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)

Several studies have indicated that in prostate cancer, frequent aberrations take place in several genomic regions. In the present study, we have analyzed allelic losses in chromosome 16 region q in 50 prostate cancer specimens of various histological grades. The most frequently deleted region was located at 16q23-16q24.2 between loci D16S504 and D16S422. The highest percentage of loss of heterozygosity (LOH) at 16q was also found within this area at loci HSD17B2 and D16S422 located at 16q24.1-q24.2. The LOH at 16q24.1-q24.2 was significantly associated with clinically aggressive behavior of the disease, metastatic disease, and higher tumor grade. Of the metastatic diseases, 83% showed LOH, whereas only 40% of the nonmetastatic diseases were found to show it. Similarly, LOH was found in 76% of the clinically aggressive diseases and in 33% of the nonaggressive diseases. The data suggest that a potentially important gene associated with prostate cancer progression is located close to 16q24.1-q24.2.
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PMID:Loss of heterozygosity at 16q24.1-q24.2 is significantly associated with metastatic and aggressive behavior of prostate cancer. 926 95

Inactivations of tumor suppressor genes are the most common genetic alterations in prostate adenocarcinoma. Such inactivations are frequently accompanied by loss of portions of the chromosome on which the tumor suppressor gene resides. Loss of portions of both 10p and 10q have been identified in a significant percentage of prostate carcinomas, as well as other malignant neoplasms, and such losses are associated with advanced clinical stage and aggressive behavior in these neoplasms. The PTEN tumor suppressor gene has recently been identified as an important tumor suppressor gene at 10q23. This gene encodes a dual specificity protein phosphatase which interacts with and controls the tyrosine phosphorylation of focal adhesion kinase (FAK), a key regulator of signal transduction via focal adhesions. Such focal adhesions are the site at which integrins cluster following interactions with extracellular matrix ligands and interact with both cytoskeletal proteins and signal transduction molecules to effect key processes such as cell migration, spreading and proliferation. The PTEN gene is inactivated in a significant proportion of prostate carcinomas, particularly metastatic prostate cancers. There is also evidence from studies of loss of heterozygosity that at least one additional tumor suppressor gene for prostate cancer is present on the distal portion of 10q. Similarly, both functional studies and direct analysis of human tumors strongly support the idea that at least one, and possibly two, tumor suppressor genes for prostate cancer are present on 10p. Given that inactivations of tumor suppressor genes on chromosome 10 are associated with advanced clinical stage in prostate cancer these genes are attractive candidates both as prognostic markers and as potential targets for therapeutic intervention.
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PMID:Chromosome 10 alterations in prostate adenocarcinoma (review). 976 64

Natural testosterone and its esters, even when applied in supraphysiological doses, rarely produce side-effects. Via a negative feedback mechanism, exogenous testosterone suppresses the production of lutenizing hormone and follicle stimulating hormone, and leads to reduced testicular sperm production and, consequently, reduced testicular volume. The main concerns for the potential adverse effects of testosterone treatment are the prostate and the cardiovascular system. Androgens play a permissive role in the development of prostate cancer and benign prostate hyperplasia; however, there are no data to indicate that testosterone administration can lead to the progression of pre-clinical or clinical prostate cancer. Whether the effects of testosterone treatment on lipid metabolism are clinically relevant is as yet undetermined. The effects of testosterone on behaviour, especially on aggression, have not been firmly established. Some androgen effects, such as virilization and coarsening of the voice, considered normal in adult men are inappropriate in women and children.
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PMID:Potential adverse effects of long-term testosterone therapy. 1033 71

The cyclin dependent kinase inhibitor p27 binds to and inhibits preferentially S-phase kinases thereby halting cell cycle progression. Loss of p27 expression has been shown to be associated with aggressive behavior in a variety of human epithelial tumors including prostate cancer. In this review, the role of p27 in cell cycle progression as well as its regulation by the ubiquitin-proteasome pathway are discussed. The experimental evidence pointing to the role of p27 as a tumor suppressor gene is outlined. The data generated to date on the prognostic significance of loss of p27 protein expression in human prostate cancers are summarized. Finally, the implications of the changes in p27 expression which occur as a result of androgen ablation in normal and neoplastic prostate are discussed.
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PMID:Role of p27 in prostate carcinogenesis. 1045 77

Prostate cancer has become epidemic, and environmental factors such as cadmium may be partly responsible. This study reports malignant transformation of the nontumorigenic human prostatic epithelial cell line RWPE-1 by in vitro cadmium exposure. The cadmium-transformed cells exhibited a loss of contact inhibition in vitro and rapidly formed highly invasive and occasionally metastatic adenocarcinomas upon inoculation into mice. The transformed cells also showed increased secretion of MMP-2 and MMP-9, a phenomenon observed in human prostate tumors and linked to aggressive behavior. Cadmium-induced malignant transformation of human prostate epithelial cells strongly fortifies the evidence for a potential role of cadmium in prostate cancer.
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PMID:Cadmium-induced malignant transformation of human prostate epithelial cells. 1121 30

Mutation of p53 is rare in localized prostate carcinoma. The oncoprotein MDM2, whose gene has a response element for p53, promotes the degradation of p53 protein and inhibits its transcriptional activation of genes related to cell cycle arrest and apoptosis, constituting a negative feedback control. We studied p53 and MDM2 expression by immunohistochemistry and looked for mutations in p53 exons 5 to 8 by polymerase chain reaction-single strand conformational polymorphism in 118 patients submitted to radical prostatectomy for localized prostate cancer. In 28 cases, we studied cell proliferation by immunohistochemistry, using antibody for Ki-67, and apoptosis by the deoxynucleotidyl transferase mediated dUTP biotin nick end labeling technique. Although no p53 mutations were found, p53 protein was detected in 31.4% of the cases, and these cases had higher Gleason scores (P = .03) and more advanced tumor stages (P = .02). MDM2 was overexpressed in 40.7% of the cases, and these cases had greater tumor volumes (P = .001). Tumors that were positive for both p53 and MDM2 were larger (P = .003) and of more advanced stage (P = .03). Within the 28-case subset, the proliferative index was higher among MDM2-positive tumors (P = .046), and the apoptotic index was lower among p53-positive tumors (P = .01). We conclude that, although p53 mutation is a rare event in prostate carcinogenesis, the detection of p53 protein by immunohistochemistry is common and is associated with decreased apoptosis and increased histologic grade and tumor stage. We also conclude that the overexpression of MDM2 has a role in prostate carcinogenesis, being frequently detected and associated with increased cell proliferation and tumor volume. Finally, we propose that the MDM2-positive/p53-positive phenotype identifies prostate cancers with aggressive behavior.
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PMID:Abnormal expression of MDM2 in prostate carcinoma. 1135 53

Concurrent with the successful life-saving efforts in terms of prostate cancer diagnosis and treatment, some men who do not need treatment are receiving it. These are men destined to die of causes other than prostate cancer. Unfortunately, at diagnosis, men needing treatment for prostate cancer cannot be differentiated from men who do not. To make such decisions correctly for individual patients would require extremely precise measures of the time to death from prostate cancer versus when the patient would die from a competing cause. Predictive tools with this level of accuracy will never be available given the inherent uncertainty of life. At the time of prostate cancer diagnosis, the date and the cause of death for the patient are matters of weak statistical speculation. Unless the date of death from prostate cancer and the date of death from non-prostate cancer causes can be precisely determined for each patient, some men will always be overtreated or undertreated. Conservative strategies result in the undertreatment of some patients who would benefit from treatment while sparing other patients unneeded treatment. Aggressive strategies result in the overtreatment of patients who do not need therapy while curing other men of prostate cancer. Both strategies are correct, but only some of the time. Better methods of determining the length of life and cause of death may improve this situation, but not by much. [figure: see text] Dramatic shifts in the incidence, grade, stage, and age of men with prostate cancer have been observed with the advent of widespread PSA-based cancer detection in the United States. Grade and stage trends suggest that more biologically relevant (the shift from well-differentiated to moderately differentiated tumors) and yet therapeutically amenable (earlier stage) tumors have been identified in large numbers of patients during the PSA era. Clearly many men have been diagnosed and treated who will not benefit from such treatment. The relative mix of these two groups of men is not known. Given the long delay between treatment and mortality that is inherent in prostate cancer (Fig. 14), the full effects of treatment on prostate cancer mortality are probably not yet seen in prostate cancer mortality data.
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PMID:Prostate cancer trends in the era of prostate-specific antigen. An update of incidence, mortality, and clinical factors from the SEER database. 1210 43

Prostate cancer is the most prevalent cancer amongst males and accounts for 13% of cancer deaths in this population in the US. Aggressive, androgen-independent, metastatic prostate cancer is incurable, and the search for new therapies has been directed towards identifying agents that block proliferation and induce differentiation and/or apoptosis of prostate cancer cells. Retinoid receptor agonists, such as all- retinoic acid, can induce apoptosis of prostate cancer cells, but clinical studies have demonstrated only mild to moderate efficacy. Retinoic acid receptor antagonists are a new class of retinoids, and pre-clinical studies have shown that they potently inhibit the growth of prostate cancer cells and induce apoptosis. Here, we review whether retinoids have a role in the fight against prostate cancer.
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PMID:The prospects of retinoids in the treatment of prostate cancer. 1239 61

In recent years, early detection techniques including PSA have resulted in a dramatic increase in the number of patients with localized prostate cancer. The natural history of localized prostate cancer is unusually favorable as compared with many other common cancers. Because of this, the management is controversial. Radical prostatectomy (RP), various techniques of irradiation (RT), endocrine therapy (ET) and watchful waiting (WW) have been utilized, but well designed randomized clinical trials with end results are lacking. Currently, RP is generally accepted as the preferred treatment option for younger patients with lower PSA level. RT has been thought to be somewhat inferior in terms of long-term survival rate compared with RP. Aggressive treatments such as RP and RT are associated with side effects: RP has more urinary and sexual side effects, while RT has more bowel symptoms. For some patients of older age, with well-differentiated tumor and lower PSA level, WW is recommended. WW is devoid of treatment-related side effects, but patients have the risk of progression. Several clinical trials of treatment for localized prostate cancer are being conducted in Western countries. However, these studies will require at least 10 years to accumulate enough study endpoints to form any conclusion. Therefore, it is important for the treatment strategies that we should carry out interventions that are neither excessive nor insufficient for each patient, and take QOL into consideration.
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PMID:[Treatment strategy of localized prostate cancer]. 1255 1

Prostate cancer is the most common life threatening cancer in males in Canada, however, relatively little is known about it etiology. Recent popular interest has focused on the role of diet. Information from a series of 13 analytic studies suggests that risk of the disease is positively related to intake of dietary fat. Furthermore, the relationship between fat consumption and prostate cancers of aggressive behavior appears to be stronger than that seen for all prostate cancers combined. Evidence from studies examining the relationship of beta-carotene and Vitamin A to prostate cancer is ambiguous with some investigations showing a direct association with risk and others showing no association. More recently, several studies have shown an inverse association between tomato products or lycopene consumption and prostate cancer. As well, indirect evidence suggests that consumption of soy based products (such as tofu) contains genistein and other isoflavones which may decrease risk of prostate cancer. Insufficient evidence is available on the relationship of prostate cancer to either lycopene or genistein to make dietary recommendations to prostate cancer patients or the general population. More research is urgently needed on the topic of dietary correlate of prostate cancer.
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PMID:Diet, micronutrients and prostate cancer: a review of the evidence. 1273 30


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