Utilidad clínica de la expresión de marcadores inmunohistoquímicos en el tumor vesical urotelial papilar sin invasión de la muscular propia (pTa/pT1) grado 2

Introducción: El tumor vesical urotelial papilar sin invasión de la muscular propia (TVU NoMinv) es uno de los tumores urológicos más frecuentes. A pesar del tratamiento, presenta una elevada tasa de recidiva y progresión. El hallazgo de factores pronósticos que nos indiquen su comportamiento clínico es fundamental para estratificar riesgos y ayudar al diseño de una estrategia terapéutica. Las variables anatomoclínicas clásicamente utilizadas no son del todo precisas en la evaluación pronóstica. La nueva clasificación histológica de la OMS 2004 tampoco ha conseguido este objetivo, presentando una importante variabilidad interobservador. Por ello, está en auge el estudio de marcadores moleculares, que precisen el comportamiento clínico y biológico de estos tumores. El principal problema de los estudios que han evaluado su utilidad es la heterogeneidad en la metodología empleada, ya que no se centran en un tipo específico de tumor. Por otra parte, dentro de los TVU NoMinv el tumor de grado 2 (G2) (OMS 1973) es el paradigma de comportamiento clínico incierto. Objetivos: Conocer la utilidad pronóstica de una batería de marcadores inmunohistoquímicos en el TVU NoMinv G2 con respecto a los periodos libres de recidiva, progresión y mortalidad cáncer específica. Material y métodos: Estudio analítico, observacional y ambispectivo de 213 pacientes con tumor vesical primario no musculoinvasivo G2. Estudio transversal de las muestras procesadas en parafina de dicho tumor, determinando la expresión inmunohistoquímica de 26 marcadores moleculares correspondientes a las distintas rutas oncológicas. Se construyeron mapas tridimiensionales para su representación. Se realizó un análisis multidimensional de los datos mediante el uso de regresión logística penalizada ¿Least absolute shrinkage and selection operator¿ (LASSO) y bosques aleatorios de supervivencia ¿Random survival forest¿ (RSF). Se efectuó un análisis de supervivencia mediante curvas Kaplan-Meier (log Rank test). Se generaron grupos de riesgo con las variables seleccionadas, comparándolos con la probabilidad de recidiva y progresión calculadas según las tablas de la EORTC.. Resultados: La media de seguimiento y de la edad fue de 58 ± 33,5 meses y 69,5 ± 10,4 años. Los porcentajes de recidiva, progresión y mortalidad cáncer-específica (CaEsp) fueron del 54,5%, 17,4%, 11,3%, respectivamente. Un 61% de la muestra correspondió a tumores T1 y un 71% a un alto grado OMS 2004. Las variables seleccionadas por LASSO y RSF influyentes en la aparición de tiempos de supervivencia cortos fueron la siguientes. Tiempo libre (TL) de recidiva: número de tumores >1 , un aumento en la expresión nuclear de Ki67, VEGFR2 y Ciclina D1 y una débil expresión citoplasmática de CtIP y p16INK4a. TL de progresión: tumor multicéntrico, expresión de Ki 67 y Survivina nuclear. TL de mortalidad CaEsp: edad >=70 años, estadio T1, expresión nuclear de GAPDH, Survivina y p53. Los grupos de riesgo generados han sido más efectivos en cuanto al análisis de supervivencia que la estratificación según la EORTC o mediante la clasificación según estadio/grado (p<0,005). Conclusiones: La expresión inmunohistoquímica de varios marcadores moleculares influye en el pronóstico clínico de los pacientes con TVU NoMinv G2, siendo posible su uso en conjunto con variables anatomoclínicas para generar grupos de riesgo

Flavonoid glycosides from Persea caerulea. Unraveling their interactions with SDS-micelles through matrix-assisted DOSY, PGSE, mass spectrometry, and NOESY

Two flavonoid glycosides derived from rhamnopyranoside (1) and arabinofuranoside (2) have been isolated from leaves of Persea caerulea for the first time. The structures of 1 and 2 have been established by 1H NMR, 13C NMR, and IR spectroscopy, together with LC–ESI–TOF and LC–ESI–IT MS spectrometry. From the MS and MS/MS data, the molecular weights of the intact molecules as well as those of quercetin and kaempferol together with their sugar moieties were deduced. The NMR data provided information on the identity of the compounds, as well as the α and β configurations and the position of the glycosides on quercetin and kaempferol. We have also explored the application of sodium dodecyl sulfate (SDS) normal micelles in binary aqueous solution, at a range of concentrations, to the diffusion resolution of these two glycosides, by the application of matrix‐assisted diffusion ordered spectroscopy (DOSY) and pulse field gradient spin echo (PGSE) methodologies, showing that SDS micelles offer a significant resolution which can, in part, be rationalized in terms of differing degrees of hydrophobicity, amphiphilicity, and steric effects. In addition, intra‐residue and inter‐residue proton–proton distances using nuclear Overhauser effect build‐up curves were used to elucidate the conformational preferences of these two flavonoid glycosides when interacting with the micelles. By the combination of both diffusion and nuclear Overhauser spectroscopy techniques, the average location site of kaempferol and quercetin glycosides has been postulated, with the former exhibiting a clear insertion into the interior of the SDS‐micelle, whereas the latter is placed closer to the surface.Junta de Andalucía P12-FQM-266

The predictive and prognostic potential of plasma telomerase reverse transcriptase (TERT) RNA in rectal cancer patients

Background: Preoperative chemoradiotherapy (CRT) followed by surgery is the standard care for locally advanced rectal cancer, but tumour response to CRT and disease outcome are variable. The current study aimed to investigate the effectiveness of plasma telomerase reverse transcriptase (TERT) levels in predicting tumour response and clinical outcome. Methods: 176 rectal cancer patients were included. Plasma samples were collected at baseline (before CRT\ubcT0), 2 weeks after CRT was initiated (T1), post-CRT and before surgery (T2), and 4\u20138 months after surgery (T3) time points. Plasma TERT mRNA levels and total cell-free RNA were determined using real-time PCR. Results: Plasma levels of TERT were significantly lower at T2 (Po0.0001) in responders than in non-responders. Post-CRT TERT levels and the differences between pre- and post-CRT TERT levels independently predicted tumour response, and the prediction model had an area under curve of 0.80 (95% confidence interval (CI) 0.73\u20130.87). Multiple analysis demonstrated that patients with detectable TERT levels at T2 and T3 time points had a risk of disease progression 2.13 (95% CI 1.10\u20134.11)-fold and 4.55 (95% CI 1.48\u201313.95)-fold higher, respectively, than those with undetectable plasma TERT levels. Conclusions: Plasma TERT levels are independent markers of tumour response and are prognostic of disease progression in rectal cancer patients who undergo neoadjuvant therapy

Wide-Geographic and Long-Term Analysis of the Role of Pathogens in the Decline of Pinna nobilis to Critically Endangered Species

A mass mortality event (MME) affecting the fan mussel Pinna nobilis was first detected in Spain in autumn 2016 and spread north- and eastward through the Mediterranean Sea. Various pathogens have been blamed for contributing to the MME, with emphasis in Haplosporidium pinnae, Mycobacterium sp. and Vibrio spp. In this study, samples from 762 fan mussels (necropsies from 263 individuals, mantle biopsies from 499) of various health conditions, with wide geographic and age range, taken before and during the MME spread from various environments along Mediterranean Sea, were used to assess the role of pathogens in the MME. The number of samples processed by both histological and molecular methods was 83. The most important factor playing a main role on the onset of the mass mortality of P. nobilis throughout the Mediterranean Sea was the infection by H. pinnae. It was the only non-detected pathogen before the MME while, during MME spreading, its prevalence was higher in sick and dead individuals than in asymptomatic ones, in MME-affected areas than in non-affected sites, and it was not associated with host size, infecting both juveniles and adults. Conversely, infection with mycobacteria was independent from the period (before or during MME), from the affection of the area by MME and from the host health condition, and it was associated with host size. Gram (-) bacteria neither appeared associated with MME.En prens

Wide-Geographic and Long-Term Analysis of the Role of Pathogens in the Decline of Pinna nobilis to Critically Endangered Species

20 Pág.A mass mortality event (MME) affecting the fan mussel Pinna nobilis was first detected in Spain in autumn 2016 and spread north- and eastward through the Mediterranean Sea. Various pathogens have been blamed for contributing to the MME, with emphasis in Haplosporidium pinnae, Mycobacterium sp. and Vibrio spp. In this study, samples from 762 fan mussels (necropsies from 263 individuals, mantle biopsies from 499) of various health conditions, with wide geographic and age range, taken before and during the MME spread from various environments along Mediterranean Sea, were used to assess the role of pathogens in the MME. The number of samples processed by both histological and molecular methods was 83. The most important factor playing a main role on the onset of the mass mortality of P. nobilis throughout the Mediterranean Sea was the infection by H. pinnae. It was the only non-detected pathogen before the MME while, during MME spreading, its prevalence was higher in sick and dead individuals than in asymptomatic ones, in MME-affected areas than in non-affected sites, and it was not associated with host size, infecting both juveniles and adults. Conversely, infection with mycobacteria was independent from the period (before or during MME), from the affection of the area by MME and from the host health condition, and it was associated with host size. Gram (-) bacteria neither appeared associated with MME.This work was funded by: DG Pesca i Medi Mari (GOIB),EsMarEs (order IEO by MITECO, Spanish government), Life UFE IP-PAF INTEMARES (LIFE15 IPE ES 012) “Gestión integrada, innovadora y participativa de la Red Natura 2000 en el medio marino español,” the research project “Estado de conservación del bivalvo amenazado Pinna nobilis en el PNAC” (OAPN 024/2010), the project RECONNECT (MIS 5017160) of the Programme Interreg V-B “Balkan-Mediterranean 2014–2020.” MTES (French Government), DREAL (Direction Régionale Environnement Aménagement Logement) and Région Occitanie (France) for funding research and monitoring of Pinna.GC and PP were contracted under the INIA-CCAA cooperative research programme for postdoctoral incorporation from the Spanish National Institute for Agricultural and Food Research and Technology (INIA) (DOC INIA 8/2013 and 15/2015). MV-L was supported by a Juan de la Cierva-Incorporación postdoctoral contract (ICJI-2016-29329, MICIU Programme). ML-S and EÁ were supported by a Personal Técnico de Apoyo contract MINECO programme (PTA2015-11709-I and PTA2015-10829- I, respectively). CP and GS were supported by the project RECONNECT (MIS 5017160) financed by the Transnational Cooperation Programme Interreg V-B “Balkan-Mediterranean 2014–2020” and co-funded by the European Union and national funds of the participating countries. CP was supported by Sorbonne University.Peer reviewe