Project description:Pancreatic cancer is the 3rd most prevalent cause of cancer related deaths in United states alone, with over 55000 patients being diagnosed in 2019 alone and nearly as many succumbing to it. Late detection, lack of effective therapy and poor understanding of pancreatic cancer systemically contributes to its poor survival statistics. Obesity and high caloric intake linked co-morbidities like type 2 diabetes (T2D) have been attributed as being risk factors for a number of cancers including pancreatic cancer. Studies on gut microbiome has shown that lifestyle factors as well as diet has a huge effect on the microbial flora of the gut. Further, modulation of gut microbiome has been seen to contribute to effects of intensive insulin therapy in mice on high fat diet. In another study, abnormal gut microbiota was reported to contribute to development of diabetes in Db/Db mice. Recent studies indicate that microbiome and microbial dysbiosis plays a role in not only the onset of disease but also in its outcome. In colorectal cancer, Fusobacterium has been reported to promote therapy resistance. Certain intra-tumoral bacteria have also been shown to elicit chemo-resistance by metabolizing anti-cancerous agents. In pancreatic cancer, studies on altered gut microbiome have been relatively recent. Microbial dysbiosis has been observed to be associated with pancreatic tumor progression. Modulation of microbiome has been shown to affect response to anti-PD1 therapy in this disease as well. However, most of the studies in pancreatic cancer and microbiome have remained focused om immune modulation. In the current study, we observed that in a T2D mouse model, the microbiome changed significantly as the hyperglycemia developed in these animals. Our results further showed that, tumors implanted in the T2D mice responded poorly to Gemcitabine/Paclitaxel (Gem/Pac) standard of care compared to those in the control group. A metabolomic reconstruction of the WGS of the gut microbiota further revealed that an enrichment of bacterial population involved in drug metabolism in the T2D group.
Project description:Off-target amplification can lead to false positive human brain microbiome detection. 16s rRNA amplicon samples from brain tissue of healthy and Parkinson's disease patients.
Project description:We used microarrays to detail the global program of gene expression underlying Parkinson's disease Experiment Overall Design: Substantia nigra tissue from postmortem brain of normal and Parkinson disease patients were used for RNA extraction and hybridization on Affymetrix microarrays: 9 replicates for the controls and 16 replicates for the Parkinson's disease patients were used. Both cohorts included males and females.
Project description:In this study we identify the gene expression changes that occur in the brain-localized immune cells in a mouse model of Parkinson's Disease. A mouse model of Parkinson's Disease was created as previously described by stereotacticaly injecting an AAV-expressing the human A53T_mutated form of a-Synuclein into the Substantia Nigra of adult mice, while control mice were injected with empty vector (EV). These mice exhibit neurodegeneration in the Substantia Nigra and Parkinson-like behaviour phenotypes. Sixteen weeks after the injection, the Substantia Nigra and Srtiatum were micro-dissected and a Percoll gradient was used to enrich for the immune cells present in these tissues. The immune cells were also isolated from the Substantia Nigra and Striatum of same-age WT uninjected mice (WT). RNA was isolated from these cells and single-end 75nt high throughput sequencing were performed on libraries prepared from the RNA. We identified over 400 genes that were differentially expressed between control and Parkinson's mice with a log2 fold-change > |0.75|. These genes were enriched for terms related to immune activation such as: cytokine processing, leukocyte activation, and antigen presentation. The genes associated with these GO terms tended to be up-regulated in the Parkinson's mice suggesting that brain-localized immune cells are more activated in Parkinson's disease.
2021-11-01 | GSE148784 | GEO
Project description:Fecal gut microbiome of patients with Parkinson's disease