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

The past four decades of epidemiological research have yielded valuable information on the risks of populations to environmental exposures such as tobacco, asbestos, and dietary components. Prevention efforts have been focused on large-scale population-based interventions to minimize exposure to such external carcinogens. While some cancers are beginning to show a decline from changing environmental exposures, hormone-related cancers, such as breast and prostate, are becoming more prevalent. The development of these cancers appears to be closely related to endogenous exposures to circulating steroid hormones. Although prevention trials using antihormone agents are proving successful in some instances, the long-term control of these cancers necessitates a clearer understanding of the metabolism and transport of the relevant hormone in vivo. The revolution in molecular biology has provided powerful genetic tools for evaluating mechanisms of cancer causation as well as the potential to better define individual susceptibility. Using tobacco exposure as an example, we and others have demonstrated that polymorphisms in genes controlling aromatic amine metabolism provide at least a partial explanation for ethnic and individual susceptibility to bladder cancer. Similar studies have examined genetic polymorphisms in the metabolism of tobacco smoke and lung cancer risk, red meat and colorectal cancer, and aflatoxin and liver cancer. Our current studies have pursued a similar paradigm of genetic polymorphism and individual cancer susceptibility in prostate and breast carcinogenesis. We are evaluating polymorphisms in the steroid 5 alpha-reductase type II and androgen receptor genes in relation to prostate cancer based on the evidence that intracellular dihydrotestosterone is the critical "carcinogen." We are pursuing genetic polymorphisms affecting estradiol metabolism, including those in the 17 beta-hydroxysteroid dehydrogenase 2 and estrogen receptor genes as they relate to susceptibility to breast cancer. The potential role of a polymorphism in the cytochrome P450c 17 alpha gene in both breast and prostate cancers is also being examined.
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PMID:Genetic susceptibility to cancer from exogenous and endogenous exposures. 902 93

Soy-based diets, rich in the isoflavones genistein and daidzein, are thought to protect against breast and prostate cancer. We used the N-methyl-N-nitrosourea (MNU)-induced mammary carcinogenesis animal model to test the effectiveness of these two isoflavones as chemopreventive agents. Each isoflavone was injected daily into 35-day-old rats for six months while we monitored the animals' body weight and mammary tumor appearance. Genistein was effective in reducing tumor multiplicity, but it reduced tumor incidence only marginally. Daidzein was less effective in reducing both tumor incidence and multiplicity. To investigate genistein's mechanism of action, we determined the topoisomerase II (topo II) activity and detected the phosphotyrosine-containing peptides in the extracts of mammary tissues isolated from control and isoflavone-treated animals. Mammary tumors contained over 60-fold higher topo II enzymatic activity than the mammary glands. Similarly, more tyrosine phosphopeptides were detectable in mammary tumors than in mammary glands. Tissue samples from genistein treated animals contained similar topo II and protein tyrosine kinase (PTK) activities as the control group. These data suggest that mammary tumorigenesis is accompanied by an extensive increase in topo II and PTK activities. The mechanism of chemoprevention by genistein, however, is independent of topo II or PTK inhibition.
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PMID:Inhibition of N-methyl-N-nitrosourea-induced mammary tumors in rats by the soybean isoflavones. 904 3

This is Part 3 of a three-part review. It deals with the possible role of oncogenes and suppressor genes in human prostate carcinoma as well applications of nontumorigenic and tumorigenic human prostate cell lines described in Parts 1 and 2 [1,2]. Several immortalized and malignant adult human prostatic epithelial cell lines have recently been developed. The three most widely used carcinoma cell lines, DU-145, PC-3, and LNCaP, developed between 1977 and 1980, have greatly contributed to our present understanding of prostate cancer. Before a cell line can be accepted as having prostatic epithelial origin, some basic characteristics must be established. Expression of specific cytokeratins but absence of desmin and factor VIII should be first determined to establish epithelial origin. Responsiveness to androgens and expression of androgen receptor and prostate-specific antigen should be examined under stringent culture conditions to establish prostatic epithelial origin. Response to growth factors and expression of their receptors facilitates further characterization of cell behavior. Cell lines immortalized by human papillomaviruses (HPVs) are of special interest because HPVs are involved in a variety of anogenital cancers and may also play a role in prostate carcinogenesis. Malignant transformation of HPV-18 immortalized cells with the ras oncogene provides cell systems for investigating the multistep process of carcinogenesis. Each cell line has some unique characteristics, whether it arose directly from a carcinoma or resulted from immortalization with simian virus 40 (SV40) or HPV, or was transformed in vitro by oncogenes. Comparisons of these characteristics should facilitate elucidation of the mechanisms involved in initiation, promotion and progression of prostate cancer. These cell lines will further serve as useful models for investigating tumor progression, invasion, metastasis, new therapeutic strategies, drug resistance and its reversal and chemoprevention. This review summarizes some applications of the currently available immortalized, non-tumorigenic as well as the tumorigenic adult human prostatic epithelial cell lines.
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PMID:Immortalized and tumorigenic adult human prostatic epithelial cell lines: characteristics and applications. Part 3. Oncogenes, suppressor genes, and applications. 905 Nov 52

This paper reviews the current advances in molecular genetics and biology of prostate cancer development. Many genetic alterations in prostate cancer have been identified. Some of these changes are early events and occur in prostatic intraepithelial neoplasia and primary cancer of prostate, some others occur in late stages of prostate cancer development. The significant genetic changes for prostate cancer include losses for chromosomes 8p, 5q, 13q, and so forth; gains for chromosomes 8q, 11p, 3q, and so forth; aneusomies of chromosomes 7 and 8; and allelic losses at chromosome regions 8p 12-21, 10q23-24, 16q22.1-24, and 7q31.1-31.2. The alteration of the p53 tumor-suppressor gene plays a role in a subset of advanced prostate cancer. Expressions of TGF-beta receptors, E-cadherin, C-CAM, KAI1, and some integrins have an inverse correlation with either prostatic carcinogenesis or progression of prostate cancer, or both. Protein expression of BCL-2 in prostate cancer is highly correlated with cancer progression and androgen-independent phenotype. More studies need to be performed to identify specific genes for those genetic alterations and to explore the clinical use of the known molecules in prostate cancer.
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PMID:Molecular advances in prostate cancer. 909 May 1

Two variant glutathione S-transferase cDNAs have been described at the GSTP1 locus, which differ by a single base pair (A-G) substitution at nucleotide 313 of the GSTP1 cDNA. This results in an amino acid substitution which alters the function of the enzyme. In this study, a novel PCR assay has been developed which demonstrates that these two variant cDNAs represent distinct GSTP1 alleles (GSTP1a and GSTP1b). In a study of individuals with different forms of cancer, the GSTP1b allele is found to be strongly associated with bladder cancer and testicular cancer. In controls 6.5% of individuals were homozygous for the GSTP1b allele. In bladder cancer cases, this rose to 19.7% [n = 71, odds ratio 3.6 (1.4-9.2), P = 0.006] and in testicular cancer to 18.7% [n = 155, odds ratio 3.3 (1.5-7.7), P = 0.002]. In addition, in prostate cancer a highly significant decrease in the frequency of the GSTP1a homozygotes was observed [control 51.0% versus 27.8% cancer cases, n = 36, odds ratio 0.4 (0.02-3.3), P = 0.008]. Increases in the frequency of GSTP1b homozygotes was also observed in lung cancer and chronic obstructive pulmonary disease. However, these were not statistically significant. No change in breast or colon cancer allele frequencies was observed.
Carcinogenesis 1997 Apr
PMID:Identification of genetic polymorphisms at the glutathione S-transferase Pi locus and association with susceptibility to bladder, testicular and prostate cancer. 911 Nov 93

This review focuses on the possible role of transforming growth factor-beta isoforms 1-3 (TGFbeta) in prostate cancer. TGFbeta1 appears to inhibit the cellular proliferation of normal prostate cells. Surprisingly, TGFbeta1 is overexpressed in prostate cancer. To help explain this apparent paradox, it has been revealed that with tumor progression, prostate cancer cells acquire reduced sensitivity to the growth-inhibitory effects of TGFbeta1. Aberrations of the TGFbeta1 signaling pathway at the prereceptor, receptor, or postreceptor level may lead to prostate cancer cell resistance to TGFbeta1 growth inhibition. Indirectly, elevated levels of TGFbeta1 may induce host effects that may be beneficial to prostate tumor growth by suppressing the immune system, promoting angiogenesis and extracellular matrix formation, and enhancing metastatic potential. Consequently, TGFbeta1 appears to be important in prostate carcinogenesis and tumorigenicity. TGFbeta2 and TGFbeta3 are only briefly presented as very little is known about their role in prostate cancer.
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PMID:Transforming growth factor-beta and prostate cancer. 911 51

Organosulfur compounds are the biologically active components of allium vegetables. Many health benefits have been ascribed to them, including inhibition of carcinogenesis. Inasmuch as several of these thioallyl compounds are quite unstable and others are rapidly inactivated in the body, we have investigated one of the stable components present in aged garlic extract, S-allylmercaptocysteine (SAMC), in an effort to determine whether it can inhibit proliferation of cancer cells. Proliferation and viability of two erythroleukemia cell lines, HEL and OCIM-1, two hormone-responsive breast and prostate cancer cell lines, MCF-7 and CRL-1740, respectively, and normal human umbilical vein endothelial cells in response to different concentrations of SAMC were studied for up to two weeks. There were variations in sensitivity to this organosulfur compound in the different cell lines examined, but the two hormone-responsive cancer cell lines of breast and prostate clearly were far more susceptible to the growth-inhibitory influence of the thioallyl compound. The antiproliferative effect of SAMC was limited to actively growing cells. Human umbilical vein endothelial cells that had reached confluence escaped the reduction in viability so noticeable in the cancer cell lines tested. Our studies thus give evidence of a direct effect of SAMC on established cancer cells.
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PMID:S-allylmercaptocysteine inhibits cell proliferation and reduces the viability of erythroleukemia, breast, and prostate cancer cell lines. 912 48

We have cloned the gene encoding the prostate-specific membrane (PSM) antigen, which is recognized by the 7E11C-5 antibody. The antigen is strongly expressed in prostate cancer, and the antibody has been approved for use as an imaging agent for detection of prostatic cancer metastasis. The gene was unique and encoded a type II membrane protein. The only clue to its potential function was found in the cDNA coding sequences from 1250 to 1700, which had a modest but significant homology with transferrin-receptor, demonstrating a 54% homology of nucleic acid sequence. In comparing the mRNA obtained from normal prostate with that obtained from cancerous or lymph node carcinoma of the prostate (LNCaP) cells, normal cells produced a shorter alternative spliced species that encoded a cytosolic form of the protein, and not a membrane protein. It appeared that, as the prostatic cells became cancerous, there was a nearly 100-fold difference in expression of the ratio of the messages encoding the 2 forms, with the cytosolic form (PSM') predominant in normal cells and the membrane form (PSM) predominant in cancer cells. The other tissue in which the membrane antigen form of PSM is highly expressed is the membrane brush border of the small intestine of the proximal, but not distal, small intestine. This is the location of a unique membrane form of a folate hydrolase. This membrane folate hydrolase and its location are necessary in human nutrition because humans require folate, and the folate in foods is poly-gamma-glutamated. Polyglutamated folates cannot be taken into the cells by folate-transporter systems. The ability to take up folate from foods requires the membrane folate hydrolase to sequentially remove the gamma-linked glutamates, freeing folate that can then be transported. PSM antigen has a similar folate hydrolase activity. Others have reported finding an enzyme in the rat brain that functions as an alpha-neurocarboxypeptidase and acts on the abundant brain peptide N-acetylaspartylglutamate to generate glutamate and N-acetylaspartate. The 3'-end of the rat brain enzyme had 84% sequence homology with PSM antigen. Because this enzyme liberates glutamate in the brain, the enzyme is considered to have regulatory activity related to glutamate receptors. Current investigations are underway to determine whether glutamate receptors are present in prostate. Thus, PSM antigen is a unique folate hydrolase-carboxypeptidase that can release glutamate with either gamma-or alpha-linkage. Its enzymatic activity raises a number of questions for consideration. In the normal prostate where the protein is intracellular, is PSM' antigen keeping folate in nonglutamated forms? If so, folate should be able to readily diffuse out of prostate cells, making the prostate gland an organ at risk for localized folate deficiency and carcinogenesis. In prostate tumor cells, with the enzyme outside of the cell, can PSM antigen be used for the activation of cytotoxic prodrugs?
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PMID:Characterization and glutamyl preferring carboxypeptidase function of prostate specific membrane antigen: a novel folate hydrolase. 912 29

In this study the effects of a Western-style diet on epithelial cell proliferation in the prostate and bladder of C57BL/6J mice were investigated. The Western-style diet contained increased fat and low calcium and vitamin D, compared with AIN-76A control diet, at levels simulating human Western diets based on nutrient density. After feeding the Western-style and AIN-76A diets for 5 and 16 weeks, mice were infused with bromodeoxyuridine (BrdU) for 72 h using s.c. implanted osmotic pumps. Findings revealed that in bladder epithelium BrdU labeling indices were not significantly different (P > 0.05) between mice on the control and Western-style diets at both time periods. However, significant increases in BrdU labeling indices occurred in epithelial cells of the anterior (P = 0.024) and dorsal (P = 0.049) lobes, but not in the ventral lobe (P = 0.21), of the mouse prostate after feeding the Western-style diet for 16 weeks, compared with mice on the control diet. These findings demonstrate Western-style diet induction of epithelial cell hyperproliferation in anterior and dorsal lobes of the mouse prostate. The findings further suggest that these nutrients may have a role in human prostatic carcinogenesis, since the anterior and dorsal lobes of the mouse prostate are homologous with the human prostate in embryological origin and histological structure and carcinomas induced in rodent models have similar characteristics to those found in human prostatic cancer.
Carcinogenesis 1997 May
PMID:Induced hyperproliferation in epithelial cells of mouse prostate by a Western-style diet. 916 86

Prostate tumor initiation and progression to malignancy may involve upregulation of the androgen receptor known to stimulate prostate cell proliferation; other etiologic mechanisms may include dysfunction of the apoptotic pathway but also deregulation in signal transduction and control of the cell cycle in prostate tissue; such abnormalities could arise from overexpression or mutations in a number of oncogenes or down-regulation by inactivating mutations, allelic loss, or other epigenetic mechanisms in tumor suppressor genes. The advantages and drawbacks of various delivery systems (retroviral, adenoviral, liposomes) used for human gene therapy are being considered. Several ex vivo and in vivo as well as cell culture studies are suggested for the therapy of the human prostate cancer using transfer and expression of genes that might be implicated in prostate carcinogenesis especially of the tumor suppressor p53. Expression of suicidal genes in prostate cancer cells using prostate-specific promoter and enhancer elements as well as targeting of the androgen receptor or the insulin-like growth factor genes with triplex technology in prostate cancer cells and their metastases, is expected to be of therapeutic value.
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PMID:Gene therapy of prostate cancer: p53, suicidal genes, and other targets. 917 86


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