The cyclin-dependent kinase PITSLRE/CDK11 is required for successful autophagy

(Macro)autophagy is a membrane-trafficking process that serves to sequester cellular constituents in organelles termed autophagosomes, which target their degradation in the lysosome. Autophagy operates at basal levels in all cells where it serves as a homeostatic mechanism to maintain cellular integrity. The levels and cargoes of autophagy can, however, change in response to a variety of stimuli, and perturbations in autophagy are known to be involved in the aetiology of various human diseases. Autophagy must therefore be tightly controlled. We report here that the Drosophila cyclin-dependent kinase PITSLRE is a modulator of autophagy. Loss of the human PITSLRE orthologue, CDK11, initially appears to induce autophagy, but at later time points CDK11 is critically required for autophagic flux and cargo digestion. Since PITSLRE/CDK11 regulates autophagy in both Drosophila and human cells, this kinase represents a novel phylogenetically conserved component of the autophagy machinery

Nitric oxide releasing-dendrimers: an overview

Platforms able to storage, release or scavenge NO in a controlled and specific manner is interesting for biological applications. Among the possible matrices for these purposes, dendrimers are excellent candidates for that. These molecules have been used as drug delivery systems and exhibit interesting properties, like the possibility to perform chemical modifications on dendrimers surface, the capacity of storage high concentrations of compounds of interest in the same molecule and the ability to improve the solubility and the biocompatibility of the compounds bonded to it. This review emphasizes the recent progress in the development and in the biological applications of different NO-releasing dendrimers and the nitric oxide release pathways in these compounds

Publisher Correction: On the issue of transparency and reproducibility in nanomedicine

Publisher Correction: On the issue of transparency and reproducibility in nanomedicin

Publisher Correction: On the issue of transparency and reproducibility in nanomedicine

Publisher Correction: On the issue of transparency and reproducibility in nanomedicin

Publisher Correction: On the issue of transparency and reproducibility in nanomedicine

© 2019, Springer Nature Limited. In the version of this Correspondence originally published, Christine Dufès was incorrectly written as Christine Dufés. This has been corrected in the online versions of the Correspondence

On the issue of transparency and reproducibility in nanomedicine.

Following our call to join in the discussion over the suitability of implementing a reporting checklist for bio-nano papers, the community responds

Targeted nonviral gene therapy in prostate cancer

Najla Altwaijry, Sukrut Somani, Christine Dufès Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK Abstract: Prostate cancer is the second-most widespread cancer in men worldwide. Treatment choices are limited to prostatectomy, hormonal therapy, and radiotherapy, which commonly have deleterious side effects and vary in their efficacy, depending on the stage of the disease. Among novel experimental strategies, gene therapy holds great promise for the treatment of prostate cancer. However, its use is currently limited by the lack of delivery systems able to selectively deliver the therapeutic genes to the tumors after intravenous administration without major drawbacks. To remediate this problem, a wide range of nonviral delivery approaches have been developed to specifically deliver DNA-based therapeutic agents to their site of action. This review provides an overview of the various nonviral delivery strategies and gene therapy concepts used to deliver therapeutic DNA to prostate cancer cells, and focuses on recent therapeutic advances made so far. Keywords: prostate cancer therapy, gene delivery, tumor targeting, nanomedicin

Improving dissolution properties of griseofulvin using solid dispersion systems with Solutol HS15 and Acconon CO-7.

Tocotrienol, an extract of vitamin E, has been shown to exert antiproliferative and tumour suppressive effects on cancer cells.However, its therapeutic potential is currently limited by its failure to reach tumours after intravenous administration, without secondary effects on normal tissues. The objectives of this study are to prepare and characterise novel transferrin-targeted vesicles encapsulating tocotrienol, able to recognise transferrin receptors overexpressed on many cancer cell lines and to evaluate in vitro and in vivo the therapeutic and targeting efficacies of this therapeutic system

Enhanced gene expression in tumors after intravenous administration of arginine-, lysine- and leucine-bearing polypropylenimine polyplex

The possibility of using non-viral gene delivery systems for the treatment of cancer is currently limited by their lower transfection efficacy compared to viral systems. On the basis that amino acids such as arginine, lysine and leucine were involved in enhancing DNA transportation into cells, we hypothesized that the grafting of these amino acids to the highly promising generation 3 diaminobutyric polypropylenimine (DAB) dendrimer would improve its transfection efficacy in cancer cells. In this work we demonstrated that the conjugation of arginine, lysine and leucine to the dendrimer led to an enhanced anti-proliferative activity of the polyplexes, by up to 47-fold for DAB-Lys in T98G cancer cells compared to the unmodified polyplex in vitro. In vivo, the intravenous administration of amino acid-bearing DAB polyplexes resulted in a significantly improved tumor gene expression, with the highest gene expression level observed after treatment with DAB-Lys polyplex. Arginine, lysine and leucine-bearing generation 3 polypropylenimine polymers are therefore highly promising gene delivery systems for gene transfection in tumors. (C) 2011 Elsevier Ltd. All rights reserve

Polyamine aza-cyclic compounds demonstrate anti-proliferative activity in vitro but fail to control tumour growth in vivo

Cationic polyamines such as the poly(propylenimine) dendrimers (DAB16) are anti-tumour agents (Dufes et al., 2005, Cancer Res 65:8079-8084). Their mechanism of action is poorly understood, but the lack of in vivo toxicity suggests cancer specificity. To explore this polyamine pharmacophore we cross-linked the aza-cyclic compound, hexacyclen, with 1,4-dibromobutane or 1,8-dibromooctane to yield the polyamines [poly(butylhexacyclen)-CL4] or [poly(octylhexacyclen)-CL8] respectively, both free of primary amines. We characterised the compounds and their respective nanoparticles and examined their interaction with the putative targets of the cationic polyamines: the cell membrane and DNA. Like DAB 16, CL4 and CL8 bind plasmid DNA and all three compounds interrupted the cell cycle of A431 epidermoid carcinoma cells in the S-phase. Additionally all three compounds disrupted erythrocyte membranes, with CL8 and DAB 16 being more active, in this respect, than CL4. CL4 (IC50 = 775.1 µg mL−1) and CL8 (IC50 = 8.4 µg mL−1), in a similar manner to DAB 16, were anti-proliferative against A431 cells; although unlike DAB 16, CL4 and CL8 were not tumouricidal against A431 xenografts in mice, indicating that primary amines may play an important role in the in vivo activity of DAB 1