Prostataerkrankungen: Ursachen und Behandlung
Prostatic diseases are characterized by increased activity of cytokines, growth factors, and cyclooxygenases- COX- 1 and 2. Activation of COX-1 and COX-2 results in increased levels of prostaglandins and the induction of angiogenic, antiapoptotic and inflammatory processes.
Inhibition of COX enzymes by members of the widely used nonsteroidal anti-inflammatory drug NSAID class of drugs decreases prostaglandin production, and exerts a variety of anti-inflammatory, antipyretic, and antinociceptive effects. While numerous in vitroin vivoand clinical studies have shown that NSAIDs inhibit the risk and progression of prostatic diseases, the relationship between NSAIDs and such diseases remains controversial.
Here we review the literature in this area, critically analyzing the benefits and caveats associated with the use of NSAIDs in the treatment of prostatic diseases. The initiation and progression of prostatic diseases involve a variety of factors, including the amplification and mutation of genes encoding the androgen receptor, tumor suppressor genes, oncogenes, growth factors, and cytokines, in addition to other processes such as infection [ 1 — 4 ].
Given the role of inflammation in the development and progression of prostatic disease, it has been suggested that inhibition of inflammation would decrease the risk of prostatic diseases. Nonsteroidal anti-inflammatory drugs NSAIDs are widely used in the world for their antinociceptive, anti-inflammatory, and antipyretic effects in many diseases, including prostate cancer and prostatic disease. In contrast, several studies have reported that the use of NSAIDs increases the risk of prostatic diseases and the relationship between this class of drugs and prostatic disease remains controversial.
Current opinion suggests that NSAID treatment would be beneficial for most prostatic diseases, in particular benign prostatic hyperplasia BPH and prostate cancer. COX-1 is constitutively expressed in most tissues and has important roles in tissue homeostasis, particularly in the stomach and kidney, as well as in blood NSAID Behandlung von Prostatitis.
In contrast, expression of COX-2 is induced by cytokines or growth factors [ 6 ]. Both enzymes convert arachidonic acid to prostaglandin G2 Figure 1which is in turn converted to various mediators of inflammation, including prostaglandin H, prostaglandin E, prostaglandin D, and thromboxane A. Since COX-1 inhibition has been associated with severe NSAID Behandlung von Prostatitis effects such as gastrointestinal bleeding and damage to gastric mucosa [ 7 ], there has been an emphasis on the development of COX-2 selective NSAIDs.
COX-2 selective NSAIDs have been shown to inhibit inflammation without damaging the gastric mucosa [ 8 ], although some have been linked with cardiovascular toxicity [ 9 ]. Collectively these data suggest that NSAIDs have potential as a novel class of drugs for the prevention of prostatic NSAID Behandlung von Prostatitis and prostate NSAID Behandlung von Prostatitis.
According to the NIH consensus classification of prostatitis syndromes includes 4 categories. While antibacterial drugs are effective in the treatment of acute bacterial prostatitis, they are less effective in the treatment of the other types of prostatitis. As a consequence, therapy for chronic prostatitis is primarily aimed at managing its symptoms.
Collectively, these data indicate that treatment with NSAIDs might hold many benefits for chronic prostatitis patients. Inflammation has been linked with the development and progression of BPH [ 1516 ], and several studies have reported the presence of intraprostatic inflammatory infiltration in BPH tissues [ 1718 ].
The inflammatory cytokine IL, which is not expressed in normal prostate, has been shown to be expressed in inflammatory prostate [ 19 ]. Jhang et al. Moreover, NSAID Behandlung von Prostatitis associated with LUTS has been shown to be improved by treatment with sedatives and analgesics, including COX-2 inhibitors [ 27 ]. Daily use of NSAIDs has been shown to result in improved urinary symptoms, increased urine flow rate, and decreased prostate volume and prostate-specific antigen levels [ 28 ].
While some studies have reported a lack of side effects associated with NSAID treatment [ 30 ], others have reported the opposite results. While data are limited, several in vitro and in vivo studies have probed the mechanism s underlying the improvement in BPH and NSAID Behandlung von Prostatitis symptoms effected by NSAIDs.
Treatment of these animals with a dual inhibitor of COX and 5-LOX decreased prostaglandin E2 levels and expression of the antiapoptotic factor Bcl-2 and increased expression of the proapoptotic factors Bax and caspase-9, resulting in the induction NSAID Behandlung von Prostatitis apoptosis.
In summary, while the determining of the efficacy of NSAIDs in the treatment of BPH requires further clinical studies, in vitro evidence suggests that NSAIDs might be beneficial for alleviating symptoms in BPH patients and for reducing the risk of the development or NSAID Behandlung von Prostatitis of the disease in unaffected individuals.
Inflammation arising from a variety of physiological insults is thought to be a major cause and promoter of various cancers, including prostate cancer [ 37 — 40 ]. Inflammation of the prostate is associated with the induction of cytokines, chemokines, and growth factors, as well as COX-2, which is also overexpressed in prostate cancer [ 2141 ].
Given their anti-inflammatory roles in the reduction of COX activity and prostaglandin synthesis, therefore [ 3742 ], it has been speculated that treatment with NSAIDs might reduce the risk of prostate cancer [ 43 ].
In vitro studies have provided evidence pointing to the suppression of prostate cancer development and progression by NSAIDs. The fact that these cell lines do not express COX-2 indicates that celecoxib inhibits prostate cancer cell line growth via a COX-2 independent mechanism. In support of this notion, a celecoxib analog deficient in NSAID Behandlung von Prostatitis inhibition has been shown to inhibit prostate cancer cell growth, also via repression of Akt and G1 arrest [ 46 ].
Other studies have investigated the relationship between NSAIDs, androgen NSAID Behandlung von Prostatitis, and radiation therapy in the context of prostate cancer.
Similar results were also obtained in xenograft models [ 47 ]. NSAIDs have also been shown to delay the progression of prostate tumors from androgen-dependent to androgen-independent growth [ 48 ].
Another paper showed the possibility for the combination of hormone ablation therapy NSAID Behandlung von Prostatitis NSAID treatment NSAID Behandlung von Prostatitis 49 ]. Celecoxib treatment increases the efficacy of androgen ablation therapy.
In the same model, celecoxib inhibits the development NSAID Behandlung von Prostatitis prostatic intraepithelial neoplasia and adenocarcinoma in the prostate in a dose-dependent manner [ 5253 ].
The net effect of celecoxib in this model is to suppress invasion and metastasis, induce apoptosis, and enhance overall survival. NSAIDs have NSAID Behandlung von Prostatitis been shown to increase cell cycle arrest and apoptosis via regulation of cell cycle regulatory protein in NSAID Behandlung von Prostatitis animal model of chemical induction of prostate cancer [ 53 ].
Collectively these experimental reports suggest that NSAIDs may be beneficial for the treatment of advanced prostate cancer. NO-NSAIDs have been shown to inhibit cancer cell growth [ 10 ] and, in prostate cancer NSAID Behandlung von Prostatitis specifically, have proapoptotic and anti-invasive properties which exceed those of classical NSAIDs [ 54 — 57 ].
Although in NSAID Behandlung von Prostatitis studies point to the ability NSAID Behandlung von Prostatitis NSAIDs to protect against cancer progression, results from clinical studies are more inconsistent.
Daily use of aspirin also reduced further prostate cancer risk. Smith et al. Relative to the placebo group, individuals in the celecoxib group had a 2-fold higher PSA doubling time and significantly decreased PSA velocity [ 61 ]. In further support of these findings, daily consumption of more than six aspirins has been shown to reduce prostate cancer risk OR 0. In contrast, other studies have failed to associate aspirin with a reduced risk of prostate cancer [ 6667 ], and one has suggested that treatment with NSAIDs increases the risk of prostate cancer odds ratio OR 1.
Interestingly, Leitzmann et al. Based NSAID Behandlung von Prostatitis these observations, the association between NSAIDs and prostate cancer risk requires further study. Many studies have demonstrated a link between inflammation and prostatic diseases, such as BPH and prostate cancer. Although there are some suggestions that NSAIDs increase NSAID Behandlung von Prostatitis risk of prostatic diseases, most of studies suggest that NSAIDs have potential to improve symptoms in, and reduce the risk of, prostatic diseases.
The authors declare that there is no conflict of interests regarding the publication of this paper. National Center for Biotechnology InformationU. Journal List Biomed Res Int v. Biomed Res Int. Published online May Author information Article notes Copyright and License information Disclaimer.
Received Dec 15; Accepted Apr Ishiguro and T. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the NSAID Behandlung von Prostatitis work is properly cited. This article has been cited by other articles in PMC. Abstract Prostatic diseases are characterized by increased activity of cytokines, growth factors, and cyclooxygenases- COX- 1 and 2.
Introduction The initiation and progression of prostatic diseases involve a variety of factors, including the amplification and mutation of genes encoding the androgen receptor, tumor suppressor genes, oncogenes, growth factors, and cytokines, in addition to other processes such as infection [ 1 — 4 ].
Open in a separate window. Figure 1. Prostatitis According to the NIH consensus classification of prostatitis syndromes includes 4 categories.
Prostate Cancer Inflammation arising from a variety of physiological insults is thought to be a major cause and promoter of various cancers, including prostate cancer [ 37 — 40 ].
Conclusions Many studies have demonstrated a link between inflammation and prostatic diseases, such as BPH and prostate cancer. Conflict of Interests The authors declare that there is no conflict of interests regarding the publication of this paper. References 1. Schrecengost R, Knudsen KE. Molecular pathogenesis and progression of prostate cancer. Seminars in Oncology. European Urology. Macoska JA. Epidemiological features and resistance pattern in uropathogens isolated from chronic bacterial prostatitis.
The Journal of Microbiology. Vane JR. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Cyclooxygenase in biology and disease. Cyclooxygenases 1 and 2. Annual Review of Pharmacology and Toxicology. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. The New England Journal of Medicine. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial.
Rigas B, Kashfi K. Trends in Molecular Medicine. NIH consensus definition and classification of prostatitis. The Journal of the American Medical Association. Use of a novel non-steroidal anti-inflammatory drug, nimesulide, in the treatment of NSAID Behandlung von Prostatitis prostatovesiculitis. A randomized, placebo controlled, multicenter study to evaluate the safety and efficacy of NSAID Behandlung von Prostatitis in the treatment of chronic nonbacterial prostatitis.
The Journal of Urology. Parsons JK. Benign prostatic hyperplasia and male lower urinary tract symptoms: epidemiology and risk factors. Current Bladder Dysfunction Reports.