Project description:Excessive reactive oxygen species (ROS) can cause oxidative stress and consequently cell injury contributing to a wide range of diseases. Addressing the critical gaps in our understanding of the adaptive molecular events downstream ROS provocation holds promise for the identification of druggable metabolic vulnerabilities. Herein, we unveil a direct molecular link between the activity of two estrogen-related receptor (ERR) isoforms and the control of glutamine utilization and glutathione antioxidant production. ERRα downregulation restricts glutamine entry into the TCA cycle while ERRγ upregulation promotes glutamine-driven glutathione production. Notably, we identify increased ERRγ expression/activation as a hallmark of oxidative stress triggered by mitochondrial disruption or chemotherapy. Enhanced tumor antioxidant capacity is an underlying feature of human breast cancer (BCa) patients that respond poorly to treatment. We demonstrate that pharmacological inhibition of ERRγ with the selective inverse agonist GSK5182 increases antitumor efficacy of the chemotherapeutic paclitaxel on poor outcome BCa tumor organoids. Our findings thus underscore the ERRs as novel redox sensors and effectors of a ROS defense program and highlight the potential therapeutic advantage of exploiting ERRγ inhibitors for the treatment of BCa and other diseases where oxidative stress plays a central role. In this study, ERRγ ChIP-seq analysis was performed under normal conditions in the breast cancer cell line BT-474.
Project description:In this study, we sought to broaden our understanding of circulatory monocyte functions captured during the acute (on hospital admission; day0) and recovery (one month follow-up) stages of patients diagnosed with community-acquired pneumonia (CAP).
Project description:In this study, we sought to broaden our understanding of circulatory monocyte functions captured during the acute (on hospital admission) and recovery (one-month follow-up) stages of patients diagnosed with community-acquired pneumonia (CAP).
Project description:The aim of the study is to identify a pattern of chemoresistive sensors able to recognise the presence of a tumoral pathology from a health state through the analysis of Volatile Organic Compounds inside the specimen.
The chemoresistive nanostructured sensors are into an innovative patented device SCENT B1 which can analyse different specimens: blood samples, tissue biopsies, cell cultures.
In this study SCENT B1 wil be used to compare the measures of:
* tumoral and health tissues taken from different neoplasms after their surgical resection
* blood samples from healthy and tumor affected people
* pre and post- operative blood samples of tumor affected people