ABSTRACT: HO-1 modulates the expression of genes involved in inflammation, angiogenesis, proliferation, apoptosis and cell adhesion in human lung cancer cells.
Project description:HO-1 modulates the expression of genes involved in inflammation, angiogenesis, proliferation, apoptosis and cell adhesion in human lung cancer cells.
Project description:The enzymatic activity of HO-1 results in decreased oxidative stress, attenuated inflammatory response, and very often in a lower rate of apoptosis. This is due to removal of heme, a potent prooxidant and proinflammatory agent, but mainly because of generation of biologically active products such as CO and bilirubin. In order to find the correlation between the HO-1 level and the expression of different genes of interest we have utilized human lung cancer cell line NCI-H292 stably overexpressing HO-1. Additionally we have checked if HO-1 can modulate genes expression in NCI-H292 cells treated with TNF. The effect of HO-1 overexpression on transcriptome was assessed by microarray analysis. We have observed that the increase in HO-1 level may affect the expression of different genes involved in cytokine synthesis, angiogenesis, apoptosis, proliferation and cell adhesion. Additionally, HO-1 may interact with the TNF treatment and influence the expression of some genes like IL-1, IL-6, IL-8, FAS and NF-kB.
Project description:The enzymatic activity of HO-1 results in decreased oxidative stress, attenuated inflammatory response, and very often in a lower rate of apoptosis. This is due to removal of heme, a potent prooxidant and proinflammatory agent, but mainly because of generation of biologically active products such as CO and bilirubin. In order to find the correlation between the HO-1 level and the expression of different genes of interest we have utilized human lung cancer cell line NCI-H292 stably overexpressing HO-1. Additionally we have checked if HO-1 can modulate genes expression in NCI-H292 cells treated with TNF. The effect of HO-1 overexpression on transcriptome was assessed by microarray analysis. We have observed that the increase in HO-1 level may affect the expression of different genes involved in cytokine synthesis, angiogenesis, apoptosis, proliferation and cell adhesion. Additionally, HO-1 may interact with the TNF treatment and influence the expression of some genes like IL-1, IL-6, IL-8, FAS and NF-kB. NCI-H292 cells, control (pcDNA) and stably overexpressig HO-1 (pcHO1) were treated for 24 h with TNF (30 ng/ul), then the cells were lysed and RNA was collected. The whole human gene expression profile was assessed with Agilent microarray analysis. Three independent experiments were performed at each time using different batch of cells.
Project description:Primary objectives: To ascertain whether orally delivered Simvastatin affects levels of apoptosis, proliferation and bone morphogenetic protein pathway activation in colorectal cancer in humans.
Primary endpoints: Levels of BMP2 and 4 and phospho-Smad1 in surgical resection specimens.levels of apoptosis and proliferation in surgical resection specimenslevels of angiogenesis in surgical resection specimens
Project description:The stromal microenvironment plays a vital role in cancer initiation and progression. We performed a comparative expression profiling of pulmonary MSC derived from NSCLC and corresponding normal lung tissue of 5 newly diagnosed patients. The analysis indicated variable expression of genes involved in DNA repair, apoptosis, proliferation or angiogenesis between NSCLC-MSC and NLT-MSC. MSC were derived from NSCLC and corresponding normal lung tissue of 5 patients. Paired SAM test was performed to screen for differentially expressed genes between NSCLC-MSC and NLT-MSC.
Project description:The stromal microenvironment plays a vital role in cancer initiation and progression. We performed a comparative expression profiling of pulmonary MSC derived from NSCLC and corresponding normal lung tissue of 5 newly diagnosed patients. The analysis indicated variable expression of genes involved in DNA repair, apoptosis, proliferation or angiogenesis between NSCLC-MSC and NLT-MSC.
Project description:Airway inflammation and remodelling are key pathophysiologic features process in many respiratory conditions such as asthma. An intact epithelial cell layer is crucial to maintain lung homeostasis, and this depends on intercellular adhesion. The Coxsackievirus Adenovirus Receptor (CAR) is highly expressed in the epithelium where it modulates cell-cell adhesion stability and acts as a receptor for immune cells to facilitate transepithelial migration. Here we investigated the mechanistic role of CAR in mediating responses to the common aeroallergen House Dust Mite (HDM). We demonstrate that administration of HDM in mice lacking CAR in the respiratory epithelium leads to loss of peri-bronchial inflammatory cell infiltration, fewer goblet-cells, decreased IL-4 and IL-13 levels and reduced matrix remodelling. In vitro analysis in human lung epithelial cells confirmed that loss of CAR led to reduced HDM-dependent inflammatory cytokine release leading to reduced inflammatory cell transmigration. Moreover, CAR was required for HDM-induced TGF release leading to enhanced airway smooth muscle cell proliferation and matrix production. Our data demonstrates that CAR is a novel central co-ordinator of lung inflammation through a dual role in leukocyte recruitment and tissue remodelling and may represent an important target for future therapeutic development in lung inflammatory diseases.
