Project description:MCF7 breast cancer cell lines: drug-resistant (OHT and ICI) cell lines vs. drug-sensitive (wild type) cell lines. Assessment of association between gene expression and methylation. Two comparisons: OHT-resistant vs. wild type, and ICI-resistant vs. wild type. OHT: 4-hydroxytamoxifen ICI: fulvestrant ((ICI 182780) This submission represents the methylation component of the study.
Project description:MCF7 breast cancer cell lines: drug-resistant (OHT and ICI) cell lines vs. drug-sensitive (wild type) cell lines. Assessment of association between gene expression and methylation.
Project description:Immune checkpoint inhibitors (ICIs) provide clinical benefits for various advanced malignancies. However, the predictive factors that determine sensitivity to ICIs have not been fully elucidated. To identify the mechanisms underlying ICI resistance, we performed a microarray analysis to compare the IFN-γ-inducible genes between ICI-sensitive AB1-HA and ICI-resistant LLC in vitro.
Project description:ER-dependent gene expression was investigated in the LY2 endocrine resistant cell line by treatment with ICI 182780. Cells were steroid depleted for 3 days prior to treatment with ICI for 6 hours. Four biological replicates were processed and analysed.
Project description:Transcriptome analysis was used to identify changes in mouse kidney cancer cells (RENCA) resistant to sunitinib (SuR) and after short and long term sunitinib withdrawal in vitro (ST-W for 48 hours and LT-W for more than 2 months, respectively).
Project description:Objective Cancer immunotherapy aims to unleash the immune system's potential against cancer cells, providing sustained relief for tumors responsive to immune checkpoint inhibitors (ICIs). While promising in gastric cancer (GC) trials, the efficacy of ICIs diminishes in the context of peritoneal dissemination. Our objective is to identify strategies to enhance the impact of ICI treatment specifically for cases involving peritoneal dissemination in GC. Design The therapeutic efficacy of anti-PD1, CTLA4 treatment alone, or in combination, was assessed using the YTN16 peritoneal dissemination tumor model mice. Peritoneum and peritoneal exudate cells were collected for subsequent analysis. Immunohistochemical staining, flow cytometry, and bulk RNA-sequence analyses were conducted to evaluate the tumor microenvironment (TME). A JAK inhibitor (JAKi) was introduced based on the pathway analysis results. Results Anti-PD1 and anti-CTLA4 combination treatment (dual ICI treatment) demonstrated therapeutic efficacy in certain mice, primarily mediated by CD8+ T cells. However, in mice resistant to dual ICI treatment, even with CD8+ T cell infiltration, most of the T cells exhibited exhaustion phenotype. Notably, resistant tumors displayed abnormal activation of the JAK-STAT pathway compared to the untreated group, with observed infiltration of macrophages, neutrophils, and Tregs in the TME. The concurrent administration of JAKi rescued CD8+ T cells function and reshaped the immunosuppressive TME, resulting in enhanced efficacy of the dual ICI treatment. Conclusion Dual ICI treatment exerts its anti-tumor effects by increasing tumor- specific CD8+ T cell infiltration, and the addition of JAKi further improves ICI resistant by reshaping the immunosuppressive TME.
Project description:Drug resistance is a major public health challenge in Leishmaniasis chemotherapy, particularly in the case of emerging Leishmania/HIV-1 co-infections. Recently, we have delineated the mechanism of cell death induced by the HIV-1 protease inhibitor, Nelfinavir, in the Leishmania parasite. In order to investigate the underlying molecular mechanism involved in Nelfinavir resistance, in vitro Nelfinavir resistant amastigotes were developed by direct drug pressure in culture. RNA expression profiling analyses of closely related Leishmania species were used as a screening tool to compare Nelfinavir-resistant and -sensitive parasites in order to identify candidate genes involved in drug resistance, and several genes were found to be differentially expressed. Comparative gene hybridization (CGH) analyses of Nelfinavir-resistant and -sensitive Leishmania using whole-genome 60-mer oligonucleotide microarrays were also carried out. RNA expression profiles and the CGH of Nelfinavir resistant vs sensitive Leishmania amastigotes suggest that parasites regulate mRNA levels either by modulating gene copy numbers through chromosome aneuploidy, or gene deletion/duplication by homologous recombination. Interestingly, supernumerary chromosomes 6 and 11 in the resistant parasites lead to upregulation of the ABC class of transporters, which are involved in vesicular trafficking. Transporter assays using radiolabeled Nelfinavir suggest that the drug accumulates in greater amounts in the resistant parasites and in a time dependent manner. Furthermore, high-resolution electron microscopy showed an increased number of vacuoles in Nelfinavir-resistant parasites. Together these results suggest that Nelfinavir is rapidly and dramatically sequestered in these intracellular vesicles. Two condition experiment: NFV-sensitive vs resistant. Biological replicates: Three. One dye swap.
Project description:Drug resistance is a major public health challenge in Leishmaniasis chemotherapy, particularly in the case of emerging Leishmania/HIV-1 co-infections. Recently, we have delineated the mechanism of cell death induced by the HIV-1 protease inhibitor, Nelfinavir, in the Leishmania parasite. In order to investigate the underlying molecular mechanism involved in Nelfinavir resistance, in vitro Nelfinavir resistant amastigotes were developed by direct drug pressure in culture. RNA expression profiling analyses of closely related Leishmania species were used as a screening tool to compare Nelfinavir-resistant and -sensitive parasites in order to identify candidate genes involved in drug resistance, and several genes were found to be differentially expressed. Comparative gene hybridization (CGH) analyses of Nelfinavir-resistant and -sensitive Leishmania using whole-genome 60-mer oligonucleotide microarrays were also carried out. RNA expression profiles and the CGH of Nelfinavir resistant vs sensitive Leishmania amastigotes suggest that parasites regulate mRNA levels either by modulating gene copy numbers through chromosome aneuploidy, or gene deletion/duplication by homologous recombination. Interestingly, supernumerary chromosomes 6 and 11 in the resistant parasites lead to upregulation of the ABC class of transporters, which are involved in vesicular trafficking. Transporter assays using radiolabeled Nelfinavir suggest that the drug accumulates in greater amounts in the resistant parasites and in a time dependent manner. Furthermore, high-resolution electron microscopy showed an increased number of vacuoles in Nelfinavir-resistant parasites. Together these results suggest that Nelfinavir is rapidly and dramatically sequestered in these intracellular vesicles. Two condition experiment: NFV-sensitive vs resistant. Biological replicates: Three. One dye swap.
Project description:Transcriptional profiling (lncRNA and mRNA) of human ovarian cancer cells comparing parental PTX-sensitive cells (OVCAR-3) vs. PTX-resistant cells (OV3R-PTX, derived from OVCAR-3).