Project description:To determine the efficacy (as measured by overall tumour response rate) of the combination of durvalumab and tremelimumab when given to previously treated patients with solid tumors harboring a high mutational load.
Project description:The carotid body is a chemoreceptor that senses decreases in blood oxygen to increase breathing in hypoxia. To look for candidate oxygen sensors in the carotid body, we compared the gene expression of the carotid body to the adrenal medulla, a similar tissue that does not have oxygen sensitivity in adults.
Project description:The carotid body is a chemoreceptor that senses decreases in blood oxygen to increase breathing in hypoxia. To look for candidate oxygen sensors in the carotid body, we compared the gene expression of the carotid body to the adrenal medulla, a similar tissue that does not have oxygen sensitivity in adults.
Project description:The carotid body is a chemoreceptor that senses decreases in blood oxygen to increase breathing in hypoxia. To look for candidate oxygen sensors in the carotid body, we compared the gene expression of the carotid body to the adrenal medulla, a similar tissue that does not have oxygen sensitivity in adults. For each sample, we pooled 18 carotid bodies and 10 adrenal medullas from 10 adult mice.
Project description:The carotid body is a chemoreceptor that senses decreases in blood oxygen to increase breathing in hypoxia. To look for candidate oxygen sensors in the carotid body, we compared the gene expression of the carotid body to the adrenal medulla, a similar tissue that does not have oxygen sensitivity in adults. For each sample, we pooled 18 carotid bodies or 10 adrenal medullas from 10 adult mice. Group numbers designate the same cohort of animals.
Project description:In order to investigate the molecular basis of carotid body chemoreceptor sensitisation in the Spontaneously Hypertensive Rat (SHR) we have sequenced the transcriptomes of bilateral carotid body samples from aged-matched, male SHR and control Wistar-Kyoto rats.
2022-01-11 | GSE178504 | GEO
Project description:EXOME ANALYSIS OF CAROTID BODY TUMOR
Project description:Mutations and expression changes of epigenetic modifiers are pervasive in human tumours, making epigenetic factors attractive as antitumour targets. However, the mutational landscape of tumours correlates with the chromatin state of their cell-of-origin, raising the concern that targeting epigenetic factors might alter the mutational burden and possibly aggravate disease progression. Nonetheless, a causal link between changes in chromatin in tissues and the mutational landscape of their cognate tumours has not yet been established. Here we show that increasing chromatin accessibility through a conditional deletion of the histone H3K9 methyltransferase G9a severely delays and reduces carcinogen-induced squamous tumour initiation and burden. Strikingly, after a prolonged latency, G9a-mutant mice develop highly aggressive tumours with an expanded cancer stem cell (SC) pool. Loss of G9a leads to extensive chromatin opening in the cells of origin of these tumours (i.e. epidermal and hair follicle SCs) . Although this does not alter the number of single-nucleotide variants, the type of substitutions, or the overall mutational topography, it significantly changes the mutational signatures (i.e. microcontext) in the tumor cells. G9a-depleted tumours also display pronounced genomic instability and a frequent accumulation of loss-of-function p53 mutations, compared to their wild-type counterparts. Our results therefore provide evidence for a causal link between chromatin modifications and mutational load in tumours and call for caution when assessing the long-term therapeutic benefits of inhibiting epigenetic factors.
Project description:This analysis compares gene expression in human carotid plaques with gene expression in major tissues and cell types in the human body (GSE1133, Su et al. 2004). Experiment Overall Design: Human carotid endarterectomies were isolated from six subjects with symptomatic carotid artery disease.
Project description:Patients with glioblastoma (GB) so far do not sufficiently benefit from recent breakthroughs with checkpoint inhibitors (CPI), for which high mutational load and responses to neo-epitopes are regarded essential. GB tumours show limited intra-tumoral immune cell infiltration and carry 30-50 non-synonymous mutations only. Exploitation of the full repertoire of tumour antigens - non-mutated and neo-epitopes – may offer more effective immunotherapies, especially for tumours with low mutational load. In the first-in-human trial GAPVAC-101, the Glioma Actively Personalized Vaccine Consortium (GAPVAC) integrated both tracks highly individualized into standard treatment to optimally exploit the limited target space for patients with newly diagnosed GB. Fifteen HLA-A*02:01+ or -A*24:02+ patients were treated with a warehouse-based vaccine (APVAC1) targeting non-mutated antigens followed by APVAC2, targeting preferentially neo-epitopes. Personalization was based on mutations, transcriptome, and immunopeptidome of the individual tumours. The GAPVAC approach was feasible and vaccinations adjuvanted by poly-ICLC and GM-CSF displayed favourable safety and excellent immunogenicity: Non-mutated APVAC1 antigens induced sustained central memory CD8+ T-cell responses. APVAC2 induced predominantly TH1 CD4+ T-cell responses against predicted neo-epitopes. www.GAPVAC.eu