El camí cap a la igualtat real. La presència de la dona en l'àmbit acadèmic

La posició de la dona dins de l’àmbit científic ha evolucionat positivament de manera signifi cativa en els últims anys, especialment en l’última dècada amb l’aprovació de mesures per a aconseguir la igualtat efectiva entre dones i homes. No obstant això, tot i que el nombre de dones és cada vegada major en les universitats, és evident que falta molt de camí per recórrer

Hacia una medicina personalizada del cáncer de mama: importancia de la clasificación molecular del tumor

La última década la podríamos definir como la más prolífica en cuanto a la generación de conocimientos en el área de la biología molecular del cáncer, y en especial del cáncer de mama. Hemos sido testigos en los últimos diez años de un cambio radical en nuestra manera de entender el cáncer de mama a nivel diagnóstico y terapéutico. Gracias a un avance tecnológico sin precedentes con la aparición y la simplificación de técnicas de biología molecular de alto rendimiento, si bien no se nos ha desvelado la verdadera naturaleza de esta enfermedad, sí hemos podido ver que se trata de una patología que implica mecanismos biológicos complejos a distintos niveles, que precisa de la participación de varias vías de señalización interconectadas entre sí, que no sólo es importante la célula desregulada, sino también el microambiente en el que se desregula y las características constitutivas del paciente, y que todos estos factores influyen en la aparición de la neoplasia, su desarrollo y su respuesta al tratamiento. Todas estas aportaciones nos han permitido entender que la enfermedad neoplásica es única en cada paciente, y con ello avanzar un poco más hacia el tratamiento personalizado

A two-gene epigenetic signature for the prediction of response to neoadjuvant chemotherapy in triple-negative breast cancer patients

Background: pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC) varies between 30 and 40% approximately. To provide further insight into the prediction of pCR, we evaluated the role of an epigenetic methylation-based signature. Methods: epigenetic assessment of DNA extracted from biopsy archived samples previous to NAC from TNBC patients was performed. Patients included were categorized according to previous response to NAC in responder (pCR or residual cancer burden, RCB = 0) or non-responder (non-pCR or RCB > 0) patients. A methyloma study was performed in a discovery cohort by the Infinium HumanMethylation450 BeadChip (450K array) from Illumina. The epigenetic silencing of those methylated genes in the discovery cohort were validated by bisulfite pyrosequencing (PyroMark Q96 System version 2.0.6, Qiagen) and qRT-PCR in an independent cohort of TN patients and in TN cell lines. Results: twenty-four and 30 patients were included in the discovery and validation cohorts, respectively. In the discovery cohort, nine genes were differentially methylated: six presented higher methylation in non-responder patients (LOC641519, LEF1, HOXA5, EVC2, TLX3, CDKL2) and three greater methylation in responder patients (FERD3L, CHL1, and TRIP10). After validation, a two-gene (FER3L and TRIP10) epigenetic score predicted RCB = 0 with an area under the ROC curve (AUC) = 0.905 (95% CI = 0.805-1.000). Patients with a positive epigenetic two-gene score showed 78.6% RCB = 0 versus only 10.7% RCB = 0 if signature were negative. Conclusions: these results suggest that pCR in TNBC could be accurately predicted with an epigenetic signature of FERD3L and TRIP10 genes. Further prospective validation of these findings is warranted

Influence of chemistry and fiber diameter of electrospun PLA, PCL and their blend membranes, intended as cell supports, on their biological behavior

.The prevalence of osteoarthritis, a degenerative cartilage disease that causes joint surface erosion and loss of mobility, emphasizes the need of producing a functional articular cartilage replacement. Tissue engineering has been the focus of recent research as a possible strategy for cartilage regeneration and repair. The most widely used technique for the manufacture of nanofibers is polymer electrospinning. Polylactic acid (PLA) and polycaprolactone (PCL) have been proved particularly suitable for nanofiber preparation, with many biomedical applications. The main aim of this work was to evaluate the behavior of adipose tissue-derived mesenchymal stem cells (ASCs) cultured on biomaterials of PLA, PCL and a combination of both (PLA/PCL), manufactured by electrospinning. We analyzed the bioactive properties of these cells in cultures on them, in terms of proliferation, adhesion, morphology, viability and differentiation. In addition, the influence of the thickness of the fibers in each biomaterial on these cellular characteristics was evaluated for their use in Cartilage Regenerative Medicine applications to promote chondrogenic differentiation. Depending on the parameter assessed, different results were obtained on each biomaterial. Using both polymers successful results on cellular viability were obtained, although in the case of PCL the cellular response in all the experiments was significantly better. As for the blends, positive outcomes were obtained, but they did not overtake the characteristics of PCL. Interestingly, ASCs were able to differentiate into chondrocytes without adding specific chondrogenic media in the three biomaterials tested. Moreover, a marked cell differentiation on PCL with 1.8 μm-fiber diameter and PLA/PCL blends was observed. These findings may play a key role in cartilage Regenerative Medicine and Tissue Engineering.S

Proteomic and transcriptomic profiling reveals a link between the PI3K pathway and lower estrogen-receptor (ER) levels and activity in ER+ breast cancer

IntroductionAccumulating evidence suggests that both levels and activity of the estrogen receptor (ER) and the progesterone receptor (PR) are dramatically influenced by growth-factor receptor (GFR) signaling pathways, and that this crosstalk is a major determinant of both breast cancer progression and response to therapy. The phosphatidylinositol 3-kinase (PI3K) pathway, a key mediator of GFR signaling, is one of the most altered pathways in breast cancer. We thus examined whether deregulated PI3K signaling in luminal ER+ breast tumors is associated with ER level and activity and intrinsic molecular subtype.MethodsWe defined two independent molecular signatures of the PI3K pathway: a proteomic (reverse-phase proteomic array) PI3K signature, based on protein measurement for PI3K signaling intermediates, and a PI3K transcriptional (mRNA) signature based on the set of genes either induced or repressed by PI3K inhibitors. By using these signatures, we scored each ER+ breast tumor represented in multiple independent expression-profiling datasets (four mRNA, n = 915; one protein, n = 429) for activation of the PI3K pathway. Effects of PI3K inhibitor BEZ-235 on ER expression and activity levels and cell growth were tested by quantitative real-time PCR and cell proliferation assays.ResultsWithin ER+ tumors, ER levels were negatively correlated with the PI3K activation scores, both at the proteomic and transcriptional levels, in all datasets examined. PI3K signature scores were also higher in ER+ tumors and cell lines of the more aggressive luminal B molecular subtype versus those of the less aggressive luminal A subtype. Notably, BEZ-235 treatment in four different ER+ cell lines increased expression of ER and ER target genes including PR, and treatment with IGF-I (which signals via PI3K) decreased expression of ER and target genes, thus further establishing an inverse functional relation between ER and PI3K. BEZ-235 had an additional effect on tamoxifen in inhibiting the growth of a number of ER+ cell lines.ConclusionsOur data suggest that luminal B tumors have hyperactive GFR/PI3K signaling associated with lower ER levels, which has been correlated with resistance to endocrine therapy. Targeting PI3K in these tumors might reverse loss of ER expression and signaling and restore hormonal sensitivity

Secondary CoQ10 deficiency, bioenergetics unbalance in disease and aging

Coenzyme Q10 (CoQ10) deficiency is a rare disease characterized by a decreased accumulation of CoQ10 in cell membranes. Considering that CoQ10 synthesis and most of its functions are carried out in mitochondria, CoQ10 deficiency cases are usually considered a mitochondrial disease. A relevant feature of CoQ10 deficiency is that it is the only mitochondrial disease with a successful therapy available, the CoQ10 supplementation. Defects in components of the synthesis machinery caused by mutations in COQ genes generate the primary deficiency of CoQ10. Mutations in genes that are not directly related to the synthesis machinery cause secondary deficiency. Cases of CoQ10 deficiency without genetic origin are also considered a secondary deficiency. Both types of deficiency can lead to similar clinical manifestations, but the knowledge about primary deficiency is deeper than secondary. However, secondary deficiency cases may be underestimated since many of their clinical manifestations are shared with other pathologies. This review shows the current state of secondary CoQ10 deficiency, which could be even more relevant than primary deficiency for clinical activity. The analysis covers the fundamental features of CoQ10 deficiency, which are necessary to understand the biological and clinical differences between primary and secondary CoQ10 deficiencies. Further, a more in-depth analysis of CoQ10 secondary deficiency was undertaken to consider its origins, introduce a new way of classification, and include aging as a form of secondary deficiency.Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía, Grant/Award Numbers: UPO-1259581, UPO-126247, UPO-1265673; Instituto de Salud Carlos III, Grant/Award Number: PI17/01286; Ministerio de Educación, Cultura y Deporte, Grant/Award Numbers: FPU14/04873, FPU16/0326

Necrosis avascular de la cabeza femoral del adulto: estudio multicéntrico

Objetivo: en este artículo se presenta un estudio multicéntrico realizado por la Sociedad Catalana de Cirugía Ortopédica y Traumatología sobre el tratamiento de la necrosis avascular de la cabeza femoral del adulto. Material y método: se elaboró un protocolo de encuesta que fue enviado a 54 centros, obteniéndose respuesta de 28 de ellos. En total se recogieron datos de 556 pacientes. Resultados: en 132 pacientes (26,7%) de estadios 0, I, II y III de Ficat se utilizó el foraje-biopsia descompresivo. Los resultados fueron buenos en 73 casos (55,3%), regulares en 15 (11,36%) y malos en 44 (33,3%). Ningún caso de estadio I II obtuvo un buen resultado. En 343 pacientes de estadios 11, III y IV se realizó artroplastia de cadera (no cementada en un 52,5%, cementada en un 24,5%, híbrida en un 23%). En 13 casos se llevó a cabo osteotomía de cadera. Conclusiones: el foraje-biopsia descompresivo debe utilizarse en los estadios iniciales de la enfermedad. La osteotomía debe emplearse en los estadios intermedios. La artroplastia de cadera debe realizarse en las fases avanzadas (estadio III con más de 130 grados de ángulo de Kerboul y estadio IV)

MicroRNA-33b Suppresses Epithelial-Mesenchymal Transition Repressing the MYC-EZH2 Pathway in HER2+ Breast Carcinoma

Downregulation of miR-33b has been documented in many types of cancers and is being involved in proliferation, migration, and epithelial-mesenchymal transition (EMT). Furthermore, the enhancer of zeste homolog 2-gene (EZH2) is a master regulator of controlling the stem cell differentiation and the cell proliferation processes. We aim to evaluate the implication of miR-33b in the EMT pathway in HER2+ breast cancer (BC) and to analyze the role of EZH2 in this process as well as the interaction between them. miR-33b is downregulated in HER2+ BC cells vs healthy controls, where EZH2 has an opposite expression in vitro and in patients' samples. The upregulation of miR-33b suppressed proliferation, induced apoptosis, reduced invasion, migration and regulated EMT by an increase of E-cadherin and a decrease of ß-catenin and vimentin. The silencing of EZH2 mimicked the impact of miR-33b overexpression. Furthermore, the inhibition of miR-33b induces cell proliferation, invasion, migration, EMT, and EZH2 expression in non-tumorigenic cells. Importantly, the Kaplan-Meier analysis showed a significant association between high miR-33b expression and better overall survival. These results suggest miR-33b as a suppressive miRNA that could inhibit tumor metastasis and invasion in HER2+ BC partly by impeding EMT through the repression of the MYC-EZH2 loop