Evaluation of serum and urine clusterin as a potential tumor marker for urinary bladder cancer.

Clusterin is a stress-associated cytoprotective chaperone up-regulated by various apoptotic triggers in many cancers and neurodegenerative diseases. No valid information about serum or urine clusterin concentration in patiens with bladder cancer exists. Aim of our paper was evaluation of the urine and serum clusterin concentrations in individuals with bladder cancer. Blood and urine samples were used from 43 patients with urothelial tumors of the urinary bladder and from 50 patients with benign urological diseases. Blood and urine were collected before cystoscopy. Enzyme-linked immunosorbent assays (ELISA) were performed for clusterin from serum and urine. Serum clusterin was higher in individuals with bladder cancer (means 185,812.5 vs 171,946.5 kU/l, p=0.04). Sensitivity for bladder cancer detection was 73% and specificity 55% (AUC 0.63); efficacy was not sufficient. Urine values of clusterin were higher in individuals with bladder cancer (197.2 vs 67.7, p=0.0007). Sensitivity for bladder cancer detection was 49% and specificity 92% (AUC 0.75, LR+ 6.1, PPV+ 84%); diagnostic efficacy was sufficient. In conclusion, serum and urine clusterin can differ between bladder cancer patients and the control group. Urine clusterin could be the possible laboratory marker of bladder cancer. Further research is warranted to confirm findings in larger studies of various clinical status.

Incorporation of carbon-14 in the biosynthesis of the macrolide antibiotic, LL-F28249-alpha.

A total of 76 mCi of 14C LL-F28249-alpha, nemadectin (1), having a specific activity of 35.2 microCi/mg was isolated from a fermentation using a mixture of approximately 600 mCi of 14C carboxyl labeled acetate, propionate and isobutyrate. Nemadectin was used to synthesize carbon-14 labeled moxidectin which is being developed as a highly efficient ectoparasitic anthelminth. The labeled positions were determined by 13C NMR analysis of 13C nemadectin which was obtained by similar incorporation of 13C carboxyl labeled acetate, propionate and isobutyrate.

Biosynthesis of the spermidine and guanidino units in the glycocinnamoylspermidine antibiotic cinodine.

The biosynthesis of the spermidine and guanidino groups has been studied with carbon-14 and carbon-13 labeled intermediates. Arginine, citrulline and ornithine are incorporated in good efficiency. The guanidino group of arginine and the ureido group of citrulline both label the guanidino group on the hexose sugar. None of the ureido groups in the antibiotic was enriched. It is likely that citrulline is converted to arginine before use in the biosynthesis. Arginine, citrulline and ornithine are incorporated as the four carbon unit of spermidine. All of the labeled 5 carbon from ornithine or from citrulline appears adjacent to the secondary amine in the four carbon unit of spermidine. This would indicate that unbound putrescine is not an immediate precursor of spermidine.

Biosynthetic origin of the carbon skeleton and oxygen atoms of the LL-F28249 alpha, a potent antiparasitic macrolide.

The biosynthesis of LL-F28249 alpha in a culture of Streptomyces cyaneogriseus has been studied using 13C, 14C and 18O labeled precursors. A complete 13C NMR spectrum of F28249 alpha has been assigned. Incorporation studies using 13C labeled precursors indicate that the carbon skeleton of F28249 alpha is derived from seven acetate, six propionate and one 2-methylpropionate units. The origin of the oxygen atoms of F28249 alpha has been examined by feeding [1-13C,18O2]acetate, [1-13C,18O2]propionate, [2-13C]acetate/18O2 and 18O2 separately to the fermentation culture and analyzing the resulting labeled LL-F28249 alpha samples by 13C NMR, electron impact MS and chemical ionization MS. Out of a total of eight oxygen atoms in LL-F28249 alpha, four oxygen atoms are derived from acetate, three from propionate and one from molecular oxygen.