A number of chemotherapeutic agents have been tested in two systems which could be useful as models in the search for effective drugs for cancer of the prostate. One system involved the effects of the administered drugs on rat prostatic 5 alpha-reductase and arginase activities. Since both enzymic systems are androgen dependent and essential for prostatic function and anatomy, the effectiveness of a drug in these systems could be indicative of its value in the treatment of prostatic cancer. Michaelis constants were obtained with Lineweaver-Burk plots and the conclusions are based on a comparison of these plots with those of the controls. Thus, the following results were obtained: (a) isophosphamide, bleomycin, and procarbazine produced definite inhibition of 5 alpha-reductase in either or both the ventral and dorsolateral glands of the rat; (b) 5-fluorouracil, vincristine, bleomycin, procarbazine, adriamycin, and hexamethyl-melamine inhibited arginase activity significantly in both glands; (c) streptozotocin and 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (NSC-45388) produced inhibition of arginase in the ventral gland only; (d) in contrast to the noncompetitive or uncompetitive inhibition of most of the drugs, particularly in the ventral gland, procarbazine, hexamethylmelamine, bleomycin, adriamycin, and NSC-45388 produced competitive inhibition of arginase in the dorsolateral gland; and (e) seven of the drugs led to an activation of 5 alpha-reductase (5-fluorouracil, vincristine, NSC-45388, hexamethylmelamine, CCNU, streptozotocin, and diglycolaldehyde). The second model system utilized the deposition of labeled estriol and testosterone in the dog prostate and the effects of drug therapy as a possible index of effectiveness in prostatic cancer. Streptozotocin and procarbazine definitely interfered with the deposition of both estriol and testosterone. On the basis of the data obtained, the model systems investigated by us could potentially serve as reliable indicators for the clinical use of drugs against cancer of the prostate.

Animals↗

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The role of the juxtaglomerular apparatus.

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Animals↗

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Tumor antigen and acid phosphatase isoenzyme in prostatic cancer.

Plasma and prostatic fluid from man, dog, and baboon were measured for carcinoembryonic antigen (CEA) by a radioimmunoassay technique. No CEA was detected in plasma, prostatic fluid, or seminal fluid in 12 dogs and three baboons. Elevated CEA (less than 2.5 ng/ml) was found in 13 of 20 human prostatic fluids. It was inferred that there was no immunologic cross-reactivity of CEA among man, dog, and baboon. CEA has been isolated and purified from liver tumors. Biochemical studies reveal that CEA consists of 60 percent carbohydrate and 40 percent protein. It contains the following carbohydrates: fucose, mannose, galactose, sialic acid, N-acetylglucosamine, and a small amount of N-acetylgalactosamine. The following amino acids were found in CEA: lysine, histidine, arginine, aspartic acid, threonine, serine, glutamic acid, proline, glycine, alanine, valine, emthionine, isoleucine, leucine, tyrosine, phenylalanine, and cysteine. The amino acid sequence (first 30 amino acids) of the N-terminal has been determined. The N-terminal amino acid was lysine. Using this study as a model, other tumor antigens from prostatic tumor tissues are being investigated. The acid phosphatase isoenzyme from prostatic tissue was also studied. After a series of purifications, two chromatographic fractions were obtained. Treatment with neuraminidase removed the sialic acid content of the molecule, changed the isoelectric focusing patterns, and abolished the chromatographic heterogeneity. Sedimentation studies indicated a molecular weight of about 100,000. Biochemical studies showed that prostatic acid phosphatase isoenzyme is a glycoprotein which consists of 7 percent carbohydrate and 93 percent protein. It contains fucose, galactose, mannose, sialic acid, N-acetylglucosamine, and the following amino acids: aspartic acid, threonine, serine, glutamic acid, proline, glycine, alanine, valine, methionine, isoleucine, leucine, tyrosine, phenylalanine, lysine, histidine, arginine, tryptophan, and cysteine. An antiserum to this purified prostatic acid phosphatase isoenzyme is being prepared in animals.

Acid Phosphatase↗