Can prostate cancer be prevented?

The goal of primary chemoprevention is to decrease the incidence of a given cancer, simultaneously reducing both treatment-related adverse events and mortality. Prostate cancer is an attractive and appropriate target for primary prevention because of its incidence, prevalence, and disease-related mortality; its long latency and molecular pathogenesis; and epidemiologic data indicating that modifiable environmental factors may decrease risk. The Prostate Cancer Prevention Trial (PCPT) demonstrated that finasteride can prevent prostate cancer, albeit with an apparently increased risk of high-grade disease. A substantial amount of epidemiologic, molecular, and clinical evidence suggests that both selenium and vitamin E might also prevent prostate cancer, and this combination is being tested in the Selenium and Vitamin E Cancer Prevention Trial (SELECT). Ultimately, the adoption of a preventive strategy hinges on its potential benefits weighed against the potential risks of the specific agents used.     

Can we prevent prostate cancer? Rationale and current status of prostate cancer chemoprevention

Prostate cancer has been one of the most frequent cancers among men in Western countries for the past decade. Investigation of prostate cancer prevention is very attractive, because prostate cancer has a high incidence, long-term natural history, regional difference in incidence, and is effected by sex steroids. Chemoprevention is defined as the use of specific agents to suppress or reverse carcinogenesis and to prevent the development of cancer. The development of chemoprevention strategies against prostate cancer would be of medical and economic importance. Basic and clinical research of chemoprevention of prostate cancer are under active investigation. This article aims to summarize and review the basic evidence and clinical trials on prostate cancer chemoprevention. Recent research has demonstrated that many agents, such as agents altering sex steroid signaling, drugs inducing antiproliferation/differentiation, retinoids, anti-inflammatory drugs, and antioxidants, could be potential preventatives for prostate cancer. Large-scale clinical trials have suggested that 5alpha-reductase inhibitor finasteride, selenium, and vitamin E can function as a chemopreventive agent. Although no definitely effective strategies of prostate cancer prevention have been identified yet, increasing evidence will provide effective and safe strategies that bring clinical benefits.     

Can mycoplasma contribute to formation of prostate cancer?

Purpose

To reveal the possible role of mycoplasmas in the etiopathogenesis of prostate cancer.

Methods

In the study, prostate biopsy was performed on 62 patients with an abnormal digital rectal examination and/or elevated PSA. The patients’ age was between 62 and 77 (mean 65.4 years) years. Thirty-one patients had adenocarcinoma of the prostate histopathologically (group 1). From these patients, the specimens were divided into two subgroups as specimens with malignant findings (group 1A) and specimens with benign findings (group 1B). The control group consisted of 31 patients with benign prostatic hyperplasia (group 2). In the specimens, the presence of mycoplasma DNA was investigated by the polymerase chain reaction method.

Results

The mycoplasma DNA was found to be positive in 11 (35.4 %) patients in group 1A and in 4 (12.9 %) patients in group 1B. There was no mycoplasma DNA in the patients in group 2. The differences between group 1A and group 1B, and between group 1A and group 2 were statistically significant (p values, respectively, 0.006 and 0.0001).

Conclusions

Our data supported the thesis that mycoplasma infections play a role in the etiopathogenesis of the prostate cancer.     

Can complexed prostate specific antigen enhance prostate cancer detection in Japanese men?

BACKGROUNDS: The aim of this study is to ascertain whether Bayer complexed PSA (cPSA) and volume referenced cPSA could enhance the detection of prostate cancer in Japanese men. METHODS: A total of 214 Japanese men whose serum total PSA (tPSA) values ranged from 1.2 ng/ml to 4600 ng/ml were enrolled from two institutions. Serum samples for tPSA, free PSA, PSA-alpha-1-antichymotripsin (PSA-ACT) and cPSA (ADVIA-Centaur) were obtained in all cases. In addition, total gland (TGV) as well as transition zone volume (TZV) were determined in all cases who underwent untrasound guided prostate biopsy (sextant and two additional transition zone biopsies). Biopsy outcome was correlated to the following parameters: tPSA, cPSA, PSA-ACT, free to total (F/T) PSA ratio, 2 complex to total (C/T) PSA ratios and 6 volume referenced parameters. RESULTS: Prostate cancer was detected in 85 of 214 patients (40%). The area under the receiver operating characteristic curve in non-volume referenced variables was highest for cPSA (0.736), followed by PSA-ACT (0.735), tPSA (0.722), F/T PSA ratio (0.613) and C/T PSA ratio (0.591). Comparing tPSA with the cutoff value of 4.0 ng/ml, the cutoff value with a 2.8 ng/ml of cPSA detected one more positive biopsy patient, decreasing one more cancer missed case and 8 more false positive cases. At sensitivities of 85% to 95% in men with tPSA between 4.00 and 10.00 ng/ml (n = 116), there were no significant differences in the corresponding specificities between tPSA and cPSA, or between cPSA and PSA-ACT. At sensitivities of 90% to 95%, the corresponding specificities of PSA-ACT adjusted for transition zone volume revealed best performance. As for the performance in men with a tPSA less than 4.0 ng/ml, the specificities of cPSA performed best, and differed significantly from PSA-ACT and F/T PSA at sensitivities of 80% to 90%. CONCLUSION: Bayer cPSA could replace the first screening test by total PSA and can enhance cancer detection, compared with PSA-ACT. However, cPSA did not provide additional value in differentiating cancer from non-cancer cases in men with a tPSA between 4.00 and 10.00 ng/ml.     

Are dietary influences on the risk of prostate cancer mediated through the insulin-like growth factor system?

OBJECTIVES: To investigate whether dietary factors that appear to affect the risk of prostate cancer may be similarly associated with serum levels of insulin-like growth factor 1 (IGF-1). Patients and methods In the context of a case-control study, 112 men were admitted to three teaching hospitals in Athens, Greece, for disorders other than cancer. Sociodemographic data and detailed histories of smoking, alcohol and coffee consumption were recorded. A validated food-frequency questionnaire was administered by an interviewer and serological measurements of IGF-1 and its binding protein-3 conducted. RESULTS: IGF-1 declined significantly by almost 25% among men aged >75 years and there was a small reduction in IGF-1 levels with increased alcohol intake, with a mean (95% confidence interval, CI) change of -1.6 (- 2.2 to -0.9)% for an increment of one drink per day. There was no evidence for an effect of either smoking or coffee consumption on IGF-1 level. Among foods, the consumption of cooked tomatoes was substantially and significantly inversely associated with IGF-1 levels, with a mean (95% CI) change of -31.5 (- 49.1 to -7.9)% for an increment of one serving per day. CONCLUSIONS: The strongest known dietary risk factor for prostate cancer (lycopene deficit, as reflected in a reduced intake of cooked tomatoes) and an important endocrine factor in the aetiology of this disease (IGF-1) seem to be related in a way that suggests that at least one, and perhaps more, exogenous factors in the development of prostate cancer may be mediated through the IGF-1 system.     

Transforming growth factor-β and prostate cancer

Summary This review focuses on the possible role of transforming growth factor- isoforms 1–3 (TGF) in prostate cancer. TGF1 appears to inhibit the cellular proliferation of normal prostate cells. Surprisingly, TGF1 is overexpressed in prostate cancer. To help explain this apparent paradox, it has been revealed that with tumor progression, prostate cancer cells acquire reduced sensitivity to the growth-inhibitory effects of TGF1. Aberrations of the TGF1 signaling pathway at the prereceptor, receptor, or postreceptor level may lead to prostate cancer cell resistance to TGF1 growth inhibition. Indirectly, elevated levels of TGF1 may induce host effects that may be beneficial to prostate tumor growth by suppressing the immune system, promoting angiogenesis and extracellular matrix formation, and enhancing metastatic potential. Consequently, TGF1 appears to be important in prostate carcinogenesis and tumorigenicity. TGF2 and TGF3 are only briefly presented as very little is known about their role in prostate cancer.     

Wertigkeit des ?nerve growth factor“ beim Syndrom der überaktiven Blase

Objectives

Several studies discussing the pathology of overactive bladder suggested changes in urinary proteins. The neurotrophin “nerve growth factor” (NGF) seems to be an important marker in overactive bladder syndrome (OAB). In this prospectively designed study we evaluated NGF blood levels (sNGF) initially and after injection of botulinum toxin type A (BTX-A) in the detrusor muscle in patients suffering from idiopathic OAB.

Materials and methods

Blood samples were obtained from 26 patients (66.5 years, 28–83) with idiopathic OAB. sNGF levels were measured before and 4 weeks after BTX-A treatment by enzyme-linked immunosorbent assay (ELISA). A group of 32 healthy persons with normal bladder function served as controls (41 years, 19–60). sNGF was evaluated in relation to clinical data and the severity of OAB (wet/dry).

Results

Significantly higher sNGF levels were detected in patients with OAB compared to the control group (58.8 vs 2.0 pg/ml, p<0.005). Further, sNGF levels were elevated in patients with wet OAB compared to patients with dry OAB (85.0 vs 0.73 pg/ml, p<0.005). Patients > 60 years showed significantly higher sNGF levels (77.2 vs 8.9 pg/ml, p<0.05) compared to younger OAB patients. After BTX-A therapy sNGF levels decreased significantly compared to baseline (p<0.005).

Conclusion

NGF appears to play a decisive role in OAB. Its use as a biomarker in both the diagnostics and follow-up after therapy seems promising. To what extent sNGF can be useful as a biomarker or in therapy monitoring needs to be examined prospectively in a larger population.     

Effect of transforming growth factor beta (TGF-β) receptor I kinase inhibitor on prostate cancer bone growth

Transforming growth factor beta 1 (TGF-β1) has been implicated in the pathogenesis of prostate cancer (PCa) bone metastasis. In this study, we tested the antitumor efficacy of a selective TGF-β receptor I kinase inhibitor, LY2109761, in preclinical models. The effect of LY2109761 on the growth of MDA PCa 2b and PC-3 human PCa cells and primary mouse osteoblasts (PMOs) was assessed in vitro by measuring radiolabeled thymidine incorporation into DNA. In vivo, the right femurs of male SCID mice were injected with PCa cells. We monitored the tumor burden in control- and LY2109761-treated mice with MRI analysis and the PCa-induced bone response with X-ray and micro-CT analyses. Histologic changes in bone were studied by performing bone histomorphometric evaluations. PCa cells and PMOs expressed TGF-β receptor I. TGF-β1 induced pathway activation (as assessed by induced expression of p-Smad2) and inhibited cell growth in PC-3 cells and PMOs but not in MDA PCa 2b cells. LY2109761 had no effect on PCa cells but induced PMO proliferation in vitro. As expected, LY2109761 reversed the TGF-β1-induced pathway activation and growth inhibition in PC-3 cells and PMOs. In vivo, LY2109761 treatment for 6weeks resulted in increased volume in normal bone and increased osteoblast and osteoclast parameters. In addition, LY2109761 treatment significantly inhibited the growth of MDA PCa 2b and PC-3 in the bone of SCID mice (p<0.05); moreover, it resulted in significantly less bone loss and change in osteoclast-associated parameters in the PC-3 tumor-bearing bones than in the untreated mice. In summary, we report for the first time that targeting TGF-β receptors with LY2109761 can control PCa bone growth while increasing the mass of normal bone. This increased bone mass in nontumorous bone may be a desirable side effect of LY2109761 treatment for men with osteopenia or osteoporosis secondary to androgen-ablation therapy, reinforcing the benefit of effectively controlling PCa growth in bone. Thus, targeting TGF-β receptor I is a valuable intervention in men with advanced PCa.