Project description:This SuperSeries is composed of the following subset Series:; GSE15455: GEMINI (Gastric Encyclopedia of Molecular Interactions and Nodes for Intervention) Phases A-C; GSE15456: Primary Gastric Cancer Expression Profiles (UK Patient Cohort); GSE15459: Gastric Cancer Project '08 (Singapore Patient Cohort); GSE15537: GEMINI (Gastric Encyclopedia of Molecular Interactions and Nodes for Intervention) Phases A-C, normal skin fibroblasts Experiment Overall Design: Refer to individual Series
Project description:Genome-wide mRNA expression profiles of normal skin fibroblasts, used as one of the (normal) references in the study. Gastric cancer (GC) is the second leading cause of global cancer mortality, with individual gastric tumors displaying significant heterogeneity in their deregulation of various oncogenic pathways. We aim to identify major oncogenic pathways in GC that robustly impact patient survival and treatment response. We used an in silico strategy based on gene expression signatures and connectivity analytics to map patterns of oncogenic pathway activation in 301 primary gastric cancers from three independent patient cohorts. Of 11 oncogenic pathways previously implicated in GC, we identified three predominant pathways (proliferation/stem cell, NF-kB, and Wnt/b-catenin) deregulated in the majority (>70%) of gastric tumors. Using a variety of proliferative, Wnt, and NF-kB-related assays, we experimentally validated the pathway predictions in multiple GC cell lines showing similar pathway activation patterns in vitro. Patients stratified at the level of individual pathways did not exhibit consistent differences in clinical outcome. However, patients grouped by oncogenic pathway combinations demonstrated robust and significant survival differences (e.g., high proliferation/high NF-kB vs. low proliferation/low NF-kB), suggesting that tumor behavior in GC is likely influenced by the combined effects of multiple oncogenic pathways. Our results demonstrate that GCs can be successfully taxonomized by oncogenic pathway activity into biologically and clinically relevant subgroups. Keywords: normal skin fibroblasts, cell culture Profiling A Normal Skin Fibroblast Cell Line on Affymetrix GeneChip Human Genome U133 Plus 2.0 Array
Project description:LncRNA and mRNA expression profiling for 7 human gastric cancr samples (3 tumor tissues and 3 tumor lymph node and 1 normal tissue) We have completed the metastasis-related Long Noncoding RNA expression profiling data microarray analysis of the 7 human gastric cancer related samples In the study presented here, a consecutively operated, well-defined cohort of three gastric cancer tissues and three metastatic lymph nodes tissues compared with the normal tissues and lymph nodes tissues, followed up more than five years, was used to acquire expression profiles of a total of 1942 lncRNA and 1976 mRNA, leading to the successful construction of supervised
Project description:Genome-wide mRNA expression profiles of normal skin fibroblasts, used as one of the (normal) references in the study. Gastric cancer (GC) is the second leading cause of global cancer mortality, with individual gastric tumors displaying significant heterogeneity in their deregulation of various oncogenic pathways. We aim to identify major oncogenic pathways in GC that robustly impact patient survival and treatment response. We used an in silico strategy based on gene expression signatures and connectivity analytics to map patterns of oncogenic pathway activation in 301 primary gastric cancers from three independent patient cohorts. Of 11 oncogenic pathways previously implicated in GC, we identified three predominant pathways (proliferation/stem cell, NF-kB, and Wnt/b-catenin) deregulated in the majority (>70%) of gastric tumors. Using a variety of proliferative, Wnt, and NF-kB-related assays, we experimentally validated the pathway predictions in multiple GC cell lines showing similar pathway activation patterns in vitro. Patients stratified at the level of individual pathways did not exhibit consistent differences in clinical outcome. However, patients grouped by oncogenic pathway combinations demonstrated robust and significant survival differences (e.g., high proliferation/high NF-kB vs. low proliferation/low NF-kB), suggesting that tumor behavior in GC is likely influenced by the combined effects of multiple oncogenic pathways. Our results demonstrate that GCs can be successfully taxonomized by oncogenic pathway activity into biologically and clinically relevant subgroups. Keywords: normal skin fibroblasts, cell culture
Project description:Primary human gastric normal fibroblast cultures (NL14 and NL32, repectivley) were establised from 2 gastrectomy specimens. Enforced expression (gain-of-function effect) of Twist1 in 2 gastric normal fibroblasts (NL14 and NL32) showed candidate target genes and CAF markers upregulated by Twist1. Experiment design: 2 normal gastric fibroblasts (NL14 and NL32) were establised and studied for Twist1 gain-of-function.
Project description:The study was designed to determine the differential gene expression between burn eschar- and normal skin-derived pericytes. A comparison was also made to determine the gene expression between normal skin pericytes and normal skin fibroblasts and (2) comparison of differential gene expression between burn eschar pericytes and normal normal skin fibroblasts
Project description:Impaired skin wound healing is a significant global health issue, especially among the elderly. Wound healing is a well-orchestrated process involving the sequential phases of inflammation, proliferation, and tissue remodeling. Although wound healing is a highly dynamic and energy-requiring process, the role of metabolism remains largely unexplored. By combining transcriptomics and metabolomics of human skin biopsy samples, we mapped the core bioenergetic and metabolic changes in normal acute as well as chronic wounds in elderly subjects. We found upregulation of glycolysis, the tricarboxylic acid cycle, glutaminolysis, and β-oxidation in the later stages of acute wound healing and in chronic wounds. To ascertain the role of these metabolic pathways on wound healing, we targeted each pathway in a wound healing assay as well as in a human skin explant model using metabolic inhibitors and stimulants. Enhancement or inhibition of glycolysis and, to a lesser extent, glutaminolysis had a far greater impact on wound healing than similar manipulations of oxidative phosphorylation and fatty acid β-oxidation. These findings increase the understanding of wound metabolism and identify glycolysis and glutaminolysis as potential targets for therapeutic intervention.
Project description:In the project “A Dual-Acting Nitric Oxide Donor and Phosphodiesterase 5 Inhibitor Activates Autophagy in Primary Skin Fibroblasts» by Esther Martínez-Martínez and Joern Dengjel, we performed expression proteomics analyzing the response of normal human fibroblasts (NHF) isolated from healthy skin to the drug TOP-N53.