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Project description:Increased HRD score in cisplatin resistant penile cancer cells
| PRJNA905440 | ENA
Project description:Background/introductionPenile cancer is a rare disease in demand for new therapeutic options. Frequently used combination chemotherapy with 5 fluorouracil (5-FU) and cisplatin (CDDP) in patients with metastatic penile cancer mostly results in the development of acquired drug resistance. Availability of cell culture models with acquired resistance against standard therapy could help to understand molecular mechanisms underlying chemotherapy resistance and to identify candidate treatments for an efficient second line therapy.MethodsWe generated a cell line from a humanpapilloma virus (HPV) negative penile squamous cell carcinoma (UKF-PEC-1). This cell line was subject to chronic exposure to chemotherapy with CDDP and / or 5-FU to induce acquired resistance in the newly established chemo-resistant sublines (PEC-1rCDDP2500, adapted to 2500 ng/ml CDDP; UKF-PEC-1r5-FU500, adapted to 500 ng/ml 5- FU; UKF-PEC1rCDDP2500/r5-FU500, adapted to 2500 ng/ml CDDP and 500 ng/ml 5 -FU). Afterwards cell line pellets were formalin-fixed, paraffin embedded and subject to sequencing as well as testing for homologous recombination deficiency (HRD). Additionally, exemplary immunohistochemical stainings for p53 and gammaH2AX were applied for verification purposes. Finally, UKF-PEC-1rCDDP2500, UKF-PEC-1r5-FU500, UKF-PEC1rCDDP2500/r5-FU500, and UKF-PEC-3 (an alternative penis cancer cell line) were tested for sensitivity to paclitaxel, docetaxel, olaparib, and rucaparib.Results and conclusionsThe chemo-resistant sublines differed in their mutational landscapes. UKF-PEC-1rCDDP2500 was characterized by an increased HRD score, which is supposed to be associated with increased PARP inhibitor and immune checkpoint inhibitor sensitivity in cancer. However, UKF-PEC-1rCDDP2500 did not display sensitivity to PARP inhibitors.
| S-EPMC9789628 | biostudies-literature
Project description:To determine the signaling networks that are dysregulated in cisplatin-resistant non-small cell lung cancer, noncoding RNA expression data were obtained from, and compared between, the lung adenocarcinoma cell line, A549, and its cisplatin-resistant derivative, A549/CDDP. Noncoding RNA expression data from a cisplatin-sensitive lung adenocarcinoma cancer cell line (A549) were collected and compared to noncoding RNA expression data from a cisplatin-resistant cell line (A549/CDDP). 3 independent experiments were completed for both the sensitive and resistant cell lines.
2013-01-15 | E-GEOD-43249 | biostudies-arrayexpress
Project description:To determine the signaling networks that are dysregulated in cisplatin-resistant non-small cell lung cancer, noncoding RNA expression data were obtained from, and compared between, the lung adenocarcinoma cell line, A549, and its cisplatin-resistant derivative, A549/CDDP. Noncoding RNA expression data from a cisplatin-sensitive lung adenocarcinoma cancer cell line (A549) were collected and compared to noncoding RNA expression data from a cisplatin-resistant cell line (A549/CDDP). 3 independent experiments were completed for both the sensitive and resistant cell lines.
2013-01-15 | E-GEOD-43493 | biostudies-arrayexpress
Project description:We aim to detect differential gene expression using RNA-seq between normal penile epithelial tissue and PB-Cre+ Smad4L/L ApcL/L penile tumors of mice
2020-04-05 | GSE130052 | GEO
Project description:Esophageal cancer is one of the most serious health problems globally because of its high incidence and mortality rate. Cisplatin (CDDP) is the primary treatment but limited by the drug resistance. However, the mechanism of cisplatin resistance remains unclear. Herein, the CDDP-resistant cell line TE-1/CDDP was established to compared with TE-1, the expression profiles of circRNAs mRNA and lncRNA were compared between TE-1/CDDP and TE-1 using microarray analysis, and used this as a basis for exploring possible mechanisms of drug resistance in genes such as HDAC9.
2023-09-14 | GSE242834 | GEO
Project description:Lung cancer is the leading cause of cancer-related deaths and its treatment is based in chemotherapy using platinum containing compounds, mainly cisplatin (CDDP). Many patients show resistance to CDDP leading to treatment failure. To understand the mechanisms involved in CDDP resistance in lung cancer, we used CDDP-sensitive (A549) and –resistant (A549/CDDP) cells to identify newly synthesized proteins in response to CDDP treatment using BONCAT technique. In addition the steady-state proteome of A549 and A549/CDDP cells was also evaluated. It was identified 70 and 69 proteins upregulated by CDDP in A549 and A549/CDDP cells, respectively. The set of proteins upregulated by CDDP in both cells are associated to GO terms related to proteostasis, telomere maintenance cell, RNA processing, cytoskeleton and response to oxidative stress. Interestingly, the profile of biological processes enriched in A549 cells after CDDP treatment is very similar to those identified in the steady-state proteome of A549/CDDP cells, suggesting their positive selection in CDDP-resistant cells development. Therefore, this study of proteomic response to CDDP is relevant to the identification of potential protein targets to development of therapeutic strategies to block drug resistance pathways.
2023-03-10 | PXD021779 | Pride
Project description:To determine the signaling networks that are dysregulated in cisplatin-resistant non-small cell lung cancer, noncoding RNA expression data were obtained from, and compared between, the lung adenocarcinoma cell line, A549, and its cisplatin-resistant derivative, A549/CDDP.
2013-01-15 | GSE43249 | GEO
Project description:The extent of intratumoral heterogeneity, the subclonal structures and the mechanisms of treatment-induced clonal selection by cisplatin was investigated in the squamous cell carcinoma cell line model FaDu. We picked 96 single cell-derived clones from the cisplatin-sensitive parental FaDu cell line. After expansion as separate cultures, these clones were tested for their sensitivity to CDDP. By this approach, we isolated individual cell clones that were primarily resistant (clones 5 & 78) and others that showed high sensitivity to CDDP (clones 46 & 54). Basal mRNA expression levels associated with CDDP sensitivity / resistance were determined in two independent microarray analyses.
2017-12-04 | E-MTAB-6022 | biostudies-arrayexpress
Project description:The emergence of cisplatin (CDDP) resistance is the main cause of treatment failure and death in patients with testicular germ cell tumors (TGCT), but its biologic background is poorly understood. To study the molecular basis of CDDP resistance in TGCT we prepared and sequenced CDDP-exposed TGCT cell lines as well as 31 primary patients’ samples. Long-term exposure to CDDP increased the CDDP resistance 10 times in the NCCIT cell line, while no major resistance was achieved in Tera-2. Development of CDDP resistance was accompanied by changes in the cell cycle (increase in G1 and decrease in S-fraction), increased number of acquired mutations, of which 3 were present within ATRX gene, as well as changes in gene expression pattern. Copy number variation analysis showed, apart from obligatory gain of 12p, several other large-scale gains (chr 1, 17, 20, 21) and losses (chr X), with additional more CNVs found in CDDP-resistant cells (e.g., further losses on chr 1, 4, 18, and gain on chr 8). In the patients’ samples, those who developed CDDP resistance and died of TGCT (2/31) showed high numbers of acquired aberrations, both SNPs and CNVs, and harbored mutations in genes potentially relevant to TGCT development (e.g., TRERF1, TFAP2C in one patient, MAP2K1 and NSD1 in another one). Among all primary tumor samples, the most commonly mutated gene was NSD1, affected in 9/31 patients. This gene encoding histone methyl transferase was also downregulated and identified among the 50 most differentially expressed genes in CDDP-resistant NCCIT cell line. Interestingly, 2/31 TGCT patients harbored mutations in the ATRX gene encoding a chromatin modifier that has been shown to have a critical function in sexual differentiation. Our research newly highlights its probable involvement also in testicular tumors. Both findings support the emerging role of altered epigenetic gene regulation in TGCT and CDDP resistance development. This submission includes complete cell lines sequencing data and processed files. The patients data are available from the authors on request.
2019-08-29 | GSE136560 | GEO