UMLS:C0376358 - FACTA Search

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

Argyrophilic nucleolar organizer regions (AgNOR) of 79 prostatic adenocarcinomas, and an immunohistochemical stain using a monoclonal antibody against proliferating cell nuclear antigen (PCNA) of 54 prostatic adenocarcinomas, obtained by needle biopsy and transurethral resection of the prostate between 1986 and 1989, were investigated. A morphological classification was devised to count silver dots based on the relations between intra- and extra-nucleolar AgNOR (type A, B, C and D). Total AgNOR counts were significantly higher in carcinoma (4.2 +/- 1.57) than in the benign prostatic lesions (1.90 +/- 0.24). Count differences of AgNOR were evident in histological differentiation, nuclear anaplasia, and presence of nucleoli, mitosis, lymphatic invasion and vascular invasion. Higher total AgNOR counts were almost always associated with type B and C AgNOR (intranucleolar AgNOR), but were not associated with type A (nucleolus without small dot) nor type D (extra-nucleolar AgNOR). This study shows the diagnostic value of AgNOR in prostatic cancer, and the importance of morphological classification of AgNOR. The survival of patients with higher AgNOR counts (> or = 4.3) was significantly poorer than survival of those with lower AgNOR counts (< 4.3). Significantly more PCNA positive cells were identified in cancer by immunohistochemical stain and correlated with the presence of mitosis, but there was no significant difference in survival rate groups classified by PCNA positivity. It is also suggested that PCNA can be a useful marker of cell proliferation in prostatic lesions, but the AgNOR counts were diagnostically and prognostically more valuable than immunohistochemical PCNA in prostatic lesions. The correlation between AgNOR and PCNA immunoreactivity was not significant.
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PMID:Nucleolar organizer regions and PCNA expression in prostatic cancers. 751 63

One hundred and twenty-four localized prostate cancer patients operated on at Johns Hopkins Hospital (JHH) since 1975 were identified. The sample was optimized for evaluation of prostate cancer progression. Based upon accurate clinical histories, these radical prostatectomy patients included 50 progressors and 74 non-progressors using appearance of serum PSA as an indication of recurrence (mean follow-up = 8.6 +/- 1.8 years, range 7-15 years). All patients included in the study had no involvement of their seminal vesicles or lymph nodes at the time of prostatectomy. Average time to progression was 3.6 +/- 2 years, range of 1-8 years. Using paraffin-embedded specimens, several five micron sections were cut and placed on Probe-On slides; one slide was H&E-stained and the other was Feulgen-stained. The H&E and Feulgen-stained slides were screened and "dotted" by pathologists at JHH and CytoDynostics, Inc. A CAS-200 Image analysis system (Cell Image Systems, Elmhurst, IL) equipped with a Cell Measurement Program version 1.2 beta, was used to capture the Feulgen-stained images and to perform the calculations. From the "dotted" areas, 150 cancer cells were selected for measurement of DNA content and 27 nuclear morphometric shape and size factors, including 21 Markovian chromatin texture variables. Additional sections were used for immunochemistry staining with an alkaline phosphatase streptavidin-biotin complex stain to detect and quantitate cancer cells binding monoclonal antibodies directed against proliferating cell nuclear antigen (PCNA) and HER-2/neu antigen. All data were entered into a statistical program (STATA) for further analysis and univariate and multivariate statistical analysis was performed using logistic regression and its stepwise variant. The biomarkers of greatest utility to detect progressors when analyzed univariately included post-operative Gleason score (p = < 0.0001), HER-2/neu antigenicity (p = 0.0147), CAS-200 DNA ploidy (p = 0.008), and twelve Markovian nuclear texture and shape features (p = < 0.0001), whereas PCNA (p = 0.160) failed. The optimal set of nuclear morphometry progression tumor features were selected using backward stepwise logistic regression estimate analysis which drops variables due to collinearity. Although post-operative Gleason score is a strong univariate predictor of progression, DNA ploidy and HER-2/neu contributed significantly to further stratification of higher risk groups within the low Gleason score subpopulation. The best Markovian features combined with post-operative Gleason score generated sensitivity = 90%, specificity = 96%, positive predictive value = 94%, negative predictive value = 93% and the area under the receiver operator curve was 0.975.
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PMID:Quantitative nuclear morphometry, Markovian texture descriptors, and DNA content captured on a CAS-200 Image analysis system, combined with PCNA and HER-2/neu immunohistochemistry for prediction of prostate cancer progression. 752 56

Surrogate endpoint biomarkers (SEBs) are needed in clinical chemoprevention trials to avoid the excessively long study periods and high costs associated with the use of cancer incidence reduction as an endpoint, particularly with relatively slow-growing tumors such as prostatic adenocarcinoma. SEBs should be directly associated with the evolution of neoplasia, and develop with high frequency in abnormal cells of susceptible individuals. If SEBs can be modified by a particular intervention regimen in short-term studies, the rationale for carrying out long-term studies may be strengthened. The consensus panel identified a small and manageable group of biomarkers measured in tissue or serum as the most promising in prostate cancer chemoprevention, including (1) prostate specific antigen (PSA); (2) morphometric markers, such as nuclear size and roundness; (3) proliferation markers, such as MIB-1 and PCNA; (4) nuclear DNA content (ploidy); (5) oncogene c-erbB-2 (HER-2/neu) expression; (6) angiogenesis; and (7) high-grade prostatic intraepithelial neoplasia (PIN). Information regarding many of these and other biomarkers is limited, calling for further investigation. Also, these factors, chosen chiefly for their proven or proposed utility as prognostic factors, may be less useful as SEBs. It was agreed that concurrent study of numerous markers rather than single markers allows comparison of their relative utility, including assessment of ease of quantitation and the sensitivity, specificity, and positive and negative predictive value.
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PMID:The most promising surrogate endpoint biomarkers for screening candidate chemopreventive compounds for prostatic adenocarcinoma in short-term phase II clinical trials. 752 57

The positive effect of castration in prostatic cancer patients is considered to be related to the induction of apoptosis in androgen-dependent tumour cells. However, castration apparently does not induce apoptosis in the highly differentiated, androgen-sensitive Dunning R3327PAP rat prostatic adenocarcinoma. To elucidate potential mechanisms of apoptotic induction in this tumour model, rats with subcutaneously implanted tumours were treated with vehicle (I), castration+vehicle (C) or castration + 50 micrograms of oestradiol benzoate per day s.c. (C + E2). The effects on tumours were examined by morphometry, in situ end labelling (ISEL) of apoptotic cells and immunohistochemically with monoclonal antibodies to proliferating cell nuclear antigen (PCNA) at different time points up to 168 h after castration. Castration inhibited tumour growth and decreased the epithelial cell apoptotic rate (from 12 h) and epithelial cell proliferation rate (from 72 h) compared with that in the I group. Tumour volume, volume densities of epithelium and stroma and stroma cell proliferation rate remained constant in the C group during the study period. C + E2 treatment resulted in increases in cell proliferation in the stroma (from 12 h) and in the volume density of stroma (from 24 h) compared with that in the C and I groups. The number of apoptotic epithelial cells was increased (from 24 h), and this was followed by decreases in the volume density of epithelium (from 24 h), the epithelial cell proliferation rate (from 72 h) and the total tumour volume (from 72 h). We conclude that in the Dunning R3327PAP tumour model C + E2 treatment is more effective than castration alone. C+E2 treatment, in contrast to C, is able to induce tumour cell death and to decrease total tumour volume. The mechanism behind this effect is unknown, but it could be related to stimulatory effects of E2 in the tumour stroma.
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PMID:Castration plus oestrogen treatment induces but castration alone suppresses epithelial cell apoptosis in an androgen-sensitive rat prostatic adenocarcinoma. 759 43

The increasing availability of means for the early detection of prostatic cancer has brought under scrutiny the criteria used for prognosis and emphasized our limitations in understanding what determines the rate of progression in these cancers. The rate of cancer cell proliferation has been under intense investigation, which, however, has yielded conflicting results. In this study we evaluated the proliferative activity of benign and neoplastic prostatic epithelium, using various existing methodologies. We first analysed the variability introduced by the methodological approach and then attempted to demonstrate whether determination of the proliferative capacity had any clinical consequence that complemented the histological grading. Tissue samples from patients, 88 with cancer and 46 with benign prostatic pathology, were studied using in vitro bromodeoxyuridine (BrdU) incorporation as well as Ki67 and the proliferating cell nuclear antigen (PCNA) to estimate the proliferative activity. Increased proliferation was found consistently in inflammation and metaplasia, but not in hyperplasia. In contrast, cancers showed marked variability. Although average proliferation indices increased with grade, there was a wide scatter of values. Correlation was stronger with stage, but also depended on the methodology. Bromodeoxyuridine indices over 10 per mile had a positive predictive value of 79 per cent for cancers extending beyond the prostatic capsule and may prove particularly helpful for evaluating patients with grade 7 cancer. This observation is significant, since grade 7 cancers are the most frequent and the least predictable.
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PMID:Proliferative activity in benign and neoplastic prostatic epithelium. 782 53

Tissue specimens from 12 patients with adenocarcinoma of the prostate and 7 patients with benign prostate hypertrophy were stained by an indirect immunoperoxidase method using antiproliferating cell nuclear antigen (PCNA) monoclonal antibody. The PCNA labeling index was determined by counting the number of PCNA-labeled cells in the tissue sections. Average PCNA labeling index of the benign prostate hypertrophy was 1.2 +/- 0.5%. Poorly differentiated tumors averaged 7.6 +/- 3.9% labeling versus 4.6 +/- 1.3% in moderately differentiated tumors, and well differentiated tumor in the series had a PCNA labeling index of 2.5 +/- 0.9%. The PCNA labeling indices for atypical hyperplasia were 1.9, and 4.1%, respectively. Our preliminary results suggest that the measurement of PCNA labeling index in prostate cancer may prove to be a new objective and quantitative assay of biological potential of individual tumor.
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PMID:Immunohistochemical detection of proliferating cell nuclear antigen (PCNA)/cyclin in human prostate adenocarcinoma. 809 65

The progression of prostatic intraepithelial neoplasia (PIN) to invasive prostate carcinoma has been analyzed in the C3(1)/T(AG) transgenic mouse model and appears very similar to the process proposed to occur in humans. PIN lesions in these transgenic mice histologically resemble those found in human PIN. Low-grade PIN was observed in the ventral and dorsolateral lobes at 2 months of age, whereas high-grade PIN was found in both lobes by 5 months of age. A progressive increase in the number of PIN lesions was observed with age. Prostate carcinomas, which appeared to arise from PIN lesions, were found by 7 months of age in the ventral lobe and 11 months of age in the dorsolateral lobe. Expression of T(AG) mRNA and protein in these lesions correlated with the development of PIN and carcinomas, as did the overexpression of p53 protein. Apoptosis levels were quite low in normal epithelial cells, moderate in low-grade PIN, and high in high-grade PIN and carcinomas. Levels of expression of proliferating cell nuclear antigen correlated with the degree of severity of the prostate lesions. Eighteen % of PIN lesions were found to already harbor Ha-ras mutations, whereas 33% of carcinomas showed various mutations in Ha-ras, Ki-ras, and/or p53. Mutations in Ha-ras may, therefore, be an early event in a significant portion of PIN lesions. Because high-grade PIN showed many characteristics similar to those observed in carcinomas and high-grade PIN was often found contiguous to carcinomas, we conclude that high-grade PIN is a precursor lesion of prostate carcinoma in this transgenic model. These transgenic mice will be useful to study mechanisms responsible for the progression of invasive carcinomas from PIN precursor lesions, as may occur during the development of prostate cancer in humans.
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PMID:Progression of prostatic intraepithelial neoplasia to invasive carcinoma in C3(1)/SV40 large T antigen transgenic mice: histopathological and molecular biological alterations. 889 41

The most efficient strategy for chemoprevention clinical trials are short-term studies which focus on surrogate endpoint biomarkers (SEBs) in high-risk target populations. High-grade prostatic intraepithelial neoplasia (PIN) is the most likely precursor of prostate cancer, and is found in a significant number of routine contemporary needle biopsies without cancer. The frequency and extent of PIN are decreased with androgen deprivation therapy, suggesting that it is a suitable endpoint biomarker for modulation. Potential SEBs for screening chemopreventive agents for prostate cancer in short-term Phase II trials include (1) histologic premalignant lesions, such as high-grade PIN; (2) biochemical markers, including prostate-specific antigen (PSA) serum concentration; and (3) morphometric markers, including nuclear texture, shape, and roundness; size and number of nucleoli; and number of apoptotic bodies; (4) proliferation markers, including MIB-1 and PCNA; (5) genetic markers, including nuclear DNA content (ploidy), oncogene c-erbB-2 (HER-2/neu) expression, fluorescence in situ hybridization for chromosome 8; and PSA-producing cells in the blood detected by reverse transcriptase polymerase chain reaction; and (6) differentiation markers, such as microvessel density as a determinant of angiogenesis. Each of these endpoint biomarkers is measured easily and accurately in serum or in tissue specimens such as formalin-fixed, paraffin-embedded needle biopsies, and may be modifiable by intervention. The clinical utility of these biomarkers as modulatable endpoints in prostate cancer chemoprevention needs to be demonstrated in future clinical trials.
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PMID:Prostatic intraepithelial neoplasia (PIN) and other prostatic lesions as risk factors and surrogate endpoints for cancer chemoprevention trials. 902 13

The role of bropirimine in prostate cancer remains unexplored. To address the efficacy of this immune modulator as neoadjuvant therapy we utilized the orthotopic placement of the Dunning AT-3 tumor. 2.4-2.6 x 10(6) Dunning AT-3 cells were injected into the ventral prostates of 50 Copenhagen X Fischer rats. Animals were then divided into 5 groups consisting of: 1) untreated controls; 2) those treated with ventral prostatectomy alone (performed 10-12 days following tumor cell inoculation); 3) those treated with ventral prostatectomy plus bropirimine (10 mg/kg) on postimplantation days 1, 3, 5, 10 and 11; 4) those treated with ventral prostatectomy plus bropirimine (100 mg/kg), at the same schedule; and 5) those treated with ventral prostatectomy plus bropirimine (500 mg/kg), at the same schedule. Animals were sacrificed 10 days after prostatectomy, autopsied, and residual disease was weighed. Prostate weights upon removal following neoadjuvant treatment and residual disease remaining after 20-22 days were expressed in grams (g). Following prostatectomy, mean prostate weights were: Group 2, 0.67 +/- 0.11; Group 3, 0.53 +/- 0.11; Group 4, 0.54 +/- 0.12; Group 5, 0.44 +/- 0.09. The effect of bropirimine was significant (p = 0.0001) by multiple regression analysis. In addition, mean residual tumor weights (expressed in grams) after 20-22 days were: Group 1, 12.7 +/- 1.9; Group 2, 6.7 +/- 4.8; Group 3, 5.2 +/- 5.9; Group 4, 3.8 +/- 3.5; and Group 5, 2.8 +/- 3.5. The effect of bropirimine was not significant (p = 0.07) by multiple regression analysis. However, prostatectomy alone, by Student's test, significantly (p = 0.04) reduced residual mean tumor weights by 47% and the additional effect of bropirimine upon residual disease was significant (p = 0.038) if a Chi-square analysis is applied. Finally, a multivariate analysis of the overall effect of bropirimine in rats treated with prostatectomy was significant (p = 0.002). The effect of bropirimine on expression of proliferating cell nuclear antigen (PCNA) and transforming growth factor beta 1 (TGF-beta 1) was also evaluated immunohistochemically and expression of both tumor markers was significantly reduced (p < 0.05). We conclude that bropirimine may have a role as a neoadjuvant therapy when combined with prostatectomy.
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PMID:Bropirimine as neoadjuvant therapy decreases residual disease and expression of markers PCNA and TGF-beta 1 in a rat orthotopic prostate adenocarcinoma. 922 52

As part of the study on the potential use of natural product-based combination therapy for treating prostate cancer, we have investigated the effects of a "HPLC standardized" herbal preparation, PC-SPES, on the prostate LNCaP cell line. Proliferation of the LNCaP cells was inhibited by a 4-6 day incubation with ethanolic extracts of PC-SPES. Decrease of cell growth was accompanied by a 60-70% down-regulation of the proliferating cell nuclear antigen (PCNA) and level of secreted PSA. A smaller and more variable decrease (20-40%) in the level of intracellular PSA was also observed. The PC-SPES-modulated PSA changes occurred concurrently with the decrease of AR expression, based on Western blot analysis and binding to the radioactive ligand [3H]R1881. A 60% decrease in R1881 binding occurred after a 24 h incubation with PC-SPES. These results suggest that PC-SPES negatively affects cell growth in part through its ability to modulate changes in PCNA, and may decrease PSA levels indirectly by suppressing AR expression.
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PMID:Regulation of androgen receptor (AR) and prostate specific antigen (PSA) expression in the androgen-responsive human prostate LNCaP cells by ethanolic extracts of the Chinese herbal preparation, PC-SPES. 924 11

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