Mutations conferring differential treatment response in breast cancer
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PROVIDER: EGAS00001003626 | EGA |
REPOSITORIES: EGA
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Project description:This experiment is designed to screen miRNAs that are deregulated during chemoresistance-associated metastasis of lung cancer cells. Chemoresistant metastatic in vivo tumor model of A549-luc-Vector cells was established after four rounds of cisplatin (CDDP) treatments compared to corresponding control solvent treatments. Upon examining profiles of miRNA expression differential between tumor-derived cultured cells from the Ctrl-4th and CDDP-4th treatments, most markedly upregulated and downregulated miRNAs in chemoresistant, metastatic A549-luc-CDDP-4th cells were identified. In order to establish a chemoresistant in vivo tumor model, after inoculation of A549-luc-Vector cells, cisplatin (CDDP) or control solvent was intraperitoneally (i.p.) injected six rounds in a two-week period and cells were isolated from corresponding resultant tumors, cultured and re-transplanted into syngeneic mice to receive the next round of treatment. In our experimental model, human lung cancer xenografts developed chemoresistance in the third round of CDDP treatment (CDDP-3rd) and chemoresistance-associated metastases following the fourth round of treatment. Tumor-derived cultured cells from Ctrl-4th and CDDP (cisplatin)-4th treatment were subjected to miRNA array (Agilent-031181 human miRNA (8*60k) V16.0) analysis, with two biological replications for each treatment.
2015-04-10 | E-GEOD-67727 | biostudies-arrayexpress
Project description:Goal of the experiment Recurrence is a frequent phenomenon in intracranial childhood ependymomas. To understand this process, we investigated whether the gene expression profiling of matched ependymomas at diagnosis and at relapse could reveal key molecular events involved in tumor progression. To gain new insight in this process and identify pathways associated with recurrence, we compared the gene expression profiles of local recurrences with the corresponding initial tumors. Brief description We analyzed 17 tumor samples at diagnosis and a total of 27 paired recurrences. Recurrences analyzed occurred after surgery only in 12 cases, surgery plus chemotherapy only in 9 cases and any treatment plus radiotherapy in 6 cases. We compared the level of gene expression for each tumor at recurrence relative to its expression at diagnosis using Agilent 44K dual color gene expression microarrays.
2010-12-31 | E-TABM-873 | biostudies-arrayexpress
Project description:We were interested in understanding the cytotoxic effects induced by miR-491-5p in IGROV1-R10 cells IGROV1-R10 cells are chemoresistant ovarian cancer cells - chemoresistance being main cause of therapeutic failure in this disease.
2020-10-23 | GSE159858 | GEO
Project description:Chemoresistance is a major cause of poor prognosis of breast cancer.More and more mRNAs and lncRNAs are reported to upregulate chemoresistance in breast cancer.To explore the how mRNAs and lncRNAs involved in chemoresistance of breast cancer,we sceened upregulated mRNAs and lncRNA from parental MCF-7 , chemoresistant MCF-7 cells as well as 4 breast cancer tissue sensitive to chemotherapy and 4 resistant to chemotherapy . Total RNA was extracted using Trizol reagent. Agilent Human lncRNA Microarray V6 (4*180K) was used to analyze the global profiling of human lncRNAs and protein-coding transcripts in these samples. The microarray contains 83,835 lncRNAs and 27,233 coding genes.
2020-02-25 | E-MTAB-8787 | biostudies-arrayexpress
Project description:The major obstacle in successfully treating triple negative breast cancer (TNBC) is resistance to cytotoxic chemotherapy, the mainstay of treatment in this disease. Previous pre-clinical models of chemoresistance in TNBC have suffered from a lack of clinical relevance. Using a single high dose chemotherapy treatment, we developed a novel MDA-MB-436 cell-based model of chemoresistance characterized by a unique and complex morphological phenotype, which consists of polyploid giant cancer cells (PGCCs) giving rise to neuron-like mononuclear daughter cells filled with smaller but functional mitochondria and numerous lipid droplets. This resistant phenotype is associated with metabolic reprogramming with a shift to a greater dependence on fatty acids and oxidative phosphorylation. We validated both the molecular and histologic features of this model in a clinical cohort of primary chemoresistant TNBCs and identified several metabolic vulnerabilities including a dependence on PLIN4, a perilipin coating the observed lipid droplets, expressed both in the TNBC resistant cells and clinical chemoresistant tumors treated with neoadjuvant doxorubicin-based chemotherapy. These findings thus reveal a novel mechanism of chemotherapy resistance that has therapeutic implications in the treatment of drug resistant cancer.
2019-11-30 | GSE138233 | GEO
Project description:Identification of specific risk groups for recurrence after surgery for colorectal liver metastases (CRLM) remains challenging due to the heterogeneity of the disease. Classical clinicopathologic parameters have limited prognostic and predictive value. The aim of this study was to identify a gene expression signature measured in CRLM discriminating early from late recurrence after surgery for CRLM. Methods: Tumour samples of CRLM from two patient groups were collected: I) patients with recurrent disease within 12 months after surgery (N=33), and II) patients without recurrences and disease free for at least 36 months (N=30). The included patients were clinically homogeneous; all patients had a low risk profile (clinical risk score 0-2) and did not receive (neo-) adjuvant chemotherapy. Extracted total RNA from both groups was hybridized to Illumina arrays, and processed for analysis. A leave-one-out cross validation (LOOCV) analysis was performed to identify a potentially prognostic gene expression signature. Results: The LOOCV yielded an 11-gene profile with prognostic value in relation to recurrent disease within 12 months after partial hepatectomy. This gene expression profile had a sensitivity of 81.8%, with a specificity of 66.7% for predicting early recurrences (within 12 months) versus no recurrences for at least 36 months after surgery (X2 P<0.0001). Conclusion: The current study yielded an 11-gene signature at mRNA level in CRLM discriminating early from late or no relapse after partial hepatectomy.
2017-01-01 | GSE81423 | GEO
Project description:Chemoresistance frequently leads to therapeutic failure in tongue squamous cell carcinoma (TSCC). Increasing evidence has shown that Long noncoding RNAs (lncRNAs) play pivotal roles in biological properties of cancer. However, the roles and mechanisms of lncRNAs in cisplatin resistance are not well understood. In this study, to identify the lncRNAs induced by chemotherapy, we profile the expression of lncRNAs in cisplatin-resistant TSCC cells using LncRNA microarrays.
2018-06-12 | GSE115119 | GEO
Project description:Goal of the experiment : Recurrence is a frequent phenomenon in intracranial childhood ependymomas. To understand this process, we investigated whether the gene expression profiling of matched ependymomas at diagnosis and at relapse could reveal key molecular events involved in tumor progression. To gain new insight in this process and identify mechanisms associated with recurrence, we compared the CGH profiles of local recurrences with the corresponding initial tumors. Brief description We analyzed 17 tumor samples at diagnosis and a total of 27 paired recurrences. Recurrences analyzed occurred after surgery only in 12 cases, surgery plus chemotherapy only in 9 cases and any treatment plus radiotherapy in 6 cases. We compared the level of CGH profile for each tumor at diagnosis and recurrence relative to normal commercial DNA using Agilent 4x44K Human CGH microarrays.
2011-06-20 | E-TABM-1023 | biostudies-arrayexpress
Project description:Treatment options for advanced gallbladder cancer (GBC) are scarce and usually rely on cytotoxic chemotherapy, but unfortunately the effectiveness of any regimen is limited, and recurrence rates are high. Here, we established and characterized two gemcitabine-resistant GBC cell sublines (NOZ GemR and TGBC1 GemR) to investigate the molecular mechanisms associated with acquired resistance in vitro. The transcriptome profiling of parental and gemcitabine resistant cells revealed differential expression of multiple protein-coding genes and enrichment of biological processes such as epithelial-to-mesenchymal transition and drug metabolism. On the other hand, quantitative phosphotyrosine proteomic analysis of NOZ GemR identified aberrantly dysregulated signaling pathways in resistant cells as well as active kinases, such as Abl, PDGFRA, EphB2 and members of the Src-family that could be novel therapeutic targets against drug resistance in GBC. In line with this, NOZ GemR cells showed increased sensitivity toward the multikinase inhibitor dasatinib compared with parental cells. In conclusion, our study describes transcriptome changes and altered signaling pathways occurring in gemcitabine-resistant gallbladder cancer cells, which greatly expands our understanding of the underlying mechanisms of acquired drug-resistance in GBC. Moreover, this new gemcitabine resistant GBC models could be exploited either to study alternative mechanisms of resistance or to explore new therapies for chemotherapy-refractory GBC.
2023-05-03 | PXD036348 | Pride
Project description:Neoadjuvant chemotherapy (NAC) is the major pre-treatment for breast cancer before surgery. Patients who achieve pathologic complete response (pCR) have a higher chance to receive lumpectomy and a better quality of life after neoadjuvant treatment. Luminal subtype breast cancer has poor NAC response compared with triple-negative breast cancer (TNBC) subtype. The molecular and cellular mechanisms underlying this chemoresistance are not fully understood. Here we report that the 17 featured transcriptional factors (TFs) in luminal and TNBC were identified. The association between 17 TFs and NAC pCR were analysis and exogenous luminal featured TF GATA3 overexpression promotes chemotherapy resistance in TNBC cell lines whereas its knockdown promotes sensitivity. In mechanism, we found that anthracycline based chemotherapy induces robust cellular ROS and Fe2+ overload in sensitivity cells; GATA3 mediates cell survival through repress CYB5R2 expression and Fenton reducing in DOX recycle which reduce cellular ROS and Fe2+ level during chemotherapy procedure. These founding altogether indicate that luminal featured transcription factor GATA3 enhance NAC resistance thorough repress ROS production and Fenton reducing. Breast cancer patient with GATA3 high expression might not suit for anthracycline based NAC regimen.
2023-01-01 | GSE216413 | GEO