Doxorubicin treatment effects on the young mouse brain transcriptome
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ABSTRACT:
PROVIDER: PRJNA741125 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14903848_1.fastq.gz | Fastqsanger.gz | |||
| SRR14903848_2.fastq.gz | Fastqsanger.gz | |||
| SRR14903849_1.fastq.gz | Fastqsanger.gz | |||
| SRR14903849_2.fastq.gz | Fastqsanger.gz | |||
| SRR14903850_1.fastq.gz | Fastqsanger.gz |
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Project description:Doxorubicin (Doxo) is a common chemotherapeutic reagent associated with mitochondrial dysfunction, DNA damage, and cognitive impairment in human cancer patients. The purpose of this study was to determine the transcriptional effects of Doxo on the brains of young mice. 4 month old C57B6/J male mice were injected with saline sham or 10mg/kg Doxo +/- MitoQ (a mitochondria-specific antioxidant). Hippocampi were harvested from these mice and RNA was isolated to perform polyA RNA-seq to profile gene expression.
2021-06-25 | GSE178812 | GEO
Project description:Doxorubicin (Dox) is a widely used treatment for cancer, which can result in chemotherapy induced cognitive impairments (chemobrain). Chemobrain is associated with inflammation and oxidative stress similar to aging. As such, Dox treatment has also been used as a model of aging. However, it is unclear if Dox induces brain changes similar to that observed during aging, since Dox does not readily enter the brain. Rather, the mechanism for chemobrain likely involves induction of peripheral cellular senescence and the release ofsenescence-associated secretory phenotype (SASP) factors, which enter the brain to disrupt cognition. We examined the effect of Dox on peripheral and brain markers of aging and cognition. In addition, we employed the senolytic, ABT-263, which also has limited access to the brain. While Dox treatment influenced several measures linked to aging, including peripheral inflammation, morphological measure of microglial activation, cognition, and synaptic function,the effects of Dox treatment on brain (i.e. dentate gyrus) gene expression did not approximate aging to the same degree as other measures.Regardless, ABT-263 prevent or limited most of the Dox induced effects, including brain gene expression. The resultsemphasize a link between cognitive decline and the release of SASP factors from peripheral senescent cells and indicate thatdifferences between aging and Dox treatment on brain gene expression are important in considering Dox treatment as a model of aging.
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Project description:Senolytic treatment alleviates doxorubicin-induced chemobrain
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Project description:The anthracycline doxorubicin is a highly effective anti-cancer drug associated with severe side effects, including secondary tumors and cardiotoxicity. Doxorubicin induces DNA damage through double-strand breaks (DSBs) and epigenetic or chromatin damage through histone eviction. We examined whether separation of these activities can help to detoxify doxorubicin, while maintaining its chemotherapeutic efficacy. We show that anthracycline variants harboring the histone eviction activity alone remain potent anti-cancer drugs, while greatly alleviating cardiotoxicity and secondary tumor formation. We thus demonstrate that treatment-limited side effects of doxorubicin can be synthesized away, yielding effective chemotherapeutics towards improved and prolonged treatment responses and higher patient quality of life.
2019-09-01 | GSE108179 | GEO
Project description:Chemotherapy treatment for breast cancer can induce cognitive impairments often involving oxidative stress. The brain, as a whole, is susceptible to oxidative stress due to its high-energy requirements, limited anaerobic respiration capacities, and limited antioxidant defenses. The goal of the current study was to determine if the manganese porphyrin SOD mimetic MnTnBuOE-2-PyP (MnBuOE) could ameliorate the effects of doxorubicin, cyclophosphamide, and paclitaxel (AC-T) on mature dendrite morphology and cognitive function. Four-month-old female C57BL/6 mice received intraperitoneal injections of chemotherapy followed by subcutaneous injections of MnBuOE. Four weeks following chemotherapy treatment, mice were tested for hippocampus-dependent cognitive performance in the Morris water maze. After testing, brains were collected for Golgi staining and molecular analyses. MnBuOE treatment preserved spatial memory during the Morris water-maze. MnBuOE/AC-T showed spatial memory retention during all probe trials. AC-T treatment significantly impaired spatial memory retention in the first and third probe trial (no platform). AC-T treatment decreased dendritic length in the Cornu Ammonis 1 (CA1) and dentate gyrus (DG) areas of the hippocampus while AC-T/MnBuOE maintained dendritic length. Comparative proteomic analysis revealed affected protein networks associated with cell morphology and behavior functions in both the AC-T and AC-T/MnBuOE treatment groups
2020-05-27 | PXD017271 | Pride
Project description:Doxorubicin is a widely used and effective anthracycline chemotherapy drug, which use is limited due to its cardiotoxic side effects. We show that gene therapy with AAV-VEGF-B can inhibit the doxorubicin-induced cardiac atrophy and whole body cachexia.
2016-09-30 | GSE81448 | GEO
Project description:Role of p300 in regulation of stress-response genes in heart is not clear. Treatment with anti-cancer drug Doxorubicin causes cardiotoxicity through generation of oxidative stress in cardiac myocytes. Loss of p300 enhances cell death and apoptosis in response to Doxorubicin. The objective of this study was to determine if expression of genes regulated by oxidative stress is dependent of presence of p300. Further we investigated if protective effect of p300 against Doxorubicin was due to gene expression effects of p300. We used microarray to compare the transcriptomes of cardiac myocytes transfected with anti-p300 or non-silencing siRNA beforebefore and after exposure to Doxorubicin.
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Project description:This phase I trial is studying the side effects and best dose of obatoclax mesylate when given together with vincristine sulfate, doxorubicin hydrochloride, and dexrazoxane hydrochloride in treating young patients with relapsed or refractory solid tumors, lymphoma, or leukemia. Obatoclax mesylate may stop the growth of cancer cells by blocking some of the proteins needed for cell growth and causing the cells to self-destruct. Drugs used in chemotherapy, such as vincristine sulfate, doxorubicin hydrochloride, and dexrazoxane hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving obatoclax mesylate together with combination chemotherapy may kill more cancer cells.
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Project description:To compare expression profiles in the cardiomyocytes with wild type top2b and those with top2b deletion after in vivo treatment of mice with doxorubicin or drug vehicle Doxorubicin is widely used in modern cancer treatments, despite the advent of targeted therapy. However, a dose-dependent cardiotoxicity often limits its clinical use. The prevailing theory hypothesizes that doxorubicin-induced cardiotoxicity is the result of reactive oxygen species (ROS) generation due to redox-cycling of doxorubicin. Here we showed that cardiomyocyte-specific deletion of Topoisomerase II beta (Top2b) markedly reduced DNA double-strand breaks, apoptosis, and functional damages in doxorubicin-treated hearts. To investigate transcriptomic changes after doxorubicin treatment in wild type mouse and mouse with cardiac specific deletion of Top2b, we examined the expression profiles in 4 groups of mice (3/group), ie. wildtype mice with or without doxorubicin treatment and mice with Top2b deletion in the cardiomyocytes with or without doxorubicin treatment. Mice were treated with doxorubicin (25mg/kg, i.p.) or PBS (drug vehicle) for 16 hr or 72 hr. The heart was removed and cardiomyocytes were isolated by using a Langendorff apparatus. After purification, total RNA was extracted from the cardiomyocytes, purified, and used for gene expression analysis. Compared with that in control cardiomyocytes or cardiomyocytes with Top2b deletion, doxorubicin caused a significant expression change in the genome of cardiomyocytes from the wildtype mice. Among the changes, multiple genes encoding mitochondrial structural protein and components of the respiratory chain complexes were down-regulated 72 hr after treatment while multiple genes in the p53 pathway were up-regulated 16 hr after treatment in the wildtype cardiomyocytes.
2012-10-28 | GSE40289 | GEO
Project description:Doxorubicin is considered one of the most potent established chemotherapeutics in the treatment of liposarcoma; however, the response rates usually below 30%, are still disappointing. This study was performed to identify gene expression changes in liposarcoma after doxorubicin treatment. Cells of 19 primary human liposarcoma were harvested intraoperatively and brought into cell culture. Cells were incubated with doxorubicin for 24 h, RNA was isolated and differential gene expression was analysed by the microarray technique. We used microarrays to detail the global gene expression changes following doxorubicin treatment of primary liposarcoma cell cultures Keywords: response to chemotherapeutic agent
2008-10-06 | GSE12972 | GEO