Apolipoprotein(a) (apo(a)) contains tandemly repeated kringle domains that are closely related to plasminogen kringle 4, followed by a single kringle 5-like domain and an inactive protease-like domain. Recently, the anti-angiogenic activities of apo(a) have been demonstrated both in vitro and in vivo. However, its effects on tumor angiogenesis and the underlying mechanisms involved have not been fully elucidated. To evaluate the anti-angiogenic and anti-tumor activities of the apo(a) kringle domains and to elucidate their mechanism of action, we expressed the last three kringle domains of apo(a), KIV-9, KIV-10, and KV, in Escherichia coli. The resultant recombinant protein, termed rhLK68, exhibited a dose-dependent inhibition of basic fibroblast growth factor-stimulated human umbilical vein endothelial cell proliferation and migration in vitro and inhibited the neovascularization in chick chorioallantoic membranes in vivo. The ability of rhLK68 to abrogate the activation of extracellular signal-regulated kinases appears to be responsible for rhLK68-mediated anti-angiogenesis. Furthermore, systemic administration of rhLK68 suppressed human lung (A549) and colon (HCT-15) tumor growth in nude mice. Immunohistochemical examination and in situ hybridization analysis of the tumors showed a significant decrease in the number of blood vessels and the reduced expression of vascular endothelial growth factor, basic fibroblast growth factor, and angiogenin, indicating that suppression of angiogenesis may have played a significant role in the inhibition of tumor growth. Collectively, these results suggest that a truncated apo(a), rhLK68, is a potent antiangiogenic and anti-tumor molecule.
Objective Despite percutaneous fluoroscopy ensuring appropriate placement of peritoneal dialysis (PD) catheters, the efficacy of this method is not well known. Therefore, we evaluated our long-term experience with fluoroscopy-assisted placement of PD catheters. Patients and Methods We retrospectively reviewed 134 PD catheters in 114 PD patients that were treated in the PD center of a university-based hospital. We evaluated complications related to PD catheters, causes for catheter removal, and catheter survival. We used the multivariate Cox proportional hazard model to identify independent factors related to PD catheter survival. Results Early complications related to insertion included 1 case of pericatheter bleeding; there were no placement failures. Early complications occurred in 8.5% of patients. Most late complications were migration and leakage, which occurred in 10.4% and 9.7% of patients respectively. The most common cause for catheter removal was intractable and recurrent peritonitis. The 12- and 24-month survival rates of the catheters were 80.0% and 74.9%. The most significant prognostic factor of percutaneous fluoroscopy-assisted PD catheter survival was late leakage ( p < 0.01). Conclusions In addition to the advantages of simplicity, minimal invasiveness, and relative safety, the survival rate of PD catheters placed using the percutaneous fluoroscopy-assisted method was comparable to that of more invasive methods. Percutaneous fluoroscopy-assisted placement of PD catheters should be considered when available, and may be preferred to other placement methods.
A method for measuring the ethanol concentration in a yeast culture broth was developed using both microtubes and a 96-deepwell microplate. The strategy involved first the solvent extraction of ethanol from the yeast culture broth and measurements of the ethanol concentration using the dichromate oxidation method. Particular focus was made on selecting the extraction solvent as well as determining the measurable range of ethanol concentrations using this solvent extraction-dichromate oxidation method. This method was developed as an assay format in 2.0-ml microtubes and 1.2-ml 96-deepwell microplates, and the ethanol concentration in the batch cultures and fed-batch fermentations was measured. Tri-n-butyl phosphate [non-alcoholic solvent, density = 0.9727, solubility in water = 0.028% (w/v)] was used for solvent extraction when measuring the ethanol concentration from the yeast culture broth. The maximum detectable ethanol concentration was 8% (v/v) when 10 g potassium dichromate in 100 ml of 5 M sulfuric acid was used. The concentrations determined from the solvent extraction-dichromate oxidation methods were remarkably similar to those of gas chromatography in which samples were prepared from seven experiments, such as four batch cultures and three fed-batch fermentations.
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