Phase II Clinical Trial With Pegylated Liposomal Doxorubicin (CAELYX®/Doxil®) and Quality of Life Evaluation (EORTC QLQ-C30) in Adult Patients With Advanced Soft Tissue Sarcomas: A study of the Spanish Group for Research in Sarcomas (GEIS)

Background: Pegylated liposomal doxorubicin (PLD), a formulation with pharmacokinetic differences with respect to doxorubicin (DXR), might benefit patients with advanced soft tissue sarcoma (STS) pretreated with DXR

A Functional Role of RB-Dependent Pathway in the Control of Quiescence in Adult Epidermal Stem Cells Revealed by Genomic Profiling

Continuous cell renewal in mouse epidermis is at the expense of a pool of pluripotent cells that lie in a well defined niche in the hair follicle known as the bulge. To identify mechanisms controlling hair follicle stem cell homeostasis, we developed a strategy to isolate adult bulge stem cells in mice and to define their transcriptional profile. We observed that a large number of transcripts are underexpressed in hair follicle stem cells when compared to non-stem cells. Importantly, the majority of these downregulated genes are involved in cell cycle. Using bioinformatics tools, we identified the E2F transcription factor family as a potential element involved in the regulation of these transcripts. To determine their functional role, we used engineered mice lacking Rb gene in epidermis, which showed increased expression of most E2F family members and increased E2F transcriptional activity. Experiments designed to analyze epidermal stem cell functionality (i.e.: hair regrowth and wound healing) imply a role of the Rb-E2F axis in the control of stem cell quiescence in epidermis

EMT and induction of miR-21 mediate metastasis development in Trp53-deficient tumours

Missense mutations in TP53 gene promote metastasis in human tumours. However, little is known about the complete loss of function of p53 in tumour metastasis. Here we show that squamous cell carcinomas generated by the specific ablation of Trp53 gene in mouse epidermis are highly metastatic. Biochemical and genome-wide mRNA and miRNA analyses demonstrated that metastases are associated with the early induction of epithelial-mesenchymal transition (EMT) and deregulated miRNA expression in primary tumours. Increased expression of miR-21 was observed in undifferentiated, prometastatic mouse tumours and in human tumours characterized by p53 mutations and distant metastasis. The augmented expression of miR-21, mediated by active mTOR and Stat3 signalling, conferred increased invasive properties to mouse keratinocytes in vitro and in vivo, whereas blockade of miR-21 in a metastatic spindle cell line inhibits metastasis development. Collectively these data identify novel molecular mechanisms leading to metastasis in vivo originated by p53 loss in epithelia

Biocontrol Potential of Forest Tree Endophytes

Peer reviewe

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Nuclear localisation of Aurora-A: its regulation and significance for Aurora-A functions in cancer.

The Aurora-A kinase regulates cell division, by controlling centrosome biology and spindle assembly. Cancer cells often display elevated levels of the kinase, due to amplification of the gene locus, increased transcription or post-translational modifications. Several inhibitors of Aurora-A activity have been developed as anti-cancer agents and are under evaluation in clinical trials. Although the well-known mitotic roles of Aurora-A point at chromosomal instability, a hallmark of cancer, as a major link between Aurora-A overexpression and disease, recent evidence highlights the existence of non-mitotic functions of potential relevance. Here we focus on a nuclear-localised fraction of Aurora-A with oncogenic roles. Interestingly, this pool would identify not only non-mitotic, but also kinase-independent functions of the kinase. We review existing data in the literature and databases, examining potential links between Aurora-A stabilisation and localisation, and discuss them in the perspective of a more effective targeting of Aurora-A in cancer therapy

Biodiversity of Arbuscular Mycorrhizal Fungi in South America: A Review

Identification of species is crucial in understanding how diversity changes affect ecosystemic processes. Particularly, soil microbial are key factors of ecosystemic functioning .Among soil microbes, arbuscular mycorrhizal fungi (AMF, phylum Glomeromycota) are worldwide distributed and form symbiotic associations with almost 80% of the vascular plants of the earth, except for one species, Geosiphon pyriformis, which associates with the cyanobacteria Nostoc. AMF comprise around 300 morphologically defined or 350–1000 molecularly defined taxa. Since AMF associate with aboveground community, their occurrence and composition can influence ecosystemic processes either through affecting plant community composition and thus its processes rates, or soil microbial communities, which are directly involved in nutrient cycling. Soil microorganisms are considered a potentially suitable target for studying regional and local effects on diversity. The symbiosis with AMF not only increases nutrient uptake by the plant of mainly phosphorus (P) and nitrogen (N) in exchange for plant-assimilated carbon (C), but also improves the tolerance of plants to various biotic and abiotic stresses such as pathogens, salinity, and drought

The Single-Phase ProtoDUNE Technical Design Report

ProtoDUNE-SP is the single-phase DUNE Far Detector prototype that is under construction and will be operated at the CERN Neutrino Platform (NP) starting in 2018. ProtoDUNE-SP, a crucial part of the DUNE effort towards the construction of the first DUNE 10-kt fiducial mass far detector module (17 kt total LAr mass), is a significant experiment in its own right. With a total liquid argon (LAr) mass of 0.77 kt, it represents the largest monolithic single-phase LArTPC detector to be built to date. It's technical design is given in this report

Cobalt-based superparamagnetic nanorings

Remarkable optical and magnetic properties were observed in a Co-thiol-polymer composite. The Co and the thiol ligand used to passivate the Co surface, instead of generating isolated nanoparticles, grow into nanorings with a radius around 2 nm. These structures consist of small clusters of metallic Co connected by alkylthiol chains. These small nanorings self-assemble into larger nanorings of ∼10 nm, which in turn self-assemble into larger nanorings in the range of 100-1000 nm in size. We formed a composite by embedding the nanorings in a polymeric matrix. The resulting material presented interesting optical properties such as absorption and emission in the visible zone of the electromagnetic spectrum, and a strong nonlinear optical behavior. The absorption and emission are mainly due to the presence of an alkylthiol-cobalt complex; and the nonlinear optical behavior is due to the presence of the Co clusters inside the polymer matrix. These composites exhibit a superparamagnetic effect down to 250 K, and below this temperature presented features very similar to those observed in spin-glass-like systems. In the nanorings a remarkable phenomenon is that, in addition to the superparamagnetic behavior, we found that during measurements with an applied external field they act as giant aromatic macromolecules and a current circulates through them. The evidence of a current circulating through the nanorings in the presence of an external field tells us about the possibility to use these structures in the design of nanosystems. Our work opens new possibilities of using magnetic transition metals to fabricate nanostructured magnetooptical materials