0000000001309875
AUTHOR
Edoardo Alesse
Mesenchymal stem cells of Systemic Sclerosis patients, derived from different sources, show a profibrotic microRNA profiling
AbstractSystemic Sclerosis (SSc) is a disease with limited therapeutic possibilities. Mesenchymal stem cells (MSCs)-therapy could be a promising therapeutic option, however the ideal MSCs source has not yet been found. To address this problem, we perform comparison between bone marrow (BM)-MSCs and adipose (A)-MSCs, by the miRs expression profile, to identify the gene modulation in these two MSCs source. MicroRNAs (miRs) are RNAs sequences, regulating gene expression and MSCs, derived from different tissues, may differently respond to the SSc microenvironment. The miRs array was used for the miRs profiling and by DIANA-mirPath tool we identified the biological functions of the dysregulated …
The prevalent KRAS exon 2 c.35 G > A mutation in metastatic colorectal cancer patients: a biomarker of worse prognosis and potential benefit of bevacizumab-containing intensive regimens?
Bevacizumab-containing chemotherapy differently predict increased efficacy in KRAS exon 2 mutant and wild-type metastatic colorectal cancer (MCRC) patients. Mutant compared to wild-type status did not significantly affect progression-free survival (PFS) and overall survival (OS) in patients fit for first line bevacizumab-containing FIr-B/FOx regimen, and after progression. In patients unfit for intensive regimens, mutant status significantly affected PFS, while not OS. Codon 12 KRAS mutations differentially affect GTPase function, and confer worse clinical behaviour. Prognostic relevance of the prevalent c.35 G. >. A KRAS mutation was retrospectively evaluated. Fit c.35 G. >. A mutant patie…
Perivascular Cells in Diffuse Cutaneous Systemic Sclerosis Overexpress Activated ADAM12 and Are Involved in Myofibroblast Transdifferentiation and Development of Fibrosis.
Objective.Microvascular damage is pivotal in the pathogenesis of systemic sclerosis (SSc), preceding fibrosis, and whose trigger is not still fully understood. Perivascular progenitor cells, with profibrotic activity and function, are identified by the expression of the isoform 12 of ADAM (ADAM12) and this molecule may be upregulated by transforming growth factor-β (TGF-β). The goal of this work was to evaluate whether pericytes in the skin of patients with diffuse cutaneous SSc (dcSSc) expressed ADAM12, suggesting their potential contribution to the fibrotic process, and whether TGF-β might modulate this molecule.Methods.After ethical approval, mesenchymal stem cells (MSC) and fibroblasts …
Blocking Jak/STAT signalling using tofacitinib inhibits angiogenesis in experimental arthritis
Abstract Objective During rheumatoid arthritis (RA), the angiogenic processes, occurring with pannus-formation, may be a therapeutic target. JAK/STAT-pathway may play a role and the aim of this work was to investigate the inhibiting role of a JAK-inhibitor, tofacitinib, on the angiogenic mechanisms occurring during RA. Methods After ethical approval, JAK-1, JAK-3, STAT-1, STAT-3 and VEGF expression was evaluated on RA-synovial-tissues. In vitro, endothelial cells (ECs), stimulated with 20 ng/ml of VEGF and/or 1 μM of tofacitinib, were assessed for tube formation, migration and proliferation, by Matrigel, Boyden chamber assay and ki67 gene-expression. In vivo, 32 mice received collagen (coll…
Additional file 2 of Blocking Jak/STAT signalling using tofacitinib inhibits angiogenesis in experimental arthritis
Additional file 2: Supplementary material 2. Arthritis score evaluation. The histogram showed the median and the range of the arthritis score evaluated the day 35. The collagen induced a significant increase of arthritis score when compared to control group, and 30 mg/Kg/day of tofacitinib prevented the increase of arthritis score (**=p=0.001; ***= p
Additional file 1 of Blocking Jak/STAT signalling using tofacitinib inhibits angiogenesis in experimental arthritis
Additional file 1: Supplementary material 1. Mice treatments. The first day (day 0) of the procedure, 64 DBA/1 J mice were divided in 2 groups. One control group (n=32) receiving saline solution and one CIA group (n=32) receiving 100 μg of bovine type II collagen, emulsified with an equal volume of Freund’s complete adjuvant. After 18 days, the control group received saline solution and CIA mice received type II collagen and Freund’s incomplete adjuvant. At the day 19, controls and CIA mice were divided into 2 subgroups: one receiving vehicle (n=16) and one receiving 30 mg/kg/day of tofacitinib (n=16). After 35 days the first collagen administration, the mice were sacrificed and the blood c…