Corrigendum to “Prostaglandin F2a-induced prostate transmembrane protein, androgen induced 1 mediates ovarian cancer progression increasing epithelial plasticity” [Neoplasia 21 (2019) 1073–1084]

Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Cyclooxygenase 2 Effector Genes as Potential Inflammation-Related Biomarkers for Colorectal Cancer Circulating Tumor Cells Detection by Liquid Biopsy

Cyclooxygenase 2 (COX2) has been implicated in cancer development and metastasis. We have identified several COX2-regulated inflammation-related genes in human colorectal cancer cells and shown that some of them play important roles in tumor progression. In this work, we have studied the COX2-regulated genes in the mouse colorectal cancer cell line CT26, to find that many are also regulated by COX2 over-expression. On the other hand, we generated a CT26 cell line expressing Gfp and Luciferase, to study tumor growth and metastasis in immunocompetent Balb/c mice. We then collected solid tissue, and blood samples, from healthy and tumor-bearing mice. Using the Parsortix cell separation system and taking advantage of the fact that the tumor cells expressed Gfp, we were able to identify circulating tumor cells (CTCs) in some of the mice. We compared the mRNA expression levels of Ptgs2 and effector genes in the samples obtained from tumor-bearing or healthy mice, namely, tumor or healthy colon, Ficoll purified buffy coat, and Parsortix-isolated cells to find different patterns between healthy, tumor-bearing mice with or without CTCs. Although for genes like Il15 we did not observe any difference between healthy and tumor-bearing mice in Ficoll or Parsortix samples; others, such as Egr1, Zc3h12a, Klf4, or Nfat5, allowed distinguishing for cancer or CTC presence. Gene expression analysis in Ficoll or Parsortix processed samples, after liquid biopsy, may offer valuable diagnostic and prognostic information and thus should be further studied.This research was funded by grants from “Ministerio de Ciencia e Innovación” (SAF2013-42850-R, SAF2016-75988-R, and PID2019-104760RB-I00), “Comunidad de Madrid (S2017/BMD-3671. INFLAMUNE-CM), Fondo de Investigaciones Sanitarias” (BIOIMID) to MF and Institutional grants from “Fundación Ramón Areces” and “Banco de Santander”. KS was the recipient of a Spanish Association Against Cancer Oncology Investigator grant (AECC AIO)

Cyclooxygenase 2 effector genes as potential inflammation-related biomarkers for colorectal cancer circulating tumor cells detection by liquid biopsy

Cyclooxygenase 2 (COX2) has been implicated in cancer development and metastasis. We have identified several COX2-regulated inflammation-related genes in human colorectal cancer cells and shown that some of them play important roles in tumor progression. In this work, we have studied the COX2-regulated genes in the mouse colorectal cancer cell line CT26, to find that many are also regulated by COX2 over-expression. On the other hand, we generated a CT26 cell line expressing Gfp and Luciferase, to study tumor growth and metastasis in immunocompetent Balb/c mice. We then collected solid tissue, and blood samples, from healthy and tumor-bearing mice. Using the Parsortix® cell separation system and taking advantage of the fact that the tumor cells expressed Gfp, we were able to identify circulating tumor cells (CTCs) in some of the mice. We compared the mRNA expression levels of Ptgs2 and effector genes in the samples obtained from tumor-bearing or healthy mice, namely, tumor or healthy colon, Ficoll purified buffy coat, and Parsortix-isolated cells to find different patterns between healthy, tumor-bearing mice with or without CTCs. Although for genes like Il15 we did not observe any difference between healthy and tumor-bearing mice in Ficoll or Parsortix samples; others, such as Egr1, Zc3h12a, Klf4, or Nfat5, allowed distinguishing for cancer or CTC presence. Gene expression analysis in Ficoll or Parsortix processed samples, after liquid biopsy, may offer valuable diagnostic and prognostic information and thus should be further studie

Prostaglandin F 2α-induced prostate transmembrane protein, androgen induced 1 mediates ovarian cancer progression increasing epithelial plasticity

The role of prostaglandin (PG) F2a has been scarcely studied in cancer. We have identified a new function for PGF2a in ovarian cancer, stimulating the production of Prostate Transmembrane Protein, Androgen Induced 1 (PMEPA1). We show that this induction increases cell plasticity and proliferation, enhancing tumor growth through PMEPA1. Thus, PMEPA1 overexpression in ovarian carcinoma cells, significantly increased cell proliferation rates, whereas PMEPA1 silencing decreased proliferation. In addition, PMEPA1 overexpression buffered TGF signaling, via reduction of SMADdependent signaling. PMEPA1 overexpressing cells acquired an epithelial morphology, associated with higher Ecadherin expression levels while catenin nuclear translocation was inhibited. Notwithstanding, high PMEPA1 levels also correlated with epithelial to mesenchymal transition markers, such as vimentin and ZEB1, allowing the cells to take advantage of both epithelial and mesenchymal characteristics, gaining in cell plasticity and adaptability. Interestingly, in mouse xenografts, PMEPA1 overexpressing ovarian cells had a clear survival and proliferative advantage, resulting in higher metastatic capacity, while PMEPA1 silencing had the opposite effect. Furthermore, high PMEPA1 expression in a cohort of advanced ovarian cancer patients was observed, correlating with Ecadherin expression. Most importantly, high PMEPA1 mRNA levels were associated with lower patient survivalThis work was supported by grants from Ministerio de Ciencia e Innovación (SAF201342850R and SAF201675988R) Comunidad de Madrid (S2017/BMD3671. INFLAMUNECM), Fondo de Investigaciones Sanitarias (BIOIMID) to M.F. and grants from the AECC (Grupos Estables de Investigacion 2011AECC GCB 110333 REVE) and the Instituto de Salud Carlos III (ISCIII: PI16/00134 and CIBEONC: CB16/12/00295) to G.M.B. K.S. was recipient of a Spanish Association Against Cancer oncology investigator grant (AECC AIO). A.J.S. and AM were recipients of FPU predoctoral fellowships from the Spanish Ministry of Education, Culture and Sports (FPU20122084 and 5338, respectively)

Dendritic cell deficiencies persist seven months after SARS-CoV-2 infection

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection induces an exacerbated inflammation driven by innate immunity components. Dendritic cells (DCs) play a key role in the defense against viral infections, for instance plasmacytoid DCs (pDCs), have the capacity to produce vast amounts of interferon-alpha (IFN-α). In COVID-19 there is a deficit in DC numbers and IFN-α production, which has been associated with disease severity. In this work, we described that in addition to the DC deficiency, several DC activation and homing markers were altered in acute COVID-19 patients, which were associated with multiple inflammatory markers. Remarkably, previously hospitalized and nonhospitalized patients remained with decreased numbers of CD1c+ myeloid DCs and pDCs seven months after SARS-CoV-2 infection. Moreover, the expression of DC markers such as CD86 and CD4 were only restored in previously nonhospitalized patients, while no restoration of integrin β7 and indoleamine 2,3-dyoxigenase (IDO) levels were observed. These findings contribute to a better understanding of the immunological sequelae of COVID-19

SARS-CoV-2 viral load in nasopharyngeal swabs is not an independent predictor of unfavorable outcome

The aim was to assess the ability of nasopharyngeal SARS-CoV-2 viral load at first patient’s hospital evaluation to predict unfavorable outcomes. We conducted a prospective cohort study including 321 adult patients with confirmed COVID-19 through RT-PCR in nasopharyngeal swabs. Quantitative Synthetic SARS-CoV-2 RNA cycle threshold values were used to calculate the viral load in log10 copies/mL. Disease severity at the end of follow up was categorized into mild, moderate, and severe. Primary endpoint was a composite of intensive care unit (ICU) admission and/or death (n = 85, 26.4%). Univariable and multivariable logistic regression analyses were performed. Nasopharyngeal SARS-CoV-2 viral load over the second quartile (≥ 7.35 log10 copies/mL, p = 0.003) and second tertile (≥ 8.27 log10 copies/mL, p = 0.01) were associated to unfavorable outcome in the unadjusted logistic regression analysis. However, in the final multivariable analysis, viral load was not independently associated with an unfavorable outcome. Five predictors were independently associated with increased odds of ICU admission and/or death: age ≥ 70 years, SpO2, neutrophils > 7.5 × 103/µL, lactate dehydrogenase ≥ 300 U/L, and C-reactive protein ≥ 100 mg/L. In summary, nasopharyngeal SARS-CoV-2 viral load on admission is generally high in patients with COVID-19, regardless of illness severity, but it cannot be used as an independent predictor of unfavorable clinical outcome

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Identification of PMEPA1 as a cyclooxygenase-2 induced gene and its potential implication in cancer progression

Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 30-06-2017Esta tesis tiene embargado el acceso al texto completo hasta el 30-12-2018Cyclooxygenase 2 (COX2) elevated expression has been associated with tumour development especially in colorectal cancer and it is well established that COX2 inhibition can help prevent cancer. In order to study the mechanisms that mediate the pro-tumourigenic effects of COX2, cell lines stably overexpressing this gene were generated and gene expression microarray analysis revealed that PMEPA1 was one of the up-regulated genes. It was originally identified as an androgen-induced gene with abundant expression in several cancers. The encoded product is a transforming growth factor-β (TGFβ)-induced transmembrane protein overexpressed in breast, prostate and colorectal cancer. We also found that PMEPA1 can be upregulated by COX2 overexpression in colon cancer cells and the prostaglandins produced by them. In view of these observations, we overexpressed PMEPA1 in human colon adenocarcinoma (HT29) and human ovarian carcinoma (SKOV3) cells to test if part of the protumourigenic effects of COX2 were due to PMEPA1. PMEPA1 overexpression increased cell proliferation rates. Also, PMEPA1 provided a negative feedback loop over TGF-β signaling, regulating SMAD and noncanonical signalling pathways. The actin cytoskeleton distribution was modified in PMEPA1 overexpressing SKOV3 cells, resulting in differences in cell morphology. Immunofluorescence revealed β-catenin nuclear translocation blockade when PMEPA1 is overexpressed. Additionally, subcutaneous and intraperitoneal mouse xenografts experiments in nude mice showed a differential effect of PMEPA1 overexpressing HT29 and SKOV3 cells, leading to a final growth delay of HT29 xenografts, while PMEPA1 overexpressing SKOV3 cells have a high survival and proliferative advantage. In addition, orthotopic mouse xenograft experiments, with SKOV3 cells, showed the same proliferative and establishment advantage when PMEPA1 is overexpressed. Different PMEPA1 transcripts have been described, that differently overlap with NKILA sequence (a lncRNA that regulates NF-κB). We found that each transcript differently coprecipitates with IκBα and with NKILA and thus regulates signaling of NF-κB and SMAD pathways. Finally, immunohistochemistry of human tumour samples revealed a high PMEPA1 expression in patients with advanced tumour stages. These findings suggest that PMEPA1 may have an important role in cancer progression, and could be a diagnostic and prognost biomarker in colorectal and ovarian tumours, but further investigations should be done.La elevada expresión de la Ciclooxigenasa 2 (COX2) ha sido asociada con el desarrollo tumoral especialmente en cáncer colorrectal y está bien establecido que la inhibición de COX2 ayuda a prevenir y tratar el cáncer. Con el objetivo de estudiar los mecanismos de los efectos tumorigénicos de COX2, se generaron líneas celulares que sobreexpresaban este gen y su análisis reveló que PMEPA1 era uno de los genes inducidos por COX2. PMEPA1 ha sido identificado previamente como un gen inducido por andrógenos y con alta expresión en varios tipos de cáncer. El producto codificante es una proteína transmembrana inducida por el factor de crecimiento transformante-β (TGF-β), sobreexpresada en cáncer de mama, próstata y colorrectal principalmente. Observamos que la expresión de PMEPA1 podía estar inducida por la sobreexpresión de COX2 y por las prostaglandinas producidas. Para analizar su efecto, PMEPA1 fue sobreexpresada en células de adenocarcinoma de colon (HT29) y de carcinoma de ovario (SKOV3) humanos para comprobar si parte de los efectos pro-tumorigénicos de COX2 son debidos a PMEPA1. La sobreexpresión de PMEPA1 incrementaba el crecimiento celular. Además, PMEPA1 ejerce una regulación negativa sobre TGF-β, regulando la señalización de las proteínas SMAD y de la vía no canónica. La distribución del citoesqueleto de actina se ve modificada en las células SKOV3 que sobreexpresan PMEPA1, que resulta en diferencias en la morfología celular. Por ello, las inmunofluorescencias revelaron que PMEPA1 bloquea la translocación nuclear de β-catenina. En paralelo, los ensayos de xenoinjertos subcutáneos e intraperitoneales con ratones nude, mostraron diferencias entre las células HT29 y SKOV3 que sobreexpresan PMEPA1, con una gran ventaja proliferativa y de supervivencia en las SKOV3 respecto de las HT29. Los modelos de xenoinjertos ortotópicos de ovario mostraron la misma ventaja proliferativa y de establecimiento celular de las SKOV3 que sobreexpresan PMEPA1. PMEPA1 tiene diferentes tránscritos que se superponen de forma diferente con la secuencia de NKILA (un RNA largo no codificante). Hemos comprobado que los distintos tránscritos co-precipitan con IκBα y NKILA de forma distinta y, por lo tanto, regulan la señalización de NF-κB y SMADs. Finalmente, las inmunohistoquímicas en muestras de tumores humanos han revelado la alta expresión de PMEPA1 en pacientes con estadíos tumorales avanzados. Por todo ello, PMEPA1 podría tener un papel importante en la progresión del cáncer y podría ser un biomarcador de diagnóstico y pronóstico en tumores colorrectales y de ovario

El amigo verdadero del pueblo (Segovia. 1868)

Título tomado de la cabeceraAlgunos n. com suplementosA partir del Año I, n. 2 (25 nov. 1868) el impresor es: Imp. de D. P. OnderoA partir del Año I, n. 39 (3 abr. 1869) el impresor es: Imp. de AlbaA partir del Año I, n. 65 (3 jul. 1869) el impresor es: Imp. de D. P. Onder

Evolution of Strategic Planning in the Industrialization of Banana Derivatives

El presente artículo de revisión tiene como objetivo analizar la evolución de la planificación estratégica dentro del campo de la agroindustria, analizando su grado de influencia en el crecimiento de las organizaciones y en los sectores estratégicos de la economía, como herramienta efectiva para el logro de los objetivos.  La investigación es de tipo descriptivo y su diseño es no experimental, de corte transversal. Para llevarlo a cabo se utilizó el método de revisión bibliográfica a través de artículos científicos sobre el tema abordado.  Además, se aplicaron métodos teóricos tales como: histórico lógico, inductivo – deductivo, análisis y síntesis. Se concluye que durante los años la planificación estratégica en la agroindustria ha pasado desde el enfoque de producción a gran escala con el propósito de ser únicamente exportado, a ser un recurso importante para iniciar proyectos de inversión para la agregación de valor al banano, implementando infraestructura de procesamiento y tecnología, para mercados locales e internacionales. Además, los sectores económico, político, social y cultural han contribuido positivamente para el mejoramiento de los elementos de la planificación estratégica y su viabilidad en la agroindustria.The objective of this review article is to analyze the evolution of strategic planning within the field of agribusiness, analyzing its degree of influence on the growth of organizations and in the strategic sectors of the economy, as an effective tool for achieving the objectives. goals.  The research is descriptive and its design is non-experimental, cross-sectional. To carry it out, the bibliographic review method was used through scientific articles on the topic addressed. In addition, theoretical methods were applied such as: historical-logical, inductive-deductive, analysis and synthesis.  It is concluded that over the years strategic planning in the agroindustry has gone from the focus of large-scale production with the purpose of being solely exported, to being an important resource to initiate investment projects for adding value to bananas, implementing infrastructure. processing and technology, for local and international markets. Furthermore, the economic, political, social and cultural sectors have contributed positively to the improvement of the elements of strategic planning and its viability in the agroindustr