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At least 1,063 records · Page 59Linked to original sources
PubMed2004

Chemoprevention of prostate cancer in men at high risk: rationale and design of the reduction by dutasteride of prostate cancer events (REDUCE) trial.

PURPOSE: Chemoprevention may significantly impact the natural history of prostate cancer. The most potent intraprostatic androgen, dihydrotestosterone, has a significant role in the pathophysiology of prostate cancer. It represents a biologically plausible target for chemoprevention through the inhibition of 5alpha-reductase isoenzymes. MATERIALS AND METHODS: The Reduction by Dutasteride of Prostate Cancer Events clinical trial is an international, multicenter, double-blind, placebo controlled chemoprevention study designed to determine if dutasteride 0.5 mg daily decreases the risk of biopsy detectable prostate cancer. A total of 8,000 men will be randomized to receive dutasteride or placebo for 4 years. Eligible men must be 50 to 75 years old, have a serum prostate specific antigen of 2.5 to 10 ng/ml (ages 50 to 60 years) or 3.0 to 10 ng/ml (older than 60 years). Men must have a negative 6 to 12 core biopsy within 6 months prior to enrollment. Repeat biopsies will be taken at 2 and 4 years. The rates of prostate cancer for each treatment group will be compared. Genetic and protein biomarkers of prostate cancer, and the effect of dutasteride on benign prostatic hyperplasia and prostatitis symptomatology and histopathology will also be assessed. RESULTS: Results remain to be determined. CONCLUSIONS: The study will examine the effects of the dual 5alpha-reductase inhibitor dutasteride on the natural history of prostate cancer in men at increased risk for this malignancy. It affords a unique opportunity to examine biomarkers and genetic linkage for prostate cancer, and assess a range of prostate health outcome measures.

5-alpha Reductase Inhibitors↗
PubMed2000

The influence of dietary and environmental factors on prostate cancer risk.

Prostate cancer is the most common malignancy found in males and one of the most common causes of cancer death. The epidemiology implicates environmental and nutritional factors in the initiation and progression of the disease. Identification of these factors would allow chemoprevention strategies to be tested. Potent mutagenic and carcinogenic heterocyclic amines and polycyclic aromatic hydrocarbons are produced in cooked meat, and following metabolic activation some of them are strongly associated with prostate carcinogenesis in rodents. Primary cell cultures of human prostate epithelial cells were obtained from patients undergoing transurethral resection of the prostate. Metabolic activation of the cooked food carcinogens 2-amino-1-methyl-6-phenylimidazo- [4,5-b]pyridine (PhIP) and benzo[a]pyrene (B[a]P) was examined and resultant DNA damage (single strand breaks) measured using the Comet assay. Increased concentrations of carcinogen were associated with increased DNA damage and comet tail length compared to controls. Prostate Cancer and Prostatic Diseases (2000) 3, 256-258

Journal Article↗
PubMed2007

Global update on defining and treating high-risk localized prostate cancer with leuprorelin: a Japanese perspective--the effect of primary androgen deprivation therapy on stage C prostate cancer.

Stage C prostate cancer, where the tumour has extended beyond the capsule of the prostate, is typically a high-risk disease. According to the National Cancer Institute Physician Data Query the treatments of choice for stage C disease comprise external beam radiation therapy (with or without the addition of adjuvant hormone therapy), androgen deprivation by either surgery or hormone therapy, radical prostatectomy, or careful observation. From 2001, the Japanese Urological Association initiated computer-based registration of all patients with prostate cancer in Japan. Data show that overall, 57% of all patients and 46% of those with T1c to T3 disease had primary androgen deprivation therapy (PADT). Similarly, the Japanese Prostate Cancer Group undertook a large-scale epidemiological surveillance study in Japan and found that the most commonly used hormone therapy is PADT, regardless of disease stage. To date, two randomized, controlled trials of the effect of PADT on stage C prostate cancer in elderly (> or =75 years old) patients have been undertaken in Japan. The results showed that patients with locally advanced prostate cancer treated with PADT are likely to have a life-expectancy similar to that of the normal population. In one study, combined androgen blockade (CAB) with leuprorelin plus chlormadinone appeared to prolong time to disease progression when compared with leuprorelin monotherapy, but there was no difference in survival between these treatment groups. In a second study CAB with an luteinizing hormone-releasing hormone (LHRH) agonist plus bicalutamide was found to prolong time to progression when compared with LHRH agonist monotherapy, but survival results for these regimens are still awaited.

Aged↗
PubMed2005

Validation of molecular targets in prostate cancer.

As prostate cancer is not a single disease, it is important to identify the pivotal pathway in the patient being treated. The molecular environment is the site of current oncological research to define new therapeutic targets for hormone-refractory disease, offering the potential to eventually individualize treatment through stratification of pathways. Targets may be validated either phenotypically (e.g. androgen receptor, cadherin) or functionally (e.g. prostate cancer-specific genes). In addition, several other candidates are potentially suitable, while others await discovery. Important initial steps have been made in the search for prostate cancer stem cells; identifying stem cells and the stromal, hormonal, and other signalling molecules that influence their behaviour would have important implications for managing prostate cancer. Although individual therapeutic pathways might be ineffective in a particular molecular environment, combinations of approaches might be capable of producing synergistic effects. A multimodal approach thus might be the best solution. Determining where best to search for a molecular target, and validating whether the target is associated with a sufficiently aggressive malignant process to justify further study is difficult, but the potential benefits are enormous.

Androgens↗
PubMed1998

Evaluation of the digital rectal examination as a screening test for prostate cancer. Rotterdam section of the European Randomized Study of Screening for Prostate Cancer.

BACKGROUND: The utility of digital rectal examination (DRE) as a screening test for early detection of prostate cancer has not been established. Therefore, we evaluated the usefulness of DRE as a stand-alone screening test and in conjunction with measured serum prostate-specific antigen (PSA) levels of 0-3.9 ng/mL and transrectal ultrasonography (TRUS). METHODS: Our study population consisted of 10,523 men aged 54-76 years who were randomly assigned to the screening arm of the Rotterdam, The Netherlands, section of the European Randomized Study of Screening for Prostate Cancer. The underlying prevalence of detectable prostate cancer was estimated by logistic regression analysis and used for calculating the sensitivity of DRE as a test. Pathologic characteristics of 105 radical prostatectomy specimens were used to determine the aggressiveness of the tumors diagnosed (and missed) by DRE. RESULTS: The overall detection rate for prostate cancer in this population when serum PSA measurement, DRE, and TRUS were used was 4.5%, and the detection rate with DRE alone was 2.5%. The positive predictive value of DRE ranged from 4% to 11% in men with PSA levels of 0-2.9 ng/mL and from 33% to 83% in men with PSA levels of 3.0-9.9 ng/mL or more. Most tumors detected by DRE in men with PSA levels of less than 4.0 ng/mL were small (mean volumes = 0.24-0.83 mL), and most were well differentiated (Gleason scores of 6 or less). Minimal, moderate, and advanced cancers were seen in 42%, 42%, and 16% of men, respectively, with a PSA level of 4.0 ng/mL or less. DRE alone allowed detection of 264 (55.8%) of 473 cancers; 82 (17.3%) of the 473 cancers would have remained undetected by PSA-based screening alone (i.e., no follow-up procedures for PSA values of 0-3.9 ng/mL). CONCLUSIONS: For PSA values of 0-3.9 ng/mL, the positive predictive value and sensitivity of DRE, tumor volume, and tumor grade were strongly dependent on PSA level. DRE has a poor performance in low PSA ranges.

Aged↗
PubMed2005

A germ line mutation that delays prostate cancer progression and prolongs survival in a murine prostate cancer model.

Circulating insulin-like growth factor-I (IGF-I) levels have been shown to be related to risk of prostate cancer in epidemiologic studies. While specific genetic loci responsible for interindividual variation in circulating IGF-I levels in normal men have not been identified, candidate genes include those involved in the growth hormone (GH)-IGF-I axis such as the hypothalamic factors GH releasing hormone (GHRH) and somatostatin and their receptors. To investigate the role of the GH-IGF-I axis on in vivo prostate carcinogenesis and neoplastic progression, we generated mice genetically predisposed to prostate cancer (the TRAMP model) to be homozygous for lit, a mutation that inactivates the GHRH receptor (GHRH-R) and reduces circulating levels of GH and IGF-I. The lit mutation significantly reduced the percentage of the prostate gland showing neoplastic changes at 35 weeks of age (P=0.0005) and was also associated with improved survival (P<0.01). These data provide an example of a germ line mutation that reduces risk in an experimental prostate carcinogenesis model. The results suggest that prostate carcinogenesis and progression may be influenced by germ line variation of genes encoding signalling molecules in the GH-IGF-I axis.

Animals↗
PubMed2005

Individualized screening interval for prostate cancer based on prostate-specific antigen level: results of a prospective, randomized, population-based study.

BACKGROUND: The aim of the present study was to evaluate the future cumulative risk of prostate cancer in relation to levels of prostate-specific antigen (PSA) in blood and to determine whether this information could be used to individualize the PSA testing interval. METHODS: The study included 5855 of 9972 men (aged 50-66 years) who accepted an invitation to participate in a prospective, randomized study of early detection for prostate cancer. We used a protocol based on biennial PSA measurements starting from 1995 and 1996. Men with serum PSA levels of 3.0 ng/mL or more were offered prostate biopsies. RESULTS: Among the 5855 men, 539 cases of prostate cancer (9.2%) were detected after a median follow-up of 7.6 years (up to July 1, 2003). Cancer detection rates during the follow-up period in relation to PSA levels were as follows: 0 to 0.49 ng/mL, 0% (0/958); 0.50 to 0.99 ng/mL, 0.9% (17/1992); 1.00 to 1.49 ng/mL, 4.7% (54/1138); 1.50 to 1.99 ng/mL, 12.3% (70/571); 2.00 to 2.49 ng/mL, 21.4% (67/313); 2.50 to 2.99 ng/mL, 25.2% (56/222); 3.00 to 3.99 ng/mL, 33.3% (89/267); 4.00 to 6.99 ng/mL, 38.9% (103/265); 7.00 to 9.99 ng/mL, 50.0% (30/60); and for men with an initial PSA of 10.00 ng/mL or higher, 76.8% (53/69). Not a single case of prostate cancer was detected within 3 years in 2950 men (50.4% of the screened population) with an initial PSA level less than 1 ng/mL. CONCLUSIONS: Retesting intervals should be individualized on the basis of the PSA level, and the large group of men with PSA levels of less than 1 ng/mL can safely be scheduled for a 3-year testing interval.

Aged↗
PubMed1996

Comparative analysis of prostate specific antigen and its indexes in the detection of prostate cancer.

PURPOSE: Prostate specific antigen (PSA) density and age referenced PSA have been proposed in an attempt to improve the power of PSA in the detection of early prostate cancer. Reported results have been controversial and disappointing. Because the association of gland volume with PSA is stronger than that of age we developed a new index, volume referenced PSA, and compared it to PSA density and other indexes. MATERIALS AND METHODS: Volume referenced PSA was developed from a control group of 408 men without clinical evidence of prostate cancer using a standardized Z score. A retrospective analysis was performed comparing PSA and all its indexes in 580 men who underwent prostate biopsy. In addition to overall analysis, PSA and its indexes were evaluated with receiver operating characteristic curves by age and volume subcategories. RESULTS: Cancer was identified in 35% of the 580 men. The number of missed cancers using established thresholds significantly favored volume referenced PSA clinically and statistically compared to all other indexes but it was equivalent to PSA alone clinically. Age referenced PSA prevented more biopsies from being done than did volume referenced PSA (39% versus 31%) but resulted in the diagnosis of 48% fewer cancers. Receiver operating characteristic curve analysis demonstrated a significantly better performance for volume referenced PSA and PSA density compared to PSA alone and age referenced PSA. CONCLUSIONS: Volume based PSA indexes are superior to PSA and age referenced PSA statistically. However, clinically volume referenced PSA is comparable to PSA, and both are superior to age referenced PSA and PSA density in the detection of prostate cancer.

Adult↗
PubMed1989

Prognosis in stage D-1 prostate cancer relative to anatomic sites of nodal metastases. National Prostatic Cancer Treatment Group.

The investigators of the National Prostatic Cancer Treatment Group (NPCTG) have entered 212 patients with surgically confirmed stage D-1 prostate cancer in studies to determine the efficacy of adjuvant therapy after either definitive surgery (Protocol 900) or definitive radiotherapy (Protocol 1000). Follow-up indicates that this group represents 70% of all patients with recurrent disease. Because patients with less than 20% nodal involvement were found to have a statistically significant better progression-free-survival (PFS) than those with greater than 20% nodal involvement, we examined the exact anatomic sites of nodal metastases. The status of obturator, external iliac, internal iliac, and common iliac nodes was compared to PFS and overall survival in 198 patients with D-1 disease in both protocols. Results demonstrate no significant difference in either PFS or overall survival relative to anatomic sites of positive nodes. These data suggest that although minimal pelvic nodal metastasis is consistent with improved PFS, there is no predictable anatomic distribution of disease consonant with that better prognosis.

Antineoplastic Agents↗
PubMed2005

Treatment of erectile dysfunction following therapy for clinically localized prostate cancer: patient reported use and outcomes from the Surveillance, Epidemiology, and End Results Prostate Cancer Outcomes Study.

PURPOSE: Erectile dysfunction (ED) persists for years following curative therapies for clinically localized prostate cancer. We report use and treatment outcomes in a 5-year interval in a population based cohort from the Surveillance, Epidemiology, and End Results Prostate Cancer Outcomes Study. MATERIALS AND METHODS: A sample of 1,977 men with localized prostate cancer who received external beam radiation therapy or radical prostatectomy in 1994 to 1995 were surveyed for 5 outcome measures of ED treatment, namely treatment, perceived helpfulness, erectile sufficiency, sexual activity frequency and erection maintenance. Subjects were surveyed 6, 12, 24 and 60 months after prostate cancer diagnosis. RESULTS: Overall 50.5% of men ever used ED treatment. The use of ED treatments increased during the study course. Subject age, regular sexual partner and baseline sexual activity were factors positively associated with ED treatments. While it was used uncommonly (1.9%), a penile prosthesis was perceived as the most helpful ED treatment (helped a lot in 52% of respondents). Sildenafil helped a lot in 12% of respondents. Erectile fullness, erection maintenance and sexual activity frequency were modestly improved in men using ED treatment compared with those in men not using ED treatment. CONCLUSIONS: Approximately half of the patients in this population based cohort of men used ED treatment during the 5 years following prostate cancer diagnosis. Men using ED treatments had modest improvement in sexual function compared with men that in who did not receive ED treatment at 60 months. More effective treatments for ED following local therapy for prostate cancer are needed.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2000

Prostate cancer in men age 50 years or younger: a review of the Department of Defense Center for Prostate Disease Research multicenter prostate cancer database.

PURPOSE: Prostate cancer in men age 50 years or younger traditionally has accounted for approximately 1% of those diagnosed with prostate cancer. Prior studies of prostate cancer in men of this age led many clinicians to believe that they have a less favorable outcome than older men. Most of these studies were conducted before the advent of prostate specific antigen (PSA) screening programs. We evaluated a surgically treated cohort of men age 50 years or younger to determine whether disease recurred more frequently among them than in those 51 to 69 years old in the PSA era. MATERIALS AND METHODS: We reviewed the medical records of 477 men who underwent radical prostatectomy between 1988 and 1997. Age, ethnicity, preoperative PSA, clinical and pathological stage, margin and seminal vesicle involvement, and recurrence were compared between 79 men age 50 years or younger (study group) and 398, 51 to 69 years old (comparison group). Disease-free survival rates were compared using Kaplan-Meier and Cox regression techniques. RESULTS: There were 6 (7.6%) recurrences in the study group (79) and 107 (26.9%) in the comparison group (398). The disease-free survival curves were significantly different (log-rank p = 0.010). Age remained a significant prognostic factor (Wald p = 0.033) in multivariate Cox regression analyses that controlled for race, clinical and pathological stage, and pretreatment PSA. Similar results were found when the comparison group was limited to 116 patients 51 to 59 years old (log-rank p = 0.034, Wald p = 0.069). CONCLUSIONS: These data suggest that patients in the PSA era who underwent radical prostatectomy and were age 50 years or younger have a more favorable disease-free outcome compared to older men.

Adenocarcinoma↗
PubMed2024

Exploring the clinical and biological significance of the cell cycle-related gene CHMP4C in prostate cancer.

BACKGROUND: Prostate cancer (PCa) stands as the second most prevalent malignancy impacting male health, and the disease's evolutionary course presents formidable challenges in the context of patient treatment and prognostic management. Charged multivesicular body protein 4&#xa0;C (CHMP4C) participates in the development of several cancers by regulating cell cycle functions. However, the role of CHMP4C in prostate cancer remains unclear. METHODS: In terms of bioinformatics, multiple PCa datasets were employed to scrutinize the expression of CHMP4C. Survival analysis coupled with a nomogram approach was employed to probe into the prognostic significance of CHMP4C. Gene set enrichment analysis (GSEA) was conducted to interrogate the functional implications of CHMP4C. In terms of cellular experimentation, the verification of RNA and protein expression levels was executed through the utilization of qRT-PCR and Western blotting. Upon the establishment of a cell line featuring stable CHMP4C knockdown, a battery of assays, including Cell Counting Kit-8 (CCK-8), wound healing, Transwell, and flow cytometry, were employed to discern the impact of CHMP4C on the proliferation, migration, invasion, and cell cycle function of PCa cells. RESULTS: The expression of CHMP4C exhibited upregulation in both PCa cells and tissues, and patients demonstrating elevated CHMP4C expression levels experienced a notably inferior prognosis. The nomogram, constructed using CHMP4C along with clinicopathological features, demonstrated a commendable capacity for prognostic prediction. CHMP4C knockdown significantly inhibited the proliferation, migration, and invasion of PCa cells (LNcaP and PC3). CHMP4C could impact the advancement of the PCa cell cycle, and its expression might be regulated by berberine. Divergent CHMP4C expression among PCa patients could induce alterations in immune cell infiltration and gene mutation frequency. CONCLUSIONS: Our findings suggest that CHMP4C might be a prognostic biomarker in PCa, potentially offering novel perspectives for the advancement of precision therapy for PCa.

Humans↗
PubMed2006

TMPRSS2:ERG fusion by translocation or interstitial deletion is highly relevant in androgen-dependent prostate cancer, but is bypassed in late-stage androgen receptor-negative prostate cancer.

Recently, a unique fusion between the prostate-specific, androgen-regulated TMPRSS2 gene and the ETS genes ERG, ETV1, or ETV4 has been described in clinical prostate cancer. We investigated mechanisms of expression of four ETS genes, ERG, ETV1, ETV4, and FLI1, in 11 xenografts representing different stages of prostate cancer. All five androgen-dependent xenografts showed as major transcript overexpression of two splice variants of TMPRSS2:ERG, linking TMPRSS2 exon 1 or 2 sequences to ERG exon 4. In one of two androgen-sensitive xenografts, fusion transcripts of TMPRSS2 and ETV1 were detected. Array-based comparative genomic hybridization and interphase fluorescence in situ hybridization indicated both interstitial deletions and translocations as mechanisms of TMPRSS2:ERG gene fusion. Importantly, TMPRSS2 to ERG fusions were also observed in three of four androgen-independent, androgen receptor (AR)-negative xenografts and in two AR-negative clinical prostate cancer specimens; however, the fusion gene was not expressed. In almost all AR-negative tumor samples, overexpression of wild-type ETV4 or FLI1 was detected. Combined, our observations indicate a key role of fusion of TMPRSS2 and ETS genes in most androgen-regulated prostate cancers, which might be bypassed by androgen-independent expression of wild-type ETS factors in late-stage disease.

Animals↗
PubMed2001

Doppler quantitative measures by region to discriminate prostate cancer.

This study was conducted to assess if sonographic discrimination between healthy and cancerous prostate tissue might be improved using regional analysis of ultrasound (US) Doppler measures. A total of 39 subjects underwent 3-D Doppler sonography before radical prostatectomy. Cancer locations were identified from hematoxylin and eosin (H&E)-stained slides. Three prostate data volumes consisting of a frequency shift and power-mode Doppler US and whole mount histology images were spatially registered for each prostate, then divided into entirely 1 mL-sized regions of cancerous or noncancerous tissue. Each prostate was visually divided into a peripheral and a periurethral region within which US Doppler measures were calculated. Receiver operating characteristic (ROC) and simulated biopsy analyses within each prostate were performed. Mean speed in colored pixels (V), and speed-weighted pixel density (SWD) are good discriminators for prostate cancer in the periurethral and the peripheral regions, respectively. Using SWD in a simulated biopsy yields increased cancer detection in the peripheral region.

Aged↗
PubMedDate not supplied

Two-dimensional electrophoresis of prostate-specific antigen in sera of men with prostate cancer or benign prostate hyperplasia.

Prostate-specific antigen (PSA), the main marker for prostate cancer (PCa), is released from the prostate into the blood stream at nanogram level and may increase in PCa and nonmalignant disease such as benign prostate hyperplasia (BPH). More recently, advantage was taken of PSA's ability to bind to protease inhibitors in serum in order to improve discrimination between PCa and BPH, using the free PSA to total PSA ratio. The understanding of this phenomenon at molecular level, which is still unknown, may promise new improvements in the field of diagnostics. For this purpose, we determined the pattern of PSA forms in PCa and BPH sera, using the high resolving power of two-dimensional electrophoresis (2-DE) in conjunction with the high sensitivity of chemiluminescence detection. Serum PSA differs drastically from seminal PSA: apart from complexed forms, serum PSA shows few cleaved forms. Moreover, 2-DE patterns from PCa are relatively homogeneous, whereas patterns from BPH may in some cases present a higher proportion of cleaved forms and in other cases present slightly more basic spots. We therefore demonstrated, for the first time, that an increase in the free to total PSA ratio in BPH cases may be due to cleaved PSA forms (which are enzymatically inactive and unable to bind inhibitors), or possibly related to basic free PSA, which may represent the zymogen forms.

Electrophoresis, Gel, Two-Dimensional↗
PubMed1981

Responses of serum levels of testicular steroid hormones to hCG stimulation in patients with prostatic cancer and benign prostatic hypertrophy.

Serum levels of testosterone (T), dihydrotestosterone (DHT), androsterone (A), 5 alpha-androstane-3 alpha, 17 beta-diol (5 alpha-diol) and estradiol-17 beta (E2) were measured by radioimmunoassay in the sera of 9 patients with untreated prostatic cancer and in 11 with benign prostatic hypertrophy (BPH). Basal levels and responses to hCG stimulation were investigated. Although no specific changes in steroid hormone levels in either disease group were found, response patterns of serum T, DHT, and E2 were shown to be those characteristic of male senescence, suggesting a relative predominance of estrogens over androgens. Neither 5 alpha-diol nor A exhibited appreciable responses to hCG stimulation in our study.

Aged↗