Antibody Validation and Dual IHC Staining of Glioblastoma Multiforme to Isolate Microglia Cells in Glial Cell Population for Biomarker Identification

https://openworks.mdanderson.org/sumexp23/1068/thumbnail.jp

Cellular and Molecular Mechanisms of Liver Fibrosis in Patients with NAFLD

The expression of immune- and cancer-related genes was measured in liver biopsies from 107 NAFLD patients. The strongest difference in overall gene expression was between liver fibrosis stages F3 and F4, with 162 cirrhosis-associated genes identified. Strong correlations with fibrosis progression from F1 to F4 were observed for 91 genes, including CCL21, CCL2, CXCL6, and CCL19. In addition, the expression of 21 genes was associated with fast progression to F3/F4 in an independent group of eight NAFLD patients. These included the four chemokines, SPP1, HAMP, CXCL2, and IL-8. A six-gene signature including SOX9, THY-1, and CD3D had the highest performance detecting the progressors among F1/F2 NAFLD patients. We also characterized immune cell changes using multiplex immunofluorescence platforms. Fibrotic areas were strongly enriched in CD3+ T cells compared to CD68+ macrophages. While the number of CD68+ macrophages increased with fibrosis severity, the increase in CD3+ T-cell density was more substantial and progressive from F1 to F4. The strongest correlation with fibrosis progression was observed for CD3+CD45R0+ memory T cells, while the most significant increase in density between F1/F2 and F3/F4 was for CD3+CD45RO+FOXP3+CD8- and CD3+CD45RO-FOXP3+CD8- regulatory T cells. A specific increase in the density of CD68+CD11b+ Kupffer cells with liver fibrosis progression was also observed

Propuesta de mejora en el procedimiento de evaluación del desempeño laboral en la empresa Electroingeniería S.A.S. de Tuluá - Valle para el año 2020

La Evaluación del Desempeño Laboral (EDL) es un proceso muy importante que consiste en integrar los elementos más importantes para medir el desempeño individual de los empleados, alineando sus actividades diarias e identificando sus fortalezas y debilidades para tener un buen desempeño y productividad en el trabajo. Por tal motivo, se realiza una propuesta para mejorar este proceso en la empresa Electroingeniería SAS de la ciudad de Tuluá, para este año 2020. Se usarán métodos e instrumentos cualitativos, como una encuesta a los empleados, para conocer el nivel de satisfacción y cuánto es la aceptación frente a los procesos actuales en la empresa. Este proceso va a ayudar a los empleados a tener un desempeño óptimo en la empresa y a reconocer el logro de las metas organizacionales, promoviendo el desarrollo y la calidad de vida de los empleados.The Assessment of the Labor Performance (ALP) is a very important process that consists in integrate the most important elements for measuring the individual performance of employers, aligning their daily activities and identifying their strengths and weakness for having a good performance and productivity in the job. For this reason, it was created a proposal to improve this process in the company Electroingenieria SAS of Tuluá city, for this year 2020. It will be used methods and qualitative instruments such as a poll to employers to know the satisfaction level and how much is the acceptance in front of the current processes in the company. This process is going to help the employees to have an optimize performance in the company and recognize the attainment of the organizational goals, promoting the development and quality of life of the employees

Tumor Suppressor DEAR1 Regulates Mammary Epithelial Cell Fate and Predicts Early Onset and Metastasis in Triple Negative Breast Cancer

Triple negative breast cancer (TNBC) is a disease of poor prognosis, with the majority classified as the basal-like subtype associated with epithelial-mesenchymal transition and metastasis. Because basal breast cancers originate from proliferative luminal progenitor-like cells upon dysregulation of proper luminal differentiation, genes regulating luminal-basal transition are critical to elucidate novel therapeutic targets to improve TNBC outcomes. Herein we demonstrate that the tumor suppressor DEAR1/TRIM62 is a critical regulator of luminal cell fate. DEAR1 loss in human mammary epithelial cells results in significantly enhanced mammosphere formation that is accelerated in the presence of TGF-β/SMAD3 signaling. Mammospheres formed following DEAR1 loss are enriched for ALDH1A1 and CK5 expression, EpCAM-/CD49f+ and CD44high/24low basal-like epithelial cells, indicating that DEAR1 regulates stem/progenitor cell properties and luminal-basal progenitor transition. We show that DEAR1 maintains luminal differentiation as a novel ubiquitin ligase for SNAI2/SLUG, a master regulator driving stemness and generation of basal-like progenitor populations. We also identify a significant inverse correlation between DEAR1 and SNAI2 expression in a 103 TNBC case cohort and show that low DEAR1 expression significantly correlates with young age of onset and shorter time to metastasis, suggesting DEAR1 could serve as a biomarker to stratify early onset TNBCs for targeted stem cell therapies

Automated Cellular-Level Dual Global Fusion of Whole-Slide Imaging for Lung Adenocarcinoma Prognosis

Histopathologic whole-slide images (WSI) are generally considered the gold standard for cancer diagnosis and prognosis. Survival prediction based on WSI has recently attracted substantial attention. Nevertheless, it remains a central challenge owing to the inherent difficulties of predicting patient prognosis and effectively extracting informative survival-specific representations from WSI with highly compounded gigapixels. In this study, we present a fully automated cellular-level dual global fusion pipeline for survival prediction. Specifically, the proposed method first describes the composition of different cell populations on WSI. Then, it generates dimension-reduced WSI-embedded maps, allowing for efficient investigation of the tumor microenvironment. In addition, we introduce a novel dual global fusion network to incorporate global and inter-patch features of cell distribution, which enables the sufficient fusion of different types and locations of cells. We further validate the proposed pipeline using The Cancer Genome Atlas lung adenocarcinoma dataset. Our model achieves a C-index of 0.675 (±0.05) in the five-fold cross-validation setting and surpasses comparable methods. Further, we extensively analyze embedded map features and survival probabilities. These experimental results manifest the potential of our proposed pipeline for applications using WSI in lung adenocarcinoma and other malignancies

Realidades interculturales, miradas hacia el género y la educación

Este texto contribuye al análisis científico de varias áreas del conocimiento como la filosofía social, la patología, la educación para el cuidado del medio ambiente y la sustentabilidad que inciden en diversas unidades de aprendizaje de la Licenciatura en Educación para la Salud y de la Maestría en Sociología de la SaludLa presente obra, es la reunión de varias investigaciones que se han dado cita para construir un libro que representa el horizonte de autores y lectores en la pasión del dialogo. Se trata de experiencias de los observadores e interpretes de la realidad de los observadores e interpretes de la realidad social quienes se aventuraron a reunir las voces de los informantes que resguardan los secretos de sus comunidades acerca de su cultura, organización simbólica, y de sus practicas y rituales engarzados en la vida cotidiana

Integrative Genomic and Transcriptomic Profiling of Pulmonary Sarcomatoid Carcinoma Identifies Molecular Subtypes Associated With Distinct Immune Features and Clinical Outcomes

BACKGROUND: Pulmonary sarcomatoid carcinoma (PSC) is a rare and aggressive subtype of non-small cell lung cancer (NSCLC), characterized by the presence of epithelial and sarcoma-like components. The molecular and immune landscape of PSC has not been well defined. METHODS: Multiomics profiling of 21 pairs of PSCs with matched normal lung tissues was performed through targeted high-depth DNA panel, whole-exome, and RNA sequencing. We describe molecular and immune features that define subgroups of PSC with disparate genomic and immunogenic features as well as distinct clinical outcomes. RESULTS: In total, 27 canonical cancer gene mutations were identified, with CONCLUSIONS: We provided detailed insight into the mutational landscape of PSC and identified two molecular subtypes associated with prognosis. IM-H tumors were associated with favorable recurrence-free survival and overall survival, highlighting the importance of tumor immune infiltration in the biological and clinical features of PSCs

El reencuentro con la naturaleza: voces femeninas en el tiempo

Este texto contribuye al análisis científico de diferentes áreas del conocimiento la filosofía social, la educación para el cuidado del medio ambiente mediante la sustentabilidad que incide en diversas unidades de aprendizaje en Educación para la Salud y de la Maestria en Sociología de la SaludEl relato de las voces femeninas que se escuchan en el tiempo, narran las luchas por defender un ideal, con frecuencia en la organización de las mujeres que pugnan por estabilizar el equilibrio de la naturaleza, por medio de tácticas educativas que van recorriendo el bachillerato, la normal y la universidad

Differential Spatial Gene and Protein Expression Associated with Recurrence Following Chemoradiation for Localized Anal Squamous Cell Cancer

The identification of transcriptomic and protein biomarkers prognosticating recurrence risk after chemoradiation of localized squamous cell carcinoma of the anus (SCCA) has been limited by a lack of available fresh tissue at initial presentation. We analyzed archival FFPE SCCA specimens from pretreatment biopsies prior to chemoradiation for protein and RNA biomarkers from patients with localized SCCA who recurred (N = 23) and who did not recur (N = 25). Tumor cells and the tumor microenvironment (TME) were analyzed separately to identify biomarkers with significantly different expression between the recurrent and non-recurrent groups. Recurrent patients had higher mean protein expression of FoxP3, MAPK-activation markers (BRAF, p38-MAPK) and PI3K/Akt activation (phospho-Akt) within the tumor regions. The TME was characterized by the higher protein expression of immune checkpoint biomarkers such as PD-1, OX40L and LAG3. For patients with recurrent SCCA, the higher mean protein expression of fibronectin was observed in the tumor and TME compartments. No significant differences in RNA expression were observed. The higher baseline expression of immune checkpoint biomarkers, together with markers of MAPK and PI3K/Akt signaling, are associated with recurrence following chemoradiation for patients with localized SCCA. These data provide a rationale towards the application of immune-based therapeutic strategies to improve curative-intent outcomes beyond conventional therapies for patients with SCCA

Phase II Trial of Neoadjuvant Sitravatinib Plus Nivolumab in Patients Undergoing Nephrectomy for Locally Advanced Clear Cell Renal Cell Carcinoma

Sitravatinib is an immunomodulatory tyrosine kinase inhibitor that can augment responses when combined with programmed death-1 inhibitors such as nivolumab. We report a single-arm, interventional, phase 2 study of neoadjuvant sitravatinib in combination with nivolumab in patients with locally advanced clear cell renal cell carcinoma (ccRCC) prior to curative nephrectomy (NCT03680521). The primary endpoint was objective response rate (ORR) prior to surgery with a null hypothesis ORR = 5% and the alternative hypothesis set at ORR = 30%. Secondary endpoints were safety; pharmacokinetics (PK) of sitravatinib; immune effects, including changes in programmed cell death-ligand 1 expression; time-to-surgery; and disease-free survival (DFS). Twenty patients were evaluable for safety and 17 for efficacy. The ORR was 11.8%, and 24-month DFS probability was 88·0% (95% CI 61.0 to 97.0). There were no grade 4/5 treatment-related adverse events. Sitravatinib PK did not change following the addition of nivolumab. Correlative blood and tissue analyses showed changes in the tumour microenvironment resulting in an immunologically active tumour by the time of surgery (median time-to-surgery: 50 days). The primary endpoint of this study was not met as short-term neoadjuvant sitravatinib and nivolumab did not substantially increase ORR