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PubMed1984

Radioimaging of the prostate and metastases of prostatic carcinoma with 99mTc-labelled prostatic acid phosphatase-specific antibodies and their Fab fragments.

A radioimmunodetection technique using 99mTc-labelled polyclonal antibodies raised in rabbits against human prostate-specific acid phosphatase was used to detect metastases of prostatic carcinoma. All the metastases observed by X-rays or bone scintigraphy in the four patients with M1-disease were revealed by the novel technique employed. In addition, in one of the patients studied, a distinct incorporation of radioactivity was also observed in the left inferior scapular region, which was not seen by conventional bone scanning, but was later confirmed by X-ray studies to be a metastatic process.

Acid Phosphatase↗
PubMed2006

Prostate derived factor in human prostate cancer cells: gene induction by vitamin D via a p53-dependent mechanism and inhibition of prostate cancer cell growth.

The secosteroid hormone 1alpha, 25-dihydroxyvitamin D3 (1,25D) has been shown to regulate the growth and differentiation of human prostate cancer (PCa) cells, although the precise molecular mechanisms mediating these effects have not been defined. Previous studies in our laboratory demonstrated that the antiproliferative effects of 1,25D on PCa cells are mediated through the nuclear vitamin D receptor (VDR). In the present study, we performed gene profiling of LNCaP human PCa cells following 1,25D treatment and identified the antitumorigenic gene, prostate derived factor (PDF), as being highly induced by 1,25D. PDF is a member of the TGF-beta superfamily and has been implicated in a variety of functions directly related totumorigenicity including antiproliferative and pro-apoptotic effects. Gene expression studies using 1,25D analogs and a VDR antagonist demonstrate that 1,25D-mediated induction of PDF message and protein in PCa cells is dependent on VDR action. PDF is a transcriptional target of the tumor suppressor, p53. Here we show that the expression of PDF in nine PCa cell lines is dependent on functional p53. Additionally, transfection of p53-null ALVA-31 PCa cells with a p53 expression plasmid, and expression of dominant negative p53 in LNCaP PCa cells, show that the ability of VDR to induce PDF requires functional p53. Importantly, forced PDF expression in PC-3 cells results in decreased cell proliferation, soft agar cloning, and xenograft tumor size. These data demonstrate that PDF exerts antitumorigenic properties on PCa cells and its regulation by 1,25D may provide insights into the action of 1,25D in PCa.

Animals↗
PubMed2005

[Classification, etiology, diagnosis and treatment of prostatitis. Other types of prostatitis. Acute and chronic prostatitis].

Prostatitis is a highly prevalent nosologic entity and hence has an enormous financial impact on health systems as well as negative repercussions on patients' quality of life. The symptoms are ambiguous, diagnostic methods are controversial and treatments are long and produce inconsistent results; consequently, although not life-threatening, prostatitis has become one of those diseases that is difficult both for the patient and for the physician who attempts to help, sometimes without success. Although an infectious etiology is accepted in most cases, there are major controversies about both the diagnostic methods used and their interpretation. Recently the National Institutes of Health in the USA has proposed a new classification of this disease to substitute that used for the last twenty years. This new classification may provide a more effective approach to the diagnosis and treatment of this insidious disease.

Acute Disease↗
PubMed1991

Study of macrophages in prostatic fluid from nonbacterial prostatitis patients. V. Relation between activation of macrophages and stage of prostatitis.

Relationship between activation of macrophages in prostatic fluid and stage of nonbacterial prostatitis was studied by observing the rate of adherence of leukocytes, percentage of macrophages among adherent leukocytes and presence of spreading of macrophages. As a result, it was found that macrophages in the early stage of NBP were more activated than macrophages in the chronic stage.

Adult↗
PubMed1994

[Clinical studies on chronic prostatitis and prostatitis-like syndrome (7). Electric acupuncture therapy for intractable cases of chronic prostatitis-like syndrome].

Seventeen patients with prostatodynia (chronic prostatitis-like syndrome) refractory to conventional medical treatment were treated with electric acupuncture at a low-wave frequency. All of them had had a complicated clinical course and pelvic hypertonicity. This therapy was administered to mitigate the congestion of pelvic circulation, especially around the prostate. The clinical efficacy of longterm treatment was considered excellent in 30% and moderate in 70% of the patients, with an overall efficacy rate of 100%. Treatment with Chinese medicines and chemical agents could be withdrawn completely in 50% of the patients, treatment with chemical agents could be withdrawn in 30% of the patients, and the dose of either type of medication could be reduced in 20% of the patients. To examine whether the efficacy of electric acupuncture was related to the induction of cytokines we also examined the serum levels of INF-gamma, IL-1 beta and IL-6, but, no significant elevation of either of them was detected.

Abdominal Pain↗
PubMed1993

Concordance of DNA content between prostatic intraepithelial neoplasia and concomitant invasive carcinoma. Evidence that prostatic intraepithelial neoplasia is a precursor of invasive prostatic carcinoma.

It has been postulated that prostatic intraepithelial neoplasia (PIN) is a precursor lesion to invasive carcinoma in the prostate, yet there has been little direct evidence for this relationship. Therefore, we studied the DNA content of the epithelial cells in PIN lesions with accompanying invasive carcinoma in seven cases. DNA content of nuclei in Feulgen-stained tissue sections was performed using the CAS200 System (Cell Analysis Systems Inc, Elmhurst, Ill), with normal and hyperplastic glands serving as controls for diploid DNA content. In four cases, the cells of both lesions (PIN and invasive carcinoma) contained only diploid DNA; in one case, an additional aneuploid tumor stem line was present only in the invasive component; and in two cases, both PIN and carcinoma cells contained aneuploid cells having similar DNA content. The concordance of DNA content between PIN and invasive carcinoma in these cases provides evidence that PIN is a precursor lesion for invasive carcinoma.

Adenocarcinoma↗
PubMed1991

Lack of association between prostate-specific acid phosphatase RFLP genotypes and prostatic cancer or benign prostatic hyperplasia.

We have previously reported the identification and basic characterization of two biallelic TaqI RFLPs, A and B, of the 3' end of the human ACPP locus in an unselected Finnish population (Winqvist et al., 1989). In the present investigation, a similar allelic distribution was observed in patients with prostatic cancer or benign hyperplasia. In addition, it was found that the DNA sequences generating RFLP-B are located further downstream from the RFLP-A sequences.

Acid Phosphatase↗
PubMed1996

Androgen receptor expression in prostatic dysplasia (prostatic intraepithelial neoplasia) in the human prostate: an immunohistochemical and in situ hybridization study.

To evaluate the role of androgens in the pathogenesis of prostatic dysplasia, we compared the localization of androgen receptor (AR) in proliferative and nonproliferative cells in normal and dysplastic acini. Basal cells, the only proliferating cells identified in normal acini, contained AR mRNA but lacked an immunodetectable receptor. Both AR mRNA and immunodetectable receptor were present, however, in secretory and stromal cells. Androgen receptor localization in dysplastic lesions was identical to normal but here the proliferative marker Ki-67 was found in both basal and secretory cells. Our findings suggest that androgens do not directly initiate the division of basal cells, the putative precursors of secretory cells. Instead, the hormone may act through its fully translated receptor to mainly mediate the differentiation of secretory cells. The presence of both AR and Ki-67 in dysplastic secretory cells may indicate an abnormal direct androgen-mediated proliferation in this compartment. This is consistent with previous evidence that secretory cell differentiation is impaired in dysplasia.

Aged↗
PubMed1992

The prognostic value of prostate-specific antigen and prostatic acid phosphatase in serum of patients with prostate cancer after orchidectomy.

Correlations between the serum levels of PAP and PSA before and 1, 3 and 6 months after orchidectomy in 27 prostatic cancer patients (advanced clinical stages C and D according to Whitemore scale) were studied. The PSA values correlated more distinctly than PAP with the general clinical condition. PSA is a reliable tumour marker when used at regular intervals, especially for monitoring therapeutic results. A high preoperative PSA level correlates with a high postoperative level and progression of the disease.

Acid Phosphatase↗
PubMed2006

Relationship among initial serum prostate specific antigen, prostate specific antigen progression and prostate cancer detection at repeat screening visits.

PURPOSE: We evaluated the probability of positive serum PSA (3 ng/ml or greater) and CaP detection at annual followup visits in men with negative initial PSA (less than 3 ng/ml) to optimize the re-screening schedule. MATERIALS AND METHODS: Data on 5,387 men 45 to 80 years old with negative PSA and no CaP diagnosis at the first screening visit were obtained from the Laval University Prostate Cancer Screening Program database. Accelerated failure time regressions were fitted to time from baseline to positive PSA and to time from positive PSA to CaP detection. The models were combined to estimate the cumulative probability of positive PSA followed by CaP detection at re-screening. RESULTS: The 5-year cumulative probability of detecting CaP at annual visits in men with baseline PSA up to 1.5 ng/ml remained below 0.8%, while it was 1.3%, 4.8% and 8.3% in men with PSA 1.5 to less than 2, 2 to less than 2.5 and 2.5 to less than 3 ng/ml, respectively. Time to positive PSA significantly decreased with increasing baseline PSA and age, while the time between positive PSA and CaP detection depended only on age. Men with PSA below 1.0 ng/ml could wait for 4 to 5 years before being re-tested, while men with PSA between 1.0 and 1.5 ng/ml should be screened every second year and men with PSA 1.5 ng/ml or greater should be screened every year. CONCLUSIONS: The proposed retesting schedule using current PSA and age decreases the number of visits by 38.1%, while delaying the detection of only 2.4% of CaPs that would have been detected using annual PSA testing.

Aged↗
PubMed1995

Using repeated measures of symptom score, uroflowmetry and prostate specific antigen in the clinical management of prostate disease. Benign Prostatic Hyperplasia Treatment Outcomes Study Group.

Measurements of American Urological Association symptom score, peak urine flow rate and prostate specific antigen (PSA) are often followed over time in urological management. However, their interpretation is confounded by within-patient variability due to chance. Data from 2 clinical trials are used to examine the magnitude of this variation. When these measures are repeated at a short interval variation is modest and might easily be misinterpreted as a true change in patient condition. For example, approximately 20% of patients might be expected to have a chance increase or decrease in symptom score by at least 4.9 points, in peak urine flow rate by at least 4.1 ml. per second or in PSA by at least 1.6 ng./ml. Clinicians can use these data to help interpret repeated measures of these variables in patients, and can consider obtaining paired measurements to decrease the effect of chance variation when they plan on following them over time.

Aged↗
PubMed1992

[Diagnostic value of prostatic specific antigen (PSA) in comparison to prostatic acid phosphatase (PAP) in prostatic cancer and adenoma].

The diagnostic value of the tumour markers: PSA, PAP and AcP was studied before treatment in 379 men (47 with prostatic cancer--PC, 306 with benign hyperplasia--PBH, and 26 healthy subjects--control group CG). PSA was determined by the enzymoimmune method, and the phosphatases were evaluated by the spectrophotometric method. Raised level of PSA was found in PBH--the highest value--23.3 ng/ml. After accepting the cutting off values (1.9 ng/ml and 23.3 ng/ml), even in 93% of patients with PC, the level of PSA exceeded the second of those values. A significant growing tendency was found of PSA together with the degree of clinical progression of PC (in stages C and D--in 100% of patients). PSA, as compared with the phosphatases, is a much more sensitive biochemical marker, exceeding them many times in sensitivity.

Acid Phosphatase↗
PubMed1993

[Clinical studies on chronic prostatitis and prostatitis-like syndrome (6). Clinical evaluation for the chronic prostatitis-like syndrome patients with severe symptoms of voiding and abnormal uroflowmetric results].

The relation between symptom scoring (Boyarsky symptom severity score) and their outcome of the treatments for the patients with prostatodynia were evaluated. The patients with poor outcome were examined by uroflowmetry. Twenty-two of the 236 patients with prostadodynia complained of severe symptoms of voiding (score over 7) at the first presentation. Since those patients fell into the poor outcome category by the conventional treatments (p < 0.01), there may be some possibility that this group suffered from conditions other than prostatitis or other unknown causes. The 9 patients with severe voiding symptoms and poor outcome indicated abnormal uroflowmetric results such as abnormal peak flows in 8 patients and abnormal uroflow curves in all 9 patients. This strongly suggests that these patients have lower urinary tract dysfunctions. In conclusion, measurement of Boyarsky symptom severity scores and uroflowmentry is a useful screening method for the patients with prostatodynia with severe voiding symptoms to rule out the lower urinary tract dysfunctions.

Adult↗
PubMed2000

Allopurinol for chronic prostatitis.

OBJECTIVES: To determine the effects of allopurinol in the treatment of chronic prostatitis SEARCH STRATEGY: Trials were searched in computerized general and specialized databases (MEDLINE, Cochrane Library, Cochrane Prostate Group database), bibliographies of obtained articles, and direct contact with authors. SELECTION CRITERIA: All randomized trials of allopurinol versus placebo used to treat patients with chronic prostatitis. Acute prostatitis, bacterial prostatitis, and asymptomatic prostatitis were excluded. The main outcome measure was the change in patient-reported discomfort. DATA COLLECTION AND ANALYSIS: The reviewers extracted the data independently for the outcomes of change in patient-reported discomfort, investigator graded prostate pain, leukocyte counts, and biochemical indices. MAIN RESULTS: Only one trial with 54 men lasting 240 days (with 330 days of follow-up) met study inclusion criteria. There was a statistically significant change favoring allopurinol in patient-reported discomfort between the study and control groups at follow-up. Between days 45-225, the mean score was -0.95 (s.d. 0.19) for the allopurinol group (7 men), compared with -0.47 (s.d. 0.21) for the placebo group (7 men). The weighted mean difference (WMD) was -0.48 (95%CI -0.690, -0.270). The mean score between days 45-135 was -1.08 (s.d. 1.29) for the 25 men in the allopurinol group, compared with -0.21 (sd 0.97) for the 14 men in the control group. The WMD was -0.87 (95%CI -1.587, -0.153). The allopurinol group had significantly less investigator graded prostate pain and had lower levels of serum urate, urine urate, and expressed prostatic secretion urate and xanthine. No significant differences between the two groups regarding leukocyte counts were found. No patient receiving allopurinol had any significant side effects. Three patients in the placebo group dropped out because of side effects. REVIEWER'S CONCLUSIONS: One small trial of allopurinol for treating chronic prostatitis showed improvements in patient-reported symptom improvement, investigator-graded prostate pain, and biochemical parameters. However, the data provided, the measures used, and the statistics presented do not make these findings convincing that changes in urine and prostatic secretion composition regarding purine and pyrimidine bases resulted in the relief of symptoms. Further studies of allopurinol treatment using standardized and validated outcomes measures and analyses are necessary to determine whether allopurinol is effective.

Allopurinol↗
PubMed1997

Transurethral biopsy of the prostate for persistently elevated or increasing prostate specific antigen following multiple negative transrectal biopsies.

PURPOSE: Treatment of the patient with persistently elevated prostate specific antigen (PSA) levels after pathologically negative transrectal or manually directed prostate needle biopsy is unclear. We retrospectively evaluated the use of transurethral biopsy of the prostate as an adjunctive study for the diagnosis of prostate cancer in these patients. MATERIALS AND METHODS: From January 1993 through February 1996, 71 patients underwent transurethral biopsy in conjunction with repeat prostatic needle biopsy for a persistently elevated PSA (greater than 4 ng./ml.) after previously negative needle biopsy. All patients had at least 1 previous ultrasound guided sextant prostatic needle biopsy (mean 1.85, range 1 to 7) with or without manually directed biopsies. Following negative prostatic needle biopsy these patients subsequently underwent a minimum of a 4-quadrant transurethral sampling of the prostatic fossa followed by repeat sextant prostatic needle biopsy. A subset of patients underwent sampling of the anterior prostatic tissue or transition zone using transrectal ultrasound guided prostatic needle biopsy at transurethral biopsy. RESULTS: Of the 71 patients with elevated PSA (mean 16.2 ng./ml., range 4.2 to 171) 17 (24%) had prostate cancer on the repeat prostatic needle biopsy. Both patients who had prostate cancer on the transurethral biopsy specimens also had prostate cancer on the repeat prostatic needle biopsy specimens. A total of 68 patients had benign prostatic tissue and 1 had high grade prostatic intraepithelial neoplasia on transurethral biopsy specimens. Of 19 patients with high grade prostatic intraepithelial neoplasia on the initial prostatic needle biopsy, transurethral biopsy specimens revealed no prostate cancer or prostatic intraepithelial neoplasia. Repeat prostatic needle biopsy in these patients with high grade prostatic intraepithelial neoplasia revealed prostate cancer in 6 and high grade prostatic intraepithelial neoplasia in 4. CONCLUSIONS: In patients with persistently elevated or increasing serum PSA after a previously negative prostatic needle biopsy, transurethral biopsy is not a useful adjunct in diagnosing prostate cancer. In this high risk group of patients transurethral biopsy adds little or no diagnostic value to prostatic needle biopsy even in those with high grade prostatic intraepithelial neoplasia.

Adult↗
PubMed1993

Prostate-specific antigen density: a new prognostic indicator for prostate cancer.

PURPOSE: Prostate specific antigen density, previously described as a ratio of serum prostate specific antigen to the volume of the prostate, has been shown to be an important factor in the discrimination of patients with occult metastatic disease and patients with benign versus malignant prostatic disease. We undertook a retrospective study to determine if prostate specific antigen density was a predictor of outcome following definitive conformal radiation therapy. METHODS AND MATERIALS: Between January 1989 and August 1991, 86 patients with localized prostate cancer (confined to the prostate, periprostatic tissue, or seminal vesicles) were treated in the Department of Radiation Oncology, Columbia-Presbyterian Medical Center with definitive radiation therapy using computed tomography-guided conformal technique. Thirteen patients were excluded on the basis of prior prostatectomy, hormonal therapy, or no pretreatment prostate specific antigen measurement. Seventy-three patients were evaluable: 19% (14/73) American Urologic Association Stage A (T1), 41% (30/73) B (T2), and 40% (29/73) C (T3). Prostate specific antigen density was defined as the ratio of the pretreatment serum prostate specific antigen to the prostate volume as determined from computed tomography treatment planning scans. Pretreatment prostate specific antigen density was calculated for each patient and ranged from 0.04-3.85 with a mean and median value of 0.66 and 0.33, respectively. Prostate specific antigen failure was defined as a rise above normal level or, for patients whose nadir was above 4 ng/ml, an increase of greater than 10% above nadir. Mean prostate specific antigen follow-up was 13 months (range 2.3-31 months) by which time 66% of patients had normal prostate specific antigen (< or = 4 ng/ml) levels. RESULTS: Nine patients experienced prostate specific antigen failure. The mean prostate specific antigen density of patients with disease-free survival versus failures was 0.53 and 1.6, respectively (p < 0.05). Kaplan-Meier analysis showed that patients with a prostate specific antigen density < or = 0.3 (n = 30) had 100% actuarial disease-free survival at 30 months compared with 62% for patients with prostate specific antigen density > 0.3 (n = 43, p < 0.01). Patients with a prostate specific antigen density < or = 0.6 (n = 52) and > 0.6 (n = 21) had an 88% and 57% actuarial disease-free survival at > 24 months (p < 0.05). CONCLUSION: Prostate specific antigen density was an excellent predictor of disease-free survival (p < 0.01) and was superior to clinical stage (p > 0.05), Gleason's score (p > 0.05), and pretreatment prostate specific antigen (p < 0.05). These results suggest that patients with low prostate specific antigen density (< or = 0.3), including those with locally advanced clinical stage, high Gleason's score, or elevated pretreatment prostate specific antigen, do well with conventional radiation therapy and should not be subjected to high risk protocols. Further follow-up will be required to determine if patients with low prostate specific antigen density will have improved overall survival.

Aged↗
PubMed1997

A dose-ranging study of the efficacy and safety of tamsulosin, the first prostate-selective alpha 1A-adrenoceptor antagonist, in patients with benign prostatic obstruction (symptomatic benign prostatic hyperplasia).

OBJECTIVE: To evaluate the efficacy and safety in a dose-ranging study of tamsulosin (once-daily) as a modified-release formulation compared with placebo in patients with lower urinary tract symptoms (LUTS) associated with benign prostatic obstruction (BPO), and to establish the optimum dosage for phase III clinical studies. PATIENTS AND METHODS: Of 169 patients with LUTS associated with BPO enrolled in a 3 week placebo run-in period, 126 were subsequently randomized to receive placebo (28), or 0.2 mg (35), 0.4 mg (30), or 0.6 mg (33) of tamsulosin once daily for 4 weeks. Free-flow and pressure-flow measurements, and modified Boyarsky symptom scores were used to determine efficacy. Safety was evaluated by monitoring adverse events and vital signs (including 8 h after the first dose), and by laboratory determinations. RESULTS: Tamsulosin 0.4 mg and 0.6 mg produced significantly greater improvements in maximum urinary flow rate (Qmax) (2.2 mL/s, 22.6%, and 1.8 mL/s, 20.2%, respectively) than did placebo (-0.1 mL/s, -0.9%). The results from the pressure-flow studies confirmed the results for Qmax in the free flow studies, with optimum and significant effects for tamsulosin 0.4 mg. This also applied for detrusor pressure at maximum flow, which decreased by 26.6 cmH2O (-28.2%) on 0.4 mg tamsulosin whereas it increased by 4.9 cm H2O (5.7%) on placebo. The greatest reductions in total symptom score were obtained with tamsulosin 0.4 mg and 0.6 mg (4.1, -28.7%, and 4.4 points, -28.2%, respectively) compared with reductions of 3.4 (-20.1%) in the tamsulosin (0.2 mg) and 2.9 points (-17.7%) in the placebo groups. The difference in effects on total symptom score between treatment groups was not statistically significant, which can be attributed to the small sample size. Tamsulosin was well tolerated; at least one adverse event was reported by 29%, 23%, 27% and 36% of patients in the placebo and tamsulosin 0.2 mg, 0.4 mg and 0.6 mg groups, respectively. There were no apparent tamsulosin dose-dependent changes in vital signs from baseline to the end of 4 weeks of randomized treatment. Tamsulosin caused no statistically significantly greater changes in blood pressure than placebo during the initial 8 h after the first dose. There were no clinically significant changes in laboratory variables. CONCLUSION: Tamsulosin is well tolerated and effective in improving urinary flow and relieving LUTS associated with BPO. Optimal effects are achieved with tamsulosin 0.4 mg administered once daily.

Adrenergic alpha-Antagonists↗