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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This chapter describes the application of the genetic epidemiological approach to the study of human prostate cancer. We review the evidence for the familial clustering of prostate cancer and the Mendelian nature of this aggregation. The nature of this clustering is such that the closer genetically a man is to an affected relative and the greater number of relatives affected in a man's family, the greater his risk of prostate cancer. A complex segregation analysis of the 691 prostate cancer families showed that prostate cancer clustering can be explained by Mendelian inheritance of a rare autosomal gene producing prostate cancer at an early age. A model of inherited prostate cancer in the setting of multistep carcinogenesis is presented. The implications of these data for clinicians who diagnose and treat prostate cancer are also discussed.
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PMID:Familial risk factors for prostate cancer. 184 57

Prostate cancer is the most frequently occurring non-skin cancer in men in the U.S.A. and other Western countries, but its etiology is poorly understood. Human prostate carcinogenesis has been viewed as a multi-step process involving progression from low histologic grade, small latent carcinoma, to large, higher grade, metastasizing carcinoma. However, recent data suggest that a variety of pathogenetic pathways exist. The precise role of hormones in the genesis of human prostate cancer remains largely undefined. It is difficult to investigate stages in the development of human prostate cancer, but some animal models provide opportunities in this regard. Short-term treatment of rats with chemical carcinogens will produce a low incidence (5-15%) of prostate cancer, provided that prostatic cell proliferation is enhanced during carcinogen exposure. A high carcinoma incidence can only be produced by chronic treatment with testosterone following administration of carcinogens such as N-methyl-N-nitrosourea (MNU). Testosterone markedly enhances prostate carcinogenesis even at doses that do not measurably increase circulating testosterone. Thus, testosterone is a strong tumor promoter for the rat prostate. All such MNU-initiated, testosterone-promoted tumors are adenocarcinomas mostly originating from the dorsolateral and anterior, but not ventral, prostate lobes. A high frequency (70%) of activation of the K-ras gene by a G35 to A mutation occurs in these carcinomas. A variable frequency of activation of H-ras and K-ras genes occurs in human prostate carcinomas. Another rat model, representing a different pathogenetic pathway, involves chronic administration of estradiol-17 beta in combination with low-dose testosterone. The resulting carcinomas are low-grade and originate exclusively from periurethral ducts of the dorsolateral and anterior prostate. We recently found a major adduct by 32P postlabeling analysis in the tissue region that includes these ducts, but not in, e.g., the ventral prostate, of rats treated for 16-24 weeks. While it is unknown whether testosterone is a tumor promoter in this system, the presence of a DNA adduct suggests that estradiol-17 beta acts as a tumor-initiating agent in this system.
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PMID:Multistage prostate carcinogenesis: the role of hormones. 184 35

Controversial views exist on the link between prostatic cancer and consumption of high-fat (HF) diet. This topic was examined in experimental prostatic cancer induced in rats by N-nitrosobis(2-oxopropyl)amine (BOP). Groups of Wistar-derived MRC rats were fed a semipurified diet containing either 5% (low fat = LF) or 24.6% (HF) corn oil for life, beginning after weaning. In the short-term study, treatment with testosterone significantly increased the rate of cellular DNA synthesis (as determined by autoradiographs after tritiated thymidine injection) that was not influenced by the level of dietary fat. HF diet alone depressed the rate significantly in the dorsal lobe only. There was a significant increase in the plasma level of estradiol, a decrease in the level of luteinizing hormone, but no changes in the level of follicle-stimulating hormone (FSH) in rats treated with testosterone, with no differences between the HF and LF groups. However, HF in the absence of testosterone depressed the serum FSH level. In the carcinogenicity experiment, all rats fed HF or LF diet developed prostatic cancers (mostly adenocarcinomas). The incidence, however, was significantly higher in testosterone-treated rats. Dietary fat did not influence the incidence, histological patterns, or anatomical distribution of tumors, and there were no differences in the parameters between the HF- and LF-fed groups. Long-term administration of testosterone significantly lowered serum levels of luteinizing hormone but did not change the FSH level and affected estradiol levels to a variable extent. These values were not influenced by dietary fat. However, in the HF-BOP group, significantly higher levels of FSH were found compared with the values in the LF-BOP group. We concluded that (a) under the described experimental conditions, dietary fat, fed ad libitum, does not influence the patterns of prostatic cancer induced in rats by BOP; (b) testosterone alters the serum levels of estradiol and luteinizing hormone; and (c) both testosterone and estradiol could be involved in carcinogenesis.
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PMID:Effects of high-fat diet on the patterns of prostatic cancer induced in rats by N-nitrosobis(2-oxopropyl)amine and testosterone. 190 29

The prevention of cancer by agents in our diet has led to the concept that oxygen radicals are a necessary component of a variety of human cancers including breast, colon and prostatic cancer. These cancers are putatively promoted by estradiol, bile acids and androgens. Epidemiological studies have shown that these cancers are suppressed in vegetarian populations. Vegetable components that may be responsible for this cancer prevention are Vitamin A, retinoids and protease inhibitors (PIs). These agents have been shown to suppress the formation of hydrogen peroxide in promoter-induced neutrophils. They also have been shown to block two-stage carcinogenesis and breast cancer when fed to animals. PIs also suppress experimentally-induced colon cancer and spontaneous liver cancer. Moreover, a new series of cancer-preventive agents, Sarcophytols (isolated by Fujiki and co-workers), are capable of suppressing two-stage carcinogenesis, breast and colon cancers in rodents when given in low concentrations. Sarcophytols were also active suppressors of H2O2 formation of 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced neutrophils. These observations point to an essential role of oxygen radicals in carcinogenesis. Suppression of the oxygen radical response of neutrophils in relation to cancer preventive agents is a facile assay of these important substances. The mechanism of action of oxygen radicals in promoting carcinogenesis is a multiple one, including: (1) activation of oncogenes, (2) modification of DNA bases, and (3) formation of single-strand breaks leading to poly(ADP)ribose polymerase activation.
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PMID:Prevention of cancer by agents that suppress oxygen radical formation. 206 Aug 47

Carcinomas of the rat prostate induced by a single injection of N-methyl-N-nitrosourea, 7,12-dimethylbenz(a)anthracene, and 3,2'-dimethyl-4-aminobiphenyl, after sequential treatment with cyproterone acetate and testosterone propionate, were evaluated as potential animal models for prostatic cancer. All ten carcinomas examined were located in the dorsolateral prostate region and did not involve the distal parts of the seminal vesicles and coagulating glands. The incidence of urinary obstruction leading to the animals' death was 6 of 10 rats, and metastases in the lung, abdominal lymph nodes, and/or liver also occurred in 6 of 10 rats. The tumors were invasive adenocarcinomas, showing frequent perineural invasion and a variable degree of differentiation. There were ultrastructural similarities with human prostatic carcinomas, such as intracellular lumina. Plasma acid phosphatase was increased. Enzyme histochemical analysis revealed similarities with the Dunning R3327H and -HI prostatic carcinomas but was not helpful in determining the site of origin of the tumors. The gross and microscopic appearance of the tumors and the observation of preneoplastic lesions exclusively located in the dorsolateral prostate suggest this lobe as site of origin of the carcinomas. Preneoplastic lesions (n = 9) included atypical hyperplasias (n = 5) and lesions with all histological characteristics of carcinoma except for local invasion and metastases, which were classified as carcinoma in situ (n = 4). Although androgen sensitivity could not be assessed, the observed characteristics of the tumors [their long latency time (46-80 weeks), the presence of preneoplastic lesions, and the short duration of the treatment, leaving the animals intact] all indicate that the present approach is a valid animal model for the study of prostatic carcinogenesis.
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PMID:Characterization of adenocarcinomas of the dorsolateral prostate induced in Wistar rats by N-methyl-N-nitrosourea, 7,12-dimethylbenz(a)anthracene, and 3,2'-dimethyl-4-aminobiphenyl, following sequential treatment with cyproterone acetate and testosterone propionate. 210 61

Histological and flow cytometry (FCM) analyses were performed of carcinogenesis of rat prostate cancer induced with N-Nitroso-N-methylurea (NMU). Ten-week-old rats were inoculated intravenously (i.v.) with twice injections of NMU (30 mg/kg body weight) and then, divided into 3 groups; Group 1: the rats were injected subcutaneously with LH-RH analogue (100 micrograms/kg b.w.) every 4 weeks. Group 2: the rats were injected subcutaneously with testosterone enanthate (10 mg/body) every 2 weeks and Group 3: the rats were untreated to serve as controls. We further divided Groups 1 and 2 into (+) and (-) subgroups at 34 weeks after initial injection. Group 1 (+) or 2 (+) rats were continuously given the drug and in Group 1 (-) or 2 (-) rats the drug was suspended. At 44 or 53 weeks after initial injection, we removed the prostate and seminal vesicles of all rats and performed histological and FCM analyses of them. Histological analysis of rat prostates revealed hyperplasia in each group, and both Groups 2 (+) and 2 (-) showed an incidence as high as 87.5%. Atypical hyperplasia was sometimes observed in each group and its incidence was not significantly different between any 2 groups. At 51 weeks after initial injection, a macroscopic adenocarcinoma (weighing about 11 g) was found in the prostate of a dead rat of Group 2 (+). Histological analysis of rat seminal vesicles revealed hyperplasia in each group, in particular in Groups 2 (+) and 2 (-). In these groups all rats showed hyperplasia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Histological and flow cytometric analyses of carcinogenesis of rat prostate cancer]. 223 32

Based upon a large body of experimental and clinical data, it is evident that multiple malignant events are necessary for a normal cell to give rise to a fully malignant cancer cell. A critical issue with regard to human prostatic carcinogenesis is the clinical significance of the large number of cancers that are present histologically in the elderly male prostate gland. A possibility is that these histological prostate cancers already have undergone all of the malignant events necessary to produce clinically manifest cancer and, thus, only further tumor growth is required to produce a clinical tumor. Alternatively, these histological cancers may have undergone some but not all of the events necessary to produce clinical disease and, therefore, despite host longevity the cancer will remain clinically silent as long as no further malignant changes occur. This issue has importance clinically with respect to the diagnosis, therapy and possible prevention of prostatic cancer. Clinical observations and the mathematical relationship between prostate cancer prevalence and host age (time) support the fact that, in addition to growth, histological prostate cancer requires further malignant events to produce clinical disease. A better understanding of the events involved in prostate cancer development will be necessary to have a greater impact on this disease in the future.
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PMID:Clinical evidence for and implications of the multistep development of prostate cancer. 231 98

In 244 cases treated by subcapsular prostatectomy during the period from April 1975 to December 1985, whole tissue specimens were prepared by a step section technique to examine them histopathologically in accordance with the handling agreement for prostatic cancer presented by the Urologic Society of Japan. The degree of differentiation, clinical stage of the disease, the size of the lesion and the distance to the margin were determined. Incidental carcinoma was found in 35 cases (14.3%), which increased with age. There were 21 cases of stage A1 and 14 cases of A2. Diffuse proliferation was found in 4 cases. Isolated carcinomatous focus was observed in 40 sites, and well, moderately, and poorly differentiated adenocarcinoma in 33, 3 and 4 sites respectively. The maximum diameter of cancer was below 5 mm in 80%, while the distance from the center of the carcinomatous focus to the surgical margin was within 3.5 mm in 905. Seven cases had plural lesions. These lines of evidence mentioned above may support carcinogenesis from the subcapsular region as well as multicentric origin of cancer.
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PMID:[Histopathological analysis of incidental prostatic carcinoma by step section technique]. 232 23

Tumorigenic response in the prostate of F344, ACI, Lewis, CD and Wistar rat strains to 3,2'-dimethyl-4-aminobiphenyl (DMAB) was examined in relation to development of other types of tumors. Rats of each strain aged 6 weeks were divided into two groups receiving DMAB s.c. at a dose of 50 mg/kg body wt once every other week for 10 times, with or without 1 week dietary ethynyl estradiol (EE) pretreatment. The experiment was terminated at week 60, carcinomas of the ventral prostate, all of microscopic size, being respectively found in 50, 17, 21, 15 and 0% of F344, ACI, Lewis, CD and Wistar strain animals treated with EE plus DMAB. The tumor yield correlated well with DMAB-DNA adduct formation. One invasive adenocarcinoma also developed in the periurethral part (occupying both of lateral and dorsal areas) of the prostate. The final survival rates were 46, 24, 65, 4 and 0% in F344, ACI, Lewis, CD and Wistar rats respectively. DMAB administration without EE pretreatment resulted in similar incidences of prostate tumors and mortalities. Tumors arose in greater than 14 different sites with strain dependency, lesions predominating in the skin/subcutis of ACI and F344, preputial gland of F344, urinary bladder of ACI, and mammary glands of CD rats respectively. Consideration of mortality and the relative incidence of prostate cancer and other types of tumors indicates the F344 rat strain to be the most appropriate for investigation of DMAB prostate carcinogenesis.
Carcinogenesis 1990 May
PMID:Different carcinogenic responses in a variety of organs, including the prostate, of five different rat strains given 3,2'-dimethyl-4-aminobiphenyl. 233 7

Presently, there is no effective therapy for increasing survival of metastatic prostatic cancer. New approaches to this major disease are, therefore, urgently needed. One approach is to study the biology of prostatic carcinogenesis in order to develop a therapeutic modality to prevent the development of clinically manifest prostatic cancer. Based upon international epidemiological data, it should be possible to lower the incidence of clinical prostatic cancer by more than 10-fold among the males of the western industrial states. An alternative approach is to study the tumor biology of prostatic cancer in order to identify new modalities to better treat already established clinical prostatic cancer. Such studies have already demonstrated that individual prostatic cancers are composed of clones of cancer cells which are phenotypically heterogeneous even before therapy is initiated. Due to this tumor cell heterogeneity, the direction of future studies should be towards combining androgen ablation plus chemotherapy early in the disease in order to affect both the androgen-dependent and -independent cancer cells present within individual prostatic cancers.
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PMID:[Recent findings on the pathogenesis and therapy of prostatic cancer]. 245 65


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