Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

F(ab')2 fragments (at concentrations of 5-30 mg/ml) derived from monoclonal antibodies raised against human prostate specific acid phosphatase were derivatized with a bicyclic anhydride of diethylenetriaminepentaacetic acid (cDTPAA) in the molar ratios of cDTPAA/F(ab')2 of 1:1, 5:1, 10:1 or 50:1. The most optimal product, aimed at radioimaging of prostatic cancer was obtained when the antibody fragment concentration was at least 10 mg/ml and the molar ratio of cDTPAA to F(ab')2 was 5:1. cDTPAA was added dissolved in dimethylsulfoxide (DMSO). Under these conditions, 1.8-2.2 DTPA molecules/F(ab')2 molecule were bound, giving a coupling efficiency of 37%-44%, and the labelling efficiency with 111In (3 mCi/1 mg protein) was 95% +/- 3% (n = 7). The antibody fragment completely retained its immunoreactivity measured by radioimmunoassay and showed no aggregation when studied using sodium dodecyl sulfatepolyacrylamide gel electrophoresis (SDS-PAGE). For evaluation of the degree of conjugation of DTPA to the antibody fragment, a novel technique was developed relying on the use of EuCl3, and the measurement of europium fluorescence employing time resolved fluorometry. Results by EuCl3 labelling were identical to those obtained by the conventional 111InCl3 labelling method.
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PMID:Radiolabelling of monoclonal antibodies: optimization of conjugation of DTPA to F(ab')2-fragments and a novel measurement of the degree of conjugation using Eu(III)-labelling. 246 81

High-dose ketoconazole (400 mg orally three times a day) and physiologic replacement doses of glucocorticoids (hydrocortisone, 20 mg 8 AM, 10 mg 4 PM, and 8 PM) were administered to 38 patients with advanced prostatic cancer, refractory to at least initial testicular androgen deprivation. Thirty patients were completely evaluable; six were withdrawn due to possible ketoconazole-related toxicity and were considered drug failures. Two patients were unevaluable due to intercurrent therapy or inability to maintain follow-up. Ketoconazole was generally well tolerated. Mild or moderate nausea and vomiting occurred in 37% of patients, but required dose modification or discontinuation in only three patients; no hepatic damage was seen. Five of 36 patients (14%) responded to ketoconazole as determined by palpable or radiographic tumor mass reduction of 50% or greater and normalization of acid phosphatase or bone scan. Fifty percent of patients entered were stable at 90 days. Plasma androstenedione and dehydroepiandrosterone sulfate (DHEAS) were reduced markedly in almost all patients. Plasma testosterone (T) levels were low and remained unchanged, while gonadotropins were persistently elevated. Mean plasma ketoconazole content was 6.6 micrograms/mL after 28 days of therapy. While ketoconazole with hydrocortisone does suppress plasma androgens in advanced prostatic cancer patients, this infrequently causes regression of cancer that has progressed despite adequate testicular androgen ablation.
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PMID:High-dose ketoconazole in advanced hormone-refractory prostate cancer: endocrinologic and clinical effects. 247 59

Both prostate specific acid phosphatase (PAP) and prostate specific anti-body (PSA) were used as the specific markers for detecting prostate cancer and its metastasis, and this was considered as the most efficient technique for detecting metastatic lesions associated with an occult carcinoma in the prostate. Altogether 44 cases were studied, including 23 cases of prostatic carcinoma, 3 cases of metastatic tumors and 18 cases of benign hypertrophy of prostate (including 4 cases with local carcinoma). Analysis of 27 cases revealed that PSA seemed more sensitive than PAP, as 17 cases of prostatic carcinoma showed positive reaction with PSA, while among them, only 3 showed negative reaction with PAP. Most of the well differentiated glandular type prostatic carcinoma showed strong positive reaction. However, the poorly differentiated solid carcinoma only showed mild positive reaction. All of the controls as well as bladder and kidney cancers showed negative reaction with either PAP or PSA.
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PMID:[Immunohistochemical detection of prostate carcinoma]. 247 52

A monoclonal antibody with high affinity to acid phosphatase isoenzyme 2 (Ab-AcP2) was selected to examine its binding to different normal and tumor tissues using the indirect immunohistochemical method. Both mature prostatic epithelial cells in the prostate and the highly dedifferentiated prostatic cancer cells in the bone marrow showed strong binding to the antibody. Among nonprostatic tissues, only bone marrow, breast, and kidney showed trace staining in some specimens. The specificity of Ab-AcP2 was much better than that of the polyclonal antibody to acid phospatase previously reported. When the antibody to the prostate-specific antigen (Ab-PSA) was used, weak background staining was often encountered, and weak to moderate stains were seen in the prostatic stroma, bone marrow, lung, skin, and melanoma.
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PMID:Improved immunohistochemical detection of prostatic acid phosphatase by a monoclonal antibody. 247 29

Serum concentrations of prostate-specific antigen (PSA), prostate-specific acid phosphatase (PAP), and transrectal prostatic ultrasound were utilized in the evaluation of 193 men with various urologic disorders. Of the 193 patients, 48 had prostate cancer, and the other 145 included 5 with genitourinary neoplasms, 69 with benign prostatic hypertrophy, and 71 with other non-neoplastic genitourinary disease. PSA levels were elevated in 35 patients with prostate cancer and in 25 of the 145 without prostate cancer. PAP levels were elevated in 15 with prostate cancer and in 2 of the 145 without prostate cancer. The data indicate that PSA is a more sensitive but less specific tumor marker than PAP in the detection of prostate cancer. PSA appears to be more sensitive than PAP in monitoring the response to treatment. The use of PSA and PAP jointly to detect and to monitor prostate cancer did not appear to enhance the clinical utility over that of PSA alone.
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PMID:Relative value of prostate-specific antigen and prostatic acid phosphatase in diagnosis and management of adenocarcinoma of prostate. Ohio State University experience. 247 31

The authors investigated 71 prostatic cancer patients and 45 BPH patients. The serum concentration of prostatic specific antigen (PSA), the prostatic acid phosphatase (PAP) by radio-immunoassay, the same enzyme (SPP) and the total acid phosphatase (SP) by enzymatic method were determined. In the untreated cancer patients the PSA concentration proved to be pathological in a higher proportion in all stage groups comparing to the results of the PAP, SPP, SP. The clearing of the PSA and PAP concentration on the following days and months after the beginning of the therapy reflects the excellent monitoring capability of the PSA determination. This was demonstrated by several cases too. The authors suggest more frequent use of this method in clinical practice.
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PMID:[Experience with prostate-specific antigen in patients with prostatic cancer]. 248 33

Following promising results in animal studies, Casodex (ICI 176,334) has been studied in the treatment of patients with advanced prostate cancer. At doses of 10, 30 and 50 mg, the drug was found to be well tolerated, with a moderate effect on sex hormone levels. The 50 mg dose of Casodex (daily) reduced previously elevated acid phosphatase levels by 50% or more in 71% of patients.
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PMID:Casodex (ICI 176,334), a new, non-steroidal anti-androgen. Early clinical results. 251 47

The European Organization for Research on Treatment of Cancer Genitourinary Group performed a multivariate statistical analysis of prognostic factors based on 436 patients entered between 1976 and 1981 in 2 randomized prospective trials that compared 4 different hormonal treatment regimens. Only previously untreated patients with advanced (stage T3/T4/M0 or M1) prostatic cancer were eligible. After identification of prognostic factors by means of univariate analyses a multivariate analysis using Cox's proportional hazards regression model was done. This test identified performance status (according to the Eastern Cooperative Oncology Group scale) as the most important factor, followed by acid phosphatase (more than 2 times normal) for stage M0 cancer patients, and alkaline phosphatase, T category and the presence or absence of associated chronic disease for stage M1 cancer patients. Based on these 4 variables nonbedridden patients with metastatic disease can be divided into 2 groups: poor and good risk patients, with median survivals of 1 and 3 years, respectively. This study shows that routine clinical and laboratory data already provide an excellent indication as to the prognosis.
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PMID:Multivariate analysis of prognostic factors in patients with advanced prostatic cancer: results from 2 European Organization for Research on Treatment of Cancer trials. 252 61

The chromosomal location of the gene encoding human prostate-specific acid phosphatase (ACPP) was determined by Southern blotting analysis of panels of human x rodent (mouse or Chinese hamster) somatic cell hybrids, using the PAP-1007 and PAP-1004EP ACPP cDNA probes. The ACPP gene was assigned to chromosome 3, which was confirmed by screening a chromosome 3-specific genomic library. Sublocalization of this gene was carried out using hybrids that had retained only various portions of human chromosome 3. The ACPP gene was found to segregate specifically with the chromosomal segment 3q21----qter. Analysis of Southern blots of TaqI-digested DNAs from unrelated individuals and members of large families from northern Finland revealed two simultaneous diallelic restriction fragment length polymorphisms (RFLPs), A and B, when using either PAP-1004EP or PAP-1006A ACPP cDNA probes, but not the 5' flanking PAP-1007 probe. Allele frequencies for polymorphism A were .09 (A1) and .91 (A2), and for polymorphism B, .38 (B1) and .62 (B2). There appears to be only a very minor linkage disequilibrium (chi 2 = 1.12, 0.35 greater than P greater than 0.25) between the two TaqI RFLPs at the ACPP locus. For reasons presently unknown, homozygotes for polymorphism B appear to be overrepresented. These polymorphisms could be of importance in characterizing human prostate cancer.
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PMID:Chromosomal localization to 3q21----qter and two TaqI RFLPs of the human prostate-specific acid phosphatase gene (ACPP). 257 85

The pretreatment bone scans on 40 patients with prostate cancer with bone involvement were reviewed and the prognostic impact of the initial extent of bone metastasis was evaluated. On the bases of the number or extent of bone metastasis, the patients were divided into 2 groups and survival for each group was compared. We also assessed the correlations between the extent on bone metastasis and other pretreatment characteristics: age, symptoms, serum acid phosphatase, serum alkaline phosphatase, and the histological differentiation of primary tumor. At the same time, the prognostic impacts of these pretreatment characteristics were evaluated. The extent of bone metastasis on the scan correlated with survival, but other characteristics did not have a predictive value except for histological grade. Though the histological differentiation of primary tumor was related to survival, the survival rates differed by the initial extent of disease among the same histological grade patients. Thus the extent of bone metastasis was shown to predict survival in metastatic prostate cancer.
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PMID:[Studies on prognosis of prostate cancer with bone metastasis by using pretreatment bone scintigraphy]. 261 Jan 78


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