Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA297725 | ENA |
REPOSITORIES: ENA
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Project description:Increased ploidy is common in tumors but treatments for tumors with excess chromosome sets are not available. Here, we characterize high-ploidy breast cancers and identify potential anticancer compounds selective for the high-ploidy state. Among 354 human breast cancers, 10% have mean chromosome copy number exceeding 3, and this is most common in triple negative and HER2-positive types. Women with high-ploidy breast cancers have higher risk of recurrence and death in two patient cohorts, demonstrating that it represents an important group for improved treatment. Because high-ploidy cancers are aneuploid, rather than triploid or tetraploid, we devised a two-step screen to identify selective compounds. The screen was designed to assure both external validity on diverse karyotypic backgrounds and specificity for high-ploidy cell types. This screen identified novel therapies specific to high-ploidy cells. First, we discovered 8-azaguanine, an antimetabolite that is activated by hypoxanthine phosphoribosyltransferase (HPRT), suggesting an elevated gene-dosage of HPRT in high-ploidy tumors can control sensitivity to this drug. Second, we discovered a novel compound, 2,3-Diphenylbenzo[g]quinoxaline-5,10-dione (DPBQ). DPBQ activates p53 and triggers apoptosis in a polyploid-specific manner, but does not inhibit topoisomerase or bind DNA. Mechanistic analysis demonstrates that DPBQ elicits a hypoxia gene signature and its effect is replicated, in part, by enhancing oxidative stress. Structure-function analysis defines the core benzo[g]quinoxaline-5,10 dione as being necessary for the polyploid-specific effects of DPBQ. We conclude that polyploid breast cancers represent a high-risk subgroup and that DPBQ provides a functional core to develop polyploid-selective therapy.
2015-10-03 | GSE73710 | GEO
Project description:Screens for agents that specifically kill epithelial cancer stem cells (CSCs) have not been possible due to the rarity of these cells within tumor cell populations and their relative instability in culture. We describe here an approach to screening for agents with epithelial CSC-specific toxicity. We implemented this method in a chemical screen and discovered compounds showing selective toxicity for breast CSCs. One compound, salinomycin, reduces the proportion of CSCs by >100-fold relative to paclitaxel, a commonly used breast cancer chemotherapeutic drug. Treatment of mice with salinomycin inhibits mammary tumor growth in vivo and induces increased epithelial differentiation of tumor cells. In addition, global gene expression analyses show that salinomycin treatment results in the loss of expression of breast CSC genes previously identified by analyses of breast tissues isolated directly from patients. This study demonstrates the ability to identify agents with specific toxicity for epithelial CSCs Experiment Overall Design: Experimentally transformed HMLER breast cancer cells were treated in culture with either paclitaxel (10nM) or salinomycin (1uM) for one week. There were three biologic replicates for each treatment condition.
2009-09-15 | E-GEOD-17215 | biostudies-arrayexpress
Project description:The high-throughput sequencing technology was performed after the treatment of human triple negative breast cancer cells MDA-MB-231 with the active compound D16 designed and synthesized by ourselves, to explore the expression of genes related to cell proliferation, adhesion, migration and invasion of human triple negative breast cancer cells MDA-MB-231 after the treatment of the active compound Changes to explore the effect of active compounds on the proliferation and motility of triple breast breast cancer cells and to find an interesting target gene, CKAP2.
2021-08-17 | GSE182063 | GEO
Project description:Breast cancer cell lines treated with EZH2 inhibitor compounds
| PRJNA152943 | ENA
Project description:Considerable evidence suggests that breast cancer therapeutic resistance and relapse can be driven by polyploid giant cancer cells (PGCCs). The number of PGCCs increases with the stages of disease and therapeutic stress. Given the importance of PGCCs, it remains challenging to eradicate them. To discover effective anti-PGCC compounds, there is an unmet need to rapidly distinguish compounds that kill non-PGCCs, PGCCs, or both. Here, we establish a single-cell morphological analysis pipeline with a high throughput and great precision to characterize dynamics of individual cells. In this manner, we screen a library to identify promising compounds that inhibit all cancer cells or only PGCCs (e.g., regulators of HDAC, proteasome, and ferroptosis). Additionally, we perform scRNA-Seq to reveal altered cell cycle, metabolism, and ferroptosis sensitivity in breast PGCCs. The combination of single-cell morphological and molecular investigation reveals promising anti-PGCC strategies for breast cancer treatment and other malignancies.
2023-12-01 | GSE248717 | GEO
Project description:Active HUMSC with distinct binding rate to MDA MB-231 breast cancer cells, distinct ability in suppressing tumorigenesis,distinct cell in cell features and distinct features under TEM then inactive HUMSC We used microarrays to detail the difference gene expression between active HUMSC and inactive HUMSC HUMSC with high MDA MB-231 breast cancer cells suppression rate was selective as active HUMSC and HUMSC with low MDA MB-231 breast cancer cells suppression rate was selective as inactive HUMSC
2012-12-31 | E-GEOD-27820 | biostudies-arrayexpress
Project description:Screens for agents that specifically kill epithelial cancer stem cells (CSCs) have not been possible due to the rarity of these cells within tumor cell populations and their relative instability in culture. We describe here an approach to screening for agents with epithelial CSC-specific toxicity. We implemented this method in a chemical screen and discovered compounds showing selective toxicity for breast CSCs. One compound, salinomycin, reduces the proportion of CSCs by >100-fold relative to paclitaxel, a commonly used breast cancer chemotherapeutic drug. Treatment of mice with salinomycin inhibits mammary tumor growth in vivo and induces increased epithelial differentiation of tumor cells. In addition, global gene expression analyses show that salinomycin treatment results in the loss of expression of breast CSC genes previously identified by analyses of breast tissues isolated directly from patients. This study demonstrates the ability to identify agents with specific toxicity for epithelial CSCs
2009-08-20 | GSE17215 | GEO
Project description:Gene Expression-Based High Throughput Screening: APL Treatment with Candidate Compounds
| PRJNA89871 | ENA
Project description:Thirteen HER2 positive breast cancer cell lines were screened with 22 commercially available compounds, mainly targeting proteins in the ErbB2 signaling pathway, and the molecular mechanisms related to treatment response were sought. To search for response predictors, genomic and transcriptomic profiling, PIK3CA mutations and PTEN status were associated to the drug responses and several genes involved in the response of the compounds were identified. Array-CGH experiments of HER2+ breast cancer cell lines grown under standard conditions. DNA from four HER2 positive breast cancer cell lines was isolated and hybridized on Agilent arrays.
2015-01-30 | E-GEOD-58886 | biostudies-arrayexpress
Project description:Gene expression response to high radiation treatment in MCF7 breast cancer cell line
| PRJNA268840 | ENA