CSDE1 Intracellular Distribution as a Biomarker of Melanoma Prognosis

RNA-binding protein; Biomarker; MelanomaProteína de unión a ARN; Biomarcador; MelanomaProteïna d'unió a l'ARN; Biomarcador; MelanomaRNA-binding proteins are emerging as critical modulators of oncogenic cell transformation, malignancy and therapy resistance. We have previously found that the RNA-binding protein Cold Shock Domain containing protein E1 (CSDE1) promotes invasion and metastasis of melanoma, the deadliest form of skin cancer and also a highly heterogeneous disease in need of predictive biomarkers and druggable targets. Here, we design a monoclonal antibody useful for IHC in the clinical setting and use it to evaluate the prognosis potential of CSDE1 in an exploratory cohort of 149 whole tissue sections including benign nevi and primary tumors and metastasis from melanoma patients. Contrary to expectations for an oncoprotein, we observed a global decrease in CSDE1 levels with increasing malignancy. However, the CSDE1 cytoplasmic/nuclear ratio exhibited a positive correlation with adverse clinical features of primary tumors and emerged as a robust indicator of progression free survival in cutaneous melanoma, highlighting the potential of CSDE1 as a biomarker of prognosis. Our findings provide a novel feature for prognosis assessment and highlight the intricacies of RNA-binding protein dynamics in cancer progression.A.I. and P.E. were supported by PhD4MD fellowships from the CRG and the Emerald program (Marie Skłodowska-Curie grant agreement 101034290), respectively. This work was supported by the following grants to F.G.: PGC2018-099697-B-I00 and PID2021-127948NB-I00 from the Spanish Ministry of Science and Innovation (MCIN) funded by MCIN/ AEI /10.13039/501100011033/ and by ERDF; “la Caixa” Foundation (ID 100010434) under the Grant LCF/PR/HR17/52150016; the Catalan Agency for Research and Universities (SGR-Cat-2021-01215) and intramural funds from the CRG on emergent translational research. We acknowledge the support of the Spanish Ministry of Science and Innovation through the Centro de Excelencia Severo Ochoa (CEX2020-001049-S, MCIN/AEI /10.13039/501100011033) and the Generalitat de Catalunya through the CERCA programme

UNR/CDSE1 expression as prognosis biomarker in resectable pancreatic ductal adenocarcinoma patients: A proof-of-concept

Tractament del càncer; Expressió gènica; Anàlisi de supervivènciaTratamiento del cáncer; Expresión génica; Análisis de supervivenciaCancer treatment; Gene expression; Survival analysisPancreatic ductal adenocarcinoma is an aggressive form of pancreatic cancer and the fourth leading cause of cancer-related death. When possible, curative approaches are based on surgical resection, though not every patient is a candidate for surgery. There are clinical guidelines for the management of these patients that offer different treatment options depending on the clinical and pathologic characteristics. However, the survival rates seen in this kind of patients are still low. The CDSE1 gene is located upstream of NRAS and encodes an RNA-binding protein termed UNR. The aim of this study was to analyze UNR expression and its correlation with outcome in patients with resectable pancreatic ductal adenocarcinoma (PDAC). For this, samples from resectable PDAC patients who underwent duodenopancreatectomy were used to evaluate UNR protein expression by immunohistochemistry using a tissue microarray. Here, we observed that low UNR expression was significantly associated with shorter progression-free survival after surgery (P = 0.010). Moreover, this prognostic marker remained significant after Cox proportional hazards model (P = 0.036). We further studied the role of CDSE1 expression in patient’s prognosis using data from public repositories (GEO and TGCA), confirming our results. Interestingly, CDSE1 expression correlated with that of genes characteristic of an immunogenic molecular subtype of pancreatic cancer. Based on these findings, UNR may be considered a potential prognostic biomarker for resectable PDAC and may serve to guide subsequent adjuvant treatment decisions.This work has been carried out with the support of the RNA-Reg CONSOLIDER Network CSD2009-00080 (J.M.-U. and J.G.-F.), and Spanish Health Research Project Funds PI16/01468 from “Instituto de Salud Carlos III” (A.C. and J.G.-F.), both of the Spanish Ministry of Economy, Industry and Competitiveness

Pobreza y enfermedad: el círculo vicioso: Poverty and disease: the vicious circle

It is known that poverty and health is an interrelated phenomenon. The poorest countries have poor health indicators in relation to the countries with the highest incomes, and within each country the poorest people with health problems. This association reflects a causal relationship that works in both directions: poverty generates poor health, and poor health perpetuates poverty (vicious circle of poverty-disease) 1. However, it also means that people with problems of health do not have the same conditions as others, because these inequalities correspond to the limitations and opportunities different from each other and with others, and not with a tendency of sometimes different groups. DOI: 10.25176/RFMH.v18.n3.1585  Se sabe que la pobreza y la mala salud son fenómenos interrelacionados. Los países pobres tienden a presentar deficientes indicadores en salud en relación a los países de mejores ingresos, y dentro de cada país las personas pobres tienen más problemas de salud que las no pobres. Esta asociación refleja una relación de causalidad que funciona en los dos sentidos: la pobreza genera mala salud, y la mala salud hace que la pobreza se perpetue (circulo vicioso pobreza-enfermedad)1. Sin embargo, también refleja un consenso creciente de que las desigualdades entre los ricos y los pobres con respecto a los resultados en salud no son justas ni equitativas, no porque los pobres sean de algún modo más merecedores que los que tienen más dinero, sino porque estas desigualdades corresponden a las limitaciones y oportunidades muy diferentes que tienen unos y otros, y no a una tendencia de los dos grupos a hacer elecciones diferentes . DOI: 10.25176/RFMH.v18.n3.1585 &nbsp

Determinants of activity and efficacy of anti-PD1/PD-L1 therapy in patients with advanced solid tumors recruited in a clinical trials unit: a longitudinal prospective biomarker-based study

Immune checkpoint inhibitors; Immunotherapy; Solid tumorsInhibidores de puntos de control inmunitarios; Inmunoterapia; Tumores sólidosInhibidors del punt de control immunitari; Immunoteràpia; Tumors sòlidsImmune-checkpoint inhibitors (ICI) have revolutionized the therapeutic landscape of cancer. However, optimal patient selection is still an unmet need. One-hundred-forty-six patients with metastatic cancer candidates to ICI at the Hospital Clinic of Barcelona Clinical Trials Unit were prospectively recruited in this observational study. Blood samples were collected at different timepoints, baseline LIPI score calculated and pre-ICI archived tissues retrieved to evaluate PD-L1, tumor-infiltrating lymphocytes (TILs) and PD1 mRNA levels. Tumor assessments were centrally reviewed by RECIST 1.1 criteria. Associations with overall response rates (ORR), durable clinical benefit (DCB), progression-free survival (PFS) and overall survival (OS) were performed with univariable/multivariable logistic and Cox regressions, where appropriate. At a median follow-up of 26.9 months, median PFS and OS were 2.7 and 12.9 months. Response rates were 17.8% with duration of response (DOR) of 4.4 months. LIPI score was independently associated with PFS (p = 0.025) and OS (p < 0.001). Immunotherapy-naïve status was independently associated with better PFS (p = 0.005). Time-to-best response (TTBR) and ORR (p < 0.001 both) were associated with better OS at univariate analysis. PFS and DOR were moderately correlated with OS (p < 0.001 both). A PD-L1 10% cut-off detected worse/best responders in terms of ORR (univariate p = 0.011, multivariate p = 0.028) and DCB (univariate p = 0.043). PD1 mRNA levels were strikingly associated to complete responses (p = 0.021). To resume, in our prospective observational pan-cancer study, baseline LIPI score, immunotherapy-naïve status, cancer type and RT before starting ICI were the most relevant clinical factors independently correlated with immunotherapy outcomes. Longer TTBR seemed to associate with better survival, while PD1 mRNA and PD-L1 protein levels might be tumor-agnostic predictive factors of response to ICI and should be furtherly explored

A Quick Guide for Using Microsoft Onenote as an Electronic Laboratory Notebook

[Abstract] Scientific data recording and reporting systems are of a great interest for endorsing reproducibility and transparency practices among the scientific community. Current research generates large datasets that can no longer be documented using paper lab notebooks (PLNs). In this regard, electronic laboratory notebooks (ELNs) could be a promising solution to replace PLNs and promote scientific reproducibility and transparency. We previously analyzed five ELNs and performed two survey-based studies to implement an ELN in a biomedical research institute. Among the ELNs tested, we found that Microsoft OneNote presents numerous features related to ELN best functionalities. In addition, both surveyed groups preferred OneNote over a scientifically designed ELN (PerkinElmer Elements). However, OneNote remains a general note-taking application and has not been designed for scientific purposes. We therefore provide a quick guide to adapt OneNote to an ELN workflow that can also be adjusted to other nonscientific ELNs

Determinants of activity and efficacy of anti-PD1/PD-L1 therapy in patients with advanced solid tumors recruited in a clinical trials unit: a longitudinal prospective biomarker-based study

Immune-checkpoint inhibitors (ICI) have revolutionized the therapeutic landscape of cancer. However, optimal patient selection is still an unmet need. One-hundred-forty-six patients with metastatic cancer candidates to ICI at the Hospital Clinic of Barcelona Clinical Trials Unit were prospectively recruited in this observational study. Blood samples were collected at different timepoints, baseline LIPI score calculated and pre-ICI archived tissues retrieved to evaluate PD-L1, tumor-infiltrating lymphocytes (TILs) and PD1 mRNA levels. Tumor assessments were centrally reviewed by RECIST 1.1 criteria. Associations with overall response rates (ORR), durable clinical benefit (DCB), progression-free survival (PFS) and overall survival (OS) were performed with univariable/multivariable logistic and Cox regressions, where appropriate. At a median follow-up of 26.9 months, median PFS and OS were 2.7 and 12.9 months. Response rates were 17.8% with duration of response (DOR) of 4.4 months. LIPI score was independently associated with PFS (p = 0.025) and OS (p < 0.001). Immunotherapy-naïve status was independently associated with better PFS (p = 0.005). Time-to-best response (TTBR) and ORR (p < 0.001 both) were associated with better OS at univariate analysis. PFS and DOR were moderately correlated with OS (p < 0.001 both). A PD-L1 10% cut-off detected worse/best responders in terms of ORR (univariate p = 0.011, multivariate p = 0.028) and DCB (univariate p = 0.043). PD1 mRNA levels were strikingly associated to complete responses (p = 0.021). To resume, in our prospective observational pan-cancer study, baseline LIPI score, immunotherapy-naïve status, cancer type and RT before starting ICI were the most relevant clinical factors independently correlated with immunotherapy outcomes. Longer TTBR seemed to associate with better survival, while PD1 mRNA and PD-L1 protein levels might be tumor-agnostic predictive factors of response to ICI and should be furtherly explored

UNR/CDSE1 expression as prognosis biomarker in resectable pancreatic ductal adenocarcinoma patients: A proof-of-concept

Pancreatic ductal adenocarcinoma is an aggressive form of pancreatic cancer and the fourth leading cause of cancer-related death. When possible, curative approaches are based on surgical resection, though not every patient is a candidate for surgery. There are clinical guidelines for the management of these patients that offer different treatment options depending on the clinical and pathologic characteristics. However, the survival rates seen in this kind of patients are still low. The CDSE1 gene is located upstream of NRAS and encodes an RNA-binding protein termed UNR. The aim of this study was to analyze UNR expression and its correlation with outcome in patients with resectable pancreatic ductal adenocarcinoma (PDAC). For this, samples from resectable PDAC patients who underwent duodenopancreatectomy were used to evaluate UNR protein expression by immunohistochemistry using a tissue microarray. Here, we observed that low UNR expression was significantly associated with shorter progression-free survival after surgery (P = 0.010). Moreover, this prognostic marker remained significant after Cox proportional hazards model (P = 0.036). We further studied the role of CDSE1 expression in patient’s prognosis using data from public repositories (GEO and TGCA), confirming our results. Interestingly, CDSE1 expression correlated with that of genes characteristic of an immunogenic molecular subtype of pancreatic cancer. Based on these findings, UNR may be considered a potential prognostic biomarker for resectable PDAC and may serve to guide subsequent adjuvant treatment decisionsThis work has been carried out with the support of the RNA-Reg CONSOLIDER Network CSD2009-00080 (J.M.-U. and J.G.-F.), and Spanish Health Research Project Funds PI16/ 01468 from ªInstituto de Salud Carlos IIIº (A.C. and J.G.-F.), both of the Spanish Ministry of Economy, Industry and Competitivenes

Análisis de los resultados y metodología de las pruebas CRECER 1998

El currículo implementado como indicador del proceso educativo / Galindo, Claudia -- Elaboración y aplicación del proyecto de desarrollo institucional en los centros educativos de primaria y secundaria / Galindo, Claudia; Indacochea, Francisco -- Rendimiento y actitudes hacia la matemática en el sistema escolar peruano / Bazán, Jorge; Espinoza, Giuliana; Farro, Cholly -- ¿Qué piensan los docentes de sus alumnos? / Andrade, Fernando -- Para explicar las diferencias en el rendimiento en matemática de cuarto grado en el Perú urbano: análisis de resultados a partir de un modelo básico / Benavides, Martín -- Diseño muestral en la aplicación nacional CRECER 1998 / Calderón, Arturo ; Farro, Cholly; Bazán, Jorge -- Estimación del error estándar en las pruebas CRECER 1998 / Farro, Cholly; Bazán, Jorge; Torreblanca, Alberto; Millones, Óscar -- Evaluación psicométrica de las preguntas de las pruebas CRECER 1998 / Bazán, Jorge; Millones, Óscar -- Evaluación psicométrica de las pruebas CRECER 1998 / Bazán, Jorge; Millones, ÓscarRecoge sobre todo la información que se ha generado a partir de la evaluación nacional CRECER 1998. Se incluye nueve informes producidos por la UMC, que pueden ser clasificados en dos grupos: 1) aquellos reportes que se basan en el análisis de resultados y orientados a la discusión teórica en el área de la investigación educativa; y, 2) aquellos orientados a la discusión de precisiones técnicas del diseño de CRECER 1998

Data mining identifies novel RNA-binding proteins involved in colon and rectal carcinomas

Colorectal adenocarcinoma (COREAD) is the second most deadly cancer and third most frequently encountered malignancy worldwide. Despite efforts in molecular subtyping and subsequent personalized COREAD treatments, multidisciplinary evidence suggests separating COREAD into colon cancer (COAD) and rectal cancer (READ). This new perspective could improve diagnosis and treatment of both carcinomas. RNA-binding proteins (RBPs), as critical regulators of every hallmark of cancer, could fulfill the need to identify sensitive biomarkers for COAD and READ separately. To detect new RBPs involved in COAD and READ progression, here we used a multidata integration strategy to prioritize tumorigenic RBPs. We analyzed and integrated 1) RBPs genomic and transcriptomic alterations from 488 COAD and 155 READ patients, 2) ∼ 10,000 raw associations between RBPs and cancer genes, 3) ∼ 15,000 immunostainings, and 4) loss-of-function screens performed in 102 COREAD cell lines. Thus, we unraveled new putative roles of NOP56, RBM12, NAT10, FKBP1A, EMG1, and CSE1L in COAD and READ progression. Interestingly, FKBP1A and EMG1 have never been related with any of these carcinomas but presented tumorigenic features in other cancer types. Subsequent survival analyses highlighted the clinical relevance of FKBP1A, NOP56, and NAT10 mRNA expression to predict poor prognosis in COREAD and COAD patients. Further research should be performed to validate their clinical potential and to elucidate their molecular mechanisms underlying these malignancies

El derecho al nombre en el hijo extramatrimonial y la intimidad personal

TesisLa presente investigación titulada: “El Derecho al Nombre en el Hijo Extramatrimonial y la Intimidad Personal” tiene como objetivo general describir los límites entre el derecho al nombre y la intimidad personal en los procesos de filiación en el Perú, 2018. La investigación fue de campo, relacional y comparativo, el instrumento consta en recabar información por medio de fichas de observación documental la misma que está estructurada por preguntas relacionadas al tema. El tema de investigación desarrollado en la presente investigación señala que el nombre constituye un derecho a la identidad de las personas, y que se forma en el caso de los hijos extramatrimoniales con el nombre de sus progenitores que lo han reconocido; el artículo 21 del código civil, establece que el padre o la madre podrá develar el nombre de la persona con quien ha procreado sin que eso signifique prueba de filiación o de reconocimiento de la paternidad, lo cual violaría el derecho a la intimidad del padre y su importancia como un valor de la persona