Search results for "type"
showing 10 items of 10618 documents
11q Deletion or ALK Activity Curbs DLG2 Expression to Maintain an Undifferentiated State in Neuroblastoma
2020
High-risk 11q deleted neuroblastomas typically display undifferentiated/poorly differentiated morphology. Neuroblastoma is thought to develop from Schwann cell precursors and undifferentiated neural crest (NC) derived cells. It is therefore vital to understand mechanisms involved in the block of differentiation. We identify an important role for oncogenic ALK-ERK1/2-SP1 signaling in maintenance of undifferentiated NC-derived progenitors via repression of DLG2, a tumor suppressor in neuroblastoma. DLG2 is expressed in the ‘bridge signature’ that represents the transcriptional transition state when neural crest cells or Schwann Cell Precursors become chromaffin cells of the adrenal gland. We …
Topoisomerase 1 inhibition suppresses inflammatory genes and protects from death by inflammation
2015
Unwinding DNA and unleasing inflammation Fighting infections often comes with collateral damage, which sometimes can be deadly. For instance, in septic shock, the overwhelming release of inflammatory mediators drives multi-organ failure. Rialdi et al. now report a potential new therapeutic target for controlling excessive inflammation: the DNA unwinding enzyme topoisomerase I (Top1) (see the Perspective by Pope and Medzhitov). Upon infection, Top1 specifically localizes to the promoters of pathogen-induced genes and promotes their transcription by helping to recruit RNA polymerase II. Pharmacological inhibition of Top1 in a therapeutic setting increased survival in several mouse models of s…
Over-expression of CsGSTU promotes tolerance to the herbicide alachlor and resistance to Pseudomonas syringae pv. tabaci in transgenic tobacco
2017
Glutathione transferases (GSTs) mainly catalyze the nucleophilic addition of glutathione to a large variety of hydrophobic molecules participating to the vacuole compartmentalization of many toxic compounds. In this work, the putative tolerance of transgenic tobacco plants over-expressing CsGSTU genes towards the chloroacetanilide herbicide alachlor was investigated. Our results show that the treatment with 0.0075 mg cm-3 of alachlor strongly affects the growth of both wild type and transformed tobacco seedlings with the sole exception of the transgenic lines overexpressing CsGSTU2 isoform that are barely influenced by herbicide treatment. In order to correlate the in planta studies with en…
Co-chaperone Hsp70/Hsp90-organizing protein (Hop) is required for transposon silencing and Piwi-interacting RNA (piRNA) biogenesis
2017
Piwi-interacting RNAs (piRNAs) are 26–30-nucleotide germ line-specific small non-coding RNAs that have evolutionarily conserved function in mobile genetic element (transposons) silencing and maintenance of genome integrity. Drosophila Hsp70/90-organizing protein homolog (Hop), a co-chaperone, interacts with piRNA-binding protein Piwi and mediates silencing of phenotypic variations. However, it is not known whether Hop has a direct role in piRNA biogenesis and transposon silencing. Here, we show that knockdown of Hop in the germ line nurse cells (GLKD) of Drosophila ovaries leads to activation of transposons. Hop GLKD females can lay eggs at the same rate as wild-type counterparts, but the e…
Variances in the Level of COX-2 and iNOS in Different Grades of Endometrial Cancer.
2019
Background:Many experimental studies have demonstrated the importance of COX-2 in the tumor angiogenesis. Inducible iNOS is responsible for a high and stable level of nitric oxide and is expressed in response to pro-inflammatory factors.Objective:The aim of this study was to evaluate the expression of COX-2 and iNOS at the protein level and to assess their potential prognostic significance in patients with endometrial cancer.Methods:The study group consisted of 45 women with endometrial cancer divided according to the degree of histological differentiation i.e. G1, 17; G2, 15; G3, 13. The control group consisted of 15 women without neoplastic changes. The expression of studied proteins was …
Selective targeting of collagen IV in the cancer cell microenvironment reduces tumor burden
2018
Goodpasture antigen-binding protein (GPBP) is an exportable1 Ser/Thr kinase that induces collagen IV expansion and has been associated with chemoresistance following epithelial-to-mesenchymal transition (EMT). Here we demonstrate that cancer EMT phenotypes secrete GPBP (mesenchymal GPBP) which displays a predominant multimeric oligomerization and directs the formation of previously unrecognized mesh collagen IV networks (mesenchymal collagen IV). Yeast two-hybrid (YTH) system was used to identify a 260SHCIE264 motif critical for multimeric GPBP assembly which then facilitated design of a series of potential peptidomimetics. The compound 3-[4''-methoxy-3,2'-dimethyl-(1,1';4',1'')terphenyl-2'…
Cytomegalovirus vector expressing RAE-1γ induces enhanced anti-tumor capacity of murine CD8+ T cells
2017
Designing of CD8 T cell vaccines which would provide protection against tumors is still considered a great challenge in immunotherapy. Here we show a robust potential of a cytomegalovirus (CMV) vector expressing the NKG2D ligand RAE-1γ as CD8 T cell-based vaccine against malignant tumors. Immunization with the CMV vector expressing RAE-1γ delayed tumor growth or even provided complete protection against tumor challenge in both prophylactic and therapeutic settings. Moreover, a potent tumor control in mice vaccinated with this vector can be further enhanced by blocking the immune checkpoints TIGIT and PD-1. Expression of RAE-1γ by the CMV vector potentiated expansion of KLRG1+ CD8 T cells wi…
Disease-Specific and Common HLA and Non-HLA Genetic Markers in Susceptibility to Rheumatoid Arthritis, Type 1 Diabetes Mellitus and Multiple Sclerosis
2016
Autoimmune diseases cause numerous health and social problems throughout the world. The common spectrum of autoimmune diseases affect the majority of tissues within the body, including pancreatic beta cells in type 1 diabetes (T1DM), myelin surrounding nerve axons in Multiple sclerosis (MS) and synovial joint antigens in Rheumatoid Arthritis (RA). The diseases are likely caused by a complex interaction between multiple HLA- and non- HLA related genes and environmental factors. The well documented co-clustering of autoimmune diseases within families and individuals, together with apparent sharing of number risk genes between the diseases suggests at least some common mechanisms of autoimmune…
Dom34 Links Translation to Protein O-mannosylation.
2016
In eukaryotes, Dom34 upregulates translation by securing levels of activatable ribosomal subunits. We found that in the yeast Saccharomyces cerevisiae and the human fungal pathogen Candida albicans, Dom34 interacts genetically with Pmt1, a major isoform of protein O-mannosyltransferase. In C. albicans, lack of Dom34 exacerbated defective phenotypes of pmt1 mutants, while they were ameliorated by Dom34 overproduction that enhanced Pmt1 protein but not PMT1 transcript levels. Translational effects of Dom34 required the 5′-UTR of the PMT1 transcript, which bound recombinant Dom34 directly at a CA/AC-rich sequence and regulated in vitro translation. Polysomal profiling revealed that Dom34 stimu…
Characterisation of CDKL5 Transcript Isoforms in Human and Mouse.
2016
Mutations in the X-linked Cyclin-Dependent Kinase-Like 5 gene (CDKL5) cause early onset infantile spasms and subsequent severe developmental delay in affected children. Deleterious mutations have been reported to occur throughout the CDKL5 coding region. Several studies point to a complex CDKL5 gene structure in terms of exon usage and transcript expression. Improvements in molecular diagnosis and more extensive research into the neurobiology of CDKL5 and pathophysiology of CDKL5 disorders necessitate an updated analysis of the gene. In this study, we have analysed human and mouse CDKL5 transcript patterns both bioinformatically and experimentally. We have characterised the predominant brai…