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The epidermal growth factor receptor (EGFR) plays an important role in tissue homeostasis and tumor progression. However, cancer patients treated with EGFR inhibitors (EGFRIs) frequently develop acneiform skin toxicities, which are a strong predictor of a patient's treatment response. We show that the early inflammatory infiltrate of the skin rash induced(More)
BACKGROUND Transcriptome analysis of circulating tumor cells (CTCs) holds great promise to unravel the biology of cancer cell dissemination and identify expressed genes and signaling pathways relevant to therapeutic interventions. METHODS CTCs were enriched based on their EpCAM expression (CellSearch®) or by size and deformability (ParsortixTM),(More)
During antibiotic drug development, media are frequently spiked with either serum/plasma or protein supplements to evaluate the effect of protein binding. Usually, previously reported serum or plasma protein binding values are applied in the analysis. The aim of this study was to evaluate this approach by experimentally measuring free, unbound(More)
BACKGROUND Urothelial bladder cancer is the ninth most common cancer. Despite surgical and chemotherapeutic treatment the prognosis is still poor once bladder cancer progresses to a muscle-invasive state. Discovery of new diagnostic markers and pathophysiologic effectors might help to contribute to novel diagnostic and therapeutic options. The extracellular(More)
Photoaged skin is clinically characterized by wrinkling, laxity and a leather-like appearance. These symptoms of actinic aging are causally connected to histological and ultrastructural changes of the connective tissue of the dermis. Changes include both enzymatic degradation and reduced de novo synthesis of collagen which cause premature wrinkling of the(More)
BACKGROUND AND PURPOSE Cyclooxygenase-2 (COX2) and hyaluronic acid (HA) are common in tumours and both independently promote tumour progression. Furthermore, COX2-dependent synthesis of prostaglandins (PGs) stimulates HA synthase-1 (HAS1) and HAS2 mRNA expression, together with HA synthesis via the cAMP/protein kinase A pathway in vascular smooth muscle(More)
BACKGROUND Hyaluronan is thought to mediate neointimal hyperplasia but also vasoprotection as an integral component of the endothelial glycocalyx. The present study addressed for the first time the effects of long-term pharmacological inhibition of hyaluronan synthesis on vascular function and atherosclerosis. METHODS AND RESULTS Four-week-old(More)
Hyaluronan (HA) and versican are key components of the dermis and are responsive to ultraviolet (UV)B-induced remodeling. The aim of this study was to explore the molecular mechanisms mediating the effects of estrogen (E(2)) on HA-rich extracellular matrix during photoaging. Hairless skh-1 mice were irradiated with UVB (three times, 1 minimal erythema dose(More)
UVB irradiation causes characteristic features of skin aging including remodeling of the dermal extracellular matrix. A key feature during this process is the up-regulation of matrix metalloproteinases and cleavage of collagen. Hyaluronic acid (HA), a major component of the dermal matrix, decreases after chronic UVB exposure. However, the factors that(More)
Even though aging and cellular senescence appear to be linked, the biological mechanisms interconnecting these two processes remain to be unravelled. Therefore, microRNA (miRNA/miR) profiles were analyzed ex vivo by means of gene array in fibroblasts isolated from young and old human donors. Expression of several miRNAs was positively correlated with donor(More)