Potential of fluorescent metalloproteinase substrates for cancer detection.

OBJECTIVES: MMP-2, MMP-9, their complexes and ADAM12 are detected in the urine of breast cancer patients and predict disease status. We assessed the use of FRET-based substrates in an assay to distinguish breast cancer patients from controls. DESIGN AND METHODS: Substrates with varying specificities for MMP-9 and MMP-2 and several ADAMs were screened. Flsub21 and Flsub13, substrates for ADAM12 and ADAM8 respectively, were studied. RESULTS: Flsub21 and Flsub13 cleavage activities were detected in the urine of patients with invasive and metastatic breast cancers at significantly higher frequencies compared to controls. Our model predicted probabilities of 90% when both Flsub21 and Flsub13 were positive, 65% when Flsub21 alone was positive, 55% when Flsub13 alone was positive and 20% when both substrates were negative. CONCLUSIONS: These data suggest the potential utility of FRET substrates to non-invasively identify invasive and/or metastatic breast cancer.

Elevation of free beta subunit of human choriogonadotropin and core beta fragment of human choriogonadotropin in the serum and urine of patients with malignant pancreatic and biliary disease.

Human choriogonadotropin (hCG), its free beta subunit (beta hCG), and the core beta hCG fragment (c beta hCG) were measured by highly sensitive time-resolved immunofluorometric assays in the serum and urine of 29 patients with pancreatic cancer, 7 patients with biliary cancer, and 45 patients with benign pancreatic or biliary diseases. The results were compared with those of an age- and sex-matched reference population of nonpregnant women and men. Of the various forms of hCG assayed in serum, beta hCG showed the best diagnostic accuracy, and c beta hCG was the best marker in urine. Elevated serum concentrations of beta hCG were observed in 72% of the patients with pancreatic cancer, in 6 of 7 patients with biliary cancer, and in 9% of those with benign disorders. The serum concentrations of c beta hCG were elevated in 45%, 57%, and 2%, respectively, and those in urine in 55%, 71%, and 11%, respectively. The molar concentrations of c beta hCG in serum were mostly lower than those of beta hCG. Thus beta hCG secreted into serum appears to be the main source of c beta hCG in urine. Provided that they are measured by sufficiently sensitive and specific assays, beta hCG in serum and c beta hCG in urine appear to be useful markers for pancreatic and biliary cancer.

Levels of polyamines and nucleic acids in human breast carcinoma.

Polyamine and nucleic acid levels were determined in normal human breasts, in primary infiltrating ductal carcinoma breasts, in the uninvolved tissues of the same carcinoma-bearing breasts and in the urine of the same patients. The results showed that the production of polyamines in the carcinoma tissue is significantly higher than in normal tissue; the presence of a carcinoma in the breast does not modify the levels of polyamines and nucleic acids in the surrounding uninvolved tissue; spermidine and spermine are correlated both with DNA and RNA in the carcinoma; the urinary polyamine levels in the carcinoma-bearing patients were not significantly different from that of controls. There appeared to be a close relationship between polyamine biosynthesis and tumoral mammary cell development and a very fine control between the biosynthesis of both spermidine and spermine and nucleic acids. In addition, the localized solid breast carcinoma, with non-proven metastases, did not provoke an increase in polyamine excretion.