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Analysis of mouse enteroids and colonoids exposed to chemotherapy agent 5-fluorouracil (5FU)

ABSTRACT: ADRs (adverse drug reactions) are one of the main reasons for treatment discontinuation or alterations in dose regimens in clinical settings. Chemotherapy-induced ADRs are common, especially gastrointestinal-induced ones. Within TransQST (transqst.org), one of the main goal is to improve the in vitro-in vivo translation in toxicological studies, as well as translation between non-clinical species (such as rat and mouse) and humans. This experimental setup therefore aimed to investigate the effects of 5FU on 3D mouse organoid cultures derived from small intestine and colon segments. Experiments were conducted in a dose-repeated (daily media refreshing with 10, 100 or 1000 uM of 5FU) and time series regimen (24, 48 and 72h). Time-matched controls (DMSO 0.1% and medium only) were measured, as well as a baseline exposure prior to the beginning of the exposures (medium only, 0h).

INSTRUMENT(S): Illumina HiSeq 2500

ORGANISM(S): Mus musculus

SUBMITTER:

PROVIDER: E-MTAB-9119 | biostudies-arrayexpress |

SECONDARY ACCESSION(S): E-MTAB-9134E-MTAB-9120

REPOSITORIES: biostudies-arrayexpress

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Analysis of human enteroids and colonoids (3D organoid models from small intestine and colon) exposed to chemotherapy agent 5-fluorouracil (5FU) in a dose-repeated exposure across three doses (10,100 and 1000uM) and sampled at three points (24, 48 and 72h) since initial exposure. Organoids were obtained from healthy human tissues.

Project description:ADRs (adverse drug reactions) are one of the main reasons for treatment discontinuation or alterations in dose regimens in clinical settings. Chemotherapy-induced ADRs are common, especially gastrointestinal-induced ones. Within TransQST (transqst.org), one of the main goal is to improve the in vitro-in vivo translation in toxicological studies, as well as translation between non-clinical species (such as rat and mouse) and humans. This experimental setup therefore aimed to investigate the effects of 5FU on 3D human organoid cultures derived from small intestine and colon segments. Experiments were conducted in a dose-repeated (daily media refreshing with 10, 100 or 1000 uM of 5FU) and time series regimen (24, 48 and 72h). Time-matched controls (DMSO 0.1% and medium only) were measured, as well as a baseline exposure prior to the beginning of the exposures (medium only, 0h). This dataset is part of the TransQST collection.

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Analysis of mid-colon and mid-jejunum segments from C57BL/6J wild-type mice exposed to 5-fluorouracil (5-FU). Intravenous exposure to 5-FU was performed with two doses (20 and 50 mg/kg), over a period of 4 days. Mucosal scrapes samples were collected for RNA isolation at 6, 24 and 96h since initial exposure. A recovery period of 2 days (sampled at 144h) followed up the 96h of repeated exposure. Samples from time-matched controls (saline 10 mM Tris/NaOH buffer pH 8.5) were also quantified.

Project description:ADRs (adverse drug reactions) are one of the main reasons for treatment discontinuation or alterations in dose regimens in clinical settings. Chemotherapy-induced ADRs are common, especially gastrointestinal-induced ones. Within TransQST (transqst.org), one of the main goal is to improve the in vitro-in vivo translation in toxicological studies, as well as translation between non-clinical species (such as rat and mouse) and humans. This experimental setup aimed to investigate the injury dynamics underlying repeated exposure to two doses of 5-FU (20 and 50 mg/kg), sampled at multiple time points (6, 24, 96 and 144h). The 144h time point comprises of recovery samples (i.e., 48h following the last dosing with 5-FU). This dataset is part of the TransQST collection.

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RNA-seq of human colon biopsy tissue of healthy segments, from advanced breast cancer patients treated with capecitabine (5-FU)

Project description:ADRs (adverse drug reactions) are one of the main reasons for treatment discontinuation or alterations in dose regimens in clinical settings. Chemotherapy-induced ADRs are common, especially gastrointestinal-induced ones. Within TransQST (transqst.org), one of the main goal is to improve the in vitro-in vivo translation in toxicological studies, as well as translation between non-clinical species (such as rat and mouse) and humans. This experimental setup therefore aimed to investigate the effects of capecitabine, which is activated into 5-FU in the body, on advanced breast cancer patients. Healthy colon tissue was collected from the patients before and after the first cycle of the monotherapy, which consists of 2 weeks treatment followed by 1 week rest. Each patient was their own control sample. Transcriptomic data collected from the colon biopsies was compared with previous data collected from colon organoids to verify for the translatability of the in vitro model to humans. This dataset is part of the TransQST collaboration.

2022-08-01 | E-MTAB-11295 | biostudies-arrayexpress

Analysis of mid-colon and mid-jejunum segments from C57BL/6J wild-type mice exposed to doxorubicin (DOX)

Project description:ADRs (adverse drug reactions) are one of the main reasons for treatment discontinuation or alterations in dose regimens in clinical settings. Chemotherapy-induced ADRs are common, especially gastrointestinal-induced ones. Within TransQST (transqst.org), one of the main goal is to improve the in vitro-in vivo translation in toxicological studies, as well as translation between non-clinical species (such as rat and mouse) and humans. This experimental setup therefore aimed to investigate the effects of DOX on mouse tissue derived from colon and jejunum biopsies. Experiments were conducted in a dose (5 and 10 mg/kg) and time series regimen (6, 24, 72 and 96h). Time-matched controls were measured as well. Intravenous exposure to DOX was performed with two doses (5 and 10 mg/kg), over a period of 4 days. Mucosal scrapes samples were collected for RNA isolation at 6, 24, 72 and 96h since initial exposure. Samples from time-matched controls (saline 10 mM Tris/NaOH buffer pH 8.5) were also quantified. This dataset is part of the TransQST collection.

2022-12-31 | E-MTAB-11339 | biostudies-arrayexpress

Transcriptional response of Schizosaccharomyces pombe to 5-Fluorouracil (5FU)

2013-11-14 | GSE46919 | GEO

Mouse HSC proteomics in basal or 5FU activated conditions

Project description:Proteomics of hemaopoietic stem cells under basal or 5FU activated conditions

2022-02-16 | PXD021340 | Pride

Transcriptional response of Schizosaccharomyces pombe to 5-Fluorouracil (5FU)

Project description:We use high-density tiling DNA microarray technology to obtain the specific transcriptome-wide response induced by 5-Fluorouracil (5FU) in the eukaryotic model Schizosaccharomyces pombe. Schizosaccharomyces pombe cultures with 5FU added to a final concentration of 500 M-NM-<M. Incubation was allowed to proceed for 0, 15, 60 and 240 minutes.Two biological replicates each.

2013-11-14 | E-GEOD-46919 | biostudies-arrayexpress

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