Survival in Pancreatic Cancer
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Christof Winter
PROVIDER: E-MEXP-2780 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Microarray analysis of 63 patients with pancreatic cancer tissues resulted in the identification of a 15-gene signature to predict overall survival RNA was extracted from microdissected frozen pancreatic tissues for gene array analysis
2015-08-28 | E-GEOD-57495 | biostudies-arrayexpress
Project description:Background: Pachymic acid (PA) is a purified triterpene extracted from medicinal fungus Poria cocos. In this paper, we investigated the anticancer effects of PA on human chemotherapy resistant pancreatic cancer cells. Methods: Gemcitabine-resistant pancreatic cancer cells PANC-1 and MIA PaCa-2 were used, along with a xenograft model of MIA PaCa-2 cells implanted in mice. Apoptosis was assessed by quantitation of cytoplasmic histone-associated DNA fragments and expression of cleaved PARP. Differential expression of genes was identified using comparative DNA microarray analysis. Protein levels were determined by immunoblotting. Toxicology studies in vivo were assessed by detecting pathological changes in organs and liver enzyme profiles in plasma. Tumor tissues were analyzed by quantification of apoptotic bodies, qRT-PCR and immunoblotting. Principal Findings: PA induced endoplasmic reticulum (ER) stress in chemotherapy resistant pancreatic cancer cells through activation of heat shock response and unfolded protein response related genes, which further triggered apoptosis. The involvement of ER stress was confirmed by increasing expression of XBP-1s, ATF4, Hsp70, CHOP and phospho-eIF2M-NM-1. Moreover, 25 mg kgM-bM-^HM-^R1 of PA significantly suppressed MIA PaCa-2 tumor growth in vivo without toxicity, which correlated with induction of apoptosis, ER stress related genes and proteins expression. Conclusions: Growth inhibition and induction of apoptosis by PA in chemotherapy resistant pancreatic cancer cells were associated with ER stress activation both in vitro and in vivo. Pancreatic cancer cell line treated with pachymic acid vs. control (untreated)
2014-12-12 | E-GEOD-64111 | biostudies-arrayexpress
Project description:Pulmonary Hypertension (PH) is a frequent complication of Pulmonary Fibrosis (PF). PH can be seen in PF in the abscence of hypoxemia, irrespective of the degree of fibrosis. At the same time, a consistent number of patients with advanced PF never develop PH. The pathogenesis of PH secondary to PF remains unclear. PF patients are often referred to lung transplantation, but they present a higher incidence of pimary graft dysfunction than other diseases. The cause of this is unknown, and the relationship with PH remains unclear. We used microarray to identifiy the gene expression profiles in PF patients with and without PH Fresh frozen lung samples were obtained from the recipients organs of 116 PF patients undergoing lung transplantation. RNA was extracted and hybridized on Affymetrix microarrays. Pulmonary artery pressures were recorded intraoperatively with right heart catheters before starting lung transplantation. Patients were divided in different groups based on the mean pulmonary artery pressure. We compared the gene expression profiles in the group with severe PH (mPAP>40 mmHg, n=17) and in that without PH (mPAP<20 mmHg, n=22)) and obtained a gene signature, which was used for clusterying analysis. The clustering analysis based on the gene signature was then validated in an Intermediate PH group (mPAP 21-39 mmHg, n=45) and in a Validation Set (n=32).
2011-06-01 | E-GEOD-24988 | biostudies-arrayexpress
Project description:Study objectives: The objectives of this study was perform the global gene expression profiling aimed at identifying differentially expressed genes in the circulating lympho-monocytes of NRLCP patients affected by Narcolepsy with Cataplexy (NRLCP). Based on the tight association to the HLA-DQB1*0602 haplotype in caucasians, it could be hypotesized an immunological dysregulation underlying the pathogenesis of the disease. Design: 10 NRLCP patients with 10 healthy controls were compared. Total RNA isolated from blood specimens was analyzed using microarray technology followed by statistical data analysis to detect genome-wide differential gene expression between patients and controls. Functional analysis of the genelist was performed in order to interpret the biological significance of the data. Results: 173 genes showed significant (p<0.01) differential expression between the two tested conditions. The biological interpretation allowed to categorize differentially expressed genes into main functional groups including includes genes involved in brain development, which could be possibly regarded as peripheral markers of the disease, along with molecular markers of the NRLCP-related dysmetabolic syndrome and immuregulatory molecules. Moreover a striking correlation within selected HLA haplotypes and HLA gene expression was detected, indicating an allele-specific trend of gene expression for the DQB1, DQA1 and DRB4 genes across all the tested subject, regardless of the disease status. Conclusions: the molecular profile associated to NRLCP suggested that molecular markers of neural, metabolic and immunological dysregulation can be detected in blood of NRLCP patients. Moreover, the allele-specific HLA gene expression could suggest a possible direct role of MHCII as a co-factor in the disease etio-pathogenesis A case-control study was performed comparing 10 narcoleptic patients (both sexes, mean age 50, median age 50) with 10 age- and sex-matched healthy controls
2010-12-31 | E-GEOD-21592 | biostudies-arrayexpress
Project description:Most cancer deaths are caused by metastases, which are the end-results of circulating tumor cells (CTC) that detach from the cancer primary and succeed to survive in distant organs. The aim of the present study was to develop a gene signature of CTC and to assess its prognostic relevance after surgery for pancreatic ductaladenocarcinoma (PDAC). A negative depletion fluorescence activated cell sorting (FACS) procedure was developed and validated with spiking experiments using cancer cell lines in whole human blood samples. This FACS-based method was used to enrich for CTC from the blood of 10 patients who underwent surgery for PDAC. Total RNA was isolated from 4 subgroup samples, i.e. CTC, haematological cells (G), original tumor (T), and non-tumoral pancreatic control tissue (P). After RNA quality control, samples of 6 patients were eligible for further analysis. Whole genome microarray analysis was performed after double linear amplification of RNA. The ‘Ingenuity Pathway Analysis’ software and AmiGO were used for functional data analyses. A CTC gene signature was developed and validated with the nCounter system on expression data of 78 primary PDAC using Cox regression analysis for disease-free (DFS) and overall survival (OS). Using stringent statistical analysis, we finally retained 8,152 genes to compare expression profiles of CTC vs. other subgroups, and found 1,059 genes to be differentially expressed. The pathway with the highest expression ratio in CTC was p38 mitogen-activated protein kinase (p38 MAPK) signaling, known to be involved in cancer cell migration. In the p38 MAPK pathway TGF-β1, cPLA2, and MAX were significantly upregulated. In addition, 9 other genes associated with both p38 MAPK signaling and cell motility were over-expressed in CTC. High co-expression of TGF-1 and our cell motility panel (≥ 4 out of 9 genes for DFS and ≥ 4 out of 9 genes for OS) in primary PDAC was identified as an independent predictor of DFS (p=0.041, HR (95% CI) = 1.885 (1.025 – 3.559)) and OS (p=0.047, HR (95% CI) = 1.366 (1.004 – 1.861)). Pancreatic CTC isolated from blood samples using a FACS-based negative depletion method,express a cell motility gene signature. The expression of this newly defined cell motility gene signature in the primary tumor is able to predict survival of patients who undergo surgical resection for pancreatic cancer. Total RNA was isolated from circulation tumor samples (CTC), haematological cells (G), original tumor (T), and non-tumor pancreatic control tissue (P) of patients with pancreatic ductal adenocarcinoma (PDAC). Gene expression profiles of CTC were compared to G, T, and P. The aim of the current study was to develop a ‘negative depletion strategy’ to isolate CTC without the exclusion of any particular subset of CTC, and to study their gene-expression profiles in order to find novel therapeutic targets and prognostic markers in patients with pancreatic cancer.
2012-12-18 | E-GEOD-18670 | biostudies-arrayexpress
Project description:We and others have shown that AGR2 is frequently upregulated during the development of pancreatic cancer. We used microarray to look at the target genes regulated by AGR2 in pancreatic cancer cell lines FA6 and MiaPaCa2. Keywords: gene knock-down, overexpression We transiently down-regulated AGR2 expression in FA6 pancreatic cancer cells using INTERFERin transfection reagent and either AGR2 siRNA or non-targeting control siRNA for 48 hours. RNA was extracted and hybridized on Affymetrix microarrays. We looked for new target genes regulated by AGR2. We generated stable cell lines by introducing control vector pCEP4 or AGR2 overexpressing vector pCEP4-AGR2 into the pancreatic cancer cell line MiaPaCa2, single cell clones were then isolated. RNA was extracted and hybridized on Affymetrix microarrays.We looked for new target genes regulated by AGR2.
2013-07-28 | E-GEOD-12513 | biostudies-arrayexpress
Project description:Pancreatic islets are central in type 2-diabetes development, which coincides with increased activity of innate immunity. Intriguingly, human pancreatic islets express many complement genes. The most highly expressed gene was the complement inhibitor CD59 that is GPI anchored to the cell membrane, which unexpectedly was found in high amounts intracellularly in beta cells. Silencing of CD59 strongly suppressed insulin secretion. Importantly, this suppression was unrelated to established CD59 functions, but rather depletion of intracellular CD59. Imaging experiments identified a distal site of inhibition in the exocytotic pathway, but prior to emptying of the insulin granules. Proximity Ligation Assays pin-pointed the mechanism to impaired turnover of exocytosis-regulating SNARE-proteins and CD59 was detected in complex with VAMP2 and syntaxin. CD59 was downregulated by 24-h glucose incubations in human islets, rat cell lines and in islets from three rodent diabetes models. Islets from cadaver donors were provided by the Nordic Islet Transplantation Programme (www.nordicislets.org), Uppsala University. The microarrays were performed using GeneChipM-BM-. Human Gene 1.0 ST whole transcript according to Affymetrix standard protocol.
2014-03-02 | E-GEOD-54279 | biostudies-arrayexpress
Project description:This project describes the establishment and validation of a murine orthotopic xenograft model using fresh human tumor samples that recapitulates the critical components of human pancreatic adenocarcinoma. The authors discuss the proven and theoretical advantages of the model as well as future translational implications. Background: Relevant preclinical models that recapitulate the key features of human pancreatic ductal adenocarcinoma (PDAC) are needed in order to provide biologically tractable models to probe disease progression and therapeutic responses and ultimately improve patient outcomes for this disease. Here, we describe the establishment and clinical, pathological, molecular and genetic validation of a murine, orthotopic xenograft model of PDAC. Methods: Human PDACs were resected and orthotopically implanted and propagated in immunocompromised mice. Patient survival was correlated with xenograft growth and metastatic rate in mice. Human and mouse tumor pathology were compared. Tumors were analyzed for genetic mutations, gene expression, receptor tyrosine kinase (RTK) activation, and cytokine expression. Results: Fifteen human PDACs were propagated orthotopically in mice. Xenografts developed peritoneal and liver metastases. Time to growth and metastatic efficiency in mice each correlated with patient survival. Tumor architecture, nuclear grade and stromal content were similar in patient and xenografted tumors. Propagated tumors closely exhibited the genetic and molecular features known to characterize pancreatic cancer (e.g. high rate of KRAS, p53, SMAD4 mutation and EGFR activation). The correlation coefficient of gene expression between patient tumors and xenografts propagated through multiple generations was 93 to 99%. Analysis of gene expression demonstrated distinct differences between xenografts from fresh patient tumors versus commercially available PDAC cell lines. Conclusions: Our orthotopic xenograft model derived from fresh human PDACs closely recapitulates the clinical, pathologic, genetic and molecular aspects of human disease. This model has resulted in the identification of rational therapeutic strategies to be tested in clinical trials and will permit additional therapeutic approaches and identification of biomarkers of response to therapy. 47 Samples in total were generated for normal pancreatic tissue in patients, pancreatic tumors in patients, pancreatic tumors propagated in a mouse xenograft model, and pancreatic cancer cell lines in vitro. Clustering analysis was performed to evaluate the differences between patient tumors, xenograft tumors, established cancer cell lines, and cell lines derived from xenografts.
2013-10-01 | E-GEOD-46385 | biostudies-arrayexpress
Project description:Muscle biopsies were taken from 6 patients with dermatomyositis, 4 with polymyositis and 5 not myopathic subjects as controls. The genome-wide expression patterns were compared using Affymetrix HG-U133A chips. Experiment Overall Design: Gene expression profiles were generated for 15 individuals.
2011-04-23 | E-MEXP-2681 | biostudies-arrayexpress
Project description:Pancreatic cancer is a devastating disease with both local invasion and distant metastasis. Identifying the genes expressed in liver metastases and signatures of metastatic progression would therefore be of particular importance as they could aid in both recurrence prediction as well as representing novel therapeutic targets. Keywords: Gene expression profiling We have performed microarray gene expression analysis of normal pancreas, primary pancreatic ductal adenocarcinoma (PDAC), normal liver and pancreatic liver metastases to identify potential therapeutic targets.
2013-08-15 | E-GEOD-19280 | biostudies-arrayexpress