Therapeutic targeting of BRAFV600E has shown a significant impact on progression-free and overall survival in advanced melanoma, but only a fraction of patients benefit from these treatments, suggesting that additional signaling pathways involved in melanoma growth/survival need to be identified. In fact MAPK and PI3K/mTOR signaling pathways are constituively activated in most cancers, including melanoma, to sustain the melanoma growth/survival. A large panel of melanoma were characterized for resistance/susceptibility to different inhibitors targeting MAPK and PI3K/mTOR signaling pathways and the synergistic effect of combinatorial treatments affecting both pathways. These effects were evaluated in terms of cell viability (MTT), apoptosis (Annexin V-PI), caspase 3/7 activity and subG1 cell fraction, highlighting a hierarchy in the combination effects. Further, a smaller panel of melanoma cell lines, were treated with inhibitors singularly and in combination to test the effects on the expression of principal proteins involved in these two pathways. Gene expression profile was performed to analyse the gene modulation induced by inhibitors to identify new strategies to fight melanoma resistance.
Primary cross-resistance to BRAFV600E-, MEK1/2- and PI3K/mTOR-specific inhibitors in BRAF-mutant melanoma cells counteracted by dual pathway blockade.
Specimen part, Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrated approaches to miRNAs target definition: time-series analysis in an osteosarcoma differentiative model.
Specimen part, Cell line, Time
View SamplesWe explored the transcriptional modification induced by CD99 transfection in the osteosarcoma cell lines SaOS-2 after 0, 7 and 14 days in differentiation medium.
Integrated approaches to miRNAs target definition: time-series analysis in an osteosarcoma differentiative model.
Specimen part, Cell line, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
High Expression of Complement Component 5 (C5) at Tumor Site Associates with Superior Survival in Ewing's Sarcoma Family of Tumour Patients.
Sex, Age, Specimen part, Disease, Cell line
View SamplesPurpose: Unlike in most adult-onset cancers, an association between typical paediatric neoplasms and inflammatory triggers is rare. We studied whether immune system related genes are activated and have prognostic significance in Ewing sarcoma family of tumours (ESFT). Experimental design: Data-analysis was performed on gene expression profiles of 44 ESFT patient, 11 ESFT cell line, and 18 normal muscle tissue samples. 238 inflammation related genes were selected based on literature and a macrophage gene expression signature was derived from SymAtlas. Differential expression of the genes was analysed by t-test and survival analysis was performed according to gene expression.
High Expression of Complement Component 5 (C5) at Tumor Site Associates with Superior Survival in Ewing's Sarcoma Family of Tumour Patients.
Sex, Age, Specimen part, Disease
View SamplesPurpose: Unlike in most adult-onset cancers, an association between typical paediatric neoplasms and inflammatory triggers is rare. We studied whether immune system related genes are activated and have prognostic significance in Ewing sarcoma family of tumours (ESFT). Experimental design: Data-analysis was performed on gene expression profiles of 44 ESFT patient, 11 ESFT cell line, and 18 normal muscle tissue samples. 238 inflammation related genes were selected based on literature and a macrophage gene expression signature was derived from SymAtlas. Differential expression of the genes was analysed by t-test and survival analysis was performed according to gene expression.
High Expression of Complement Component 5 (C5) at Tumor Site Associates with Superior Survival in Ewing's Sarcoma Family of Tumour Patients.
Sex, Age, Specimen part, Disease, Cell line
View SamplesThis study compares cardiac induction time-courses using (i) wild-type hESCs subjected to a standard directed differentiation protocol, (ii) EOMES knockout hESCs subjected to the same protocol, and (iii) EOMES KO / TET-ON hESCs subjected to a TET-ON protocol.
Cardiogenic programming of human pluripotent stem cells by dose-controlled activation of EOMES.
Cell line, Time
View SamplesAffymetrix gene expression data of 21 high-grade osteosarcomas located in the extremities.This gene expression profiling was performed in order to evaluate the expression of candidate prognostic and therapeutic targets in high-grade osteosarcoma.
Targeting CDKs with Roscovitine Increases Sensitivity to DNA Damaging Drugs of Human Osteosarcoma Cells.
Age, Specimen part
View SamplesIntravenous Immunoglobulin (IVIg) is widely used as an immunomodulatory therapy. We have recently demonstrated that IVIg protects against airway hyper-reactivity (AHR) and inflammation in mouse models of allergic airway disease (AAD), associated with induction of Foxp3+ regulatory T cells (Treg). Using DEREG (DEpletion of REGulatory T cell) mice, in which endogenous Treg can be ablated with Diphtheria toxin (DTx) treatment, we demonstrate that IVIg generates a de novo population of induced Treg (iTreg) in the absence of endogenous Treg. IVIg-generated iTreg were sufficient for inhibition of ovalbumin-induced AHR in an antigen-driven murine model of AAD. In the absence of endogenous Treg, IVIg failed to confer protection against AHR and airway inflammation. Adoptive transfer of purified IVIg-generated iTreg prior to antigen challenge effectively prevented airway inflammation and AHR in an antigen-specific manner.
Peripherally Generated Foxp3<sup>+</sup> Regulatory T Cells Mediate the Immunomodulatory Effects of IVIg in Allergic Airways Disease.
Specimen part
View SamplesDevelopment of systems allowing the maintenance of native properties of mesenchymal stromal cells (MSC) is a critical challenge for studying physiological functions of skeletal progenitors, as well as towards cellular therapy and regenerative medicine applications. Conventional stem cell culture in monolayer on plastic dishes (2D) is associated with progressive loss of functionality, likely due to the absence of a biomimetic microenvironment and the selection of adherent populations. Here we demonstrate that 2D MSC expansion can be entirely bypassed by culturing freshly isolated bone marrow cells within the pores of 3D scaffolds in a perfusion-based bioreactor system, followed by enzymatic digestion for cell retrieval. The 3D-perfusion system supported MSC growth while maintaining cells of the hematopoietic lineage, and thus generated a cellular environment mimicking some features of the bone marrow stroma. As compared to 2D-expansion, sorted CD45- cells derived from 3D-perfusion culture after the same time (3 weeks) or a similar extent of proliferation (7-8 doublings) maintained a 4.3-fold higher clonogenicity and exhibited a superior differentiation capacity towards all typical mesenchymal lineages, with similar immunomodulatory function in vitro. Transcriptomic analysis performed on MSC from 5 donors validated the robustness of the process and indicated a reduced inter-donor variability as well as a significant upregulation of multipotency-related gene clusters following 3D-perfusion as compared to 2D expansion. The described system offers a model to study how factors of a 3D engineered niche may regulate MSC function and, by streamlining conventional labor-intensive processes, is prone to automation and scalability within closed bioreactor systems.
Expansion of human mesenchymal stromal cells from fresh bone marrow in a 3D scaffold-based system under direct perfusion.
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