Transcription profiling of human lung cancer cell lines
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
DISEASE(S): small cell cancer
SUBMITTER: Akihiko Gemma
PROVIDER: E-GEOD-4127 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Anticancer drug clustering in lung cancer based on gene expression profiles. We performed gene expression analysis in lung cancer cell lines. (used: Affymetrix GeneChip Human Genome U133 Array Set HG-U133A). We also examines the sensitivity of these cell lines to commonly used anti-cancer agents (docetaxel, paclitaxel, gemcitabine, vinorelbine, 5-FU, SN38, cisplatin, and carboplatin) via MTT assay. We related the cytoxic activity of each of these agents to corresponding expression pattern in each of the cell lines using modified NCI program. Keywords: cytotoxicity, lung cancer, anticancer drugs
2006-02-10 | GSE4127 | GEO
Project description:In order to ascertain the potential for histone deacetylase (HDAC) inhibitor-based treatment in non-small cell lung cancer (NSCLC), we analyzed the anti-tumour effects of Trichostatin A (TSA) and suberoylanilide hydroxamic acid (vorinostat) in a panel of 16 NSCLC cell lines via MTT assay. TSA and vorinostat both displayed strong anti-tumor activities in a proportion of NSCLC cell lines, and suggesting the need for the use of predictive markers to select patients receiving this treatment. There was a strong correlation between the responsiveness to TSA and vorinostat (P < 0.0001). To identify a molecular model of sensitivity to HDAC inhibitor treatment in NSCLC, we conducted a gene expression profiling study using cDNA arrays on the same set of cell lines and related the cytotoxic activity of TSA to corresponding gene expression pattern using a modified NCI program. In addition, pathway analysis was performed with Pathway Architect software. We used nine genes, which were identified by gene-drug sensitivity correlation and pathway analysis, to build a support vector machine (SVM) algorithm model by which sensitive cell lines were distinguished from resistant cell lines. The prediction performance of the SVM model was validated by an additional seven cell lines, resulting in a prediction value of 100% in respect to determining response to TSA. Our results suggested that [1] HDAC inhibitors may be promising anticancer drugs to NSCLC, and [2] the nine gene classifer is useful in predicting drug sensitivity to HDAC inhibitors and may contribute to achieving individualized therapy for NSCLC patients. training sample set:; GSM94303 PC9; GSM94304 PC7; GSM94305 PC14; GSM94306 A549; GSM94308 LK2; GSM94313 RERF LC-KJ; GSM94314 RERF LC-MS; GSM94315 RERF-LC-AI; GSM94316 PC-1; GSM94317 PC-3; GSM94319 PC-10; GSM94323 ABC-1; GSM94324 EBC-1; GSM94325 LC2/ad; GSM94328 SQ-5; GSM94329 QG-56; test sample set:; GSM94307 LU65; GSM94326 LC1/sq; GSM94327 LC-1F; GSM254967 LCOK; GSM254968 LCD; GSM254969 H1650; GSM254970 H1975 Experiment Overall Design: gene expression analyis in lung cancer cell lines
2008-06-11 | E-GEOD-10089 | biostudies-arrayexpress
Project description:We evaluted the synergyistic interactions of cannabidiol (CBD) with standard chemotherapeutic agents such as Docetaxel (DOC), doxorubicin (DOX), paclitaxel (PTX), vinorelbine (VIN), and 7-Ethyl-10-hydroxycamptothecin (SN38) in MCf7 cells ultising different synergy metrics. Then we explored the synergistic mechanisms on the proteome level of the most synergistic combination (CBD and SN38 in a molar ratio of 371:1, respectively)
2021-11-03 | PXD026587 | Pride
Project description:Six non- and drug-resistant colorectal cancer cell lines were selected in this study, which were non-resistant cell lines: HCT116 and LoVo, four drug-resistant cell lines: HCT116-OxPt, HCT116-SN38, LoVo-OxPt, LoVo-SN38.Proteins extraced from three HCT116 related cell lines were labled and pooled together, and proteins from other three LoVo related cell lines were labled and pooled together.
2022-03-04 | PXD004070 | Pride
Project description:Purpose: Irinotecan (SN38) and oxaliplatin are chemotherapeutic agents used in the treatment of colorectal cancer. However, the frequent development of resistance to these drugs represents a considerable challenge in the clinic. Alus as retrotransposons comprise 11% of the human genome. Genomic toxicity induced by carcinogens or drugs can reactivate Alus by altering DNA methylation. Whether or not reactivation of Alus occurs in SN38 and oxaliplatin resistance remains unknown. Methods: We applied reduced representation bisulfite sequencing (RRBS) to investigate the DNA methylome in SN38- or oxaliplatin-resistant colorectal cancer cell line models. Moreover, we extended the RRBS analysis to tumor tissue from 14 patients with colorectal cancer who either did or did not benefit from capecitabine + oxaliplatin treatment. For the clinical samples, we applied a concept of DNA methylation entropy to estimate the diversity of DNA methylation states of the identified resistance phenotype-associated methylation loci observed in the cell line models. Results: We identified different loci being characteristic for the different resistant cell lines. Interestingly, 53% of the identified loci were Alu sequences -- especially the Alu Y subfamily. Furthermore, we identified an enrichment of Alu Y sequences that likely results from increased integration of new copies of Alu Y sequence in the drug-resistant cell lines. In the clinical samples, SOX1 and other SOX gene family members were shown to display variable DNA methylation states in their gene regions. The Alu Y sequences showed remarkable variation in DNA methylation states across the clinical samples. Our findings imply a crucial role of Alu Y in colorectal cancer drug resistance. Our study underscores the complexity of colorectal cancer aggravated by mobility of Alu elements and stresses the importance of personalized strategies, using a systematic and dynamic view, for effective cancer therapy. Investigation of the representive methylome of well-established SN38 and Oxaliplatin resistant cell line models and 14 clinical colorectal metastatic samples that have developed resistance to XELOX to review the epigenetic mechnism of the drug resistance.
2015-04-01 | E-GEOD-56269 | biostudies-arrayexpress
Project description:Carboplatin and paclitaxel are the most widely prescribed chemotherapeutic agents for ovarian cancer. Not all patients respond to treatment, so there is a need for biomarkers that reliably predict resistance in ovarian tumors. Expression of such biomarkers may be dynamically controlled. Gene expression was assessed for a period of 14 days after treatment with carboplatin or combined carboplatin-paclitaxel in xenografts from two ovarian cancer models: chemosensitive serous adenocarcinoma derived OV1002 and slow growing, chemoresistant HOX424 of clear cell origin. Tumour volume reduction was observed in both cell lines post treatment, with a more prominent effect in OV1002, which subsided in late time points. In OV1002, hierarchical clustering classified differentially expressed genes into four time-related patterns, upregulated and downregulated groups for each early and late expressed genes. Upregulated genes were involved in DNA repair, cell cycle and apoptosis, while downregulated groups were involved in oxygen consuming metabolic processes and apoptosis control. Carboplatin-paclitaxel treatment triggered a more comprehensive response. HOX424 responded only to the combined treatment, while the observed reduction in tumour growth was limited. Several apoptosis and cell cycle genes were upregulated, while Wnt signaling was downregulated in the exclusively late expression pattern observed in this cell line. Late downregulated gene groups post carboplatin-taxane treatment were capable of predicting overall survival in two independent clinical datesets. Pathways overrepresented in these clusters were also predictive of outcome. This longitudinal gene expression study may help characterization of chemotherapy response, identification of resistance biomarkers and guiding timing of biopsies. 101 samples from 2 cell lines, untreated, carboplatin (Carbo) treated, carboplatin-paclitaxel (Carbotax) treated, over 5 time points (days 1,2,4,7,14)
2014-06-16 | E-GEOD-49577 | biostudies-arrayexpress
Project description:Purpose: Irinotecan (SN38) and oxaliplatin are chemotherapeutic agents used in the treatment of colorectal cancer. However, the frequent development of resistance to these drugs represents a considerable challenge in the clinic. Alus as retrotransposons comprise 11% of the human genome. Genomic toxicity induced by carcinogens or drugs can reactivate Alus by altering DNA methylation. Whether or not reactivation of Alus occurs in SN38 and oxaliplatin resistance remains unknown. Methods: We applied reduced representation bisulfite sequencing (RRBS) to investigate the DNA methylome in SN38- or oxaliplatin-resistant colorectal cancer cell line models. Moreover, we extended the RRBS analysis to tumor tissue from 14 patients with colorectal cancer who either did or did not benefit from capecitabine + oxaliplatin treatment. For the clinical samples, we applied a concept of DNA methylation entropy to estimate the diversity of DNA methylation states of the identified resistance phenotype-associated methylation loci observed in the cell line models. Results: We identified different loci being characteristic for the different resistant cell lines. Interestingly, 53% of the identified loci were Alu sequences -- especially the Alu Y subfamily. Furthermore, we identified an enrichment of Alu Y sequences that likely results from increased integration of new copies of Alu Y sequence in the drug-resistant cell lines. In the clinical samples, SOX1 and other SOX gene family members were shown to display variable DNA methylation states in their gene regions. The Alu Y sequences showed remarkable variation in DNA methylation states across the clinical samples. Our findings imply a crucial role of Alu Y in colorectal cancer drug resistance. Our study underscores the complexity of colorectal cancer aggravated by mobility of Alu elements and stresses the importance of personalized strategies, using a systematic and dynamic view, for effective cancer therapy.
2015-04-01 | GSE56269 | GEO
Project description:Purpose: Despite advances in radical surgery and chemotherapy delivery, ovarian cancer is the most lethal gynecologic malignancy. Most of these patients are treated with platinum-based chemotherapies, but there is no biomarker model to guide their responses to these therapeutic agents. We have developed and independently tested our novel multivariate molecular predictors for forecasting patients' responses to individual drugs on a cohort of 58 ovarian cancer patients. Experimental Design: We adapted and applied the previously-published COXEN algorithm to develop molecular predictors for therapeutic responses of patients' tumors based on expression signatures derived from the NCI-60 in vitro drug activities and genomic expression data. Genome-wide candidate biomarkers were first triaged by examining expression patterns of frozen and formalin-fixed paraffin embedded (FFPE) tissue samples. We then identify initial drug sensitivity biomarkers for carboplatin and paclitaxel, respectively. These biomarkers were further narrowed by examining concordant expression patterns between cell lines and a historical set of ovarian cancer patients. Multivariate predictors were obtained from the NCI-60 cell lines and refined using historical patient cohorts. To independent validate these molecular predictors, we performed genome-wide profiling on FFPE samples of 58 ovarian cancer patients obtained prior to adjuvant chemotherapy. Results: Carboplatin predictor significantly stratified platinum sensitive and resistant patients (p = 0.019) with sensitivity = 93%, specificity = 33%, PPV = 65%, and NPV = 78%. Paclitaxel predictor also significantly stratified patients' responses (p = 0.033) with sensitivity = 96%, specificity = 26%, PPV = 61%, and NPV = 86%. The combination predictor for platinum-taxane combination demonstrated a significant survival difference between the predicted responders and nonresponders with median survival of 12.9 months vs. 8.1 months (p = 0.045). Conclusions: COXEN predictors successfully stratified platinum resistance and taxane response in this retrospective cohort, especially based on their FFPE tumor samples. Accurate prediction of chemotherapeutic response, especially to platinum agents is highly clinically relevant and could alter primary management of ovarian cancer. Gene expression data from 58 stage III-IV ovarian cancer patients treated with Carboplatin and Taxol agents
2012-08-21 | E-GEOD-30161 | biostudies-arrayexpress
Project description:Anti-tumor drugs can effectively shrink the lesions of primary lung cancer; however, it has limited therapeutic effect on patients with brain metastasis (BM). A BM preclinical model based on a multi-organ microfluidic chip has been established proficiently in our previous work. In this study, the BM subpopulation (PC9-Br) derived from the parental PC9 cell line was isolated from the chip model and found to develop obvious resistance to antineoplastic drugs including chemotherapeutic agents (cisplatin, carboplatin, pemetrexed) and tyrosine kinase inhibitors (TKIs) which target epidermal growth factor receptor (EGFR); this suggested that the acquisition of drug-resistance by brain metastatic cells was attributable to the intrinsic changes in PC9-Br. Hence, we performed proteomic and revealed a greatly altered spectrum of BM protein expression compared with primary lung cancer cells.
2021-09-09 | PXD021760 | Pride
Project description:Platinum-derived drugs such as cisplatin and carboplatin are among the most commonly used cancer chemotherapy drugs, but very few specific molecular and cellular markers to predict different sentivity to these agents in a given tumor type have been clearly identified. Because epigenetic gene silencing is increasingly being recognized as a factor in conferring distinct tumoral drug sensitivity, we have used a comprehensive DNA methylation microarray platform to interrogate the widely characterized NCI60 panel of human cancer cell lines according to CpG methylation status and cisplatin/carboplatin sensitivity. Using this approach, we have identified that promoter CpG island hypermethylation-associated silencing of the putative DNA/RNA helicase Schlafen-11 (SLFN11) is associated with increased resistance to platinum-derived compounds. We have also experimentally validated these findings in vitro. In this setting, we were also able to identify the BRCA1 interacting DHX9 RNA helicase (also known as RHA) as a protein partner for SLFN11, suggesting a mechanistic pathway for the observed chemoresistance effect. Most importantly, we were able to extend these findings to the clinical setting where we observed that those patients with ovarian and non-small cell lung cancer carrying SLFN11 hypermethylation showed poor response to cisplatin and carboplatin treatments. Overall, these results identify SLFN11 epigenetic inactivation as a predictor of resistance to platin-derived drugs in human cancer.
2015-11-30 | GSE66872 | GEO