Amino acid-nucleotide-lipids: effect of amino acid on the self-assembly properties.

Hybrid amphiphiles composed of a lipid covalently linked to biomolecules are attracting considerable attention, owing to their unique physicochemical and biological properties. Herein, we have synthesized novel amino acid-nucleotide-lipids (ANLs), presenting phenylalanine and thymidine residues and saturated or unsaturated diacyl glycerol lipid moieties to investigate the effect of the specific aminoacid moieties on both aggregation properties and interactions of ANLs with single strand polyA RNA. Physicochemical studies (DLS, cryo-TEM, and small angle X-ray scattering) indicate that phenylanaline amino acids inserted at the 5' position of the nucleotide-lipids stabilize multilamellar systems, whereas unilamellar vesicles are formed preferentially in the case of nucleotide-lipids (NLs).

mTOR inhibitors in advanced renal cell carcinomas: from biology to clinical practice.

To date, oral everolimus is indicated for the treatment of patients with advanced renal cell carcinoma, whose disease has progressed on or after treatment with vascular endothelial growth factor-targeted therapy, and intravenous temsirolimus for the first-line treatment of patients with poor prognosis metastatic renal cell carcinoma. However, some factors could guide the treatment choice aiming to individualize a treatment plan. Besides the crucial issue of treatment efficacy, other factors are to be considered such as disease status, histological subtype, extent of the disease, patient-specific factors, and agent-specific factors.

Design of synthetic autonomous VH domain libraries and structural analysis of a VH domain bound to vascular endothelial growth factor.

We compared the capacity of an autonomous heavy chain variable (VH) domain (VH-B1a) to support diversity within its antigen-binding site relative to the conventional antigen-binding fragment (Fab) from which it was derived. We find that VH-B1a can tolerate significant diversity within all three complementarity-determining regions (CDRs) and also within framework 3, and thus, VH-B1a and the Fab are similar in terms of the regions of the antigen-binding site that can tolerate diversity without compromising stability. We constructed libraries of synthetic VH domains and isolated binders with moderate affinity for vascular endothelial growth factor (VEGF) from a library in which only CDR3 was randomized.

[Attractiveness of France for international clinical trials in 2012: 6(th) survey assessed by Leem (French association of pharmaceutical companies)].

Since 2002, the Leem (French Association of Pharmaceutical Companies) has conducted a survey every two years to update the attractiveness of France for international clinical trials. Thirty companies (68% of the French market) have participated in this 6(th) survey which involved 79 countries, a greater number of Phases I/II, II and III studies (420 versus 352 in 2010), a relatively stable number of included patients (246,895 versus 249,704 in 2010) and a greater number of centers (32,965 versus 24,337 in 2010). The evolution of time-lines for the go-ahead by French Authorities is heterogeneous (shorter time-lines by the French National Agency of Drug and Health Products Safety [ANSM] but longer time-lines by Research Ethics Comittees [CPP]).

Genotoxic and mutagenic effects of lipid-coated CdSe/ZnS quantum dots.

We proposed to evaluate the genotoxicity and mutagenicity of a new quantum dots (QDs) nanoplatform (QDsN), consisting of CdSe/ZnS core-shell QDs encapsulated by a natural fusogenic lipid (1,2-di-oleoyl-sn-glycero-3-phosphocholine (DOPC)) and functionalized by a nucleolipid N-[5'-(2',3'-di-oleoyl) uridine]-N',N',N'-trimethylammoniumtosylate (DOTAU). This QDs nanoplatform may represent a new therapeutic tool for the diagnosis and treatment of human cancers. The genotoxic, mutagenic and clastogenic effects of QDsN were compared to those of cadmium chloride (CdCl(2)).

Duration of adjuvant trastuzumab treatment in routine practice.

Background: Trastuzumab is used for the adjuvant (postoperative) treatment of (HER2)-positive early breast cancer. The duration of treatment is set at one year. The goal of our study was to examine the effective duration of trastuzumab treatment in routine clinical practice.

Prevalence and management of gastroesophageal reflux disease in children and adolescents: a nationwide cross-sectional observational study.

Unlabelled: This cross-sectional observational study aimed to determine the nationwide prevalence of gastroesophageal reflux disease (GORD) in French children and adolescents. Four hundred four general practitioners and 180 paediatricians compiled a register of all children and adolescents (n = 10,394, aged 0 to 17 years, mean 3.8 ± 5.

[Risk factors of upper gastrointestinal complications in outpatients on antiplatelet therapy: description and management].

Objectives: Patients on antiplatelet therapy have a gastrointestinal bleeding risk. It is increased by risk factors. The frequency of those risk factors, the prevalence of upper digestive symptoms and their management in patients on antiplatelet agents is unknown.

Formation of supramolecular systems via directed Nucleoside-Lipid recognition.

We report the synthesis of a new series of Ketal Nucleoside Lipids (KNLs) featuring saturated hydrophobic double chains and either adenosine or uridine as nucleosides (KNL(A) and KNL(U), respectively). Physicochemical studies (differential scanning calorimetry, small angle X ray scattering, transmission electronic microscopy, atomic force microscopy, Langmuir isotherm, infrared spectroscopy) show that the KNLs form hydrogels below the main phase transition temperature (Tm), whereas fluid lamellar phases are obtained above T(m). Mixing complementary KNLs affords a new stable Combined Supramolecular Systems (CSSs) due to complementary A-U recognition.

Chemical details on nucleolipid supramolecular architecture: molecular modeling and physicochemical studies.

Nucleolipids are currently under investigation as vectors for oligonucleotides (ON) delivery thanks to their supramolecular organization properties and their ability to develop specific interactions (i.e., stacking and potential Watson and Crick hydrogen bonds) for lipoplexes formation.

Charge-reversal lipids, peptide-based lipids, and nucleoside-based lipids for gene delivery.

Twenty years after gene therapy was introduced in the clinic, advances in the technique continue to garner headlines as successes pique the interest of clinicians, researchers, and the public. Gene therapy's appeal stems from its potential to revolutionize modern medical therapeutics by offering solutions to myriad diseases through treatments tailored to a specific individual's genetic code. Both viral and non-viral vectors have been used in the clinic, but the low transfection efficiencies when non-viral vectors are used have lead to an increased focus on engineering new gene delivery vectors.

Unexpected bilayer formation in Langmuir films of nucleolipids.

Langmuir monolayers have been extensively investigated by various experimental techniques. These studies allowed an in-depth understanding of the molecular conformation in the layer, phase transitions, and the structure of the multilayer. As the monolayer is compressed and the surface pressure is increased beyond a critical value, usually occurring in the minimal closely packed molecular area, the monolayer fractures and/or folds, forming multilayers in a process referred to as collapse.

A thermosensitive low molecular weight hydrogel as scaffold for tissue engineering.

Hydrogels that are non-toxic, easy to use, cytocompatible, injectable and degradable are valuable biomaterials for tissue engineering and tissue repair. However, few compounds currently fulfil these requirements. In this study, we describe the biological properties of a new type of thermosensitive hydrogel based on low-molecular weight glycosyl-nucleosyl-fluorinated (GNF) compound.

Incidence, risk profile and morphological pattern of lower extremity venous thromboembolism after urological cancer surgery.

Purpose: We examined the incidence of asymptomatic and symptomatic lower extremity venous thromboembolism in patients who underwent urological surgery for cancer, and identified preoperative and operative risk factors predictive of the thromboembolism.

Materials And Methods: A cohort of 583 consecutive patients undergoing urological cancer surgery was prospectively assessed using complete lower limb ultrasound at postoperative day 7 from January 2005 to July 2009. In all patients heparin and mechanical thromboprophylaxis were prescribed until complete ambulation.

Glycosylated nucleoside lipid promotes the liposome internalization in stem cells.

We report new glycosyl-nucleoside-lipid based liposomes decorated with sugar moieties. The GNL-liposomes feature a suitable glycosylated surface for their internalization into ADSC stem cells.

Nucleoside-lipid-based nanoparticles for cisplatin delivery.

The use of delivery vehicles to selectively transport anticancer agents to tumors is very attractive to address both toxicity and efficacy issues. We report a novel approach based on hybrid nucleoside-lipids allowing the efficient encapsulation and delivery of cisplatin. We demonstrate that the nucleoside polar heads guide the self-assembly of the aggregates into highly loaded and stable nanoparticles.

Sleep disturbances associated with gastro-oesophageal reflux disease: prevalence and impact of treatment in French primary care patients.

Aim: To evaluate the prevalence of sleep disturbances in French patients with gastro-oesophageal reflux disease and the impact of gastro-oesophageal reflux disease treatment on sleep.

Methods: A registry was compiled of all gastro-oesophageal reflux disease patients seen during a 2-week period by 1983 French primary care physicians. Data from the first two patients with nocturnal gastro-oesophageal reflux disease symptoms and gastro-oesophageal reflux disease-related sleep disturbances seen by each physician were derived from physician questionnaires and medical records.

Hybrid lipid oligonucleotide conjugates: synthesis, self-assemblies and biomedical applications.

Hybrid lipid oligonucleotide conjugates are finding more and more biotechnological applications. This short critical review highlights their synthesis, supramolecular organization as well as their applications in the field of biotechnology (111 references).

New strategies for medical management of castration-resistant prostate cancer.

Although advanced prostate cancer patients respond very well to front-line androgen deprivation, failure to hormonal therapy most often occurs after a median time of 18-24 months. The care of castration-resistant prostate cancer (CRPC) has significantly evolved over the past decade, with the onset of first-line therapy with docetaxel. Although numerous therapy schedules have been investigated alongside docetaxel, in either first-line or salvage therapy, results were dismal.

Synthesis, characterization, and in vitro transfection activity of charge-reversal amphiphiles for DNA delivery.

A series of charge-reversal lipids were synthesized that possess varying chain lengths and end functionalities. These lipids were designed to bind and then release DNA based on a change in electrostatic interaction with DNA. Specifically, a cleavable ester linkage is located at the ends of the hydrocarbon chains.

Perspectives on gastroesophageal reflux disease in primary care: the REFLEX study of patient-physician agreement.

Background: Physicians may be unaware of the severity and extent of gastroesophageal reflux disease (GERD) in their patients. The aim of this study was to evaluate patient-physician agreement concerning proton pump inhibitor (PPI) treatment.

Methods: 1818 French primary-care physicians and 5174 adult patients with GERD who were taking PPIs answered questions regarding symptoms and treatment satisfaction.

Reduction-triggered delivery using nucleoside-lipid based carriers possessing a cleavable PEG coating.

A new non-ionic nucleoside based lipid (DOU-SS-PEG(2000), 5'-PEG(2000)-2',3'-dioleoyluridine) featuring uridine (U) as nucleoside and 2',3'-dioleyl (DO), as lipid moieties and a poly(ethylene glycol) (PEG) thiolytic cleavable spacer for in vitro delivery of drugs is described. The PEG detachable nucleotide lipid (DOU-SS-PEG(2000)) was prepared via a convergent synthesis starting from HS-PEG-OMe and uridine. The reduction-triggered delivery using the PEG detachable nucleoside lipid DOU-SS-PEG(2000) was evaluated on both liposomal and micellar objects.

Anderson localization of near-visible light in two dimensions.

We report on the observation of Anderson localization of near-visible light in two-dimensional systems. Our structures consist of planar waveguides in which disorder is introduced by randomly placing pores with controlled diameter and density. We show how to design structures in which localization can be observed and describe both the realization of the materials and the actual observation of Anderson localized modes by near-field scanning microscopy.

Role of quenching on superdiffusive transport in two-dimensional random media.

Transport in random media is known to be affected by quenched disorder. From the point of view of random walks, quenching induces correlations between steps that may alter the dynamical properties of the medium. This paper is intended to provide more insight into the role of quenched disorder on superdiffusive transport in two-dimensional random media.

Adjuvant chemotherapy in elderly patients with early breast cancer. Impact of age and comprehensive geriatric assessment on tumor board proposals.

Purpose Of The Study: Elderly breast cancer (EBC) patients are often denied adjuvant chemotherapy because of age. Breast cancer is among the most frequent cancer in Western Countries and recent data suggest that adjuvant chemotherapy could be active in selected elderly patients. We investigated the impact of age and comprehensive geriatric assessment (CGA) among other variables taken into account in tumor boards to recommend adjuvant chemotherapy in EBC patients.