Objective. Systemic sclerosis (SSc) is a severe connective tissue disease of unknown etiology, characterized by fibrosis of the skin and multiple internal organs. Recent findings suggested that the disease is driven by stimulatory autoantibodies to platelet-derived growth factor receptor (PDGFR), which stimulate the production of reactive oxygen species (ROS) and collagen by fibroblasts. These results opened novel avenues of research into the diagnosis and treatment of SSc. The present study was undertaken to confirm the presence of anti-PDGFR antibodies in patients with SSc.Methods. Immunoglobulins from 37 patients with SSc were purified by protein A/G chromatography. PDGFR activation was tested using 4 different sensitive bioassays, i.e., cell proliferation, ROS production, signal transduction, and receptor phosphorylation; the latter was also tested in a separate population of 7 patients with SSc from a different research center.Results. Purified IgG samples from patients with SSc were positive when tested for antinuclear autoantibodies, but did not specifically activate PDGFR␣ or PDGFR␤ in any of the tests. Cell stimulation with PDGF itself consistently produced a strong signal.Conclusion. The present results raise questions regarding the existence of agonistic autoantibodies to PDGFR in SSc.

CYP2D6 genotyping and/or phenotyping could not fully predict EDF concentrations. Monitoring EDF itself could be considered during TAM therapy.

Severe and sustained cardiotoxicity following VEN overdose may be related to the amount ingested, as well as to the genetic polymorphism for CYP2D6 leading to a delayed elimination of active metabolite.

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"First trimester placental growth factor and soluble fms-like tyrosine kinase 1 are significantly related to PAPP-A levels" Sibylle Loibl, Sileny N Han, Gunter von Minckwitz, Marijke Bontenbal, Alistair Ring, Jerzy Giermek, Tanja Fehm, Kristel Van Calsteren, Sabine C Linn, Bettina Schlehe, Mina Mhallem Gziri, Pieter J Westenend, Volkmar Müller, Liesbeth Heyns, Brigitte Rack, Ben Van Calster, Nadia Harbeck, Miriam Lenhard, Michael J Halaska, Manfred Kaufmann, Valentina Nekljudova, Frederic Amant SummaryBackground Little is known about the treatment of breast cancer during pregnancy. We aimed to determine whether treatment for breast cancer during pregnancy is safe for both mother and child.