dsRNAi-mediated silencing of PIAS2beta specifically kills anaplastic carcinomas by mitotic catastrophe.

The E3 SUMO ligase PIAS2 is expressed at high levels in differentiated papillary thyroid carcinomas but at low levels in anaplastic thyroid carcinomas (ATC), an undifferentiated cancer with high mortality. We show here that depletion of the PIAS2 beta isoform with a transcribed double-stranded RNA-directed RNA interference (PIAS2b-dsRNAi) specifically inhibits growth of ATC cell lines and patient primary cultures in vitro and of orthotopic patient-derived xenografts (oPDX) in vivo. Critically, PIAS2b-dsRNAi does not affect growth of normal or non-anaplastic thyroid tumor cultures (differentiated carcinoma, benign lesions) or cell lines.

The Inflammatory Pattern of Chronic Limb-Threatening Ischemia in Muscles: The TNF-α Hypothesis.

: Vascular inflammation plays a crucial role in peripheral arterial disease (PAD), although the role of the mediators involved has not yet been properly defined. The aim of this work is to investigate gene expression and plasma biomarkers in chronic limb-threating ischemia (CLTI). Using patients from the GHAS trial, both blood and ischemic muscle samples were obtained to analyze plasma markers and mRNA expression, respectively.

RET signalling provides tumorigenic mechanism and tissue specificity for AIP-related somatotrophinomas.

It is unclear how loss-of-function germline mutations in the widely-expressed co-chaperone AIP, result in young-onset growth hormone secreting pituitary tumours. The RET receptor, uniquely co-expressed in somatotrophs with PIT1, induces apoptosis when unliganded, while RET supports cell survival when it is bound to its ligand. We demonstrate that at the plasma membrane, AIP is required to form a complex with monomeric-intracellular-RET, caspase-3 and PKCδ resulting in PIT1/CDKN2A-ARF/p53-apoptosis pathway activation.

GFRα 1-2-3-4 co-receptors for RET Are co-expressed in Pituitary Stem Cells but Individually Retained in Some Adenopituitary Cells.

The RET tyrosine kinase receptor is expressed by the endocrine somatotroph cells of the pituitary where it has important functions regulating survival/apoptosis. However, RET is also expressed by the GPS pituitary stem cells localized in a niche between the adenopituitary and the intermediate lobe. To bind any of its four ligands, RET needs one of four co-receptors called GFRα1-4.

Quality indicators in gastroscopy. Gastroscopy procedure.

Within the project "Quality indicators in digestive endoscopy", pioneered by the Spanish Society for Digestive Diseases (SEPD), the objective of this research is to suggest the structure, process, and results procedures and indicators necessary to implement and assess quality in the gastroscopy setting. First, a chart was designed with the steps to be followed during a gastroscopy procedure. Secondly, a team of experts in care quality and/or endoscopy performed a qualitative review of the literature searching for quality indicators for endoscopic procedures, including gastroscopies.

Unmasking a new prognostic marker and therapeutic target from the GDNF-RET/PIT1/p14ARF/p53 pathway in acromegaly.

Background: Acromegaly is produced by excess growth hormone secreted by a pituitary adenoma of somatotroph cells (ACRO). First-line therapy, surgery and adjuvant therapy with somatostatin analogs, fails in 25% of patients. There is no predictive factor of resistance to therapy.

Quality indicators for endoscopic retrograde cholangiopancreatography. The procedure of endoscopic retrograde cholangiopancreatography.

The goal of the project encompassing the present paper is to propose useful quality procedures and indicators in order to improve quality in digestive endoscopy units. In this third part outcome procedures and indicators are suggested for endoscopic retrograde cholangiopancreatography (ERCP). First, a diagram of pre- and post-ERCP steps was developed.

[Relevance of the socioeconomic and health context in patient satisfaction].

Objective: To determine which factors of the socioeconomic and health contexts influence the perception of the satisfaction of the population with the health services.

Methods: The data come from the European Health Survey of 2009. In the 22,188 subjects surveyed, the relationship between the perception of satisfaction with the health services received and the individual and contextual variables was studied, applying a multilevel analysis.

Quality indicators in digestive endoscopy: introduction to structure, process, and outcome common indicators.

The general goal of the project wherein this paper is framed is the proposal of useful quality and safety procedures and indicators to facilitate quality improvement in digestive endoscopy units. This initial offspring sets forth procedures and indicators common to all digestive endoscopy procedures. First, a diagram of pre- and post-digestive endoscopy steps was developed.

Rewiring of the apoptotic TGF-β-SMAD/NFκB pathway through an oncogenic function of p27 in human papillary thyroid cancer.

Papillary thyroid carcinoma (PTC), the most frequent thyroid cancer, is characterized by low proliferation but no apoptosis, presenting frequent lymph-node metastasis. Papillary thyroid carcinoma overexpress transforming growth factor-beta (TGF-β). In human cells, TGF-β has two opposing actions: antitumoral through pro-apoptotic and cytostatic activities, and pro-tumoral promoting growth and metastasis.

[Sociodemographic characteristics and geographic variability associated with patient satisfaction in Primary Care].

Background: Patient satisfaction with health services plays an important role in programs to improve the quality of care from the point of view of users. The objectives of this study were: To identify sociodemographic characteristics associated with patient satisfaction in the care provided by family doctors in Primary Health Care (PHC) centres, and describe the geographical variability of this phenomenon in the Spanish National Health Service.

Material And Methods: The data come from the European Health Survey (2009).

[Economic recession (2006-2012) and changes in the health status of the Spanish population].

Objective: To analyze the relationship of mental health problems in Spanish population with the economic recession (2006-2012), and find out how it affects the self-perception of health status.

Materials And Methods: Cross-sectional study using the National Health Survey of Spain, 2006/2007 and 2011/2012. Using logistic regression models, three indicators linked to mental health and perceived health were analyzed.

Humanized medium (h7H) allows long-term primary follicular thyroid cultures from human normal thyroid, benign neoplasm, and cancer.

Context: Mechanisms of thyroid physiology and cancer are principally studied in follicular cell lines. However, human thyroid cancer lines were found to be heavily contaminated by other sources, and only one supposedly normal-thyroid cell line, immortalized with SV40 antigen, is available. In primary culture, human follicular cultures lose their phenotype after passage.

Defining stem cell types: understanding the therapeutic potential of ESCs, ASCs, and iPS cells.

Embryonic, adult, artificially reprogrammed, and cancer…- there are various types of cells associated with stemness. Do they have something fundamental in common? Are we applying a common name to very different entities? In this review, we will revisit the characteristics that define 'pluripotency', the main property of stem cells (SCs). For each main type of physiological (embryonic and adult) or synthetic (induced pluripotent) SCs, markers and functional behavior in vitro and in vivo will be described.

Craniopharyngiomas express embryonic stem cell markers (SOX2, OCT4, KLF4, and SOX9) as pituitary stem cells but do not coexpress RET/GFRA3 receptors.

Context: Adult stem cells maintain some markers expressed by embryonic stem cells and express other specific markers depending on the organ where they reside. Recently, stem/progenitor cells in the rodent and human pituitary have been characterized as expressing GFRA2/RET, PROP1, and stem cell markers such as SOX2 and OCT4 (GPS cells).

Objective: Our objective was to detect other specific markers of the pituitary stem cells and to investigate whether craniopharyngiomas (CRF), a tumor potentially derived from Rathke's pouch remnants, express similar markers as normal pituitary stem cells.

Direct promoter induction of p19Arf by Pit-1 explains the dependence receptor RET/Pit-1/p53-induced apoptosis in the pituitary somatotroph cells.

Somatotrophs produce growth hormone (GH) and are the most abundant secretory cells of the pituitary. Somatotrophs express the transcription factor Pit-1 and the dependence receptor RET, its co-receptor GFRa1 and ligand GDNF. Pit-1 is a transcription factor essential for somatotroph proliferation and differentiation and for GH expression.

Functional role of the RET dependence receptor, GFRa co-receptors and ligands in the pituitary.

The RET receptor is a tyrosine kinase receptor implicated in kidney and neural development. In the adenopituitary RET and the co-receptor GFRa1 are expressed exclusively in the somatotrophs secreting GH. RET is implicated in a clever pathway to maintain at physiological levels the number of somatotrophs and the GH production.

Expression of exogenous proteins and short hairpin RNAs in human primary thyrocytes.

Recently, it has been shown that commercial human thyroid lines were in fact derived from colon, mammary carcinoma, or melanoma. Others have demonstrated the absence of a common pattern of gene expression between available thyroid cancer cell lines and tumors from patients. Thus, it is important to use several primary cells with a common pathological origin to achieve reproducible results, and it is necessary to find common methods for manipulation of protein expression in such various cultures.