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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Differential expression of the desired gene product in the target tissue is central to the concept of gene therapy. One approach is to use a tissue-specific promoter to drive therapeutic genes, such as the p53 tumor suppressor gene. To determine the feasibility of tissue-specific gene therapy for prostate cancer using prostate specific antigen (PSA) promoter and/or enhancer, in this study, we developed a tissue specific expression vector using a PSA promoter and enhancer. Our results showed that the cloned PSA promoter actively drives gene expression in the PSA-producing prostate cancer cell line (LNCaP). However, barely any promoter activity was detected in the non-PSA producing prostate cancer cell lines (DU145, PC-3) or the non-prostate cell lines (HEK-293, SAOS-2). The wild-type p53 gene driven by this PSA-promoter efficiently suppressed the growth of LNCaP. Moreover, p53 driven by the PSA enhancer-promoter cassette more efficiently suppressed the growth of the PSA-producing prostate cancer cell line (LNCaP) in vitro. This suggest that we were able to manage the tissue specificity by PSA enhancer and promoter. Additionally, the juxtaposed enhancer-promoter cassette showed great enhancement of p53 expression and apoptosis in vitro. Taken together, these results show that PSA enhancer-promoter may be a potential tool for gene therapy for prostate cancer.
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PMID:Development of a new plasmid vector with PSA-promoter and enhancer expressing tissue-specificity in prostate carcinoma cell lines. 1076 89

Several investigators have reported the correlation of p53 and bcl-2 immunoreactivity with post operative prostate specific antigen (PSA) recurrence. Focal and or clustered expression is typical for these biomarkers. The purpose of this study was to compare the effectiveness of tissue microarrays to detect p53 and bcl-2 overexpression and their prognostic significance. Tissue microarrays (TMA) of 99 patients with mean follow-up of 61 months contained 760 samples from 241 carcinomas, 431 benign glands, and 88 foci of prostatic intraepithelial neoplasia (PIN). Overexpression of p53 was seen in 43.3% of 97 patients, whereas bcl-2 overexpression was noted in 23.7% of 97 patients using TMA technology, compared to 66.0% and 26.9%, respectively in the corresponding radical prostatectomy samples. The tissue microarray technology is a powerful tool to study the multifocal and heterogeneous nature of prostate cancer. However, the prognostic value of p53 and bcl-2 could not be confirmed using this technology in contrast to radical prostatectomy sections. The TMA technique is probably more informative and reliable in evaluating the prognostic value of homogeneously expressed biomarkers.
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PMID:Limitations of tissue microarrays in the evaluation of focal alterations of bcl-2 and p53 in whole mount derived prostate tissues. 1246 73

Prostate carcinomas located in the transition zone are suspected to behave differently from the more frequent peripheral zone cancers. In this study, large transition zone prostate cancers were investigated for pathological and clinical features. From 365 consecutive radical prostatectomy specimens, 73 cases were disclosed with tumours larger than 10 cm(3). Of these, 14 were predominantly (>70% tumour area) located in the transition zone. Pathological investigations included a complete histological work-up, immunohistochemistry for p53 and bcl-2, and interphase cytogenetics for chromosomes 7, 8, 17, and X. Despite large tumour volumes and high preoperative prostate specific antigen (PSA)-values, most tumours showed quite favourable pathological features. Only two of these patients suffered from a postoperative PSA-recurrence during a median follow-up of 50 months. For comparison, 36 cases that contained tumours predominantly located in the peripheral zone mostly displayed adverse prognostic signs and 68.8% of these patients suffered from postoperative PSA-recurrence. We conclude that the peculiar pathological and clinical characteristics of large prostate cancers in the transition zone might be important for prognostic considerations.
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PMID:Pathological and clinical characteristics of large prostate cancers predominantly located in the transition zone. 1262 12

Prostate cancer is the most common cancer diagnosed in American males, and is the second leading cause of cancer-related deaths. Most patients who develop metastatic disease will initially respond to androgen deprivation, but response is invariably temporary. Most patients will develop androgen-independent ("hormone-refractory") disease that results in progressive clinical deterioration and ultimately death. This progression to androgen independence is accompanied by increasingly evident DNA instability and alterations in genes and gene expression, including mutations in p53, over-expression of Bcl2, and mutations in the androgen receptor gene, among others. Treatment options for hormone refractory disease include intensive supportive care, radiotherapy, bisphosphonates, second-line hormonal manipulations, cytotoxic chemotherapy and investigational agents. A post-treatment reduction in the level of prostate specific antigen (PSA) by 50% has been shown to correlate with survival and has been accepted by consensus as a valid endpoint in clinical trials. Chemotherapeutic agents such as mitoxantrone, estramustine, and the taxanes have yielded improved response rates and palliative benefit, but not improved survival. Therefore, current efforts must be focused on enrolling patients onto clinical trials of investigational agents with novel mechanisms of action, and on using survival, time to progression, and quality of life as end points in routine clinical practice.
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PMID:Current strategies in the management of hormone refractory prostate cancer. 1278 12

Prostatic ductal adenocarcinoma represents a rare histological variant of prostatic carcinoma with features of a papillary lesion at cystoscopy. There are conflicts regarding the existence, origin, staging, grading, treatment and clinical behavior of this tumor. The aim of the present study is to examine the expression of Bcl-2 and p53 in prostatic ductal adenocarcinoma and to evaluate its origin by analyzing prostate specific antigen, prostate specific acid phosphatase, cytokeratins, epithelial membrane antigen and carcinoembryonic antigen expressions. The results confirmed the expression of prostate specific antigen and prostate specific acid phosphatase in prostatic ductal adenocarcinoma. The demonstrated expression of Bcl-2 was predominant in the better-differentiated tumor. Bcl-2 expression appears not to be associated with neuroendocrine differentiation as assessed by chromogranin A reactivity. Thus, the first case of a prostatic ductal adenocarcinoma showing Bcl-2 expression is presented. The tumor was negative for p53.
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PMID:Prostatic ductal adenocarcinoma showing Bcl-2 expression. 1537 52

Neuroendocrine (NE) differentiation in prostate cancer is typically detected by immunohistochemistry as single cells in conventional adenocarcinoma. Prostatic NE tumors, such as carcinoid or small cell carcinoma, are rare and large cell NE carcinoma (LCNEC) is described only in case reports. We identified 7 cases of LCNEC and compiled their clinicopathologic characteristics. In 6 cases, there was a history of adenocarcinoma treated with hormone therapy for a mean of 2.4 years (range: 2 to 3 y). The remaining case was de novo LCNEC. LCNEC was incidentally diagnosed in palliative transurethral resection specimens in 5 cases. The mean patient age at diagnosis with LCNEC was 67 years (range: 43 to 81 y). LCNEC comprised solid sheets and ribbons of cells with abundant pale to amphophilic cytoplasm, large nuclei with coarse chromatin and prominent nucleoli along with brisk mitotic activity and foci of necrosis. In 6 cases, there were foci of admixed adenocarcinoma, 4 of which showed hormone therapy effects. LCNEC was strongly positive for CD56, CD57, chromogranin A, synaptophysin, and P504S/alpha methylacyl CoA racemase. There was strong bcl-2 overexpression, expression of MIB1, and p53 in >50% of nuclei, focally positive staining for prostate specific antigen and prostatic acid phosphatase and negative androgen receptor staining. Follow-up was available for 6 patients, all of who died with metastatic disease at mean of 7 months (range: 3 to 12 mo) after platinum-based chemotherapy. LCNEC of prostate is a distinct clinicopathologic entity that typically manifests after long-term hormonal therapy for prostatic adenocarcinoma and likely arises through clonal progression under the selection pressure of therapy.
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PMID:Large cell neuroendocrine carcinoma of prostate: a clinicopathologic summary of 7 cases of a rare manifestation of advanced prostate cancer. 1672 45

Epidemiological studies and clinical trials show that selenium supplementation results in reduction of prostate cancer incidence; however, the form of selenium and mechanisms underlying protection remain largely unknown. Toward this end, we compared the effects of naturally occurring selenomethionine (SM) and Se-methylselenocysteine (MSC) and synthetic 1,4-phenylenebis(methylene)selenocyanate (p-XSC) and p-xylylbis(methylselenide) p-XMS) organoselenium compounds in androgen responsive (AR) LNCaP and its androgen independent clone (AI) LNCaP C4-2 human prostate carcinoma cells on cell growth, secretion of prostate specific antigen (PSA), intracellular redox status and genomic profiles with emphasis on identifying redox sensitive genes. Both p-XSC and p-XMS reduced cell number and total protein concentration compared to control-treated AR and AI cells, while SM and MSC exhibited no effect on growth of AR and AI cells. SM, p-XSC and p-XMS but not MSC inhibited levels of secreted PSA in AR cells. SM, MSC and p-XMS increased glutathione (GSH) levels in AI LNCaP cells. By contrast, in both cell types, only p-XSC significantly decreased GSH concentrations to <50% of control suggesting either an increase in intracellular oxidative stress or a change in GSH/GSSG ratio. On the basis of RT-PCR analysis, SM and p-XSC increased p53 gene expression by 2-fold in AR cells but not in AI cells and only SM enhanced epidermal growth factor receptor in AR cells. Depending on the structure, organoselenium compounds exhibit differential effects on growth, PSA secretion, oxidative stress and selective gene responses in human prostate cancer cells and suggest the potential of developing novel organoselenium compounds as chemopreventive agents in models of human prostate cancer.
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PMID:Differential effects of naturally occurring and synthetic organoselenium compounds on biomarkers in androgen responsive and androgen independent human prostate carcinoma cells. 1720 24

PC-SPES is an eight-herb mixture that has an activity against prostate cancer. Recently, we purified Saw Palmetto (Serenoa repens) from PC-SPES and found that Saw Palmetto induced growth arrest of prostate cancer LNCaP, DU145, and PC3 cells with ED50s of approximately 2.0, 2.6, and 3.3 microl/ml, respectively, as measured by mitochondrial-dependent conversion of the the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Saw Palmetto induced apoptosis of LNCaP cells in a time- and dose-dependent manner as measured by TUNEL assays. Also, Saw Palmetto increased the expression of p21waf1 and p53 protein in LNCaP cells. In addition, we found that Saw Palmetto down-regulated DHT- or IL-6-induced expression of prostate specific antigen in conjunction with down-regulation of the level of androgen receptor in the nucleus as measured by Western blot analysis. Moreover, Saw Palmetto down-regulated the IL-6-induced level of the phosphorylated form of STAT 3 in LNCaP cells. Furthermore, Saw Palmetto inhibited the growth of LNCaP cells present as tumor xenografts in BALB/c nude mice without adverse effect. These results indicate that Saw Palmetto might be useful for the treatment of individuals with prostate cancer.
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PMID:Saw Palmetto induces growth arrest and apoptosis of androgen-dependent prostate cancer LNCaP cells via inactivation of STAT 3 and androgen receptor signaling. 1767 86

Numerous studies have demonstrated the apoptotic index to be significantly higher in benign prostatic lesions than in PIN and adenocarcinoma. Furthermore, a lower apoptotic index in epithelial cell populations has been shown to correlate with decreased immunoreactivity for prostate specific antigen that may be seen in higher Gleason grade tumors. It is suggested that the loss of function of some apoptotic regulators contributes to the development of PIN and prostatic adenocarcinoma. Of these, three signaling molecules involved in apoptotic functions ofTGF-beta have now been intensively investigated, including transmembrane receptor II (T betaRII), cell cycle inhibitor p27(Kp1) and Smad4, effectors of TGF-beta signaling pathway. Increased expression of p53 and decreased expression of maspin, a serine protease inhibitor, also play a major role in the apoptotic process. Changes in the expression of these markers may serve as a reliable criterion on making the diagnosis in biopsy material and may help choose an appropriate therapeutic approach.
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PMID:[Apoptosis in pathologic prostatic processes]. 1999 47

The balance between proliferation and apoptosis is represented by changes in the expression of the tissue markers, Bcl-2 and p53, and the presence of silver-stained nucleolar organizing regions (AgNOR) on DNA in prostate adenocarcinomas. Identifying a mathematical model that would take into account the opposing nature of both processes and relate this to cancer stage and grade would be a useful adjunct for studying disease behaviour. This retrospective study investigated tissue marker expression in prostate adenocarcinoma biopsy samples from 17 patients. Staining for p53 was inversely correlated with patient age. Staining for Bcl-2 correlated with the presence of advanced metastatic cancer and American Joint Committee on Cancer (AJCC) disease stage. A mathematical model was developed which combined coded staining intensity data for Bcl-2 and AgNOR, as markers of proliferation, and for p53, as a marker of apoptotis. The mathematical model significantly correlated with Gleason score, AJCC stage and serum prostate specific antigen level, whereas each tissue marker alone did not correlate with all these measures.
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PMID:p53, Bcl-2 and AgNOR tissue markers: model approach in predicting prostate cancer characteristics. 2014 85


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