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)

Both amplification and overexpression of c-erb B-2/neu have been associated with the progression and possible prognosis of a number of human cancers. In this study, we demonstrated that c-erb B-2/neu may also play an important role in human prostate cancer. Our conclusion is based on the following observations: (1) A monoclonal antibody raised against a peptide sequence from the C-terminal domain of the human c-erb B-2/neu gene product reacted positively with 68.7% (11 of 16) of the human prostatic cancer tissue extracts analyzed by western blot procedure. These results were supported by the immunohistochemical staining of the prostatic cancer specimens; 80% (12 of 15) showed positive staining, primarily around the plasma membranes of the prostatic cancer cells. c-erb B-2/neu oncoprotein was not detectable in normal prostate tissues (five examined by immunohistochemical staining and three by western blotting) or in human benign prostatic hyperplasia (two examined by immunohistochemical staining and six by western blotting) and was expressed less abundantly with lower intensity in "normal" human prostate tissues adjacent to cancerous prostate tissue (5 of 12 examined by immunohistochemical staining). We observed no evidence of c-erb B-2/neu gene amplification in 10 fresh human prostatic cancer specimens examined by Southern blotting and in the cultured human prostatic cancer cell lines PC-3, DU-145, and LNCaP. (2) The c-erb B-2/neu protein was detected in both androgen-receptor-positive (LNCaP) and -negative (PC-3 and DU-145) human prostate cancer cell lines. Positive immunostaining of c-erb B-2/neu protein was found to be associated predominantly with the plasma membranes of PC-3 cells, but was also found to be widespread in the cytoplasmic region of the LNCaP cells and in the perinuclear region of the DU-145 cells. (3) Like prostate-specific antigen (PSA) expression, c-erb B-2/neu mRNA expression was also positively regulated by androgen in androgen-receptor-positive LNCaP cells in vitro and LNCaP tumors in vivo. When LNCaP tumors were grown in castrated male hosts, levels of c-erb B-2/neu and PSA mRNA expression decreased initially, but rebounded at 3 wk to levels comparable to those expressed by tumors maintained in intact adult male hosts.
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PMID:Expression of c-erb B-2/neu proto-oncogene in human prostatic cancer tissues and cell lines. 135 65

An evaluation of the effects of blood transfusion on recurrence and survival after radical surgery for prostate cancer was performed. Between 1982 and 1986, 315 consecutive patients underwent radical retropubic prostatectomy by a single surgeon; of 309 patients for whom transfusion data were available, 94 received homologous blood (Group I) and 215 received autologous blood or no blood (Group II). At the time of surgery, there were no differences between Group I and Group II with respect to age, preoperative cancer stage, preoperative histologic grade (Gleason grade), prostatic acid phosphatase score, and preoperative potency. At discharge, the groups were similar in the status of neurovascular bundles, capsular involvement, seminal vesicle involvement, lymph node involvement, postoperative Gleason grade, and postoperative potency. No adjuvant hormone therapy or radiation therapy was administered until tumor recurrence. The patients were followed annually by physical examinations and measurements of prostate-specific antigen. Cancer recurrence was detected in 23 (24.5%) Group I patients and 49 (22.7%) Group II patients. These proportions were not significantly different in univariate or multivariate analysis, and the time to recurrence curves overlapped. It is concluded that homologous blood transfusions are not associated with more rapid tumor recurrence or death after radical surgery for prostate cancer than is seen with autologous transfusions. These results differ from previous reports, which suggested that transfusions may cause recurrence of cancer in patients with colorectal or prostate cancer because of the immunosuppressive effects of blood transfusions.
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PMID:Prostate cancer recurrence in radical surgery patients receiving autologous or homologous blood. 137 May 92

The LNCaP prostatic carcinoma cell line was examined for the presence of specific receptors for 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25-(OH)2D3]. Whole cell binding studies identified approximately 2500 high-affinity (Kd = 1.4 x 10(-9) binding sites per cell. Competition studies revealed that these receptors are specific for the 1 alpha,25(OH)2 metabolite. Binding studies using the synthetic androgen R1881 indicate that separate androgen and vitamin D3 receptors exist in LNCaP cells. The vitamin D3 receptors sediment at approximately 3.5S on linear sucrose gradients. The sedimentation coefficient could be shifted with a monoclonal anti-vitamin D3 receptor antibody (9A7 gamma) but not with a monoclonal antibody to the androgen receptor (AN1-15). The receptor/ligand complex elutes from native DNA cellulose at 0.2 M KCl. Northern blot analysis identified an mRNA of approximately 4.6 kilobases which hybridized with a specific vitamin D3 receptor complementary DNA probe (hVDR). In the absence of androgens, 1 alpha,25(OH)2D3 stimulated growth and prostate-specific antigen production by LNCaP cells in a dose-dependent fashion. Dose-response curves indicated that at physiological concentrations (10(-9) M) 1 alpha,25(OH)2D3 was mitogenic, whereas at higher concentrations (10(-8) M) it promotes differentiation. These studies suggest that 1 alpha,25(OH)2D3 could play an important role in the natural history of and response to hormone therapy by prostatic cancer.
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PMID:The human prostatic carcinoma cell line LNCaP expresses biologically active, specific receptors for 1 alpha,25-dihydroxyvitamin D3. 137 Jun 48

Prostate-specific antigen is a specific immunohistochemical marker of benign prostatic epithelium and prostate cancer. A subpopulation of neuroendocrine cells seen in 50% of cancers do not produce this protein marker. These cells appear to secrete prostate-specific acid phosphatase. This finding may explain the marked variation in serum prostate-specific antigen levels in all stages of prostate cancer.
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PMID:Prostate-specific antigen and prostate-specific acid phosphatase in neuroendocrine cells of prostate cancer. 137 Aug 78

The participating institutions of the American Cancer Society National Prostate Cancer Detection Project did 520 biopsies on 2425 men over a 3.5-year period. A total of 88 cancers were confirmed pathologically, 93% of which clinically were organ confined. In 324 men (62.3%), a recommendation for biopsy was made based solely on the results of transrectal ultrasonography (TRUS); in 69 patients (13.3%), solely on the digital rectal examination (DRE); in 116 patients (22.3%), on abnormal DRE and TRUS examinations; and in 11 patients (2.1%), in whom DRE and TRUS were normal, on elevated prostate-specific antigen (PSA) levels. The TRUS was abnormal in 80.6% of men found to have cancer, and the PSA level and DRE were abnormal for 67% and 50% of cancers, respectively. The influence of PSA level on cancer detection increased as the serum level increased above 4 ng/ml. The positive predictive values of both the DRE and TRUS were influenced significantly by the presence of an elevated PSA level (P = 0.044 and P less than 0.001, respectively). The results of this ongoing multicenter study support the following statements: (1) the prostate cancer detection rate is influenced by this diagnostic triad and (2) the detection rate of organ-confined disease can be improved substantially by early detection programs.
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PMID:The relationship of prostate-specific antigen to digital rectal examination and transrectal ultrasonography. Findings of the American Cancer Society National Prostate Cancer Detection Project. 137 Dec 33

The American Cancer Society National Prostate Cancer Detection Project is a prospective, multidisciplinary, and multicenter trial to assess the potential for early detection of prostate cancer by transrectal ultrasonography (TRUS), digital rectal examination (DRE), and serum prostate-specific antigen assay (PSA). By November 1990, 2805 men between the ages of 55 and 70 years with no known signs or symptoms of prostate cancer were enrolled in the study, which is planned to run for 5 years. Annual TRUS, DRE, and PSA tests were done on these subjects, and biopsies were recommended for suspicious lesions when detected. To study the performance of PSA testing in presumed normal subjects, all men were eliminated who had (1) prostate cancer detected on their initial examinations and proven by biopsy or (2) cancer detected during the year or subsequent examinations. Additionally, all men with TRUS or DRE findings that were interpreted as suspicious for cancer but who are being followed and have not yet had biopsies done were removed from this series. This left a unique, extensively screened group of 1695 men who were free of prostate cancer, as far as could be determined. Analyses of the PSA levels in this large population in the appropriate age range for increasing risk of prostate cancer revealed several important findings. First, there was a direct relationship between serum PSA levels and estimated prostate volume for both the currently available monoclonal and polyclonal PSA assays. Individuals with benign prostatic hyperplasia and larger gland volume have a higher normal limit of PSA than men with normal gland volume. Second, analyses showed no relationship between age and PSA levels or between symptoms of prostatism and PSA levels independent of gland enlargement. It was concluded that volume-adjusted upper limits of normal PSA can be determined for different levels of specificity desired. This information may be applicable to the use of PSA in men not already suspected of having prostate cancer and may increase its effectiveness as a tool for early detection.
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PMID:Prostate-specific antigen levels in 1695 men without evidence of prostate cancer. Findings of the American Cancer Society National Prostate Cancer Detection Project. 137 Dec 34

Prostate-specific antigen (PSA) is the most sensitive marker available for monitoring the progression of prostate cancer and response to therapy. In a previous study, we demonstrated tissue-specific expression of PSA glycoprotein and mRNA and its regulation through the androgen receptor. In this study, we examine the effects of protein kinase A (PKA) and protein kinase C (PKC) on the androgen regulation of PSA in a human adenocarcinoma cell line, LNCaP. Northern blot analysis demonstrated that forskolin, an activator of PKA, had no effect on the androgen regulation of PSA. However, the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA), a direct activator of PKC, showed a time- and dose-dependent repression of the androgen regulation of PSA glycoprotein and mRNA. The biologically inactive phorbol ester, 4 alpha-phorbol-12,13-didecanoate, had no effect. Staurosporine, a PKC inhibitor, blocked the TPA-mediated repression of the androgenic stimulation of PSA glycoprotein. In addition, the calcium ionophore, A23187, was able to simulate the actions of TPA, presumably through activation of PKC via calcium mobilization. In summary, the androgenic regulation of PSA protein and mRNA is repressed by tumor-promoting phorbol esters through the PKC pathway. This indicates that the effects of TPA may be secondary to repressed gene transcription or altered mRNA stability. In addition, this study emphasizes that the androgenic regulation of PSA is complex and may involve other extracellular transduction signals.
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PMID:Tumor-promoting phorbol ester down-regulates the androgen induction of prostate-specific antigen in a human prostatic adenocarcinoma cell line. 137 17

The ability of prostate-specific antigen (PSA) to predict tumor volume and stage in patients with prostate cancer would be improved if factors regulating its production and clearance were better defined. A thorough understanding of the pharmacokinetics (regulation of production, metabolism, and excretion) of PSA has been precluded, however, by the absence of an in vivo animal model. The purposes of this study are to develop a murine model for evaluating PSA pharmacokinetics in vivo and to assess factors that influence PSA production in vitro. The human prostate cancer cell line, LNCaP, was chosen because it is androgen sensitive and PSA positive. Although LNCaP cells are usually nontumorigenic when inoculated s.c. in athymic mice, coinoculation of 1 x 10(6) LNCaP cells with 1 x 10(6) human bone fibroblasts reliably produces PSA-secreting carcinomas. This LNCaP model provides accurate correlation between tumor volume and serum PSA levels (r = 0.94) and demonstrates that tumor volume and androgens are codeterminants of circulating PSA levels. Following castration, serum PSA levels decrease rapidly up to 8-fold and increase up to 20-fold following androgen supplementation, without detectable castration-induced tumor cell death or concomitant changes in tumor volume. Serum PSA levels increase 0.24 ng/ml/mm3 of tumor, which is approximately 5-fold less than that estimated for humans. Most likely this reduced PSA index (PSA:tumor volume ratio) results from a 7-fold faster clearance of PSA in athymic mice than in humans; other than this shorter half-life, PSA elimination in the murine model appears similar to that in humans, with both following first-order kinetics characteristic of a two-compartment model. Interestingly, following prolonged growth (greater than 21 days) in castrate hosts, LNCaP tumors are capable of adapting to an androgen-deprived environment whereby LNCaP tumors regain the ability to secrete PSA in amounts similar to the precastrate state. In LNCaP cells, androgens increase PSA mRNA levels 4-fold in vivo and in vitro. PSA mRNA expression is also altered by various growth factors. Changes in PSA production induced by androgens and growth factors do not always parallel changes in LNCaP cell growth rate induced by these factors, suggesting that PSA production occurs independently of cell growth rate and may be influenced by various interrelated factors, including hormonal and stromal milieu. Observations from this murine model suggest that androgens and tumor volume are independent determinants of serum PSA levels and imply that decreases in circulating PSA following antiandrogen therapy may not always reflect a corresponding reduction in tumor volume.
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PMID:Serum prostate specific antigen levels in mice bearing human prostate LNCaP tumors are determined by tumor volume and endocrine and growth factors. 137 18

Over a 4 1/2 year period, 1,940 asymptomatic men were entered in a prostate cancer detection program consisting of digital rectal examination (DRE), prostate-specific antigen (PSA), and transrectal prostate ultrasound (TRUS). Four hundred and sixteen biopsies were performed resulting in the diagnosis of 79 cancers; 82% had clinically organ confined tumors. A recommendation for biopsy was made in 260 (62%) based on the TRUS alone, 55 (13%) by DRE alone, 92 (22%) when the DRE and TRUS were both abnormal, and in 9 (2.2%) cases when only PSA levels were elevated. The DRE, PSA, and TRUS were abnormal in 1,261 (65%), 989 (51%), and 1,552 (80%) of the patients with cancer, respectively. Prostate cancer detection increased as the serum PSA level increased above 4 ng/ml. The positive predictive value of both DRE and TRUS were significantly influenced by an elevated PSA, (P = .042 and P less than .00005, respectively). The results of this study support the idea that, although the prostate cancer detection rate is influenced by these three modalities and the detection rate of localized disease can be improved by early detection programs, its effect on mortality rates remains undefined at this time.
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PMID:Prostate-specific antigen, digital rectal examination, and transrectal ultrasound in predicting the probability of cancer. 137 76

The effect of digital rectal examination (DRE) on measurement of serum prostate-specific antigen was investigated during a prostate cancer screening program of 2,736 ambulatory men. Serum samples were collected before and after DRE and values compared using the nonparametric Wilcoxon signed rank test. Small, yet statistically significant, increases were found associated with DRE. The magnitude of these increases, however, was of minor clinical importance. Patients who exhibited the largest increases with initial values greater than the upper limit of normal (4 micrograms/L) were found to have either benign prostatic hyperplasia, prostatitis, or prostatic carcinoma. The benign prostatic hyperplasia patients showed relatively low initial prostate-specific antigen values with similarly small increases related to DRE, whereas the prostatitis and cancer patients exhibited both higher initial prostate-specific antigen values and larger increases associated with DRE. Finally, patients with increases in prostate-specific antigen from less than 4 micrograms/L to greater than or equal to 4 micrograms/L comprised less than 2% of the reference range population, the majority of whom had post-DRE measurements of less than 5 micrograms/L. Thus, DRE does not appear to be a significant factor in falsely elevating prostate-specific antigen levels and should be of limited concern to the clinician obtaining serum samples after DRE.
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PMID:Digital rectal examination-associated alterations in serum prostate-specific antigen. 137 86


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