Biochemical Biopsy Research Articles

A blood tumor marker combination assay produces high sensitivity and specificity for cancer according to the natural history.

Diagnosis using a specific tumor marker is difficult because the sensitivity of this detection method is under 20%. Herein, a tumor marker combination assay, combining growth‐related tumor marker and associated tumor marker (Cancer, 73(7), 1994), was employed. This double‐blind tumor marker combination assay (TMCA) showed 87.5% sensitivity as the results, but a low specificity, ranging from 30 to 76%. To overcome this low specificity, we exploited complex markers, a multivariate analysis and serum fractionation by biochemical biopsy. Thus, in this study, a combination of new techniques was used to re‐evaluate these serum samples. Three serum panels, containing 90, 120, and 97 samples were obtained from the Mayo Clinic. The final results showed 80‐90% sensitivity, 84‐85% specificity, and 83‐88% accuracy. We demonstrated a notable tumor marker combination assay with high accuracy. This TMCA should be applicable for primary cancer detection and recurrence prevention.

Serum Enzymes Derived from Liver Cell Fractions

This report tests the hypothesis that serum enzymes may reflect injury to the various subcellular organelles of liver cells, and serve as a biochemical biopsy which might be useful in differential diagnosis. The enzymes studied are found in liver cells but in different subcellular fractions: sorbitol dehydrogenase (cytoplasm), ornithine carbamyl transferase (mitochondria), microsomal liver esterase (endoplasmic reticulum), arylsulfatase-B (lysosomes), and nicotinamide mononucleotide adenylyl transferase (nuclei). As a model of acute hepatocellular injury, a single intragastric dose of CCl4 (0.25 ml per 100 g) was given to rats and the temporal changes of these enzymes were measured in serum, subcellular fractions, and liver homogenate over a 96hr period. Serum sorbitol dehydrogenase activity increased by 3 hr and serum ornithine carbamyl transferase between 6 and 12 hr, times corresponding to the known onset of CCl4 injury to cellular and mitochondrial membranes, respectively. Serum microsomal esterase did not increase until 23 hr after the onset of CCl4 injury to the endoplasmic reticulum, however. The serum lysosomal and nuclear enzymes were normal throughout. No correlations were apparent between the serum activities of the first three enzymes and their specific activities in cell fractions or homogenates. Although the appearance in serum of an enzyme derived from a certain subcellular fraction is qualitative evidence of injury to the membrane system containing the enzyme, so many variables affect serum enzymes that the timing or degree of elevation does not predict the onset or severity of intracellular injury.

Biochemical Biopsy of Skeletal System Lesions

Utilizing quantitative microchemical techniques developed by Lowry, an attempt was made to obtain biochemical biopsy specimens and to determine the enzyme content of morphologically selected areas from malignant and benign lesions of the skeletal system. Osteosarcoma, chondrosarcoma, proliferating bone from Paget's disease, and tissue from polyostotic fibrous dysplasia were analyzed for enzymes of carbohydrate metabolism, hexosamine, and total phosphate content. Generally the areas and lesions characterized by rapid proliferation were the most active enzymatically and in the selections from malignant neoplasms lactic dehydrogenase was predominant. Benign proliferating bone in Paget's disease was featured by more active aerobic pathways with more malic dehydrogenase. Comparison of neoplastic cartilage from the osteosarcoma with the morphologically similar cartilage from chondrosarcoma demonstrated considerable chemical differences between the two cartilage types. In general, the clinical course and manifestations of the lesions studied could be correlated with the metabolic activity as determined by the alkaline phosphatase and carbohydrate intermediate enzyme content.

Enzymatic assay and glucose and amino-acid uptake of intestinal biopsy specimens.

1. An approach to the evaluation of human intestinal function is presented, based on the use of tissue segments obtained by peroral biopsy or surgical removal. Such segments possess the ability to take up radioactive amino acids and glucose in vitro. Homogenates of human intestinal tissue were utilized to estimate enzyme activities, thus allowing a “biochemical biopsy.” Correlation of the histologic appearance of intestinal tissue with its accumulative ability and enzyme content may provide an index of gut function. 2. Comparison of the mesenteric and antimesenteric halves of the hamster small intestine did not reveal statistically significant differences in amino-acid uptake, glucose uptake, or lactic-dehydrogenase activity. Hence although intestinal activities may vary with length, there is no clear evidence that they depend upon radial direction.