To analyze putative biomarkers for prostate cancer (PCA) characterization, the second leading cause of cancer-associated mortality in men. Quantification of the expression level of
c-myc
and
HIF-1α
...was performed in 72 prostate cancer specimens. A cohort of 497 prostate cancer patients from The Cancer Genome Atlas (TCGA) database was further analyzed, in order to test our hypothesis. We found that high
c-myc
level was significantly associated with
HIF-1α
elevated expression (
p
= 0.008) in our 72 samples. Statistical analysis of 497 TCGA prostate cancer specimens confirmed the strong association (
p
= 0.0005) of
c-myc
and
HIF-1α
expression levels, as we found in our series. Moreover, we found high
c-myc
levels significantly associated with low Glutatione S-transferase P1 (GSTP1) expression (
p
= 0.01), with high Transketolase (TKT) expression (
p
< 0.0001). High TKT levels were found in TCGA samples with low GSTP1 mRNA (p < 0.0001), as shown for
c-myc
, and with ERG increased expression (
p
= 0.02). Finally, samples with low
GSTP1
expression displayed higher
ERG
mRNA levels than samples with high
GSTP1
score (
p
< 0.0001), as above shown for
c-myc
. Our study emphasizes the notion of a potential value of
HIF-1α
and
c-myc
as putative biomarkers in prostate cancer; moreover TCGA data analysis showed a putative crosstalk between c-myc, HIF-1α, ERG, TKT, and GSTP1, suggesting a potential use of this axis in prostate cancer.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract We previously showed that endothelin A (ETA ) receptor antagonist BQ-123 partially inhibited cyclopiazonic acid (CPA)-enhanced endothelin-1 (ET-1)-induced contractions suggesting enhancement ...of ETA receptor internalization in caveolar structures by sarco/endoplasmic reticulum Ca + 2 ATPase (SERCA) blockade. Since serotonin (5-Hydroxytryptamine, 5-HT) receptors are reported to be localized on caveolar membranes, we investigated whether SERCA inhibition affects 5-HT-induced responses and 5-HT receptor antagonism. For this purpose, vascular responses were measured in thoracic aorta segments from male Wistar albino rats using isolated tissue experiments. Data showed that CPA inhibits 5-HT- and PE-induced contractions in intact vessels while potentiating those in endothelium-denuded. Furthermore, non-selective 5-HT receptor blocker methysergide partially inhibited CPA-induced 5-HT contractions. However, α1 -adrenergic receptor antagonist prazosin totally inhibited CPA-potentiated PE contractions. We suggest that SERCA inhibition results in 5-HT receptor internalization similar to ETA receptors possibly through protein kinase C activation by increased subsarcolemmal Ca 2 + levels, eventually preventing 5-HT receptor antagonism.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The purpose of our study was to investigate whether endothelium-derived relaxations induced by store depletion are altered in aging rat thoracic aorta. Vascular responses were measured in aortic ...segments isolated from young (2-4 month) and old (20-24 month) male Sprague-Dawley rats. In phenylephrine-contracted intact tissues, receptor-mediated and receptor-independent endothelium-derived relaxations were induced by acetylcholine (ACh) and sarcoplasmic/endoplasmic reticulum Ca
ATPase (SERCA) blocker cyclopiazonic acid (CPA), respectively. In addition, CPA-induced changes in intracellular calcium levels were monitored in fura-2-loaded endothelium-denuded tissues. Real-time quantitative reverse transcription polymerase chain reaction and western blot analysis were performed to determine the transient receptor potential canonical (TRPC) 4 mRNA and protein levels. Endothelial TRPC4 mRNA levels were apparently decreased in aging rats. Immunoblot analysis showed that TRPC4 protein levels significantly decreased in intact aorta from 20- to 24-month-old rats compared to that from 2- to 4-month-old rats. ACh- and CPA-induced endothelium-dependent relaxations decreased in old rat aorta without any change in direct vasodilation induced by sodium nitroprusside. Store-operated Ca
entry (SOCE) induced by CPA was significantly decreased, whereas sarcoplasmic reticulum Ca
release was unaffected in endothelium-denuded aging rat aorta. In conclusion, TRPC4 downregulation could be associated with decreased endothelium-dependent vasorelaxations. As endothelial nitric oxide synthase is activated by SOCE-induced caveolar internalization, tracking the expression levels of SERCA, ion channels, and/or associated proteins involved in SOCE would lead to the development of novel therapeutics for age-related vasospastic disorders with dysfunctional endothelium.
Adult soft tissue sarcomas in general, and those arising from the urological organs in particular, are a group of rare tumours with a generally poor prognosis, only a few studies are available. We ...report our experience with this type of tumours in a multicenter study carried out in a single region of Central Italy (Tuscany).
Pre-treatment and follow-up data were obtained from 22 adult patients, all residing in Tuscany, treated consecutively between 1984 and 2002 for primary or locally recurrent genito-urinary sarcomas in 8 urology departments in the area. All cases were classified according to the French Federation of Cancer Center System Grading Scheme for Adult Sarcomas (FFCC) and Broders System. The crude survival probability was estimated by using the Kaplan–Meier method and differences between patient sub-groups were assessed by the log rank test.
The study series included 18 males and 4 females. The mean age at diagnosis was 61
±
21.5 years (range: 15.3–89.1). The most common site was paratesticular (
n
=
9, 40.9%), followed by kidney (
n
=
8, 36.4%), prostate (
n
=
3, 13.6%) and penis and bladder (1 case each, 4.6%). 15 cases (68.2%) were classified as FFCC III, and 16 (72.7%) as Broders IV. The most common histological type was leiomyosarcoma (8 cases, 36.7%), followed by liposarcoma (6, 27.3%), rhabdomyosarcoma (3, 13.6%) and other histological types (5, 22.7%). At the last follow-up (mean: 3.66
±
3.25 years; range 0.15–10.0), 11 of the 22 patients (50%) were still alive. The overall survival rate at 1, 3 and 5 years was 85.9%, 62.0% and 48.8%, respectively. There were no significant differences in survival according to sex, age or histological type. When we compared paratesticular vs. kidney and prostate cancer cases, a significant difference in survival emerged (
p
=
0.02). According to size and grade of the tumour we also found a significant difference in survival (
p
=
0.0006 and
p
=
0.01, respectively).
In our representative series, 3 tumor parameters (site, size and grade) appeared to represent the most important prognostic factors in adult genitourinary sarcomas.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Department of Pharmacology, Faculty of Pharmacy, Ege University, Izmir, Turkey
Submitted 23 March 2006
; accepted in final form 11 December 2006
This study tested whether sarcoplasmic-endoplasmic ...reticulum Ca 2+ -ATPase regulates the ability of endothelin receptor antagonist to inhibit the endothelin-1 constriction. The endothelin A receptor antagonist BQ-123 (1 µM) completely relaxed constriction to 10 nM endothelin-1 in endothelium-denuded rat aorta. Challenge with cyclopiazonic acid (10 µM), a sarcoplasmic-endoplasmic reticulum Ca 2+ -ATPase inhibitor, during the plateau of endothelin-1 constriction enhanced the constriction by 30%. BQ-123 relaxed the endothelin-1 plus cyclopiazonic acid constriction by only 10%. In contrast, prazosin (1 µM), an -adrenergic receptor antagonist, still completely relaxed the 0.3 µM phenylephrine constriction in the presence of cyclopiazonic acid. Verapamil relaxed the endothelin-1 plus cyclopiazonic acid constriction by 30%, whereas Ni 2+ and 2-aminoethoxydiphenyl borate, nonselective cation channel and store-operated channel blockers, respectively, completely relaxed the constriction. These results suggest that lowered sarcoplasmic-endoplasmic reticulum Ca 2+ -ATPase activity selectively decreases the ability of endothelin receptor antagonist to inhibit the endothelin A receptor. The decreased antagonism may be related to the opening of store-operated channels and subsequent greater internalization of endothelin A receptor.
BQ-123; vascular smooth muscle; store-operated calcium; caveola
Address for reprint requests and other correspondence: M. Tosun, Dept. of Pharmacology, Faculty of Pharmacy, Ege Univ., Izmir, Turkey (e-mail: metiner.tosun{at}ege.edu.tr )
Purpose
The aims of this study were to: (a) analyse the most frequent morphofunctional features of the lower urinary tract observed during videourodynamic examination in patients with neurogenic ...bladder due to multiple sclerosis; (b) investigate the role of the videourodynamic examination in the clinical management of these patients; and (c) demonstrate the relationship between morphological and functional variables.
Materials and methods
We performed videourodynamic examinations in 75 patients affected by neurogenic bladder secondary to multiple sclerosis.
Results
The introduction of pharmacological therapy, based on clinical and functional evaluation of the lower urinary tract, is correlated with satisfactory morphofunctional outcomes, reducing moderate-to-severe postvoid residual (PVR;
p
< 0.1) and compliance (
p
< 0.05) at the price of reduced bladder sensation. Clinical management of these patients based on morphological evaluation of the lower urinary tract decreased the occurrence of detrusor-sphincter dyssynergy (DSD) and detrusor overactivity incontinence at the following examination.
Conclusions
Our study confirmed a relationship between detrusor overactivity and hypertonic bladder, bladder diverticula, vesicoureteral reflux, between detrusor underactivity and PVR and between DSD and bladder diverticula. Our data show how the videourodynamic examination may improve evaluation and urological management of these patients.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Ninety-six patients with chronic bacterial prostatitis (CBP) and evidence of infection were randomized to receive a 4-week oral course of either prulifloxacin (a new fluoroquinolone) 600 mg or ...levofloxacin 500 mg once daily. They were evaluated with the Meares-Stamey test and the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) at baseline and one week after therapy completion. Patients with microbiological eradication were evaluated again with the Meares-Stamey test 6 months after therapy completion. The microbiological eradication rate was 72.73% for prulifloxacin and 71.11% for levofloxacin (p=0.86) and the reduction in the NIH-CPSI was 10.75 and 10.73, respectively (p=0.98). Safety was comparable, with 18.18% adverse events for prulifloxacin and 22.22% for levofloxacin (p=0.79). Thus, a 4-week course of prulifloxacin 600 mg once daily is at least as effective and safe as levofloxacin 500 mg once daily in the treatment of CBP.
Prostate cancer synchronously or metachronously metastasizing to the testis is a rare finding. We herein report on the first case of a solitary testicular metastasis from an organ-confined prostate ...cancer, diagnosed 6 months after a radical prostatectomy, without evidence of previous or concomitant biochemical and local recurrence.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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