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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epidemiological studies have shown an association between a high-fat diet and a high mortality rate from breast, colon, and prostate cancer. However, the promotional effect of a high-fat diet on experimental carcinogenesis has not been fully established for the prostate. In this study, the effect on prostatic carcinogenesis of two-generation exposure to a high-fat diet was investigated using ACI/Seg rats, a strain with high incidence of spontaneous prostate cancer. A high-fat diet (20% corn oil) or a low-fat diet (5% corn oil) was given to mother rats during pregnancy and the newborn male rats were fed the same diets for 60 or 100 weeks after weaning. At 100 weeks, atypical hyperplasia and adenocarcinoma of the prostate were respectively found in 73.3% (11/15) and 20.0% (3/15) of the high-fat diet group and in 20.0% (3/15) and 0% (0/15) of the low-fat diet group. There was a significant increase of atypical hyperplasia in the high-fat diet group (P < 0.05). The serum concentrations of sex hormones and the prostatic proliferative activity as measured by flow cytometry or bromodeoxyuridine labeling were not significantly affected by diet. These results showed that feeding a high-fat diet before conception and from the beginning of organogenesis had a marked promotional effect on the early stage of prostate carcinogenesis in rats.
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PMID:Promotional effect of two-generation exposure to a high-fat diet on prostate carcinogenesis in ACI/Seg rats. 752 54

Instability of dinucleotide tandem repeat sequences has been reported to play a major role in the carcinogenic pathway of familial colon cancer, as well as a potential role in the carcinogenesis of other sporadic neoplasms. To determine the frequency of short tandem repeat instability in adenocarcinoma of the prostate, we studied 40 tumors that were stratified according to tumor grade. The tissue samples were screened with di-, tri- and tetranucleotide markers spanning a wide range of chromosomal loci, including an androgen receptor gene trinucleotide repeat. Microsatellite instability was observed overall in only one of the 40 (2.5%) prostate adenocarcinomas studied. This replication error-positive tumor demonstrated repeat length alterations at two loci. Five other tumors showed an alteration in microsatellite size at a single locus. These tumors were not considered to have the microsatellite instability phenotype. All changes were identified either within tetranucleotide sequences or within the androgen receptor gene repeat (4 or 20 total markers analyzed). Both repeat length expansions and contractions were identified. The replication error-positive case also included separate metastatic nodal tissue. Additional microsatellite analysis of the metastatic tumor tissue revealed allelic patterns identical with the normal tissue control. Our data indicate that microsatellite instability is rare in prostate adenocarcinoma. Therefore, observation of this low replication error frequency suggests that most prostate carcinomas develop in the absence of widespread accumulation of somatic mutations in short tandem repeat sequences. Additionally, these genetic alterations appear to occur more often in tetranucleotide repeat sequences as well as in an androgen receptor gene trinucleotide repeat.
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PMID:Microsatellite instability in adenocarcinoma of the prostate. 767 91

Neuroendocrine cells are thought to have a regulatory role in prostatic epithelial growth and may be prognostically useful in prostatic adenocarcinoma. To determine the extent of neuroendocrine differentiation in high-grade prostatic intraepithelial neoplasia (PIN), a putative precursor of cancer, we studied the immunohistochemical expression of 10 markers in 26 radical prostatectomy specimens with PIN and adenocarcinoma. Expression was measured as mean percent of positive cases and positive high-power (x40) fields. The highest percentage of cases showed immunoreactivity for serotonin (73%, PIN; 54%, carcinoma), neuron-specific enolase (NSE) (67%, PIN; 46%, carcinoma), chromogranin (62%, PIN; 65%, carcinoma), and human chorionic gonadotropin (hCG) (30%, PIN; 22%, carcinoma); the remaining markers showed immunoreactivity in fewer than 5% of cases (somatostatin, calcitonin, corticotropin) or in no cases (thyrotropin, prolactin, and glucagon). At least one of the markers was present in 88% of cases of PIN and 92% of carcinoma. Non-neoplastic epithelial cells expressed serotonin, NSE, chromogranin, and hCG in every case, and the expression was significantly greater than in PIN and cancer. Stepwise regression analysis revealed the following positive correlations: chromogranin expression in PIN and patient age, NSE expression in cancer and number of lymph node metastases, and hCG expression in cancer and percentage of Gleason pattern 5; serotonin expression in PIN and cancer did not correlate with any of the clinical and pathologic factors. Neuroendocrine differentiation is downregulated in prostatic carcinogenesis, with intermediate levels of expression in PIN compared with normal cells and carcinoma.
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PMID:Neuroendocrine differentiation in prostatic intraepithelial neoplasia and adenocarcinoma. 797 47

High-grade PIN is the most likely precursor of prostatic adenocarcinoma, according to virtually all available evidence to date. The clinical importance of recognizing PIN is based on its strong association with prostatic carcinoma. PIN has a high predictive value as a marker for adenocarcinoma. Its identification in biopsy specimens of the prostate warrants further search for concurrent invasive carcinoma. PIN is associated with progressive abnormalities of phenotype and genotype intermediate between normal prostatic epithelium and cancer, indicating impairment of cell differentiation and regulatory control with advancing stages of prostatic carcinogenesis. There is progressive gain or loss of a wide variety of biomarkers, including morphometric markers, differentiation markers, stromal markers, growth factors and associated receptors, oncogenes, tumor suppressor genes, and chromosomes. Abnormalities in expression of most biomarkers are amplified in the progression from high-grade PIN to localized cancer, metastatic cancer, and hormone-refractory cancer. Oncogenesis of prostatic carcinoma probably occurs through the selection of several genetic changes, each modifying the expression or function of genes controlling cell growth and differentiation. Further studies are needed to evaluate the function and prognostic value of oncogene expression in the normal, preneoplastic, and neoplastic prostate.
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PMID:Molecular biology of prostatic intraepithelial neoplasia. 870 Aug 1

The Dunning H rat prostate tumor (R3327H) is a widely used experimental model of human prostatic adenocarcinoma (CaP). The Dunning H tumor has been characterized as androgen-sensitive, androgen-receptor (AR) positive, prostate-specific antigen and prostatic acid phosphatase (PAP) positive. To date, the tumor has been maintained by serial passage in vivo because of the lack of an in vitro cell line that retains the characteristics of the in vivo tumor. The objective of the present study was to establish a propagable cell line from R3327H adenocarcinoma that maintained androgen sensitivity and expression of AR, PSA and PAP. Tissue harvested from an in vivo R3327H tumor was dissociated with collagenase and placed into Richter's improved media (with supplements). A cytokeratin-positive epithelial cell line (HUNC-E) and a vimentin-positive stromal cell line (HUNC-S) were generated from the primary culture, subcultured continuously for >300 days, and passaged >50 times. Survival of the HUNC-E cell line in vitro depended on several media supplements, including nicotinamide, insulin, transferrin, selenium and epidermal growth factor (EGF). HUNC-E cells expressed AR and produced PSA and PAP throughout the culture period, as confirmed by immunocytochemistry and Western blot analyses. Addition of 14 nM testosterone (T) or dihydrotestosterone (DHT) to HUNC-E cells, stimulated DNA synthesis as well as anchorage-independent growth and PSA production, which demonstrated the androgen-sensitive nature of the cells in vitro. When HUNC-E and HUNC-S cells were combined in a 3:1 ratio and introduced subcutaneously into syngeneic male hosts, tumors formed in 2/3 animals with an average latency of 7 months. RT-PCR and immunocytochemical characterization of the HUNC cell lines revealed that the cells expressed several growth factors and their cognate receptors, including HGF, TGF-alpha and the TGF-betas, indicating the establishment of potential autocrine loops in the neoplastic cells. The HUNC-E and HUNC-S CaP cell lines, which retain the characteristics of the epithelial and stromal components of the in vivo R3327H tumor, will allow a more thorough and informative molecular and biological analysis of prostatic adenocarcinoma.
Carcinogenesis 1998 Apr
PMID:Isolation and characterization of propagable cell lines (HUNC) from the androgen-sensitive Dunning R3327H rat prostatic adenocarcinoma. 960 Mar 41

Although adenocarcinoma of the prostate is recently becoming one of most common malignancies in Japanese men, it still poses many questions regarding its etiology, pathology, pathogenesis and clinical management. Many reports have been made on oncogene and tumor suppressor gene, however, frequent genetic alterations have not been identified during prostate cancer development. Loss of heterozygosity (LOH) on 8p might be an important event in the early stage of prostatic carcinogenesis, whereas alteration in 17p is now considered a late event. Numerous reports about the androgen receptor (AR) gene have revealed that mutations in the coding region of AR possibly results in an acquired resistance to androgen blockade therapy and anti-androgen withdrawal syndrome. It has been also shown that shorter CAG repeats of AR gene are associated with a higher risk of prostate cancer. Regarding molecular diagnosis, prostate-specific membrane antigen (PSM) appears to be a new molecule with many potentially valuable applications. PSM-reverse transcriptase-polymerase chain reaction (RT-PCR) is probably more sensitive and specific than PSA-RT-PCR to predict micrometastatic disease. Gene therapy based on the above molecular aspect is currently under investigation but not generally used yet.
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PMID:[Molecular biological aspect]. 961 16

In previous studies we demonstrated that the growth of human prostatic adenocarcinoma is associated with aberrant accumulation of transforming growth factor (TGF) beta1, a growth factor that has been shown to be a potent inhibitor of epithelial cell proliferation. We investigated the expression of TGF-beta receptor II (TGFbetaR-II) in benign prostate tissue and in prostate cancer using standard immunohistochemical techniques. Quantitation of immunopositivity for TGFbetaR-II was assessed on a visual analogue scale ranging from 0 (absence of staining) to 4+ (intensely positive staining). All of the benign glandular epithelia stained intensely, either 3+ or 4+, representative of the ubiquitous nature of TGFbetaR-II in normal tissue. Overall, staining was reduced in prostate cancer sections, and there was progressively diminished staining as the histological grade of the cancer increased (P < 0.01, Kruskal-Wallis test). This immunohistochemical study indicates that a decline in the levels of TGFbetaR-II is correlated with advancing histological aggressiveness of the cancer and suggests that aberrant TGFbetaR-II function may play a role in human prostate carcinogenesis.
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PMID:Reduced levels of transforming growth factor beta receptor type II in human prostate cancer: an immunohistochemical study. 981 13

Hepatocyte growth factor (HGF) and c-met proto-oncogene product (c-Met) have varied biological functions in different tissues and have been implicated in mitogenic, motogenic and morphogenic responses in both organ regeneration and carcinogenesis. Some studies have suggested that the overexpression of c-Met and epidermal growth factor receptor (EGFR) are associated with growth advantage, while transforming growth factor-beta receptor II (TGF beta R II) is associated with growth disadvantage of human prostatic adenocarcinoma. However, it is unclear if the expression of c-Met correlates with the expression of EGFR and TGF beta R II, and with the proliferative status of human prostatic adenocarcinoma. Using immunohistochemical staining with anti-c-Met (C-12), anti-EGFR (NCL-EGFR) and anti-TGF beta R II (L-21) antibodies, we determined the frequency of expression of c-MET, EGFR, and TGF beta R II respectively in a series of 134 radical prostatectomy specimens. We evaluated the relationship between the expression of these receptors and clinicopathological characteristics. Overall, c-Met immunostaining was detected in 54 of 134 (40.3%) cases, EGFR in 45 (33.6%) and TGF beta R II in 64 (48.4%). The overexpression of c-Met was significantly more common in poorly differentiated (P < 0.0001) and in the diffusely infiltrated specimens (P < 0.0005). In contrast, TGF beta R II was significantly overexpressed in the well differentiated specimens (P < 0.0001) and associated negatively with c-Met (P < 0.0001). Overall, these data suggest that c-Met/HGF receptor and TGF beta R II overexpression may be involved in the differentiation of human prostatic adenocarcinoma, c-Met with de-differentiation and TGF beta R II with differentiation.
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PMID:Overexpression of c-Met/hepatocyte growth factor receptors in human prostatic adenocarcinoma. 987 67

Allelic variations at the NQO1 locus encoding for NAD(P)H:quinone oxidoreductase have recently been implicated in carcinogenesis, cancer chemoprevention and chemotherapy. Two naturally occurring alleles differ at nucleotide position 609 with the variant allele leading to diminished or absent enzyme activity. Using polymerase chain reaction-restriction fragment length polymorphic analysis, NQO1 genotyping was performed in DNA from blood cells from 54 patients with prostatic adenocarcinoma, 49 patients with benign prostatic hyperplasia and 100 healthy control subjects. Prostatic adenocarcinoma patients and healthy controls demonstrated almost identical genotype distribution and frequencies of the variant allele (17.6 versus 17.5%). The variant allele was slightly more frequent in benign prostatic hyperplasia patients (23.5%). Established prostate cancer-derived cell lines LnCAP, DU-145, and PC-3 demonstrated NQO1 wild-type genotype. Our study does not support the hypothesis that the variant NQO1 allele is a risk modifier for prostatic adenocarcinoma and/or benign prostatic hyperplasia in the Caucasian population.
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PMID:609 C --> T polymorphism in NAD(P)H:quinone oxidoreductase gene in patients with prostatic adenocarcinoma or benign prostatic hyperplasia. 1007 23

We investigated the changes in serum and tissue zinc levels in the Noble rat prostate gland under different pathological conditions induced by the administration of a combination of testosterone and 17beta-estradiol. The results showed that there were significant differences in serum zinc values between normal and hormone-treated rats with prostatic hyperplasia, dysplasia and prostatic carcinoma (p < 0.05), although there was no significant difference among rats with different forms of prostatic lesions (i.e. hyperplasia, dysplasia and prostatic adenocarcinoma). There was also a difference in zinc content between the lateral prostate (LP), ventral prostate (VP) and dorsal prostate (DP) in normal rats. The zinc levels of LP were several times greater than those of either VP or DP (p < 0.01). There was also a great difference in zinc levels between the normal and the hyperplastic/dysplastic and carcinomatous LP and VP (p < 0. 05). The levels of zinc in both LP and VP were increased in hyperplasia/dysplasia and carcinoma. On the other hand, the zinc levels of LP were much higher than those of VP in hyperplasia/dysplasia and carcinoma (p < 0.01), which may be correlated with the incidence of prostate cancers in these lobes (i. e. higher in LP and much lower in VP). In contrast, in DP, the levels of zinc were not affected, which may be correlated with the very low incidence of carcinoma in this lobe. Our data suggest that the difference in zinc levels among these lobes reflect the heterogeneity in zinc content in various lobes of the rat prostate. The growth and development of prostatic lesions in LP and VP may be positively correlated with the significant increase in tissue zinc levels in these lobes. On the other hand, the lack of response of DP to carcinogenesis may be due to its relatively stable low zinc levels. It is suggested that tissue zinc content may be used as a marker for prostatic lesions, including hyperplasia, dysplasia and carcinoma, while serum zinc levels may be a useful indicator for abnormal prostatic growth.
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PMID:Changes in serum and tissue zinc levels in sex hormone-induced prostatic carcinogenesis in the noble rat. 1100 73


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