Endoglin is a transforming growth factor-β coreceptor with a crucial role in angiogenesis. A soluble form of endoglin is present in the circulation, but the role of soluble endoglin (sEndoglin) is poorly understood. In addition, the endoglin shedding mechanism is not known. Therefore, we examined the role of sEndoglin in tumor angiogenesis and the mechanism by which the extracellular domain of endoglin is released from the membrane. In colorectal cancer specimens, we observed high endothelial endoglin protein expression, accompanied with slightly lower sEndoglin levels in the circulation, compared with healthy controls. In vitro analysis using endothelial sprouting assays revealed that sEndoglin reduced spontaneous and vascular endothelial growth factorinduced endothelial sprouting. Human umbilical vascular endothelial cells were found to secrete high levels of sEndoglin. Endoglin shedding was inhibited by matrix metalloproteinase (MMP) inhibitors and MMP

Methotrexate (MTX) is one of the most widely prescribed drugs in the treatment of rheumatoid arthritis (RA). The mechanism by which MTX exerts its anti-rheumatic effect has not yet been defined. The aim of the present study was to investigate the effect of MTX treatment (7.5-15 mg/week) on synovial tissue in RA. For this purpose, synovial biopsies were taken from 11 RA patients before and 16 weeks after initiation of MTX therapy. Immunohistochemistry was performed using monoclonal antibodies (MAb) specific for CD3, CD4, CD8, CD22, CD25, CD38, CD68, MAb67, Ki67, interferon gamma (IFN-gamma), interleukin (IL)-1alpha, IL-1beta, tumour necrosis factor alpha (TNF-alpha), E-selectin, ICAM-1 and VCAM-1. All parameters for disease activity improved during the period of treatment. Immunohistochemical analysis revealed a statistically significant decrease in scores for CD3, CD8, CD38, CD68, Ki67, IL-1beta, TNF-alpha and the adhesion molecules E-selectin and VCAM-1. The observed decrease in synovial scores for inflammatory cells, monokines and adhesion molecules suggests that the anti-inflammatory effect of MTX is, in part, dependent on a reduction in monokine-inducible vascular adhesion molecules and subsequent reduction of cell traffic into joints.

The present report concerns a patient with a malignant gastrin-producing neuroendocrine tumour (ie, Zollinger-Ellison syndrome) with recurrent hepatic gastrinomas, in whom no gastrinoma in the duodenum, pancreas or other extrahepatic sites could be identified despite the use of multiple, repeatedly performed imaging and exploration techniques over the past 20 years. A short review on primary liver gastrinomas published since 1981 is also given. Interestingly, our patient is the only case with documented recurrent gastrinoma in the liver. None of the cases in the literature had liver gastrinomas as part of the multiple endocrine neoplasia type I syndrome. The interpretation of hepatic gastrinomas as primary lesions is questionable unless comprehensive investigation and well documented long-term follow-up is performed.

We suggest that endoglin is a potential marker to indicate and predict metastases, which might be useful in the post-resection therapeutic approach of patients with GEP-NETs.

The incidence of duodenopancreatic nonfunctional neuroendocrine tumors in The Netherlands increased over 1991 to 2009. The etiology for this change includes improved diagnostic techniques and clinical awareness, as discussed.

T-lymphocytes are involved in the inflammatory response that occurs in affected joints of patients with rheumatoid arthritis (RA). Some second-line disease modifying anti-rheumatic drugs used in the treatment of patients with RA are known to block T-cell activation. The present study assessed whether tenidap, an investigational anti-rheumatic drug, affects in vitro T-cell responses such as proliferation and cytokine production. It was found that tenidap, in contrast to several nonsteroidal anti-inflammatory drugs, inhibits anti-CD3 or IL-2 driven proliferative responses of cloned human T-cells. Furthermore, tenidap was found to inhibit IFN-gamma production as well as the induction of mRNA encoding IFN-gamma or TNF-alpha. The results indicate that tenidap may exert at least part of its anti-inflammatory activity via inhibition of T-cell function and cytokine production.

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