Search results for "otc"

Abstract PR10: Inhibition of deacetylase SIRT1 offers a novel treatment option in metastatic Ewing sarcoma

2014

Abstract Metastasis is the major cause of disease-related death in Ewing sarcoma. Patients, who present with clinically overt disseminated disease at diagnosis and those who relapse early with distant metastases have a poor outcome despite multi-modal high-dose chemotherapy. Therefore, new treatment options are highly warranted. Ewing sarcoma pathogenesis is driven by the chimeric ETS oncogene EWS-FLI1. We here describe regulation of sirtuin SIRT1 by EWS-FLI1 and its role in metastasis. SIRT1 belongs to a family of NAD+-dependent group III deacetylases that target histone and non-histone proteins in response to metabolic stress resulting in widespread gene expression changes through epigene…

2015

Notch receptors play an essential role in the regulation of central cellular processes during embryonic and postnatal development. The mammalian genome encodes for four Notch paralogs (Notch 1-4), which are activated by three Delta-like (Dll1/3/4) and two Serrate-like (Jagged1/2) ligands. Further, non-canonical Notch ligands such as EGFL7 have been identified and serve mostly as antagonists of Notch signaling. The Notch pathway prevents neuronal differentiation in the central nervous system by driving neural stem cell maintenance and commitment of neural progenitor cells into the glial lineage. Notch is therefore often implicated in the development of brain tumors, as tumor cells share vari…

Abstract 1918: Gene characterization of lung-tumorspheres for their usage as an in vitro screening platform for testing new therapeutic strategies

2017

Abstract Background: Lung cancer features like treatment resistance or tumor relapse have been linked to cancer stem cells (CSCs), a population of cells with self-renewal properties, and the ability to grow forming tumorspheres in non-adherent conditions. The aim of this study was to isolate and characterize tumorspheres from lung cancer cell lines and tumor tissue from resectable non-small cell lung cancer (NSCLC) patients and to use them as an in vitro platform for drug screening. Methods: This study was performed on cells from seven NSCLC tumor samples and five cell lines (H1650, H1993, H1395, A549 and PC9) grown in monolayer and as spheroids. The expression of 60 genes, including CSC-ma…

Masse cardiache e paracardiache

2010

Vascular niche factor PEDF modulates Notch-dependent stemness in the adult subependymal zone.

2009

We sought to address the fundamental question of how stem cell microenvironments can regulate self-renewal. We found that Notch was active in astroglia-like neural stem cells (NSCs), but not in transit-amplifying progenitors of the murine subependymal zone, and that the level of Notch transcriptional activity correlated with self-renewal and multipotency. Moreover, dividing NSCs appeared to balance renewal with commitment via controlled segregation of Notch activity, leading to biased expression of known (Hes1) and previously unknown (Egfr) Notch target genes in daughter cells. Pigment epithelium-derived factor (PEDF) enhanced Notch-dependent transcription in cells with low Notch signaling,…

The complex interplay between Notch signaling and Snail1 transcription factor in the regulation of epithelial–mesenchymal transition (EMT)

2015

Background The epithelial–mesenchymal transition (EMT) is a highly coordinated process observed during embryonic development and adult tissue repair. It is characterized by the loss of cell–cell adhesion and apicobasal polarity, and the transition to a cell type with a spindle-like phenotype able to migrate through the basal membranes. Methods This review article includes available date from peer-reviewed publications associated with the role of Notch signaling and Snail1 transcription factor in activation and regulation of EMT. Results Growing evidences in the past few years demonstrated a significant role of Notch in EMT activation. It is not surprising because this pathway is the nexus o…

Notch in T Cell Differentiation: All Things Considered.

2015

Differentiation of naive T cells into effector cells is required for optimal protection against different classes of microbial pathogen and for the development of immune memory. Recent findings have revealed important roles for the Notch signaling pathway in T cell differentiation into all known effector subsets, raising the question of how this pathway controls such diverse differentiation programs. Studies in preclinical models support the therapeutic potential of manipulating the Notch pathway to alleviate immune pathology, highlighting the importance of understanding the mechanisms through which Notch regulates T cell differentiation and function. We review these findings here, and outl…

Presenilin is the molecular target of acidic γ-secretase modulators in living cells.

2012

The intramembrane-cleaving protease γ-secretase catalyzes the last step in the generation of toxic amyloid-β (Aβ) peptides and is a principal therapeutic target in Alzheimer's disease. Both preclinical and clinical studies have demonstrated that inhibition of γ-secretase is associated with prohibitive side effects due to suppression of Notch processing and signaling. Potentially safer are γ-secretase modulators (GSMs), which are small molecules that selectively lower generation of the highly amyloidogenic Aβ42 peptides but spare Notch processing. GSMs with nanomolar potency and favorable pharmacological properties have been described, but the molecular mechanism of GSMs remains uncertain an…

P041 Differences in NOTCH signalling between stricturing and penetrating behaviour in Crohn’s disease

2019

Ovarian tissue cryopreservation and transplantation in menopause: new perspective of therapy in postmenopausal women and the importance of ethical an…

2023

Menopausal transition entails a progressive decrease in hormone production by the ovaries that lead to important physical and psychological changes that could significantly affect quality of life. Hormone replacement therapy (HRT) administered from the onset of menopausal symptoms usually improves quality of life and life expectancy. Nevertheless, it is not risk-free. Ovarian tissue cryopreservation (OTC) has been investigated as a potential new strategy for delaying menopause and/or to avoid HRT. This review analyzes the critical points of HRT to assess whether OTC and subsequent reimplantation can affect postmenopausal management. We assessed available randomized clinical trials in PubMed…