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1.
Pharmacol Rep ; 68(5): 874-80, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27351942

ABSTRACT

BACKGROUND: Norcantharidin, a modified pure compound from blister beetles, was previously demonstrated to induce apoptosis of cancer cells. This study investigated its anti-cancer activity in prostate cancer cells and the mechanisms involved. METHODS: Two human prostate cancer cell lines, 22Rv1 and Du145, were treated with norcantharidin at concentrations ranging from 3 to 30µg/ml. Cytotoxic effect of norcantharidin was determined by use of the 3-(4,5-dimethylthiazol-yl)-diphenyl tetrazoliumbromide (MTT) assay. The effects of apoptosis were evaluated by cell death assay, Caspase-3, -8, -9 activity and cytochrome c release. The apoptotic related protein expressions (Bcl-2 family and inhibitor of apoptosis proteins) were determined using western blotting. RESULTS: An MTT assay revealed that norcantharidin induced cytotoxicity against both prostate cancer cells in dose- and time-dependent manners. Treatment with norcantharidin at 3µg/ml or higher significantly increased oligonucleosomal formation with concomitant appearance of PARP cleavage, implicating the induction of apoptosis. Norcantharidin intrinsically elevated cytosolic cytochrome c levels and activated caspase-3, -8, and -9. Extrinsically, it upregulated the expression of not only the death receptors Fas and DR5 in 22Rv1 cells, but also of RIP and TRADD adaptor proteins in Du145 cells. Mechanistically, norcantharidin increased ratios of pro-/anti-apoptotic proteins and decreased expression of IAP family member proteins, including cIAP1 and survivin, regardless of the distinct status of androgen receptor expression in both cells. CONCLUSIONS: Norcantharidin exhibited cytotoxicity against 22Rv1 and Du145 prostate cancer cells by inducing both intrinsic and extrinsic apoptotic pathways and could thus potentially be a remedy for prostate cancer.


Subject(s)
Apoptosis/drug effects , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Prostatic Neoplasms/drug therapy , Signal Transduction/drug effects , Caspases/metabolism , Cell Line, Tumor , Cytochromes c/metabolism , Humans , Male , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , Proto-Oncogene Proteins c-bcl-2/metabolism , Receptors, TNF-Related Apoptosis-Inducing Ligand/metabolism , TNF Receptor-Associated Death Domain Protein/metabolism , Up-Regulation/drug effects , bcl-2-Associated X Protein/metabolism , fas Receptor/metabolism
2.
Medicine (Baltimore) ; 95(5): e2644, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26844483

ABSTRACT

To determine which surgical treatment for lower urinary tract symptoms, which is suggestive of benign prostatic hyperplasia (BPH), is more cost-effective and yields a better patient's preference. Treatment outcome, cost, and perioperative complications to assess the treatment effectiveness of using laser prostatectomy as a treatment for BPH were investigated in this study.This retrospective study included 100 patients who underwent transurethral resection of prostate (TUR-P) and another 100 patients who received high-powered 120 W (GreenLight HPS) laser prostatectomy between 2005 and 2011.International Prostate Symptom Score and uroflow parameters were collected before the surgery and the uroflow and postvoiding residual volumes were evaluated before treatment and at 3, 6, 12, and 24 months after treatment. The results of 100 treatments after HPS laser prostatectomy were compared with the results of 100 patients who received TUR-P from the same surgeon. Complication rates and admission costs were analyzed.From 2005 to 2011, 200 consecutive patients underwent endoscopic surgery. Study participants were men with BPH with mean age of 71.3 years old. The peak flow rate went from 8.47 to 15.83 mL/s for 3 months after laser prostatectomy. Laser therapy groups showed better improvement in symptom score, shortened length of stay, and quality of life score when compared with those of TUR-P procedures. The estimated cost for laser prostatectomy was high when compared with cost of any other TUR-P procedural option at Chang Gung Hospital (P = 0.001). All admission charges were similar except for the cost of the laser equipment and accessories (mainly the laser fiber) (P = 0.001). Due to this cost of equipment, it increased the total admission charges for the laser group and therefore made the cost for the laser group higher than that of the TUR-P group.Perioperative complications, such as the need for checking for bleeding, urinary retention rate or urosepsis rate within 30 days after the surgery, held no significant differences between both groups.Compared with alternative treatment options, laser prostatectomy of the prostate is clinically effective but yields a high cost of treatment for symptomatic BPH.


Subject(s)
Cost-Benefit Analysis , Prostatectomy/economics , Prostatic Hyperplasia/surgery , Transurethral Resection of Prostate/economics , Aged , Aged, 80 and over , Hospital Costs , Humans , Length of Stay , Male , Middle Aged , Postoperative Complications/epidemiology , Prostatectomy/statistics & numerical data , Prostatic Hyperplasia/economics , Quality of Life , Retrospective Studies , Severity of Illness Index , Transurethral Resection of Prostate/statistics & numerical data , Treatment Outcome
3.
Ann Surg Oncol ; 22 Suppl 3: S1580-6, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26350365

ABSTRACT

BACKGROUND: Postprostatectomy incontinence (PPI) is one of the most bothersome complications of radical prostatectomy. A postoperative image survey may better predict PPI than a preoperative survey. OBJECTIVE: The aim of this study was to determine whether postoperative cystography bladder patterns can predict PPI at short- and long-term follow-up. METHODS: In total, 180 patients who underwent robot-assisted radical prostatectomy (RARP) from September 2008 to September 2014, and who were followed for at least 6 months, were enrolled in this study. All patients underwent cystography within 2 weeks after RARP before Foley catheter removal, and all parameters were analyzed to evaluate the relationship with PPI at 1, 6, 12, and 24 months post-RARP. Patients were also divided into four bladder neck level groups, according to the relative position of the bladder neck to the pubic symphysis. RESULTS: A total of 119 patients were followed for at least 48 months after RARP. Cystography patterns were analyzed, including the downward bladder neck, bladder height, bladder width, height to width ratio, and bladder neck angle. A more downward bladder neck and a sharper bladder neck angle were significant predictors of PPI at 1, 6, 12, and 24 months after RARP. Patients with a larger bladder height or height to width ratio (prolate bladder shape) tended to have poor outcomes regarding PPI. Clinicians can also use a bladder neck level classification to rapidly predict the outcome of PPI. CONCLUSIONS: Postoperative cystography is a reliable and cost-effective tool for predicting PPI. A more downward bladder neck and a sharper bladder neck angle have the greatest predictive power for short- and long-term PPI.


Subject(s)
Postoperative Complications , Prostatectomy/adverse effects , Prostatic Neoplasms/surgery , Robotic Surgical Procedures/adverse effects , Urinary Incontinence/diagnostic imaging , Urography/methods , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Staging , Prognosis , Retrospective Studies , Urinary Incontinence/etiology
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