Intradermal tacrolimus prevent scar hypertrophy in a rabbit ear model: a clinical, histological and spectroscopical analysis.

Background: Keloids and hypertrophic scars (HSc) affect 4.5-16% of the population. Thus far, the different approaches of keloid treatment are not very efficient, with a 50% relapse rate and many ongoing researches are looking for simple, safe and more efficient therapeutic methods.

Blood and body fluid exposures among US medical students in Botswana.

Introduction: Medical students from resource-rich countries who rotate in resource-limited settings have little pre-departure experience performing procedures, and lack familiarity with local equipment. The risk of blood and body fluid exposures during such rotations is significant.

Aim: 1) Determine whether a simulation-based intervention reduced exposures among US medical students on a rotation in Botswana; 2) determine whether exposures were underreported; 3) describe exposures and provision of human immunodeficiency virus (HIV) post-exposure prophylaxis (PEP).

Electrostatic interactions between diffuse soft multi-layered (bio)particles: beyond Debye-Hückel approximation and Deryagin formulation.

We report a steady-state theory for the evaluation of electrostatic interactions between identical or dissimilar spherical soft multi-layered (bio)particles, e.g. microgels or microorganisms.

Photochemical internalization for pDNA transfection: evaluation of poly(d,l-lactide-co-glycolide) and poly(ethylenimine) nanoparticles.

The main objective of this study was to prepare two types of nanoparticles with poly(d,l-lactide-co-glycolide) (PLGA) and polyethylenimine (PEI) polymers. Plasmid DNA (pDNA) was adsorbed either on PLGA/PEI nanoparticles, or as PEI/DNA complex onto the surface of PLGA nanoparticles. Both types of nanoparticles were prepared by the double emulsion method.

Cellular response to cetuximab in PTEN-silenced head and neck squamous cell carcinoma cell line.

The implication of loss of PTEN expression in resistance to targeted therapy has already been described in many tumor types. The absence of response to anti-EGFR agents in PTEN-deficient tumors relies on persistent activation of signaling pathways downstream of pEGFR. To investigate the role of PTEN loss of expression in head and neck squamous cell carcinoma (HNSCC) response to cetuximab, we used siRNA in Cal 27 cells and then evaluated key signaling protein activation (pAKT and pERK 1/2) as well as cell viability and proliferation.

Quantification of functional selectivity at the human α(1A)-adrenoceptor.

Although G protein-coupled receptors are often categorized in terms of their primary coupling to a given type of Gα protein subunit, it is now well established that many show promiscuous coupling and activate multiple signaling pathways. Furthermore, some agonists selectively activate signaling pathways by promoting interaction between distinct receptor conformational states and particular Gα subunits or alternative signaling proteins. We have tested the capacity of agonists to stimulate Ca(2+) release, cAMP accumulation, and changes in extracellular acidification rate (ECAR) at the human α(1A)-adrenoceptor.

A computational tool for identifying minimotifs in protein-protein interactions and improving the accuracy of minimotif predictions.

Protein-protein interactions are important to understanding cell functions; however, our theoretical understanding is limited. There is a general discontinuity between the well-accepted physical and chemical forces that drive protein-protein interactions and the large collections of identified protein-protein interactions in various databases. Minimotifs are short functional peptide sequences that provide a basis to bridge this gap in knowledge.

Partitioning of minimotifs based on function with improved prediction accuracy.

Background: Minimotifs are short contiguous peptide sequences in proteins that are known to have a function in at least one other protein. One of the principal limitations in minimotif prediction is that false positives limit the usefulness of this approach. As a step toward resolving this problem we have built, implemented, and tested a new data-driven algorithm that reduces false-positive predictions.

Re-assessment of chronic radio-induced tissue damage in a rat hindlimb model.

Radiotherapy is successfully used to treat neoplastic lesions, but may adversely affect normal tissues within the irradiated volume. However, additional clinical and para-clinical data are required for a comprehensive understanding of the pathogenesis of this damage. We assessed a rat model using clinical records and medical imaging to gain a better understanding of irradiation-induced tissue damage.

The M3-muscarinic acetylcholine receptor stimulates glucose uptake in L6 skeletal muscle cells by a CaMKK-AMPK-dependent mechanism.

The role of muscarinic acetylcholine receptors (mAChRs) in regulating glucose uptake in L6 skeletal muscle cells was investigated. [(3)H]-2-Deoxyglucose uptake was increased in differentiated L6 cells by insulin, acetylcholine, oxotremorine-M and carbachol. mAChR-mediated glucose uptake was inhibited by the AMPK inhibitor Compound C.

Additional value of EGFR downstream signaling phosphoprotein expression to KRAS status for response to anti-EGFR antibodies in colorectal cancer.

KRAS mutations are a strong predictive marker of resistance to anti-epidermal growth factor receptor (EGFR) antibodies in advanced colorectal cancer (CRC) but only a subset of wild-type (WT) KRAS patients are responders, suggesting the existence of additional markers of resistance to this treatment. The activation of EGFR downstream signaling pathways may be one of these ones. In a series of 42 patients with advanced CRC treated with cetuximab/panitumumab, for whom KRAS status was previously determined, we retrospectively analyzed the intratumor expression of EGFR downstream signaling phosphoproteins of the RAS/MAPK and PI3K/AKT pathways (pERK1/2, pMEK1, pAKT, pP70S6K and pGSK3beta) using Bio-Plex phosphoprotein array.

[HBsAg screening during pregnancy in the French province Picardy].

Objective: Screening for maternal hepatitis B surface antigen (HBsAg) is mandatory in France since 1992, however, no evaluation is available. We studied the traceability of HBsAg screening and its prevalence in pregnant women in Picardy for year 2006.

Patients And Methods: Traceability of HBsAg screening was studied in a sample of 1198 hospital case files, which were randomized and stratified for all the 20 clinics of the region (22,114 deliveries), both public and private.

Optimization of a new non-viral vector for transfection: Eudragit nanoparticles for the delivery of a DNA plasmid.

The development of new vectors to deliver DNA into cells for therapy of cancers or genetic diseases has been a major area of research for many years. However, the clinical application of this technology requires the development of efficient, reliable and sterile vectors enabling the transfer of genes in vivo. Non viral, polymer or lipid-based vectors offer a new impetus to gene therapy because they are less toxic than viral vectors (no endogenous recombination, fewer immunological reactions, easy production and delivery of large-sized plasmid).

Validation of a phosphoprotein array assay for characterization of human tyrosine kinase receptor downstream signaling in breast cancer.

Background: Human epidermal growth factor receptor (HER) downstream signaling kinases have important effects on tumor response to anti-HER monoclonal antibodies and tyrosine kinase inhibitors. We validated an assay that uses phosphoprotein arrays for measurement of HER downstream signaling functionality in breast carcinomas.

Methods: Using the Bio-Plex(R) phosphoprotein array (BPA), we performed multiplex immunoanalysis to investigate the expression of phosphorylated epidermal growth factor receptor and phosphorylated HER downstream signaling proteins (phosphorylated protein kinase B, phosphorylated glycogen synthase kinase -3beta, phosphorylated P70 ribosomal protein S6 kinase, and phosphorylated extracellular signal regulated kinase 42/44) in 49 frozen specimens of ductal infiltrating breast carcinoma taken at diagnosis.

Rehabilitation of irradiated head and neck tissues by autologous fat transplantation.

Background: Treatment of head and neck cancers allows good carcinologic results but induces aesthetic and functional sequelae. Autologous fat transplants have been used to correct aesthetic defects since the past century and exhibit many of the qualities of the ideal filler. Results reported here stem from experiences from 2000, with abdominal fat grafting in 11 patients who were referred to the authors' center for aesthetic subcutaneous or submucous head and neck reconstruction after radiotherapy.

PTEN expression controls cellular response to cetuximab by mediating PI3K/AKT and RAS/RAF/MAPK downstream signaling in KRAS wild-type, hormone refractory prostate cancer cells.

Overexpression of epidermal growth factor receptor (EGFR) and mutation of pten tumor suppressor gene in human cancer cells leads to activated EGFR downstream signaling including PI3-kinase/AKT (PI3K/AKT) and/or mitogen-activated protein kinases (RAS/RAF/MAPK) and have been linked to resistance to anti-EGFR targeted therapies. Cetuximab is a chimeric IgG1 monoclonal antibody that binds the EGFR with high specificity and have been developed as promising therapeutic anticancer treatments in several solid tumors, including colorectal and head and neck squamous cell carcinomas. Cetuximab activity is related to PI3K/AKT and RAS/RAF/MAPK signaling pathways functionality and its activity has been shown to be higher in wild-type KRAS tumors.

P53 and PTEN expression contribute to the inhibition of EGFR downstream signaling pathway by cetuximab.

Cetuximab (Erbitux) is an anti-epidermal growth factor receptor (EGFR) monoclonal antibody whose activity is related to the inhibition of EGFR downstream signaling pathways. P53 and phosphatase and tensin homologue deleted on chromosome 10 (PTEN) have been reported to control the functionality of PI3K/AKT signaling. In this study we evaluated whether reintroducing P53 using non-viral gene transfer enhances PTEN-mediated inhibition of PI3K/AKT signaling by cetuximab in PC3 prostate adenocarcinoma cell line bearing p53 and pten mutations.

Damaged DNA binding protein 2 plays a role in breast cancer cell growth.

The Damaged DNA binding protein 2 (DDB2), is involved in nucleotide excision repair as well as in other biological processes in normal cells, including transcription and cell cycle regulation. Loss of DDB2 function may be related to tumor susceptibility. However, hypothesis of this study was that DDB2 could play a role in breast cancer cell growth, resulting in its well known interaction with the proliferative marker E2F1 in breast neoplasia.

[Translational research and Cancer Plan].

The French Cancer Plan 2003-2007 has made translational research central to its research programme, to ensure the care-research continuum and the quickest application possible for the most recent discoveries, for the patients' benefit. This is a new field of research, still little-known or ill-understood. A working group, composed of physicians and researchers from academic research and industrial research, sought to define translational research in cancerology and define the issues at stake in it.

[Molecular diagnosis and response prediction to anti-tyrosine kinase receptors in oncology].

Tyrosine kinase receptors are an important family of membrane receptors implicated in oncogenesis. Their activation triggers signaling cascades that activate cell growth, proliferation and controls cell death. Inhibiting these receptors leads to signaling impairments and favors antitumor activity.

Eradication of p53-mutated head and neck squamous cell carcinoma xenografts using nonviral p53 gene therapy and photochemical internalization.

Photochemical internalization (PCI) technology has been used for PEI-mediated p53 gene transfer in mice bearing head and neck squamous cell carcinoma (HNSCC) xenografts. Using luciferase as a reporter gene, PCI led to a 20-fold increase in transgene expression 48 h after transfection and sustained transgene expression for 7 days. Therefore, iterative p53 gene transfer was performed by means of a weekly single injection of PEIGlu4/p53 complexes alone or with PCI for 5 (group A) or 7 (group B) weeks.

Hepatitis C virus antibodies and other markers of blood-transfusion-transmitted infection in multi-transfused Cuban patients.

Background: HCV was initially identified in 1989 when it was found to be the primary causative agent of non-A, non-B hepatitis,a condition associated with high rates of progressive and end-stage liver disease, cirrhosis, and hepatocellular carcinoma. Since then, appreciation of the significant worldwide health impact of HCV infection has grown. HCV infection was identified as a public health problem in Cuba in the 1990s.

Topotecan can compensate for protracted radiation treatment time effects in high grade glioma xenografts.

Purpose: Several studies reported that prolongation of overall treatment time of fractionated radiotherapy reduces the chance of tumor control. In the present study, we hypothesize that combining topotecan with irradiation could compensate for this detrimental time effect on the radioresponse. Therefore, we investigated the efficiency of different schedules of topotecan (TPT), radiotherapy (RT) or concomitant combination TPT + RT.

All-optical switching in a nematic liquid crystal twist cell.

Continuous wave photorefractive-like all-optical switching was demonstrated using a twisted nematic liquid crystal cell composed of the liquid crystal 5CB (4-pentyl-4'-cyanobiphenyl) with polyvinyl alcohol (PVA) aligning layers. The nonlinear optical effect involved is due to optical control of surface charge on the polyvinyl alcohol alignment layer. The cell exhibits strong optical control of the Friedericksz transition by an argon ion laser.

Uncoupling of oxidative phosphorylation and Smac/DIABLO release are not sufficient to account for induction of apoptosis by sulindac sulfide in human colorectal cancer cells.

Non-steroidal anti-inflammatory drugs (NSAIDs) have shown chemopreventive properties in colorectal cancer, involving both cyclooxygenase (COX)-dependent and -independent mechanisms. Apart from their selectivity for COX isoenzymes, NSAIDs differ in their acidic character which supports ability to uncouple oxidative phosphorylation. To assess the possible contribution of uncoupling to their antineoplastic properties, we compared the effect of sulindac sulfide (SS), an acidic NSAID and NS-398, a non-acidic tricyclic, on mitochondrial function and apoptosis in colorectal cancer cell lines (HT29, Caco-2, HCT15 and HCT116).