Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007112 (prostatic adenocarcinoma)
 2,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Transforming growth factor alpha (TGF alpha) expression was analyzed immunocytochemically on formalin-fixed wax-embedded sections obtained from 24 benign prostatic hyperplasia (BPH) specimens and 76 prostatic carcinoma tissues, 3 human prostatic tumor xenografts, normal kidney, and salivary gland. Low amounts of TGF alpha immunopositivity were encountered in the epithelium of BPH glandular tissues, whereas in the prostatic adenocarcinoma samples, a greater heterogeneity and intensity of TGF alpha immunostaining was observed. The most intense staining was exhibited by the least differentiated tumors, although a few of these were weakly stained. Statistical analysis of the relationship of histopathological grade of tumor with TGF alpha expression in the carcinomas showed a significant correlation of these parameters, 0.01 > P > 0.001. The expression of the proliferation markers Ki-67 and PCNA was also analyzed in the carcinoma specimens, and the relationship of these to TGF alpha expression indicated that there was no significant correlation in this series of tumors between increased growth activity and TGF alpha expression (p approximately 0.25 with both markers). The prostatic carcinoma xenografts TEN12 and TEN15 contained low levels of immunoreactive TGF alpha, which was uniformly distributed, whilst heterogeneous immunostaining was observed in the uroepithelial xenograft TEN16. In the normal human kidney, TGF alpha was concentrated in the epithelium of the distal convoluted tubules (DCT) and the collecting tubules (CT), and lower amounts were identified in the proximal convoluted tubules (PCT). As in the prostatic carcinomas, the immunostaining was eliminated by prior absorption of the antibody with pure TGF alpha and not with human or mouse EGF. No crossreactivity of the TGF alpha antibody with salivary EGF was demonstrated. This study concludes that, in prostate carcinoma, the least differentiated tumors more often expressed greater amounts immunoreactive TGF alpha; however, no relationship between TGF alpha expression and cellular proliferation markers was found.
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PMID:An immunocytochemical analysis of TGF alpha expression in benign and malignant prostatic tumors. 768 82

This paper evaluates the use of quantitative methods to accurately assess cell proliferation and death in untreated and treated prostate lesions. The analysis of proliferating cell nuclear antigen (PCNA)-stained nuclei allow precise evaluation of the proliferating cells and exact identification of their location in the progression of untreated prostatic intraepithelial neoplasia (PIN) to prostatic adenocarcinoma (PAC). The evaluation of the frequency and location of apoptotic bodies (ABs) gives accurate information on the apoptotic phenomenon in PIN compared to normal prostate (NP) and PAC. In fact, the frequency of ABs increases from NP to PIN to PAC and parallels that observed with PCNA. However, the AB-related values were approximately one-eighth to one-tenth of those obtained with PCNA immunostaining. Combination endocrine therapy (CET) decreases the proliferative activity and enhances the apoptosis phenomenon in NP, PIN, and PAC. This might indicate that CET could induce a certain degree of regression not only of PAC, but also of PIN.
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PMID:Quantitative characterization of the frequency and location of cell proliferation and death in prostate pathology. 782 97

Prostatic carcinomas vary in their biological potential, even when stratified by grade and stage. Measurement of cellular proliferation by various methods has been shown to correlate with outcome for several human cancers, including prostatic carcinoma. Uptake of bromodeoxyuridine (BrdUrd), a thymidine analogue, has been accepted as a measure of cellular proliferative rate. However, the technique is somewhat complex, requiring incubation with fresh tissue. We compared cellular proliferation as measured by BrdUrd uptake with two more simple immunohistochemical methods in 44 prostatic adenocarcinoma specimens and correlated the results with standard clinical parameters. The tissue was obtained via needle biopsy, channel transurethral resection, and radical prostatectomy. Specimens were incubated in vitro with BrdUrd and then fixed and paraffin embedded. Sections were immunohistochemically stained with antibodies to BrdUrd, proliferating cell nuclear antigen (PCNA), and Ki-67. At least 1,000 cells were scored, and a labeling index (LI) was calculated (number of positive cells/total number of cells). The mean LI determined by all three indices was low (BrdUrd = 3.0, PCNA = 7.0, Ki-67 = 3.4), consistent with the knowledge that prostatic tumors grow slowly. In 36 patients who had not been treated at the time of analysis, the LI as determined by all three methods correlated well with clinical stage and pathological grade. Furthermore, the LIs discriminated between those with tumor confined to the prostate and those with extension to the seminal vesicles, lymph nodes, or bone (P = 0.003, 0.004, 0.008 for BrdUrd, PCNA, and Ki-67, respectively). The LIs for PCNA and Ki-67 correlated well with that for BrdUrd (r = 0.84; r = 0.85), while the LIs for Ki-67 and PCNA correlated slightly less well with each other (r = 0.78). PCNA and Ki-67 expression appear to reflect essentially the same biological process as BrdUrd uptake. Either can substitute for BrdUrd as a measure of cellular proliferation, and Ki-67 seems to offer the fewest technical problems.
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PMID:Cellular proliferation in prostatic adenocarcinoma as assessed by bromodeoxyuridine uptake and Ki-67 and PCNA expression. 785 2

Expression and location of Proliferating Cell Nuclear Antigen immunostaining in epithelial nuclei were assessed on histological sections from 32 cases of invasive adenocarcinoma of the prostate gland: 20 untreated and 12 treated with combination endocrine therapy or CET. The PCNA-positive nuclei showed homogeneous or granular types of staining or a mixture of both, and a gradation in the intensity of staining. Nuclei with homogeneous patterns appeared darker brown than the lighter granular and mixed patterns. Darker nuclei were more frequently noted, mainly among the epithelial cells adjacent to the stroma, in the untreated cases. In contrast, nuclei with pyknotic chromatin, unstained and corresponding to apoptotic bodies, were more frequently seen in the treated patients. For the untreated invasive adenocarcinomas, the mean proportion of PCNA-stained epithelial nuclei in the 10 cases with an acinar pattern (small and large) was 8.86% (SE 0.23%). The mean value in the 5 cases with a cribriform pattern was 11.76% (SE 0.52%), that is, greater than in the acinar pattern, and decreased from the nuclei in the basal position, or adjacent to the stroma, toward the lumen: 14.40% (SE 0.61%) in the basal position, 11.84% (SE 1.30%) in the intermediate and 9.26% (SE 0.66%) in the lumenal. In the 5 cases with a solid/trabecular pattern, the proportion of PCNA-positive nuclei was 15.74% (SE 2.30%), that is, higher than in all the other patterns, and decreased from the cell layer adjacent to the stroma (17.60%, SE 2.92%) toward the other layers (13.88%, SE 1.71%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prostatic invasive adenocarcinoma. Effect of combination endocrine therapy (LHRH agonist and flutamide) on the expression and location of proliferating cell nuclear antigen (PCNA). 791 Mar 94

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

Expression and location of Proliferating Cell Nuclear Antigen in epithelial nuclei were assessed in invasive adenocarcinoma of the prostate gland. The PCNA-positive nuclei showed homogeneous or granular types of immunostaining or a mixture of both, and a gradation in the intensity of staining. Nuclei with homogeneous pattern appeared darker brown than the lighter granular and mixed patterns. Darker nuclei were quite frequently noted, mainly among the epithelial cells adjacent to the stroma. For the marginal zone of invasive adenocarcinoma, the mean proportion of PCNA-stained nuclei in the small acinar pattern was somewhat similar to that in the large acinar pattern, i.e., 8.66% and 9.06%, respectively. In contrast, the mean values in the cribriform pattern were greater than in the small and large acinar patterns, and decreased from the nuclei in the basal position, or adjacent to the stroma, toward the lumen: 14.40% in the basal position, 11.84% in the intermediate and 9.26% in the lumenal. In the solid/trabecular pattern, the proportions of PCNA-positive nuclei were higher than in all the other patterns: 17.60% in the cell layer adjacent to the stroma and 13.88% in the other layers. The trend of value changes in the central zone of the tumour was similar to that obtained in the marginal zone. However, the proportions were lower and the differences statistically significant. This might indicate that the proliferation state is higher in the marginal zone and that the tumour grows eccentrically rather than centrally.
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PMID:Proliferating cell nuclear antigen (PCNA) in prostatic invasive adenocarcinoma. Is the proliferation state in the marginal zone of the tumour higher than in the central part? 809 89

Prostate cancer is a disease associated with androgens. It has been hypothesized that reducing the conversion of testosterone (T) to dihydrotestosterone (DHT) in the prostate by the use of the drug finasteride, a 5alpha-reductase inhibitor, will reduce the incidence of prostate cancer. We investigated the chemopreventive potential of finasteride by evaluating its effect on the prostate gland of men with elevated serum prostate-specific antigen (PSA). Fifty-two men with elevated PSA and prostate sextant biopsies negative for cancer were randomized to receive finasteride 5 mg day(-1) (27 patients) or no medication (25 patients) for 12 months and were rebiopsied at 12 months. The biopsies were evaluated for the presence of cancer, the proportion of glandular and hyperplastic tissue, and the presence of high-grade prostatic intraepithelial neoplasia (PIN). Epithelial proliferation was assessed in the prestudy and 12-month biopsies by immunohistochemistry using antibody to proliferating cell nuclear antigen (PCNA). Serum blood samples were drawn at baseline and after 1, 3, 6 and 12 months of study. In the control group, serum levels of PSA and T were unchanged throughout the 12 months. In the finasteride group, PSA decreased 48% (P < 0.001), DHT decreased 67% (P < 0.001) and T increased 21% (P < 0.001). Histological evaluation of prestudy and 12-month biopsy specimens revealed that the finasteride group had a 30% reduction in the percentage of hyperplastic epithelial tissue (P = 0.002), although this decrease was not statistically significantly different between the finasteride and control groups (P = 0.11). In patients with PIN on prestudy biopsy, no change occurred in the PIN lesions with finasteride treatment. Finasteride also had no effect on the proliferation index of prostatic epithelial cells. Of the 27 patients treated with finasteride, eight (30%) had adenocarcinoma of the prostate detected on the 12-month biopsy, compared with one (4%) of the control patients (P = 0.025). In the treatment group, six cancers occurred in the eight patients with PIN on the prestudy biopsy; in the observation group no cancers were detected in the five patients with PIN on the prestudy biopsy (P = 0.021). Two cancers occurred in the 19 men in the treatment group with no evidence of PIN on the prestudy biopsy, compared with one cancer in the 20 men in the observation group with no evidence of PIN on the prestudy biopsy (P = 0.60). This study, using a novel model for evaluating short-term efficacy of chemopreventive or therapeutic agents in men at high risk of prostate cancer, provides little evidence that finasteride is an effective chemopreventive agent for prostate cancer in men with elevated PSA.
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PMID:The effect of finasteride on the prostate gland in men with elevated serum prostate-specific antigen levels. 1048 32

Diagnostic and prognostic markers for prostatic cancer (PCa) include conventional protein markers (e.g., PAP, PSA, PSMA, PIP, OA-519, Ki-67, PCNA, TF, collagenase, and TIMP 1), angiogenesis indicator (e.g., factor VIII), neuroendocrine differentiation status, adhesion molecules (E-cadherin, integrin), bone matrix degrading products (e.g., ICPT), as well as molecular markers (e.g., PSA, PSMA, p53, 12-LOX, and MSI). Currently, only PSA is used clinically for early diagnosis and monitoring of PCa. The histological differential diagnosis of prostatic adenocarcinoma includes normal tissues such as Cowper's gland, paraganglion tissue and seminal vesicle or ejaculatory duct as well as pathological conditions such as atypical adenomatous hyperplasia, atrophy, basal cell hyperplasia and sclerosing adenosis. A common PCa is characterized by a remarkable heterogeneity in terms of its differentiation, microscopic growth patterns and biological aggressiveness. Most PCa are multifocal with signi ficant variations in tumor grade between anatomically separated tumor foci. The Gleason grading system which recognizes five major grades defined by patterns of neoplastic growth has gained almost uniform acceptance. In predicting the biologic behavior of PCa clinical and pathological stages are used as the major prognostic indicators. Among the cell proliferation and death regulators androgens are critical survival factors for normal prostate epithelial cells as well as for the androgen-dependent human prostatic cancer cells. The androgen ablation has been shown to increase the apoptotic index in prostatic cancer patients and castration also promotes apoptotic death of human prostate carcinoma grown in mice. The progression of PCa, similarly to other malignancies, is a multistep process, accompanied by genetic and epigenetic changes, involving phenomenons as adhesion, invasion and angiogenesis (without prostate specific features).
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PMID:Prostate Cancer - Old Problems and New Approaches. (Part II. Diagnostic and Prognostic Markers, Pathology and Biological Aspects). 1117 6


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