GLYCOSYLATION STATUS ASSAYS FOR DIAGNOSTIC TUMOR MARKERS

CERTAIN SERUM GLYCOPROTEINS THAT ARE ELEVATED IN THE SERUM OR URINE OF CANCER PATIENTS ARE CONSIDERED TO BE TUMRO MARKERS. ANALYSES OF THE OLIGOSACCHARIDE SIDE-CHAINS ON MANY OF THESE GLYCOPROTEINS, INCLUDING A-FETORPROTEIN (AFP), GAMMA-GLUTAMYLTRANSPEPTIDASE AND HUMAN CHRONIC GONADOTROPIN, WHICH ARE DERIVDE FROM MALIGNANT TISSUES, DEMONSTRATE THAT THEIR GLYCOSYLATION STATUS IS MARKEDLY DIFFERENT FROM THEIR NON-MALIGNANT COUNTERPARTS. THUS, INFORMATION ABOUT THE GLYCOSYLATION STATUS OF CERTAIN SERUM AND URINARY GLYCOPROTEINS MAY HAVE MORE DIAGNOSTIC SIGNIFICANCE THAN MEASUREMENTS OF LEVELS OF THESE MARKERS. THE TECHNIQUES PRESENTLY AVAILABLE TO MEASURE GLYCOSYLATION STATUS EMPLOY EITHER DETAILED CHEMICAL ANALYSES OR LECTIN-AFFINITY CHROMATOGRAPHY. THESE PROCEDURES, ALTHOUGH ELEGANT, ARE COMPLEX, TIME CONSUMING, EXPENSIVE, AND NOT READILY AUTOMATABLE. WE HAVE DEVELOPED NOVEL SOLID PHASE BIOLUMINESCENT IMMUNOASSAYS (BIA) IN A MICROTITER PLATE FORMAT THAT ARE EXTREMELY SENSITIVE, EASY TO USE, AND READILY ADAPTABLE FOR SCREENING AND CLINICAL USE. THE SPECIFIC AIM OF PHASE I IS TO DEVELOP A BIA TO MONITOR THE GLYCOFORMS OF AFP WHOSE GLYCOSYLATION STATUS HAS BEEN SHOWN TO BE POTENTIALLY DIAGNOSTIC FOR HEPATOCELLULAR CARCINOMA BOTH IN HUMANS AND IN AN ANIMAL MODEL. THIS PHASE I APPLICATION WILL DEMONSTRATE THE FEASIBILITY TO DEVELOP GLYCOSYLATION STATUS ASSSAYS FOR OTHER TUMOR MARKERS AND THE TECHNOLOGY TO DEVELOP ASSAY KITS FOR INEXPENSIVE MONITORING OF THE GLYCOSYLATION STATUS OF OTHER GLYCOPROTEINS.