Hospital Universitario La Paz

About: Hospital Universitario La Paz is a healthcare organization based out in Madrid, Spain. It is known for research contribution in the topics: Population & Medicine. The organization has 8960 authors who have published 11499 publications receiving 191509 citations.

Insights on the CXCL12-CXCR4 axis in hepatocellular carcinoma carcinogenesis

Abstract: Chemokines, a group of small chemotactic cytokines, and their G-protein-coupled receptors were originally identified for their ability to mediate various pro- and anti-inflammatory responses. Beyond the influence of chemokines and their cognate receptors in several inflammatory diseases, several malignancies have been shown to be dependent of chemokines for progression, tumor growth, cellular migration and invasion, and angiogenesis; those later facilitating the development of distant metastases. In hepatocellular carcinoma (HCC), chemokines were shown to affect leukocyte recruitment, neovascularization and tumor progression. CXCL12 (stromal-derived factor 1 alpha- SDF-1) is the primary ligand for the seven transmembrane G-protein coupled receptor CXCR4. The CXCR4/CXCL12 axis exerts a variety of functions at different steps of HCC tumor progression, using autocrine and/or paracrine mechanisms to sustain tumor cell growth, to induce angiogenesis and to facilitate tumor escape through evasion of immune surveillance. In this review, we have comprehensively described the role of CXCR4/CXCL12 in HCC and also investigated the role of CXCR7, an alternative receptors that also binds CXCL12 with potentially distinct downstream effects. Preclinical data converge to demonstrate that inhibition of the CXCR4/CXCL12 axis may lead to direct inhibition of tumor migration, invasion, and metastases. This pathway is under investigation to identify potential novel treatments in HCC and other cancers. However, one of the major challenges faced in this emerging field targeting the CXCR4/CXCL12 signaling pathway, is the translation of current knowledge into the design and development of effective inhibitors of CXCR4 and/or CXCL12 for cancer therapy.

Hypermethylation of the DNA repair gene MGMT: association with TP53 G:C to A:T transitions in a series of 469 nervous system tumors.

Abstract: O6-Methylguanine-DNA methyltransferase (MGMT) plays a major role in repairing DNA damage from alkylating agents. By removing alkyl groups from the O6-position in guanine, MGMT can prevent G:C to A:T transition mutations, a type of variation frequently involving TP53 mutations in brain tumors. Promoter hypermethylation of CpG islands in tumor-related genes can lead to their transcriptional inactivation, and this epigenetic mechanism has been shown to participate in MGMT silencing in some cancers, including those affecting the nervous system. Accordingly, a link between both genetic and epigenetic anomalies may exist in these neoplasms. To determine the relevance of defective MGMT function due to aberrant methylation in relation to the presence of TP53 mutations, we studied 469 nervous system tumors (including all major histological subtypes) for MGMT promoter methylation and TP53 mutations at exons 5–8. Overall, aberrant methylation occurred in 38% of the samples (180/469), with values higher than 50% in the more malignant forms such as glioblastomas and anaplastic gliomas including those with astrocytic, oligodendroglial and ependymal differentiation. In contrast, the non-glial tumors displayed an overall aberrant MGMT promoter methylation of 26%, even though this group includes highly malignant tumors such as neuroblastomas, medulloblastomas and brain metastases. Overall, TP53 mutations were found in 25% of the methylated MGMT tumors (45/180), whereas only 10% of the unmethylated MGMT tumors (30/289) showed TP53 changes (P

Platelet-Rich Plasma in the Treatment of Patellar Tendinopathy A Systematic Review

Abstract: Background:Patellar tendinopathy (PT) is a major cause of morbidity in both high-level and recreational athletes. While there is good evidence for the effectiveness of eccentric exercise regimens in its treatment, a large proportion of patients have disease that is refractory to such treatments. This has led to the development of novel techniques, including platelet-rich plasma (PRP) injection, which aims to stimulate a normal healing response within the abnormal patellar tendon. However, little evidence exists at present to support its use.Purpose:To determine the safety and effectiveness of PRP in the treatment of PT and to quantify its effectiveness relative to other therapies for PT.Study Design:Systematic review.Methods:A systematic review was conducted in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. A literature review was conducted of the Medline, EMBASE, and Cochrane databases as well as trial registries. Both single-arm and comparativ...

Efficacy and safety of sevelamer hydrochloride and calcium acetate in patients on peritoneal dialysis

Abstract: Background. Inadequate phosphorus control is associated with increased morbidity and mortality in patients with CKD stage 5. Although phosphate binders are often used in patients on peritoneal dialysis (PD), no large randomized controlled studies evaluating their use solely in this population have previously been reported. Methods. In this multicentre, open-label study, adult patients on PD with serum phosphorus >5.5 mg/dl were randomized (2:1) to 12 weeks of treatment with sevelamer hydrochloride or calcium acetate. Doses were titrated to achieve serum phosphorus of 3.0–5.5 mg/dl. Changes in serum phosphorus, calcium, intact parathyroid hormone (iPTH), lipids and plasma biomarkers were assessed. Results.Atotalof253patientswerescreened,143ofwhom were randomized (sevelamer hydrochloride, n = 97; calciumacetate,n =46).Treatmentgroupswerewellbalanced with regard to baseline demographics. Serum phosphorus levels were significantly reduced after 12 weeks with both sevelamer hydrochloride and calcium acetate (P < 0.001). Serum PTH was also reduced in both groups while serum calcium increased in the calcium acetate group (P = 0.001) but not in the sevelamer hydrochloride group. Sevelamer hydrochloride was also associated with decreases in total cholesterol, low-density lipoprotein cholesterol and uric acid and an increase in bone-specific alkaline phosphatase (all P < 0.001 versus baseline). Both treatments were well tolerated and safety profiles were consistent with previous reports in haemodialysis patients. Hypercalcaemia was experienced by more calcium acetate-treated patients (18 versus 2%; P = 0.001). Conclusions. In summary, sevelamer hydrochloride provides a reduction in serum phosphorus compared to that