Changes in tissue prostatic acidic phosphatase during endocrine treatment of patients with prostatic carcinoma

OBJECTIVE: We have previously developed methods for the quantification of different macromolecules in aspiration biopsy material and described the changes in prostate-specific antigen (T-PSA) during cancer treatment. We have now studied the changes in tissue prostatic acidic phosphatase (T-PAP) in 58 endocrine-treated patients with prostatic carcinoma and compared these data with cancer development data and tissue PSA (T-PSA) levels. MATERIAL AND METHODS: PAP and PSA were quantified in aspiration biopsies taken before treatment and after 6 and 12 months of treatment. Patients were followed until death or for >98 months. RESULTS: Pretreatment T-PSA was more strongly associated with survival than T-PAP. Both T-PSA and T-PAP decreased in responders during treatment. In non-responders, T-PSA and T-PAP increased after 12 months in 17/18 and 7/13 patients, respectively. Estrogen-treated responders had significantly higher T-PSA, but not T-PAP, treatment values than those treated with orchidectomy or gonadotropin-releasing hormone. CONCLUSIONS: The inferiority of serum PAP compared to PSA for monitoring cancer treatment may reflect its less pronounced changes at the tissue level, indicating different in vivo regulation of the two markers. Estrogen stimulation of PSA synthesis in vivo may underlie the higher PSA levels observed during estrogen treatment.     

Single-drug parenteral estrogen treatment in prostatic cancer: a study of two maintenance-dose regimens

Treatment of 17 patients with prostatic cancer with 320 mg polyestradiol phosphate (PEP) as intramuscular injections every fourth week suppressed serum testosterone (T) values to orchidectomy levels within 1 month, and serum estradiol-17 beta (E2) rose to a mean level of 2,456 pmol/liter after 6 months. Following 6 months of treatment, the PEP dose was reduced to 80 mg/4 weeks in 9 and 160 mg/4 weeks in eight patients. Mean T levels, increased significantly after dose reduction in both groups and were above the upper orchidectomy limit at 1 month after dose reduction in the 80 mg group. Mean T levels, however, remained below this level at 5 months in the 160 mg group. Dose reduction caused a rise in gonadotropin levels in the 80 mg but not in the 160 mg group. While 320 mg/4 weeks may be a suitable initial dosage, doses less than or equal to 160 mg/4 weeks are insufficient as maintenance dosages if orchidectomy values of T are required.     

Novel assay for pancreatic cellular damage: 1. Characterization of protein profiles in human pancreatic cytosol and purification and characterization of a pancreatic specific protein

The protein patterns of cytosols from normal human pancreas and pancreatic carcinoma were studied by a two-dimensional separation technique using high-performance liquid chromatography followed by isoelectric focusing on polyacrylamide gels and visualization of the focused proteins by Coomassie Blue staining. Almost identical protein patterns were obtained for 20 different specimens from normal pancreas, whereas quite different protein patterns were found in 12 samples of pancreatic carcinoma. A major protein in normal pancreatic cytosol, not identical to any macromolecule previously tested as a marker for pancreatic function, was selected for further studies. The protein was not found in specimens of pancreatic carcinoma. It was purified by a single step chromatofocusing procedure, focused at pH 6.9, and moved as one single band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis with an apparent molecular weight of 44,500 daltons. Total amino acid analysis revealed a high concentration of glutamic acid, leucine, and lysine. The purified protein had no amylase activity or lipase immunoactivity. It constituted approximately 2% of the total normal pancreatic cytosol protein. Later immunological studies have shown the protein to be highly specific for normal human pancreas, indicating a possible future use as a marker for pancreatic cell damage.     

A novel serum assay for pancreatic cellular damage. II. High tissue specificity of a pancreatic protein

A previously unknown major protein in human pancreatic cytosol has been purified and partly characterized. The protein, designated pancreas specific protein (PASP), has a molecular weight of 44,500 and a pI of 6.9. A two-dimensional gel separation technique revealed the protein to be specific for normal pancreatic tissue. Antibodies against PASP were raised in rabbits and a radioimmunoassay was developed for the quantitation of this protein. The following concentrations of PASP (mg/kg wet weight) were found in human tissues: normal pancreas 100-1,000; pancreatic carcinoma 0.1-20; prostate 0.5-5; and 13 other tissues less than 0.5. The levels of PASP in peripheral serum were less than 0.1 mg/L in normal subjects, 0.7-3 mg/L in cases of acute pancreatitis, and less than 0.1 mg/L in cases of pancreatic carcinoma, prostatic diseases, and other abdominal diseases investigated. The high tissue specificity and the specific elevation of serum PASP levels in acute pancreatitis may indicate a use of this protein as a marker of this pancreatic condition.     

Adenocarcinoma of the pancreas--a hormone sensitive tumor? A preliminary report on Nolvadex treatment

There are indications of possible effects of sex hormones on the pancreas. These include reports on steroid receptor proteins in pancreatic tissue, the purification and characterization of a highly specific, high capacity oestrogen binding protein in the human pancreas and capacity of human pancreatic tissue to convert the main peripheral oestrogen, oestrone sulphate, into the terminal biologically active oestradiol-17 beta. Furthermore, experiments in mice have shown accumulation of an anti-oestrogen, tamoxifen, in the pancreas. With this background, we have tried tamoxifen in 14 patients with unresectable adenocarcinoma of the pancreas. The median survival time was 8.5 months and three patients had a remarkably long survival time of 22 months. In a historical control group the median survival time was 2.5 months and no patients survived for more than 21 months. We have therefore started a randomized trial with tamoxifen in patients with unresectable pancreatic cancer. Even if anti-oestrogens are not the optimal form of therapy, other sorts of hormonal manipulation ought to be tried in pancreatic cancer.     

Tissue PSA from fine-needle biopsies of prostatic carcinoma as related to serum PSA, clinical stage, cytological grade, and DNA ploidy

BACKGROUND: The mechanisms behind changes in serum PSA (S-PSA) levels in patients with prostatic carcinoma (CAP) are not completely known. To further elucidate the factors affecting the serum levels of this important tumor marker, we measured PSA concentrations in serum and in aspiration biopsies (tissue PSA; T-PSA) from patients with prostatic disease and correlated the values to tumor stage, cytological grade, and DNA ploidy. METHODS: T-PSA and S-PSA were measured in 91 metastasis-free patients with newly diagnosed, untreated CAP and 13 patients with benign prostatic hyperplasia, and the values were related to tumor stage, cytological grade, and DNA ploidy. RESULTS: Significant negative correlations were found between T-PSA and S-PSA in the total clinical material and various subgroups of patients with CAP. T-PSA showed significant negative associations to T-stage and to cytological grading, and T-PSA concentrations were significantly lower in tetra-/aneuploid tumors than in diploid tumors. On the other hand, S-PSA showed corresponding positive associations and was significantly higher in tetra-/aneuploid tumors than in diploid tumors. CONCLUSIONS: The negative association between S-PSA and T-PSA values indicates that S-PSA values in metastasis-free patients reflect the degree of leakage from the tumor tissue rather than the intracellular concentration of PSA. Factors such as tissue volume, condition of gland structure, and vascularization may thus be more important for S-PSA than the production of PSA in the prostatic tissue.