Cell growth in aggregates determines gene expression, proliferation, survival, chemoresistance, and sensitivity to immune effectors in follicular lymphoma.

Lymphomas grow as dense aggregates in patients, but whether this spatial organization affects lymphoma cell biology is unknown. We grew follicular lymphoma (FL) cells in vitro as multicellular aggregates of lymphoma cells to investigate this question. Gene expression analysis revealed that 612 genes were differentially expressed when cells grew in multicellular aggregates of lymphoma cells rather than in suspension.

Encoding of mixtures in a simple olfactory system.

Natural odors are usually mixtures; yet, humans and animals can experience them as unitary percepts. Olfaction also enables stimulus categorization and generalization. We studied how these computations are performed with the responses of 168 locust antennal lobe projection neurons (PNs) to varying mixtures of two monomolecular odors, and of 174 PNs and 209 mushroom body Kenyon cells (KCs) to mixtures of up to eight monomolecular odors.

Water-mediated structuring of bone apatite.

It is well known that organic molecules from the vertebrate extracellular matrix of calcifying tissues are essential in structuring the apatite mineral. Here, we show that water also plays a structuring role. By using solid-state nuclear magnetic resonance, wide-angle X-ray scattering and cryogenic transmission electron microscopy to characterize the structure and organization of crystalline and biomimetic apatite nanoparticles as well as intact bone samples, we demonstrate that water orients apatite crystals through an amorphous calcium phosphate-like layer that coats the crystalline core of bone apatite.

Impact of bipolar electrodes contact on fractionation index measurement.

Signals such as Complex Fractionated Atrial Electrograms (CFAE) are tracked during ablation procedures to locate the arrhythmical substrate regions. Most of CFAE classification tools use fractionation indexes. However, recordings from intracardiac catheter depend on electrode contact quality.

Phase space reconstruction of an experimental model of cardiac field potential in normal and arrhythmic conditions.

Cardiac arrhythmias are one of the most important death causes in the world. Compared to the numerical models, the experimental ones provide a more realistic tool to study the mechanisms of cardiac arrhythmias. The in vitro culture of cardiac cells developed on the Multi-Electrodes Array (MEA) constitutes a suitable model in this context.

First immunochemotherapy outcomes in elderly patients with CLL: a retrospective analysis.

Background: To date, the majority of trials on chronic lymphocytic leukemia (CLL) focused on patients considerably younger than the median age of onset for CLL. As a result, no definitive treatment exists for elderly patients, especially less medically fit patients.

Objectives: The objectives of this study are to examine the impact of comorbidities on outcome as well as to compare three different therapeutic regimens in outcome efficacy.

SIRT4 represses peroxisome proliferator-activated receptor α activity to suppress hepatic fat oxidation.

Sirtuins are a family of protein deacetylases, deacylases, and ADP-ribosyltransferases that regulate life span, control the onset of numerous age-associated diseases, and mediate metabolic homeostasis. We have uncovered a novel role for the mitochondrial sirtuin SIRT4 in the regulation of hepatic lipid metabolism during changes in nutrient availability. We show that SIRT4 levels decrease in the liver during fasting and that SIRT4 null mice display increased expression of hepatic peroxisome proliferator-activated receptor α (PPARα) target genes associated with fatty acid catabolism.

Highly enantioselective aza-Diels-Alder reaction of 1-azadienes with enecarbamates catalyzed by chiral phosphoric acids.

On demand: A highly enantio- and diastereoselective synthesis of 6-amino- trisubstituted tetrahydropyridine compounds has been developed through the inverse-electron-demand aza-Diels-Alder reaction of N-aryl α,β-unsaturated ketimines with enecarbamates (E)-1. Chiral phosphoric acid catalysts achieve simultaneous activation of both the 1-azadiene and dienophile partners.

Insights from the use in clinical practice of eculizumab in adult patients with atypical hemolytic uremic syndrome affecting the native kidneys: an analysis of 19 cases.

Background: Atypical hemolytic uremic syndrome (aHUS) is a devastating form of renal thrombotic microangiopathy. Despite plasma exchange, the standard treatment of aHUS for decades, the renal prognosis for patients with aHUS has remained poor. We assessed the off-trial use of eculizumab in adult patients with aHUS affecting the native kidneys.

Recombinant human IL-15 trans-presentation by B leukemic cells from chronic lymphocytic leukemia induces autologous NK cell proliferation leading to improved anti-CD20 immunotherapy.

Recombinant human IL-15 (rhIL-15) is one of the most promising cytokines for antitumor immunotherapy. In physiology IL-15 trans-presentation by accessory cells leads to pleiotropic activities, including activation of immune cells, such as NK cells. NK cells are largely involved in Ab-dependent cellular cytotoxicity mediated by therapeutic mAbs, such as rituximab, in chronic lymphocytic leukemia (CLL).

The serine-threonine kinase p90RSK is a new target of enzastaurin in follicular lymphoma cells.

Background And Purpose: Follicular lymphoma is the second most common non-Hodgkin's lymphoma and, despite the introduction of rituximab for its treatment, this disease is still considered incurable. Besides genetic alterations involving Bcl-2, Bcl-6 or c-Myc, follicular lymphoma cells often display altered B-cell receptor signalling pathways including overactive PKC and PI3K/Akt systems.

Experimental Approach: The effect of enzastaurin, an inhibitor of PKC, was evaluated both in vitro on follicular lymphoma cell lines and in vivo on a xenograft murine model.

Attosecond pulse characterization.

In this work we propose a novel procedure for the characterization of attosecond pulses. The method relies on the conversion of the attosecond pulse into electron wave-packets through photoionization of atoms in the presence of a weak IR field. It allows for the unique determination of the spectral phase making up the pulses by accurately taking into account the atomic physics of the photoionization process.

Anti-tumor activity of obinutuzumab and rituximab in a follicular lymphoma 3D model.

Follicular lymphomas (FLs) account for 35-40% of all adult lymphomas. Treatment typically involves chemotherapy combined with the anti-CD20 monoclonal antibody (MAb) rituximab (RTX). The development of the type II anti-CD20 MAb obinutuzumab (GA101) aims to further improve treatment.

SIRT4 coordinates the balance between lipid synthesis and catabolism by repressing malonyl CoA decarboxylase.

Lipid metabolism is tightly controlled by the nutritional state of the organism. Nutrient-rich conditions increase lipogenesis, whereas nutrient deprivation promotes fat oxidation. In this study, we identify the mitochondrial sirtuin, SIRT4, as a regulator of lipid homeostasis.

HDAC6 and SIRT2 regulate the acetylation state and oncogenic activity of mutant K-RAS.

Unlabelled: Activating point mutations in K-RAS are extremely common in cancers of the lung, colon, and pancreas and are highly predictive of poor therapeutic response. One potential strategy for overcoming the deleterious effects of mutant K-RAS is to alter its posttranslational modification. Although therapies targeting farnesylation have been explored, and have ultimately failed, the therapeutic potential of targeting other modifications remains to be seen.

Mesenchymal stem cells as vectors for lung cancer therapy.

Despite recent advances in treatment, lung cancer accounts for one third of all cancer-related deaths, underlining the need of development of new therapies. Mesenchymal stem cells (MSCs) possess the ability to specifically home into tumours and their metastases. This property of MSCs could be exploited for the delivery of various anti-tumour agents directly into tumours.

[Anticancer drug adherence].

A large number of anticancer drugs have been introduced during the two last decades with significant impact for survival, making cancer a chronic disease in a growing number of indications. However, these drugs are costly, induce adverse effects and their efficacy frequently depends on the dose. For all these reasons, adherence in cancer therapy is critical for an optimal benefit-risk ratio.

Mapping the future for pulmonary fibrosis: report from the 17th International Colloquium on Lung and Airway Fibrosis.

Pulmonary fibrosis is the ultimate outcome of various interstitial lung diseases, many of which have a dismal prognosis. Pulmonary fibrosis, therefore, represents a critical unmet medical need. Progress in research over the past 30 years has been encouraging.

Pharmacological inhibition of macrophage migration inhibitory factor interferes with the proliferation and invasiveness of squamous carcinoma cells.

Recent clinical observations and experimental studies of our group indicate that macrophage migration inhibitory factor (MIF) may contribute to tumor progression in head and neck squamous cell carcinomas (HNSCC). The present study was undertaken to examine the effects of the irreversible MIF inhibitor 4-iodo-6-phenylpyrimidine (4-IPP) on proliferation and invasiveness of the squamous carcinoma cell line SCCVII. Cell counting, crystal violet assay and flow cytometry were used to analyze the effects of 4-IPP on SCCVII cell growth.

CIP4 controls CCL19-driven cell steering and chemotaxis in chronic lymphocytic leukemia.

Solid tumor dissemination relies on the reprogramming of molecular pathways controlling chemotaxis. Whether the motility of nonsolid tumors such as leukemia depends on the deregulated expression of molecules decoding chemotactic signals remains an open question. We identify here the membrane remodeling F-BAR adapter protein Cdc42-interacting protein 4 (CIP4) as a key regulator of chemotaxis in chronic lymphocytic leukemia (CLL).

Airway deposition of nebulized gene delivery nanocomplexes monitored by radioimaging agents.

Receptor-targeted nanocomplexes are nonviral vectors developed for gene delivery to the airway epithelium for the treatment of pulmonary disease associated with cystic fibrosis. The present study aimed to optimize the delivery of the nanocomplex by nebulization, and to monitor the in vivo deposition of radiolabeled vector in the airways of a large animal model by γ-camera scintigraphy. Large White weaner pigs were nebulized with nanocomplexes mixed with technetium-99m radiopharmaceuticals.

Clinical impact of the implantable loop recorder in patients with isolated syncope, bundle branch block and negative workup: a randomized multicentre prospective study.

Background: Few studies have compared conventional testing with prolonged monitoring using an implantable loop recorder (ILR) following the first syncope episode in patients with bundle branch block (BBB) and negative workup.

Objectives: To compare two syncope evaluation strategies-primary use of an ILR (Group 1) versus conventional testing (Group 2)-and to estimate the prevalence of significant arrhythmias in the ILR patient subset.

Methods: From January 2005 to December 2010, 78 patients admitted after one syncope episode were randomized to ILR (n=41) or conventional follow-up (n=37).