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Investigation of gene expression alterations of pancreatic cancer caused by Deferasirox administration

ABSTRACT: To investigate the genetic effect of Deferasirox in pancreatic cancer, we examined gene expression alternations in the removed tumors exposed to Deferasirox.

ORGANISM(S): Homo sapiens

PROVIDER: GSE81363 | GEO | 2016/05/13

SECONDARY ACCESSION(S): PRJNA321527

REPOSITORIES: GEO

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Investigation of gene expression alterations of pancreatic cancer caused by Deferasirox administration

Project description:To investigate the genetic effect of Deferasirox in pancreatic cancer, we examined gene expression alternations in the removed tumors exposed to Deferasirox. Pancreatic cancer cells (BxPC-3) in culture were harvested and viable cells were injected subcutaneously into the backs of the mice. When tumor volumes reached 150 mm3, treatment began. The treatment group of mice received Deferasirox suspended in saline, which was administered by oral gavage every second day, with three treatments per week, over 21 days at concentrations of 200 mg/kg. The control mice were treated with the vehicle alone. At the end of the experiment, the mice were sacrificed and the tumors were excised and processed for genetic analyses. A total of 6 tumors were analyzed. Of these, 3 tumors were removed from vehicle-treated mice, and the other 3 tumors were removed from Deferasirox 200 mg/kg-treated mice.

2016-05-13 | E-GEOD-81363 | biostudies-arrayexpress

Deferasirox in Treating Iron Overload Caused By Blood Transfusions in Patients With Hematologic Malignancies

Project description:RATIONALE: Deferasirox may remove excess iron from the body caused by blood transfusions. PURPOSE: This clinical trial studies deferasirox in treating iron overload caused by blood transfusions in patients with hematologic malignancies.

| 2100588 | ecrin-mdr-crc

Genome-wide transcriptomics leads to the identification of deregulated genes after deferasirox therapy in low-risk MDS patients

Project description:The iron chelator deferasirox is widely used in patients with iron overload. Patients with low-grade myelodysplastic syndromes (MDS) get transfusion dependency and need to be treated with deferasirox to avoid iron overload. Moreover, in some patients an increase in both erythroid and platelets have been observed after deferasirox therapy. However, the mechanisms involved in these clinical findings are poorly understood. The aim of this work was to analyze, in patients treated with deferasirox, the changes in the gene expression profile after receiving the treatment. A total of fifteen patients with the diagnosis of low-grade MDS were studied. Microarrays were carried out in RNA from peripheral blood before and after 14 weeks of deferasirox therapy. Changes in 1,457 genes and 54 miRNAs were observed: deferasirox induced the downregulation of genes related to the Nf kB pathway leading of an overall inactivation of this pathway. In addition, the iron chelator also downregulated gamma interferon. Altogether these changes could be related to the improvement of erythroid response observed in these patients after therapy. Moreover, the inhibition of NFE2L2/ NRF2, which was predicted in silico, could be playing a critical role in the reduction of reactive oxygen species (ROS). Of note, miR-125b, overexpressed after deferasirox treatment, could be involved in the reduced inflammation and increased hematopoiesis observed in the patients after treatment. In summary this study shows, for the first time, the mechanisms that could be governing deferasirox impact in vivo.

2019-12-13 | GSE141958 | GEO

Effect of deferasirox and deferoxamine treatment on hematopoietic stem cells gene expression

Project description:To investigate new molecular pathways affected by deferasirox or deferoxamine able to explain hematopoiesis restoration

2019-09-02 | E-MTAB-6658 | biostudies-arrayexpress

Gene expression profiling in myelodysplastic syndrome patients treated with deferasirox

Project description:Deferasirox (DFX) is an oral iron chelator used to reduce iron overload caused by frequent red blood cell transfusions in anemic myelodysplastic syndrome (MDS) patients. To study molecular mechanisms by which DFX improves outcome in MDS, we analyzed gene expression patterns in MDS patients before and after DFX therapy.

2020-11-04 | GSE160727 | GEO

Iron Chelator Deferasirox Reduces Candida albicans Invasion of Oral Epithelial Cells and Infection Levels in Murine Oropharyngeal Candidiasis

Project description:Candida albicans, the causative agent of mucosal infections including oropharyngeal candidiasis (OPC) as well as bloodstream infections is becoming increasingly resistant to existing treatment options. In the absence of novel drug candidates, drug repurposing aimed at using existing drugs to treat off label diseases is a promising strategy. C. albicans requires environmental iron for survival and virulence while host nutritional immunity deploys iron-binding proteins to sequester iron and reduce fungal growth. Here we evaluated the role of iron-limitation using Deferasirox (an FDA approved iron chelator for treatment of patients with iron overload) during murine OPC; and assessed Deferasirox-treated C. albicans for its interaction with human oral epithelial (OE), neutrophils, and antimicrobial peptides. Therapeutic Deferasirox treatment significantly reduced salivary iron levels while a non-significant reduction in fungal burden was observed. Preventive treatment that allowed for two additional days of drug administration in our murine model, resulted in significant reduction of C. albicans colony forming units (CFU)/g of tongue tissue, a significant reduction in salivary iron levels, and significantly reduced neutrophil-mediated inflammation. C. albicans harvested from tongues of animals undergoing preventive treatment had differential expression of 106 genes, including those involved in iron metabolism, adhesion, and response to host innate immunity. Moreover, Deferasirox-treated C. albicans cells had two-fold reduction in survival in neutrophil phagosomes (with greater susceptibility to oxidative stress); and reduced adhesion and invasion of OE cells, in vitro. Thus Deferasirox treatment has the potential to alleviate OPC by affecting C. albicans gene expression and reducing virulence

2018-12-04 | GSE123277 | GEO

Gene expression alterations of pancreatic intraepithlial neoplasia

Project description:Gene expression data from the RNA sequencing of laser microdissected pancreatic intraepithelial neoplasia and pancreatic normal ducts.

2018-03-17 | GSE96784 | GEO

Gene expression profiling in myelodysplastic syndrome patients treated with deferasirox

Project description:Gene expression profiling in myelodysplastic syndrome patients treated with deferasirox

| PRJNA674306 | ENA

Pancreatic Tumor vs Various Tissue Normals

2008-09-15 | GSE11838 | GEO

Pancreatic Tumor vs Various Tissue Normals

Project description:Pancreatic Tumor samples from biopsy collected at different stages along with normal tissue samples from various organ sites including commercial normals arrayed on 2channel Agilent 60mer Oligo arrays (human v1 & v2), median normalized for cross comparison. Some normal samples temporarily removed to public due to Intelectual property conflict. Keywords: Pancreatic tumor comparison to normals for multimetric study Single channel array expression from two Agilent versions (V1:18k,V2: 22k) (i.e: GPL885,GPL887) combined based on matching probes, remove repeating control substituted with median values, final probe down to ~17k.

2008-09-15 | E-GEOD-11838 | biostudies-arrayexpress

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