Prostate Cancer最新文献

Genome-wide association studies (GWAS) have implicated single nucleotide polymorphisms (SNPs) on chromosomes 2p15, 6q25, 7p15.2, 7q21, 8q24, 10q11, 10q26, 11q13, 17q12, 17q24, 19q13, and Xp11, with prostate cancer (PCa) susceptibility and/or tumour aggressiveness, in populations of African, European, and Asian ancestry. The objective of this study was to confirm these associations in South African Mixed Ancestry and White men. We evaluated 17 prioritised GWAS SNPs in South African cases (331 Mixed Ancestry and 155 White) and controls (178 Mixed Ancestry and 145 White). The replicated SNP associations for the different South African ethnic groups were rs7008482 (8q24) (p = 2.45 × 10(-5)), rs6983267 (8q24) (p = 4.48 × 10(-7)), and rs10993994 (10q11) (p = 1.40 × 10(-3)) in Mixed Ancestry men and rs10993994 (p = 1.56 × 10(-9)) in White men. No significant associations were observed for the analyses stratified by disease aggressiveness in the individual and the combined population group analysis. The present study demonstrates that a number of known PCa susceptibility variants may contribute to disease susceptibility in South African men. Larger genetic investigations extended to other South African population groups are warranted to confirm the role of these and other SNPs in disease susceptibility.

Background. Prostate cancer is the most common noncutaneous cancer and second leading cause of cancer-related mortality in men in the US. Growing evidence suggests that oxidative stress is involved in prostate cancer. Methods. In this study, thioredoxin 1 (Trx 1), an enzyme and subcellular indicator of redox status, was measured in prostate biopsy tissue from 55 men from the North Carolina-Louisiana Prostate Cancer Project. A pathologist blindly scored levels of Trx 1. The association between Trx 1 and the Gleason score, erythrocyte antioxidant enzyme activity, and dietary antioxidant intake was determined using Fisher's exact test. Results. Trx 1 levels in benign prostate tissue in men with incident prostate cancer were positively associated with the Gleason score (P = 0.01) and inversely associated with dietary antioxidant intake (P = 0.03). In prostate cancer tissue, Trx 1 levels were associated with erythrocyte glutathione peroxidase activity (P = 0.01). No association was found for other erythrocyte enzymes. Greater Gleason score of malignant tissue corresponds to a greater difference in Trx 1 levels between malignant and benign tissue (P = 0.04). Conclusion. These results suggest that the redox status of prostate tissue is associated with prostate cancer grade and both endogenous and exogenous antioxidants.

This prospective, noninterventional, open-label, multicentre, Belgian study assessed the prevalence of moderate to severe lower urinary tract symptoms (LUTS) in patients with locally advanced or metastatic prostate cancer scheduled to receive triptorelin therapy and its effects on LUTS were evaluated focusing on symptom relief and changes in quality of life (QOL) related to urinary symptoms (November 2006 to May 2010). Inclusion criteria were age >18 years, histologically confirmed advanced or metastatic prostate cancer, and life expectancy ≥12 months. Exclusion criteria were treatment with any LHRH analogue within the last 6 months or any other investigational agent within the last 3 months before study entry. Patients who received one or more triptorelin doses and had one or more efficacy assessments were evaluated. In total, 325 patients were included with a median age of 74 years (50 to 95 years). Mean age at first diagnosis was 73 ± 8 years. Moderate (IPSS 8-19) to severe (IPSS ≥ 20) LUTS were observed in 62% of patients. Triptorelin reduced LUTS severity. This improvement was perceived within the first 24 weeks of treatment and was maintained after 48 weeks. A decrease in PSA level was also observed.

Objective. To describe urologists' practice patterns when managing patients with advanced prostate cancer (PCa) in Spain. Methods. This was an observational study conducted by 120 urologists using retrospective data of advanced PCa patients attending hospitals and outpatient centers. Results. Urologists evaluated a total of 375 patients (mean age: 75 years; ECOG 0-1: 77%; mean serum PSA levels at study entry: 50.5 ng/Ml). Approximately 50% of patients had bone metastases, and 60.6% experienced pain as the main symptom of progressive disease. Primary androgen deprivation therapy (ADT) use was 99.7%, with continuous ADT as the dominant strategy (91.9%). After failure of initial ADT, antiandrogen withdrawal was the next method most commonly used in 57% of patients. Choice of secondary hormonal treatment was made mostly by urologists (96%), who continued to monitor patients. Patient follow-up after chemotherapy and supportive care were mainly done in urology units, although responsibility was shared with medical oncologists and radiologists. Conclusion. The urologists' attitudes towards management of PCa in the routine practice in Spain show the urologist as an integral component even when patients progress to advanced stages of the disease.

Purpose. Experimental data suggest that tumour cells can reversibly transition between epithelial and mesenchymal states (EMT and MET), a phenomenon known as cellular plasticity. The aim of this review was to appraise the clinical evidence for the role of cellular plasticity in prostate cancer (PC) bone metastasis. Methods. An electronic search was performed using PubMed for studies that have examined the differential expression of epithelial, mesenchymal, and stem cell markers in human PC bone metastasis tissues. Results. The review included nineteen studies. More than 60% of the studies used ≤20 bone metastasis samples, and there were several sources of heterogeneity between studies. Overall, most stem cell markers analysed, except for CXCR4, were positively expressed in bone metastasis tissues, while the expression of EMT and MET markers was heterogeneous between and within samples. Several EMT and stemness markers that are involved in osteomimicry, such as Notch, Met receptor, and Wnt/β pathway, were highly expressed in bone metastases. Conclusions. Clinical findings support the role of cellular plasticity in PC bone metastasis and suggest that epithelial and mesenchymal states cannot be taken in isolation when targeting PC bone metastasis. The paper also highlights several challenges in the clinical detection of cellular plasticity.

Purpose. Atypical small acinar proliferation (ASAP) is diagnosed in 1-2% of prostate biopsies. 30-40% of patients with ASAP may be diagnosed with prostate cancer (PCa) on repeat biopsy. Our objective was to examine the association between ASAP and subsequent diagnosis of intermediate/high risk PCa. Materials and Methods. Ninety-six patients who underwent prostate biopsy from 2000 to 2013 and were diagnosed with ASAP were identified. Clinicopathologic features were analyzed. Comparison was made between those with subsequent PCa on repeat biopsy and those with benign repeat pathology. Results. 56/96 (58%) patients had a repeat biopsy. 22/56 (39%) were subsequently diagnosed with PCa. There was no significant difference in patients' characteristics. Presence of HGPIN on initial biopsy was associated with a benign repeat biopsy (68% versus 23%). 17/22 (77%) had Gleason grade (GG) 3+3 disease and only 5/22 (23%) had GG 3+4 disease. Conclusions. 22/56 patients (39%) of patients who underwent a subsequent prostate biopsy following a diagnosis of ASAP were found to have PCa. 77% of these men were diagnosed with GG 3+3 PCa. Only 23% were found to have intermediate risk PCa and no high risk PCa was identified. Immediate repeat prostate biopsy in patients diagnosed with ASAP may be safely delayed. A multi-institutional cohort is being analyzed.

Background. New nontoxic targeted approaches are needed for patients with castrate resistant prostate cancer (CRPC). Our preclinical studies show that activated T cells (ATC) armed with anti-CD3 x anti-Her2 bispecific antibody (Her2Bi) kill prostate cancer cells lines, induce a Th1 cytokine pattern upon engagement of tumor cells, prevent the development of prostate tumors, and retard tumor growth in immunodeficient mice. These studies provided strong rationale for our phase I dose-escalation pilot study to test ATC armed with Her2Bi (aATC) for safety in men with CRPC. Methods. Seven of 8 men with CRPC were evaluable after receiving two infusions per week for 4 weeks. The men received 2.5, 5 or 10 × 10(9) aATC per infusion with low dose interleukin-2 and granulocyte-macrophage colony stimulating factor. Results. There were no dose limiting toxicities, and there was 1 partial responder and 3 of 7 patients had significant decreases in their PSA levels and pain scores. Immune evaluations of peripheral blood mononuclear cells in 2 patients before and after immunotherapy showed increases in IFN-γ EliSpot responses and Th1 serum cytokines. Conclusions. These results provide a strong rationale for developing phase II trials to determine whether aATC are effective for treating CRPC.

Objective. We sought to evaluate the accuracy of transperineal mapping biopsy (TMB) by comparing it to the pathology specimen of patients who underwent radical prostatectomy (RP) for localized prostate cancer. Methods. From March 2007 to September 2009, 78 men at a single center underwent TMB; 17 of 78 subsequently underwent RP. TMB cores were grouped into four quadrants and matched to data from RP whole-mount slides. Gleason score, tumor location and volume, cross-sectional area, and maximal diameter were measured; sensitivity and specificity were assessed. Results. For the 17 patients who underwent RP, TMB revealed 12 (71%) had biopsy Gleason grades ≥ 3 + 4 and 13 (76%) had bilateral disease. RP specimens showed 14 (82%) had Gleason scores ≥ 3 + 4 and 13 (76%) had bilateral disease. Sensitivity and specificity of TMB for prostate cancer detection were 86% (95% confidence interval [CI] 72%-94%) and 83% (95% CI 62%-95%), respectively. Four quadrants negative for cancer on TMB were positive on prostatectomy, and six positive on TMB were negative on prostatectomy. Conclusion. TMB is a highly invasive procedure that can accurately detect and localize prostate cancer. These findings help establish baseline performance characteristics for TMB and its utility for organ-sparing strategies.

Objectives: To present the results of a prospective phase IIa study assessing the role of primary zonal High Intensity Focused Ultrasound (HIFU) for prostate cancer treatment.

Methods: 31 consecutive patients with unilateral organ confined prostate cancer primarily treated by zonal HIFU (from February 2007 to June 2011) were recruited into a single centre prospective phase IIa feasibility study. Complications were prospectively recorded and graded according to the Clavien-Dindo score. Postoperatively, patients were followed with serial serum PSA determinations and digital rectal examinations. An individual PSA nadir was identified in each patient. Followup also included whole gland biopsies performed in the event of a PSA rising>2.0 ng/mL above nadir value (Phoenix criteria).

Results: At a median followup of 38 months, biochemical recurrence free survival was 100%, 89%, and 82.7% at 1, 2, and 3 years, respectively, with overall and cancer specific survival of 100%. The procedure was safe and well tolerated with no major adverse events. All patients were continent at their last followup and 55.2% (16/29) had erectile function sufficient for penetration.

Conclusion: Primary zonal HIFU is a valid focal therapy strategy, safe and feasible in day to day practice with good promising results [corrected].

Background. Levels of the protein kinase aPKC have been previously correlated with prostate cancer prognosis in a British cohort. However, prostate cancer incidence and progression rates, as well as genetic changes in this disease, show strong ethnic variance, particularly in Asian populations. Objective. The aim of this study was to validate association of aPKC expression with prostatic adenocarcinoma stages in a Japanese cohort. Methods. Tissue microarrays consisting of 142 malignant prostate cancer cases and 21 benign prostate tissues were subject to immunohistological staining for aPKC. aPKC staining intensity was scored by three independent pathologists and categorized as absent (0), dim (1+), intermediate (2+), and bright (3+). aPKC staining intensities were correlated with Gleason score and tumor stage. Results. Increased aPKC staining was observed in malignant prostate cancer, in comparison to benign tissue. Additionally, aPKC staining levels correlated with Gleason score and tumor stage. Our results extend the association of aPKC with prostate cancer to a Japanese population and establish the suitability of aPKC as a universal prostate cancer biomarker that performs consistently across ethnicities.