Publications by authors named "Raul Pena"

Background: As in most solid cancers, the emergence of cells with oncogenic mutations in the mammary epithelium alters the tissue homeostasis. Some soluble factors, such as TGFβ, potently modify the behavior of healthy stromal cells. A subpopulation of cancer-associated fibroblasts expressing a TGFβ target, the SNAIL1 transcription factor, display myofibroblastic abilities that rearrange the stromal architecture.

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IoT platforms for the transportation industry are portable with limited battery life and need real-time and long-term monitoring operations. Since MQTT and HTTP are widely used as the main communication protocols in the IoT, it is imperative to analyze their power consumption to provide quantitative results that help maximize battery life in IoT transportation systems. Although is well known that MQTT consumes less power than HTTP, a comparative analysis of their power consumption with long-time tests and different conditions has not yet been conducted.

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Article Synopsis
  • * Deleting Snail1 in CAFs reduced their ability to polarize bone-marrow-derived macrophages (BMDMΦs) towards an immunosuppressive phenotype, compared to those exposed to active CAFs, which inhibited macrophage cytotoxicity.
  • * Active CAFs also promoted gene expressions related to immunosuppression in macrophages and the activation of regulatory T cells (T-regs), suggesting that CAFs in the tumor microenvironment hinder anti-tumor immunity. *
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Colon tumors of the mesenchymal subtype have the lowest overall survival. Snail1 is essential for the acquisition of this phenotype, characterized by increased tumor stemness and invasion, and high resistance to chemotherapy. Here, we find that Snail1 expression in colon tumor cells is dependent on an autocrine noncanonical Wnt pathway.

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Ligand-dependent corepressor (LCOR) mediates normal and malignant breast stem cell differentiation. Cancer stem cells (CSCs) generate phenotypic heterogeneity and drive therapy resistance, yet their role in immunotherapy is poorly understood. Here we show that immune-checkpoint blockade (ICB) therapy selects for LCOR CSCs with reduced antigen processing/presentation machinery (APM) driving immune escape and ICB resistance in triple-negative breast cancer (TNBC).

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Purpose: To characterize expression of neuregulin-1 (NRG1), an HER3 ligand, in HER2-positive breast cancer and its relation with the efficacy of trastuzumab with or without pertuzumab.

Experimental Design: Characterization of NRG1 expression in tumor cell lines, in tumor specimens, and in cancer-associated fibroblasts (CAFs). Patient-derived CAFs were used to investigate NRG1 impact on the activity of trastuzumab with or without pertuzumab in HER2-positive breast cancer cells.

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Snail1 is a transcriptional factor required for epithelial to mesenchymal transition and activation of cancer-associated fibroblasts (CAF). Apart from that, tumor endothelial cells also express Snail1. Here, we have unraveled the role of Snail1 in this tissue in a tumorigenic context.

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Tumors are complex tissues composed of transformed epithelial cells as well as cancer-activated fibroblasts (CAF) that facilitate epithelial tumor cell invasion. We show here that CAFs and other mesenchymal cells rely much more on glutamine than epithelial tumor cells; consequently, they are more sensitive to inhibition of glutaminase. Glutamine dependence drove CAF migration toward this amino acid when cultured in low glutamine conditions.

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  • The inflammatory immune response can contribute to the development of colorectal cancer (CRC) if not properly regulated.
  • A study using transcriptomics analysis found a significant connection between inflammation and the expression of granzyme A (GzmA) in human CRC.
  • In mouse models, inhibiting GzmA reduced gut inflammation and prevented CRC, highlighting its role in promoting cancer through mechanisms involving NF-κB and STAT3 activation, suggesting GzmA could be a potential therapeutic target for CRC.
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  • Myofibroblasts, influenced by the transcription factor Snail1, are linked to poor cancer survival and can promote tumor metastasis through changes in the tumor microenvironment.
  • Therapeutic strategies targeting fibroblast activity need to be carefully considered, as normal fibroblast functions can actually help limit tumor spread.
  • Research identified specific epigenetic modifications induced by TGFβ/Snail1 and demonstrated that methyltransferase inhibitors can effectively reduce myofibroblast activity, offering potential treatment options for conditions like breast cancer and pulmonary fibrosis.
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In cancer cells, epithelial-to-mesenchymal transition (EMT) is controlled by Snail1, a transcriptional factor also required for the activation of cancer-associated fibroblasts (CAF). Snail1 is short-lived in normal epithelial cells as a consequence of its coordinated and continuous ubiquitination by several F-box-specific E3 ligases, but its degradation is prevented in cancer cells and in activated fibroblasts. Here, we performed an siRNA screen and identified USP27X as a deubiquitinase that increases Snail1 stability.

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Carcinomas, such as colon cancer, initiate their invasion by rescuing the innate plasticity of both epithelial cells and stromal cells. Although Snail is a transcriptional factor involved in the Epithelial-Mesenchymal Transition, in recent years, many studies have also identified the major role of Snail in the activation of Cancer-Associated Fibroblast (CAF) cells and the remodeling of the extracellular matrix. In CAFs, Platelet-derived growth factor (PDGF) receptor signaling is a major functional determinant.

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Canonical and noncanonical Wnt pathways share some common elements but differ in the responses they evoke. Similar to Wnt ligands acting through the canonical pathway, Wnts that activate the noncanonical signaling, such as Wnt5a, promote Disheveled (Dvl) phosphorylation and its binding to the Frizzled (Fz) Wnt receptor complex. The protein kinase CK1ε is required for Dvl/Fz association in both canonical and noncanonical signaling.

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The continuous technological advances in favor of mHealth represent a key factor in the improvement of medical emergency services. This systematic review presents the identification, study, and classification of the most up-to-date approaches surrounding the deployment of architectures for mHealth. Our review includes 25 articles obtained from databases such as IEEE Xplore, Scopus, SpringerLink, ScienceDirect, and SAGE.

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Hypothyroidism is a commonly encountered clinical condition with variable prevalence. It has profound effects on cardiac function that can impact cardiac contractility, vascular resistance, blood pressure, and heart rhythm. With this review, we aim to describe the effects of hypothyroidism and subclinical hypothyroidism on the heart.

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Snail1 transcriptional factor is essential for triggering epithelial-to-mesenchymal transition (EMT) and inducing tumor cell invasion. We report here an EMT-independent action of Snail1 on tumor invasion, as it is required for the activation of cancer-associated fibroblasts (CAF). Snail1 expression in fibroblasts requires signals derived from tumor cells, such as TGFβ; reciprocally, in fibroblasts, Snail1 organizes a complex program that stimulates invasion of epithelial cells independent of the expression of Snail1 in these cells.

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Lung cancer (LC) remains the leading cause of cancer mortality worldwide, and non-small cell LC (NSCLC) represents 80% of all LC. Oxidative stress and inflammation, autophagy, ubiquitin-proteasome system, nuclear factor (NF)-κB, and mitogen activated protein kinases (MAPK) participate in LC pathophysiology. Currently available treatment for LC is limited and in vivo models are lacking.

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The Snail1 transcriptional factor is required for correct embryonic development, yet its expression in adult animals is very limited and its functional roles are not evident. We have now conditionally inactivated Snail1 in adult mice and analyzed the phenotype of these animals. Snail1 ablation rapidly altered pancreas structure: one month after Snail1 depletion, acinar cells were markedly depleted, and pancreas accumulated adipose tissue.

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The recognition of clinical manifestations in both video images and physiological-signal waveforms is an important aid to improve the safety and effectiveness in medical care. Physicians can rely on video-waveform (VW) observations to recognize difficult-to-spot signs and symptoms. The VW observations can also reduce the number of false positive incidents and expand the recognition coverage to abnormal health conditions.

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This survey aims to encourage the multidisciplinary communities to join forces for innovation in the mobile health monitoring area. Specifically, multidisciplinary innovations in medical emergency scenarios can have a significant impact on the effectiveness and quality of the procedures and practices in the delivery of medical care. Wireless body sensor networks (WBSNs) are a promising technology capable of improving the existing practices in condition assessment and care delivery for a patient in a medical emergency.

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Crosstalk between tumor and stromal cells in the tumor microenvironment alter its properties in ways that facilitate the invasive behavior of tumor cells. Here, we demonstrate that cancer-associated fibroblasts (CAF) increase the stiffness of the extracellular matrix (ECM) and promote anisotropic fiber orientation, two mechanical signals generated through a Snail1/RhoA/αSMA-dependent mechanism that sustains oriented tumor cell migration and invasiveness. Snail1-depleted CAF failed to acquire myofibroblastic traits in response to TGFβ, including RhoA activation, αSMA-positive stress fibers, increased fibronectin fibrillogenesis, and production of a stiff ECM with oriented fibers.

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Article Synopsis
  • - Snail1 is a key transcriptional repressor that triggers epithelial-to-mesenchymal transition (EMT) and is crucial for maintaining stem cells, but its expression is low in adult animals.
  • - Increased levels of Snail1 in mesenchymal cells enhance their tumorigenic potential, while its removal reduces tumor growth and prevents mesenchymal stem cells (MSCs) from forming sarcomas.
  • - High Snail1 expression is found in human sarcomas, especially in undifferentiated tumors, which are linked to poorer patient outcomes, suggesting a significant role for Snail1 in sarcoma development.
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Background: Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy in humans and approximately 5% metastasize, usually to regional lymph nodes. Epithelial to mesenchymal transition (EMT) is a process involving loss of intercellular adhesion, acquisition of a mesenchymal phenotype and enhanced migratory potential; epithelial markers, such as E-cadherin, are down-regulated and mesenchymal proteins (Vimentin), increased.

Objective: To investigate the expression of EMT markers in metastatic SCC (MSCC) and their corresponding metastases, and to correlate them with clinico-pathological factors associated with an increased risk of metastasis.

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Background: The transcription factor Snail1 induces epithelial-to-mesenchymal transition (EMT), a process responsible for the acquisition of invasiveness during tumorigenesis. Several transcriptomic studies have reported Snail1-regulated genes in different cell types, many of them involved in cell adhesion. However, only a few studies have used proteomics as a tool for the characterization of proteins mediating EMT.

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