Airway epithelial cells from smokers treated with myo-inositol or placebo
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE86422 | GEO | 2016/09/26
SECONDARY ACCESSION(S): PRJNA341833
REPOSITORIES: GEO
Similar Datasets
Project description:Cytologically normal airway epithelial samples were collected during bronchoscopy of current and former smokers. Subjects enrolled in this study were either under suspicion of having lung cancer, had dysplasia in their airway, or were a healthy current, former or never smoker. We supplemented existing GEO series (GSE4115 and GSE7895) with the samples in this study to explore PI3K pathway activity in the these cohorts. This study contains: 2 arrays from smokers with COPD (no lung cancer), 1 array from smoker without COPD (no lung cancer); 2 samples from patients with lung cancer, 2 samples from patients without lung cancer; 20 samples from 10 matched individuals with airway dysplasia before and after treatment with myo-inositol, 6 additional samples from individuals with airway dysplasia; 27 samples from mammary epithelial cells used in oncogenic pathway analysis that have either the PI3K pathway activated, the Np63 pathway activated, or are a GFP control.
2010-04-11 | E-GEOD-12815 | biostudies-arrayexpress
Project description:Airway epithelial cells from smokers treated with myo-inositol or placebo
| PRJNA341833 | ENA
Project description:Cytologically normal airway epithelial samples were collected during bronchoscopy of current and former smokers. Subjects enrolled in this study were either under suspicion of having lung cancer, had dysplasia in their airway, or were a healthy current, former or never smoker. We supplemented existing GEO series (GSE4115 and GSE7895) with the samples in this study to explore PI3K pathway activity in the these cohorts.
2010-04-12 | GSE12815 | GEO
Project description:Plants develop mutualistic association with beneficial rhizobacteria. To understand this important phenomenon, early mechanisms for establishing the mutualism are critical. Here we report that active DNA demethylation in plants controls root secretion of myo-inositol, which triggers and further facilitates colonization of the beneficial rhizobacteria Bacillus megaterium strain YC4, thereby allowing for plant growth-promotion. YC4 promotes plant growth but the beneficial effects were lost in the Arabidopsis mutant rdd that is defective in active DNA demethylation. Roots of rdd failed to associate with YC4, meanwhile the level of myo-inositol in root exudates was drastically reduced in rdd. Supplementation of myo-inositol to rdd restored YC4 colonization and plant growth-promotion, while plants with defective myo-inositol monophosphatase also failed in establishing mutualism with YC4. myo-Inositol not only induced chemotaxis of YC4 but also increased YC4 biofilm production, consistent with the transcriptional regulation of YC4 by myo-inositol. In addition, myo-inositol preferentially attracts Bacillus megaterium among the examined bacteria species. Regardless of YC4 inoculation, myo-inositol biosynthesis and catabolism genes are down- and up-regulated, respectively, in rdd compared to wild type plants. The differential expression of myo-inositol homeostasis genes is correlated with local DNA hypermethylation, whereas genetic disruption of the RNA-directed DNA methylation pathway abolished these epigenetic marks and reset the corresponding gene expression patterns, resulting in restored YC4 colonization and plant growth-promotion. Importantly, that active DNA demethylation controls myo-inositol-mediated mutualism between YC4 and plants was also demonstrated in Solanum lycopersicum. Our results uncover an important function of myo-inositol in plant-microbe interactions and its dependence on plant epigenetic regulation.
2022-12-19 | GSE143434 | GEO
Project description:Plants develop mutualistic association with beneficial rhizobacteria. To understand this important phenomenon, early mechanisms for establishing the mutualism are critical. Here we report that active DNA demethylation in plants controls root secretion of myo-inositol, which triggers and further facilitates colonization of the beneficial rhizobacteria Bacillus megaterium strain YC4, thereby allowing for plant growth-promotion. YC4 promotes plant growth but the beneficial effects were lost in the Arabidopsis mutant rdd that is defective in active DNA demethylation. Roots of rdd failed to associate with YC4, meanwhile the level of myo-inositol in root exudates was drastically reduced in rdd. Supplementation of myo-inositol to rdd restored YC4 colonization and plant growth-promotion, while plants with defective myo-inositol monophosphatase also failed in establishing mutualism with YC4. myo-Inositol not only induced chemotaxis of YC4 but also increased YC4 biofilm production, consistent with the transcriptional regulation of YC4 by myo-inositol. In addition, myo-inositol preferentially attracts Bacillus megaterium among the examined bacteria species. Regardless of YC4 inoculation, myo-inositol biosynthesis and catabolism genes are down- and up-regulated, respectively, in rdd compared to wild type plants. The differential expression of myo-inositol homeostasis genes is correlated with local DNA hypermethylation, whereas genetic disruption of the RNA-directed DNA methylation pathway abolished these epigenetic marks and reset the corresponding gene expression patterns, resulting in restored YC4 colonization and plant growth-promotion. Importantly, that active DNA demethylation controls myo-inositol-mediated mutualism between YC4 and plants was also demonstrated in Solanum lycopersicum. Our results uncover an important function of myo-inositol in plant-microbe interactions and its dependence on plant epigenetic regulation.
2022-12-19 | GSE143433 | GEO
Project description:Plants develop mutualistic association with beneficial rhizobacteria. To understand this important phenomenon, early mechanisms for establishing the mutualism are critical. Here we report that active DNA demethylation in plants controls root secretion of myo-inositol, which triggers and further facilitates colonization of the beneficial rhizobacteria Bacillus megaterium strain YC4, thereby allowing for plant growth-promotion. YC4 promotes plant growth but the beneficial effects were lost in the Arabidopsis mutant rdd that is defective in active DNA demethylation. Roots of rdd failed to associate with YC4, meanwhile the level of myo-inositol in root exudates was drastically reduced in rdd. Supplementation of myo-inositol to rdd restored YC4 colonization and plant growth-promotion, while plants with defective myo-inositol monophosphatase also failed in establishing mutualism with YC4. myo-Inositol not only induced chemotaxis of YC4 but also increased YC4 biofilm production, consistent with the transcriptional regulation of YC4 by myo-inositol. In addition, myo-inositol preferentially attracts Bacillus megaterium among the examined bacteria species. Regardless of YC4 inoculation, myo-inositol biosynthesis and catabolism genes are down- and up-regulated, respectively, in rdd compared to wild type plants. The differential expression of myo-inositol homeostasis genes is correlated with local DNA hypermethylation, whereas genetic disruption of the RNA-directed DNA methylation pathway abolished these epigenetic marks and reset the corresponding gene expression patterns, resulting in restored YC4 colonization and plant growth-promotion. Importantly, that active DNA demethylation controls myo-inositol-mediated mutualism between YC4 and plants was also demonstrated in Solanum lycopersicum. Our results uncover an important function of myo-inositol in plant-microbe interactions and its dependence on plant epigenetic regulation.
2022-12-19 | GSE143427 | GEO
Project description:We comprehensively characterized the gene expression alterations occurring during squamous lung cancer development. Fresh frozen human bronchial biopsies (N=122) at successive morphological stages of lung squamous carcinogenesis were obtained by fluorescence bronchoscopy and analyzed using gene expression microarrays. A total of 122 biopsies from 77 individuals, 35 former and 42 current smokers, were included. The 122 biopsies were distributed according to histology and fluorescence status as follows: 13 biopsies with normal histology and normofluorescent (8/5 biopsies from former/current smokers), 14 with normal histology and hypofluorescent (8/6), 15 hyperplasia (7/8), 15 metaplasia (5/10), 13 mild dysplasia (8/5), 13 moderate dysplasia (7/6), 12 severe dysplasia (2/10), 13 carcinoma in situ (5/8) and 14 squamous cell carcinoma (SCC, 5/9). In addition, normal bronchial biopsies from 16 never-smokers were collected and pooled for use as reference RNA.
2014-10-31 | E-GEOD-33479 | biostudies-arrayexpress
Project description:Iloprost, a prostacyclin analog, has lung cancer preventive activity in preclinical models and improved dysplasia in former smokers in a phase IIb trial. Oral iloprost is currently unavailable.We performed a phase Ib trial of inhaled iloprost in former smokers to assess tolerance and compliance. Participants self-administered nebulized iloprost (5ug) or placebo four (QID) or two (BID) times daily. As QID dose was well tolerated and due to expiration of the placebo, the BID dosing and placebo were eliminated early on in the trial. Bronchoscopy with biopsy at six standard sites was performed at treatment initiation and two months post-iloprost, with exploratory histological analysis. Bulk RNA sequencing, single cell RNA sequencing and an in vitro assay of epithelial progenitor cell iloprost response were performed on a subset of biopsies in an exploratory investigation of response mechanisms and predictive biomarkers. Thirty-four of a planned 48 participants were recruited to the trial. Inhaled iloprost was well tolerated with no adverse events > grade 2. Compliance was 67% in the QID group. The trial was not powered to detect histologic response and none was found. Bulk RNA sequencing of biopsies pre/post iloprost suggest that iloprost is immunomodulatory and downregulates cell proliferation pathways.Single cell RNA sequencing showed an increase in CD8-positive T cells with upregulation of genes in interferon γ signaling. In vitro iloprost response by epithelial progenitor cells correlated with histologic response with kappa coefficient of 0.81 (95% CI 0.47, 1.0). Inhaled iloprost was well tolerated with suboptimal compliance. Molecular analysis suggested that iloprost has immunomodulatory and antiproliferative effects. The progenitor cell iloprost response assay may be a promising avenue to develop predictive biomarkers.
2023-09-21 | GSE240001 | GEO
Project description:Iloprost, a prostacyclin analog, has lung cancer preventive activity in preclinical models and improved dysplasia in former smokers in a phase IIb trial. Oral iloprost is currently unavailable.We performed a phase Ib trial of inhaled iloprost in former smokers to assess tolerance and compliance. Participants self-administered nebulized iloprost (5ug) or placebo four (QID) or two (BID) times daily. As QID dose was well tolerated and due to expiration of the placebo, the BID dosing and placebo were eliminated early on in the trial. Bronchoscopy with biopsy at six standard sites was performed at treatment initiation and two months post-iloprost, with exploratory histological analysis. Bulk RNA sequencing, single cell RNA sequencing and an in vitro assay of epithelial progenitor cell iloprost response were performed on a subset of biopsies in an exploratory investigation of response mechanisms and predictive biomarkers. Thirty-four of a planned 48 participants were recruited to the trial. Inhaled iloprost was well tolerated with no adverse events > grade 2. Compliance was 67% in the QID group. The trial was not powered to detect histologic response and none was found. Bulk RNA sequencing of biopsies pre/post iloprost suggest that iloprost is immunomodulatory and downregulates cell proliferation pathways.Single cell RNA sequencing showed an increase in CD8-positive T cells with upregulation of genes in interferon γ signaling. In vitro iloprost response by epithelial progenitor cells correlated with histologic response with kappa coefficient of 0.81 (95% CI 0.47, 1.0). Inhaled iloprost was well tolerated with suboptimal compliance. Molecular analysis suggested that iloprost has immunomodulatory and antiproliferative effects. The progenitor cell iloprost response assay may be a promising avenue to develop predictive biomarkers.
2023-09-21 | GSE240000 | GEO
Project description:Individuals who present with premalignant endobronchial lesions are considered at high risk of lung cancer. Nonetheless, premalignant lesions behave erratically and only a minority progresses towards lung cancer. Therefore, biomarkers need to be discovered that can aid in assessing an individual’s risk for subsequent cancer to better tailor treatment choices and avoid unnecessary follow-up procedures. We recently proposed a classifier of DNA copy number alterations (CNAs) at 3p26.3-p11.1, 3q26.2-29, and 6p25.3-24.3 as risk predictor for endobronchial cancer. The current study was set out to validate the classifier among an independent series of premalignant endobronchial lesions with various histological grades. A series of 36 endobronchial premalignant lesions (8 squamous metaplasia, and 28 various grades of dysplasia) identified during autofluorescence bronchoscopy of 12 case subjects who had carcinoma in situ or carcinoma (≥CIS) during follow-up bronchoscopy at the initial site and 24 control subjects who remained cancer-free, was subjected to array Comparative Genomic Hybridization (arrayCGH). DNA copy number profiles were related to lesion outcome. Prediction accuracy of the previously defined molecular classifier to predict endobronchial cancer in this series was determined. Unsupervised hierarchical clustering analysis revealed a significant association between cluster assignment and lesion outcome (p< 0.001), independent of histological grade, with quiescent profiles in controls (24/24) and aberrant profiles in the majority of cases (9/12). Our pre-defined classifier demonstrated 92% accuracy for predicting cancer outcome in the current sample series. Our validated classifier holds great promise for stratification of patients with premalignant endobronchial lesions for risk of subsequent cancer. Fresh frozen specimens of 36 premalignant endobronchial biopsies. Test samples were compared to an external pool of normal male/female reference DNA.
2013-12-03 | E-GEOD-45287 | biostudies-arrayexpress