Project description:Oxaliplatin resistance was induced in 2 colorectal cancer cell lines (LoVo-92, wt-p53 and LoVo-Li, functionally inactive p53) and one ovarian cancer cell line (A2780, wt-p53). Resistance was induced by weekly exposure to oxaliplatin for 4 hrs or 72 hrs with increasing concentrations for a period of 7 months Genomic DNA of oxaliplatin and cisplatin resistant colorectal cancer and ovarian cancer cell lines as well as the parental cell lines were labeled and subsequently hybridized against pooled reference DNA of healthy volunteers of the opposite gender using across array hybridization. Extracted raw-data were normalised and smoothend using the R-script NOWAVE resulting in normalised log2 ratio profiles of resistant cell line versus parental cell line and parental cell line versus reference DNA.
Project description:Resistance to chemotherapy drugs, including oxaliplatin, remains a major challenge in the treatment of colorectal cancer, often leading to treatment failure and poor patient outcomes. Overcoming chemoresistance by sensitizing tumor cells represents a critical therapeutic goal. Adenoviral early region 1A (E1A) has been proposed as a promising gene therapy agent capable of modulating cellular pathways to enhance sensitivity to chemotherapeutic agents. This dataset contains RNA-seq profiling of human colorectal cancer cell lines that are either oxaliplatin-sensitive (HCT116) or oxaliplatin-resistant (HCT116 oxpl-R), treated with oxaliplatin, in the context of doxycycline-induced adenoviral E1A expression. The experiment includes eight conditions: untreated controls, E1A expression alone, oxaliplatin treatment alone, and combined E1A expression with oxaliplatin treatment, each in both sensitive and resistant cell lines. The comprehensive experimental design enables the dataset to be divided into three independent analyses: A) Comparison of baseline transcriptomic profiles between oxaliplatin-sensitive and resistant cells (conditions 1 and 5); B) Investigation of the transcriptional response to oxaliplatin in sensitive and resistant cells (conditions 1, 3, 5, and 7); C) Evaluation of the impact of adenoviral E1A expression on the transcriptomes of sensitive and resistant cells alone (conditions 1, 2, 5, and 6) and in combination with oxaliplatin treatment (all eight conditions); This dataset provides valuable insights into the molecular mechanisms underlying oxaliplatin resistance and the potential role of E1A gene therapy in sensitizing colorectal cancer cells to chemotherapy.
Project description:Oxaliplatin resistance frequently leads to therapeutic failure in colorectal cancer (CRC). Increasing evidence has shown that noncoding RNAs (ncRNAs) play pivotal roles in chemoresistance of CRC. However, the roles and mechanisms of ncRNAs in oxaliplatin resistance are not well understood. In this study, to identify the ncRNAs induced by oxaliplatin, we profile the expression of ncRNAs in oxaliplatin-resistant HCT116 CRC cells (HCT116oxR) and parental HCT116 cells using next-generation sequencing technology.
Project description:Oxaliplatin resistance was induced in 2 colorectal cancer cell lines (LoVo-92, wt-p53 and LoVo-Li, functionally inactive p53) and one ovarian cancer cell line (A2780, wt-p53). Resistance was induced by weekly exposure to oxaliplatin for 4 hrs or 72 hrs with increasing concentrations for a period of 7 months
Project description:Oxaliplatin resistance was induced in 2 colorectal cancer cell lines (LoVo-92, wt-p53 and LoVo-Li, functionally inactive p53) and one ovarian cancer cell line (A2780, wt-p53). Resistance was induced by weekly exposure to oxaliplatin for 4 hrs or 72 hrs with increasing concentrations for a period of 7 months.
Project description:Despite advances in contemporary chemotherapeutic strategies, long term survival still remains elusive for patients with metastatic colorectal cancer. A better understanding of the molecular markers of drug sensitivity to match therapy with patient is needed to improve clinical outcomes. In this study, we used in vitro drug sensitivity data from the NCI-60 cell lines together with their Affymetrix microarray data to develop a gene expression signature to predict sensitivity to oxaliplatin. In order to validate our oxaliplatin sensitivity signature, Patient-Derived Colorectal Cancer Explants (PDCCEs) were developed in NOD-SCID mice from resected human colorectal tumors. Analysis of gene expression profiles found similarities between the PDCCEs and their parental human tumors, suggesting their utility to study drug sensitivity in vivo. The oxaliplatin sensitivity signature was then validated in vivo with response data from 14 PDCCEs treated with oxaliplatin and was found to have an accuracy of 92.9% (Sensitivity=87.5%; Specificity=100%). Our findings suggest that PDCCEs can be a novel source to study drug sensitivity in colorectal cancer. Furthermore, genomic-based analysis has the potential to be incorporated into future strategies to optimize individual therapy for patients with metastatic colorectal cancer.