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PubMed2002

Leukocyte and bacterial counts do not correlate with severity of symptoms in men with chronic prostatitis: the National Institutes of Health Chronic Prostatitis Cohort Study.

PURPOSE: We examine whether leukocytes and bacteria correlate with symptom severity in men with chronic prostatitis/chronic pelvic pain syndrome. MATERIALS AND METHODS: All 488 men screened into the National Institutes of Health Chronic Prostatitis Cohort Study before close of recruitment on August 22, 2001 were selected for analysis. The National Institutes of Health Chronic Prostatitis Symptom Index, including subscores, were used to measure symptoms. Urethral inflammation was defined as white blood cell (WBC) counts of 1 or more (1+) in the first voided urine. Participants were classified as category IIIa based on WBC counts of 5 or more, or 10 or more (5+, 10+) in the expressed prostatic secretion, or 1+ or 5+ either in the post-expressed prostatic secretion urine (voided urine 3) or semen. Uropathogens were classified as localizing if the designated bacterial species were absent in voided urine 1 and voided urine 2 but present in expressed prostatic secretion, voided urine 3 or semen, or present in expressed prostatic secretion, voided urine 3 or semen at 2 log concentrations higher than at voided urine 1 or 2. Associations between symptoms, and inflammation and infection were investigated using generalized Mantel-Haenszel methods. RESULTS: Of all participants 50% had urethral leukocytes and of 397 with expressed prostatic secretion samples 194 (49%) and 122 (31%) had 5+ or 10+ WBCs in expressed prostatic secretion, respectively. The prevalence of category IIIa ranged from 90% to 54%, depending on the composite set of cut points. None of the index measures were statistically different (p >0.10) for selected leukocytosis subgroups. Based on prostate and semen cultures, 37 of 488 men (8%) had at least 1 localizing uropathogen. None of the index measures were statistically different (p >0.10) for selected bacterial culture subgroups. CONCLUSIONS: Although men with chronic prostatitis routinely receive anti-inflammatory and antimicrobial therapy, we found that leukocytes and bacterial counts as we defined them do not correlate with severity of symptoms. These findings suggest that factors other than leukocytes and bacteria also contribute to symptoms associated with chronic pelvic pain syndrome.

Chronic Disease↗
PubMed1994

Natural history of changes in prostate specific antigen in early stage prostate cancer.

Until recently, the only information on the growth rate of prostate tumors has been derived from cross-sectional histological labeling studies, autopsy data and clinical studies of patients managed expectantly. However, serial measurements of prostate specific antigen (PSA) may now allow studies of the natural history of the earliest stages of prostate cancer. Frozen sera samples from the Baltimore Longitudinal Study of Aging have been used to compare the patterns of change in PSA levels in men with and without prostate cancer up to 25 years before the diagnosis of cancer. Men with no prostatic disease exhibited a slow linear increase in PSA levels, whereas benign prostatic hyperplasia cases showed a gradual acceleration in the rate of change in PSA. In contrast, cancer cases exhibited an early linear phase followed by an exponential phase of increase in PSA levels before diagnosis. On average, the exponential phase of PSA increases began 7 to 9 years before the tumors were detected clinically. Thus, there is a significant window of opportunity for early detection of prostate cancer. The changes in PSA observed in men with and without prostate cancer are consistent with available information on prostatic growth and the long natural history of prostate cancer. A better understanding of the various factors that affect serum PSA levels may allow more effective use of PSA measurements to detect early stage tumors and predict the biological potential of a tumor.

Adult↗
PubMed2001

Low levels of prostate-specific antigen predict long-term risk of prostate cancer: results from the Baltimore Longitudinal Study of Aging.

OBJECTIVES: To evaluate the relationship between low prostate-specific antigen (PSA) levels that are considered normal and the long-term risk of prostate cancer. METHODS: The relative risk of, and cumulative probability of freedom from, prostate cancer by PSA level and age decade was evaluated in male participants of a longitudinal aging study, the Baltimore Longitudinal Study of Aging (National Institute on Aging). The relative risk was estimated from a Cox proportional hazards regression model for men aged 40 to 49.9 (n = 351) and 50 to 59.9 (n = 445). The disease-free probability was determined by Kaplan-Meier survival analysis. RESULTS: The relative risk of prostate cancer for men aged 40 to 49.9 was 3.75 (range 1.6 to 8.6) when the PSA level was at or greater than the median (0.60 ng/mL) compared with men with PSA levels less than the median. This risk was similar for men aged 50 to 59.9 when comparing those with PSA levels greater than and less than the median (0.71 ng/mL). At 25 years, the cumulative probability of freedom from prostate cancer for men aged 40 to 49.9 was 89.6% (range 81% to 97%) and 71.6% (range 60% to 83%) when the PSA level was less than and greater than the median, respectively. The 25-year disease-free probability for men aged 50 to 59.9 was 83.6% (range 76% to 91%) and 58.9% (range 48% to 70%) when the PSA level was less than and greater than the median, respectively. CONCLUSIONS: The association between the baseline serum PSA level and the subsequent risk of prostate cancer suggests that the biologic events that predispose to prostate cancer begin early in middle age. Men who have baseline PSA levels that are "normal" but reflect a higher risk of prostate cancer may be the most appropriate candidates for future prevention trials. Those men with the lowest risk of prostate cancer on the basis of the baseline PSA measurements are unlikely to benefit from frequent PSA surveillance in an effort to detect prostate cancer early.

Adult↗
PubMed2003

Best approach for prostate cancer detection: a prospective study on transperineal versus transrectal six-core prostate biopsy.

OBJECTIVES: To compare the efficacy of transperineal versus transrectal six-core prostate biopsy. Transrectal sextant biopsy is the most common method for prostate cancer detection. However, the cancer detection rate with this technique is increasingly considered inadequate. Different prostate biopsy procedures, mainly based on addition of additional transrectal cores to traditional sextant biopsy, have been proposed to increase the cancer diagnosis rate. The efficacy of the transperineal approach has not yet been fully established. METHODS: In a prospective study, 107 patients with elevated prostate-specific antigen levels (greater than 4.0 ng/mL) underwent prostate biopsy with six transperineal cores, using a "fan" scheme, plus six transrectal cores, according to the sextant technique. The median prostate-specific antigen level was 8.2 ng/mL (range 4.1 to 240). RESULTS: The overall cancer detection rate was 40% (43 of 107); prostate cancer was found in 38% (41 of 107) of patients with the transperineal approach and in 32% (34 of 107) of patients with the transrectal approach. Of 43 diagnosed cancers, 41 (95%) were found with the transperineal approach and 34 (79%) with the transrectal approach (P = 0.012). No patient had low-grade cancer (Gleason score 2 to 4), 25 patients had intermediate-grade cancer (Gleason score 5 to 6), and 18 patients had high-grade cancer (Gleason score 7 to 10). CONCLUSIONS: This is the first report comparing in vivo two different approaches to prostate biopsy. Transperineal biopsy seems superior to transrectal biopsy to detect prostate cancer. Both the transperineal and the transrectal approach should be familiar to the urologist who needs to obtain an adequate cancer detection rate. Transrectal sextant biopsy cannot be considered the standard technique for prostate cancer detection.

Aged↗
PubMed1998

Comparison of prostate-specific antigen corrected for total prostate volume and transition zone volume in a population-based screening study.

OBJECTIVES: To compare the discriminatory potential between prostate cancer and benign conditions of the prostate in a population-based screening study, of serum prostate-specific antigen levels (PSA) and PSA corrected for both the total prostate volume (PSA-D) and the transition zone volume (PSA-T). METHODS: In a randomized population-based screening study (Rotterdam section of the European Randomized Study of Screening for Prostate Cancer), in which 10,865 men have been screened, the biopsy results of 1202 men with PSA levels of 4 ng/mL or more were evaluated. Planimetric and prolate ellipsoid volumes of the total prostate as well as of the transition zone were measured. The measured volumes were compared with the volumes of 57 radical prostatectomy specimens through Spearman's rank correlation coefficient and agreement tests. A receiver operating characteristic (ROC) curve analysis was done of sensitivity and specificity of biopsy indications through PSA and PSA corrected for the volumes measured with transrectal ultrasound. RESULTS: In the 1202 men studied, 361 cases of prostate cancer were diagnosed. Both PSA-D and PSA-T showed a significantly higher area under the ROC curve (0.77 and 0.79, respectively) than PSA alone (area 0.65). There was no significant difference between PSA-D and PSA-T. The use of a PSA-D threshold value of 0. 10 ng/mL/cc would have avoided 28% of biopsies at the cost of 10% of detectable cancers. A PSA-D threshold of 0.15 ng/mL/cc would have avoided 73.8% of biopsies at the cost of not diagnosing 43.8% of detectable cancers. CONCLUSIONS: The planimetrically obtained prostate volume showed a more favorable agreement with the radical prostatectomy volume than the prolate ellipsoid volume. The discriminatory potential of the corrected PSA value is better at predicting the results of needle biopsy of the prostate when compared with PSA alone. The use of the transition zone volume for this correction results in a higher discriminatory potential when compared to the use of the total prostate volume; however, the observed difference was not statistically significant.

Aged↗
PubMedDate not supplied

Incidental detection of population-based prostate cancer incidence rates through transurethral resection of the prostate.

OBJECTIVE: To provide an updated assessment of the influence transurethral resection of the prostate (TURP) has on incidental detection of prostate cancer and to characterize stage, histologic grade, and treatment patterns among these cases. METHODS: Analyses were based on 17,310 histologically confirmed prostate cancer cases ages 45 years and older recorded in the Utah Cancer Registry between 1980 and 1999 and 6426 TURP procedures recorded in the Utah Hospital Discharge Database from 1992 through 1999. An algorithm was developed for identifying TURP-detected prostate cancer incidence. RESULTS: Age-specific TURP-detected prostate cancer incidence rates tended to be flat between 1980 and 1990, decline through 1994, and then level off. Much of the decrease corresponds to the prostate-specific antigen (PSA) screening induced peak and subsequent fall in total prostate cancer incidence rates. Leveling off in the TURP-detected rates between 1994 and 1999 corresponds with a leveling off in the total prostate cancer incidence rates. The percentage of prostate cancer detected by TURP significantly increases with age, within each age group, but decreases over calendar years. For ages 45 years and older, the percentage of TURP-detected cases was 39.0% in 1980 to 1984, 33.9% in 1985 to 1989, 12.2% in 1990 to 1994, and 7.4% in 1995 to 1999. TURP-detected cases were significantly less likely to undergo radical prostatectomy or radiation therapy across age groups, despite having lower stage and histologic grade at diagnosis. CONCLUSION: TURP-detected prostate cancer rates have leveled off in the latter part of the 1990s, explaining about 10% of all detected cases. These cases have relatively good biologic potential and are less likely to pursue aggressive therapy.

Aged↗
PubMedDate not supplied

Significance of high-grade prostatic intraepithelial neoplasia on prostate biopsy.

The early diagnosis of prostate cancer has been facilitated by the development of serum prostate-specific antigen (PSA) testing and evolution in transrectal ultrasound-guided biopsy of the prostate. Over a decade has passed since the initial recommendations for systematic sextant sampling of the prostate to increase the accuracy of cancer detection. Subsequently, variations in the number and location of biopsies have been proposed to maximize prostate cancer detection and obtain more complete information regarding tumor grade, tumor volume, and local stage. Although current biopsy strategies provide a wide sampling of the prostate gland, biopsy histology may not be conclusive for either the presence or absence of adenocarcinoma. High-grade prostatic intraepithelial neoplasia (HGPIN) is found in a significant fraction of patients undergoing transrectal prostate biopsies. In this article, we discuss the significance of high-grade prostatic intraepithelial neoplasia and other abnormal histology findings and current evidence addressing the presence of cancer and need for additional prostate biopsies.

Adenocarcinoma↗
PubMed2007

Serum prostate-specific antigen as a predictor of prostate volume in Korean men with lower urinary tract symptoms.

The aim of the study was to assess the utility of prostate-specific antigen (PSA) as a predictor of prostate volume indexes (total prostate volume (TPV), transition zone volume and transition zone index) in Korean men with lower urinary tract symptoms (LUTS). From September 2003 to April 2006, 3431 patients with LUTS were included in the study; they had a median age of 63.8 years, a median prostate volume of 22.6 ml and a median serum PSA of 1.04 ng/ml. Men with a baseline PSA of >10 ng/ml were excluded, to reduce the likelihood of including occult prostate cancer. Prostate volume indexes and serum PSA levels had an age-dependent log-linear relationship. Receiver operating characteristic curve analysis showed that PSA had good predictive value for various prostate volume indexes thresholds. The approximate age-specific criteria for detecting men with a TPV of >40 ml are PSA levels of 1.20, 1.44 and 1.72 ng/ml for men with LUTS in their sixth, seventh and eighth decades, respectively. The results show that serum PSA identifies Korean men with large prostates reasonably well. Korean men may produce and/or release more PSA per unit prostate volume than white men. The cutoffs for PSA and prostate volume to response to LUTS therapy should be determined in this population.

Aged↗
PubMed2000

Change in the ratio of free-to-total prostate-specific antigen during progression of advanced prostate cancer.

BACKGROUND: The ratio of free-to-total prostate-specific antigen (PSA) is different in benign prostatic hyperplasia and in the early stage of prostate cancer. The present study was undertaken to examine the ratio of free-to-total PSA in the advanced stage of this cancer and its subsequent change during course of the disease. METHODS: Free and total PSA were measured in sera collected from the following patients with benign and cancerous prostatic diseases: 47 cases of benign prostatic hypertrophy, nine in TIC with less than 10 ng/mL of total PSA, 11 in stage C, 16 in D2, 22 in remission under endocrine therapy, and 12 in relapse. In addition, PSA was measured sequentially in four other patients who were also in relapse. RESULTS: The ratio of free-to-total PSA was similar in early and advanced stages of untreated prostate cancer and was lower than that in benign prostatic hyperplasia. The ratio increased to the level of benign prostatic hyperplasia during remission from stages C and D2 under endocrine therapy. There was no correlation with the intervals from the start of the therapy to examination. Following relapse, the ratio came down gradually to the level obtained in untreated prostate cancer. CONCLUSION: The ratio of free-to-total PSA was similar in all stages of untreated prostate cancer. Response and relapse to endocrine therapy were associated with increase and decrease in ratio, respectively.

Disease Progression↗
PubMed2001

Variation in percentage-free prostate-specific antigen (PSA) with prostate volume, age and total PSA level.

OBJECTIVE: To examine the correlation between prostate volume, patient age and total prostate-specific antigen (tPSA) with the percentage-free PSA (f/tPSA) in a population-based cohort of men with no prostate cancer and with a tPSA of < 10.0 ng/mL. SUBJECTS AND METHODS: Men who in 1988-1989, after randomized selection in the general population, participated in a population-based screening study for prostate cancer, were investigated. In all, 1622 of the men (aged 55-70 years) were considered free from prostate cancer and had a tPSA level of < 10.0 ng/mL. The f/tPSA and tPSA were determined in frozen sera from each individual, and related to prostate volume and age measured at the time of the study. The entire population was investigated, as were four subpopulations based on tPSA levels (< 2.0, 2.0-3.9, 4.0-6.9 and 7.0-9.9 ng/mL). Statistical calculations included multiple regression and correlation analysis. RESULTS: The f/tPSA level varied with prostate volume and age, but the decisive factor for this variation was the tPSA level. The closest correlation was in the tPSA interval 7.0-9.9 ng/mL, where volume and age together explained 47% of the variation in f/tPSA. Also, for men with tPSA levels in each of the intervals 2.0-3.9, 4.0-6.9 and 7.0-9.9 ng/mL, the f/tPSA increased with higher prostate volumes and age. In men with tPSA levels of < 2.0 ng/mL the f/tPSA was not affected by variations in prostate volume or age. CONCLUSION: The variation in f/tPSA with prostate volume, age and tPSA is highly dependent on the tPSA level. Volume and age in the tPSA interval 7.0-9.9 ng/mL can explain almost half the variation in f/tPSA, whereas this influence is insignificant in men with a tPSA of < 2.0 ng/mL.

Age Factors↗
PubMed1991

Measurement of prostate-specific antigen in serum as a screening test for prostate cancer.

BACKGROUND: Prostate-specific antigen (PSA) is secreted exclusively by prostatic epithelial cells, and its serum concentration is increased in men with prostatic disease, including cancer. We evaluated its usefulness in the detection and staging of prostate cancer. METHODS: We measured serum PSA concentrations in 1653 healthy men 50 or more years old. Those with PSA values greater than or equal to 4.0 micrograms per liter then underwent rectal examination and prostatic ultrasonography. Ultrasound-directed prostatic needle biopsies were performed in the men with abnormal findings on rectal examination, ultrasonography, or both. The results were compared with those in 300 consecutively studied men 50 or more years old who underwent ultrasound-directed biopsy because of symptoms or abnormal findings on rectal examination. RESULTS: Serum PSA levels ranged from 4.0 to 9.9 micrograms per liter in 6.5 percent of the 1653 men (107). Nineteen of the 85 men in this group (22 percent) who had prostatic biopsies had prostate cancer. Serum PSA levels were 10.0 micrograms per liter or higher in 1.8 percent of the 1653 men (30). Eighteen of the 27 men in this group (67 percent) who had prostatic biopsies had cancer. If rectal examination alone had been used to screen the men who had biopsies, 12 of the 37 cancers (32 percent) would have been missed. If ultrasonography alone had been used to screen these men, 16 of the 37 cancers (43 percent) would have been missed. Serum PSA measurement had the lowest error rate of the tests, and PSA measurement plus rectal examination had the lowest error rate of the two-test combinations. CONCLUSIONS: The combination of measurement of the serum PSA concentration and rectal examination, with ultrasonography performed in patients with abnormal findings, provides a better method of detecting prostate cancer than rectal examination alone.

Age Factors↗
PubMed2002

Expression of colony-stimulating factor 1 receptor during prostate development and prostate cancer progression.

Colony-stimulating factor-1 receptor (CSF-1R) is the major regulator of macrophage development and is associated with epithelial cancers of the breast and ovary. Immunohistochemistry analysis of murine prostate development demonstrated epithelial expression of CSF-1R during the protrusion of prostatic buds from the urogenital sinus, during the prepubertal and androgen-driven proliferative expansion and branching of the gland, with a decline in older animals. Models of murine prostate cancer showed CSF-1R expression in areas of carcinoma- and tumor-associated macrophages. Several human prostate cancer cell lines and primary cultures of human prostate epithelial cells had low but detectable levels of CSF-1R. Human prostatectomy samples showed low or undetectable levels of receptor in normal glands or benign prostatic hypertrophy specimens. Staining was strongest in areas of prostatic intraepithelial neoplasia or carcinoma of Gleason histological grade 3 or 4. The activated form of the receptor reactive with antibodies specific for phosphotyrosine modified peptide sequences was observed in samples of metastatic prostate cancer. Immunohistochemistry showed strong expression of CSF-1R by macrophage lineage cells, including villous macrophages and the syncytiotrophoblast layer of placenta, Kupper cells in the liver, and histiocytes infiltrating near prostate cancers. These observations correlate CSF-1R expression with changes in the growth and development of the normal and neoplastic prostate.

Animals↗
PubMed2002

Polymorphic CAG repeats in the androgen receptor gene, prostate-specific antigen polymorphism and prostate cancer risk.

As the development of prostate cancer is androgen-dependent, it has been hypothesized that variation in transcriptional activity by the androgen receptor (AR) related to polymorphic CAG repeats in exon 1, influences prostate cancer risk. The AR regulates gene transcription by binding to androgen-response elements (AREs) in target genes, such as the prostate-specific antigen (PSA). In the ARE-I sequence of the PSA gene an adenine to guanine polymorphism is described. It has been hypothesized that the AR binds the two PSA alleles (A and G) with differing affinities and may, thereby, differentially influence prostate cancer risk. To examine the role of the polymorphisms in the AR and PSA genes in prostate cancer susceptibility, we conducted a case-control study of Austrian Caucasians with 190 newly diagnosed prostate cancer patients and 190 age-matched control men with benign prostatic hyperplasia (BPH). The polymorphisms were determined by polymerase chain reaction (PCR)-based methods using DNA from peripheral white blood cells. Logistic regressions were performed to calculate odds ratios (OR) and confidence limits (CL) and to control for possible confounders. Our data provide no evidence for an association between prostate cancer and CAG repeat length. However, we found a significant influence of the ARE-I PSA polymorphism on prostate cancer risk, when calculating the combination of the A/G and G/G genotypes relative to subjects with the A/A genotype (OR = 0.63; 95% CL 0.39-0.99; P = 0.048), suggesting that the G allele has a protective effect. In a case analysis according to Gleason score, the PSA G/G genotype was significantly more frequent in patients with Gleason score >7 (35.1%) than in patients with Gleason score <7 (21.5%), providing evidence that the PSA G/G genotype is associated with more advanced disease at time of diagnosis. However, the ambivalent role of the PSA during prostate carcinogenesis needs further investigation.

Aged↗
PubMed2005

Differently regulated androgen receptor transcriptional complex in prostate cancer compared with normal prostate.

BACKGROUND: The coregulators of androgen receptors (AR) influence the transcriptional activity of AR. In order to better understand the mechanism of carcinogenesis in the prostate, we investigated the relationship between AR and AR coregulators in the early stage of prostate cancer. METHODS: mRNA was purified from 15 samples of prostate cancer and normal tissue and transcribed into cDNA. We screened eight AR coregulators for different gene expressions in prostate cancer, comparing these with normal tissue by a real-time polymerase chain reaction Syber green method, then quantified each component of the AR transcriptional complex by a real-time PCR hybri-probe method. The extent of gene expression similarity was compared by simple Pearson correlation coefficient analysis between prostate cancer and normal tissue. We applied a z-test to calculate significant differences between r-values. RESULTS: We found that the gene expression level of FHL2 decreased in prostate cancer compared with that of normal tissue and the gene expressions of PSA, AR and SMRT were not significant. The correlation coefficient analysis revealed that strong associations were found in the pairs of AR versus SMRT, AR versus FHL2 and SMRT versus FHL2 in prostate cancer, whereas similarity was found only in the pair of AR versus FHL2 in normal tissue. No association was observed between prostate-specific antigen and other genes. CONCLUSION: These results demonstrate that the AR-AR coregulator relationship is different between prostate cancer and normal tissue, leading to the hypothesis that the AR transcriptional complex is regulated differently between prostate cancer and normal tissue.

Aged↗
PubMed2005

Volume-adjusted prostate-specific antigen (PSA) variables in detecting impalpable prostate cancer in men with PSA levels of 2-4 ng/mL: transabdominal measurement makes a significant contribution.

OBJECTIVE: To examine whether prostate-specific antigen (PSA) levels adjusted according to prostate volume improve prostate cancer detection using transrected biopsies in men with PSA levels of 2-4 ng/mL, and benign findings on a digital rectal examination (DRE). PATIENTS AND METHODS: Men aged < or = 79 years and with serum PSA levels of 2-4 ng/mL and normal DRE findings were prospectively enrolled. Eligible patients were recommended for transrectal prostate biopsies after measuring prostate volumes with transrectal (TRUS) and transabdominal (TAUS) ultrasonography, and transition zone volumes with TRUS. In addition to PSA levels and the free-to-total PSA ratio, volume-adjusted PSA levels, PSA densities determined by TRUS (PSAD(TRUS)), and TAUS (PSAD(TAUS)), and PSA transition zone densities (PSATzD) were compared using receiver operating characteristic analysis. RESULTS: Prostate cancer was diagnosed in 31 (22%) of the 139 men who had prostate biopsies. The area under the curve (AUC) of PSAD(TRUS) (0.796) and PSATzD (0.792) was similar and significantly greater than that of PSA (AUC 0.588) and the free-to-total PSA ratio (AUC 0.658). PSAD(TAUS) was a significantly better indicator of prostate cancer than PSA levels alone (P = 0.043). CONCLUSION: As predictors of prostate cancer, there were no significant differences between PSAD(TRUS) and PSATzD. Although PSAD(TAUS) was worse than PSA variables adjusted by total and transition zone prostate volumes determined by TRUS, it was a better predictor than the PSA value alone in men with a low PSA level. These results indicate that TAUS is worthwhile where the routine use of TRUS before biopsy is difficult.

Adult↗
PubMed1995

The alpha 1C-adrenoceptor in human prostate: cloning, functional expression, and localization to specific prostatic cell types.

1. Benign prostatic hyperplasia (BPH) causes urinary obstruction in aging men that frequently requires surgery to relieve the symptoms of urinary retention, nocturia, and micturition. Smooth muscle tone which contributes to the urethral constriction in the enlarged gland appears to be mediated by the alpha 1-adrenoceptors. In this paper, molecular and pharmacological approaches are used to establish the role played by the alpha 1C-adrenoceptor subtype in the prostate. 2. The alpha 1-adrenoceptor subtype(s) expressed in human prostate were investigated by use of polymerase chain reaction (PCR), Northern blot, and in situ hybridization. The alpha 1C subtype was found in both prostate stromal and glandular cells while alpha 1B and alpha 1D subtypes were expressed in glandular cells. High expression levels for alpha 1C were observed in prostate cancer tissues in both stroma and glandular cells. 3. Full length alpha 1C-adrenoceptor cDNA was cloned from human prostate. Stable mammalian cell lines expressing human alpha 1B-, alpha 1C-, and alpha 1D-adrenoceptors were made. Membranes prepared from these cell lines and human prostate were used to evaluate the pharmacological profiles of human alpha 1B-, alpha 1C- and alpha 1D-adrenoceptors in comparison to human prostate. Leverage plot analysis of compound affinities determined by competition for [125I]-I-HEAT binding demonstrated that the alpha 1C subtype is the predominant alpha 1-adrenoceptor in human prostate. 4. The alpha 1-adrenoceptors cause smooth muscle constriction by coupling to IP3 turnover and intracellular Ca2+ release. Using stable cell lines to measure IP3 production in response to noradrenaline, alpha 1C stimulated IP3 production most efficiently, with alpha 1B at an intermediate level, while little IP3 above background could be detected with alpha 1D. These results supported a functional role of the alpha 1C-adrenoceptor on prostate smooth muscle constriction by noradrenaline stimulation.

Amino Acid Sequence↗
PubMed1986

Prostatic carcinoma and benign prostatic hyperplasia: inability of MR imaging to distinguish between the two diseases.

Forty patients with prostatic carcinoma or benign prostatic hyperplasia (BPH) underwent magnetic resonance (MR) imaging of the prostate. In vitro MR images of six prostate specimens were also obtained. The prostatic parenchyma was best evaluated by a T2-weighted spin-echo pulse sequence. The prostate both in patients with prostatic carcinoma and patients with BPH often had an inhomogeneous and nodular appearance on T2-weighted images. While most of the prostatic carcinomas appeared hyperintense relative to muscle and adjacent prostatic parenchyma, some of the hyperplastic nodules had a signal intensity similar to carcinoma. With current imaging techniques, MR imaging cannot differentiate prostatic carcinoma from BPH with certainty.

Adult↗
PubMed2004

PC cell-derived growth factor expression in prostatic intraepithelial neoplasia and prostatic adenocarcinoma.

PURPOSE: PCDGF (PC cell-derived growth factor), also called progranulin, is a M(r) 88000 glycoprotein precursor of granulin. It is a novel growth factor that stimulates cell proliferation, confers epithelial tumorigenesis, and promotes tumor invasion. Here we investigate the potential of PCDGF as a therapeutic target for prostate cancer. EXPERIMENTAL DESIGN: We studied the expression of PCDGF in invasive prostate cancer, adjacent high-grade prostatic intraepithelial neoplasia (PIN), and benign prostate tissue from 99 human prostate specimens. The level of PCDGF expression was correlated with various clinicopathological characteristics. RESULTS: Normal prostate tissue did not express (53/99), or expressed low levels (46/99) of PCDGF. In the 46 normal prostate specimens that expressed PCDGF, most of them had less than 10% of cells expressing PCDGF. PCDGF expression could be detected in more than 50% of cells in all specimens of PIN and invasive prostate cancer. The expression of PCDGF in normal prostate tissue was much less intense and in a smaller fraction of cells than in PIN and invasive adenocarcinoma (P < 0.0001). There was no correlation of PCDGF expression with age, Gleason score, pathological stage, status of lymph node metastasis, extraprostatic extension, perineural invasion, surgical margins, and vascular invasion. CONCLUSIONS: Our data suggest that the induction of PCDGF expression occurs during the development of PIN. PCDGF may be a new molecular target for the treatment and prevention of prostate cancer.

Adenocarcinoma↗