Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA100375 | ENA |
REPOSITORIES: ENA
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Project description:This model is built by COPASI 4.24(Build 197), based on paper:
Mathematical Approach to Differentiate Spontaneous and Induced Evolution to Drug Resistance During Cancer Treatment.
Author:
James M. Greene, Jana L. Gevertz, Eduardo D. sontag
Abstract:
PURPOSE:Drug resistance is a major impediment to the success of cancer treatment. Resistance is typically thought to arise from random genetic mutations, after which mutated cells expand via Darwinian selection. However, recent experimental evidence suggests that progression to drug resistance need not occur randomly, but instead may be induced by the treatment itself via either genetic changes or epigenetic alterations. This relatively novel notion of resistance complicates the already challenging task of designing effective treatment protocols. MATERIALS AND METHODS:To better understand resistance, we have developed a mathematical modeling framework that incorporates both spontaneous and drug-induced resistance. RESULTS:Our model demonstrates that the ability of a drug to induce resistance can result in qualitatively different responses to the same drug dose and delivery schedule. We have also proven that the induction parameter in our model is theoretically identifiable and propose an in vitro protocol that could be used to determine a treatment's propensity to induce resistance.
2019-09-26 | BIOMD0000000825 | BioModels
Project description:Genetic changes in high-grades serous ovarian cancer
| PRJNA119491 | ENA
Project description:The hallmark of human cancer is heterogeneity, mirroring the complexity of genetic and epigenetic alterations acquired during oncogenesis. We extracted RNA of 34 cultured human ovarian carcinoma cell lines and performed expression microarrays so that cultured cell lines can represent in vivo human tumors. 34 ovarian carcinoma cell lines expression data.
2013-05-21 | E-GEOD-28724 | biostudies-arrayexpress
Project description:Background. Genome-wide expression changes are associated with development of chemoresistance in patients with ovarian cancer (OVCA); the BCL2 antagonist of cell death (BAD) apoptosis pathway may play a role in clinical outcome. Methods. We analyzed specimens and/or genomic data from 1,406 patients and 116 cancer cell lines. Genome-wide expression changes and cisplatin-resistance were evaluated in OVCA cell lines subjected to a total of 144 (cisplatin)-treatment/recovery cycles. Pathway analysis was performed on genes associated with increasing cisplatin-resistance. BAD protein phosphorylation was studied in patient samples and cell lines, and small interfering RNAs (siRNA) used to explore the pathway as a therapeutic target. We evaluated the influence of BAD-pathway expression on chemosensitivity and/or clinical outcome using genomic data from 60 human cancer cell lines and ovarian, breast, colon, and brain cancers from 1,258 patients. Results. The BAD pathway was associated with evolution of OVCA cell line cisplatin-resistance (P<0.001) and resistance of 7 human cancer cell types to 8 cytotoxic agents (P<0.05). OVCA chemoresistance was associated with BAD protein phosphorylation, and targeted siRNA modulation produced corresponding changes in chemosensitivity. Expression of a 47-gene BAD-pathway signature was associated with survival of 1,258 patients with ovarian, breast, colon, and brain cancer. The OVCA BAD-pathway signature survival advantage was independent of surgical cytoreductive status. Conclusions. The BAD apoptosis pathway influences the sensitivity of human cancers to a variety of chemotherapies, likely via modulation of BAD-phosphorylation. The pathway has clinical relevance as a potential biomarker of therapeutic response, patient survival, and as a promising therapeutic target. Twenty-eight (28) advanced-stage serous epithelial ovarian cancers were resected at the time of primary surgery from patients who would receive platinum-based therapy. The tumors were arrayed on Affymetrix HG-U133A GeneChips. The samples were analyzed with respect to the BAD pathway for correlation to overall survival and cisplatin response.
2011-10-02 | E-GEOD-23554 | biostudies-arrayexpress
Project description:The hallmark of human cancer is heterogeneity, mirroring the complexity of genetic and epigenetic alterations acquired during oncogenesis. We extracted RNA of 34 cultured human ovarian carcinoma cell lines and performed expression microarrays so that cultured cell lines can represent in vivo human tumors.
2013-05-21 | GSE28724 | GEO
Project description:The hallmark of human cancer is heterogeneity, mirroring the complexity of genetic and epigenetic alterations acquired during oncogenesis. We extracted DNA of 14 cultured human ovarian carcinoma cell lines subjected to pooled shRNA screen using TRC 1.0 library, and performed DNAseq. 14 ovarian carcinoma cell lines DNAseq data.
2013-05-21 | E-GEOD-45420 | biostudies-arrayexpress
Project description:The hallmark of human cancer is heterogeneity, mirroring the complexity of genetic and epigenetic alterations acquired during oncogenesis. We extracted DNA of 14 cultured human ovarian carcinoma cell lines subjected to pooled shRNA screen using TRC 1.0 library, and performed DNAseq.
2013-05-21 | GSE45420 | GEO
Project description:Here we investigated whether a combination of cell-free infection and cell-to-cell spread confers a selective advantage in the evolution of resistance to an inhibitor relative to cell-to-cell spread alone due to the stronger selection pressure against drug sensitive virus. We propagated HIV infection using coculture of infected with uninfected cells in the face of the reverse transcriptase inhibitor efavirenz (EFV), and compared the effect on drug resistance evolution of including one cycle of cell-free infection. In the presence of a single cell-free infection step, we obtained earlier evolution of resistance to EFV. When we increased selective pressure by adding emtricitabine (FTC as a second drug, infection with the cell-free step evolved multidrug resistance and was able to replicate, while infection without a cell-free step failed to evolve multidrug resistance. In conclusion, our results suggest that, HIV cell-to-cell spread has a decreased capacity to rapidly evolve resistance to inhibitors, which is conferred by cell-free infection.
2020-09-05 | GSE157511 | GEO
Project description:Background. Genome-wide expression changes are associated with development of chemoresistance in patients with ovarian cancer (OVCA); the BCL2 antagonist of cell death (BAD) apoptosis pathway may play a role in clinical outcome. Methods. We analyzed specimens and/or genomic data from 1,406 patients and 116 cancer cell lines. Genome-wide expression changes and cisplatin-resistance were evaluated in OVCA cell lines subjected to a total of 144 (cisplatin)-treatment/recovery cycles. Pathway analysis was performed on genes associated with increasing cisplatin-resistance. BAD protein phosphorylation was studied in patient samples and cell lines, and small interfering RNAs (siRNA) used to explore the pathway as a therapeutic target. We evaluated the influence of BAD-pathway expression on chemosensitivity and/or clinical outcome using genomic data from 60 human cancer cell lines and ovarian, breast, colon, and brain cancers from 1,258 patients. Results. The BAD pathway was associated with evolution of OVCA cell line cisplatin-resistance (P<0.001) and resistance of 7 human cancer cell types to 8 cytotoxic agents (P<0.05). OVCA chemoresistance was associated with BAD protein phosphorylation, and targeted siRNA modulation produced corresponding changes in chemosensitivity. Expression of a 47-gene BAD-pathway signature was associated with survival of 1,258 patients with ovarian, breast, colon, and brain cancer. The OVCA BAD-pathway signature survival advantage was independent of surgical cytoreductive status. Conclusions. The BAD apoptosis pathway influences the sensitivity of human cancers to a variety of chemotherapies, likely via modulation of BAD-phosphorylation. The pathway has clinical relevance as a potential biomarker of therapeutic response, patient survival, and as a promising therapeutic target.
2011-10-03 | GSE23554 | GEO
Project description:PE5 is a nuclear-directed human ribonuclease variant that exhibits selective cytotoxicity against cancer cells. Onconase is a natural cytotoxic ribonuclease that has reached advanced clinical trials for the treatment of different types of cancer. Onconase also posses established antiviral effects. In the present work, we have used global gene expression microarrays to study the effects caused by PE5 and onconase, and therefore elucidate the mechanism by which these ribonucleases induce cytotoxicity. Transcriptional profiling of human ovarian cancer cells treated with PE5 or onconase were compared with that of control untreated cells. The study were carried out with the multidrug resistance cell line NCI/ADR-RES and its parental cell line OVCAR8.
2016-12-08 | GSE75494 | GEO