Short-term effect of Boost versus Radical doses of Intraoperative electron Radiotherapy in breast cancer tumor bed using high-throughput approaches
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE119204 | GEO | 2018/08/30
REPOSITORIES: GEO
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Project description:The gene expression changes induced upon electron radiation in cancer cells is largely unexplored. We investigated the effect of electron radiation generated from 8 MeV Microtron in Daltons lymphoma ascites (DLA) cells bearing mice model. Mice implanted with DLA cells in their peritoneal cavity were exposed to 2 Gy dose of electron radiation. 48 Hours after irradiation, tumor cells were harvested from peritoneal cavity of both treatment-naive and total body irradiated mice. Microarray based genome-wide mRNA profiling approach was used to identify the differentially expressed genes between control and treated groups. 249 genes were found altered in DLA cells upon electron irradiation, of which 176 genes were upregulated and 73 genes were downregulated. The microarray results from this study were validated using reverse transcriptase PCR (RT-PCR) for selected candidate genes. In summary, total body irradiation with 8 MeV electrons has potential to inhibit the tumor cell proliferationin in vivo lymphoma model with the changes in specific signaling pathways and gene expression. Mice implanted with DLA cells in their peritoneal cavity were exposed to 2 Gy dose of electron radiation. Total RNA was isolated from DLA cells retrieved from control (treatment-naive) and irradiated mice (2 Gy) at 48 hours after radiation exposure.
2013-03-05 | E-GEOD-44908 | biostudies-arrayexpress
Project description:The gene expression changes induced upon electron radiation in cancer cells is largely unexplored. We investigated the effect of electron radiation generated from 8 MeV Microtron in Daltons lymphoma ascites (DLA) cells bearing mice model. Mice implanted with DLA cells in their peritoneal cavity were exposed to 2 Gy dose of electron radiation. 48 Hours after irradiation, tumor cells were harvested from peritoneal cavity of both treatment-naive and total body irradiated mice. Microarray based genome-wide mRNA profiling approach was used to identify the differentially expressed genes between control and treated groups. 249 genes were found altered in DLA cells upon electron irradiation, of which 176 genes were upregulated and 73 genes were downregulated. The microarray results from this study were validated using reverse transcriptase PCR (RT-PCR) for selected candidate genes. In summary, total body irradiation with 8 MeV electrons has potential to inhibit the tumor cell proliferationin in vivo lymphoma model with the changes in specific signaling pathways and gene expression.
2013-03-05 | GSE44908 | GEO
Project description:Treatment-related morbidities have been linked to the large post-operative treatment volumes required for external beam partial breast irradiation (PBI). Alternative PBI techniques require equipment that is not readily available. To address these issues, we designed a phase I trial utilizing widely available technology to 1) evaluate the safety of a single radiation treatment delivered preoperatively to the small-volume, intact breast tumor and 2) identify imaging and genomic markers of radiation response. Women 55 or older with clinically node negative, ER+ and/or PR+, HER2-, T1 invasive carcinomas or low-intermediate grade in situ disease â¤2cm were enrolled (n=32). Intensity-modulated radiotherapy was used to deliver 15 Gy (n=8, patients 01-08), 18 Gy (n=8, patients 09-16), or 21Gy (n=16, patients 17-32) to the tumor with a 1.5cm margin. Lumpectomy was performed within 10 days. Paired pre- and post-radiation MRI images and patient tumor samples were analyzed.
2015-10-31 | E-GEOD-65505 | biostudies-arrayexpress
Project description:Intraoperative Electron Radiation Therapy (IOERT) is a therapeutic technique that delivers a single high dose of ionizing radiation (IR) directly to the tumor bed during cancer surgery. The main goal of IOERT is to counteract tumor growth by acting on residual cancer cells in the site at high risk for recurrence as well as to preserve healthy surrounding tissue from the side effects of radiation therapy. The high IR dose used during IOERT treatment induces a strong stress response resulting in the activation of pro- and anti-proliferative cell signaling pathways in both tumor and normal cells. The radiobiology of healthy tissue response to IR is a topic of interest which may contribute to avoid the impairment of normal tissue/organ function and to decrease the risks of secondary cancers. In this study, we examined changes in gene expression in MCF10A breast epithelial cell line exposed to 9Gy and 23Gy high single dose of IR delivered by IOERT. Changes in gene expression in MCF10A breast epithelial cell line exposed to 9Gy and 23Gy high single dose of IR (named MCF10A_9Gy and MCF10A_23Gy respectively), were analyzed as two-color hybridizations using Agilent Technologies whole human genome 4x44K microarrays
2015-07-06 | E-GEOD-65954 | biostudies-arrayexpress
Project description:Intraoperative Electron Radiation Therapy (IOERT) is a therapeutic technique that delivers a single high dose of ionizing radiation (IR) directly to the tumor bed during cancer surgery. The main goal of IOERT is to counteract tumor growth by acting on residual cancer cells in the site at high risk for recurrence as well as to preserve healthy surrounding tissue from the side effects of radiation therapy. The high IR dose used during IOERT treatment induces a strong stress response resulting in the activation of pro- and anti-proliferative cell signaling pathways in both tumor and normal cells. The radiobiology of healthy tissue response to IR is a topic of interest which may contribute to avoid the impairment of normal tissue/organ function and to decrease the risks of secondary cancers. In this study, we examined changes in gene expression in MCF10A breast epithelial cell line exposed to 9Gy and 23Gy high single dose of IR delivered by IOERT.
2015-07-06 | GSE65954 | GEO
Project description:This study aims to compare the cell heterogeneity and mRNA expression between irradiated and non-irradiated rat skin tissues at the single cell level. In this study, the skin was isolated from rats with radiation or non-irradiated rats. Male Sprague Dawley (SD) rats (6 weeks of age) were used. For irradiation, the hair on the gluteal region of the rats was shaved using a razor. The animals were immobilized using adhesive tape on a plastic plate to minimize motion during radiation exposure. A 3-cm-thick piece of lead was used to shield the animals and localize the radiation field (3-4 cm). Irradiation was performed on the treatment area at a dose rate of 1000 cGy/min using a 6-MeV electron beam accelerator. Irradiated skin was taken on day 7, 14, 28 and 60 for RNA-seq, respectively. The control group of skin were collected from four rats without radiation and mixed for RNA-seq.
2022-01-19 | GSE193564 | GEO
Project description:This is a genome-wide approach to identifying genes persistently induced in the mouse mammary gland by acute whole body low dose ionizing radiation (10cGy), 1 and 4 weeks after exposure. Gene expression that is modified under these parameters were compared between Tgfb1 wild type and heterozygote littermates in order to determine which genes induced or repressed by radiation were mediated via Tgfb1 status. Differential gene expression was analyzed in Tgfb1 heterozygote and wild type littermate 4th mammary glands, after whole body exposure to an acute dose of 10cGy ionizing radiation. Estrus cycle was normalized in all mice two days prior to irradiation by injection with an estrogen and progesterone mixture. It is widely believed that the carcinogenic action of ionizing radiation is due to targeted DNA damage and resulting mutations, but there is also substantial evidence that non-targeted radiation effects alter epithelial phenotype and the stromal microenvironment. Activation of transforming growth factor beta 1 (TGFbeta) is a non-targeted radiation effect that mediates cell fate decisions following DNA damage and regulates microenvironment composition; it could either suppress or promote cancer. Gene expression profiling shown herein demonstrates that low dose radiation (10 cGy) elicits persistent changes in Tgfb1 wild type and heterozygote murine mammary gland that are highly modulated by TGFbeta. We asked if such non-targeted radiation effects contribute to carcinogenesis by using a novel radiation chimera model. Unirradiated Trp53 null mammary epithelium was transplanted to the mammary stroma of mice previously exposed to a single low (10 -100 cGy) radiation dose. By 300 days, 100% of transplants in irradiated hosts at either 10 or 100 cGy had developed Trp53 null breast carcinomas compared to 54% in unirradiated hosts. Tumor growth rate was also increased by high, but not low, dose host irradiation. In contrast, irradiation of Tgfb1 heterozygote mice prior to transplantation failed to decrease tumor latency, or increase growth rate at any dose. Host irradiation significantly reduced the latency of invasive ductal carcinoma compared to spindle cell carcinoma, as well as those tumors negative for smooth muscle actin in wild type but not Tgfb1 heterozygote mice. However, irradiation of either host genotype significantly increased the frequency of estrogen receptor negative tumors. These data demonstrate two concepts critical to understanding radiation risks. First, non-targeted radiation effects can significantly promote the frequency and alter the features of epithelial cancer. Second, radiation-induced TGFbeta activity is a key mechanism of tumor promotion. Keywords: Differential gene expression after low dose irradiation Two genotypes: TGBbeta1 heterozygote and wildtype mouse mammary glands. Two time points post-10cGy-irradiation per genotype (1 week, 4 weeks); control time point was 1 week post-sham-irradiation. Two or three replicates per time point.
2010-03-07 | E-GEOD-18216 | biostudies-arrayexpress
Project description:While modern radiotherapy technologies can precisely deliver higher doses of radiation to tumors; thus, reducing overall radiation exposure to normal tissues, moderate dose and normal tissue toxicity still remains a significant limitation. The present study profiled the global effects on transcript and miR expression in Human Coronary Artery Endothelial Cells (HCAECs) using single-dose irradiation (SD, 10Gy) or multi-fractionated irradiation (MF, 2Gy x 5) regimens. Longitudinal timepoints were collected after a SD or final dose of MF irradiation for analysis using Agilent Human Gene Expression and miRNA microarray platforms. Compared to SD, the exposure to MF resulted in robust transcript and miR expression changes in terms of the number and magnitude. For data analysis, statistically significant mRNAs (2-fold) and miRs (1.5-fold) were processed by Ingenuity Pathway Analysis (IPA) to uncover miRs associated with target transcripts from several cellular pathways post-irradiation. Interestingly, MF radiation induced a cohort of mRNAs and miRs that coordinate the induction of immune response pathway under tight regulation. Additionally, mRNAs and miRs associated with DNA replication, recombination and repair, apoptosis, cardiovascular events and angiogenesis were revealed. Human Coronary Artery Endothelial Cells (HCAECs) were irradiated in a PANTAK high frequency X-ray generator (Precision X-ray Inc., N. Bedford, CT), operated at 300kV and 10MA. The dose rate was 1.6 Gy per min. Cells were plated into T75cm2 flasks (1-1.5 x 10^6 for single dose radiation and 0.6-0.8 x 10^6 for fractionated radiation). After 24h, cells were exposed to a total of 10 Gy radiation administered either as a single-dose radiation (SD), or as multi-fractionated radiation of 2 Gy x 5 (MF). These non-isoeffective doses were selected to simulate clinical hypofractionated and conventionally fractionated radiotherapy regimens. For the MF protocol, cells were exposed to 2 Gy radiation twice a day, at 6h interval. The cells were approximately 90% confluent at the time of harvesting. For both protocols, radiation-induced changes were analyzed at 6h and 24h after a SD and 6h and 24h after the final dose of fractionated irradiation. Separate controls were maintained for SD and MF radiation protocols.
2014-07-01 | E-GEOD-56824 | biostudies-arrayexpress
Project description:While modern radiotherapy technologies can precisely deliver higher doses of radiation to tumors; thus, reducing overall radiation exposure to normal tissues, moderate dose and normal tissue toxicity still remains a significant limitation. The present study profiled the global effects on transcript and miR expression in Human Coronary Artery Endothelial Cells (HCAECs) using single-dose irradiation (SD, 10Gy) or multi-fractionated irradiation (MF, 2Gy x 5) regimens. Longitudinal timepoints were collected after a SD or final dose of MF irradiation for analysis using Agilent Human Gene Expression and miRNA microarray platforms. Compared to SD, the exposure to MF resulted in robust transcript and miR expression changes in terms of the number and magnitude. For data analysis, statistically significant mRNAs (2-fold) and miRs (1.5-fold) were processed by Ingenuity Pathway Analysis (IPA) to uncover miRs associated with target transcripts from several cellular pathways post-irradiation. Interestingly, MF radiation induced a cohort of mRNAs and miRs that coordinate the induction of immune response pathway under tight regulation. Additionally, mRNAs and miRs associated with DNA replication, recombination and repair, apoptosis, cardiovascular events and angiogenesis were revealed. Human Coronary Artery Endothelial Cells (HCAECs) were irradiated in a PANTAK high frequency X-ray generator (Precision X-ray Inc., N. Bedford, CT), operated at 300kV and 10MA. The dose rate was 1.6 Gy per min. Cells were plated into T75cm2 flasks (1-1.5 x 10^6 for single dose radiation and 0.6-0.8 x 10^6 for fractionated radiation). After 24h, cells were exposed to a total of 10 Gy radiation administered either as a single-dose radiation (SD), or as multi-fractionated radiation of 2 Gy x 5 (MF). These non-isoeffective doses were selected to simulate clinical hypofractionated and conventionally fractionated radiotherapy regimens. For the MF protocol, cells were exposed to 2 Gy radiation twice a day, at 6h interval. The cells were approximately 90% confluent at the time of harvesting. For both protocols, radiation-induced changes were analyzed at 6h and 24h after a SD and 6h and 24h after the final dose of fractionated irradiation. Separate controls were maintained for SD and MF radiation protocols.
2014-07-01 | E-GEOD-57059 | biostudies-arrayexpress
Project description:It is widely believed that the carcinogenic action of ionizing radiation is due to targeted DNA damage and resulting mutations, but there is also substantial evidence that non-targeted radiation effects alter epithelial phenotype and the stromal microenvironment. Activation of transforming growth factor β1 (TGFβ) is a non-targeted radiation effect that mediates cell fate decisions following DNA damage and regulates microenvironment composition; it could either suppress or promote cancer. We asked if such non-targeted radiation effects contribute to carcinogenesis by using a novel radiation chimera model. Unirradiated Trp53 null mammary epithelium was transplanted to the mammary stroma, previously divested of endogenous epithelia, of mice previously exposed to a single low (10 -100 cGy) radiation dose. By 300 days, 100% of transplants in irradiated hosts at either 10 or 100 cGy had developed Trp53 null breast carcinomas compared to 54% in unirradiated hosts. Tumor growth rate was also increased by high, but not low, dose host irradiation. In contrast, irradiation of Tgfb1 heterozygote mice prior to transplantation failed to decrease tumor latency, or increase growth rate at any dose. Host irradiation significantly reduced the latency of invasive ductal carcinoma compared to spindle cell carcinoma. However, irradiation of either host genotype significantly increased the frequency of estrogen receptor negative tumors. These data demonstrate two concepts critical to understanding radiation risks. First, non-targeted radiation effects can significantly promote the frequency and alter the features of epithelial cancer. Second, radiation-induced TGFβ activity is a key mechanism of tumor promotion. Keywords: Differential gene expression after low dose irradiation
2010-03-01 | GSE18216 | GEO