Novel synthetic pharmacophores inducing a stabilization of cellular microtubules.

Microtubule drugs have been widely used in cancer chemotherapies. Although microtubules are subject to regulation by signal transduction mechanisms, their pharmacological modulation has so far relied on compounds that bind to the tubulin subunit. Using a cell-based assay designed to probe the microtubule polymerization status, we identified two pharmacophores, CM09 and CM10, as cell-permeable microtubule stabilizing agents.

[Mechanisms of resistance to anti-BRAF treatments].

Context: In patients with melanoma positive for the BRAF V600 mutation, clinical response to specific BRAF inhibitors is usually rapid and striking, with significant benefits in terms of progression-free survival and overall survival. However, resistance to treatment almost invariably arises, typically within a median timeframe of 6 months. Indeed, very few patients exhibit long-lasting response to these targeted therapies.

Cell cycle disruption and apoptosis as mechanisms of toxicity of organochlorines in Zea mays roots.

Organochlorine pesticides (OCPs) are widespread environmental pollutants; two of them are highly persistent: lindane (γHCH) and chlordecone (CLD). Maize plants cope with high levels of OCP-environmental pollution, however little is known about cellular mechanisms involved in plant response to such OCP-exposures. This research was aimed at understanding the physiological pathways involved in the plant response to OCPs in function of a gradient of exposure.

Protease inhibitor-based triple therapy in chronic hepatitis C: guidelines by the French Association for the Study of the Liver.

The recent marketing authorizations and hence availability of the new protease inhibitors, telaprevir and boceprevir, have profoundly changed the management of chronic hepatitis C patients. Guidelines for the use of these new drugs as part of a triple therapy, in combination with the standard therapy of peginterferon plus ribavirin, are proposed. The guidelines have been drawn up and evaluated by a meeting of the French Association for the Study of the Liver, posted online for comments, and extensively reviewed by international experts.

Smoking and asthma: disentangling their mutual influences using a longitudinal approach.

Background: The association between smoking and asthma remains unclear and has mostly been assessed in cross-sectional studies, with potential selection bias ("healthy smoker effect").

Aims: Using a longitudinal approach, the aims were to assess whether 1) childhood asthma modifies smoking initiation, 2) active smoking influences asthma incidence in adults and 3) active smoking among subjects with asthma influences the persistence of the disease or the 12-year evolution in lung function in children and adults.

Methods: Subjects (513 children and 1190 adults) were recruited and followed-up for 12 years in the context of the EGEA study (Epidemiological study on the Genetics and Environment of Asthma).

Identifying adult asthma phenotypes using a clustering approach.

There is a need to improve asthma characterisation by integrating multiple aspects of the disease. The aim of the present study was to identify distinct asthma phenotypes by applying latent class analysis (LCA), a model-based clustering method, to two large epidemiological studies. Adults with asthma who participated in the follow-up of the Epidemiological Study on the Genetics and Environment of Asthma (EGEA2) (n = 641) and the European Community Respiratory Health Survey (ECRHSII) (n = 1,895) were included.

[Hepatitis C, cirrhosis and hepatocellular carcinoma].

The screening for the detection of hepatocellular carcinoma is based on ultrasound sonography which should be realised in patients with post-hepatitis C cirrhosis with a delay between 3 and 6 months according to the most identified risk factors, in particular age and sex male. In the case of discovery of hypoechogen nodule < or = 1cm, a follow-up is mandatory because it is usually untypical by ultrasound sonography and to propose a liver biopsy in the case of an increasing in size is shown. The ultrasound guided cutting biopsy can precise the histological characteristics of the nodule, the grade, and indicate prognostic factors.

[The patient with uncontrolled chronic hepatitis B].

The treatment of chronic hepatitis B is now based on the using of pegylated interferon or nucleoside or nucleotide analogs. In the majority of cases, these drugs can control viral replication with an hepatitis B virus (HBV) DNA negativation after approximately 6 months of therapy. In case of primary non response, it is necessary to modify antiviral therapy and if resistance appears to combine a nucleoside and a nucleotide analog.

BMP2 and BMP7 play antagonistic roles in feather induction.

Feathers, like hairs, first appear as primordia consisting of an epidermal placode associated with a dermal condensation that is necessary for the continuation of their differentiation. Previously, the BMPs have been proposed to inhibit skin appendage formation. We show that the function of specific BMPs during feather development is more complex.

[Secretome: definitions and biomedical interest].

Introduction: The secretome, or secretomics refers to the global study of proteins that are secreted by a cell, a tissue or an organism.

Exegesis: The secretome is an important class of proteins that control many biological and physiological processes. Many secretion pathways are implicated in the release of these proteins.