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1.
Urologe A ; 60(4): 498-503, 2021 Apr.
Article in German | MEDLINE | ID: mdl-31970426

ABSTRACT

On 1 September 1958, Prof. Dr. med. Hans-Dieter Marquardt was appointed chief physician of the largest urological hospital in Germany in terms of beds at the time. As the head of the clinic from 1958 until 1983; his skills and guidance were paramount for the smooth transition from a municipal hospital to a urological department of the University of Ulm; under his direction, the clinic developed into a well-known training center with special expertise in transurethral prostate surgery and a regionally and nationally important center for patient care. Professor Marquardt was a gifted physician and surgeon. He can be ranked as one of the pioneers in the field of endoscopic prostate surgery.


Subject(s)
Physicians , Universities , Germany , History, 20th Century , Hospitals , Hospitals, Municipal , Humans , Male
2.
World J Urol ; 31(2): 253-9, 2013 Apr.
Article in English | MEDLINE | ID: mdl-22763628

ABSTRACT

PURPOSE: To evaluate the clinical value of the pre-treatment calculated free testosterone (fT), total testosterone (tT), sexual hormone-binding globulin (SHBG) and estradiol (E2) levels as potential predictors of pathological stage and grade in patients with clinically localized prostate cancer. METHODS: Preoperative sex hormone serum levels were prospectively measured in 137 patients who underwent radical prostatectomy at the University Hospital Ulm from February 2011 to February 2012. We related sex hormone levels to clinicopathologic data including tumour stage, Gleason score and prostate specific antigen (PSA). (Non)parametric statistical tests and receiver operating characteristics (ROC) analyses were performed. RESULTS: Preoperative serum fT levels were significantly associated with advanced disease (pT3-4 and/or pN+; p = 0.047) and lymph node involvement (pN+) (p = 0.027). Patients with low (<0.047 µg/l) vs. normal fT values (≥0.047 µg/l) were associated with higher tumour stage (p = 0.049), positive lymph node status (pN+ , p = 0.038) and advance disease (p = 0.016). Moreover, low tT values (≤0.193 µg/l; p = 0.018) and elevated SHBG levels (>48.4 nmol/l, p = 0.043) correlated with a higher Gleason score. Conversely, E2 levels were not associated with tumour stage or grade. Applying multivariate analysis, unlike tT, SHBG, and E2 levels, low fT levels were a significant independent predictor of advanced disease (relative hazard ratio 3.05, p = 0.028). CONCLUSIONS: Low pre-treatment fT levels were significantly associated with tumour stage and extraprostatic tumour spread and might-in addition or combination with PSA-serve as a useful prognostic parameter for prostate cancer patients prior to radical prostatectomy.


Subject(s)
Prostatic Neoplasms/blood , Testosterone/blood , Aged , Estradiol/blood , Humans , Kallikreins/blood , Male , Middle Aged , Neoplasm Grading , Neoplasm Staging , Prospective Studies , Prostate-Specific Antigen/blood , Prostatectomy , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgery , ROC Curve , Sex Hormone-Binding Globulin/metabolism
3.
Aging Male ; 15(4): 253-7, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23078021

ABSTRACT

BACKGROUND: Symptoms of the "male climacteric" are often at least in part referred to an age-dependent decline of serum androgen levels. Therefore, we evaluated the relationship of climacteric symptoms as assessed by the "Aging Males' Symptoms" (AMS) Questionnaire with circulating androgen levels. METHODS: 146 ambulatory men (age, 27-85 years) were surveyed with the AMS Questionnaire and sampled for serum values of total testosterone (tT) and sexual hormone binding globulin (SHBG). Free testosterone (fT) was calculated from tT and SHBG. A total AMS score ≥37 was considered pathological; the lower limits for tT and fT were set to 8 nmol/l and 180 pmol/l, respectively. RESULTS: A significant deficit in tT and fT was shown in 25 (17.1%) and 34 (24.5%) men, respectively; the AMS Questionnaire showed pathological results for 66 (45.2%) men. In predicting a tT deficit, the AMS Questionnaire rendered a sensitivity of 76% and a specificity of 61.6%, only. However, multiple regression analysis revealed a significant correlation of lowered tT with a pathological somatovegetative and psychological AMS subscore (p = 0.042 and p = 0.01) and a correlation of lowered fT with a pathological sexual subscore (p = 0.039). CONCLUSION: In predicting hypogonadism the AMS Questionnaire in total did not render a sufficient diagnostic efficiency.


Subject(s)
Aging/physiology , Climacteric/blood , Hypogonadism/complications , Surveys and Questionnaires , Testosterone/deficiency , Adult , Aged , Aged, 80 and over , Climacteric/physiology , Humans , Hypogonadism/diagnosis , Hypogonadism/physiopathology , Male , Middle Aged , Sex Hormone-Binding Globulin/analysis , Testosterone/blood
4.
J Cell Biochem ; 109(6): 1192-200, 2010 Apr 15.
Article in English | MEDLINE | ID: mdl-20127713

ABSTRACT

The androgen receptor (AR) is a ligand-dependent transcription factor belonging to the steroid hormone receptor superfamily. Under normal conditions, in the absence of a ligand, the AR is localized to the cytoplasm and is actively transported into the nucleus upon binding of androgens. In advanced prostate cancer (PCa) cell lines, an increased sensitivity to dihydrotestosterone (DHT), enabling the cells to proliferate under sub-physiological levels of androgens, has been associated with increased stability and nuclear localization of the AR. There is experimental evidence that the glycogen synthase kinase-3beta (GSK-3beta), a multifunctional serine/threonine kinase is involved in estrogen and AR stability. As demonstrated in the following study by immunoprecipitation analysis, GSK-3beta binds to the AR forming complexes in the cytoplasm and in the nucleus. Furthermore, inhibition of GSK-3beta activity by pharmacological inhibitors like the maleimide SB216761, the chloromethyl-thienyl-ketone GSK-3 inhibitor VI or the aminopyrazol GSK-3 inhibitor XIII in cells grown in the presence of DHT triggered a rapid nuclear export of endogenous AR as well as of green fluorescent AR-EosFP. The nuclear export of AR following GSK-3beta inhibition could be blocked by leptomycin B suggesting a CRM1-dependent export mechanism. This assumption is supported by the localization of a putative CRM1 binding site at the C-terminus of the AR protein. The results suggest that GSK-3beta is an important element not only in AR stability but also significantly alters nuclear translocation of the AR, thereby modulating the androgenic response of human PCa cells.


Subject(s)
Glycogen Synthase Kinase 3/metabolism , Karyopherins/metabolism , Prostatic Neoplasms/metabolism , Receptors, Androgen/metabolism , Receptors, Cytoplasmic and Nuclear/metabolism , Active Transport, Cell Nucleus/drug effects , Binding Sites , Blotting, Western , Cell Line, Tumor , Dihydrotestosterone/pharmacology , Enzyme Inhibitors/pharmacology , Fatty Acids, Unsaturated/pharmacology , Glycogen Synthase Kinase 3/antagonists & inhibitors , Glycogen Synthase Kinase 3 beta , Humans , Immunoprecipitation , Karyopherins/antagonists & inhibitors , Male , Microscopy, Fluorescence , Protein Binding/drug effects , Receptors, Cytoplasmic and Nuclear/antagonists & inhibitors , Exportin 1 Protein
5.
Neoplasia ; 11(9): 956-63, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19724689

ABSTRACT

Localized prostate cancer (CaP) can be cured using several strategies. However, the need to identify active substances in advanced tumor stages is tremendous, as the outcome in such cases is still disappointing. One approach is to deliver human tumor antigen-targeted therapy, which is recognized by T cells or antibodies. We used data mining of the Cancer Immunome Database (CID), which comprises potential immunologic targets identified by serological screening of expression libraries. Candidate antigens were screened by DNA microarrays. Genes were then validated at the protein level by tissue microarrays, representing various stages of CaP disease. Of 43 targets identified by CID, 10 showed an overexpression on the complementary DNA array in CaP metastases. The RHAMM (CD168) gene, earlier identified by our group as an immunogenic antigen in acute and chronic leukemia, also showed highly significant overexpression in CaP metastases compared with localized disease and benign prostatic hyperplasia. At the protein level, RHAMM was highest in metastatic tissue samples and significantly higher in neoplastic localized disease compared with benign tissue. High RHAMM expression was associated with clinical parameters known to be linked to better clinical outcome. Patients with high RHAMM expression in the primaries had a significantly lower risk of biochemical failure. The number of viable cells in cell cultures was reduced in blocking experiments using hormone-sensitive and hormone-insensitive metastatic CaP cell lines. Acknowledging the proven immunogenic effects of RHAMM in leukemia, this antigen is intriguing as a therapeutic target in far-advanced CaP.


Subject(s)
Antigens, Neoplasm/metabolism , Extracellular Matrix Proteins/metabolism , Hyaluronan Receptors/metabolism , Prostatic Hyperplasia/metabolism , Prostatic Neoplasms/metabolism , Antigens, Neoplasm/genetics , Apoptosis , Cell Proliferation , Databases, Factual , Extracellular Matrix Proteins/genetics , Gene Expression Profiling , Humans , Hyaluronan Receptors/genetics , Immunoenzyme Techniques , Lymphatic Metastasis , Male , Oligonucleotide Array Sequence Analysis , Prostate/metabolism , Prostate/pathology , Prostatic Hyperplasia/genetics , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Survival Rate , Tissue Array Analysis , Tumor Cells, Cultured
6.
World J Urol ; 27(5): 619-25, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19234708

ABSTRACT

OBJECTIVE: To evaluate [(11)C]choline positron emission tomography/computed tomography ([(11)C]choline PET/CT) for the detection of a biochemical recurrence of prostate cancer after radical prostatectomy. METHODS: Retrospective analysis of [(11)C]choline PET/CT performed in 41 consecutive prostate cancer patients with a rising PSA. The mean time to biochemical relapse was 24 months. PSA levels were determined at time of examination, and patients received either a targeted biopsy or surgery. Histopathology reports served as reference for the evaluation of the [(11)C]choline PET/CT findings. RESULTS: Mean PSA in [(11)C]choline PET/CT positive patients was 3.1 ng/ml (median 2.2 ng/ml, range 0.5-11.6 ng/ml) and 0.86 ng/ml in [(11)C]choline PET/CT negative patients (median 0.83 ng/ml, range 0.41-1.40 ng/ml). Six of 12 patients with PSA < 1.5 ng/ml [(11)C]choline PET/CT revealed a pathological uptake. Histopathology was positive in 6/12 patients in this group. At PSA levels ranging from 1.5 to 2.5 ng/ml all [(11)C]choline PET/CT were positive (n = 16), a positive histology was found in 12/16 patients (75%) and at PSA 2.5-5 ng/ml [(11)C]choline PET/CT was positive in 8/8 patients, confirmed by histology in 7/8 patients. Finally, at PSA higher than 5 ng/ml [(11)C]choline PET/CT identified 5/5 patients positive all confirmed by histology. The sensitivity of [(11)C]choline PET/CT for the detection of recurrence at PSA < 2.5 ng/ml was 89% with a positive predictive value of 72%. CONCLUSION: [(11)C]choline PET/CT is useful for re-staging of prostate cancer in patients with rising PSA even at levels below 1.5 ng/ml. Our study confirms results from other published studies on [(11)C]choline PET/CT in prostate cancer relapse.


Subject(s)
Choline/analogs & derivatives , Neoplasm Recurrence, Local/diagnosis , Positron-Emission Tomography , Prostatectomy , Prostatic Neoplasms/diagnosis , Tomography, X-Ray Computed , Aged , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/blood , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , Retrospective Studies
7.
Urol Int ; 81(2): 191-7, 2008.
Article in English | MEDLINE | ID: mdl-18758218

ABSTRACT

INTRODUCTION: In this prospective study we set out to investigate the diagnostic value of [(11)C]choline-PET/CT in patients with suspected lymph node metastases before salvage lymph node dissection. PATIENTS AND METHODS: 15 consecutive patients with rising PSA underwent [(11)C]choline-PET/CT and consecutive open salvage pelvic/retroperitoneal extended lymph node dissection due to uptake of [(11)C]choline in at least 1 lymph node. Mean age was 62.1 (range 53-73). RESULTS: [(11)C]choline-PET/CT results were compared with the histopathology reports and clinical follow-up (mean 13.7 months, range 6-24). Mean time to progression was 23.6 months (range 4-81). [(11)C]choline uptake was observed in nodes along the external and internal and common iliac arteries and in the paraaortic region. A positive histology was reported in 8/15 patients. Only one patient had a PSA nadir of <0.1 ng/ml after salvage surgery. Another patient had stable disease with a PSA of 0.5 ng/ml. Three patients developed bone metastases during follow-up. CONCLUSIONS: This interim analysis indicates that [(11)C]choline-PET/CT may be a useful technique in detection of lymph node metastases when rising PSA occurs after definite prostate cancer therapy. The presented cohort is limited in size, but there is still strong evidence that the patients benefit from [(11)C]choline-PET/CT and consecutive salvage lymph node dissection is rather small.


Subject(s)
Lymph Node Excision , Neoplasm Recurrence, Local , Positron-Emission Tomography , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgery , Tomography, X-Ray Computed , Aged , Biomarkers , Choline , Humans , Lymphatic Metastasis , Male , Middle Aged , Prospective Studies , Prostate-Specific Antigen/blood , Prostatic Neoplasms/diagnostic imaging , Radiopharmaceuticals
8.
Neoplasia ; 10(6): 624-34, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18516299

ABSTRACT

The glycogen synthase kinase 3 (GSK-3) is a serine/threonine kinase widely expressed in mammalian tissues. Initially identified by its ability to modulate glycogen synthesis, GSK-3 turned out to be a multifunctional enzyme, able to phosphorylate many proteins, including members of the steroid receptor superfamily. Although GSK-3 was shown to phosphorylate the androgen receptor (AR), its effects on AR transcriptional activity remain controversial. Analysis of short hairpin RNA (shRNA)-mediated downmodulation of GSK-3 proteins in prostate cancer cells showed a reduction in AR transcriptional activity and AR protein levels. Pharmacological GSK-3 inhibitors such as the maleimide SB216763 or the aminopyrazole GSK inhibitor XIII inhibited AR-dependent reporter gene activity and AR expression in vitro. Analysis of androgen-induced nuclear translocation of the AR was performed in PC3 cells transfected with pAR-t1EosFP coding for EosAR, a green fluorescent AR fusion protein. When grown in presence of androgens, EosAR was predominantly nuclear. Incubation with SB216763 before and after androgen treatment almost completely reduced nuclear EosAR. In contrast, the thiazole-containing urea compound AR-A014418 increased rather than decreased AR-expression/function. Although not all GSK inhibitors affected AR-stability/function, our observations suggest a potential new therapeutic application for some of these compounds in prostate cancer.


Subject(s)
Androgens/metabolism , Glycogen Synthase Kinase 3/metabolism , Prostatic Neoplasms/metabolism , Active Transport, Cell Nucleus , Antineoplastic Agents/pharmacology , Cell Proliferation , Enzyme Inhibitors/pharmacology , Green Fluorescent Proteins/metabolism , Humans , Indoles/pharmacology , Male , Maleimides/pharmacology , RNA, Small Interfering/metabolism , Receptors, Androgen/metabolism , Signal Transduction , Transcription, Genetic
9.
Urology ; 71(6): 1196-8, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18295313

ABSTRACT

OBJECTIVES: Selective clamping techniques are an attractive surgical option in nephron-sparing surgery. We describe the use of the Nussbaum clamp for this procedure and point out the advantages of this clamping technique. TECHNICAL CONSIDERATIONS: The perirenal fat overlying the tumor is removed from the kidney. It is unnecessary to expose the renal artery and vein. The Nussbaum clamp is placed around the tumor 1 to 2 cm proximal to the line of resection. Afterward, the tumor is excised and a hemostasis achieved. Twelve patients underwent nephron-sparing surgery that used the Nussbaum clamp between January 2006 and November 2006. The indications for nephron-sparing surgery were complicated renal cysts or a suspected renal carcinoma in 3 and 9 patients, respectively. The location of the tumor was in the upper pole, lower pole, middle portion, and in a horseshoe-shaped kidney in 4, 6, 1, and 1 patient, respectively. The median time of selective clamping and intraoperative blood loss was 19 minutes (range 12 to 31 minutes) and 300 mL (range: 100 to 500 mL), respectively. CONCLUSIONS: The Nussbaum clamp is a commercially available, easy-to-use and effective instrument for selective clamping in nephron-sparing surgery.


Subject(s)
Kidney Neoplasms/surgery , Nephrectomy/methods , Aged , Constriction , Equipment Design , Female , Humans , Male , Middle Aged , Nephrectomy/instrumentation
10.
Prostate ; 67(16): 1751-60, 2007 Dec 01.
Article in English | MEDLINE | ID: mdl-17929268

ABSTRACT

BACKGROUND: Deregulation of the canonical Wnt/beta-catenin-pathway is known to play an important role in the progression of various tumour cell types including prostate cancer (PCa). Recently, the tumour-suppressor p53 was shown to down-regulate beta-catenin-signalling in colon cancer. As p53 is frequently mutated in late stage PCa we investigated the effect of wild-type p53 (p53wt) as well as p53-mutants on beta-catenin-signalling in PCa-cell lines. METHODS: The effects of p53wt and p53-mutants on Wnt/beta-catenin-signalling were studied using reporter gene assays. Expression of beta-catenin levels was monitored by Western blotting. RESULTS: Overexpression of p53wt as well as p53(249Ser) (a structural mutant) and p53(273His) (a DNA-contact-mutant) almost completely inhibited beta-catenin-mediated transcriptional activity of the T-cell factor (TCF) whereas p53(175His), a structural mutant, and a p53-mutant with a C-terminal deletion in the tetramerization domain (Deltap53) were unable to do so. Co-transfection experiments with p53wt and a dominant negative p53-mutant reversed the down-regulation of TCF-signalling, while Deltap53 was unable to interfere with p53wt-function. Down-regulation of TCF-signalling by p53wt and p53(273His) was accompanied by a reduction in beta-catenin protein level. CONCLUSIONS: p53wt, p53(273His)- and p53(249Ser)-mutants are able to down-regulate beta-catenin-signalling in PCa-cells probably via degradation of beta-catenin. The degradation of beta-catenin in PCa by p53 is not linked to transcriptional activity of p53. So far the mechanism how p53 interferes with beta-catenin-signalling is unknown. For the first time we provide experimental evidence that the C-terminus of p53 plays an important role in the down-regulation of beta-catenin-mediated TCF-signalling in PCa-cell lines possibly via p53 transrepressional function.


Subject(s)
Mutation , Prostatic Neoplasms/metabolism , TCF Transcription Factors/metabolism , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , beta Catenin/metabolism , Blotting, Western , Cell Line, Tumor , Down-Regulation , Gene Expression Regulation, Neoplastic , Genes, p53 , Glycogen Synthase Kinase 3/metabolism , Glycogen Synthase Kinase 3 beta , Humans , Male , Promoter Regions, Genetic , Prostatic Neoplasms/genetics , Signal Transduction , TCF Transcription Factors/genetics , Transcription Factor 7-Like 2 Protein , Transcriptional Activation , Transfection , beta Catenin/agonists
11.
BJU Int ; 100(4): 786-93, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17822459

ABSTRACT

OBJECTIVE: To evaluate [(11)C]-choline positron-emission tomography (PET)/computed tomography (CT) for detecting clinical recurrence after primary treatment for prostate cancer. PATIENTS AND METHODS: In all, 50 patients with prostate cancer who had had initial therapy (radical prostatectomy in 40, external beam radiation in three and interstitial brachytherapy in seven) had PET/CT using [(11)C]-choline in the presence of an increased or increasing prostate-specific antigen (PSA) level. The mean (range) time to biochemical progression was 22 (2-136) months. Current PSA levels were determined in all patients at the time of examination. The results were correlated with the histopathology reports after targeted biopsy or surgery, and with the clinical follow-up. RESULTS: The mean (median, range) PSA level in patients with positive PET/CT was 3.62 (2.42, 0.5-13.1) ng/mL, and that in patients with a negative scan was 0.90 (0.95, 0.41-1.40) ng/mL. PET/CT was positive in seven of 13 patients with a PSA level of <1.5 ng/mL, and histology was positive in this group in nine. In 17 patients with PSA levels of 1.5-2.5 ng/mL PET/CT was positive in all and the histology was positive in 13; in 11 men with a PSA level of 2.5-5 ng/mL PET/CT was positive in all 11 and the histology was positive in 10; in nine men with PSA levels of >5 ng/mL PET/CT identified all as positive and the histology was positive in eight. The sensitivity at a PSA level of <2.5 ng/mL of PET/CT for detecting recurrence was 91% (95% confidence interval, 71-99%) with a specificity of 50% (16-84)%. CONCLUSION: [(11)C]-choline PET/CT seems to be useful for re-staging prostate cancer after curative therapy and with increasing PSA levels; this was verified by histological examination. We recommend this method at PSA levels of <2.5 ng/mL.


Subject(s)
Neoplasm Recurrence, Local/diagnostic imaging , Prostatic Neoplasms/diagnostic imaging , Tomography, Emission-Computed/standards , Aged , Choline , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Staging , Prognosis , Prostate-Specific Antigen/blood , Prostatectomy/methods , Prostatic Neoplasms/therapy , Radiopharmaceuticals , Sensitivity and Specificity
12.
Urol Int ; 79(1): 41-3, 2007.
Article in English | MEDLINE | ID: mdl-17627167

ABSTRACT

BACKGROUND: It was the aim of this study to evaluate the serum levels of cathepsin D (Cath D) as a diagnostic tool in patients with renal cell carcinoma (RCC) in comparison with healthy volunteers. METHODS: Cath D serum levels were measured in serum samples obtained preoperatively from 32 patients with histologically confirmed RCC versus 30 healthy individuals using an enzyme immunoassay. Additionally, for the tumor group, Cath D serum levels were correlated with tumor stage and grade as determined according to the 2002 TNM classification. RESULTS: The serum Cath D concentration was not significantly different in patients with RCC compared with healthy individuals (mean 16.58 vs. 16.64 ng/ml; p = 0.43). Furthermore, there was no significant association between Cath D serum levels and several patient or tumor characteristics such as tumor stage, tumor grade, lymph node status, presence of metastasis, gender or age. CONCLUSIONS: In contrast to overexpression of Cath D in primary RCC tissue, serum Cath D is not altered in RCC patients when compared with healthy volunteers. In this small cohort, Cath D serum levels did not reveal additional clinical information in patients diagnosed with a small renal mass. Further prospective multicenter studies might shed more light on the value of Cath D in the diagnostics of RCC.


Subject(s)
Biomarkers, Tumor/blood , Carcinoma, Renal Cell/blood , Cathepsin D/blood , Kidney Neoplasms/blood , Aged , Female , Humans , Male , Predictive Value of Tests , Reproducibility of Results , Retrospective Studies
13.
Neoplasia ; 9(3): 246-53, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17401464

ABSTRACT

Butyrates and retinoids are promising antineoplastic agents. Here we analyzed effects of sodium butyrate and N-(4-hydroxyphenyl)-retinamide (4-HPR) on prostate cancer cells as monotherapy or in combination in vitro and in vivo. Sodium butyrate and 4-HPR induced concentration-dependent growth inhibition in prostate cancer cells in vitro. The isobologram analysis revealed that sodium butyrate and 4-HPR administered together antagonize effects of each other. For the in vivo studies, a water-soluble complex (4-HPR with a cyclodextrin) was created. A single dose of sodium butyrate and 4-HPR showed a peak level in chicken plasma within 30 minutes. Both compounds induced inhibition of proliferation and apoptosis in xenografts of the chicken chorioallantoic membrane. Analysis of the cytotoxic effects of the drugs used in combination demonstrated an antagonistic effect on inhibition of proliferation and on induction of apoptosis. Prolonged jun N-terminal kinase phosphorylation induced by sodium butyrate and 4-HPR was strongly attenuated when both compounds were used in combination. Both compounds induced inhibition of NF-kappaB. This effect was strongly antagonized in LNCaP cells when the compounds were used in combination. These results indicate that combinational therapies have to be carefully investigated due to potential antagonistic effects in the clinical setting despite promising results of a monotherapy.


Subject(s)
Butyrates/pharmacology , Fenretinide/pharmacology , Prostatic Neoplasms/drug therapy , Animals , Butyrates/antagonists & inhibitors , Butyrates/pharmacokinetics , Cell Line, Tumor , Cell Proliferation/drug effects , Chickens , Chorioallantoic Membrane/drug effects , Dose-Response Relationship, Drug , Fenretinide/antagonists & inhibitors , Fenretinide/pharmacokinetics , Humans , Male , Mitogen-Activated Protein Kinases/drug effects , Mitogen-Activated Protein Kinases/physiology , Neoplasm Transplantation , Prostatic Neoplasms/pathology , Transplantation, Heterologous
14.
BJU Int ; 99(6): 1421-6, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17355373

ABSTRACT

OBJECTIVE: To evaluate and compare the role of (11)C-choline positron emission tomography (PET) and transrectal ultrasonography (TRUS) in the preoperative staging of clinically localized prostate cancer. PATIENTS AND METHODS: Fifty-five consecutive patients with biopsy-confirmed prostate cancer had TRUS and (11)C-choline PET as a part of their clinical staging programme before radical retropubic prostatectomy (RP). The PET images were prospectively interpreted by a consensus decision of two nuclear medicine physicians and one radiologist with special expertise in the field. The TRUS was done by one experienced urologist. The criteria evaluated prospectively in each patient were extracapsular extension (ECE), seminal vesicle invasion (SVI) and bladder neck invasion (BNI). The results were compared with the histopathological findings after RP. RESULTS: At pathology, 32 patients were classified pT2, 16 as pT3a and three had pT3b lesions. In four patients the histopathological examination showed pT4 with BNI. The overall accuracy of PET in defining local tumour stage (pT2 and pT3a-4) was 70%; the overall accuracy by TRUS was 26%. PET was more sensitive than TRUS for detecting ECE (pT3a) and SVI (pT3b) in advanced stages, and in pT4 stages. The sensitivity and positive predictive value (PPV) (95% confidence interval) in stages pT3a-pT4 for PET were 36 (17-59)% and 73 (39-89)%. The sensitivity and PPV in stages pT3a-pT4 for TRUS were 14 (3-35)% and 100 (29-100)%. CONCLUSIONS: (11)C-choline PET and TRUS tended to understage prostate cancer. This series shows the current limited value of TRUS and PET for making treatment decisions in patients with clinically localized prostate cancer, especially if a nerve-sparing RP is considered. Treatment decisions should not be based on TRUS and (11)C-choline PET findings alone. In future studies, the combination of metabolic and anatomical information of PET and endorectal magnetic resonance imaging should be evaluated, as this might optimize the preoperative staging in prostate cancer.


Subject(s)
Choline , Positron-Emission Tomography/methods , Prostatic Neoplasms/diagnostic imaging , Aged , Carbon Radioisotopes , Humans , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Predictive Value of Tests , Preoperative Care/standards , Prospective Studies , Prostatectomy , Prostatic Neoplasms/surgery , Sensitivity and Specificity , Tomography, X-Ray Computed/methods , Ultrasonography
15.
J Clin Ultrasound ; 34(9): 440-5, 2006.
Article in English | MEDLINE | ID: mdl-17109402

ABSTRACT

PURPOSE: To describe our experience with transrectal ultrasound (TRUS)-guided needle biopsy of pelvic malignancies. METHODS: Eleven patients with clinical suspecion of advanced malignant pelvic tumor were referred to our institution with a history of unsuccessful CT-guided biopsy, although a target lesion was demonstrated on pelvic CT or MRI. Cholin-PET and FDG-18-PET were also obtained individually in each patient. TRUS was performed using a commercially available three-dimensional scanner. Biopsies were performed with an 18G biopsy gun. In 9 of 11 patients, biopsy was successfully performed under analgesia, whereas general anesthesia was required in the other 2 patients. RESULTS: The lesions were identified with TRUS in all patients, and biopsies were taken successfully under TRUS guidance. In all patients, the harvested material was of excellent quality and was adequate for definitive pathological diagnosis. Pathological results included 6 nodal metastases from transitional cell carcinoma, 1 case of lymph node metastasis from prostate cancer, 1 paravesical recurrence of cervical cancer, 1 metastasis from cecal cancer, and 2 cases of paravesical metastasis of a gastric cancer. CONCLUSION: TRUS-guided biopsy is a useful technique for the diagnosis of pelvic malignancies. It is faster and less expensive than CT-guided biopsy, and in most cases sufficient material can be harvested for a definitive pathological diagnosis.


Subject(s)
Biopsy/methods , Pelvic Neoplasms/diagnostic imaging , Ultrasonography, Interventional , Adult , Aged , Female , Humans , Male , Middle Aged , Pelvic Neoplasms/pathology , Rectum
16.
BJU Int ; 95(9): 1289-92, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15892819

ABSTRACT

OBJECTIVE: To assess the extent and mechanism of renal reabsorption and excretion in patients with an ileal neobladder, as mild metabolic acidosis cause by proton reabsorption is common after such surgery, and long-term pharmacological correction is often necessary. PATIENTS AND METHODS: The study comprised 30 patients (29 men and one woman) with ileal neobladders after oncological surgery; before surgery all had normal retention values. Before and after withdrawing the transurethral catheter, serum creatinine and urea were analysed and used to assess the effect of the neobladder on retention values, expressed as the percentage change from baseline (Delta creatinine and urea). RESULTS: There was a significant correlation between the Delta-creatinine and Delta-urea values (P < 0.001; r = 0.66); 15 patients (50%) showed resorption of creatinine and urea, eight (27%) excreted creatinine into the neobladder and resorbed urea from it at the same time, and three (10%) showed the reverse response, i.e. creatinine resorption and urea excretion. Interestingly, four patients (13%) excreted both creatinine and urea into the neobladder. CONCLUSIONS: We assume that there was both a resorptive and excretory function. Probably the metabolic state (resorption or secretion) of the neobladder depends on its mucus production and on the internal surface, or on diuresis. Further investigation is required to characterize these different influences.


Subject(s)
Urinary Bladder Neoplasms/surgery , Urinary Diversion/methods , Urinary Reservoirs, Continent/physiology , Aged , Creatinine/metabolism , Female , Humans , Ileum/metabolism , Ileum/transplantation , Intestinal Absorption/physiology , Male , Middle Aged , Postoperative Period , Urea/metabolism
17.
J Urol ; 169(2): 570-4, 2003 Feb.
Article in English | MEDLINE | ID: mdl-12544309

ABSTRACT

PURPOSE: The tension-free vaginal tape procedure has become a state of the art operation for female stress urinary incontinence. Cases of complications requiring surgical revision are reported to be rare. We report on 6 patients with complications necessitating surgery. MATERIALS AND METHODS: Six patients who previously underwent the tension-free vaginal tape procedure required surgical management of complications, including intravesical polypropylene mesh tape with incrustation and chronic urinary tract infection in 2, vaginal mucosal mesh erosion of the vaginal incision in 1 and permanent urinary retention in 3. RESULTS: The intravesical tapes were resected via a suprapubic approach. In the case of disturbed wound healing the periurethral part of the tape was resected transvaginally. A patient in urinary retention underwent resection of the periurethral sling, while in the other 2 the tapes were transected transvaginally. Two patients in whom incontinence recurred were successfully treated with a repeat tension-free vaginal tape procedure during followup. CONCLUSIONS: Complications of the tension-free vaginal tape procedure that require surgical intervention are rare. The surgeon must be aware that this operation may lead to an additional surgical procedure, significantly increasing morbidity.


Subject(s)
Surgical Mesh , Urinary Incontinence, Stress/surgery , Urologic Surgical Procedures/adverse effects , Aged , Aged, 80 and over , Female , Humans , Middle Aged , Postoperative Complications/surgery , Urologic Surgical Procedures/methods , Vagina
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