Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007112 (prostatic adenocarcinoma)
 2,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

From the original Dunning R-3327 rat prostatic adenocarcinoma, several distinct sublines have been obtained. These sublines include a well-differentiated, slow-growing, androgen-sensitive tumor (R-3327-H); a well-differentiated, slow-growing, androgen-insensitive tumor (R-3327-HI); and a fast-growing, androgen-insensitive, anaplastic tumor (R-3327-AT). These three sublines were compared in order to develop new model methods for the prediction of the androgen sensitivity and the degree of differentiation of prostatic adenocarcinomas. The R-3327-AT was very distinct in all parameters examined except the tissue protein electrophoretic patterns which contained a uniform pattern in all tumors. The significant differences between R-3327-H and -HI sublines were (a) the inability of testosterone to stimulate DNA synthesis in the R-3327-HI tumor and (b) the difference in the enzymatic profiles of these sublines. The specific activity of three enzymes (3 alpha-hydroxysteroid dehydrogenase, leucine aminopeptidase, lactic dehydrogenase) increased while the activity of another three enzymes (6 alpha,7 alpha-hydroxylase, 5 alpha-reductase, alkaline phosphatase) decreased in the sublines which are androgen insensitive and less differentiated. An arbitrary index was constructed, based upon these enzyme differences, which clearly discriminates the degree of androgen sensitivity and differentiation of these R-3327 rat prostatic adenocarcinomas.
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PMID:Models for development of nonreceptor methods for distinguishing androgen-sensitive and -insensitive prostatic tumors. 44 68

Genetic alterations of multiple loci that serve as markers for the induction and progression of disease have been identified in several adenocarcinomas, but not in adenocarcinoma of the prostate. To determine if similar genetic alterations occur in prostate carcinoma and could serve as markers for the extent of clinical disease, we have examined 23 predominantly moderately-differentiated, localized prostate carcinomas and one prostatic dysplasia for changes in the structure and copy number of ten selected genes. These genes include 1) those important to androgen metabolism in the prostate, the androgen receptor and steroid 5 alpha reductase genes; 2) those that map to the 10q (PLAU) and 7q (MET) chromosomal regions found deleted in some prostate carcinomas, and 3) proto-oncogenes (ERBB2, INT2, and MYC) and tumor suppressor gene loci (RB1, TP53 and D17S5) found altered in adenocarcinomas of the breast, colon and lung. Gene alterations were detected in one specimen, a lymph node metastasis from a poorly differentiated tumor. This specimen exhibited loss of heterozygosity for two loci putatively active in tumor suppression, TP53 and D17S5, on the short arm of chromosome 17. This study indicates that gross genetic alterations were not evident and could not be used as markers of tumor development in well- or moderately-differentiated, localized lesions, but that loss of the 17p region may be a useful marker for advanced carcinomas in the prostate.
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PMID:Loss of the 17p chromosomal region in a metastatic carcinoma of the prostate. 155 12

Growth of androgen-dependent human prostatic adenocarcinoma implanted in the nude mouse (Honda tumour), is inhibited by 6-methyleneprogesterone. This steroid is a potent inhibitor of both rat and human prostatic 5 alpha-reductase in-vitro. In-vivo, at the studied dose level, it reduces metabolic conversion of testosterone to dihydrotestosterone with minimal effects upon circulating LH and testosterone. These data support the hypothesis that dihydrotestosterone and not testosterone is the main trophic androgen of the human prostatic neoplasm.
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PMID:A new approach to prostate cancer. 257 Aug 57

Data are presented showing that human prostatic adenocarcinoma depends on dihydrotestosterone (DHT) and not testosterone (T) for growth. It follows that androgen ablative therapy should be directed toward elimination of DHT with retention of circulating T. This can be achieved by using a 5 alpha-reductase inhibitor such as 6-methyleneprogesterone (6-MP) (VII). Arguments are presented showing that 6-MP (VII) is expected 1) to function as a prophylactic agent against prostate cancer, 2) to represent an attractive therapeutic modality for palliative treatment of the hormone-responsive disease, and 3) to be compatible with other therapeutic modalities when very low prostatic levels of DHT should be within reach.
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PMID:The dihydrotestosterone (DHT) hypothesis of prostate cancer and its therapeutic implications. 353 93

The effect of 4-methyl-4-aza-steroidal inhibitors of 5 alpha-reductase has been evaluated on tumor growth in the Noble rat model of prostatic adenocarcinoma. The growth characteristics of the tumor line 2Pr-121D(1) were consistent with heterogeneity of cell types, composed of androgen-sensitive and androgen-insensitive malignant cells. Both sodium 4-methyl-3-oxo-4-aza-5 alpha-pregnane-20 (s)-carboxylate and 17 beta-N,N-diethylcarbamoyl-4-methyl-4-aza-5 and 17 beta-N,N-diethylcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one significantly retarded tumor progression. Each agent increased tumor volume doubling time by approximately 62%. On the basis of their similarities to female rats and male castrate group, in terms of growth rate, tumor doubling time, and histologic characteristics, the treatments with the 4-methyl-4-aza-steroids appeared to produce effects common to both castration and estrogenization (chronic administration of pharmacologic doses of estrogen). The failure of 5 alpha-reductase inhibitors to be active as antiprostatic agents in vivo has hitherto detracted from their use of therapeutic agents. Present studies demonstrate that the 4-methyl-4-aza-steroidal inhibitors of 5 alpha-reductase may represent an alternative to orchiectomy and chronic estrogen therapy for the management of the hormone-dependent phase of prostate cancer.
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PMID:Retardation of prostate tumor progression in the Noble rat by 4-methyl-4-aza-steroidal inhibitors of 5 alpha-reductase. 385 54

Growth of the Dunning R3327-H prostatic adenocarcinoma, implanted in the rat, is inhibited by 6-methylene progesterone. This compound is a potent inhibitor of rat prostatic 5-alpha-reductase and in-vivo produced marked involution of the prostate. Thus the tumor requires dihydrotestosterone and not testosterone for growth.
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PMID:Endocrine dependence of prostatic cancer upon dihydrotestosterone and not upon testosterone. 614 81

This study represents a continuing effort to find a new biomarker for the diagnosis and management of prostatic cancer. Polyclonal antibodies were prepared to a peptide (CAKP) representing amino acids 28 to 43 of the 5 alpha-reductase type 2 isozyme. Using immunoaffinity-purified antibodies, the sera of 62 patients were examined by Western blot following polyacrylamide gel electrophoresis. A positive band was detected in the sera of several patients at 42 kDa compatible with the purified native glycosylated 5 alpha-reductase type 2. These bands were nullified on coincubation of the antibody with the CAKP peptide. Analysis by high-performance liquid chromatography and amino acid sequencing by N-terminal Edman degradation of the immunoaffinity-purified antigen to the antipeptide antibodies of a patient with adenocarcinoma of the prostate suggests that the 5 alpha-reductase type 2 isozyme may be linked to an immunoglobulin. An identical immunoaffinity-purified antigen to the CAKP peptide was isolated from a section of prostatic tissue from a different patient showing benign prostatic hypertrophy with severe dysplasia. It is suggested that an immunological response to the 5 alpha-reductase type 2 isozyme was elicited in both instances.
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PMID:Immunochemical detection of 5 alpha-reductase in human serum. 891 60

The objective of this study was to find a biomarker, easily detectable and measurable, that could be useful to the physician for the diagnosis and management of prostate cancer. An immunoaffinity-purified polyclonal antibody to the 5 alpha-reductase type 2 isozyme was prepared following standard procedures in New Zealand White rabbits. One hundred and seven urine samples were examined for the presence of this isozyme by Western blot, dot blot, and enzyme-linked immunosorbent assay assays. In a control group of 91 subjects (46 females and 45 males) with no history of prostate disease, only 1 female tested positive. In a test group of 16 males, 4 males with adenocarcinoma of the prostate under treatment with lupron/flutamide tested negative. Four males with untreated adenocarcinoma of the prostate tested positive. Two males with transitional cell carcinoma invading the prostatic ducts and two males with basal cell hyperplasia of the prostate with intraductal dysplasia tested positive. These results support the need for an extended study to explore the use of the Western blot or the simple dot blot and enzyme-linked immunosorbent assays for the detection of 5 alpha-reductase type 2 in urine as a potential marker for prostate disease.
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PMID:Preliminary evaluation of 5 alpha-reductase type 2 in urine as a potential marker for prostate disease. 938 16

Although the androgens, testosterone (T) and its highly active metabolite dihydrotestosterone (DHT) play a role in the development and progression of prostate cancer, the mechanism(s) are unclear. Furthermore, 5 alpha-reductase which catalyze the conversion of T to DHT, has been a target of manipulation in the treatment of prostatic cancer, hence synthetic 5 alpha-reductase activity inhibitors have shown therapeutic promise. To demonstrate that nutrients derived from dietary sources can exert similar therapeutic promise, this study was designed using benign hyperplastic cells (BHC) and malignant tumorigenic cells (MTC) derived from Lobund-Wistar (L-W) rat model of prostatic adenocarcinoma to test the effects of gamma-linolenic acid (GLA), eicosapentaenoic acid (EPA) and their 15-lipoxygenase metabolites on cellular 5 alpha-reductase activity. Our data revealed: (i) that incubation of MTC with [3H]-T resulted in marked conversion to [3H]-DHT when compared to similar incubation with BHC; (ii) that DHT-enhanced activity of 5 alpha-reductase was inhibited 80% by 15S-hydroxyeicosatrienoic acid, the 15-lipoxygenase metabolite of GLA, when compared to 55% by 15S-hydroxyeicosapentaenoic acid, the 15-lipoxygenase metabolite of EPA; and (iii) that their precursor fatty acids, respectively, exerted moderate inhibition. Taken together, the study underscores the biological importance of 15-lipoxygenase metabolites of polyunsaturated fatty acids (PUFAs) in androgen metabolism.
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PMID:5 alpha-reductase-catalyzed conversion of testosterone to dihydrotestosterone is increased in prostatic adenocarcinoma cells: suppression by 15-lipoxygenase metabolites of gamma-linolenic and eicosapentaenoic acids. 1258 47

Established risk factors for prostatic adenocarcinoma include increasing age, ethnical origin (race), and familial/hereditary factors. Moreover, the epidemiology of the disease gives some indications that its etiology is probably not only genetic but also environmental. Pathological studies support the fact that geographic differences in incidence and prevalence do not stem from genetic variations as men with the same genetic background raised in different environments present the risk of prostate cancer associated with their country of residency. Prostate cancer is basically an ideal candidate for exogenous preventive measures, such as dietary and pharmacological prevention, due to some specific features: high prevalence, long latency, endocrine dependency, availability of serum markers (prostate-specific antigen) and histological precursor lesions (prostatic intraepithelial neoplasia). Dietary/nutritional factors that may influence disease development include total energy intake (as reflected by body mass index), dietary fat, cooked meat, micronutrients and vitamins (carotenoids, retinoids, vitamins C, D, and E), fruit and vegetable intake, minerals (calcium, selenium), and phytoestrogens (isoflavonoids, flavonoids, lignans). Pharmacological prevention may use drugs that act on intraprostatic testosterone metabolism (finasteride, dutasteride) or induce apoptosis and inhibit tumor growth and metastasis (statins). Since most studies reported to date are case-control analyses, there remain more questions than evidence-based data. However, several large randomized trials are ongoing to clarify the potential for successful prostate cancer prevention. Until we have the results, lifestyle changes could be recommended to men at risk for developing clinical prostate cancer and 5-alpha-reductase inhibitors need to be discussed with men who are concerned about prostate cancer.
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PMID:Prevention of prostate cancer: more questions than data. 1730 90


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