Biomedical subjects

Georg Bartsch

Publications and source records attributed to Georg Bartsch.

At least 127 records · Page 7Linked to original sources

PubMed2004

Complication rate of transrectal ultrasound guided prostate biopsy: a comparison among 3 protocols with 6, 10 and 15 cores.

PURPOSE: We assessed the complication rate of ultrasound guided prostate biopsies performed at a single center in a screening population. Moreover the impact of different biopsy protocols comprising varying numbers of biopsy cores on the complication rate was evaluated. MATERIALS AND METHODS: A total of 5957 biopsies performed in 4303 clinically healthy men between January 1993 and August 2002 was evaluated retrospectively. Due to changes in the biopsy protocol, the number of biopsies obtained increased with time from 6 cores (January 1993 to October 1995) to 10 (November 1995 to March 2000) to 15 cores (March 2000 to August 2002). RESULTS: Minor complications such as hematospermia (36.3%), hematuria (14.5%) and rectal bleeding persisting for up to 2 days (2.3%) were noted frequently, while major complications requiring further treatment were far less common. Post-biopsy fever was seen in 48 patients (0.8%), rectal bleeding requiring surgical intervention or persisting for more than 2 days occurred in 36 patients (0.6%) and urinary retention was observed in 12 patients (0.2%). The increase in biopsy cores with time did not result in increased post-biopsy morbidity. Prostate cancer at biopsy was not associated with a higher complication rate. CONCLUSIONS: Prostate specific antigen screening has led to an increase in the number of patients undergoing prostate biopsy which, in turn, has increased the incidence of post-biopsy complications. However, most of the complications are minor and self-limiting. In this large study population the increased number of biopsy cores did not result in an increased incidence of major post-biopsy complications.

Adult↗

PubMed2004

Serum pro-prostate specific antigen preferentially detects aggressive prostate cancers in men with 2 to 4 ng/ml prostate specific antigen.

PURPOSE: Pro forms of prostate specific antigen (PSA) have been reported to be more cancer specific markers of prostate cancer than total PSA and they also may preferentially detect the more aggressive forms of the disease. MATERIALS AND METHODS: Research immunoassays with high specificity for pro-PSA forms were used to study 1091 retrospective serum specimens, including 555 with 2 to 4 and 536 with 4 to 10 ng/ml PSA, from men enrolled in prostate cancer screening studies who underwent prostate biopsy. RESULTS: In the 2 to 4 ng/ml PSA range the ratio of pro- to free-PSA (percent pro-PSA) using a cutoff of 1.8% for recommending prostate biopsy detected 90% of cancers, including 16 of 16 extracapsular tumors and 28 of 29 tumors with a pathology Gleason score of 7 or greater, while avoiding 19% of unnecessary biopsies. Serum percent pro-PSA was significantly increased for Gleason score 7 or greater vs less than 7 (p = 0.0018). In the PSA range of 4 to 10 ng/ml percent pro-PSA had the highest cancer specificity, avoiding 31% of unnecessary biopsies, while detecting 34 of 35 cancers with a pathology Gleason score of 7 or greater and 29 of 31 extracapsular tumors. Neither percent free PSA nor complexed PSA enhanced the detection of aggressive cancers in the 4 to 10 ng/ml PSA range. CONCLUSIONS: Percent pro-PSA was superior to percent free and calculated complexed PSA for the detection of prostate cancer in the PSA range of 2 to 10 ng/ml and it had selectivity for detecting more aggressive cancers, as indicated by Gleason score 7 or greater and/or extracapsular tumor extension.

Aged↗

PubMed2004

Extracellular matrix degradation and reduced nerve supply in refluxing ureteral endings.

PURPOSE: Extracellular matrix (ECM) degrading enzymes and the nerve supply of the ureterovesical junction were investigated using immunohistochemical methods to gain insight into the pattern of refluxing ureteral endings. MATERIALS AND METHODS: Specimens were obtained from ureterorenal units of 36 children undergoing reflux surgery with a mean age of 62.5 months and 9 age matched controls without reflux. Routine histological paraffin embedded sections were stained for general morphology. Indirect immunohistochemical methods assessing matrix metalloproteinase 1 were used to study the intensity of matrix turnover, and activated macrophage marker CD68 was quantified to describe scavenging of damaged ECM. The intramural neuronal network was explored using nerve specific immunoperoxidase for S-100 protein. RESULTS: Refluxing ureteral endings demonstrated structural deficiencies of the smooth muscle wrap associated with a 3.8-fold increase of cellular matrix metalloproteinase 1 production and a significant increase of CD68+ macrophages, respectively. The S-100 pattern yielded significant diminution. Lacking B and T lymphocytes in the ECM precluded chronic inflammation. CONCLUSIONS: Refluxing ureteral endings showed a pathologically increased matrix remodeling combined with deprivation of the intramural nerve supply. Macrophage activation referring to altered morphology was represented by an increased expression of CD68 at the sites of increased ECM turnover.

Antigens, CD↗

PubMed2004

Age and lean body weight related growth curves of kidneys using real-time 3-dimensional ultrasound in pediatric urology.

PURPOSE: Kidney volume and growth are important parameters for evaluating and monitoring several diseases in pediatric urology. Studies have shown the significant relationship of kidney volume and function. Until now normal values of kidney size and growth have been based on 2-dimensional measurements combined with arithmetic formulas for the ellipsoid. Real-time 3-dimensional (RT3D) ultrasound is a new imaging modality. Moreover, corresponding software allows RT3D imaging within a short time exposure. We created nomograms of kidney volumes for routine diagnostics that could serve as a standard for pediatric renal growth assessment, decreasing the need for invasive tests. MATERIALS AND METHODS: RT3D volumetry of a total of 620 kidneys in 310 children with a homogeneous age distribution (range newborn to 10 years) and without any evidence of renal impairment was performed using a Voluson 730 (Kretztechnik, Ultrasound, Zipf, Austria) system. Polynomial regression analysis was applied for the prediction and estimation of growth variables of kidney volumes as a function of gender, age, body mass index or lean body weight. RESULTS: Stepwise multiple regression analysis incorporating the different independent variables indicated with significant correlation that age and lean body weight were the strongest predictors of kidney volumes in children. CONCLUSIONS: This study shows that RT3D ultrasound is particularly qualified for evaluating kidney volume in pediatric urology. RT3D volumetry is suitable for monitoring renal growth, reflecting kidney function. Furthermore, this methodology is feasible in screening programs assessing congenital urogenital diseases.

Age Factors↗

PubMed2004

Laparoscopic radical nephrectomy in the elderly.

OBJECTIVE: To evaluate the efficacy and outcome of laparoscopic radical nephrectomy (LRN) in patients aged >75 years, and to compare the results with those obtained from patients younger than this undergoing laparoscopic surgery for the same indication. PATIENTS AND METHODS: From a retrospective review of 33 patients aged >75 years undergoing LRN, 28 were for tumour. A group of 28 consecutive patients aged <75 years undergoing laparoscopy for the same indication were used for comparison. The two groups were compared for American Society of Anesthesiology (ASA) physical status score, comorbidity, previous surgical history, operative duration, estimated blood loss, tumour size, complications during and after surgery, conversion rates, time to oral intake and drain removal, perioperative mortality and hospital stay. RESULTS: Only the initial ASA score was significantly higher for the older patients. All other variables before, during and after surgery were similar for both groups. CONCLUSIONS: The final outcome of laparoscopic surgery in elderly patients was as promising as in their younger counterparts. Therefore, elderly patients should not be excluded from LRN, even though they usually present with more comorbidities.

Aged↗

PubMed2004

Evaluation of urinary extravasation and results after continence-preserving radical retropubic prostatectomy.

OBJECTIVE: To evaluate the feasibility of urinary catheter removal 10 days after a radical retropubic prostatectomy (RRP) by assessing the incidence of urinary extravasation and its effect on postoperative stricture and continence rates. PATIENTS AND METHODS: During a 4.5-year period, 619 patients undergoing RRP were evaluated. If no extravasation was detected on gravity cystography, the urinary catheter was removed 10 days after RRP. In patients with significant extravasation the catheter was left in place for 3 weeks. Overall stricture and continence rates were recorded in patients at 3, 6 and 12 months after surgery. RESULTS: There was extravasation during cystography in 29 patients (4.6%). At 3, 6 and 12 months, continence rates after catheter removal at 10 days were 74.9%, 87.9%, and 93.6%, respectively, while in the late-removal group they were 72.4%, 84.6% and 90.9%, respectively, with no significant difference between the groups. At 3 months the overall continence rate was 74.8% and at 12 months up to 93.5%. There was no difference in stricture rates between the groups, with an overall stricture rate of 0.7%. CONCLUSIONS: Catheter removal 10 days after RRP is feasible, giving excellent early and late continence rates, with low anastomotic stricture rates obtained using good surgical technique. Extravasation at 10 days was rare and with proper management did not influence the final results.

Adult↗

PubMed2004

Single-agent chemotherapy with docetaxel significantly reduces PSA levels in patients with high-grade localized prostate cancers.

OBJECTIVE: Chemotherapy has been shown to be effective in the management of prostate cancer in patients with androgen-independent metastatic disease, however, a survival benefit has not been demonstrated yet. Docetaxel alone or in combination with estramustine has been shown to exhibit a high level of activity in the treatment of hormone-refractory prostate cancer. To date there are only few reports on chemotherapy for localized prostate cancer. METHODS: The efficacy and safety of neoadjuvant chemotherapy with docetaxel as a single agent given prior to radical retropubic prostatectomy (RRP) has been evaluated in 5 patients presenting with Gleason score 8 prostate cancers at biopsy. RESULTS: The mean reduction in prostate-specific antigen levels in the 5 patients was 66.5% (range 47.6-94.0%). Histology after RRP yielded pT2N0MxR0 prostate cancers in all subjects. Testosterone and secretoneurin levels were not significantly affected by docetaxel monotherapy. CONCLUSIONS: Although the use of neoadjuvant chemotherapy prior to RRP is still experimental, the dramatic prostate-specific antigen decrease during chemotherapy and the pathologic findings after radical prostatectomy are encouraging. Studies including larger number of patients will have to confirm the present results.

Aged↗

PubMed2004

Measurement of intracellular versus extracellular prostate-specific antigen levels in peripheral macrophages: a new approach to noninvasive diagnosis of prostate cancer.

Although prostate-specific antigen (PSA) is a useful screening marker in prostate cancer, it has limited specificity. Previously it was shown that the amount of surface-bound PSA present on circulating macrophages was different between patients with localized prostate cancer and those with metastatic prostate cancer. It was recently demonstrated that intracellular PSA in macrophages can be measured by flow cytometry. In the context of searching for a noninvasive, highly reliable method for prostate cancer diagnosis, we assessed the extent to which extracellular (ie, surface-bound) and intracellular PSA-positive macrophages might differentiate patients with benign versus malignant prostatic disease. In a pilot study, the levels of complexed, surface-bound, and intracellular PSA were measured in 25 patients with elevated serum PSA values and histologically confirmed disease. In this group, no significant differences for serum PSA and complexed PSA levels, respectively, could be detected among patients with benign prostatic hyperplasia, prostatitis, and prostate cancer. Significant differences, however, were detected in intracellular PSA, although not in surface-bound PSA, among the 3 groups of patients. Intracellular PSA was measured prospectively in a second cohort of 189 patients who had a transrectal biopsy because of a serum PSA constellation suspicious for prostate cancer. In the expanded cohort, highly significant differences in intracellular PSA were observed between benign and malignant disease of the prostate, even in patients with serum PSA level<4 ng/mL. Screening of serum PSA alone or in combination with complexed PSA does not clearly distinguish patients with prostate cancer from those with prostatitis or benign prostatic hyperplasia. Macrophage intracellular PSA might represent a more.

Aged↗

PubMed2004

The influence of left renal vein entrapment on outcome after surgical varicocele repair: a color Doppler sonographic demonstration.

OBJECTIVE: To evaluate the impact of left renal vein entrapment on outcome after surgical varicocele repair using color Doppler sonography. METHODS: Eighty-four men had varicoceles on color Doppler sonography (2 right sided, 74 left sided, and 8 bilateral), which were diagnosed on the basis of a venous diameter of 3 mm or greater and venous retrograde flow in the pampiniform plexus of veins during the Valsalva maneuver or when changing from a supine to an upright position. Diagnosis of the left renal vein entrapment was based on the following criteria: antero-posterior diameter of greater than 1 cm and peak velocity of less than 15 cm/s for the left renal vein at the mid portion and anteroposterior diameter of less than 0.2 cm and peak velocity of greater than 110 cm/s (or, alternatively, a diameter ratio and peak velocity ratio of >5) for the left renal vein between the aorta and superior mesenteric artery. All patients underwent surgical varicocele repair. In postoperative follow-up, we compared the presence of left renal vein entrapment with the frequency of varicocele recurrence. RESULTS: Sixteen (19%) of 84 patients had left renal vein entrapment with a left-sided varicocele. Postoperatively (mean follow-up +/- SD, 19.3 +/- 11.7 months), 27 (32.2%) of 84 had varicocele recurrence, including all 16 patients with left renal vein entrapment and 11 (20.1%) of 68 patients without left renal vein entrapment. The varicocele recurrence rate was significantly greater in patients with left renal vein entrapment (P < .001, Fisher exact test). CONCLUSIONS: The presence of left renal vein entrapment resulted in a significantly higher varicocele recurrence rate. Patients with varicoceles should routinely be evaluated for the presence of left renal vein entrapment before surgical repair.

Adult↗

PubMed2003

Early detection of prostate cancer with low PSA cut-off values leads to significant stage migration in radical prostatectomy specimens.

BACKGROUND: The introduction of prostate-specific antigen (PSA) contributed to a shift in tumor stage at diagnosis in patients with prostate cancer. The aim of the present study was to evaluate the effects of PSA screening with low PSA cut-off values on mean total and percent-free PSA levels in patients with prostate cancers at the time of diagnosis as well as on pathologic stage and mean Gleason scores in positive biopsies and radical prostatectomy specimens. METHODS: Data of 875 patients who were diagnosed with prostate cancers between 1996 and 2001 were analyzed. Patients were stratified into six groups according to the year of biopsy. Annual changes in total and percent-free PSA values, in Gleason scores of biopsies and radical prostatectomy specimens, and in pathologic stages of radical prostatectomy specimens were assessed. RESULTS: Mean PSA of patients diagnosed with prostate cancer decreased from 13.11 ng/ml (percent-free PSA: 11.89%) in 1996 to 7.33 ng/ml (percent-free PSA: 12.58%) in 2001 (P < 0.05). The percentage of organ-confined prostatectomy specimens increased from 64.3% in 1996 to 81.5% in 2001 (P < 0.05). However, mean Gleason scores increased from 5.23 to 6.33 over the 6 years (P < 0.05). The percentage of patients with biopsy-proven prostate cancers and PSA values below 4 ng/ml increased from 14.0% in 1996 to 39.2% in 2001. In the group with PSA values below 4 ng/ml organ-confined cancers were found in 80.0-95.2% of patients. CONCLUSIONS: PSAg screening with low cut-off levels has led to a significant reduction of mean baseline PSA levels in prostate cancer patients and to a significant increase in the percentage of organ-confined radical prostatectomy specimens, whereas mean Gleason scores have remained relatively constant.

Adult↗

PubMed2003

Increased growth factor production in a human prostatic stromal cell culture model caused by hypoxia.

BACKGROUND: Local hypoxia may be one of the triggers of embryonic reawakening of the stroma and subsequent hyperplastic growth in the prostate. Using a cell culture model of human prostatic stromal cells, we investigated the effects of hypoxia on activation of hypoxia-inducible factor 1 (HIF 1) and on the production of growth factors. METHODS: Primary prostatic stromal cells were grown in normal and hypoxic (1% O(2)) atmosphere. Activation of HIF 1 was evaluated after different time intervals by Western blot. Induced secretion of growth factors VEGF, FGF-7, TGF-beta, IL 8, and FGF-2 were analyzed by ELISA. To confirm the in vitro findings we also performed immunohistochemistry of HIF 1alpha as well as pro-collagen I, collagens I, III, and IV in the benign tissue of radical prostatectomy specimens. RESULTS: HIF 1 is activated in a time-dependent manner, already starting 1 hr after exposure of stromal cells to hypoxic conditions. Secretion of VEGF, FGF-7, TGF-beta, FGF-2, and IL 8 is increased under hypoxic in vitro conditions in comparison to normoxia. Levels of TGF-beta, VEGF, and IL 8 were rapidly and statistically significantly increased in the supernatant of hypoxic cells. Consistent with the in vitro findings, immunohistochemistry of HIF 1alpha in (benign prostatic hyperplasia) BPH tissue revealed strong HIF 1alpha nuclear staining in hyperplastic areas. No difference was observed in the collagen pattern between hyperplastic and normal prostate tissue. CONCLUSIONS: Prostatic stromal cells respond to hypoxia by upregulation of secretion of several growth factors suggesting that hypoxia can trigger prostatic growth. Therefore, hypoxia might be a key factor contributing to the pathogenesis of BPH.

Cell Line↗

PubMed2003

Gene expression changes following androgen receptor elimination in LNCaP prostate cancer cells.

We have shown recently that inhibition of androgen receptor (AR) expression with an antisense AR oligonucleotide (ODN) inhibits LNCaP prostate tumor cells in vitro as well as in vivo. In this study, we investigated gene expression changes that occur after AR signaling blockade, either through AR elimination by antisense treatment or through complete androgen receptor inhibition by androgen deprivation combined with the antiandrogen bicalutamide, in order to search for genes that are directly or indirectly regulated through the AR. Gene expression changes were investigated with cDNA NIH 10K gene microarrays in response to treatment over 48 h. Expression of selected genes was further analyzed by real-time reverse transcriptase (RT)-polymerase chain reaction (PCR), Western blotting, and radioimmunoassay. A comparison of antisense-treated and androgen-deprived cells revealed several concordances such as significant downregulation of prostate-specific genes, cell-cycle regulatory genes, genes of the cholesterol biosynthesis pathway, and several cytoskeletal genes. However, there were also several genes that were differentially regulated. Among the genes that were exclusively changed by treatment with the antisense AR ODN were the insulin-like growth factor binding protein 2 (IGFBP2) and the phosphatidylinositol-4-phosphate 5-kinase type I alpha (PIP5KIA). On the other hand, complete androgen receptor blockade induced changes in the expression of the prostate overexpressed gene 1 and the S100 calcium binding protein P. In summary, we identified a cohort of interesting genes whose expression was highly affected by elimination of the AR in LNCaP prostate cancer cells. Further investigations are warranted to clarify their role in the AR signaling pathway and their susceptibility as a target for the treatment of prostate cancer.

Anilides↗

PubMed2003

Stromal testis tumors in infants. a report of two cases.

Gonadal stroma tumors account for 8% of pediatric testicular tumors and are therefore exceedingly rare. They generally exhibit a benign behavior. We report two consecutive cases of gonadal stroma tumors in infants. A 5-month-old boy presented with a Sertoli cell tumor and a 2-month-old boy with a juvenile granulosa cell tumor without systemic disease. Both were diagnosed incidentally during routine examinations. Organ-sparing surgery and radical orchiectomy, respectively, was the therapy of choice. Although neonatal testicular tumors are rare, they should be considered in the differential diagnosis of a newborn with a scrotal mass.

Cryptorchidism↗

PubMed2003

Volume indexes of total, free, and complexed prostate-specific antigen enhance prediction of extraprostatic disease extension in men with nonpalpable prostate cancer.

OBJECTIVES: To analyze the ability of volume-adjusted total, complexed, and free prostate-specific antigen (PSA) to predict organ-confined cancer at radical prostatectomy in patients with nonpalpable disease. METHODS: Collected sera were assayed for total PSA (tPSA), complexed PSA (cPSA), and free PSA (fPSA) in 78 men who underwent radical prostatectomy with nonpalpable prostate cancer. The pathologic results (organ-confined versus extraprostatic extension [EPE]), tPSA, cPSA, fPSA/tPSA ratio, cPSA/tPSA ratio, fPSA/cPSA ratio, tPSA density (tPSAD), cPSA density (cPSAD), and fPSA density (fPSAD) were compared by the Mann-Whitney U test and receiver operating characteristic curves. RESULTS: Fifteen men (19.2%) had pathologic EPE. After stratifying the patients on the basis of the Beckman tPSA, the cPSAD, tPSAD, and fPSAD were significant predictors of EPE when comparing their respective medians in individuals with tPSA greater than 4.0 ng/mL. Statistically significant differences were noted between patients with and without EPE for tPSAD (P = 0.0015), cPSAD (P = 0.0018), and fPSAD (P = 0.0022), but not for the fPSA/tPSA, cPSA/tPSA, and fPSA/cPSA ratios. The area under the receiver operating characteristic curve was similar for tPSA (0.539) and cPSA (0.542), as it was for tPSAD (0.708), cPSAD (0.700), and fPSAD (0.731). The specificity and diagnostic accuracy of tPSAD, cPSAD, and fPSAD were significantly greater than those of tPSA and cPSA (specificity P <0.001; diagnostic accuracy P <0.05). CONCLUSIONS: In men with nonpalpable prostate cancer, the density parameters of tPSA, cPSA, and fPSA performed equivalently and appeared to enhance the predictability of EPE.

Adenocarcinoma↗

PubMed2003

The transcriptional co-activator cAMP response element-binding protein-binding protein is expressed in prostate cancer and enhances androgen- and anti-androgen-induced androgen receptor function.

Progression of human prostate cancer toward therapy resistance occurs in the presence of wild-type or mutated androgen receptors (ARs) that, in some cases, exhibit aberrant activation by various steroid hormones and anti-androgens. The AR associates with a number of co-activators that possess histone acetylase activity and act as bridging molecules to components of the transcription initiation complex. In previous reports, it was shown that the transcriptional co-activator CREB (cAMP response element-binding protein)-binding protein (CBP) enhances AR activity in a ligand-dependent manner. In the present study, we have investigated whether CBP modifies antagonist/agonist balance of the nonsteroidal anti-androgens hydroxyflutamide and bicalutamide. In prostate cancer DU-145 cells, which were transiently transfected with CBP cDNA, hydroxyflutamide enhanced AR activity to a greater extent than bicalutamide in the presence of either wild-type or the mutated AR 730 val-->met. In two sublines of LNCaP cells that contain the mutated AR 877 thr-->ala and overexpressed CBP, increase in AR activity was observed after treatment with hydroxyflutamide but not with bicalutamide. Anti-androgens did not influence AR expression in cells transfected with CBP cDNA, as judged by Western blot analysis. Endogenous CBP protein was detected by Western blot in nuclear extracts from the three prostate cancer cell lines, LNCaP, PC-3, and DU-145, all derived from therapy-resistant prostate cancer. In addition, CBP was expressed in both basal and secretory cells of benign prostate epithelium, high-grade prostate intraepithelial neoplasia, and prostate cancer clinical specimens, as evidenced by immunohistochemical staining. Taken together, our findings demonstrate the selective enhancement of agonistic action of the anti-androgen hydroxyflutamide by the transcriptional co-activator CBP, which is a new, potentially relevant mechanism contributing to the acquisition of therapy resistance in prostate cancer.

Androgen Antagonists↗

PubMed2003

Accelerated in vivo growth of prostate tumors that up-regulate interleukin-6 is associated with reduced retinoblastoma protein expression and activation of the mitogen-activated protein kinase pathway.

Interleukin-6 (IL-6) is a multifunctional cytokine that activates the signaling pathways of Janus kinases-signal transducers and activators of transcription (STAT) and/or mitogen-activated protein kinases (MAPK) in various tumors. Thus, it modulates cell growth and apoptosis. IL-6 levels are elevated in tissues and sera from prostate cancer patients and IL-6 receptor expression has been detected in prostate cancer cell lines and clinical specimens. Continuous exposure of prostate cancer cells to IL-6 might alter their responsiveness to this cytokine. To gain more insight into the function of IL-6 in prostate carcinoma, we have inoculated LNCaP-IL-6+ cells, generated after prolonged treatment with IL-6, into nude mice (total n = 16, two independent experiments). Controls included animals bearing LNCaP-IL-6- cells, passaged at the same time as LNCaP-IL-6+ cells without supplementation of IL-6. LNCaP-IL-6+ tumor volumes were larger than those of their counterparts at all time points. There were no signs of cachexia in any of the experimental animals and all mice were free of metastases. To better understand the mechanisms responsible for accelerated growth of LNCaP-IL-6+ tumors, we have investigated the expression of cell-cycle regulatory molecules by Western blot analysis. The levels of cyclin-dependent kinase 2 were elevated in LNCaP-IL-6+ cells. There was a strong down-regulation of cyclins D1 and E in the LNCaP-IL-6+ subline. The cell-cycle inhibitor p27 was expressed at a low level in LNCaP-IL-6+ cells and could not be up-regulated by addition of IL-6. Most notably, LNCaP-IL-6+ cells exhibited a reduced expression of the hypophosphorylated form of the retinoblastoma protein (pRb). Accelerated tumor growth in our model system was also associated with alterations in IL-6-signaling pathways. The ability of IL-6 to induce tyrosine phosphorylation of STAT3 was abolished in the LNCaP-IL-6+ subline. In contrast, the levels of the MAPK extracellular signal-regulated kinases 1/2 increased in cells generated after long-term IL-6 treatment. The inhibitor of MAPK kinase PD 98059 retarded the proliferation of LNCaP-IL-6+ but not that of control cells. In summary, we show in the present study that chronic exposure of prostate cancer cells to IL-6 facilitates tumor growth in vivo by abolishment of the growth control by pRb and activation of the MAPK signaling pathway. These findings could be relevant to understand the role of IL-6 in prostate cancer progression.

Animals↗

PubMed2003

Efficacy and tolerability of doxazosin and finasteride, alone or in combination, in treatment of symptomatic benign prostatic hyperplasia: the Prospective European Doxazosin and Combination Therapy (PREDICT) trial.

OBJECTIVES: To evaluate the efficacy and tolerability of the selective alpha(1)-adrenergic antagonist doxazosin and the 5-alpha-reductase inhibitor finasteride, alone and in combination, for the symptomatic treatment of benign prostatic hyperplasia. METHODS: In a prospective, double-blind, placebo-controlled trial, 1095 men aged 50 to 80 years were randomized to treatment for 52 weeks with doxazosin, finasteride, the combination of doxazosin and finasteride, or placebo. The dose of finasteride (or its matched placebo) was 5 mg/day. Doxazosin (or its matched placebo) was initiated at 1 mg/day, and titrated up to a maximum of 8 mg/day over approximately 10 weeks according to the response of the maximal urinary flow rate (Qmax) and International Prostate Symptom Score (IPSS). The IPSS and Qmax were assessed at baseline and at weeks 10, 14, 26, 39, and 52 or at the endpoint. RESULTS: An intent-to-treat analysis of 1007 men showed doxazosin and doxazosin plus finasteride combination therapy produced statistically significant improvements in total IPSS and Qmax compared with placebo and finasteride alone (P <0.05). Finasteride alone was not significantly different statistically from placebo with respect to total IPSS and Qmax. All treatments were generally well tolerated. CONCLUSIONS: Doxazosin was effective in improving urinary symptoms and urinary flow rate in men with benign prostatic hyperplasia, and was more effective than finasteride alone or placebo. The addition of finasteride did not provide further benefit to that achieved with doxazosin alone.

5-alpha Reductase Inhibitors↗

PubMed2003

Photodynamic therapy with intravesical instillation of 5-aminolevulinic acid for patients with recurrent superficial bladder cancer: a single-center study.

OBJECTIVES: Photodynamic therapy (PDT) is an effective treatment option for patients with superficial bladder cancer uncontrolled by transurethral resection and/or intravesical bacille Calmette-Guérin (BCG) immunotherapy alone. We determined the efficacy and side effects of PDT in patients with recurrent superficial bladder cancer. METHODS: Between April 1994 and July 2001, PDT was performed in 31 patients (23 men and 8 women). 5-Aminolevulinic acid (50 mL) in a 3% concentration was instilled intravesically. Patients were instructed to hold the solution as long as possible and were irradiated transurethrally with a mean light dose of 3.9 W using laser light emitting a wavelength of 633 nm for a mean time of 1260 seconds. RESULTS: The mean patient age at the procedure was 70.2 years. At an average follow-up of 23.7 months (range 1 to 73), 16 patients were free of tumor recurrence; 15 patients had developed tumor recurrence after a mean of 8.3 months. Of 10 patients with prior BCG treatment, 4 were free of tumor recurrence. Treatment was well tolerated, with the only side effect being dysuria due to urinary tract infection in 4 patients and hematuria in 7 patients. No phototoxic skin reactions were observed. CONCLUSIONS: PDT represents a safe, effective, and less-invasive treatment for patients with recurrent superficial bladder cancer. Because of the favorable side-effect profile, PDT can also be applied to patients with comorbidity precluding surgical treatment. Furthermore, PDT represents a second-line treatment for patients with tumor recurrence after BCG failure.

Administration, Intravesical↗