Project description:Recently, senescence has been suggested as a defense mechanism to block sporadic induction of cancer cells. Radiation treatment induces proliferating cancer cells to turn into non-proliferating senescent cells in vitro. To characterize transcriptional reprogramming after radiation treatment, we measured the gene expression profiles of MCF7 at different time points after treatment. In these experiments, we found that IR induced premature senescence in MCF7 cells, and IR treatment resulted in significant changes in the expression of 305 marker genes (less than 1% FDR), which were strongly correlated (|r|>0.9) with IR treatment in a time-dependent manner. Functional analysis of these markers indicated that the dynamics of cytoskeletal structure and lysosomal activity gradually increased. The expression of marker genes for modulator proteins, that were responsible for the dynamics of actin stress fibers and focal adhesion, displayed a particularly strong positive correlation with senescence-associated (SA) morphological changes through time. We also observed a strong induction of genes related to lysosomal metabolic activity, which was accompanied by an increase in the number of SA-beta-Gal positive cells. However, the expression of genes for the cell cycle progression, the post-transcription and the translation activities gradually decreased after radiation treatment. Especially, we observed clear cell cycle arrest specifically at the S and G2/M phases with consistent down-regulation of genes for microtubule assembly/disassembly or spindle biogenesis. Gene expression profiles were obtained from human MCF7 cells after ionizing radiation (6 Gy) at day 0 (no ionizing radiation), day 1 (after ionizing radiation), day 2, day 3, and day 4.
Project description:Autophagy inhibition through small-molecule inhibitors is one of the approaches to increasing the efficiency of radiotherapy of oncological patients. A new inhibitor, Lys05, with potential to accumulate within lysosomes and to block autophagy has been discovered recently. Several studies have described its chemosensitizing effects, but nothing is known about its impact in the context of ionizing radiation (IR). To investigate the mechanisms underlying its role in radiosensitization we employed radioresistant human non-small cell lung carcinoma cells (H1299, p53-negative) in combination with multiple approaches (cell biology techniques to reveal the phenotypes, and quantitative phosphoproteomics to comprehensively describe Lys05-induced changes in irradiated cells). In the presented study, we report for the first time that Lys05 could be utilized in combination with IR as a promising future strategy in eradication of lung cancer cells.
Project description:gDNA from patient samples with multiple basal cell carcinomas and possible exposure to ionizing radiation was hybridized Vs. GM12878 gDNA to assess CNAs. We aimed to find a possible common aberration pattern related to ionizing radiation or a rare metastasis.
Project description:Tardigrades can survive remarkable doses of ionizing radiation, up to about 1000 times the lethal dose for humans. How they do so is incompletely understood. We found that the tardigrade Hypsibius exemplaris suffers DNA damage upon gamma irradiation, but damage is repaired. We show that tardigrades have a specific and robust response to ionizing radiation: irradiation induces a rapid, dramatic upregulation of many DNA repair genes. By expressing tardigrade genes in bacteria, we validate that increased expression of some repair genes can suffice to increase radiation tolerance. We show that at least one such gene is necessary for tardigrade radiation tolerance. Tardigrades’ ability to sense ionizing radiation and massively upregulate specific DNA repair pathway genes may represent an evolved solution for maintaining DNA integrity.
Project description:Intraoperative radiotherapy (IOERT) is a high radiation therapeutic technique which administers a single high dose of ionizing radiation (IR) immediately after surgical tumor removal in order to destroy the residual cancer cells in the site at high risk for recurrence. IR is able to regulate several genes and factors involved in cell-cycle progression, survival and/or cell death, DNA repair and inflammation modulating an intracellular response radiation dependent producing an imbalance in cell fate decision. In this study, we examined changes in gene expression in MCF7 breast cancer cell line exposed to 9Gy and 23Gy high single dose of IR delivered by IOERT. Changes in gene expression in MCF7 breast cancer cell line exposed to 9Gy and 23Gy high single dose of IR (named MCF7_9Gy and MCF7_23Gy respectively), were analyzed as two-color hybridizations using Agilent Technologies whole human genome 4x44K microarrays
Project description:Intraoperative radiotherapy (IOERT) is a high radiation therapeutic technique which administers a single high dose of ionizing radiation (IR) immediately after surgical tumor removal in order to destroy the residual cancer cells in the site at high risk for recurrence. IR is able to regulate several genes and factors involved in cell-cycle progression, survival and/or cell death, DNA repair and inflammation modulating an intracellular response radiation dependent producing an imbalance in cell fate decision. In this study, we examined changes in gene expression in MCF7 breast cancer cell line exposed to 9Gy and 23Gy high single dose of IR delivered by IOERT.
Project description:Genome-wide expression analysis comparison with and without ionizing radiation in p53 mutant and wild type Drosophila larvae Genome-wide expression analysis comparison with and without ionizing radiation in p53 mutant (p53^5A-1-4) and wild type (y^1 w^1118) Drosophila third instar larvae. 4000R of X-rays used in IR-treated Drosophila. Analyzed 2hr and 18hr after exposure with age-matched larvae in non-treated controls.