Plasma Prostate-specific Antigen Levels Research Articles

Neoadjuvant Exercise Therapy in Prostate Cancer

Observational data have shown that postdiagnosis exercise is associated with reduced risk of prostate cancer death. The feasibility and tumor biological activity of exercise therapy is not known. To identify recommended phase 2 dose of exercise therapy for patients with prostate cancer. This single-center, phase 1a dose-finding trial was conducted at a tertiary cancer center using a patientcentric, decentralized platform and included 53 inactive men with treatment-naive localized prostate cancer scheduled to undergo surgical resection between June 2019 and January 2023. Data were analyzed in June 2024. Six escalated exercise therapy dose levels ranging from 90 to 450 minutes per week of individualized, moderate-intensity treadmill walking, allocated using adaptive continual reassessment. All exercise therapy sessions were conducted remotely with real-time monitoring. Feasibility was evaluated by relative exercise dose intensity (REDI). A dose level was considered feasible if 70% or more of patients achieved an REDI of 75% or greater. Activity end points were changes in tumor cell proliferation (Ki67) and plasma prostate-specific antigen levels between pretreatment and postintervention. Safety and changes in patient physiology were also assessed. A total of 53 men were enrolled (median [IQR] age, 61 [56-66] years). All dose levels were feasible (≥75% REDI). The mean (95% CI) changes in Ki67 were 5.0% (-4.3% to 14.0%) for 90 minutes per week, 2.4% (-1.3% to 6.2%) for 150 minutes per week, -1.3% (-5.8% to 3.3%) for 225 minutes per week, -0.2% (-4.0% to 3.7%) for 300 minutes per week, -2.6% (-9.2% to 4.1%) for 375 minutes per week, and 2.2% (-0.8% to 5.1%) for 450 minutes per week. Changes in prostate-specific antigen levels were 1.0 ng/mL (-1.8 to 3.8) for 90 minutes per week, 0.2 ng/mL (-1.1 to 1.5) for 150 minutes per week, -0.5 ng/mL (-1.2 to 0.3) for 225 minutes per week, -0.2 (-1.7 to 1.3) for 300 minutes per week, -0.7 ng/mL (-1.7 to 0.4) for 375 minutes per week, and -0.9 ng/mL (-2.4 to 0.7) for 450 minutes per week. No serious adverse events were observed. Overall, 225 minutes per week (approximately 5 minutes per treatment at 5 times weekly) was selected as the recommended phase 2 dose. The results of this nonrandomized clinical trial suggest that neoadjuvant exercise therapy is feasible and safe with promising activity in localized prostate cancer. ClinicalTrials.gov Identifier: NCT03813615.

Detection efficacy of PET/CT with 18F-FSU-880 in patients with suspected recurrent prostate cancer: a prospective single-center study.

Our objective was to investigate the efficacy of PET/CT with a novel prostate-specific membrane antigen (PSMA)-targeted PET probe, 18F-FSU-880, for detection and localization of recurrent disease in prostate cancer patients in whom recurrence was suspected based on an increase in plasma prostate-specific antigen (PSA) levels after initial treatment. This study was a prospective institutional review board-approved study of 72 patients (age 56-84years, PSA level 0.22-40.00ng/ml) with suspected relapse of prostate cancer after primary therapy, including radical prostatectomy (RP) (n = 35) or radiation therapy (RT) (n = 37). Patients underwent PET/CT approximately 1h and 3h after injection of 18F-FSU-880 (101.8-380MBq). The correlation between patient-based detection rate and Gleason score (GS) of the primary tumor and plasma PSA levels at the time of PET/CT was evaluated. Maximum standardized uptake values (SUVmax) of the positive uptakes at 1h post-injection were compared with those at 3h post-injection. In total, 51 patients (71%) showed at least one positive PSMA PET result. The PSA-stratified detection rates were 22% (2/9), 36% (4/11), 89% (16/18) and 85% (29/34) for PSA levels of 0.2 to < 0.5, 0.5 to < 1.0, 1.0 to < 2.0 and ≥ 2.0ng/ml, respectively. The GS-stratified detection rates were 33% (2/6), 67% (16/24), 70% (16/23) and 89% (17/19) for GS 6, 7, 8 and 9, respectively. In lesion-based analysis, 157 positive lesions were detected at 3h post-injection, 18 in the prostate or prostate bed, 65 in lymph nodes, 71 in the bone and 3 in the lung. Two local recurrences, eight pelvic lymph nodes and one distant lymph node were depicted only at 3h post-injection. SUV max at 3h post-injection was significantly higher than SUVmax at 1h post-injection (p < 0.001). Our preliminary data suggest that 18F-FSU-880 might be a promising new PSMA-targeting tracer for detecting recurrence after initial treatment in patients with prostate cancer.

Association of decreased sperm motility and increased seminal plasma IGF-I, IGF-II, IGFBP-2, and PSA levels in infertile men.

Previous studies have suggested the involvement of serum insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs) in the regulation of the female reproductive system. Little is known of these peptides in the seminal plasma (SP) of men and their potential effects on fertility. We assessed SP levels of these peptides in infertile men with low sperm motility (asthenozoospermic; AZ) and low sperm counts (oligozoospermic; OZ), its effects on in vivo sperm motility, and whether there is a correlation with aging. Twenty-eight infertile men (AZ; n = 18 and OZ; n = 10) and 20 fertile normozoospermic (NZ) men were studied. Seminal plasma IGF-I, IGF-II, IGFBP-2, IGFBP-3, and prostate-specific antigen (PSA) levels were measured, and spermatozoa mRNA transcript patterns were examined. Asthenozoospermic men had higher SP IGF-I, IGF-II, IGFBP-2, and PSA levels than NZ and OZ men, whereas SP IGFBP-3 levels were similar between the three groups. Sperm count positively correlated with SP IGF-I, IGF-II, and IGFBP-2; sperm motility negatively correlated with SP IGF-II and IGFBP-2; and age correlated positively with SP IGF-II. The expression of IGF-I and IGF-II mRNA and mRNA receptors was detectable, but no variations in transcript levels were noted. Decreased sperm motility, but not sperm count, in infertile AZ men is associated with increased SP IGF-I, IGF-II, IGFBP-2, and PSA levels. Changes in SP IGFs and their interactions with IGFBPs and IGF receptors, and PSA levels suggest a role of these SP peptides in modulating sperm motility and possibly prostate disease development in aging men.

Prostate-specific antigen (PSA) related to the anthropometric profile among patients admitted at the Hospital II Huamanga Carlos Tuppia García-Godos, EsSalud. Ayacucho

Objective: To determine the association between plasma and mass prostate-specific antigen (PSA) levels and theanthropometric profile, taking into account the risk of prostate pathologies. Materials and methods: A correlational, quantitative, cross-sectional and retrospective study conducted with a sampleof 156 medical records of male patients with PSA tests and anthropometric data. Spearman's Rho with a 95 % confidencelevel was used to analyze the relationship between the variables. Results: The average age of the patients was 67.85 ± 10.83 years and their mean PSA value was 3.57 ± 7.30 ng/mL. Fifteen (15)patients (9.60 %) had a low risk (PSA = 4.1 – 9.90 ng/mL), eight (5.10 %) a medium risk (PSA = 10 – 19.90 ng/mL) and six (3.80 %)a high risk (PSA ≥ 20 ng/mL) of developing prostate pathologies. The mean body mass index (BMI) was 26.37 ± 3.81 kg/m2: 85patients (54.50 %) were overweight and 18 (11.50 %) were obese. The mean mass PSA was 14.89 ± 30.50 μg, the body surfacearea (BSA) was 3.93 ± 2.72 m2 and the plasma volume was 4.18 ± 0.21 L. A very low positive correlation was evidencedbetween plasma PSA and age (rho = 0.184; p = 0.022) and between mass PSA and age (rho = 0.176; p = 0.028). There was amoderate positive association between plasma PSA and BSA (rho = 0.456; p = 0.000) and between mass PSA and BSA(rho = 0.463; p = 0.000). No relationship was found between BMI and PSA. Conclusions: The association between plasma and mass PSA levels and the anthropometric profile was demonstrated,taking into account the risk of prostate pathologies, which increased with BSA and age.

Association of long-chain non-coding RNA GAS5 gene polymorphisms with prostate cancer risk and prognosis in Chinese Han population.

Background:To investigate the correlation between growth arrest-specific transcript 5 (GAS5) gene polymorphism and the risk and prognosis of prostate cancer in Chinese Han population.Methods:Sanger sequencing was used to analyze genotypes at the rs17359906 and rs1951625 loci of the GAS5 gene in 218 prostate cancer patients and 220 healthy controls. The follow-up period was from August 2016 to August 2019, and the relationships between GAS5 gene polymorphisms at the rs17359906 and rs1951625 loci and the recurrence-free survival rate of prostate cancer patients were analyzed.Results:GAS5 A-allele carriers at the rs17359906 locus were 3.44 times more likely to develop prostate cancer than G-allele carriers (95% confidence interval (CI): 2.38–4.96, P < .001). Carriers of the GAS5 A allele at the rs1951625 locus had a 1.40-fold higher risk of prostate cancer than carriers of the G allele (95% CI: 1.05–1.86, P = .027). Plasma prostate-specific antigen (PSA), body mass index (BMI), and rs17359906 and rs1951625 loci were independent risk factors for prostate cancer. GAS5 AA genotype and A-allele carriers (GA + AA) at the rs1951625 locus were significantly correlated with Gleason scores ≤7 (P < .05). GAS5 genes rs17359906 G > A and rs1951625 G > A were associated with high plasma PSA levels. The recurrence-free survival rate of patients with prostate cancer with AA genotype at the rs17359906 locus of GAS5 (66.67%) was significantly lower than that of the GA genotype (76.47%), whereas the GG genotype was the highest (91.96%), and the difference was statistically significant (P = .002). The recurrence-free survival rate of patients with prostate cancer with the AA genotype at the rs1951625 locus of GAS5 (75.00%) was significantly lower than that of the GA genotype (81.82%), whereas the GG genotype was the highest (87.76%) with a statistically significant difference (P = .025).Conclusion:GAS5 rs17359906 G > A and rs1951625 G > A are significantly associated with an increased risk of prostate cancer and a reduction in three-year relapse-free survival.

COMBINING MODALITY THERAPY WITH SURGERY CAN PROVIDE LONG-TERM SURVIVAL WITH IMPROVED QUALITY OF LIFE FOR PATIENTS WHO HAVE PROSTATE CANCER WITH INTRACRANIAL DURAL METASTASIS: A CASE REPORT

A 61-year-old man visited our hospital with a headache and left visual field defect. A head MRI showed an intracranial dural tumor with cerebral compression, which was suspected to be metastatic. Analysis of the tumor markers revealed an increase in prostate-specific antigen (PSA) levels (172.8 ng/mL), and therefore prostate cancer was suspected as the primary tumor. Histological diagnosis of a prostatic tissue sample using a transrectal needle biopsy gave a prostate carcinoma with Gleason score of 5+4=9. Additional imaging examinations revealed metastatic lesions in the intra-pelvic lymph node and bones. These data indicated to us that curative surgery was unlikely to be successful, but finally we decided to perform a craniotomy for tumor resection for the intracranial dural tumor to remove his neurological symptoms. After surgery, his headache and visual field defect improved. The pathological finding was intracranial dural metastasis from prostate cancer and the clinical stage was diagnosed as T3bN1M1c in the UICC criteria (ver. 8). Endocrine therapy with degarelix and bicalutamide was started for the primary and residual metastatic prostate cancers. After one year of initial treatment, bicalutamide was changed to enzalutamide because of a tendency towards increased plasma PSA levels. The patient has survived for two and a half years after surgery with no new metastatic tumors or intracranial tumors. Our experience indicates that combined modality therapy with surgery can provide long-term survival with no cranial nerve disorders for patients who have prostate cancer with intracranial dural metastasis.

Thiol Groups as a Biomarker for the Diagnosis and Prognosis of Prostate Cancer

Oxidative stress (OS) is associated with the onset of prostate cancer (PCa). The aims of this study are to examine whether OS biomarkers may be employed as external validating criteria for the diagnosis PCa. This case-control study recruited 204 subjects, 73 patients with PCa, 67 patients with benign prostate hyperplasia (BPH), and 64 healthy controls (HC) and assayed plasma prostate-specific antigen (PSA), protein thiol (−SH) groups, lipid hydroperoxides, carbonyl proteins (PCB), advanced oxidation protein products (AOPP), and total radical-trapping antioxidant parameter (TRAP). -SH groups were significantly and inversely associated with PSA levels. PCa was characterized by lowered -SH groups and red blood cell TRAP levels, and higher PSA, AOPP and PCB levels as compared with BPH and HC. Support vector machine with 10-fold cross-validation showed that PSA values together with -SH groups, PCB and AOPP yielded a cross-validation accuracy of 96.34% for the differentiation of PCa from BPH and HC. The area under the ROC curve using PSA and -SH differentiating PCa from BPH and controls was 0.945. Moreover, lowered -SH, but not PSA, are associated with PCa metastasis and progression. Inflammatory biomarkers were not associated with PCa or BPH. PCa, its progression and metastatic PCa are characterized by lowered antioxidant defenses, especially lowered thiol groups, and increased oxidative stress toxicity, suggesting that these processes play a key role in the pathophysiology of PCa. An algorithm based on -SH and PSA values may be used to differentiate patients with PCa from those with BPH and controls.

Pharmacoeconomic study of the degarelix drug use for treatment of hormone-dependent prostate cancer compared to gonadotropin-releasing hormone analogs

Objective: to determine clinical and economic consequences of using the degarelix drug instead of gonadotropin-releasing hormone (GnRH) analogs for treatment of advanced hormone-sensitive prostate c ancer. Materials and methods. The main criteria of therapy effectiveness were overall survival and progression-free survival. Cost of the drugs being compared, as well as expenses associated with therapy after prostate cancer progression (per the dynamics of plasma prostate-specific antigen levels), were considered. A Markov model of prostate cancer progression was used including states “without progression”, “after progression”, and “death”. The modeling time horizon was 3 years. The main source of information on drug costs was the registry of maximal retail pricese for vital and essential drugs. The target population only included patients with high (>20 ng/ml) baseline level of prostate-specific antigen. Information on effectiveness was obtained based on analysis of the results of randomized comparative clinical trials of degarelix and leuprorelin. Results. Compared to leuprorelin, degarelix use was characterized by more favorable effectiveness and safety profiles (based on all criteria considered in the analysis). In the basic modeling script, progression-free survival was 27.9 and 20.1 months for degarelix and GnRH agonists, respectively. Despite higher cost of therapy prior to progression (359,000 and 268,000 rubles, respectively), degarelix use instead of GnRH agonists leads to 31 % decrease in direct budget medical expenses on drug provision under the state guarantee program (1,322,000 vs. 1,907,000 rubles), as well as to a decrease in the cost-effectiveness ratio (47,408 rubles/month without prostate cancer progression versus 94,651 rubles/ month without prostate cancer progression) Conclusion. Compared to treatment with GnRH agonists, use of degarelix as the 1st line therapy for treatment of prostate cancer leads to significant savings of healthcare budget expenses.

Fibrinogen and D-dimer levels in prostate cancer: Preliminary results.

BackgroundProstate cancer is one of the most common malignancy in men. The main risk factors for coagulation activation and thrombosis are malignancy and older age. The thrombosis risk may be associated with increased level of coagulation markers such as fibrinogen and D-dimer. The aim of this study is evaluate the relationship between coagulation markers and prostate cancer.MethodsThis prospective study includes the patients who underwent transrectal ultrasound guided prostate biopsy and prostate surgery was performed between January 2015 and January 2016. Plasma prostate specific antigen (PSA), free PSA (fPSA), percentage fPSA, D-dimer and fibrinogen levels were measured before the procedures. The patients were divided into two groups according to the pathology results. The patients with benign prostate hyperplasia were in group 1 and the patients with prostate cancer were in group 2.ResultsThere were 76 patients in the current study. There were 53 patients in group 1 and 23 patients in group 2. The mean age of the patients, PSA, fPSA, fibrinogen and D-dimer levels was 65.33 ± 7.47 years, 8.21 ± 4.59, 1.41 ± 0.74 ng/ml, 309.75 ± 80.46 mg/dl, 0.42 ± 0.39 ug/ml in group 1. In group 2; the mean age of the patients, PSA, fPSA, fibrinogen and D-dimer levels was 66.08 ± 6.7 years, 145.69 ± 509.35, 7.32 ± 15 ng/ml, 312.16 ± 69.48 mg/dl, 1.09 ± 2.11 ug/ml. The prostate biopsy and transurethral surgery were performed in 64(%84.21) and 12(%15.79) patients.ConclusionThe present study demonstrated that plasma D-dimer level was higher in patients with prostate cancer. Further studies that include large number of patients are needed to define the relationship between prostate cancer and coagulation disorder.

Progression of benign prostatic hyperplasia is associated with pro-inflammatory mediators and chronic activation of prostate-infiltrating lymphocytes.

Benign prostatic hyperplasia (BPH) is a common chronic non-malignant condition whose prevalence substantially increases with age. Immune cell infiltration and pro-inflammatory mediators have been implicated in the pathogenesis. Here, we characterized 21 extracellular markers on prostate-infiltrating lymphocytes (PILs) and analyzed expression of 26 soluble proteins in prostate tissue obtained from BPH patients (n = 31). These data were correlated with clinical parameters and compared with peripheral blood mononuclear cells (PBMCs) (n = 10). Increased frequencies of T cells expressing co-inhibitory receptors LAG-3, PD-1, TIM-3 or CTLA-4, and co-stimulatory receptors CD28, OX40 or 4-1BB were observed in BPH tissue compared to PBMCs. These findings are consistent with chronic activation and possible functional exhaustion of PILs that may be further augmented by several identified pro-inflammatory factors, such as IL-8 and MCP-1, promoting inflammation and chemotaxis of immune cells to the prostate. Prostate size and plasma prostate-specific antigen levels positively correlated with IL-8 and MCP-1 concentrations, and frequencies of T cells expressing CTLA-4 and TIM-3. It remains to be established whether the link between inflammation and BPH progression supported by our findings reflects a progressive failure of the immune system leading to decreased immune surveillance and development of prostate cancer.

Abstract A148: Concomitant activation of pro- and antiproliferative mechanisms abrogate tumor growth inhibition by kale sprout intervention in a human prostate cancer xenograft model

Abstract Cruciferous vegetables are rich in glucosinolates, which are converted to isothiocyanates (ITCs) and indole-based compounds by the enzymatic activity of myrosinase. Tumor-growth inhibitory efficacy of purified constituents derived from cruciferous vegetables has been demonstrated in animal models at various organ sites including the prostate. However, except induction of detoxifying enzymes, relatively little is known on mechanisms affected by dietary intervention with cruciferous vegetables, which represent a mixture of various constituents potentially enhancing or blocking their activities (Pappa et al., 2007). In the present study, we tested the tumor growth inhibitory potential of kale sprouts in a human prostate cancer xenograft model. LNCaP human prostate cancer cells were injected to male nude Balb/c mice (10 per group). Mice were fed with either regular rodent chow or chow supplemented with 20% kale sprouts (containing about 60 µmol glucosinolates per 5 g chow consumed daily, together with active myrosinase) from a week before cell injection until sacrifice after 7.5 weeks of intervention. Compared with normal diet, kale sprout intervention did not significantly inhibit average tumor weights. Secreted prostate specific antigen (PSA), which is used as a biomarker for prostate cancer, was highly correlated with tumor size in both intervention groups. Interestingly however, plasma PSA levels in the kale sprout group were 2.5-fold higher (p&amp;lt;0.05) than in the control group. In tumor tissue, mRNA expression of hormone-regulated genes such as PSA, androgen receptor, insulin-like growth factor-1 and its receptor were significantly increased. We also observed an increase in histone H4 acetylation, which was not linked to inhibition of HDAC activity. As a consequence however, p21 mRNA and protein expression was upregulated by kale sprout intervention. In addition, although there was no difference in the expression of PCNA as a proliferation marker, phosphorylated histone H3 staining as an indication of mitotic arrest was enhance in the kale sprout group. Interestingly, hemoglobin levels in tumor cell lysate, and vessels in tumor sections were significantly reduced by consuming kale sprout powder, indicating anti-angiogenic potential. This was associated with downregulated VEGF-c mRNA expression. Overall, our in vivo study indicates that components in kale sprouts or their metabolites concomitantly affect both anti-proliferative (histone H4 acetylation, cell cycle arrest, anti-angiogenesis) and pro-proliferative mechanisms (hormone signaling), which in combination may abrogate inhibitory effects on tumor growth. These data may contribute to a better understanding of the effects of cruciferous vegetable consumption in cancer prevention. Citation Information: Cancer Prev Res 2010;3(1 Suppl):A148.

Association of reported prostate cancer risk alleles with PSA levels among men without a diagnosis of prostate cancer

Prostate specific antigen (PSA) is widely used for prostate cancer screening but its levels are influenced by many non cancer-related factors. The goal of the study is to estimate the effect of genetic variants on PSA levels. We evaluated the association of SNPs that were reported to be associated with prostate cancer risk in recent genome-wide association studies with plasma PSA levels in a Swedish study population, including 1,722 control subjects without a diagnosis of prostate cancer. Of the 16 SNPs analyzed in control subjects, significant associations with PSA levels (P < or = 0.05) were found for six SNPs. These six SNPs had a cumulative effect on PSA levels; the mean PSA levels in men were almost twofold increased across increasing quintile of number of PSA associated alleles, P-trend = 3.4 x 10(-14). In this Swedish study population risk allele frequencies were similar among T1c case patients (cancer detected by elevated PSA levels alone) as compared to T2 and above prostate cancer case patients. Results from this study may have two important clinical implications. The cumulative effect of six SNPs on PSA levels suggests genetic-specific PSA cutoff values may be used to improve the discriminatory performance of this test for prostate cancer; and the dual associations of these SNPs with PSA levels and prostate cancer risk raise a concern that some of reported prostate cancer risk-associated SNPs may be confounded by the prevalent use of PSA screening.

Effects of G/A polymorphism, rs266882, in the androgen response element 1 of the PSA gene on prostate cancer risk, survival and circulating PSA levels

Prostate-specific antigen (PSA) is a protease produced in the prostate that cleaves insulin-like growth factor binding protein-3 and other proteins. Production is mediated by the androgen receptor (AR) binding to the androgen response elements (ARE) in the promoter region of the PSA gene. Studies of a single nucleotide polymorphism (PSA −158 G/A, rs266882) in ARE1 of the PSA gene have been conflicting for risk of prostate cancer and effect on plasma PSA levels. In this nested case–control analysis of 500 white cases and 676 age- and smoking-matched white controls in the Physicians' Health Study we evaluated the association of rs266882 with risk and survival of prostate cancer and prediagnostic total and free PSA plasma levels, alone or in combination with AR CAG repeats. We used conditional logistic regression, linear regression and Cox regression, and found no significant associations between rs266882 (GG allele vs AA allele) and overall prostate cancer risk (RR=1.21, 95% confidence intervals (CI): 0.88–1.67) or prostate cancer-specific survival (RR=0.94, 95%CI: 0.56–1.58). Similarly, no associations were found among high grade or advanced stage tumours, or by calendar year of diagnosis. There was no significant association between rs266882 and baseline total or free PSA levels or the AR CAG repeats, nor any interaction associated with prostate cancer risk. Meta-analysis of 12 studies of rs266882 and overall prostate cancer risk was null.

Effect of the consumption of tomato paste on plasma prostate-specific antigen levels in patients with benign prostate hyperplasia

The consumption of tomatoes and tomato products has been associated with a reduced risk of prostate cancer. We observed a decrease of 10.77% in prostate-specific antigen (PSA) levels in patients with benign prostate hyperplasia who were submitted to daily ingestion of tomato paste. This was an experimental rather than a controlled study with a sample of 43 men ranging in age from 45 to 75 years, all with histological diagnoses of benign prostate hyperplasia and plasma PSA levels of 4-10 ng/mL. All patients received 50 g of tomato paste once a day for 10 consecutive weeks and PSA levels were analyzed before, during and after the consumption of tomato paste. ANOVA for repeated measures was used to compare PSA levels before, during and after the consumption of tomato paste. The mean +/- SD PSA level was 6.51 +/- 1.48 ng/mL at baseline and 5.81 +/- 1.58 ng/mL (P = 0.005) after 10 weeks. Acceptance was good in 88.3, regular in 9.3, and poor in 2.3% of the patients. Dietary ingestion of 50 g of tomato paste per day for 10 weeks significantly reduced mean plasma PSA levels in patients with benign prostate hyperplasia, probably as a result of the high amount of lycopene in tomato paste. This was not a prostate cancer prevention study, but showed some action of tomato paste in prostate biology. The development of prostate cancer is typically accompanied by an increase in plasma PSA levels, thus any intervention that affects plasma PSA levels can suggest an impact in the progression of disease.

Prostate carcinoma incidence in relation to prediagnostic circulating levels of insulin‐like growth factor I, insulin‐like growth factor binding protein 3, and insulin

There have been several epidemiologic studies investigating the association between circulating levels of insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 3 (IGFBP-3), and insulin in relation to the risk of prostate carcinoma, with conflicting results. To examine this issue further, the authors conducted a nested case-control study within the Cardiovascular Health Study cohort. In men who were diagnosed with prostate carcinoma (cases) between 1990 and 1999 (n=174), the levels of IGF-I, IGFBP-3, and insulin were measured on blood samples that were obtained 1-9 years prior to diagnosis (mean, 3.4 years). Similar measurements were made on 174 male participants without prostate carcinoma (controls) who were matched to cases based on the year blood was drawn, survival until the date of diagnosis, race, and age. Relative to the men with IGF-I levels in the first (lowest) quartile of the distribution, the risk of prostate carcinoma for men in the second, third, and fourth (upper) quartiles were 0.77 (95% confidence interval [95% CI], 0.43-1.38), 0.73 (95% CI, 0.41-1.30), and 0.67 (95% CI, 0.37-1.25), respectively. The results were influenced little by adjustment for levels of IGFBP-3 or, instead, by evaluating the molar IGF-I/IGFBP-3 ratio. An analysis that was restricted to men who had plasma prostate-specific antigen levels <4 ng/mL at the time of the blood draw yielded similar results. The corresponding relative risks for IGFBP-3 were 0.91 (95% CI, 0.49-1.68), 0.47 (95% CI, 0.25-0.94), and 0.65 (95% CI, 0.35-1.20), respectively. The distribution of serum insulin levels in cases and controls were nearly identical. The IGF-I level was not associated positively with the risk of prostate carcinoma; however, an increase in the IGFBP-3 level was associated with a modest decrease in risk.

ELAC2/HPC2 polymorphisms, prostate-specific antigen levels, and prostate cancer.

The ELAC2 gene has been proposed to be a prostate cancer susceptibility gene and is being referred to as HPC2, in part because three case-control studies suggested that two common polymorphisms (Ser217Leu and Ala541Thr) are associated with risk. However, four subsequent larger studies have not confirmed this association. In five of the seven total studies, subject selection was influenced by prostate-specific antigen (PSA) levels. We examined the association and possible effect of subject selection in a larger study and a meta-analysis. In a population-based study in Australia, 825 case patients and 732 control subjects were genotyped for the Ser217Leu and Ala541Thr polymorphisms of ELAC2. Odds ratios (ORs) for prostate cancer were estimated by unconditional logistic and polytomous regression. A meta-analysis was conducted combining our data with those from seven published studies. The association of genotype with the logarithm of plasma PSA levels in control subjects was analyzed by linear regression. The ORs for prostate cancer were 0.74 (95% confidence interval [CI] = 0.50 to 1.09) for Leu217 homozygotes and 1.01 (95% CI = 0.68 to 1.50) for Thr541 heterozygotes and homozygotes compared with Ser217 and Ala541 homozygotes, respectively. ORs were not changed by excluding control subjects with elevated PSA levels. Among control subjects, there were no statistically significant associations between genotype frequencies and PSA level for either polymorphism (both P>.4). The meta-analysis gave pooled OR estimates of 1.04 (95% CI = 0.85 to 1.26) for Leu217 homozygotes and 1.18 (OR = 0.98 to 1.42) for Thr541 homozygotes and heterozygotes. There is no evidence that either ELAC2 polymorphism is associated with prostate cancer or PSA level.

Lycopene in the treatment of prostate cancer

Abstract Dietary intake of lycopene is associated with reduced risk of prostate cancer (PCa). We conducted a clinical trial in men with prostate cancer to investigate the biological and clinical effects of lycopene supplementation. Twenty-six men with prostate cancer were randomly assigned to receive a lycopene supplement or no supplement for three weeks before radical prostatectomy. Subjects in the intervention group (n = 15) were instructed to take a tomato oleoresin extract soft gel capsule (Lyc-O-Mato®, LycoRed Company, Beer Sheva, Israel) containing 15 mg lycopene, 1.5 mg phytoene, 1.5 mg phytofluene, and 5 mg tocopherol twice daily with meals. Prostatectomy specimens were evaluated for pathologic stage, Gleason score, volume of cancer, and extent of high-grade prostatic intraepithelial neoplasia (HGPIN). Biomarkers of cell proliferation and apoptosis were assessed by Western blot analysis in benign and cancerous tissue samples obtained from the prostatectomy specimens. Oxidative stress was assessed by measuring the peripheral blood lymphocyte DNA oxidation product 5-hydroxymethyl-deoxyuridine (5-OH-mdU). Plasma levels of lycopene, insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), and prostate-specific antigen (PSA) were measured at baseline and after three weeks of study period. After the intervention, more men in the intervention group had smaller (&lt;4 cc) tumors, organ-confined disease without involvement of surgical margins or extra-prostatic tissues, and focal involvement of the prostate with HGPIN compared to the control group. Mean plasma PSA levels were lower in the intervention group compared to the control group. This pilot study suggests that a tomato extract containing lycopene and other tomato carotenoids and phytochemicals may have a potential role in the treatment of prostate cancer. Larger clinical trials are necessary to definitively address potential uses of lycopene or tomato extract in the prevention or treatment of prostate cancer.