june, 2021

04jun12:0013:00SEMINAR: Paula Soriano / Carlos Manuel Cuesta12:00 - 13:00 Event Type :SEMINAR Event TagsSEMINAR

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Event Details

12:00 – 12:30 Paula Soriano

Inflammatory Tumor Microenvironment as Target in the Design of Nanoconjugates for the Treatment of Advanced Breast Cancer

Inflammasomes are essential components of the innate immune response that mediate the activation and release of pro-inflammatory cytokines to ensure the removal of harmful stimuli and repair the damaged tissue   However, inflammasome activation can have a dual role in any inflammatory response. Although the activation of the inflammasome prevents the spread of the infection and the development of tumors, a dysregulation of the inflammatory process is implicated in numerous diseases such as cancer. Specially, in breast cancer, the elimination of the inflammasome components and the associated reduction in pro-inflammatory cytokine release decrease tumor size and metastasis, and, therefore, may represent a target for patient treatment. However, the use of direct inflammasome inhibitors in breast cancer models remains relatively unexplored. Now, we have identified a new inflammasome inhibitor, MM01, that inhibits the process of ASC oligomerization, thereby preventing release of pro-inflammatory cytokines. Herein, we employed MM01 as a chemical tool to investigate the role of the inflammasome in breast cancer progression. Furthermore, we also propose the use of rationally designed polypeptide-based nanoconjugates as chemical tools to specifically target the inflammasome to fully understand its role in breast tumor progression.

12:30 – 13:00 Carlos Manuel Cuesta

Metagenomic analyses of chronic alcoholic mice and the impact of Toll-Like Receptor 4 in Gut Microbiota and Intestine

Chronic alcohol abuse induces an inflammatory response in the intestinal tract with damage to the integrity of the mucosa and the epithelium, and dysbiosis in the gut microbiome. However, it is not well understood the role of the gut bacteria in the effects of ethanol and how interact these microorganisms with the immune system. Here we hypothesize that ethanol consumption is able to alter microbiota profile and causes inflammatory response, and TLR4 could participate in these events. Wild-type (WT) and TLR4-knockout (TLR4-KO) mice were treated with or without chronic ethanol consumption for 3 months to analyze the microbiota through high throughput 16S rRNA gene sequencing of DNA extracted from faecal samples. Colon sample were used to evaluate the inflammation and gut integrity. Chronic ethanol consumption reduced the microbiota diversity and caused dysbiosis in WT mice. In addition, ethanol also upregulated inflammatory genes (IL-1β, iNOS, TNF-α) and miRNAs (miR 155-5p, miR 146a-5p) as well as altered structural and permeability genes (INTL1, CDH1, CFTR) in colon from WT mice. However, TLR4-KO mice exhibited a distinct microbiota and were protected against the activation of the immune system and alterations in the colon integrity induced by ethanol. In summary, our results demonstrate that TLR4 is a key factor to determine the gut microbiota, which is involved in the dysbiosis and inflammatory response induced by alcohol consumption.

Time

(Friday) 12:00 - 13:00

Location

Centro de Investigación Príncipe Felipe

Eduardo Primo Yúfera, 3 Valencia Spain

Organizer

Centro de Investigación Príncipe Felipeevents@cipf.es Eduardo Primo Yúfera, 3