Project description:To explore the mechanisms underlying the radioresistance of hypopharyngeal carcinoma, we first established specifically radioresistant FaDu cell line (FaDu-RR cells) derived from FaDu cell lines by repeatedly exposing to different doses of ionizing radiation. Then, the aberrantly expressed mRNAs and IncRNAs were detected using microarrays and their bioinformatics were analyzed.
Project description:Interventions: Gold Standard:tissue or cytopathology;Index test:secreted LncRNA
Primary outcome(s): Differential expression of LncRNA in peripheral blood exosomes of patients
Study Design: Single arm
Project description:microRNA regulates cellular responses to ionizing radiation (IR) through the translational control of target genes. We analyzed time-series changes in microRNA expressions upon γ-irradiation in H1299 lung cancer cell lines using microarray. Significantly changed microRNAs were selected based on ANOVA analysis, target genes of which were enriched to MAPK signaling pathway. Concurrent analysis of mRNA and microRNA uncovered that the expression of miR-26b and its target ATF2 mRNA were inversely correlated in γ-irradiated H1299 cells. The overexpression of miR-26b induced the suppression of ATF2 in γ-irradiated cells. When we inhibit the MAPK signaling pathway using SP600125, JNK inhibitor, the expression of miR-26b was induced even in γ-irradiated H1299 cells. From these results, we concluded that the expression of miR-26b was coordinated regulated by MAPK signaling pathway upon ionizing radiation, and MAPK signaling pathway was regulated by miR-26b in turn. We analyzed the time-series miRNA profiles of radioresistant H1299 cells in response to 2 Gy of ionizing radiation (IR) by performing quadratic regression (QR) analysis to identify genes associated with radioresistance
Project description:Nu61, a radiation-resistant human tumor xenograft, was selected from a parental radiosensitive tumor SCC-61 by eight serial cycles of passage in athymic nude mice and in vivo irradiation. Obtained tumors were profiled using Affymetrix U133A arrays. Most abundant gene pattern associated with radioresistant phenotype was presented by IFN-inducible, Stat1-dependent pathway Keywords: Pair-wise comparison of radiosensitive vs radioresistant tumors; time course of irradation response
Project description:Based on a time-course study of cisplatin response in ovarian cancer cells with/without suppression of annexin A11 expression using whole genome oligonucleotide microarrays, we identified a set of differentially expressed genes associated with annexin A11 expression and patterns of gene expressions in response to cisplatin exposure. Keywords: human ovarian cancer cell lines
Project description:This is a mathematical model comprised of non-linear ordinary differential equations describing the dynamic relationship between hypoxia-inducible factor-1 alpha (HIF-1a) mRNA, HIF-1a protein, and interleukin-15-mediated upstream signalling events in natural killer cells from human blood. Regulatory expressions are also included for mammalian target of rapamycin (mTOR), nuclear factor-kappa beta, and signal transducer and activator of transcription 3 (STAT3).
Project description:Radiotherapy is a potent component of the standard of care for breast cancer. However, surviving radioresistant cells can repopulate following treatment and provoke relapse. Better understanding of the molecular mechanisms of radiation resistance may help improve treatment of radioresistant tumours. To emulate radiation therapy at the cellular level, we exposed MCF7 breast cancer cells to daily radiation doses of 2 Gy up to an accumulated dose of 20 Gy. Fractionally irradiated cells (FIR20) displayed increased clonogenic survival and population doubling time as compared to age-matched sham-irradiated cells and untreated, parental MCF7 cells. RNA-sequencing revealed a core signature of 229 mRNAs and 7 circRNAs significantly altered in the FIR20 cells. The FIR20 cell transcriptome overlapped significantly with canonical radiation signatures, and demonstrated a remarkable commonality with radiation and endocrine therapy resistance expression profiles, suggesting crosstalk between both acquired resistance pathways. Using predictive analyses and functional enrichment, we identified a gene-regulatory network of circRNA and mRNA that promotes stemness and inflammatory signaling in FIR20 cells. We propose that these phenotypic traits render breast cancer cells more radioresistant and may therefore serve as potential modules for combination therapies.
Project description:We established radioresistant cell sublines, named as BxPC3/RR1 and BxPC3/RR2 which were derived from parental human pancreatic cancer cell line BxPC3. The miRNA expression profiles of the radioresistant pancreatic cancer cells were then compared with their parental cells. Three samples were analysed. miRNAs that were differentially expressed (increased or decreased in expression by M-bM-^IM-%1.5-fold) between the radioresistant and parental cells were identified.
