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)

Prostate cancer progression can be predicted in human tumor biopsies by abundant hyaluronan (HA) and its processing enzyme, the hyaluronidase HYAL1. Accumulation of HA is dictated by the balance between expression levels of HA synthases, the enzymes that produce HA polymers, and hyaluronidases, which process polymers to oligosaccharides. Aggressive prostate tumor cells express 20-fold higher levels of the hyaluronan synthase HAS3, but the mechanistic relevance of this correlation has not been determined. We stably overexpressed HAS3 in prostate tumor cells. Adhesion to extracellular matrix and cellular growth kinetics in vitro were significantly reduced. Slow growth in culture was restored either by exogenous addition of hyaluronidase or by stable HYAL1 coexpression. Coexpression did not improve comparably slow growth in mice, however, suggesting that excess hyaluronan production by HAS3 may alter the balance required for induced tumor growth. To address this, we used a tetracycline-inducible HAS3 expression system in which hyaluronan production could be experimentally controlled. Adjusting temporal parameters of hyaluronan production directly affected growth rate of the cells. Relief from growth suppression in vitro but not in vivo by enzymatic removal of HA effectively uncoupled the respective roles of hyaluronan in growth and angiogenesis, suggesting that growth mediation is less critical to establishment of the tumor than early vascular development. Collectively results also imply that HA processing by elevated HYAL1 expression in invasive prostate cancer is a requirement for progression.
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PMID:Inducible hyaluronan production reveals differential effects on prostate tumor cell growth and tumor angiogenesis. 1750 71

Increasingly, the tumor microenvironment and hypoxia are being studied as potential prognostic factors in prostate cancer given their effects on the hypoxia inducible factor-1alpha and vascular endothelial growth factor signaling pathways. Based on immunohistochemical studies using hypoxic cell markers and direct oxygen-electrode measurements, clinically relevant levels of hypoxia are detected in 30-90% of prostate cancers. Exciting new data suggest that hypoxia can alter cell-cycle checkpoints and DNA repair within the prostate epithelium, thereby driving genetic instability and tumor aggression. Novel therapies designed to target the hypoxic response and resulting defective DNA repair may therefore be effective as chemoprevention agents or as adjuncts to surgery, radiotherapy and chemotherapy to improve clinical outcome.
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PMID:Tumor hypoxia, DNA repair and prostate cancer progression: new targets and new therapies. 1754 28

We characterized the redox profiles in two different human prostate carcinoma cell lines (LNCaP vs PC3) that are known to exhibit varying degrees of invasiveness/metastatic ability. We confirmed that PC3 cells were more invasive than LNCaP cells through an in vitro analysis. The present study documented higher 8-hydroxy-2'-deoxyguanosine levels in PC3 cells than in LNCaP cells. The levels of lipid peroxidation were higher in LNCaP cells than in PC3 cells. The reduced glutathione (GSH)/glutathione disulfide (GSSG) ratio increased to a greater extent during cell growth in PC3 cells than in LNCaP cells, whereas both reduced GSH and GSSG levels were higher in the medium of PC3 cells than in that of LNCaP cells. The levels of reactive oxygen (ROS) and reactive nitrogen species (RNS), both intracellularly and in the medium, were higher for LNCaP cells than for PC3 cells during cell growth. In addition, our results demonstrated higher ROS/RNS levels in LNCaP cells than in PC3 cells in S and G(2)/M phases of the cell cycle during logarithmic growth. Each cell type showed distinct cytotoxic responses to low-molecular-weight redox-modulating compounds. Our results document that human prostate cancer cell lines of varying degrees of aggressive behavior have distinct redox properties, findings that could lead to novel therapeutic interventions.
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PMID:Characterization of redox state of two human prostate carcinoma cell lines with different degrees of aggressiveness. 1760 30

Metastases to the thyroid gland are rarely encountered in clinical practice. They may originate from various primary sites, mainly kidney, lung, breast, esophagus and uterus. Prostate cancer is one of the most frequent malignancies in men. It generally has a favorable course, and autopsy series have shown occult prostate cancer in many subjects, especially in aged males. However, prostate cancer sometimes exhibits an aggressive behavior and cases with a poor prognosis have been reported. Occasional reports of metastasis from prostate cancer to the thyroid gland have been documented. We describe the case of a 73-year-old patient presenting with thyroid metastasis from long-standing prostate cancer.
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PMID:Prostate cancer metastasis to thyroid gland. 1767 67

Monoamine oxidase A (MAO-A) expression is associated with high-grade prostate cancer. Immunohistochemistry showed that MAO-A is also expressed in the basal epithelial cells of normal prostate glands. Using cultured primary prostatic epithelial cells as a model, we showed that MAO-A prevents basal epithelial cells from differentiating into secretory cells. Under differentiation-promoting conditions, clorgyline, an irreversible MAO-A inhibitor, induced secretory cell-like morphology and repressed expression of cytokeratin 14, a basal cell marker. More importantly, clorgyline induced mRNA and protein expression of androgen receptor (AR), a hallmark of secretory epithelial cells. In clorgyline-treated cells, androgen induced luciferase activity controlled by the promoter of prostate-specific antigen, an AR target gene, in a dose-dependent manner. This activity was blocked by the AR antagonist Casodex, showing that AR is functional. In turn, androgen decreased MAO-A expression in clorgyline-treated, secretory-like cells. Our results demonstrated that cultured basal epithelial cells have the potential to differentiate into secretory cells, and that inhibition of MAO-A is a key factor in promoting this process. Increased expression of MAO-A in high-grade prostate cancer may be an important contributor to its de-differentiated phenotype, raising the possibility that MAO-A inhibition may restore differentiation and reverse the aggressive behavior of high-grade cancer.
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PMID:Inhibition of monoamine oxidase A promotes secretory differentiation in basal prostatic epithelial cells. 1824 94

Although tobacco use has been recognized as one of the leading causes of cancer morbidity and mortality, a role of smoking in the occurrence of prostate cancer has not been established. However, evidence indicates that factors that influence the incidence of prostate cancer may differ from those that influence progression and fatality from the disease. Thus, we reviewed and summarized results from prospective cohort studies that assessed the relation between smoking and fatal prostate cancer risk, as well as epidemiological and clinical studies that focused on aggressive behavior in prostate cancer, such as poorer survival, advanced stage, or poorer differentiation at diagnosis. The majority of the prospective cohort studies showed that current smoking is associated with a moderate increase of ~30% in fatal prostate cancer risk compared to never/non-smokers. This association is likely to be an underestimate of the effect of smoking because most studies had a single assessment of smoking at baseline and long follow-up times, and the association was considerably stronger in some sub-groups of heaviest smokers, or when smoking was assessed in a relatively short period (within 10 years) prior to cancer mortality. Using aggressive behavior of prostate cancer as outcome, current smoking was associated with significantly elevated risk, ranging from around twofold to threefold or higher. Although alternative explanations, such as publication bias, residual confounding, screening bias, and the influence of smoking-related comorbidities cannot be ruled out entirely, these findings suggest that smoking is associated with aggressive behavior of prostate cancers or with a sub-group of rapidly progressing prostate cancer. Based on evidence presented in this review, cigarette smoking is likely to be a risk factor for prostate cancer progression and should be considered as a relevant exposure in prostate cancer research and prevention of mortality from this cancer.
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PMID:Smoking and aggressive prostate cancer: a review of the epidemiologic evidence. 1956 92

E1AF is associated with malignant aggressiveness via regulation of matrix metalloproteinases (MMPs), which play pivotal roles in invasion through the degradation of extracellular matrix of tissues surrounding tumors. However, the clinical significance of E1AF and MMPs in patients with prostate cancer is not fully understood. We reviewed 50 tissue samples from patients with T2-3N0M0 prostate cancer who had undergone radical operation. Expression levels of E1AF, MMP-1, -3, -7, -9 and -14 were determined semiquantitatively by immunohistochemistry. The mean +/- SD percentage of E1AF-stained cancer cells was 8.56 +/- 5.22, and it was significantly higher (p < 0.001) than the E1AF-immunostaining index of normal cells (1.17 +/- 0.61). E1AF immunostaining index in pT3 (12.74 +/- 4.80) was significantly higher (p < 0.001) than that in pT2 (5.78 +/- 3.31). Although E1AF expression correlated with that of MMP-7 and MMP-9 (r = 0.47, p < 0.001 and r = 0.41, p = 0.004, respectively), multivariate analysis showed that E1AF correlated with only MMP-7 expression (OR = 5.81, 95% CI = 1.27-26.59, p = 0.023). Our results demonstrated that increased expression of E1AF is involved in tumor aggression of prostate cancer. This finding may be influenced by regulation of MMP-7. We speculate that E1AF is a possible target in treatment and prevention of tumor growth in prostate cancer.
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PMID:E1AF expression is associated with extra-prostatic growth and matrix metalloproteinase-7 expression in prostate cancer. 1984 29

Ductal adenocarcinoma of the prostate is an aggressive malignancy, often presenting at an advanced stage. In mixed ductal and acinar adenocarcinomas, the relationship between the proportion of the ductal component of the tumor and the pathologic stage and whether or not aggressive behavior is simply a function of grade remains undetermined. From 268 consecutive radical prostatectomies undertaken as a curative procedure for clinical localized prostate cancer, we identified 34 cases (12.7%) with ductal adenocarcinoma of the prostate comprising 5% to 100% of the total tumor volume. For cases with a ductal adenocarcinoma of the prostate component, the mean age at diagnosis of 60 years (range 49-69 years), mean serum prostate-specific antigen of 8.4 ng/mL (range, 0.8-21 ng/mL) and positive surgical margin rate of 17.6% did not differ significantly from that of the pure adenocarcinoma group. All 34 patients with ductal adenocarcinoma of the prostate had peripheral zone involvement while 16 (46%) also had transition zone involvement. Twenty-five (73%) cases with ductal adenocarcinoma of the prostate had extraprostatic extension (pT3), which compared to 32.9% with acinar adenocarcinoma. The presence of ductal adenocarcinoma of the prostate (P < .0001), high tumor volume (P = .001) and Gleason score >7 (P = .04) significantly predicted pT3 staging category, and the presence of ductal adenocarcinoma of the prostate remained a significant predictor for pT3, after adjusting for tumor volume and Gleason score >7. The proportion of ductal adenocarcinoma of the prostate did not significantly modify the strength of the observed association with pathological stage. In view of the significant association with extraprostatic extension we would recommend that in both core biopsies and radical prostatectomy specimens any proportion of ductal adenocarcinoma of the prostate should be reported.
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PMID:Any proportion of ductal adenocarcinoma in radical prostatectomy specimens predicts extraprostatic extension. 2123 85

Although the incidence is extremely rare in clinical practice, due to its highly aggressive behavior and a similar presentation as prostate cancer, the primary malignant melanoma of the prostate should be given more attention. We report a case in a 29-year-old male who presented with one-month history of dysuria. Based on clinical examination, ultrasound and computed tomography imaging, surgical operation and histopathological studies, a definitive diagnosis was made. Further characteristic images and pathology of this disease are discussed.
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PMID:Primary malignant melanoma of the prostate. 2037 30

Prognostic markers that can distinguish indolent from aggressive prostate cancer could have substantial patient benefit, helping to target patients most in need of radical intervention, while avoiding overtreatment of a highly prevalent condition. The search for novel cancer biomarkers has been facilitated by the development of technologies for "global" biomolecular profiling, used in the sciences of transcriptomics, proteomics and metabolic profiling (metabonomics/metabolomics). Using an NMR-based approach we compared intracellular and extracellular metabolic profiles from the immortalised, non-tumourigenic prostate epithelial cell line, RWPE-1 and two tumourigenic sublines with increasing malignant phenotypes, WPE1-NB14 and WPE1-NB11, generated by N-methyl-N-nitrosourea (MNU) mutagenesis. Collectively, these cell lines present an in vitro model of prostate cancer progression and disease aggression. We observed progressive alterations to intracellular levels of multiple metabolites from choline and branched chain amino acid metabolic pathways from RWPE-1 to WPE1-NB14 to WPE1-NB11 cells. In addition specific perturbations to intracellular glycine and lactate and extracellular lactate and alanine were observed relative to the parent line. The pathways implicated by comparative metabolic profiling in this model are known to be altered in human prostate cancer, and potentially represent a source of biomarkers for prostate cancer aggression.
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PMID:Metabolic signatures of malignant progression in prostate epithelial cells. 2063 96


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