ABSTRACT
The vast majority of surgical patients suffer from postoperative pain, which has an enormous influence on quality of life and the progress of the stationary stay. This article gives practical advice on perioperative pain management, taking into consideration the European Association of Urology guidelines for 2009 and the S3 guideline on the treatment of acute perioperative and traumatic pain.
Subject(s)
Pain, Postoperative/etiology , Pain, Postoperative/therapy , Perioperative Care/standards , Practice Guidelines as Topic , Practice Patterns, Physicians'/standards , Urologic Surgical Procedures/adverse effects , Urology/standards , Acute Disease , Adult , Europe , Humans , Pain, Postoperative/diagnosis , Urologic Surgical Procedures/standardsABSTRACT
New perspectives in prostate cancer genesis and putative clinical management have emerged in recent years . Apoptosis plays a major role in this environment. Proteasome inhibitors block the action of a multicatalytic proteinase complex involved in the degradation of intracellular proteins, particularly with regard to cell cycle regulation and apoptosis. Numerous in vitro studies have demonstrated the ability of these compounds to induce apoptosis and enhance the activity of conventional tumoricidal agents in many cancer cell types, including prostate cancer cells. They point out the use of these potent inhibitors as a new potential molecular approach to the therapeutic management of prostate cancer. Furthermore, the action of proteasome inhibitors has been tested in animal models and in patients with hormone refractory prostate cancer, resulting in both PSA and tumor volume decrease. PS-341 (bortezomib, Velcade) is the first proteasome inhibitor with clinical application in cancer therapy that has been used in clinical trials to date. This report reviews the current status of those papers that have tried to analyze the connection between the proteasome pathway and apoptosis. We present our results of proteasome inhibition in individual prostate cancer cell lines. Proteasomal inhibition may offer a new therapeutic access in "molecular targeting" of prostate cancer.
Subject(s)
Antineoplastic Agents/therapeutic use , Apoptosis/drug effects , Boronic Acids/therapeutic use , Prostatic Neoplasms/drug therapy , Protease Inhibitors/therapeutic use , Proteasome Inhibitors , Pyrazines/therapeutic use , Animals , Apoptosis/physiology , Boronic Acids/pharmacology , Bortezomib , Clinical Trials, Phase I as Topic , Clinical Trials, Phase II as Topic , Humans , Male , Mice , Mice, Nude , Neoplasms, Experimental/drug therapy , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , Tumor Cells, Cultured/drug effects , Tumor Necrosis Factor-alpha/administration & dosage , Tumor Necrosis Factor-alpha/therapeutic useABSTRACT
The 26S proteasome is a ubiquitin-dependent proteolytic system that has been implicated in the regulation of cell cycle progression and apoptosis. We investigated the effects of the proteasome inhibitors MG115 and PSI alone or in combination with different concentrations of the antiandrogen hydroxyflutamide on the cellular proliferation, apoptosis and viability of 10 prostatic adenocarcinoma cell cultures. Treatment with both proteasome inhibitors resulted in apoptosis induction, whereas the combinations with hydroxyflutamide generally did not, with the exception of MG115 combined with 10(-7) M hydroxyflutamide. MG115 caused a significant decrease in cellular proliferation, as did the combinations of both proteasome inhibitors with hydroxyflutamide, whereas hydroxyflutamide alone was only effective at a concentration of 10(-5) M. Cellular viability was significantly reduced when both proteasome inhibitors were combined with 10(-5) M hydroxyflutamide. Although the results varied among different cell lines, we conclude that proteasome inhibitors are able to induce apoptosis and reduce cellular proliferation. They might prove effective as antineoplastic substances in prostatic adenocarcinoma alone or in combination with antiandrogens.
