions are promising prostate cancer (PCa) specific biomarkers that can be measured in urine. OBJECTIVE: To evaluate the diagnostic and prognostic value of Progensa PCA3 and TMPRSS2-ERG gene fusions (as individual biomarkers and as a ...

ABSTRACT: BACKGROUND: Lysosomal storage disorders (LSD) are a rare cause of non immunological hydrops fetalis (NIHF) and congenital ascites. The reported incidence is about 1%. The incidence of idiopathic NIHF is estimated to be about 18%.Patients and methodsWe report four cases with transient hydrops fetalis resulting from LSD and performed ...

miR-199a-5p plays a critical role in controlling cardiomyocyte survival. However, its significance in endothelial cell biology remains ambiguous. Here, we report the first evidence that miR-199a-5p negatively regulates angiogenic responses by directly targeting v-ets erythroblastosis virus E26 oncogene homolog 1 (Ets-1). Induction of miR-199a-5p in human dermal microvascular endothelial cells ...

Hyperinsulinaemic hypoglycaemia (HH) is characterized by unregulated insulin secretion from pancreatic β-cells. Untreated hypoglycaemia in infants can lead to seizures, developmental delay, and subsequent permanent brain injury. Early identification and meticulous management of these patients is vital to prevent neurological insult. Mutations in eight different genes (ABCC8, KCNJ11, GLUD1, CGK, ...

Approximately half of prostate cancers (PCa) carry TMPRSS2-ERG translocations; however, the clinical impact of this genomic alteration remains enigmatic. Expression of v-ets erythroblastosis virus E26 oncogene like (avian) gene (ERG) promotes prostatic epithelial dysplasia in transgenic mice and acquisition of epithelial-to-mesenchymal transition (EMT) characteristics in human prostatic epithelial cells (PrECs). ...

Angiotensin II (Ang II) plays a major role in the pathogenesis of end-organ injury in hypertension via its diverse hemodynamic and nonhemodynamic effects. Erythroblastosis virus E26 oncogen homolog-1 (ETS-1) is an important transcription factor recently recognized as an important mediator of cell proliferation, inflammation, and fibrosis. In the present studies, ...

BACKGROUND: Most personalized cancer care strategies involving DNA sequencing are highly reliant on acquiring sufficient fresh or frozen tissue. It has been challenging to comprehensively evaluate the genome of advanced prostate cancer (PCa) because of limited access to metastatic tissue. OBJECTIVE: To demonstrate the feasibility of a novel next-generation sequencing ...

The Vectra platform (Caliper Life Sciences, Hopkinton, MA) is an advanced multispectral imaging system for biomarker quantitation in tissue microarray or intact tissue sections. This is the first study to validate its reliability for quantitating spatially overlapping biomarkers using chromogenic multiplexed immunohistochemistry on prostate tissue microarrays. Two tissue microarray cohorts ...

Interleukin-17A (IL-17A) is the signature cytokine produced by Th17 CD4(+) T cells and has been tightly linked to autoimmune pathogenesis. In particular, the transcription factors NFAT and RORγt are known to activate Il17a transcription, although the detailed mechanism of action remains incompletely understood. Here, we show that the nuclear orphan ...

Approximately 50% of prostate cancers are characterized by TMPRSS2 (transmembrane protease serine 2)-ERG (avian v-ets erythroblastosis virus E26 oncogene homolog) gene fusions resulting in an androgen-regulated overexpression of the transcription factor ERG. Some studies have suggested prognostic or predictive relevance of ERG status in prostate cancer. Such concepts could be ...

ABSTRACT: BACKGROUND: Therapy resistance remains one of the major challenges to improve the prognosis of patients with pancreatic cancer. Chemoresistant cells, which potentially also display cancer stem cell (CSC) characteristics, can be isolated using the side population (SP) technique. Our aim was to search for a SP in human pancreatic ...

Fusions of androgen-regulated genes and v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG) occur in approximately 50% of prostate cancers, encoding a truncated ERG product. In prostatectomy specimens, ERG rearrangements are greater than 99% specific for prostate cancer or high-grade prostatic intraepithelial neoplasia adjacent to ERG-rearranged prostate cancer by fluorescence ...

Unique insights for the reprograming of cell lineages have come from embryonic development in the ascidian Ciona, which is dependent upon the transcription factors Ci-ets1/2 and Ci-mesp to generate cardiac progenitors. We tested the idea that mammalian v-ets erythroblastosis virus E26 oncogene homolog 2 (ETS2) and mesoderm posterior (MESP) homolog ...

Over-expression of MDR1 confers multidrug resistance (MDR) in cancers and remains a major cause for the failure of chemotherapy. In the present study, we found that V-Ets erythroblastosis virus E26 oncogene homolog 2 (ETS2) could activate MDR1 transcription and P-glycoprotein (P-gp) expression in SGC7901 cells. Knockdown of ETS2 attenuated MDR1 ...

Whether the genomic rearrangement transmembrane protease, serine 2 (TMPRSS2):v-ets erythroblastosis virus E26 oncogene homolog (ERG) has prognostic value in prostate cancer is unclear. Among men with prostate cancer in the prospective Physicians' Health and Health Professionals Follow-Up Studies, we identified rearrangement status by immunohistochemical assessment of ERG protein expression. We ...

Androgens are essential for the development of the prostate and prostate cancer. We examined androgen-regulated gene expression in the human prostate. Samples from benign and malignant prostate tissue and samples containing prostate tissue obtained from prostate cancer patients three days after surgical castration were further processed as probes for a ...

CONTEXT: Despite widespread screening for prostate cancer (PCa) and major advances in the treatment of metastatic disease, PCa remains the second most common cause of cancer death for men in the Western world. In addition, the use of prostate-specific antigen testing has led to the diagnosis of many potentially indolent ...

To present intensive intrauterine treatment of recurrent early onset fetal erythroblastosis due to anti-M alloimmunization. A 33-year-old woman, gravid 3, para 1, had anti-M IgG antibody, which caused alloimmunization of her previous pregnancies. This time she visited our hospital for intensive intervention. No evidence of fetal hydrops was found during ...

Breast cancer is the most common malignancy, and it is also the major cause of cancer-related deaths of women worldwide. Breast cancer treatment involves surgery, chemotherapy, radiation therapy, or combination therapy, and novel strategies are needed to boost the oncologic outcome. The non-metabolizable glucose analogue, 2-deoxy-D-glucose (2-DG) which inhibits glucose ...