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#28753201   // Save this To Up

Delivery of human erythropoietin gene with an adeno-associated virus vector through parotid glands to treat renal anaemia in a swine model.

Anaemia is a common complication of chronic kidney disease, for which there is presently no adequate treatment. The delivery of human erythropoietin (hEPO) cDNA to salivary glands reportedly increases red blood cell counts, haematocrit (HCT) and haemoglobin concentration, representing a potential new method of renal anaemia treatment. However, no studies have examined the effects of this method in an animal model of renal anaemia. Here we established a miniature pig animal model of renal anaemia through continuous feeding with adenine. In these animals, we delivered the AAV2hEPO gene to the parotid glands through Stensen's duct. As a control, we transferred AAVLacZ. Enzyme-linked immunosorbent assay was used to detect hEPO in serum and saliva. Red blood counts and serum biochemistry were used to evaluate how hEPO gene administration affected renal anaemia. Compared with the control group, we found increased hEPO concentrations in parotid saliva and serum, respectively, at 2 and 6 weeks after AAV2hEPO administration to the anaemic animals. HCT and haemoglobin were also increased after AAV2hEPO was delivered; most serum indicators of renal damage were not changed over the time span of the experiment, suggesting the adenine-induced kidney damage had not been completely reversed. However, blood urea nitrogen and B2 microglobulin levels showed small but significant improvement. Overall, our present findings suggest that adeno-associated virus 2 (AAV2)-mediated gene transduction of hEPO via the parotid gland is a promising potential alternative therapy for renal anaemia.

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#25162001   // Save this To Up

Serum soluble TACI, a BLyS receptor, is a powerful prognostic marker of outcome in chronic lymphocytic leukemia.

BLyS is involved in CLL biology and its low soluble serum levels related to a shorter time to first treatment (TFT). TACI is a BLyS receptor and can be shed from cells' surface and circulate in soluble form (sTACI). We investigated the impact of serum BLyS and sTACI levels at diagnosis in CLL patients and their relationship with disease parameters and patients' outcome. Serum BLyS was determined in 73 patients, while sTACI in 60. Frozen sera drawn at diagnosis were tested by ELISA. sTACI concentrations correlated with BLyS (P = -0.000021), b2-microglobulin (P = 0.005), anemia (P = -0.03), thrombocytopenia (P = 0.04), Binet stage (P = 0.02), and free light chains ratio (P = 0.0003). Soluble BLyS levels below median and sTACI values above median were related to shorter TFT (P = 0.0003 and 0.007). During a ten-year followup, sTACI levels, but not BLyS, correlated with survival (P = 0.048). In conclusion, we confirmed the prognostic significance of soluble BLyS levels with regard to TFT in CLL patients, and, more importantly, we showed for the first time that sTACI is a powerful prognostic marker, related to parameters of disease activity and staging and, more importantly, to TFT and OS.

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#19693535   // Save this To Up

The serum levels of soluble interleukin-2 receptor alpha and lactate dehydrogenase but not of B2-microglobulin correlate with selected clinico-pathological prognostic factors and response to therapy in childhood soft tissue sarcomas.

To establish the clinical utility of serum soluble IL-2 receptor (sIL-2R alpha), lactate dehydrogenase (LDH) [corrected] and B2-microglobulin [corrected] (B2-M) as markers for diagnosis, prognosis and treatment monitoring in childhood soft tissue sarcomas (STS).

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