[Precision medicine : at the crossroad of molecular biology, information sciences and humanities].

Precision medicine aims to tailor prevention and treatment to individual data. Although different markers can be used (e.g.

Exosomal lipids impact notch signaling and induce death of human pancreatic tumoral SOJ-6 cells.

Exosomes are of increasing interest as alternative mode of cell-to-cell communication. We previously reported that exosomes secreted by human SOJ-6 pancreatic tumor cells induce (glyco)protein ligand-independent cell death and inhibit Notch-1 pathway, this latter being particularly active during carcinogenesis and in cancer stem cells. Therefore, we asked whether exosomal lipids were key-elements for cell death and hypothesized that cholesterol-rich membrane microdomains were privileged sites of exosome interactions with tumor cells.

IRF6 is a mediator of Notch pro-differentiation and tumour suppressive function in keratinocytes.

While the pro-differentiation and tumour suppressive functions of Notch signalling in keratinocytes are well established, the underlying mechanisms remain poorly understood. We report here that interferon regulatory factor 6 (IRF6), an IRF family member with an essential role in epidermal development, is induced in differentiation through a Notch-dependent mechanism and is a primary Notch target in keratinocytes and keratinocyte-derived SCC cells. Increased IRF6 expression contributes to the impact of Notch activation on growth/differentiation-related genes, while it is not required for induction of 'canonical' Notch targets like p21(WAF1/Cip1), Hes1 and Hey1.

Targeting Notch signaling in pancreatic cancer.

Importance Of The Field: With some 220,000 new cases/year in the world, pancreatic adenocarcinoma is the fourth highest cause of death by cancers. Among newly diagnosed patients about 210,000 will die within 9 months following diagnosis. Therefore, effective adjuncts to current treatment strategies are necessary.

Resveratrol increases iodide trapping in the rat thyroid cell line FRTL-5.

Background: Resveratrol, a polyphenol found in grapes, exhibits several beneficial health effects by its antioxidant, antiinflammatory, and chemopreventive properties. The aim of the present study was to determine the effect of resveratrol on iodide trapping and efflux as well as its mode of action using FRTL-5 cells, having in mind the pivotal role of the natrium iodide symporter (NIS) in the treatment of differentiated thyroid cancers.

Methods: Cells were treated with resveratrol for various times and doses, in the presence or absence of thyrotropin (TSH).

Protective effect of resveratrol against LPS-induced extracellular lipoperoxidation in AR42J cells partly via a Myd88-dependent signaling pathway.

Lipopolysaccharides (LPS) are major components of the cell wall of Gram negative bacteria implicated in the pathogenesis of bacterial infection. Resveratrol is a polyphenolic phytoalexin exhibiting antioxidant and anti-inflammatory properties. We investigated the protective effects of this natural compound on LPS-induced proinflammatory effect using non-myeloid AR42J pancreatic cells.

Essential role of Notch signaling in apoptosis of human pancreatic tumoral cells mediated by exosomal nanoparticles.

We previously reported that exosomal nanoparticles secreted by human pancreatic tumoral cell lines decrease tumoral cell proliferation through the mitochondria-dependent apoptotic pathway, because of activation of pro-apoptotic phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and of glucose synthase kinase-3beta (GSK-3beta). Interactions between exosomal nanoparticles and cells are thought to involve membrane lipid rafts. However, the underlying mechanism is unknown.

Cyclic AMP signaling as a mediator of vasculogenic mimicry in aggressive human melanoma cells in vitro.

Aggressive melanoma cells can engage in a process termed vasculogenic mimicry (VM) that reflects the ability of tumor cells to express a multipotent, stem cell-like phenotype. Melanoma cell plasticity contributes to the lack of efficient therapeutic strategies targeting metastatic tumors. This study reveals cyclic AMP as a mediator of VM in vitro.

Human tumor nanoparticles induce apoptosis of pancreatic cancer cells.

Exosomes are vesicles secreted by most hematopoietic cells on fusion of multivesicular endosomes with the plasma membrane. Many studies have reported that exosomes may also be released by tumor cells. Exosomes are believed to play an antitumor role through immune cells.

In vitro polyphenol effects on activity, expression and secretion of pancreatic bile salt-dependent lipase.

The relationship between cholesterol and atherosclerosis has gained wide credence and red wine polyphenols have been shown to have an anti-atherogenic activity. In the present in vitro studies, we have evaluated and compared the effects of resveratrol, an active compound of red wine, and of a whole red wine polyphenolic extract (RWE) on the pancreatic bile salt-dependent lipase (BSDL). BSDL is involved in the duodenal hydrolysis of lipid esters and in part of cholesteryl esters thus favoring the bioavailability of free cholesterol.