Abstract:
BACKGROUND:Heat shock protein 27 (Hsp-27) encoded by gene HSPB1 is a critical regulator of the behavioral phenotype of human prostate cancer (PCa) cells, enhanced expression being associated with highly aggressive disease and poor clinical outcome. In contrast, the protein is not expressed in PCas of low malignant potential. To gain insight into the mechanism regulating its expression, we tested the hypothesis that differential methylation of CpG islands within HSPB1 controls transcription and subsequent translation of the gene. METHODS:We studied prostate epithelial cell lines and tissue biopsies, including 59 BPH and 415 PCas, of which 367 were a cohort of men with up to 20 years of follow-up. Methylation across the gene (DNA methylation (DNAme)) was assayed by pyrosequencing. Hsp-27 expression was assessed by western blot and immunohistochemistry. RESULTS:In cancer tissues, methylation increased in a 3' direction (P < 0.0001) whereas in benign hyperplasia methylation was constantly below 5%, a cutoff giving a specificity of 100% and sensitivity of 50%. Although methylation of the promoter region was significantly discriminating between benign and malignant prostatic epithelia, it compared poorly with methylation of the first intron. The prognostic value of HSPB1 DNAme was confirmed by both univariate (hazard ratio 1.77 per 50% increment, P = 0.02) and multivariate models. Interaction between HSPB1 methylation and Gleason score revealed high DNAme to be a reliable prognostic marker of poor outcome in men with low Gleason score (P = 0.014). CONCLUSIONS:Our data indicate CpG methylation of the first HSPB1 intron to be an important biomarker that identifies aggressive PCas otherwise regarded as low risk by current clinical criteria but that, biologically, require immediate active management.
journal_name
Prostate Cancer Prostatic Disjournal_title
Prostate cancer and prostatic diseasesauthors
Vasiljević N,Ahmad AS,Beesley C,Thorat MA,Fisher G,Berney DM,Møller H,Yu Y,Lu YJ,Cuzick J,Foster CS,Lorincz ATdoi
10.1038/pcan.2012.47subject
Has Abstractpub_date
2013-03-01 00:00:00pages
35-40issue
1eissn
1365-7852issn
1476-5608pii
pcan201247journal_volume
16pub_type
杂志文章abstract:BACKGROUND:Certain patients presenting with either low or very-low-risk prostate cancer (PCa) can represent a therapeutic dilemma for physicians. The oncologic outcomes of active surveillance (AS) for men with very-low-risk PCa are overall excellent. However, there are concerns about AS related to the potential for upg...
journal_title:Prostate cancer and prostatic diseases
pub_type: 杂志文章,评审
doi:10.1038/pcan.2016.56
更新日期:2017-06-01 00:00:00
abstract::Men with diabetes mellitus are less likely to be diagnosed with prostate cancer (PCa). As diabetic men have lower serum PSA, it is unclear if this is due to lower PCa incidence or reflects detection bias from fewer PSA-triggered biopsies. To account for differential biopsy rates, we used multivariate regression to exa...
journal_title:Prostate cancer and prostatic diseases
pub_type: 杂志文章
doi:10.1038/pcan.2011.28
更新日期:2011-12-01 00:00:00
abstract:BACKGROUND:Several randomized control trials (RCTs) have showed that adding either abiraterone acetate (AA) or docetaxel (D) to androgen-deprivation therapy (ADT) improves survival of metastatic castration-sensitive prostate cancer patients (mCSPC). Yet, the cost-effectiveness of these treatment options has not been fu...
journal_title:Prostate cancer and prostatic diseases
pub_type: 杂志文章
doi:10.1038/s41391-019-0161-2
更新日期:2020-03-01 00:00:00
abstract::To determine whether needle size influences a patient's perception of pain, 50 patients requiring hormonal manipulation for prostate cancer were blindfolded and randomised to receive two goserelin ('Zoladex') or two leuprorelin ('Prostap') injections, using 16- or 23-gauge needles, respectively. Median visual analogue...
journal_title:Prostate cancer and prostatic diseases
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1038/sj.pcan.4500778
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:Approximately 29-38% of all positive surgical margins (PSMs) at radical prostatectomy (RP) involve the apex. The prognostic significance of apical PSM remains unclear. We therefore compared the long-term oncologic outcomes of men with apical PSMs to those with negative PSMs, apical and other PSMs, and other ...
journal_title:Prostate cancer and prostatic diseases
pub_type: 杂志文章
doi:10.1038/pcan.2016.45
更新日期:2016-12-01 00:00:00
abstract::Functional expression of voltage-gated sodium channel alpha-subunits (VGSCalphas), specifically Nav1.7, is associated with strong metastatic potential in prostate cancer (CaP) in vitro. Furthermore, VGSC activity in vitro directly potentiates processes integral to metastasis. To investigate VGSCalpha expression in CaP...
journal_title:Prostate cancer and prostatic diseases
pub_type: 杂志文章
doi:10.1038/sj.pcan.4500796
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:CYR61 (cysteine-rich protein 61, also named IGFBP10) is a secreted signaling molecule that promotes angiogenesis and tumor growth. The goal of this study is to determine whether a functional polymorphism in the promoter region of the CYR61 gene (rs3753793) is associated with prostate cancer (PCa) risk and ge...
journal_title:Prostate cancer and prostatic diseases
pub_type: 杂志文章
doi:10.1038/pcan.2012.41
更新日期:2013-03-01 00:00:00
abstract::In addition to androgen, autonomic nerves may be involved in prostatic function. As patients with spinal cord injury (SCI) have impaired innervation of the prostate, the prostate volume and prostate-specific antigen (PSA) level in patients with SCI may be different from those of healthy men. Experiments in rats with S...
journal_title:Prostate cancer and prostatic diseases
pub_type: 杂志文章,评审
doi:10.1038/sj.pcan.4500865
更新日期:2006-01-01 00:00:00
abstract:BACKGROUND:Unlike in other mouse models of atherogenesis, it has recently been suggested that orchiectomy plays a role in accelerating atherosclerosis and inhibiting the progression of cardiovascular disease in the ApoE-/-:Ins2+/Akita mouse model of hyperglycemia. Androgen-deprivation therapy (ADT) is a common treatmen...
journal_title:Prostate cancer and prostatic diseases
pub_type: 杂志文章
doi:10.1038/s41391-020-00288-y
更新日期:2020-09-28 00:00:00
abstract::Epidemiological studies have suggested an association between low selenium levels and the development of prostate cancer. Human cellular glutathione peroxidase I (hGPX1) is a selenium-dependent enzyme that protects against oxidative damage and its peroxidase activity is a plausible mechanism for cancer prevention by s...
journal_title:Prostate cancer and prostatic diseases
pub_type: 杂志文章
doi:10.1038/sj.pcan.4500569
更新日期:2002-01-01 00:00:00
abstract::Antiandrogen therapy is an important modality in the treatment of prostate cancer. Recent research into the role of angiogenesis in tumour growth and metastasis has uncovered links between antiandrogen therapy, radiation therapy and angiogenesis, which have exciting implications for the treatment of prostate cancer. A...
journal_title:Prostate cancer and prostatic diseases
pub_type: 杂志文章,评审
doi:10.1038/sj.pcan.4500779
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:Intermittent androgen suppression (IAS) is an increasingly popular treatment option for castrate-sensitive prostate cancer. On the basis of previous data with anti-angiogenic strategies, we hypothesized that pan-inhibition of the vascular endothelial growth factor receptor using pazopanib during the IAS off ...
journal_title:Prostate cancer and prostatic diseases
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1038/pcan.2011.49
更新日期:2012-03-01 00:00:00
abstract:BACKGROUND:Currently, there are multiple commercially available RNA-based biomarkers that are Medicare approved and suggested for use by the National Comprehensive Cancer Network guidelines. There is uncertainty as to which patients benefit from genomic testing and for whom these tests should be ordered. Here, we exami...
journal_title:Prostate cancer and prostatic diseases
pub_type: 杂志文章
doi:10.1038/pcan.2016.38
更新日期:2016-12-01 00:00:00
abstract:OBJECTIVE:To survey UK urologists and radiation oncologists in the evaluation and treatment of localised prostate cancer in the adjuvant and salvage setting. METHODS:Postal questionnaires were mailed to 292 urologists and 98 radiation oncologists in the UK. RESULTS:In all, 188 (48%) questionnaires were returned. In t...
journal_title:Prostate cancer and prostatic diseases
pub_type: 杂志文章
doi:10.1038/sj.pcan.4500816
更新日期:2005-01-01 00:00:00
abstract:PURPOSE:To determine whether quantitative flow cytometric androgen receptor density expression (MFC ratio) in prostate cancer was associated with S-phase fraction. METHODS:Flow cytometry was performed to determine DNA aneuploidy, S-phase fraction, percentage of androgen receptor (AR)-positive cells, and MFC ratio in p...
journal_title:Prostate cancer and prostatic diseases
pub_type: 杂志文章
doi:10.1038/sj.pcan.4500672
更新日期:2003-01-01 00:00:00
abstract:BACKGROUND:The Gleason grading system in prostatectomy specimens following receipt of neoadjuvant therapy has been considered inaccurate. However, with continuing expansion of novel therapeutics, it is important to understand whether the Gleason system can be effectively utilized in this setting. The aim of this study ...
journal_title:Prostate cancer and prostatic diseases
pub_type: 杂志文章
doi:10.1038/pcan.2014.30
更新日期:2014-12-01 00:00:00
abstract::Increasingly animal and clinical studies suggest that intermittent therapy may improve the duration of hormone dependence in patients with prostate cancer. However there remains uncertainty as to optimal duration of treatment and level of prostate-specific antigen (PSA) before treatment is restarted. The aim of this s...
journal_title:Prostate cancer and prostatic diseases
pub_type: 杂志文章
doi:10.1038/sj.pcan.4500483
更新日期:2000-12-01 00:00:00
abstract::Chronic fatigue (CF) is a distressing symptom that follows cancer treatment; however, it has rarely been studied in hormone-naïve prostate cancer survivors after radical prostatectomy (RP) or definitive radiotherapy (RAD). We investigated CF in prostate cancer survivors after RP or RAD as monotherapy and explored asso...
journal_title:Prostate cancer and prostatic diseases
pub_type: 杂志文章
doi:10.1038/pcan.2009.61
更新日期:2010-06-01 00:00:00
abstract::Prostate cancer appears to result from complex interactions among genetic, endocrine and environmental factors. Identification of risk factors for development and progression of prostate cancer is needed. This will allow researchers to design strategies to reduce the morbidity and mortality from this cancer and to ide...
journal_title:Prostate cancer and prostatic diseases
pub_type: 杂志文章
doi:10.1038/sj.pcan.4500471
更新日期:2000-12-01 00:00:00
abstract::Prostate cancer has been known to run in families for about 40 years and epidemiological studies have demonstrated an increased risk to close relatives of cases. This risk rises markedly when the closeness and number of cases in a cluster increases. There has been considerable debate about the genetic model, in partic...
journal_title:Prostate cancer and prostatic diseases
pub_type: 杂志文章
doi:10.1038/sj.pcan.4500279
更新日期:1999-01-01 00:00:00
abstract:BACKGROUND:Patients with high-risk prostate cancer have an increased likelihood of experiencing a relapse following radical prostatectomy (RP). We previously conducted three neoadjuvant androgen-deprivation therapy (ADT) trials prior to RP in unfavorable intermediate and high-risk disease. METHODS:In this analysis, we...
journal_title:Prostate cancer and prostatic diseases
pub_type: 杂志文章
doi:10.1038/s41391-017-0009-6
更新日期:2018-09-01 00:00:00
abstract::To describe practice patterns of primary care physicians (PCPs) for the diagnosis, treatment and management of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), we surveyed 556 PCPs in Boston, Chicago, and Los Angeles (RR=52%). Only 62% reported ever seeing a patient like the one described in the vignette. I...
journal_title:Prostate cancer and prostatic diseases
pub_type: 杂志文章
doi:10.1038/pcan.2009.9
更新日期:2009-01-01 00:00:00
abstract::As earlier detection of prostate cancer increases because of prostate-specific antigen (PSA) testing, appropriate use for watchful waiting warrants re-evaluation. We have drawn together the significant watchful waiting literature and used it to evaluate the use of watchful waiting in the PSA era. We conducted literatu...
journal_title:Prostate cancer and prostatic diseases
pub_type: 杂志文章,评审
doi:10.1038/sj.pcan.4500857
更新日期:2006-01-01 00:00:00
abstract::Testosterone depletion is the keystone for therapy of patients metastic prostatic carcinoma. Our objective was to investigate Leydig cell function and testosterone levels after withdrawal of long-term endocrine treatment in patients with prostatic carcinoma. Thirteen patients with prostatic carcinoma, previously treat...
journal_title:Prostate cancer and prostatic diseases
pub_type: 杂志文章
doi:10.1038/sj.pcan.4500310
更新日期:1999-07-01 00:00:00
abstract::The aim of this paper is to review the inhibitors of apoptosis proteins, a recently discovered group of caspase inhibitors. We will briefly review the relevance of apoptosis in prostate cancer and some of the control mechanisms, before describing the structure, function and regulation of these molecules. Lastly, we wi...
journal_title:Prostate cancer and prostatic diseases
pub_type: 杂志文章
doi:10.1038/sj.pcan.4500502
更新日期:2001-01-01 00:00:00
abstract:BACKGROUND:Focal therapy is an emerging mini-invasive treatment modality for localized prostate cancer aimed to reduce the morbidity associated with radical therapy while maintaining optimal cancer control. We report the mid-term oncological and functional results of primary hemiablation high-intensity focused ultrasou...
journal_title:Prostate cancer and prostatic diseases
pub_type: 临床试验,杂志文章
doi:10.1038/pcan.2015.55
更新日期:2016-03-01 00:00:00
abstract::This study provides further insights into those preoperative parameters that predict side-specific risk of pathological stage in men undergoing radical prostatectomy (RP). The transrectal ultrasound-guided tissue biopsy cores obtained from the right and left sides of the prostate were collected in separate jars and ex...
journal_title:Prostate cancer and prostatic diseases
pub_type: 杂志文章
doi:10.1038/pcan.2009.2
更新日期:2009-01-01 00:00:00
abstract:BACKGROUND:In men with high Gleason PC and rapid PSA progression after surgery, failure rates remain unacceptably high despite salvage radiation. We explored a novel multimodality approach of docetaxel with anti-angiogenic therapy before salvage radiotherapy (RT). METHODS:This was a phase 2 single-arm prospective open...
journal_title:Prostate cancer and prostatic diseases
pub_type: 杂志文章
doi:10.1038/pcan.2015.59
更新日期:2016-03-01 00:00:00
abstract:OBJECTIVE:To determine the prognostic value of serum chromogranin-A (CGA) in a two-cohort study of men with metastatic castrate resistant prostate cancer (mCRPC) and to compare with circulating tumor cells (CTCs)-based prognosis. PATIENTS AND METHODS:A two-cohort-based evaluation for serum CGA for prognostication in C...
journal_title:Prostate cancer and prostatic diseases
pub_type: 杂志文章
doi:10.1038/s41391-018-0046-9
更新日期:2018-09-01 00:00:00
abstract::Prostate cancer is the commonest non-skin malignancy in the United States and has a substantial mortality rate despite the use of PSA-based screening. Furthermore, therapy for prostate cancer by surgery, radiotherapy or hormonal manipulation carries a significant risk of treatment-related morbidity. Recent analysis of...
journal_title:Prostate cancer and prostatic diseases
pub_type: 杂志文章
doi:10.1038/sj.pcan.4500412
更新日期:2000-11-01 00:00:00