A Randomized Trial of Lycopene Supplementation in Tobago Men with High Prostate Cancer Risk

This unblinded, randomized, Phase I clinical trial was conducted to determine whether lycopene supplementation lowered serum prostate specific antigen (PSA), surrogate endpoint for prostate cancer initiation or progression, in men with elevated prostate cancer risk. Afro-Caribbean men (n = 81) with high-grade prostatic intraepithelial neoplasia, atypical foci or repeated non-cancerous biopsies, ascertained in a population-based screening program, were randomized to four months intervention with 30 mg/day lycopene (Lyc-O-Mato®) plus a multivitamin, or to multivitamin, only. Serum PSA and lycopene were compared at randomization, 1, and 4 mo using two-sided χ ² and t-tests for independent samples. Treatment groups were similar at baseline. Serum lycopene levels approximately doubled in the lycopene intervention group. Serum PSA declined during the first month of treatment, but returned to randomization level by month 4. The PSA response was nearly identical in both treatment groups. No adverse effects attributed to lycopene supplementation were documented. We conclude that the PSA lowering response to antioxidant supplementation observed in previous 3-wk studies in men awaiting prostatectomy may have been a transient response, perhaps not specific to lycopene. Lowering of serum PSA may not be an appropriate endpoint for the long-term studies needed to evaluate lycopene supplementation for reducing prostate cancer initiation or progression.     

A randomized trial of lycopene supplementation in Tobago men with high prostate cancer risk

This unblinded, randomized, Phase I clinical trial was conducted to determine whether lycopene supplementation lowered serum prostate specific antigen (PSA), surrogate endpoint for prostate cancer initiation or progression, in men with elevated prostate cancer risk. Afro-Caribbean men (n=81) with high-grade prostatic intraepithelial neoplasia, atypical foci or repeated non-cancerous biopsies, ascertained in a population-based screening program, were randomized to four months intervention with 30 mg/day lycopene (Lyc-O-Mato) plus a multivitamin, or to multivitamin, only. Serum PSA and lycopene were compared at randomization, 1, and 4 mo using two-sided chi2 and t-tests for independent samples. Treatment groups were similar at baseline. Serum lycopene levels approximately doubled in the lycopene intervention group. Serum PSA declined during the first month of treatment, but returned to randomization level by month 4. The PSA response was nearly identical in both treatment groups. No adverse effects attributed to lycopene supplementation were documented. We conclude that the PSA lowering response to antioxidant supplementation observed in previous 3-wk studies in men awaiting prostatectomy may have been a transient response, perhaps not specific to lycopene. Lowering of serum PSA may not be an appropriate endpoint for the long-term studies needed to evaluate lycopene supplementation for reducing prostate cancer initiation or progression.     

PSA、f-PSA和f-PSA/PSA在前列腺疾病诊断中的作用

目的探讨血清前列腺特异抗原(PSA)、游离态的PSA(f-PSA)和f-PSA/PSA比值在前列腺良恶性疾病诊断中的作用。方法采用双抗体夹心磁微粒化学发光法测定正常对照91例、未经治疗前列腺癌(PCa)69例和良性前列腺增生(BPH)86例患者血清中的PSA、f-PSA含量并计算f-PSA/PSA比值。结果前列腺疾病患者各项指标均显著高于正常对照组(p<0.01),以PCa组升高较明显,与BPH组比较亦在显著性差异(p<0.01)。两组患者间PSA无显著性差异(p>0.05),两组患者间f-PSA/PSA比值有显著性差异(p<0.01)。结论前列腺良恶性疾病的诊断,f-PSA/PSA比值的诊断价值,明显优于单纯使用PSA。     

Rye whole grain and bran intake compared with refined wheat decreases urinary C-peptide, plasma insulin, and prostate specific antigen in men with prostate cancer

Rye whole grain and bran intake has shown beneficial effects on prostate cancer progression in animal models, including lower tumor take rates, smaller tumor volumes, and reduced prostate specific antigen (PSA) concentrations. A human pilot study showed increased apoptosis after consumption of rye bran bread. In this study, we investigated the effect of high intake of rye whole grain and bran on prostate cancer progression as assessed by PSA concentration in men diagnosed with prostate cancer. Seventeen participants were provided with 485 g rye whole grain and bran products (RP) or refined wheat products with added cellulose (WP), corresponding to ~50% of daily energy intake, in a randomized controlled, crossover design. Blood samples were taken from fasting men before and after 2, 4, and 6 wk of treatment and 24-h urine samples were collected before the first intervention period and after treatment. Plasma total PSA concentrations were lower after treatment with RP compared with WP, with a mean treatment effect of -14% (P = 0.04). Additionally, fasting plasma insulin and 24-h urinary C-peptide excretion were lower after treatment with RP compared with WP (P < 0.01 and P = 0.01, respectively). Daily excretion of 5 lignans was higher after the RP treatment than after the WP treatment (P < 0.001). We conclude that whole grain and bran from rye resulted in significantly lower plasma PSA compared with a cellulose-supplemented refined wheat diet in patients with prostate cancer. The effect may be related to inhibition of prostate cancer progression caused by decreased exposure to insulin, as indicated by plasma insulin and urinary C-peptide excretion.     

PSA、f／tPSA、PV和PSAD在前列腺癌早期诊断中的比较

目的探讨血清总前列腺特异抗原（tPSA）、血清游离PSA与总PSA比值（f／tPSA）、前列腺体积（PV）及前列腺特异抗原密度（PSAD）在早期前列腺癌（PCa）诊断中的价值。方法回顾性分析252例BPH患者和49例PCa患者的血清PSA值及相关检测结果。经直肠超声（TRUS）测定前列腺体积（PV）,并计算f／tPSA和PSAD值。比较BPH和PCa组间血清tPSA、f／tPSA、PV和PSAD检测结果间的差异,分析这四项指标的ROC曲线下面积、诊断敏感性和诊断特异性的差异。结果PCa组患者tPSA、PSAD明显高于BPH组（P〈0．05）,而f／tPSA、PV中PCa组患者明显低于BPH组（P〈0．01或P〈0．05）。ROC曲线下面积,血清tPSA（0．8013）、f／tPSA（0．7390）、PV（0．5613）三者检测诊断价值较低,PSAD（0．9214）值的检测诊断价值较前三者明显,即PSAD〉tPSA〉f／tPSA〉PV。当PSA取正常值高限4ng／ml时,诊断敏感性为91．49％,诊断特异性为51．05％,当f／tPSA取临界值0．16时,诊断敏感性57．78％,诊断特异性为78．72％,当PSAD取临界值0．15时,诊断敏感性88．24％,诊断特异性为81．52％。结论PSA、f／tPSA和PSAD都是前列腺癌早期诊断穿刺或随访的指标,提高前列腺癌的诊断敏感性和特异性,其中PSAD较PSA和f／tPSA具有更高的诊断价值。     

18F-FDG PET/CT显像联合血清学指标在前列腺癌原发灶诊断及骨转移评估中的价值研究

目的:探讨18F-氟代脱氧葡萄糖(18F-FDG)PET/CT显像和前列腺血清学指标检测在鉴别前列腺癌(PCa)与前列腺增生(BPH)及是否合并骨转移中的价值。方法:选取在医院就诊的因怀疑前列腺恶性肿瘤而行穿刺活检的132例患者,确诊后将其分别纳入PCa组(92例)和BPH组(40例);另将PCa组患者分为PCa骨转移组(67例)和非骨转移组(25例)。分析PCa组和BPH组患者、PCa骨转移组和非骨转移组患者的18F-FDG PET/CT最大标准摄取值(SUVmax)与血清前列腺特异性抗原(PSA)检测结果,比较组间前列腺SUVmax及血液中总PSA(T-PSA)、游离PSA(f-PSA)、f/T-PSA、PSA密度(PSAD)、(f/T-PSA)/PSAD水平的差异,并采用受试者工作特征(ROC)曲线下面积(AUC)分析各指标对PCa骨转移的诊断价值。结果:除f/T-PSA指标外,PCa组患者原发病灶SUVmax与血液中各肿瘤标记物水平均明显高于BPH组(t=11.10,t=13.80,13.68,t=10.77,t=-5.98;P=0.05);PCa骨转移组患者PSAD与(f/T)/PSAD水平明显高于非骨转移组(t=2.186,t=-3.183;P<0.05),前列腺原发灶(f/T)/PSAD和PSAD的AUC分别为0.734和0.704,(f/T)/PSAD的AUC大于PSAD。结论:SUVmax值、T-PSA、f-PSA、PSAD和(f/T)/PSAD能很好鉴别PCa与BPH;PSAD和(f/T)/PSAD能提高PCa骨转移诊断的敏感性和特异性,且(f/T)/PSAD的诊断价值更高。     

Combined lycopene and vitamin E treatment suppresses the growth of PC-346C human prostate cancer cells in nude mice

Epidemiologic studies have repeatedly associated a high intake of lycopene and vitamin E with reduced prostate cancer risk. The present study examined the ability of the 2 compounds to reduce tumor growth and prostate-specific antigen (PSA) plasma levels in the PC-346C orthotopic mouse model of human prostate cancer. Three days after intraprostatic tumor injection, NMRI nu/nu mice were administered a daily oral dose of synthetic lycopene [5 or 50 mg/kg body weight (BW)], vitamin E in the form of alpha-tocopheryl acetate (5 or 50 mg/kg BW), a mixture of lycopene and vitamin E (5 mg/kg BW each), or vehicle. Intraprostatic tumor volume and plasma PSA concentrations were measured at regular intervals. Mice were killed when the tumor load exceeded 1000 mm(3) or on d 95 when the study was terminated. Prostate and liver were analyzed by HPLC for lycopene isomers and alpha- and gamma, delta-tocopherol concentrations. None of the single treatments significantly reduced tumor volume. In contrast, combined treatment with lycopene and vitamin E, at 5 mg/kg BW each, suppressed orthotopic growth of PC-346C prostate tumors by 73% at d 42 (P < 0.05) and increased median survival time by 40% from 47 to 66 d (P = 0.02). The PSA index (PSA:tumor volume ratio) did not differ between experimental groups, indicating that PSA levels were not selectively affected. Lycopene was detected only in mice supplemented with lycopene. As in humans, most tissue lycopene was in the cis-isomer conformation, whereas 77% trans-lycopene was used in the dosing material. Liver alpha-tocopherol concentrations were increased in mice supplemented with both 50 mg/kg (226%, P < 0.05) and 5 mg/kg vitamin E (41%, P < 0.05), whereas prostate alpha-tocopherol concentrations were increased only by the higher dose (83%, P < 0.05). Our data provide evidence that lycopene combined with vitamin E may inhibit the growth of prostate cancer and that PSA can serve as a biomarker of tumor response for this treatment regimen.     

Cost effectiveness of chemoprevention for prostate cancer with dutasteride in a high-risk population based on results from the REDUCE Clinical trial

Background

The REDUCE trial examined whether chemoprevention with the dual 5-alpha reductase inhibitor, dutasteride, reduced risk of prostate cancer (PCa) detection on biopsy.

Objective

We examined the cost effectiveness of dutasteride compared with placebo in preventing PCa in men at increased risk as seen in REDUCE, from a US payer perspective.

Methods

A Markov model was developed to compare costs and outcomes of chemoprevention with dutasteride 0.5 mg/day or placebo with usual care in men aged 50–75 years, with serum prostate-specific antigen (PSA) of 2.5–10 ng/mL (men aged <60 years) or 3.0–10 ng/mL (men aged ≥60 years), and with a single negative prostate biopsy in the prior 6 months. The model simulated the REDUCE cohort annually through different health states over 4-, 10-year and lifetime time horizons. Risks of PCa for men receiving placebo and dutasteride were obtained from REDUCE. Rates of acute urinary retention events and benign prostate hyperplasia-related surgeries also came from REDUCE. Costs and utilities were obtained from published literature. All costs are reported in $US, year 2009 values.

Results

The model indicated that, over 10 years, dutasteride patients would experience fewer PCas (251 vs 312 per 1000 patients) at increased cost ($US15341 vs $US12316) than placebo patients. Although life-years were not substantially affected, the model calculated an increase in QALYs of 0.14 for dutasteride patients. Chemoprevention with dutasteride appeared to be cost effective, with an incremental cost per QALY of $US21 781 and cost per PCa avoided of $US50 254. The 4-year and lifetime incremental costs per QALY were $US18 409 and $US22498, respectively.

Conclusions

Despite increased cost due to taking a drug for prevention, dutasteride 0.5 mg/day may be cost effective in men at increased risk for PCa.     

前列腺上皮肉瘤的PSAD与前列腺癌比较

本文报告经病理和免疫组化确诊的前列腺癌（PCa）57例,前列腺上皮肉瘤（PIN）54例和前列腺增生104例,比较各组的前列腺体积（PV）,血清前列腺特异性抗原（PSA）和PSA密度（PSAD）。结果显示PIN与BPH的PSA、、PV和PSAD差异不明显（P＞0．05）,但与PCa组差异显著（P＜0.01）。以PSA10ng／ml和PSAD0.2为界值,评价PCa组,其敏感性备为49％和42％,特异性79％和84％,准确性64％和63％。     

Lycopene and soy isoflavones in the treatment of prostate cancer

Dietary intake of lycopene and soy has been associated with a lower risk of prostate cancer. In vitro studies with lycopene and genistein, a soy isoflavone, have shown induction of apoptosis and inhibition of cell growth in androgen-sensitive (LNCaP) and androgen-independent (PC3 and VeCaP) prostate cancer cell lines. In a previous Phase II clinical trial in prostate cancer patients, we observed prostate-specific antigen (PSA) stabilization with soy isoflavone intake. In this Phase II clinical trial, we investigated the efficacy of lycopene alone or in combination with soy isoflavones on serum PSA levels in men with prostate cancer. To be eligible for the study, men with prostate cancer had to have rising serum PSA following local therapy or while on hormone therapy. Study population included 71 eligible patients who had 3 successive rising PSA levels or a minimum PSA of 10 ng/ml at 2 successive evaluations prior to starting therapy. Subjects were randomly assigned to receive a tomato extract capsule containing 15 mg of lycopene alone (n = 38) or together with a capsule containing 40 mg of a soy isoflavone mixture (n = 33) twice daily orally for a maximum of 6 mo. One patient on the lycopene arm did not receive therapy due to his inability to ingest the study pill. There was no decline in serum PSA in either group qualifying for a partial or complete response. However, 35 of 37 (95%) evaluable patients in the lycopene group and 22 of 33 (67%) evaluable patients in the lycopene plus soy isoflavone group achieved stable disease described as stabilization in serum PSA level. The data suggest that lycopene and soy isoflavones have activity in prostate cancer patients with PSA relapse disease and may delay progression of both hormone-refractory and hormone-sensitive prostate cancer. However, there may not be an additive effect between the 2 compounds when taken together. Future studies are warranted to further investigate the efficacy of lycopene and soy isoflavones in prostate cancer as well as the mechanism of potential negative interaction between them.     

MRI、MRS对前列腺癌及前列腺增生的诊断价值

目的探讨MRI、MRS在前列腺癌及前列腺增生诊断中的应用。方法回顾性分析经病理证实的28例前列腺癌和32例前列腺增生患者的MRI前列腺形态、信号改变及MRS测量枸橼酸盐（Citrate）、胆碱（Choline）、肌酸（Creatine）的峰值、（胆碱＋肌酸）／枸橼酸盐[（Cho＋Cre）／Cit,CC／C]的比值。结果MRS测得PCa癌区和BPH中央带的CC／C平均值分别为（2．24±0．96）和（0．67±0．21）,组间差异有统计学意义（t=3．989,P〈0．001）。28例前列腺癌患者MRI确诊为前列腺癌21例,准确率75％;MRI联合MRS确诊为前列腺癌26例,准确率为92．9％。32例BPH患者MRI影像诊断确诊为前列腺增生23例,不除外前列腺癌9例,准确率为71．9％。MRS波谱分析结合MRI影像诊断确诊为前列腺增生29例,不除外前列腺癌3例,准确率为90．6％。结论MRI能很好地显示BPH和PCa的形态和信号特点,MRS能提供前列腺良、恶性组织的代谢信息,两者联合诊断有助于提高PCa和BPH的诊断的准确性。     

观察等待治疗方案下良性前列腺增生症患者24个月随访数据分析

目的 掌握观察等待治疗方案下良性前列腺增生症(BPH)患者主要临床指标的具体数据变化规律,分析影响病情进展的主要危险因素.方法 按照试验规定的纳入和排除标准,选择初诊BPH患者纳入观察等待治疗方案组,对入组患者的国际前列腺增生症症状评分(IPSS)、前列腺体积、血清前列腺特异性抗原(PSA)、最大尿流率、平均尿流率、残余尿进行24个月的随访观察.结果 IPSS、前列腺体积、PSA(ng/ml)、最大尿流率(ml/s)在基线、12个月、24个月时分别为7±4、4±3、4±3;33.0±9.0、33.8±7.6、30.9±6.8;1.53±1.35、1.43±0.95、1.22±0.99;17.1±5.0、17.2±6.1、19.2±8.0.在随访24个月时,61例观察等待的患者,除前列腺体积均数有缓慢地进展外,其他观察指标均略有好转,其中有42例(69%)患者病情进展缓慢,甚至有所好转.而随访IPSS评分均数与入组时之差值的差异有统计学意义(P＜0.0001).用logistic回归对影响病情进展的因素进行分析,结果显示只有前列腺体积(P=0.0910)、残余尿(P=0.0780)具有成为影响因素的趋势.结论 在观察等待治疗方案下,入组的BPH患者在24个月中病情进展缓慢,大部分病例不必转入其他治疗方案.对观察等待BPH患者的随访情况进行数据化分析,能够为更加合理、精确地选择BPH的干预时间和治疗方案提供有意义的数据化参考.     

Effects of tomato sauce consumption on apoptotic cell death in prostate benign hyperplasia and carcinoma

Population studies have suggested that lycopene, which is mostly found in tomato and tomato products, may reduce the risk of prostate cancer. We previously found that tomato sauce consumption prior to prostatectomy for prostate cancer decreased serum prostate specific antigen, decreased oxidative DNA damage, and increased lycopene concentrations in prostate tissue (Chen et al., 2001). Here, we extended those investigations to determine whether apoptotic cell death and associated Bcl-2 and Bax proteins were modulated by tomato sauce intervention. Thirty-two patients diagnosed by biopsy with prostate carcinoma were given tomato sauce pasta entrees (30 mg lycopene/day) for 3 wk before prostatectomy. Thirty-four patients with prostate cancer who did not consume tomato sauce and underwent prostatectomy served as controls. When tumor areas with the most apoptotic cells were compared in the biopsy (before) and resected prostate tissue (after), tomato sauce consumption increased apoptotic cells in benign prostate hyperplasia (BPH) from 0.66 +/- 0.10% to 1.38 +/- 0.31% (P = 0.013) and in carcinomas from 0.84 +/- 0.13% to 2.76 +/- 0.58% (P = 0.0003). When comparable morphological areas were counted, apoptotic cell death in carcinomas increased significantly with treatment, from 0.84 +/- 0.13% to 1.17 +/- 0.19% (P = 0.028), and apoptotic cell death in BPH showed a tendency toward an increase from 0.66 +/- 0.10% to 1.20 +/- 0.32% (P = 0.20). When the values of apoptotic cells in BPH and carcinomas of patients who consume tomato sauce were compared with corresponding control lesions of the patients who did not consume tomato sauce in resected prostate tissue, the differences of values were not significant [BPH 1.38 +/- 0.31% vs. 1.14 +/- 0.32% (P = 0.97); carcinomas 2.76 +/- 0.58% vs. 1.91 +/- 0.32% (P = 0.24)]. Tomato sauce consumption did not affect Bcl-2 expression but decreased Bax expression in carcinomas. These data provide the first in vivo evidence that tomato sauce consumption may suppress the progression of the disease in a subset of patients with prostate cancer by increasing apoptotic cell death. However, because of the relatively small number of control and tomato sauce-supplemented patients and the variability in the values of apoptotic cells in BPH and carcinomas, a much larger number of patients needs to be examined to support the data generated in this study.     

Economic Evaluation of Urine-Based or Magnetic Resonance Imaging Reflex Tests in Men With Intermediate Prostate-Specific Antigen Levels in the United States

ObjectivesFor men with intermediate prostate-specific antigen (PSA) levels (4-10 ng/mL), urine-based biomarkers and multiparametric magnetic resonance imaging (MRI) are increasingly used as reflex tests before prostate biopsy. We assessed the cost effectiveness of these reflex tests in the United States.MethodsWe used an existing microsimulation model of prostate cancer (PCa) progression and survival to predict lifetime outcomes for a hypothetical cohort of 55-year-old men with intermediate PSA levels. Urine-based biomarkers—PCa antigen (PCA3), TMPRSS2:ERG gene fusion (T2:ERG), and the MyProstateScore (MPS) for any PCa and for high-grade (Gleason score ≥7) PCa (MPShg)—were generated using biomarker data from 1112 men presenting for biopsy at 10 United States institutions. MRI results were based on published sensitivity and specificity for high-grade PCa. Costs and utilities were sourced from literature and Medicare reimbursement schedules. Outcome measures included life years, quality-adjusted life years (QALYs), and lifetime medical costs per patient. Incremental cost-effectiveness ratios were empirically calculated on the basis of simulated life histories under different reflex testing strategies.ResultsBiopsying all men provided the most life years and QALYs, followed by reflex testing using MPShg, MPS, MRI, T2:ERG, PCA3, and biopsying no men (QALY range across strategies 15.98-16.09). Accounting for costs, MRI and MPShg were dominated by other strategies. PCA3, T2:ERG, and MPS were likely to be the most cost-effective strategy at willingness-to-pay thresholds of $100 000/QALY, $125 000/QALY, and $150 000/QALY, respectively.ConclusionsUsing PCA3, T2:ERG, or MPS as reflex tests has greater economic value than MRI, biopsying all men, or biopsying no men with intermediate PSA levels.     

Carotenoids in human buccal mucosa cells after 4 wk of supplementation with tomato juice or lycopene supplements.

BACKGROUND: Lycopene has been identified as a phytochemical with potentially protective health benefits. OBJECTIVE: Our objective was to monitor lycopene changes in buccal mucosa cells (BMCs) in response to 3 vehicles for oral delivery of lycopene. DESIGN: Fifteen healthy subjects ingested lycopene-rich tomato juice, tomato oleoresin, lycopene beadlets (each containing 70-75 mg lycopene) and a placebo for 4 wk each in a randomized crossover design while consuming self-selected diets. A 6-wk washout period separated the treatment periods. BMCs were collected at baseline and after 4 wk of supplementation. RESULTS: Lycopene in BMCs increased significantly ( approximately 2-fold) after 4 wk of ingestion of oleoresin and of beadlets to 4.95 (P < 0.001) and 3.75 microg/g protein (P = 0.053), respectively, but was not significantly affected by tomato juice treatment. The placebo treatment produced a significant decrease in BMC lycopene concentrations (P = 0.018). We observed significant treatment differences between oleoresin and tomato juice, oleoresin and placebo, and beadlets and placebo. BMC concentrations of phytofluene and beta-carotene, which were present in small amounts in the lycopene-containing treatments, increased significantly with ingestion of these products. Strong correlations were found between plasma and BMC concentrations of lutein, beta-cryptoxanthin, alpha-carotene, and beta-carotene. In contrast, correlations between lycopene concentrations in plasma and in BMCs were weak and not significant for any treatment. CONCLUSIONS: The cellular content of lycopene and other tomato-related carotenoids with proposed beneficial health effects can be increased through prolonged supplementation.     

经尿道等离子前列腺电切在诊断前列腺穿刺活检阴性的前列腺癌患者中的作用

目的探讨经尿道等离子前列腺电切术（PKRP）在前列腺穿刺活检阴性的前列腺增生症患者中,诊断前列腺癌的重要临床意义。方法回顾性分析50例行经尿道等离子电切术（PKRP）患者．按不同的治疗措施随机分为两组：组1PKRP术前行经直肠超声（TRUS）前列腺穿刺活检阴性者,其中术后证实为前列腺癌者为组1A,术后证实为良性前列腺增生者为组1B;组2PKRP术前未行穿刺活检者。同时检测所有患者前列腺特异性抗原（PSA）、直肠指检（DKE）、前列腺切除量、术后病理、TRUS穿刺活检结果。结果两组对前列腺癌的检出率（组1：14％,组2：8．5％）有显著性差异（P〈0．05）。其中组1中A组和B组间前列腺体积、移行区体积,PSA和PSAD值无显著性差异（P〉0．05）：TRUS低回声区发生率两组间比较有显著性差异（P〈0．01）。异常直肠指检（DIKE）有显著性差异（P〈0．05）。前列腺癌的检出率与PSA值呈正相关性。结论经尿道等离子前列腺电切术（PKRP）对疑有前列腺癌和良性前列腺增生症患者都具有良好手术效果和安全性,而且对诊断前列腺活检穿刺阴性的前列腺癌具有重要的作用。     

Effect of lycopene supplementation on insulin-like growth factor-1 and insulin-like growth factor binding protein-3: a double-blind, placebo-controlled trial

OBJECTIVE: Studies have suggested a link between lycopene and insulin-like growth factor-1 (IGF-1). The aim of this study was to test the effect of lycopene supplementation on IGF-1 and binding protein-3 (IGFBP-3) status in healthy male volunteers. DESIGN, SETTING, SUBJECTS AND INTERVENTION: This was a 4 week randomized, double-blind, placebo-controlled study of lycopene supplementation (15 mg/day) in healthy male volunteers (n=20). Fasting blood samples were collected at baseline and after 4 weeks. Samples were analysed for lycopene by high-performance liquid chromatography (HPLC) and IGF-1 and IGFBP-3 by enzyme-linked immunosorbent assay (ELISA). Changes in end points from baseline were compared in those who received placebo versus those who received the lycopene supplement. RESULTS: Median change in lycopene from baseline (post-supplement - baseline) was higher in subjects in the intervention than those on placebo (lycopene group 0.29 (0.09, 0.46); placebo group 0.03 (-0.11, 0.08) micromol/l; median (25th, 75th percentiles), P<0.01). There was no difference in median change in IGF-1 concentrations (lycopene group -0.6 (-2.6, 1.9); placebo group -1.15 (-2.88, 0.95) nmol/l, P=0.52), or median change in IGFBP-3 concentrations (lycopene group 245 (-109, 484); placebo group 101 (-34, 234) nmol/l, P=0.55) between intervention and control groups. Change in lycopene concentration was associated with the change in IGFBP-3 in the intervention group (r=0.78; P=0.008; n=10). CONCLUSIONS: Lycopene supplementation in healthy male subjects has no effect on IGF-1 or IGFBP-3 concentrations in a healthy male population. However, the association between change in lycopene concentration and change in IGFBP-3 in the intervention group suggests a potential effect of lycopene supplementation on IGFBP-3.     

Risk factors for clinical benign prostatic hyperplasia in a community-based population of healthy aging men

We defined risk factors for a clinical diagnosis of benign prostatic hyperplasia (BPH) among subjects of the population-based Massachusetts Male Aging Study. In 1987-89 1709 men aged 40-70 provided baseline risk factor data and were followed for a mean of 9 years; 1019 men without prostate cancer provided follow-up data. We classified men with clinical BPH at follow-up if they reported (1) frequent or difficulty urinating and were told by a health professional that they had an enlarged or swollen prostate or (2) if they reported having surgery for BPH. At follow-up the prevalence of clinical BPH was 19.4%, increasing from 8.4% of men aged 38-49 years to 33.5% of men aged 60-70 years (P < 0.001 for trend). Elevated free PSA levels (age- and total PSA-adjusted OR, top vs. bottom quartile ng/mL 4.4, 95% CI 1.9-10.5), heart disease (age-adjusted OR 2.1, CI 1.3-3.3), and use of beta-blocker medications (OR 1.8, CI 1.1-3.0) increased odds for BPH, while current cigarette smoking (OR 0.5, CI 0.3-0.8) and high levels of physical activity (top vs. bottom quartile kcals/day OR 0.5, CI 0.3-0.9) decreased odds of BPH. All but the medication effects persisted in fully adjusted multivariable models. Total or fat calorie intake, sexual activity level, alcohol intake, body mass index, waist-hip ratio, diastolic blood pressure, a history of diabetes, hypertension, vasectomy, or serum levels of androgens or estrogens did not individually predict clinical BPH. We conclude that physical exercise and cigarette smoking appear to protect against development of clinical BPH. Elevated free PSA levels predict clinical BPH independent of total PSA levels. Risk associated with heart disease does not appear to be due solely to detection bias or to effects of heart disease medications. A wide variety of other characteristics appear to have no influence on risk for clinical BPH.     

老年男性患者血清前列腺特异性抗原增高96例临床病理分析

目的探讨血清前列腺特异性抗原(PSA)增高在老年男性前列腺疾病中的临床意义。方法对96例临床检测血清PSA>4ng/ml老年男性患者前列腺按病理诊断分为3组:良性前列腺增生(BPH)47例、前列腺癌前病变(PPC)23例、前列腺癌(PCa)26例。经直肠B超检测前列腺体积,分析各组患者血清PSA、游离PSA与血清PSA比值(FPSA/PSA)、PSA密度(PSAD)等计量资料以及分区域计数资料与病理诊断结果关系。结果各组患者血清PSA、FPSA/PSA、PSAD差异有统计学意义(P<0.01,P<0.05);将患者按PSA、PSAD、FPSA/PSA值大小分区,各组患者在各区间人数分布差异有统计学意义(P<0.01);按血清PSA>20ng/ml并FPSA/PSA<0.25、PSA为10～20ng/ml并FPSA/PSA<0.15标准判断PCa,特异性为66.7%,灵敏度为85.7%。结论PSA是早期诊断PCa的重要线索,结合FPSA/PSA比值对早期诊断PCa有较大意义,PSAD可以作为PCa早期诊断的辅助指标。     

Lycopene supplementation elevates circulating insulin-like growth factor binding protein-1 and -2 concentrations in persons at greater risk of colorectal cancer

BACKGROUND: Higher circulating insulin-like growth factor I (IGF-I) concentrations have been related to a greater risk of cancer. Lycopene intake is inversely associated with cancer risk, and experimental studies have shown that it may affect the IGF system, possibly through an effect on IGF-binding proteins (IGFBPs). OBJECTIVE: The objective of our study was to investigate the effect of an 8-wk supplementation with tomato-derived lycopene (30 mg/d) on serum concentrations of total IGF-I, IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3. DESIGN: We conducted a randomized, placebo-controlled, double-blinded crossover study in 40 men and 31 postmenopausal women with a family history of colorectal cancer, a personal history of colorectal adenoma, or both. RESULTS: Lycopene supplementation significantly (P = 0.01) increased serum IGFBP-1 concentrations in women (median relative difference between serum IGFBP-1 concentrations after lycopene supplementation and after placebo, 21.7%). Serum IGFBP-2 concentrations were higher in both men and women after lycopene supplementation than after placebo, but to a lesser extent (mean relative difference 8.2%; 95% CI: 0.7%, 15.6% in men and 7.8%; 95% CI: -5.0%, 20.6% in women). Total IGF-I, IGF-II, and IGFBP-3 concentrations were not significantly altered by lycopene supplementation. CONCLUSIONS: This is the first study known to show that lycopene supplementation may increase circulating IGFBP-1 and IGFBP-2 concentrations. Because of high interindividual variations in IGFBP-1 and IGFBP-2 effects, these results should be confirmed in larger randomized intervention studies.