Lycopene for the prevention and treatment of benign prostatic hyperplasia and prostate cancer: a systematic review

Background

Prostate cancer is a leading cancer affecting men worldwide. Benign prostatic hyperplasia (BPH) is a common disease of the prostate affecting men as they age, and a risk factor for developing prostate cancer. Lycopene is a member of the carotenoid family, whose strong anti-oxidant properties have been hypothesised to assist in the prevention and treatment of BPH and prostate cancer. The aim of this systematic review was to examine the effectiveness of lycopene for the prevention and treatment of BPH and prostate cancer.

Methods

A search of the MEDLINE, EMBASE, AMED (Allied and Complementary Medicine) and the Cochrane Library databases was performed for published randomised controlled trials (RCTs) comparing lycopene to placebo (or other interventions) for the treatment of BPH and prostate cancer. All included studies were assessed for methodological quality using the Cochrane Collaboration's risk of bias tool.

Results

Eight RCTs met the inclusion criteria for this systematic review. All included studies were heterogeneous with respect to their design and implementation of lycopene. Methodological quality of three studies was assessed as posing a ‘high’ risk of bias, two a ‘low’ risk of bias and the remaining three an ‘unclear’ risk of bias. Meta-analysis of four studies identified no significant decrease in the incidence of BPH (RR (relative risk) = 0.95, 95%CI 0.63, 1.44) or prostate cancer diagnosis (RR = 0.92, 95%CI 0.66, 1.29) between men randomised to receive lycopene and the comparison group. Meta-analysis of two studies indicated a decrease in PSA levels in men diagnosed with prostate cancer, who received lycopene (MD (mean difference) = −1.58, 95%CI −2.61, −0.55).

Conclusions

Given the limited number of RCTs published, and the varying quality of existing studies, it is not possible to support, or refute, the use of lycopene for the prevention or treatment of BPH or prostate cancer.     

Cancer/testis antigen SPATA19 is frequently expressed in benign prostatic hyperplasia and prostate cancer

Spermatogenesis‐associated 19 (SPATA19) is a cancer/testis antigen overexpressed in various cancers. However, its protein expression profile in malignant or non‐malignant tissues remains unknown. Thus, in this study, we investigated SPATA19 protein expression patterns in a panel of non‐malignant human samples and primary prostate cancer (PCa) with or without benign prostatic hyperplasia (BPH) tissues. SPATA19 was absent in all non‐malignant tissues investigated (n=14) except testis and prostate tissues. In terms of malignancies, all PCa cases were positive for SPATA19 exhibiting frequency between 20 and 100% (median 85%) with 63 (52.5%) and 57 (47.5%) cases demonstrating weak/moderate and strong intensities, respectively. Thirty‐nine PCa cases (32.5%) contained BPH, and all BPH glands were SPATA19 positive (frequency between 20 and 100%; median 90%) with 13 (33.3%) demonstrating strong SPATA19 expression. Higher SPATA19 expression (higher frequency, intensity, or H‐score) was not associated with overall survival or disease‐specific survival (DFS) in all PCa cases. However, biochemical recurrence (BR) was associated with worse DFS (p = 0.005) in this cohort of 120 patients, and cases with strong SPATA19 intensity were associated with BR (p = 0.020). In conclusion, we showed that SPATA19 protein was frequently expressed in both BPH and PCa glands, and this warrants future investigations on its pathogenic roles in the disease.     

钬激光前列腺剜除术与经尿道等离子前列腺剜除电切术治疗良性前列腺增生患者的临床效果分析

目的:比较钬激光前列腺剜除术(Holmium laser enucleation of the prostate,HOLEP)与经尿道等离子前列腺剜除电切术(Transurethral plasmakinetic enucleation of prostate,PKEP)治疗良性前列腺增生的效果。方法:选取2017年3月至2019年12月间我院收治的68例良性前列腺增生患者,随机分成两组(n=34),其中对照组患者采用HOLEP术式而试验组患者采用PKEP术式进行治疗。比较手术指标、恢复时间和术后并发症,评价前列腺症状和疼痛程度。结果:两组患者手术时间、术中出血量、住院时间无显著差异(P>0.05)。与试验组相比,对照组术后并发症发生率更低(P<0.05)。与术前相比,两组的国际前列腺症状评分(International prostate symptom score,IPSS)和视觉模拟评分(Visual analogue score,VAS)评分均明显降低(P<0.05),其中对照组更为显著(P<0.05)。结论:HOLEP术式治疗良性前列腺增生的疗效优于PKEP术式,能减少术后并发症、改善前列腺症状,具有推广价值。     

细胞周期蛋白依赖性激酶cdk2和cdk4在前列腺增生和癌变组织中的表达

目的：探讨细胞周期蛋白依赖性激酶ｃｄｋ２和ｃｄｋ４在前列腺增生（ＢＰＨ）和前列腺癌（ＰＣ）的发生发展过程中作用及其与ＰＣＮＡ之间关系。方法：应用免疫组化ＳＰ法检测１８例正常前列腺（ＮＰ）、６２例ＢＰＨ和３３例ＰＣ组织中ｃｄｋ２、ｃｄｋ４和ＰＣＮＡ的表达。结果：前列腺上皮和间质组织中均见ｃｄｋ２和ｃｄｋ４表达。ＮＰ中两者表达均分别显著低于ＢＰＨ和ＰＣ;ＢＰＨ的上皮细胞中两者表达均分别显著低于ＰＣ,但ＢＰＨ的间质细胞中两者表达与ＰＣ相比均无显著性差异。ＢＰＨ和ＰＣ中ｃｄｋ２及ｃｄｋ４表达与ＰＣＮＡ指数均呈正相关。结论：ｃｄｋ２和ｃｄｋ４异常表达参与ＢＰＨ和ＰＣ的发生发展过程,其可能是通过改变细胞周期及促进细胞异常增殖而起作用的。     

前列腺癌与前列腺增生HER-2及C-myc基因mRNA表达的研究

目的 检测良性前列腺增生(BPH)与前列腺癌(PCa)组织标本HER-2及C-mvc mRNA相对值,探讨此值对PCa诊断的特异性意义.方法 通过实时荧光定量PCR检测63例PCa、37例BPH及3例正常前列腺组织HER-2及C-myc mRNA的表达,比较其在PCa与BPH中组织定量的差异.结果 相对于BPH,PCa HER-2及C-myc mRNA表达相对值分别为4.25±0.03,7.24±0.06,PCa HER-2及C-myc表达相对值较BPH高,差异有统计学意义(均为P<0.05).结论 实时荧光PCR定量检测HER-2及C-myc mRNA为PCa的诊断提供了重要的辅助指标.     

Frequency of IL-10+CD19+ B cells in patients with prostate cancer compared to patients with benign prostatic hyperplasia

BackgroundThe function of the immune system in prostate cancer (PC) might promote carcinogenesis. PC is a common cancer in men. Regulatory B cells (Bregs) are a new subtype of B cells that have suppressive roles in the immune system. Interleukin-10 (IL-10) is a dominant mediator of immune suppression released by Bregs.ObjectiveThe purpose of this research was to examine the frequency of CD19+IL10+ B cells and IL-10 mRNA expression in patients with PC compared to patients with benign prostatic hyperplasia (BPH).MethodsForty paraffin tissue samples from patients with PC and 32 paraffin tissue samples from patients with BPH were entered in this study. The immunohistochemistry staining was used to evaluate the pattern expression of CD19 and IL-10 markers. IL-10 mRNA expression in fresh tissue was determined by real time-polymerase chain reaction (RT-PCR).ResultsThe frequency of CD19+IL-10+ B cells and IL-10 mRNA expression in PC patients were significantly higher than patients with BPH. Also, there was no meaningful relationship between the frequency of IL-10+CD19+ B cells and gleason scores in patients with PC.ConclusionsOur findings suggested that frequency of IL-10+CD19+ B cells correlates with progressive stage of PC.     

Aberrant promoter methylation of the PAQR3 gene is associated with prostate cancer

Methylation markers are promising tools for diagnosis, prognosis and targeted treatment of cancer. In prostate carcinoma, aberrant promoter hypermethylation occurs earlier in the disease course and more consistently than recurrent somatic mutations. PAQR3, a tumor suppressor gene, was recently found to be downregulated in prostate cancer cell lines. We hypothesized that promoter methylation could be responsible for PAQR3 silencing in prostate cancer tissues. We aimed to investigate PAQR3 promoter methylation in prostate cancer by comparing it to benign prostatic hyperplasia (BPH). A total of 154 human prostate tissue samples, including 92 cases with prostate cancer and 62 cases with BPH, were examined by methylation-specific PCR. Clinicopathological correlation between PAQR3 promoter methylation and prognostically relevant variables was studied by statistical analysis. Promoter methylation of PAQR3 was significantly more frequent in prostate carcinoma compared to BPH (73.9% vs. 25.8%, p < 0.01). The high prevalence of PAQR3 methylation in cancer foci was also confirmed with microdissection technique in 12 samples of prostate adenocarcinoma. PAQR3 hypermethylation was associated with perineural invasion (p = 0.03), an adverse clinicopathological feature of prostate cancer. We concluded that PAQR3 can be a promising methylation marker candidate for the detection and monitoring of prostate cancer.     

碱性成纤维细胞生长因子在前列腺增生和癌组织中表达的临床意义

目的 :探讨碱性成纤维细胞生长因子 (b FGF)在前列腺增生和前列腺癌组织中表达的临床意义。方法 :采用斑点杂交技术和免疫组化染色 ,测定 40例正常前列腺 (NP)、3 8例前列腺增生症 (BPH )和 3 6例前列腺癌组织 (Pca)中b FGF的表达。结果 :BPH和Pca组织中 ,b FGF的表达明显高于NP组织 (P <0 .0 1)。b FGF表达升高的程度与BPH的分度、Pca的病理分级和临床分期均无明显关系。结论 :b FGF可能为BPH和Pca组织自身分泌 ,与其发生发展过程密切相关     

Differential expression of MST4, STK25 and PDCD10 between benign prostatic hyperplasia and prostate cancer

Both benign prostatic hyperplasia (BPH) and prostate cancer (PC) are common diseases for men around the world. Both serine/threonine protein kinase MST4 (MST4) and serine/threonine kinase 25 (STK25) belong to the Ste20-like kinases and interact with programmed cell death 10 (PDCD10) which is closely linked to cancer diseases. To clarify the roles of MST4, STK25 and PDCD10 in prostate carcinogenesis, we examined MST4, STK25 and PDCD10 expression in tissue microarray blocks containing 110 cores of BPH and 160 cores of PC immunohistochemically and evaluated their correlation with clinicopathological findings. MST4 was not expressed in all the BPH cases and expressed in 38.7% of PC cases (P < 0.0001). STK25 expression was found in 77.3% of BPH cases and 93.1% of PC cases (P < 0.0001). PDCD10 staining was considered weak in 82 (74.5%) and strong in 28 (25.5%) of BPH cases. However, in prostate cancer cases, PDCD10 staining was weak in 95 (59.4%) and strong in 65 (40.6%) (P < 0.05). PDCD10 and STK25 immunostaining were associated with age in prostatic hyperplasia cases (P < 0.05). The staining intensity for STK25 was significantly greater in Gleason grades 3-5 (47.1% of such cases staining strongly) compared with other grades of prostate cancer (only 26.5% of these cases staining strongly; P < 0.05). Our results suggest that MST4, STK25 and PDCD10 are unregulated in prostate cancer and may play roles in prostate tumorigenesis. MST4 may be a helpful marker for identifying prostate cancer.     

CCR2 and CCR5 genes polymorphisms in benign prostatic hyperplasia and prostate cancer

Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are two chronic conditions, very common in aged men, that have been associated to inflammatory process. Chemokines and their receptors are recognized as critical mediators of inflammatory responses, they regulate immune cell migration and are implicated in tumor pathogenesis. The impact of two chemokine receptor gene polymorphisms, CCR2-64I (rs1799864) and CCR5-Δ32 (rs333), was evaluated in BPH and PCa. 385 DNA samples (130 BPH, 136 PCa, 119 healthy control) were genotyped. The allele frequencies were similar among control, BPH and PCa groups. Median of serum PSA levels was different between groups: 0.79, 1.45 and 6.91 ng/mL in control, BPH and PCa groups, respectively (all p < 0.001). The prostate volume median was 20.00 cm³ in the control group, thus, lower than BPH (35.35 cm³) and PCa (35.80 cm³) (both p < 0.001), nevertheless no statistical significant difference was observed between BPH and PCa patients (p = 0.172). Remarkably, CCR2-64I was a protective factor to PCa when compared with BPH (OR = 0.550; 95%CI = 0.311–0.975), although the statistically significant difference was lost after correction for multiple comparisons. No significant associations of CCR5-Δ32 variant were observed with BPH, PCa or PCa clinicopathologic status. Our data suggest the influence of CCR2-64I variant in the development of prostate cancer.     

Patterns in the diagnosis and management of benign prostatic hyperplasia in a country that does not have country-specific clinical practice guidelines

Purpose

We have evaluated the patterns of diagnostic and treatment practices for benign prostatic hyperplasia (BPH) in a country that does not have country-specific clinical practice guidelines.

Materials and Methods

Probability samples were taken from the Korean Urological Association Registry of Physicians, and randomly sampled Korean urologists were asked to complete a questionnaire. The survey explored practice characteristics and attitudes, as well as diagnostic and treatment strategies, for the management of BPH.

Results

Of the 850 questionnaires sent, 302 were returned, and 277 of those were included in the final analysis (response rate 32.6%). For the initial evaluation, most urologists routinely used digital rectal examinations (DRE) and urinalysis. Uroflowmetry was used 34.7% of the time. Pressure-flow studies were rarely done. Symptom assessment was used in only 46.9% of cases. In addition, a significant number (58.8%) reported that treatment decisions were not based on the symptom questionnaire. Before surgery, almost all urologists routinely used DRE, urinalysis, and prostate-specific antigen tests. Of the respondents, 55.6% and 41.9% had prescribed alpha-blockers and alpha-blockers with 5-alpha reductase inhibitors, respectively. 81.2% of urologists perceived that selective alpha-blockers are different in terms of efficacy, and 82.7% felt that they differed in safety. Most respondents prescribed 5-alpha reductase inhibitors based on the prostate size.

Conclusion

These data provide a picture of current practices regarding the management of BPH in Korea. The diagnostic and treatment practices for BPH do not follow published guidelines. Our findings ask the question "How influential are international guidelines, and do they really affect patient management in countries that do not have country-specific guidelines?"     

Neuro-fuzzy classification of prostate cancer using NEFCLASS-J

Medical diagnosis has been the most proper area for the implementations of artificial intelligence for approximately 20 years. In this paper, a new approach based on neuro-fuzzy classification (NEFCLASS) tool has been presented to classify prostate cancer. The tool has the features of batch learning, automatic cross validation, automatic determination of the rule base size, and handling of missing values to increase its interpretability. We have investigated how good medical data analysis could be done with NEFCLASS-J, and what effects selected parameters have on classifier performances. Medical data were obtained from patients with real prostate cancer and benign prostatic hyperplasia (BPH). The reason for the selection of these two illnesses was the fact that their symptoms are very similar yet their differentiation is very crucial. The results showed that, for creating high performance of classifier appropriate for the data used, firstly it is necessary to decide well on the membership type and the number of fuzzy sets and then validation procedure. After a good classifier has been found, other parameters should be investigated to improve this classifier. In the light of this study, we can present a foresight for the diagnosis of the patients with prostate cancer or BPH.     

大豆异黄酮抑制大鼠前列腺增生及其作用机制

目的观察大豆异黄酮(SI)对良性前列腺增生(BPH)大鼠体内性激素、生长因子及细胞凋亡相关基因的影响,探讨SI对BPH的防治及作用机制。方法选择SPF级健康成年雄性SD大鼠100只,随机分为正常对照(NC)组、BPH模型组、低剂量[6 mg/(kg·d)]SI组、中剂量[12 mg/(kg·d)]SI组及高剂量[24 mg/(kg·d)]SI组,每组各20只。灌胃给药4周后麻醉处理大鼠,腹主动脉取血,制备血清;完整摘取大鼠前列腺组织。称重测定前列腺组织湿质量,计算前列腺指数(PI);酶联免疫吸附法(ELISA)测定大鼠血清雌二醇(E2)、睾酮(T)水平;免疫质印迹法(Western blotting)检测前列腺组织Fas、Fas L、Bax、Bcl-2、表皮生长因子(EGF)及其受体EGFR的表达。结果与NC组比,BPH组前列腺组织湿质量及PI均较明显增加(P<0.05);血清E2及T水平均显著升高(P<0.05);前列腺组织中Fas L、Bcl-2、EGF及EGFR表达水平均显著升高(P<0.05),而Fas和Bax表达水平均显著降低(P<0.05)。与BPH组比,中、高剂量SI组前列腺组织湿质量及PI均明显减少(P<0.05);血清E2及T水平均显著下降(P<0.05);前列腺组织中Fas L、Bcl-2、EGF及EGFR表达水平均显著降低(P<0.05),而Fas和Bax表达水平显著升高(P<0.05);其中,中剂量SI组各指标变化较低、高剂量组更显著(P<0.05)。结论 SI对BPH具有较好的抑制作用,其中中剂量SI作用效果更佳,其作用机制可能与调节机体性激素水平,下调生长因子及其受体表达以及调控细胞凋亡基因表达有关。     

Prostatic specific antigen in prostatic cancer and benign hyperplasia

Total and free prostatic specific antigens were measured using heterogeneous two-step streptavidin enzyme immunoassay. Serum concentrations of both antigens were significantly increased in patients with prostatic cancer in comparison with those with benign hyperplasia and controls. The levels of prostatic specific antigen in patients with benign prostatic hyperplasia varied within the normal range (75%), while in 92.2% of patients with cancer these values were higher than the threshold value of 4.0 ng/ml. A statistically significant difference between the levels of total and free prostatic specific antigens reflects the difference in the expression of bound and free forms of the antigen in malignant and benign processes. Analysis of the concentrations of total antigen and the ratio of free to total prostatic specific antigen permits an accurate differentiation between cancer and benign hyperplasia of the prostate at total antigen concentrations of up to 10.0 ng/ml. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 9, 327–330, September, 1997     

Morphogenetic concepts of normal and abnormal growth in the human prostate

 Benign prostatic hyperplasia (BPH) and prostate cancer are multifactorial disease processes, involving a growing number of biochemical, genetic and epigenetic factors. Their pathogenesis, however, remains poorly understood. The present review examines current morphogenetic concepts of normal and abnormal growth in the human prostate. This includes the role of basal cells in organogenesis and cancerogenesis, the impact of cell–matrix interactions, and the importance of cellular heterogeneity in tumour progression and hormone-insensitive growth. Knowledge of morphogenesis and morphology is required in any scientific approach to BPH and prostate cancer. Received: 21 March 1998 / Accepted: 25 May 1998     

Dietary supplements for benign prostatic hyperplasia: An overview of systematic reviews

Benign prostatic hyperplasia (BPH) is a common chronic condition in older men. The aim of this overview of systematic reviews (SRs) is to summarise the current evidence on the efficacy and adverse effects of dietary supplements for treating BPH with lower urinary tract symptoms. We searched 5 electronic databases and relevant overviews without limitations on language or publication status. Six SRs of 195 articles were included in this overview. Serenoa repens was reviewed in 3 studies and no specific effect on BPH symptoms and urinary flow measures was observed. However, β-sitosterol, Pygeum africannum and Cernilton were reviewed in one study each, and significant improvement was observed for all three. All the included compounds have mild and infrequent adverse effects. SRs on β-sitosterol, Pygeum africannum and Cernilton have not been updated since 2000, thus an update of reviews on these compounds will be necessary in the future.     

Immunohistochemical analysis of the impact of ischemic change in benign prostatic hyperplasia

ObjectiveWe conducted experiments to elucidate the impact of ischemic change on benign prostatic hyperplasia (BPH) using immunohistochemistry.MethodsMedical records of consecutive patients over 60 years of age who underwent transurethral resection of the prostate for BPH between January 2009 and September 2012 were evaluated. As vascular risk factors, the presence or absence of diabetes mellitus, hypertension, current smoking, obesity, dyslipidemia, and diseases related to bladder function were investigated. As BPH-related factors, International Prostate Symptom Score, quality of life, maximal flow rate, postvoid residual volume, prostate-specific antigen, prostate volume, prostate calculi, and medication state for BPH were investigated. Immunohistochemistry was performed for hypoxia-inducible factor (HIF-1α), sex hormone receptors, and smooth muscle actin. Additionally, microvessel density (MVD) and diffuse fibrosis (DF) were evaluated.ResultsA total of 101 patients were included and HIF-1α expression in stroma and glands were observed in 56 (55.4%) and 34 (33.7%) cases, respectively. There was no significant association between HIF-1α expression and vascular risk factors or BPH-related variables. However, there was a significant correlation between the HIF-1α expression in stroma and higher MVD. HIF-1α expression in the stroma was also significantly correlated with higher expressions of the androgen and progesterone receptors in the stroma. DF was frequently found in cases with higher HIF-1α expression in the stroma than in those with lower HIF-1α expression.ConclusionIn patients with response to ischemic changes of the prostate, HIF-1α expression could be confirmed, and the expression of the androgen receptor was significantly lower in these patients. Chronic ischemic damage in the prostate can progress to a condition that is refractory to pharmacologic therapy. Chronic ischemic damage, which can progress to refractory phase to pharmacologic therapy, is correlated with the hormonal status of prostate.     

前列腺增生腺体的局部解剖观察和临床应用

目的：了解认识前列腺增生腺体的局部解剖结构,改进治疗前列腺增生的手术方式。方法：解剖观察10例耻骨上经膀胱前列腺剜除术的完整标本,在标本上模拟设计尿道外增生腺体摘除的手术方法,在12例实际手术中验证方法。结果：10例标本的尿道起始部与增生腺体前上部分腺体之间存在一隐窝,是两侧增生腺体前面的内侧缘弧线形相交形成的夹角区域,为无增生腺体覆盖的三角形尿道裸区,由这一区域分离尿道与增生腺体,可将增生腺体解剖为外层包绕的薄层组织和两侧增生腺体的主体,并由增生腺体中完整分离出尿道,予以完整保留。实际手术中,12例尿道外全部摘除增生的腺体,完整保留尿道,2例尿道有小的纵行裂口。结论：前列腺存在一个无增生腺体覆盖的尿道裸区,利用这个解剖标志可建立一种新的彻底摘除前列腺增生腺体并保留尿道手术的方法。