Project description:Two expression profilings were conducted in order to identify drug-associated genes in ovarian cancers. The first expression profiling was performed between RNAs from chemosensitive ovarian cancers and chemoresistant ovarian cancers. The second analysis was using a drug sensitive ovarian cancer cell line and a multi-drug resistant ovarian cancer cell line.
Project description:Two expression profilings were conducted in order to identify drug-associated genes in ovarian cancers. The first expression profiling was performed between RNAs from chemosensitive ovarian cancers and chemoresistant ovarian cancers. The second analysis was using a drug sensitive ovarian cancer cell line and a multi-drug resistant ovarian cancer cell line. Keywords: other
Project description:ChIP-seq was performed in BIN-67, BIN-67 p53ko, BIN-67 with SMARCA4 restoration and BIN-67 p53ko cells with SMARCA4 restoration to assess the impact of SMARCA4 and p53 on the pull downs of p300, H3K27ac, p53, HDAC1 and HDAC2.
Project description:High-grade serous ovarian cancer (HGSOC) remains the most lethal gynecologic malignancy and novel treatment approaches are needed. Here, we used unbiased quantitative protein mass spectrometry to assess the cellular response profile to drug perturbations in ovarian cancer cells for the rational design of potential combination therapies. Analysis of the perturbation profiles revealed proteins responding across several drug perturbations (called frequently responsive below) as well as drug-specific protein responses. The frequently responsive proteins included proteins that reflected general drug resistance mechanisms such as changes in drug efflux pumps. Network analysis of drug-specific protein responses revealed known and potential novel markers of resistance, which were used to rationalize the design of anti-resistance drug pairs. We experimentally tested the anti-proliferative effects of 12 of the proposed drug combinations in 6 HGSOC cell lines. Drug combinations tested with additive or synergistic effects are plausible candidates for overcoming or preventing resistance to single agents; these include several combinations that were synergistic (with PARPi, MEKi, and SRCi). Additionally, we observed 0.05-0.11 micromolar response to GPX4 inhibitors as single agents in the OVCAR-4 cell line. We propose several drug combinations as potential therapeutic candidates in ovarian cancer, as well as GPX4 inhibitors as single agents
Project description:Effective clinical management of advanced epithelial ovarian cancer (EOC) remains a major challenge, with most patients relapsing despite standard therapies, emphasizing the need for individualized treatment strategies and predictive approaches. Here, functional ex vivo drug testing may provide a translational approach to match patients with effective, personalized therapies based on drug sensitivity. We present DRUGSENS, a scalable and clinically adaptable ex vivo drug response screening platform that enables quantitative assessment of single-cell, on-target effects in both cultured cell lines and patient-derived samples. DRUGSENS supports high-resolution analysis of cellular responses to individual therapeutic agents and clinically relevant drug combinations, with the potential to inform personalized treatment strategies across diverse tumor types and tissue contexts. This semi-automated ex vivo assay integrates immunofluorescence-based confocal imaging with computational analysis using QuPath, Fiji, and a developed DRUGSENS R package. We successfully generated individualized drug sensitivity profiles for 21 samples derived from 17 patients across both chemotherapy-naive and relapsed disease states, achieving a 100% success rate of culture efficiency and generating individualized drug profiles within a 10-day turnaround time. Notably, most resistant samples showed poor response to multiple agents, suggesting a multidrug-resistant phenotype. Ex vivo drug responses significantly correlated with clinical outcomes, including progression-free and overall survival. In conclusion, DRUGSENS platform enables rapid, clinically relevant functional profiling of therapeutic responses in EOC and represents a valuable tool to guide treatment recommendations and suggest drug prioritization for clinical application.
2026-07-22 | GSE308072 | GEO
Project description:The impact of different restoration measures on soil microbial functions
Project description:Cisplatin and carboplatin are the primary first-line therapies for the treatment of ovarian cancer. However, resistance to these platinum-based drugs occurs in the large majority of initially responsive tumors, subsequently resulting in a poor long-term prognosis. To model the onset of drug resistance, and investigate the DNA methylation alterations associated with cisplatin resistance, we treated clonally derived, drug-sensitive A2780 epithelial ovarian cancer cells with increasing concentrations of cisplatin. After several cycles of drug selection, the isogenic drug-sensitive and -resistant pairs were subjected to global CGI methylation microarray analyses. We treated clonally derived, drug-sensitive A2780 epithelial ovarian cancer cells with increasing concentrations of cisplatin. After several cycles of drug selection, the isogenic drug-sensitive and -resistant pairs were subjected to global CGI methylation analyses by differential methylation hybridization (DMH) using a customed 44K promoter CGI microarray.