Corporacio Sanitaria Parc Tauli Institute Universitari

Sabadell, Spain

Corporacio Sanitaria Parc Tauli Institute Universitari

Sabadell, Spain
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Gallego A.,University Pompeu Fabra | Gallego A.,University of Magallanes | Hartasanchez D.A.,University Pompeu Fabra | Hartasanchez D.A.,University of Magallanes | And 14 more authors.
Gene | Year: 2017

RNA editing is being recognized as an important post-transcriptional mechanism that may have crucial roles in introducing genetic variation and phenotypic diversity. Despite microRNA editing recurrence, defining its biological relevance is still under extended debate. To better understand microRNA editing function and regulation we performed an exhaustive characterization of the A-to-I site-specific patterns in mir-376a-1, a mammalian microRNA which RNA editing is involved in the regulation of development and in disease. Thorough an integrative approach based on high-throughput small RNA sequencing, Sanger sequencing and computer simulations we explored mir-376a-1 editing in samples from various individuals and primate species including human placenta and macaque, gorilla, chimpanzee and human brain cortex. We observed that mir-376a-1 editing is a common phenomenon in the mature and primary microRNA molecules and it is more frequently detected in brain than in placenta. Primary mir-376a-1 is edited at three positions, − 1, + 4 and + 44. Editing frequency estimations and in silico simulations indicated that editing was not equally recurrent along the three mir-376a-1 sites, nevertheless no epistatic interactions among them were observed. Particularly, the + 4 site, located in the seed region of the mature miR-376a-5p, reached the highest editing frequency in all samples. Secondary structure predictions revealed that the + 4 position was the one that conferred the highest stability to the mir-376a-1 hairpin. We suggest that molecular stability might partially explain the editing recurrence observed in certain microRNAs and that editing events conferring new functional regulatory roles in particular tissues and species could have been conserved along evolution, as it might be the case of mir-376a-1 in primate brain cortex. © 2017


Folprecht G.,University Cancer Center | Pericay C.,Corporacio Sanitaria Parc Tauli Institute Universitari | Saunders M.P.,The Christie NHS Foundation Trust | Thomas A.,University of Leicester | And 15 more authors.
Annals of Oncology | Year: 2016

Background: The combination of aflibercept with FOLFIRI has been shown to significantly prolong overall survival in patients with metastatic colorectal cancer (mCRC) after progression on oxaliplatin-based therapy. This trial evaluated the addition of aflibercept to oxaliplatin-based first-line treatment of patients with mCRC. Patients and methods: Patients with mCRC were randomized to receive first-line therapy with mFOLFOX6 plus aflibercept (4 mg/kg) or mFOLFOX6 alone. The primary end point of this phase II study was the progression-free survival (PFS) rate at 12 months in each arm. The analysis of efficacy between the arms was a pre-planned secondary analysis. Results: Of 236 randomized patients, 227 and 235 patients were evaluable for the primary efficacy analysis and safety, respectively. The probabilities of being progression-free at 12 months were 25.8% [95% confidence interval (CI) 17.2- 34.4] for the aflibercept/mFOLFOX6 arm and 21.2% (95% CI 12.2-30.3) for the mFOLFOX6 arm. The median PFS was 8.48 months (95% CI 7.89-9.92) for the aflibercept/mFOLFOX6 arm and 8.77 months (95% CI 7.62-9.27) for the mFOLFOX6 arm; the hazard ratio of aflibercept/mFOLFOX6 versus mFOLFOX6 was 1.00 (95% CI 0.74-1.36). The response rates were 49.1% (95% CI 39.7-58.6) and 45.9% (95% CI 36.4-55.7) for patients treated with and without aflibercept, respectively. The most frequent treatment-emergent grade 3/4 adverse events (AEs) excluding laboratory abnormalities reported for aflibercept/mFOLFOX6 versus mFOLFOX6 were neuropathy (16.8% versus 17.2%) and diarrhea (13.4% versus 5.2%). Neutropenia grade 3/4 occurred in 36.1% versus 29.3%. The most common vascular endothelial growth factor inhibition class-effect grade 3/4 AEs for aflibercept/mFOLFOX6 versus mFOLFOX6 were hypertension (35.3% versus 1.7%), proteinuria (9.2% versus 0%), deep vein thrombosis (5.9% versus 0.9%) and pulmonary embolism (5.9% versus 5.2%). Conclusion: No difference in PFS rate was observed between treatment groups. Adding aflibercept to first-line mFOLFOX6 did not increase efficacy but was associated with higher toxicity. © The Author 2016.


Montesinos J.,Clinical Research Unit | Bare M.,Institute Universitari | Dalmau E.,Corporacio Sanitaria Parc Tauli Institute Universitari | Saigi E.,Corporacio Sanitaria Parc Tauli Institute Universitari | And 5 more authors.
Open Respiratory Medicine Journal | Year: 2011

Background: In Europe, approximately 381,500 patients are diagnosed with non-small cell lung cancer (NSCLC) every year. The aim of this study is to analyse the changes in diagnosis, treatment and evolution during the last two decades, using data from a hospital registry. Material and Methods: Patients diagnosed with NSCLC at the Corporació Sanitària Parc Taulí-Sabadell (Catalonia, Spain) during the periods 1990-1997 (n=748) and 2003-2005 (n=311) were included. The hospital tumour registry was used for prospective data collection. Results: Our series shows a significant increase in women diagnosed with NSCLC (6% vs 10.3%; p 0.01) in the latter period; the incidence of adenocarcinomas increased by 20% (31% vs 51.1%), whereas that of squamous cell carcinomas fell (51.3% vs 32.5%; p<0.001). The proportion of patients receiving active treatment also increased significantly, from 56.6% to 76.5% (p<0.001). Disease stage at diagnosis and the number of patients treated by radical surgical resection remained unchanged. Among the favourable independent prognostic factors for survival were: gender (women), age less than 70 years old, Karnofsky index ≥70%, early stage at diagnosis, treatment with chemotherapy, and being diagnosed in the latter period 2003-2005 (HR 0.67). Over this 10-year period, absolute gain in mean survival in our series was 115 days. Conclusions: The absolute gain in mean survival in NSCLC patients in the period studied was 3.8 months, with a 6.75% increase in 5-year survival. Hospital registry data may help the correct assessment of epidemiological changes and the real effectiveness of treatments, which are sometimes overestimated in clinical trials. © Montesinos et al.


PubMed | Mount Vernon Cancer Center, Korea University, Samara Regional Oncology Dispensary, University of Southampton and 14 more.
Type: Journal Article | Journal: Annals of oncology : official journal of the European Society for Medical Oncology | Year: 2016

The combination of aflibercept with FOLFIRI has been shown to significantly prolong overall survival in patients with metastatic colorectal cancer (mCRC) after progression on oxaliplatin-based therapy. This trial evaluated the addition of aflibercept to oxaliplatin-based first-line treatment of patients with mCRC.Patients with mCRC were randomized to receive first-line therapy with mFOLFOX6 plus aflibercept (4 mg/kg) or mFOLFOX6 alone. The primary end point of this phase II study was the progression-free survival (PFS) rate at 12 months in each arm. The analysis of efficacy between the arms was a pre-planned secondary analysis.Of 236 randomized patients, 227 and 235 patients were evaluable for the primary efficacy analysis and safety, respectively. The probabilities of being progression-free at 12 months were 25.8% [95% confidence interval (CI) 17.2-34.4] for the aflibercept/mFOLFOX6 arm and 21.2% (95% CI 12.2-30.3) for the mFOLFOX6 arm. The median PFS was 8.48 months (95% CI 7.89-9.92) for the aflibercept/mFOLFOX6 arm and 8.77 months (95% CI 7.62-9.27) for the mFOLFOX6 arm; the hazard ratio of aflibercept/mFOLFOX6 versus mFOLFOX6 was 1.00 (95% CI 0.74-1.36). The response rates were 49.1% (95% CI 39.7-58.6) and 45.9% (95% CI 36.4-55.7) for patients treated with and without aflibercept, respectively. The most frequent treatment-emergent grade 3/4 adverse events (AEs) excluding laboratory abnormalities reported for aflibercept/mFOLFOX6 versus mFOLFOX6 were neuropathy (16.8% versus 17.2%) and diarrhea (13.4% versus 5.2%). Neutropenia grade 3/4 occurred in 36.1% versus 29.3%. The most common vascular endothelial growth factor inhibition class-effect grade 3/4 AEs for aflibercept/mFOLFOX6 versus mFOLFOX6 were hypertension (35.3% versus 1.7%), proteinuria (9.2% versus 0%), deep vein thrombosis (5.9% versus 0.9%) and pulmonary embolism (5.9% versus 5.2%).No difference in PFS rate was observed between treatment groups. Adding aflibercept to first-line mFOLFOX6 did not increase efficacy but was associated with higher toxicity.NCT00851084, www.clinicaltrials.gov, EudraCT 2008-004178-41.


PubMed | Institute Oncologic del Valles and Corporacio Sanitaria Parc Tauli Institute Universitari
Type: | Journal: BioMed research international | Year: 2014

High throughput methods such as next generation sequencing are increasingly used in molecular diagnosis. The aim of this study was to develop a workflow for the detection of BRCA1 and BRCA2 mutations using massive parallel sequencing in a 454 GS Junior bench top sequencer. Our approach was first validated in a panel of 23 patients containing 62 unique variants that had been previously Sanger sequenced. Subsequently, 101 patients with familial breast and ovarian cancer were studied. BRCA1 and BRCA2 exon enrichment has been performed by PCR amplification using the BRCA MASTR kit (Multiplicom). Bioinformatic analysis of reads is performed with the AVA software v2.7 (Roche). In total, all 62 variants were detected resulting in a sensitivity of 100%. 71 false positives were called resulting in a specificity of 97.35%. All of them correspond to deletions located in homopolymeric stretches. The analysis of the homopolymers stretches of 6bp or longer using the BRCA HP kit (Multiplicom) increased the specificity of the detection of BRCA1 and BRCA2 mutations to 99.99%. We show here that massive parallel pyrosequencing can be used as a diagnostic strategy to test for BRCA1 and BRCA2 mutations meeting very stringent sensitivity and specificity parameters replacing traditional Sanger sequencing with a lower cost.

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