Project description:Fluoropyrimidines, including 5-fluororacil (5FU) and its pro-drug Capecitabine, are the common treatment for colorectal, breast, neck and head cancers – either as monotherapy or in combination therapy. Adverse reactions (ADRs) to the treatment are common and often result in treatment discontinuation or dose reduction. Factors contributing to ADRs, including genetic variation, are poorly characterized. We performed exome array analysis to identify genetic variants that contribute to adverse reactions.Our final dataset consisted of 504 European ancestry individuals undergoing fluoropyrimidine-based therapy for gastrointestinal cancer. A subset of 254 of these were treated with Capecitabine. All individuals were genotyped on the Illumina HumanExome Array.
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.
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.
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 3D human organoid cultures derived from healthy small intestine and colon segments. Experiments were conducted in a dose (1,10, 30 and 60uM) and time series regimen (24, 48 and 72h). Time-matched controls (DMSO 0.1% and medium only) were measured as well. This dataset is part of the TransQST collection.
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 gefitinib on 3D human organoid cultures derived from small intestine and colon segments. Experiments were conducted with a dose (0.1, 1, 10 and 30uM of gefitinib) and time series regimen (24, 48 and 72h). Time-matched controls (DMSO 0.1% and medium only) were also included. This dataset is part of the TransQST collection.
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 3D mouse organoid cultures derived from healthy small intestine and colon segments. Experiments were conducted in a dose (0.1, 1, 10 and 30uM) and time series regimen (24, 48 and 72h). Time-matched controls (DMSO 0.1% and medium only) were measured as well. This dataset is part of the TransQST collection.
Project description:ADRs are immune mediated skin reactions of diverse severity and etiology. The patho-mechanisms are however not well understood. We used a gene expression array for the comparison of the gene expression profile of 2 cutaneous adverse drug reactions (MPR and AGEP) to normal skin.
Project description:Lung cancer is the leading cause of cancer-related morbidity and mortality worldwide. The initial treatment of lung cancer depends on the definition of the tumor type and its staging. The most common treatment is chemotherapy, and the first-line treatment is a combination of carboplatin and paclitaxel. Although this treatment has good efficacy, there is a high prevalence of adverse reactions, especially hematological reactions. Studies on new biomarkers related to these adverse reactions, such as circulating miRNAs, are very important for optimizing the quality of life of patients. miRNAs have high stability in several biological fluids and they have specific expressions in different tissues or pathologies. Thus, this study aimed to verify the relationship between circulating miRNAs and adverse hematologic reactions caused by treatment with carboplatin and paclitaxel in patients with lung cancer. miRNAs were extracted from samples collected from six patients without anemia and six patients with anemia using the miRNeasy Serum/Plasma Kit (Qiagen, cat no. 217184). After miRNA extraction, microarray analysis was performed. The samples went through processes of marking, insertion in the chips, hybridization for 18 h, washing, and scanning. All procedures were performed using the Affymetrix multi-user platform®, and were in accordance with the user guide of the commercial kit MicroArrayFlashTag™Biotin HSR RNA Labeling Kit Genechip®4.0 (ThermoFisher, Cat No. /ID: 902445,900720,900454).
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.
