| 1. |
- Vallbo, Christina, 1964, et al.
(författare)
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The expression of thrombospondin-1 in benign prostatic hyperplasia and prostatic intraepithelial neoplasia is decreased in prostate cancer.
- 2004
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Ingår i: BJU Int. - : Wiley. ; 93:9, s. 1339-1343
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To evaluate the immunohistochemical expression of thrombospondin (TSP), a potent inhibitor of angiogenesis, in human benign prostatic hyperplasia (BPH) and prostate cancer. MATERIALS AND METHODS The expression of TSP-1, TSP-2 and CD36 receptor was assessed in 73 tissue specimens using immunohistochemistry; specimens were from 32 patients with BPH, seven with prostatic intraepithelial neoplasia (PIN) and 34 with cancer. RESULTS Immunohistochemistry showed that all 39 patients with BPH and PIN had TSP-1-positive glands. In contrast, none of the 34 patients with cancer had positive TSP-1 staining in the cancer tissue. All 73 patients were positive for TSP receptor CD36 and negative for TSP-2. CONCLUSIONS TSP is expressed in BPH, down-regulated in PIN and absent in prostate cancer tissue. This may indicate that TSP is important in prostate cancer progression. Further studies are needed to understand the significance of these findings for the malignant transformation of the prostate gland.
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| 2. |
- Benigni, F, et al.
(författare)
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Oral treatment with a vitamin D3 analogue (BXL628) has anti-inflammatory effects in rodent model of interstitial cystitis
- 2006
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Ingår i: BJU International. - : Blackwell Publishing Ltd. - 1464-4096 .- 1464-410X. ; 97:3, s. 617-624
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the effects of a vitamin D3 analogue (BXL628) in a model of chronic cystitis, as calcitriol analogues might be an interesting new therapeutic option for interstitial cystitis, for although the cause of the disease remains unclear, the increase in mast cells in the mucosa and detrusor muscle are significant. We devised a mouse model of allergen-induced allergic cystitis that is associated with the up-regulation of genes for interleukin-13, Fc epsilon RI alpha and mast cells-derived proteases, a massive inflammatory reaction in the bladder tissue, and augmented levels of mast cell-derived protease 1 (MMCP1) detected in mouse sera. Oral administration of BXL628 significantly reduced the expression of interleukin-13, Fc epsilon RI alpha and MMCP1 in the bladder. Furthermore, histological analysis showed a decrease in oedema and leukocyte infiltration in the bladder wall. BXL628 treatment reduced serum MMCP1 levels, indicating an effect on mast cell degranulation in vivo. Vitamin D3 analogues may successfully be used as anti-inflammatory agents in allergen-mediated inflammatory reactions. Moreover, the modulatory effect shown on mast cell activation by the BXL628 analogue strongly supports its potential therapeutic use in a possibly mast cell-dependent disease such as human interstitial cystitis.
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| 3. |
- Bivalacqua, Trinity J., et al.
(författare)
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Dysregulation of cGMP-dependent protein kinase 1 (PKG-1) impairs erectile function in diabetic rats: influence of in vivo gene therapy of PKG1 alpha
- 2007
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Ingår i: BJU International. - 1464-4096 .- 1464-410X. ; 99:6, s. 1488-1494
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the expression of cGMP-dependent protein kinase 1 (PKG1)alpha and PKG1 beta in the corpus cavernosum, and to evaluate the effect of adenoviral gene transfer of PKG1 alpha to the erectile compartment on erectile function in a rat model of diabetes. Diabetic (DM; induced by streptozotocin) male Sprague Dawley rats were transfected with adenoviruses (AdCMV beta gal or AdCMVPKG1 alpha, in 10 rats each) 2 months after the induction of DM. Intracavernosal pressure (ICP) during stimulation of the cavernosal nerve (CN) was assessed, and compared with mean arterial pressure (MAP). Erectile tissue was harvested for Western blot analysis, immunohistochemistry and total PKG activity. Ten age-matched rats without DM served as the control. Compared to controls, AdCMV beta gal-transfected DM rats had significantly lower peak ICP responses, ICP/MAP ratios, and filling rates during CN stimulation. In DM rats transfected with AdCMVPKG1 alpha, peak ICP, ICP/MAP ratios and filling rates were significantly better than in DM rats transfected with the reporter gene. As assessed by Western blot and immunohistochemistry, expression of PKG1 alpha and PKG1 beta was lower in corporal tissue from DM AdCMV beta gal-transfected rats than in controls. PKG1 alpha expression was improved after AdCMVPKG1 alpha gene therapy. Total PKG activity was lower in DM rat corporal tissue than in controls, and PKG1 alpha gene transfer significantly improved DM corporal PKG activity to a value greater than in the control. PKG1 alpha and PKG1 beta activities are reduced in the erectile tissue of the diabetic rat, and gene transfer of PKG1 alpha to the penis restored PKG activity and erectile function in vivo in diabetic rats. Gene therapy procedures targeting PKG1 alpha might be an interesting future therapeutic approach to overcome diabetic erectile dysfunction resistant to oral pharmacotherapy.
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| 4. |
- Björk, Thomas, et al.
(författare)
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The prognostic value of different forms of prostate specific antigen and their ratios in patients with prostate cancer
- 1999
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Ingår i: BJU International. - : Wiley. - 1464-4096 .- 1464-410X. ; 84:9, s. 1021-1027
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To assess the prognostic value for patient survival of different forms of PSA and ratios thereof, before treatment for prostate cancer, by considering the forms and ratios both as independent markers and by comparing them with other commonly used prognostic markers, e.g. tumour grade, local stage (T-stage) and absence or presence of skeletal metastases (M-stage). PATIENTS AND METHODS: Blood samples were collected consecutively from men diagnosed with prostate cancer at our department in 1988. From this group, 66 men were followed until death, or for >/=9 years. Twenty-five patients died from their prostate cancer and 21 from other causes during the follow-up period. Forty-eight patients received hormonal treatment, whereas 18 remained untreated or received no treatment for their cancer before they died from other causes. Assays measuring the serum levels of free prostate specific antigen (fPSA), PSA complexed to alpha1-antichymotrypsin (PSA-ACT), and total PSA (tPSA) were used to calculate the percentage of free to total PSA (f/tPSA) fPSA/ACT and ACT/tPSA at diagnosis. Based on the initial levels or ratios of the PSA forms, the patients were divided into three numerically comparable groups (tertiles) for survival analysis. Prognostic factors predicting patient survival were evaluated using univariate (Kaplan-Meier life-tables with the log-rank test) and multivariate techniques (Cox proportional hazards regression model). RESULTS: Univariate analysis using the log-rank test showed that the serum level of each molecular form of PSA, i.e. tPSA (P=0.001), PSA-ACT (P<0.001) and fPSA (P<0.001), as well as grade (P<0.001), T-stage (P=0.00355) and M-stage (P<0.001), provided statistically significant prognostic information. Log-rank tests showed that none of the ratios, i.e. f/tPSA, fPSA/ACT and ACT/tPSA, were informative of prognosis (P>0.05). However, in a multivariate analysis regression model, not only M-stage (risk ratio 4.2; P=0. 026) and grade (risk ratio 2.6; P=0.022), but also f/tPSA (risk ratio 1.8; P=0.037), provided significant prognostic information. CONCLUSION: The values of tPSA, fPSA and PSA-ACT, as well as grade and T- and M-stage, are all independent prognostic factors of prostate cancer survival. In a multivariate analysis, not only M-stage and grade but also f/tPSA provided significant prognostic information.
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| 5. |
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| 6. |
- CARLSSON, STEFAN, 1987, et al.
(författare)
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Age at surgery, educational level and long-term urinary incontinence after radical prostatectomy
- 2011
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Ingår i: BJU International. - 1464-4096 .- 1464-410X. ; 108:10, s. 1572-1577
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To identify predictors for long-term urinary leakage after radical prostatectomy. PATIENTS AND METHODS A consecutive series of 1411 patients who underwent radical prostatectomy (open surgery or robot-assisted laparoscopic surgery) at Karolinska University Hospital between 2002 and 2006 were invited to complete a study-specific questionnaire. Urinary leakage was defined as use of two or more pads per day. RESULTS Questionnaires were received from 1288 (91%) patients with a median follow-up of 2.2 years. Age at surgery predicts in an exponential manner long-term urinary incontinence at follow-up with an estimated relative increase of 6% per year. Among the oldest patients, 19% had urinary incontinence compared with 6% in the youngest age group, translating to a prevalence ratio of 2.4 (95% confidence interval [CI], 1.5-8.1). Low educational level, as compared with high, yielded an increased age-adjusted prevalence ratio of 2.5 (95% CI, 1.7-3.9). Patients who had undergone salvage radiation therapy had an increased prevalence of urinary incontinence (2.5; 95% CI, 1.6-3.8), as did those with respiratory disease (2.4; 95% CI, 1.3-4.4). Body mass index, prostate weight, presence of diabetes or previous transurethral resection did not appear to influence the prevalence of urinary incontinence. CONCLUSIONS In this series, a patient's age at radical prostatectomy influenced, in an exponential manner, his risk of long-term urinary incontinence. Other predictors are low educational level, salvage radiation therapy and respiratory disease. Intervention studies are needed to understand if these data are relevant to the prevalence of urinary leakage if a radical prostatectomy is postponed in an active monitoring programme.
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| 7. |
- Carlsson, Sigrid V., et al.
(författare)
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Can one blood draw replace transrectal ultrasonography-estimated prostate volume to predict prostate cancer risk?
- 2013
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Ingår i: BJU International. - 1464-4096 .- 1464-410X. ; 112:5, s. 602-609
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Tidskriftsartikel (refereegranskat)abstract
- Objective To explore whether a panel of kallikrein markers in blood: total, free and intact prostate-specific antigen (PSA) and kallikrein-related peptidase 2, could be used as a non-invasive alternative for predicting prostate cancer on biopsy in a screening setting. Subjects and Methods The study cohort comprised previously unscreened men who underwent sextant biopsy owing to elevated PSA (3 ng/mL) in two different centres of the European Randomized Study of Screening for Prostate Cancer, Rotterdam (n = 2914) and Gteborg (n = 740). A statistical model, based on kallikrein markers, was compared with one based on established clinical factors for the prediction of biopsy outcome. Results The clinical tests were found to be no better than blood markers, with an area under the curve in favour of the blood measurements of 0.766 vs. 0.763 in Rotterdam and 0.809 vs. 0.774 in Gteborg. Adding digital rectal examination (DRE) or DRE plus transrectal ultrasonography (TRUS) volume to the markers improved discrimination, although the increases were small. Results were similar for predicting high-grade cancer. There was a strong correlation between the blood measurements and TRUS-estimated prostate volume (Spearman's correlation 0.60 in Rotterdam and 0.57 in Gteborg). Conclusions In previously unscreened men, each with indication for biopsy, a statistical model based on kallikrein levels was similar to a clinical model in predicting prostate cancer in a screening setting, outside the day-to-day clinical practice. Whether a clinical approach can be replaced by laboratory analyses or used in combination with decision models (nomograms) is a clinical judgment that may vary from clinician to clinician depending on how they weigh the different advantages and disadvantages (harms, costs, time, invasiveness) of both approaches.
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| 8. |
- Ekman, Mari, et al.
(författare)
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Receptor-induced phasic activity of newborn mouse bladders is inhibited by protein kinase C and involves T-type Ca channels.
- 2009
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Ingår i: BJU International. - 1464-4096 .- 1464-410X. ; 104:5, s. 690-697
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To investigate the mechanisms involved in the phasic contractile activity after muscarinic receptor activation of newborn urinary bladders and to compare neonatal and adult bladders. MATERIALS AND METHODS Detrusor muscle strips were isolated from newborn mice (aged 0-2 days) and compared with preparations from adult mice (aged 10-12 weeks). The effects of an activator (phorbol 12,13-dibutyrate, PDBu) and an inhibitor (GF109203X) of protein kinase C (PKC) on contractions were investigated. T-type Ca(2+) channels were blocked with NiCl(2). RESULTS The newborn urinary bladders responded with prominent phasic contractile activity in response to carbachol (1 microm). GF109203X (3 microm) reduced carbachol-induced force by approximately 60% in the newborn, compared with 30% in the adult. PDBu (1 microm) enhanced the muscarinic receptor-mediated contraction in adult bladder muscle, whereas it completely abolished the responses in the newborn. There was no inhibition after activation with depolarization (high-K(+)) or purinergic agonists (ATP, alpha,beta-methylene ATP). NiCl(2) (>30 microm) inhibited the peak responses to carbachol in the newborn and at 300 microm it completely abolished the phasic contractile response. The responses of the adult bladder muscle were only marginally affected by NiCl(2). CONCLUSIONS Muscarinic receptor stimulation recruits the PKC signalling pathway in both the adult and neonatal urinary bladder. Potent PKC activation is inhibitory on carbachol-induced activation in the newborn and stimulatory in the adult bladder. Furthermore, muscarinic receptor stimulation activates T-type Ca(2+) channels in the newborn, but not the adult bladder.
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| 9. |
- Ekman, Mari, et al.
(författare)
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Signal transduction pathways of muscarinic receptor mediated activation in the newborn and adult mouse urinary bladder.
- 2009
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Ingår i: BJU International. - 1464-4096. ; 103:1, s. 90-97
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To study the role of M(2) and M(3) muscarinic receptor subtypes, sources of activator Ca(2+), and mechanisms involved in increased force oscillations in muscarinic contractions in the bladders of newborn and adult mice, as in the adult bladder muscarinic M(3) receptors are considered to mediate the main part of bladder contraction, and this has not been established in the newborn bladder. MATERIALS AND METHODS Bladder preparations from newborn (0-2 days) and adult (10-12 weeks) mice were mounted for in vitro force registration and activated with carbachol and high-K(+) solution in the presence of M(3) (4-DAMP 30 nm) or M(2) (methoctramine, 100 nm) receptor antagonists. Thapsigargin (1 microm) or ryanodine (10 microm) were used to inhibit sarcoplasmic reticulum Ca(2+) release. L-NAME (300 microm) and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 microm) were used to inhibit nitric oxide synthase and guanylyl cyclase, respectively. Gap-junction function was inhibited with by 18-beta-glycyrrhetinic acid (18-beta-GA; 0.1-100 microm). Big-conductance (BK) and small-conductance (SK) K(+) channels were inhibited by apamine and charybdotoxin (0.3 microm), respectively. RESULTS Concentration-response relations for carbachol in the presence of 4-DAMP and methoctramine showed that M(3) receptors are the main activating pathway also in the newborn bladder. Neither thapsigargin nor ryanodine influenced the muscarinic responses of the newborn and adult bladders. Carbachol-induced contractions were not influenced by L-NAME or ODQ. The 18-beta-GA inhibited carbachol-induced contractions in both newborn and adult tissue in a similar manner. Apamine and charybdotoxin slightly increased the amplitude of the contractile responses. CONCLUSION These results suggest that in the newborn mouse bladder, as in adult bladders, the M(3) muscarinic receptor subtype is mainly responsible for carbachol-induced contractile responses. The main mechanism for muscarinic receptor-induced activation is influx of Ca(2+) from the extracellular medium, and there seems to be no major contribution of Ca(2+) release from intracellular stores. The phasic contractile activity induced by carbachol in the newborn bladder is not influenced by gap junction inhibition and does not involve SK and BK channels.
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| 10. |
- Gudjonsson, Sigurdur, et al.
(författare)
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The value of bladder mapping and prostatic urethra biopsies for detection of carcinoma in situ (CIS)
- 2012
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Ingår i: BJU International. - : Wiley. - 1464-4096 .- 1464-410X. ; 110:2B, s. E41-E45
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES To assess the value of bladder mapping and prostatic urethra biopsies for detection of urothelial carcinoma in situ (CIS). CIS of the urinary bladder is a flat high-grade lesion of the mucosa associated with a significant risk of progression to muscle-invasive disease. CIS is difficult to identify on cystoscopy, and definite diagnosis requires histopathology. Traditionally, if CIS is suspected, multiple cold-cup biopsies are taken from the bladder mucosa, and resection biopsies are obtained from the prostatic urethra in males. This approach is often called bladder mapping (BMAP). The accuracy of BMAP as a diagnostic tool is not known. PATIENTS AND METHODS Male patients with bladder cancer scheduled for cystectomy underwent cold-cup bladder biopsies (sidewalls, posterior wall, dome, trigone), and resection biopsies were taken from the prostatic urethra. After cystectomy, the surgical specimen was investigated in a standardised manner and subsequently compared with the BMAP biopsies for the presence of CIS. RESULTS The histopathology reports of 162 patients were analysed. CIS was detected in 46% of the cystoprostatectomy specimens, and multiple (greater than= 2) CIS lesions were found in 30%. BMAP (cold-cup bladder biopsies + resection biopsies from the prostatic urethra) provided sensitivity of 51% for any CIS, and 55% for multiple CIS lesions. The cold-cup biopsies for CIS in the bladder mucosa showed sensitivity and specificity of 46% and 89%, respectively. CONCLUSION Traditional cold-cup biopsies are unreliable for detecting CIS in bladder mucosa and negative findings must be interpreted with caution.
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