Immunotherapy of prostatic cancer with Bacillus Calmette-Guérin and purified protein derivative. Preliminary results.
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Adenocarcinoma↗
Biomedical subjects
C Merrin
Publications and source records attributed to C Merrin.
Immunotherapy of prostatic carcinoma with bacillus Calmette-Guerin.
Seventeen patients with histologically proven adenocarcinoma of the prostate were selected for evaluation of their immunologic competence and therapy with bacillus Calmette-Guérin (BCG). All patients were in stage D. The immune response was explored in two main aspects: cell-mediated and humoral immunity. Delayed skin hypersensitivity reaction with purified protein derivative (PPD), streptokinase-streptodornase (varidase), Candida, mumps antigen, and Trichophyton were tested. Lymphocyte reactivity was measured by in vitro blastogenesis. Serum immunoglobulin levels and serum protein electrophoresis were also measured. The patients were then divided in two groups according to the skin test response to PPD. Group 1 (PPD-positive) consisted of seven patients. Group 2 (PPD-negative) consisted of ten patients. In group 1, two patients were treated with intraprostatic injection of BCG every week in the following doses: 1 cc the first week, 2 cc the second week, 4 cc the third week, and 6 cc the fourth week. The five remaining patients in this group received only 1 cc every week for 4 weeks. The group 2 patients (PPD-negative) were stimulated by oral intake of BCG in an attempt to convert their skin tests to positive. All patients revealed varying degrees of immunodepression. None of the patients in group 2 (stimulated by oral intake of BCG) converted to positive skin tests. Three patients in group 1 treated with BCG showed necrosis of the tumor. The different aspects of immunodepression in this disease are analyzed and correlated to the clinical staging, histologic grading, and response to therapy. The mechanism of BCG action in advanced prostatic carcinoma is discussed.
Adenocarcinoma↗
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↗
Prelinimary report on combination therapy for advanced prostatic cancer.
Fifteen patients with carcinoma of the prostate (ten, stage D; three, stage C; and two, stage B) were treated with the combination of radical retropubic prostatectomy, bilateral orchiectomy, estrogen therapy, and chemotherapy with 5-fluorouracil and cyclophosphamide. Fourteen patients have been clinically free of disease from 2 to 20 months. One patient died free of disease from myocardial infarction in the post-operative period. Lymphangiography was accurate in 14 of the 15 patients. Acid phosphatase levels in serum did not reflect with precision the extension of the tumor in seven of ten patients with stage D disease. The rationale of this therapeutic approach is discussed.
Castration↗