Methotrexate is a cytostatic drug applied in adjuvant chemotherapy and associated with cognitive impairment in part of the cancer patients. In this paper we studied in rats whether a reduction in blood supply to the brain or neuroinflammation are possible mediators of this cognitive dysfunctionality. Methotrexate reduced hippocampal blood vessel density 1 week and 3 weeks after treatment as measured immunohistochemically with an enclothelial barrier antigen. Since reduced brain vascularization may relate to lowered central glucose metabolism [(18)F]FDG PET was performed. Methotrexate reduced tracer uptake in the hippocampal...

Somatostatin receptor expression has been demonstrated on a number of plasma cell lines. Therefore, we questioned whether somatostatin receptor scintigraphy (SRS) can be used to demonstrate in vivo multiple myeloma (MM) activity. SRS was performed in newly diagnosed (n = 9) or relapsing (n = 18) MM patients or in patients with localized plasmacytoma (n = 2). The results were compared with radiographic findings. A positive SRS was demonstrated in 44% of the newly diagnosed patients, in 83% of the relapsed patients and in both patients with plasmacytoma....

Melenhorst WB, Visser L, Timmer A, van den Heuvel MC, Stegeman CA, van Goor H. ADAM17 upregulation in human renal disease: a role in modulating TGF-alpha availability? Am J Physiol Renal Physiol 297: F781-F790, 2009. First published June 17, 2009; doi:10.1152/ajprenal.90610.2008.-A disintegrin and metalloproteinase (ADAM) 17 sheds growth factors from the cell membrane, including epidermal growth factor receptor (EGFR) ligand transforming growth factor (TGF)-alpha. In mice, angiotensin II infusion induces renal fibrosis via ADAM17-mediated TGF-alpha shedding and subsequent EGFR activation. Pharmacological ADAM17 inhibition reduced renal fibrotic lesions and...

Mantle cell lymphoma (MCL) is characterized by genetic instability and a poor prognosis. Many blastoid variants are (hypo)tetraploid and have ail even worse prognosis. We investigated the role of signalling by mitogen-activated protein kinases (MAPKs) in MCL. As compared to normal tonsil B cells, MCL, cells showed higher activation of the JNK MAPK in both an MAPK array and a sandwich ELISA assay. Immunohistochemistry showed overexpression of phospho (p)-JNK (Thr183/Tyr185) in 30 of 37 MCL cases. Inhibition of p-JNK with SP600125 resulted in growth arrest in all four...

CD45 is the most prominent membrane protein on lymphocytes. The function and regulation of this protein tyrosine phosphatase remain largely obscure, mainly because of the lack of a known ligand, and it still remains unknown whether such tyrosine phosphatases are subject to extracellular control at all. We report that an anti-CD45RB antibody (Ab) that prevents rejection and induces tolerance activates CD45RB tyrosine phosphatase enzymatic activity in T lymphocytes, allowing us to directly monitor the effects of increased CD45RB activity on signal transduction. Using both kinase substrate peptide arrays...