Surgical and Adjuvant Treatment of Pancreatic Cancer

Pancreatic cancer, including ampullary, distal bile duct and pancreatic head cancer, is one of the most lethal human cancers and still is a major unsolved health problem at the start of the 21st century. It has been estimated that this disease causes 30.000 deaths per year in the USA with an incidence of 9-10 cases per 100.000 and slightly increased male: female and black: white ratios. The incidence of pancreatic cancer in the Netherlands is approximately 8.4 per 100.000 patients. This number has been quite steady over the past ten years. Pancreatic cancer currently ranks as the fifth most common cause of cancer related deaths in the western countries. Over the past 20 years the disease continuous to have an appalling prognosis with less than 1% of patients surviving more than 5 years from diagnosis, so that mortality rates and annual incidence are virtually identical

Serum levels of soluble forms of T cell activation antigens CD27 and CD25 in systemic lupus erythematosus in relation with lymphocytes count and disease course

Systemic lupus erythematosus (SLE) patients are characterized by a low lymphocyte count, which is considered a specific disease marker and is related to disease activity. The membrane bound molecules CD25 and CD27 are expressed and released in a soluble CD25 (sCD25) and soluble CD27 (sCD27) form by activation of predominantly T cells. In previous studies it was claimed that sCD25 as well sCD27 might be used as parameters for activation of the immune system; a correlation between the sCD25 profile with the disease course in SLE patients was also shown. To assess the relationship between lymphocyte count and these T cell activation markers, we performed a cross-sectional and a longitudinal study. In the longitudinal study three SLE patients who were known for a long time at our outpatient clinic were studied. Both T cell markers strongly correlated with each other and formed a reflection of the disease course. In all 7 periods of exacerbation, which we observed in the 3 investigated patients, both levels increased preceding this period; however, no correlation was found with the lymphocyte count. In the cross sectional study of 69 patients with SLE, sCD25 and sCD27 levels were correlated with defined disease manifestations; sCD25 was elevated in all periods of increased disease activity. The same holds true for sCD27, with the exception of patients with nephritis in which the highest levels were observed. Both profiles of sCD25 and sCD27 were strongly correlated during the whole disease course. Our data prove that in the pathogenesis of SLE an active recruitement of unprimed and primed T cells takes place

Conserved UBE3A subcellular distribution between human and mice is facilitated by non-homologous isoforms

The human UBE3A gene, which is essential for normal neurodevelopment, encodes three Ubiquitin E3 ligase A (UBE3A) protein isoforms. However, the subcellular localization and relative abundance of these human UBE3A isoforms are unknown. We found, as previously reported in mice, that UBE3A is predominantly nuclear in human neurons. However, this conserved subcellular distribution is achieved by strikingly distinct cis-acting mechanisms. A single amino-acid deletion in the N-terminus of human hUBE3A-Iso3, which is homologous to cytosolic mouse mUBE3A-Iso2, results in its translocation to the nucleus. This singe amino-acid deletion is shared with apes and Old World monkeys and was preceded by the appearance of the cytosolic hUBE3A-Iso2 isoform. This hUBE3A-Iso2 isoform arose after the lineage of New World monkeys and Old World monkeys separated from the Tarsiers (Tarsiidae). Due to the loss of a s

Well-defined polymer architectures for controlled assembly: Beta-sheet containing hybrid block copolymers

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Polymer protein hybrids

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Fibril formation by triblock copolymers of silklike beta-sheet polypeptides and poly(ethylene glycol)

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