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Sequeiros T.,Autonomous University of Barcelona | Bastaros J.M.,Autonomous University of Barcelona | Sanchez M.,Autonomous University of Barcelona | Rigau M.,Autonomous University of Barcelona | And 12 more authors.
Prostate | Year: 2015

INTRODUCTION. High-grade prostatic intraepithelial neoplasia (HGPIN) is a recognized precursor stage of PCa. Men who present HGPIN in a first prostate biopsy face years of active surveillance including repeat biopsies. This study aimed to identify non-invasive prognostic biomarkers that differentiate early on between indolent HGPIN cases and those that will transform into actual PCa. METHODS. We measured the expression of 21 candidate mRNA biomarkers using quantitative PCR in urine sediment samples from a cohort of 90 patients with initial diagnosis of HGPIN and a posterior follow up of at least two years. Uni- and multivariate statistical analyses were applied to analyze the candidate biomarkers and multiplex models using combinations of these biomarkers. RESULTS. PSMA, PCA3, PSGR, GOLM, KLK3, CDH1, and SPINK1 behaved as predictors for PCa presence in repeat biopsies. Multiplex models outperformed (AUC=0.81-0.86) the predictive power of single genes, including the FDA-approved PCA3 (AUC=0.70). With a fixed sensitivity of 95%, the specificity of our multiplex models was of 41-58%, compared to the 30% of PCA3. The PPV of our models (30-38%) was also higher than the PPV of PCA3 (27%), suggesting that benign cases could be more accurately identified. Applying statistical models, we estimated that 33% to 47% of repeat biopsies could be prevented with a multiplex PCR model, representing an easy applicable and significant advantage over the current gold standard in urine sediment. DISCUSSION. Using multiplex RTqPCR-based models in urine sediment it is possible to improve the current diagnostic method of choice (PCA3) to differentiate between benign HGPIN and PCa cases. © 2015 Wiley Periodicals, Inc.

Llaurado M.,University of British Columbia | Llaurado M.,Barcelona Institute for Research in Biomedicine | Majem B.,Barcelona Institute for Research in Biomedicine | Altadill T.,Barcelona Institute for Research in Biomedicine | And 22 more authors.
Molecular and Cellular Endocrinology | Year: 2014

Ovarian cancer (OC) is the most lethal gynecological malignancy among women. Over 70% of women with OC are diagnosed in advanced stages and most of these cases are incurable. Although most patients respond well to primary chemotherapy, tumors become resistant to treatment. Mechanisms of chemoresistance in cancer cells may be associated with mutational events and/or alterations of gene expression through epigenetic events. Although focusing on known genes has already yielded new information, previously unknown non-coding RNAs, such as microRNAs (miRNAs), also lead insight into the biology of chemoresistance. In this review we summarize the current evidence examining the role of miRNAs as biomarkers of response and survival to therapy in OC. Beside their clinical implications, we also discuss important differences between studies that may have limited their use as clinical biomarkers and suggest new approaches. © 2014 Elsevier Ireland Ltd.

Ocana O.,Institute Neurociencias CSIC UMH | Corcoles R.,Institute Neurociencias CSIC UMH | Fabra A.,IDIBELL Bellvitge Biomedical Research Institute | Moreno-Bueno G.,Uam Institute Investigaciones Biomedicas Alberto Sols Csic Uam | And 5 more authors.
Cancer Cell | Year: 2012

The epithelial-mesenchymal transition (EMT) is required in the embryo for the formation of tissues for which cells originate far from their final destination. Carcinoma cells hijack this program for tumor dissemination. The relevance of the EMT in cancer is still debated because it is unclear how these migratory cells colonize distant tissues to form macrometastases. We show that the homeobox factor Prrx1 is an EMT inducer conferring migratory and invasive properties. The loss of Prrx1 is required for cancer cells to metastasize in vivo, which revert to the epithelial phenotype concomitant with the acquisition of stem cell properties. Thus, unlike the classical EMT transcription factors, Prrx1 uncouples EMT and stemness, and is a biomarker associated with patient survival and lack of metastasis. © 2012 Elsevier Inc.

Munoz-Pinedo C.,Cell Death Regulation Group | Gonzalez-Suarez E.,Transformation and Metastasis Group | Portela A.,Bellvitge Biomedical Research Institute IDIBELL | Gentilella A.,IDIBELL Bellvitge Biomedical Research Institute | And 3 more authors.
Cancer Research | Year: 2013

Patient stratification according to drug responses, together with the discovery of novel antitumor targets, is leading to a new era of personalized cancer treatments. With the aim of identifying emerging pathways and the challenges faced by clinicians during clinical trials, the IDIBELL Cancer Conference on Personalized Cancer Medicine took place in Barcelona on December 3-4, 2012. This conference brought together speakers working in different areas of cancer research (epigenetics, metabolism and the mTOR pathway, cell death and the immune system, clinical oncology) to discuss the latest developments in personalized cancer medicine. © 2013 AACR.

Cambra-Moo O.,Autonomous University of Madrid | Nacarino Meneses C.,Autonomous University of Madrid | Rodriguez Barbero M.A.,CSIC - Institute of Ceramics and Glass | Garcia Gil O.,Autonomous University of Madrid | And 5 more authors.
Journal of Anatomy | Year: 2014

For many years, clinical and non-clinical investigations have investigated cortical bone structure in an attempt to address questions related to normal bone development, mineralisation, pathologies and even evolutionary trends in our lineage (adaptations). Research in the fields of medicine, materials science, physical anthropology, palaeontology, and even archaeobiology has contributed interesting data. However, many questions remain regarding the histomorphological and histochemical variations in human cortical bone during different stages of life. In the present work, we describe a study of long bone cortex transformations during ontogeny. We analysed cross-sections of 15 human humeri histomorphologically and histochemically from perinatal to adult age, marking and quantifying the spatial distribution of bone tissue types using GIS software and analysing the mineral composition and crystallinity of the mineralised cortex using Raman spectroscopy and X-ray diffraction. Our results allowed us to propose that human cortical bone undergoes three main 'events' through ontogeny that critically change the proportions and structure of the cortex. In early development, bone is not well mineralised and proportionally presents a wide cortex that narrows through the end of childhood. Before reaching complete maturity, the bone mineral area increases, allowing the bone to nearly reach the adult size. The medullary cavity is reduced, and the mineral areas have a highly ordered crystalline structure. The last event occurs in adulthood, when the 'oldest' individuals present a reduced mineralised area, with increasing non-mineralised cavities (including the medullary cavity) and reduced crystalline organisation. © 2014 Anatomical Society.

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