Project description:Spheroid cells derived from colon cancer patients was treated with Y-27632, a ROCK inhibitor, and we have performed whole genome microarray expression assay.
Project description:Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with very limited therapeutic options. We have recently shown that the combined inhibition of EGFR and ROCK in TNBC cells results in cell cycle arrest and ultimately cell death. However, the underlying mechanisms by which co-inhibition of EGFR and ROCK induces cell death remain unclear. To investigate the synergistic effect of the combination treatment on TNBC cells, in the present study we applied a mass spectrometry-based proteomic approach to identify proteins altered upon single and combination treatments.
Project description:Carbapenem-resistant Acinetobacter baumannii (CRAB) is a critical nosocomial pathogen with limited treatment options. Although antibiotic resistance in CRAB is well-characterized, its interactions with host immunity and the contribution of outer membrane vesicles (OMVs) to pathogenesis remain poorly understood. We examined a clinical CRAB isolate and compared it with the reference strain A19606. Antimicrobial susceptibility testing revealed complete resistance of CRAB to commonly used antibiotics in clinical practice, while A19606 remained susceptible to most agents. In murine intranasal infection models and bone marrow-derived macrophages, CRAB induced significantly stronger activation of inflammatory signaling pathways and elevated levels of pro-inflammatory cytokines relative to A19606. Transcriptomic analysis of infected lung tissue identified differentially expressed genes, enriched for inflammatory response pathways. proteomics showed upregulated proteins in CRAB related to secretion systems. OMVs characterization revealed that CRAB-derived OMVs highly enriched in proteins associated with periplasmic and outer membrane spaces, and more potent in triggering macrophage inflammatory signaling. CRAB displays expansive antibiotic resistance and enhanced pro-inflammatory potential mediated in part by unique OMVs properties. Targeting OMVs formation or host immune modulation may represent effective strategies for combating CRAB infections.