TY  - JOUR
A1  - Al-Janabi, Omar
A1  - Taubert, Helge
A1  - Lohse-Fischer, Andrea
A1  - Fröhner, Michael
A1  - Wach, Sven
A1  - Stöhr, Robert
A1  - Keck, Bastian
A1  - Burger, Max
A1  - Wieland, Wolf
A1  - Erdmann, Kati
A1  - Wirth, Manfred P.
A1  - Wullich, Bernd
A1  - Baretton, Gustavo
A1  - Magdolen, Viktor
A1  - Kotzsch, Mathias
A1  - Füssel, Susanne
T1  - Association of Tissue mRNA and Serum Antigen Levels of Members of the Urokinase-Type Plasminogen Activator System with Clinical and Prognostic Parameters in Prostate Cancer
JF  - Biomed Research International
N2  - The objective was to determine the mRNA expression and protein levels of uPA system components in tissue specimens and serum samples, respectively, from prostate cancer (PCa) patients and to assess their association with clinicopathological parameters and overall survival (OS). The mRNA expression levels of uPA, its receptor (uPAR), and its inhibitor type 1 (PAI-1) were analyzed in corresponding malignant and adjacent nonmalignant tissue specimens from 132 PCa patients by quantitative PCR. Preoperative serum samples from 81 PCa patients were analyzed for antigen levels of uPA system members by ELISA. RNA levels of uPA system components displayed significant correlations with each other in the tumor tissues. A significantly decreased uP AmRNA expression in PCa compared to the corresponding nonmalignant tissue was detected. High uPA mRNA level was significantly associated with a high Gleason score. Elevated concentration of soluble uPAR (suPAR) in serum was significantly associated with a poor OS of PCa patients (P = 0.022). PCa patients with high suPAR levels have a significantly higher risk of death (multivariate Cox's regression analysis; IIR - 7.12, P - 0.027). The association of high suPAR levels with poor survival of PCa patients suggests a prognostic impact of suPAR levels in serum of cancer patients.
KW  - receptor splice variant
KW  - primary breast cancer
KW  - radical prostatectomy
KW  - tumor tissue
KW  - progression
KW  - potential marker
KW  - inhibitor PAI-1
KW  - gastric cancer
KW  - biomarkers UPA
KW  - expression
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117967
SN  - 2314-6141
IS  - 972587
ER  - 
TY  - JOUR
A1  - Propping, Stefan
A1  - Lorenz, Kristina
A1  - Michel, Martin C.
A1  - Wirth, Manfred P.
A1  - Ravens, Ursula
T1  - beta-Adrenoceptor-mediated Relaxation of Urinary Bladder Muscle in beta 2-Adrenoceptor Knockout Mice
JF  - Frontiers in Pharmacology
N2  - Background and Objective: 
In order to characterize the β-adrenoceptor (AR) subtypes involved in agonist-stimulated relaxation of murine urinary bladder we studied the effects of (-)-isoprenaline and CL 316,243 on tonic contraction and spontaneous contractions in detrusor strips of wild-type (WT) and β2-AR knockout (β2-AR KO) mice.

Materials and Methods: 
Urinary bladders were isolated from male WT and β2-AR KO mice. β-AR subtype expression was determined with quantitative real-time PCR. Intact muscle strips pre-contracted with KCl (40 mM) were exposed to cumulatively increasing concentrations of (-)-isoprenaline or β3-AR agonist CL 316,243 in the presence and absence of the subtype-selective β-AR blockers CGP 20712A (β1-ARs), ICI 118,551 (β2-ARs), and L748,337 (β3-ARs).

Results: 
Quantitative real-time PCR confirmed lack of β2-AR expression in bladder tissue from β2-AR KO mice. In isolated detrusor strips, pre-contraction with KCl increased basal tone and enhanced spontaneous activity significantly more in β2-AR KO than in WT. (-)-Isoprenaline relaxed tonic tension and attenuated spontaneous activity with similar potency, but the concentrations required were two orders of magnitude higher in β2-AR KO than WT. The concentration-response curves (CRCs) for relaxation were not affected by CGP 20712A (300 nM), but were shifted to the right by ICI 118,551 (50 nM) and L748,337 (10 μM). The -logEC50 values for (-)-isoprenaline in WT and β2-AR KO tissue were 7.98 and 6.00, respectively, suggesting a large receptor reserve of β2-AR. (-)-CL 316,243 relaxed detrusor and attenuated spontaneous contractions from WT and β2-AR KO mice with a potency corresponding to the drug’s affinity for β3-AR. L743,337 shifted the CRCs to the right.

Conclusion: 
Our findings in β2-AR KO mice suggest that there is a large receptor reserve for β2-AR in WT mice so that this β-AR subtype will mediate relaxation of tone and attenuation of spontaneous activity under physiological conditions. Nevertheless, upon removal of this reserve, β3-AR can also mediate murine detrusor relaxation.
KW  - detrusor muscle
KW  - relaxation
KW  - mucosa
KW  - beta2-adrenoceptor knockout
KW  - beta3 CL 316,243
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165245
VL  - 7
IS  - 118
ER  -