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Biomedical subjects

Hannes Steiner

Publications and source records attributed to Hannes Steiner.

At least 19 recordsLinked to original sources
PubMed2006

Regulation of growth of prostate cancer cells selected in the presence of interleukin-6 by the anti-interleukin-6 antibody CNTO 328.

BACKGROUND: Interleukin-6 (IL-6) is a multifunctional regulator of cellular events in prostate cancer. LNCaP-IL-6+ cells selected in the presence of IL-6 were taken for assessment of effects of the chimeric monoclonal anti-IL-6 antibody CNTO 328. METHODS: Cell viability was assessed after treatment with CNTO 328 by the ATP assay. Expression of Bcl-2 and Bax and activation of signaling pathways were evaluated by Western analysis. Nude mice were inoculated with LNCaP-IL-6+ cells and treated with CNTO 328. The tumors were analyzed by immunohistochemistry for expression of Ki-67, tissue transglutaminase, and vascular endothelial growth factor. RESULTS: CNTO 328 caused a statistically significant inhibition of cell viability. The protein levels of Bcl-2 and the phosphorylation of ERK1/2 mitogen-activated protein kinases were decreased by the anti-IL-6 antibody. Treatment with CNTO 328 yielded an increase in the phosphorylation of signal transducers and activators of transcription factor 3. The mean tumor volume in animals inoculated with LNCaP-IL-6+ cells and treated with CNTO 328 was insignificantly lower than that in animals treated with the control antibody. There was a statistically significant decrease in the percentage of Ki-67-positive cells in CNTO 328-treated tumors. CONCLUSION: CNTO 328 has a potential in prostate cancer therapy and could be further tested in various combination experimental treatments.

Animals↗
PubMed2006

Relapse after radical prostatectomy correlates with preoperative PSA velocity and tumor volume: results from a screening population.

OBJECTIVES: To evaluate, in a screening population, the impact of tumor volume and prostate volume on prostate-specific antigen (PSA) velocity (PSAV) and to find predictors of biochemical failure after radical prostatectomy. Longitudinal PSA changes in men with prostate cancer have been reported to be significantly different from those without prostate cancer. METHODS: PSAV was assessed in 102 men undergoing radical retropubic prostatectomy. The pathologic findings of specimens obtained at radical retropubic prostatectomy and pelvic lymph node dissection were analyzed separately for all patients. RESULTS: The median preoperative PSA in the 102 patients was 6.4 ng/mL, the median prostate volume was 32.8 cm3, and the median tumor volume was 1.27 cm3. The PSAV correlated significantly with tumor volume (P <0.05) but not with prostate volume (P = 0.142). The median tumor volume in men with biochemical progression after radical retropubic prostatectomy was 2.55 cm3 versus 0.94 cm3 in men who were free of disease 5 years after surgery. The median PSAV in the year before diagnosis in men with relapse after radical prostatectomy was 1.98 ng/mL/yr versus 1.05 ng/mL/yr in men who had no evidence of disease. CONCLUSIONS: The results of our study have shown that the main factor contributing to the PSAV in patients with prostate cancer is cancer load and that prostate volume is not significantly associated with the PSAV. Men with a PSAV of more than 2 ng/mL/yr in the year before cancer diagnosis are at a high risk of relapse. The PSAV may be helpful in identifying patients with small tumors and thus increase the detection rate of potentially curable prostate cancers.

Adult↗
PubMed2006

Management of incidental impalpable intratesticular masses of < or = 5 mm in diameter.

OBJECTIVE: To gain more insight into the histology of small incidental intratesticular lesions and evaluate the need for surgical management, as exploratory surgery is the only way to exclude malignancy in testicular tumours. PATIENTS AND METHODS: Between September 2000 and April 2005, incidental intratesticular masses of < or = 5 mm in diameter were found in 20 men undergoing scrotal ultrasonography for reasons other than suspected testicular tumour. After staging, an organ-sparing approach including frozen-section analysis was used to obtain histological data. RESULTS: The mean diameter of the detected tumour masses was 3.5 mm, and the mean (range) age of the patients was 36.4 (26-58) years. Four men (20%) had orchidectomy because the tumours were found to be malignant; the resected specimens yielded multifocal testicular intraepithelial neoplasia (TIN) in all patients and additional seminomatous tumour cells elsewhere in the testis in one. Frozen-section results were false-negative in one patient and he had orchidectomy after having established the definitive histological diagnosis. The 16 patients with benign lesions were correctly diagnosed and their testicles were not removed. CONCLUSIONS: Advanced and innovative ultrasonography technology allows the detection of increasingly small testicular masses. In the present series, most incidental intratesticular lesions were benign. In patients with malignant lesions, multifocal TIN and/or distant seminomatous foci were present despite the tumour being small. Therefore, it is essential to perform exploratory surgery as it is the only way to obtain accurate histological findings, thus providing oncological efficacy and precluding removal of a testicle bearing a benign lesion.

Adult↗
PubMed2006

Two cycles of cisplatin-based chemotherapy for low-volume retroperitoneal stage II nonseminomatous germ cell tumours.

OBJECTIVE: To evaluate the oncological efficacy of reducing cisplatin-based chemotherapy to two cycles in patients with low-volume retroperitoneal stage II nonseminomatous germ cell tumours (NSGCTs). PATIENTS AND METHODS: From October 1988 until January 2004, two cycles of cisplatin-based chemotherapy were administered in 59 patients with low-volume retroperitoneal clinical stage II NSGCT (retroperitoneal mass of <5 cm in diameter). Regardless of remission detected on computed tomography, 6 weeks after chemotherapy the patients had a retroperitoneal lymph node dissection (RPLND) to assess residual active tumour or mature teratoma (open modified bilateral RPLND until 1992, then laparoscopic unilateral template RPLND). RESULTS: The chemotherapy was effective, as no active tumour was found in any of RPLND specimens. Mature teratoma was present in lymphatic tissue in 23 of 59 patients (39%). In one patient there was a pulmonary recurrence, successfully treated with cisplatin-based salvage chemotherapy. One patient died from an accident but with no evidence of tumour, and 56 patients remained free of disease at a mean follow-up of 98.6 months. No patient died from disease. All patients had antegrade ejaculation after laparoscopic RPLND, as did 89% after open RPLND. CONCLUSION: In this pilot study, the oncological efficacy of two cycles of cisplatin-based chemotherapy was favourable, but this approach still cannot be recommended as a standard treatment for patients with low-volume retroperitoneal stage II disease. RPLND after chemotherapy has diagnostic (detecting active tumour) and therapeutic (removing mature teratoma) value and can be done laparoscopically. Based on the present results a prospective randomized trial seems reasonable.

Adolescent↗
PubMed2006

The androgen receptor pathway is by-passed in prostate cancer cells generated after prolonged treatment with bicalutamide.

BACKGROUND: Experimental work in various prostate cancer models revealed that the androgen receptor is frequently upregulated and implicated in tumor progression. However, little attention has been paid to the androgen receptor-signaling pathway in the development of therapy resistance in patients who receive chronic treatment with a non-steroidal anti-androgen. METHODS: We have generated a novel subline, LNCaP-Bic, after prolonged treatment with androgen and bicalutamide in vitro. Proliferation of LNCaP-Bic cells in the absence or presence of androgen, tocopherol succinate, and/or bicalutamide was assessed by cell counting. Androgen receptor expression was determined by Western blot. Luciferase activity was measured in cells transfected with an androgen-responsive reporter. RESULTS: In basal conditions, proliferation of LNCaP-Bic cells increased more than threefold over that of control LNCaP cells. Neither synthetic androgen R1881 nor bicalutamide showed any effect on LNCaP-Bic growth in vitro. Androgen receptor expression did not differ between the cell subline generated in the presence of bicalutamide and parental LNCaP cells. The ability of R1881 to induce reporter gene activity in LNCaP-Bic cells was reduced by 56%. Tocopherol succinate caused inhibition of proliferation only in the parental cell line although the androgen receptor and prostate-specific antigen were down regulated by the vitamin E derivative in both parental LNCaP and LNCaP-Bic cells. CONCLUSIONS: Androgen receptor-mediated signal transaction is not enhanced in cells selected in the presence of bicalutamide. Our data may suggest that a more differentiated approach in targeting the androgen receptor is needed in prostate cancers that become resistant to classic endocrine treatment.

Androgen Antagonists↗
PubMed2006

Tumor recurrence in the remnant urothelium of females undergoing radical cystectomy for transitional cell carcinoma of the bladder: long-term results from a single center.

PURPOSE: We analyzed the risk factors and incidence of secondary TCC of the remnant urothelium in women following radical cystectomy for TCC of the bladder. MATERIALS AND METHODS: A total of 85 women with a mean age of 64.5 years with clinically localized TCC of the bladder underwent radical cystectomy between 1992 and 2004. Orthotopic bladder substitution was performed in 46 females, while 39 underwent nonorthotopic urinary diversion. Of the entire cohort 22 (26%) patients underwent cystectomy for multifocal or recurrent TCC. Followup examinations were performed at 6-month intervals. RESULTS: Mean followup in the entire cohort was 49.8 months (median 42). Intraoperative frozen sections obtained from the urethra and distal ureters were negative for TCC and CIS in all patients. Four women (4.7%) had TCC in the remnant urothelium at a mean of 56 months postoperatively. These patients had undergone cystectomy for multifocal or recurrent TCC (4 of 22 or 18%). No secondary TCC was seen in the 63 patients with solitary invasive or nonrecurrent bladder cancer (p <0.05). Urethral recurrence was found in 2 patients (4.3%) 65 and 36 months after orthotopic neobladder surgery, respectively. In the orthotopic group 1 patient (2.1%) had an upper urinary tract tumor 76 months after surgery, while in the nonorthotopic group 1 (2.5%) was found to have an upper urinary tract tumor 48 months postoperatively. CONCLUSIONS: Recurrent or multifocal TCC may represent a risk factor for secondary TCC of the remnant urothelium after cystectomy. In our series all recurrent tumors were late recurrences (more than 36 months postoperatively). Because the rate of urethral recurrence in the current series corresponds to that reported in men (2% to 6%), urethra sparing cystectomy with orthotopic bladder replacement does not appear to compromise the oncological outcome in women.

Adult↗
PubMed2006

Suppressor of cytokine signaling-3 antagonizes cAMP effects on proliferation and apoptosis and is expressed in human prostate cancer.

Interleukin-6, levels of which are elevated in prostate cancer, activates different signal transduction pathways including that of Janus kinases/signal transducer and activator of transcription (STAT)3. However, phosphorylation of STAT3 has been reported to be associated with either stimulatory or inhibitory effects on cellular proliferation. To better understand the mechanisms of STAT3 regulation in benign and malignant prostate, we have investigated the role of suppressor of cytokine signaling (SOCS)-3. Cell lines that did not express phosphorylated STAT3 were found to be SOCS-3-positive. SOCS-3 was re-expressed in LNCaP cells after treatment with a demethylating agent. SOCS-3 immunohistochemistry revealed a negative or weak reaction in benign areas, whereas its expression was detected in tumor tissue. To investigate the involvement of SOCS-3 in regulation of cellular events, we incubated cancer cells with a cAMP derivative. This treatment yielded higher SOCS-3 levels, reduced [3H]thymidine incorporation, and increased percentage of apoptotic cells. However, down-regulation of SOCS-3 by a short interfering RNA approach resulted in inhibition of proliferation and an increased apoptotic rate. Collectively, our results show that SOCS-3 antagonizes regulation of cellular events by cAMP and is expressed in human prostate cancer.

Apoptosis↗
PubMed2005

Metastatic spermatocytic seminoma--an extremely rare disease.

Metastatic spermatocytic seminoma is an extremely rare disease with only one documented case in literature. We present another patient with metastatic disease confirmed by histological work-up after laparoscopic retroperitoneal lymph node dissection (L-RPLND).

Adult↗
PubMed2005

Longitudinal PSA changes in men with and without prostate cancer: assessment of prostate cancer risk.

BACKGROUND: To determine longitudinal PSA changes over a period of 10 years in patients with and without prostate cancer. METHODS: Serial PSA measurements performed over 10 years were evaluated in 353 men who eventually developed prostate cancer and in 2.462 participants of a screening program without prostatic malignancy. RESULTS: In men with cancer, mean tPSA increased from 2.28 ng/ml at 10 years before diagnosis to 6.37 ng/ml at the time of postive biopsy (PSA velocity: 0.409 ng/ml/year). PSA velocity was significantly associated with Gleason scores and pathologic stage. In the benign group (n=2.462), mean tPSA increased from 1.18 to 1.49 ng/ml over a period of 10 years (PSA velocity of 0.03 ng/ml/year). Of the subjects with tPSA levels of 2 ng/ml or less, 2 years prior to cancer diagnosis, 11.4% had tPSA values of more than 4 ng/ml at the time of biopsy. Of the 972 men with tPSA below 1 ng/ml 2 years before the most recent measurement was obtained, 966 (99.4%) had no evidence of prostate cancer 2 years later, while six were found to have malignancies (0.6%). CONCLUSIONS: Longitudinal PSA changes in men with and without prostate cancer are significantly different. Annual testing may not be required in men with baseline tPSA levels of 1 ng/ml or below, whereas in patients with levels higher than 1 ng/ml, it seems to be indicated because of the significant percentage of men presenting with tPSA levels of more than 4 ng/ml two years later.

Adult↗
PubMed2005

Interleukin-6 and oncostatin M stimulation of proliferation of prostate cancer 22Rv1 cells through the signaling pathways of p38 mitogen-activated protein kinase and phosphatidylinositol 3-kinase.

INTRODUCTION: Interleukin-6 (IL-6) is a pleiotropic regulator of prostate cancer cell growth. Oncostatin M (OSM), an IL-6-type cytokine, affects the growth of prostate cancers in a paracrine and autocrine manner. In order to understand better the mechanisms controlling proliferation and intracellular signaling by these cytokines in advanced prostate carcinoma, we performed studies in 22Rv1 cells derived from the relapsed xenograft CWR22R. METHODS: Expression of IL-6 and OSM receptors (OSMR-beta) and elements of signal transduction pathways in 22Rv1 cells were investigated by RT-PCR. Proliferation was assessed by cell counting after treatment with either IL-6 or OSM. IL-6 secretion was measured in conditioned medium from 22Rv1 cells by ELISA. Expression and phosphorylation status of signal transducers and activators of transcription factor (STAT) 3, mitogen-activated protein kinases (MAPK) p44/p42 and p38, and protein kinase B (Akt) was investigated by Western blot. RESULTS: 22Rv1 cells express both subunits of the IL-6 receptor (gp80 and gp130) and leukemia inhibitory factor receptor-beta (LIFR-beta) but not OSMR-beta. Their proliferation was stimulated by IL-6 or OSM and the maximal effect was observed at a concentration of 10 ng/ml of either cytokine. Interestingly, neither IL-6 nor OSM induced phosphorylation of STAT3. OSM modestly increased the phosphorylation of p38 and both cytokines exerted an effect on Akt phosphorylation. CONCLUSIONS: IL-6 and OSM stimulate proliferation of 22Rv1 cells, at least in part through activation of the phosphatidylinositol 3-kinase (PI 3-K) signaling pathway. Our data provide additional evidence for the growth-stimulatory role of IL-6 and related cytokines in advanced prostate cancer and may serve as a basis for the development of novel experimental therapies.

Cell Line, Tumor↗
PubMed2005

Interleukin-6 regulation of prostate cancer cell growth.

Interleukin-6 (IL-6) is involved in regulation of immune reaction and cell growth and differentiation. It causes multifunctional responses ranging from inhibition of proliferation to promotion of cell survival. IL-6 effects may depend on experimental conditions such as passage numbers and serum composition. IL-6 signals in target tissues through the receptor that is composed of the ligand-binding and signal-transducing subunits. IL-6 is expressed in benign and malignant prostate tissue and the levels of the cytokine and its receptor increase during prostate carcinogenesis. IL-6 is considered a positive growth factor for most prostate cells. The only exemption seems to be the LNCaP cell line, in which IL-6 causes growth arrest and induces differentiation function. In contrast, IL-6 acts as an autocrine growth factor in the subline LNCaP-IL-6+ established after chronic treatment with IL-6. IL-6 is a candidate for targeted therapy in prostate cancer because of its association with morbidity. Activation of signaling pathways of Janus kinase/signal transducers and activators of transcription factors, mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3-kinase has been reported in various prostate cancer cell lines. IL-6 and the related cytokine oncostatin M induce activation of the androgen receptor (AR) in the absence of androgen. IL-6 is also involved in regulation of vascular endothelial growth factor expression as well as neuroendocrine differentiation in prostate. Anti-IL-6 antibodies showed an inhibitory effect on the PC-3 xenograft. However, the development of this therapy in prostate cancer is in early stages.

Animals↗
PubMed2005

A comparison of one-stage procedures for post-traumatic urethral stricture repair.

OBJECTIVE: To compare the results and complication rates of various one-stage treatments for repairing a post-traumatic urethral stricture. PATIENTS AND METHODS: The medical records of 153 patients who had a post-traumatic urethral stricture repaired between 1977 and 2003 were evaluated retrospectively, and analysed for the different types of urethral reconstruction. RESULTS: The procedures included direct end-to-end anastomosis in 86 (56%) patients, free dorsal onlay graft urethroplasty using preputial or inguinal skin in 40 (26%), ventral onlay urethroplasty using buccal mucosa in seven (5%) and ventral fasciocutaneous flaps on a vascular pedicle in 20 (13%). At a mean (median, range) follow-up of 75.2 (38, 12-322) months, 121 (79%) patients had no evidence of recurrent stricture, while in 32 men (21%) they were detected at a mean follow-up of 30.47 (1-96) months. Patients having a dorsal onlay urethroplasty had the longest strictures. The re-stricture rate was lowest after a dorsal onlay urethroplasty (5% vs 27% when treated with end-to-end anastomosis, 15% after fasciocutaneous flaps and 57% after a ventral buccal mucosal graft). The surgical technique used had no effect on postoperative incontinence or erectile dysfunction rates. CONCLUSION: In patients with strictures which are too long to be excised and re-anastomosed, tension-free dorsal onlay urethroplasty is better than ventral graft or flap techniques. In patients with short urethral strictures direct end-to-end anastomosis remains an option for the one-stage repair of urethral stricture.

Adolescent↗
PubMed2005

Vascular damage as a risk factor for benign prostatic hyperplasia and erectile dysfunction.

OBJECTIVE: To assess benign prostatic hyperplasia (BPH) and erectile dysfunction (ED), both considered to be associated with urogenital ageing, in ageing men in a cross-sectional population study, comparing them with healthy controls by using symptom scores and contrast-enhanced colour Doppler ultrasonography (CDUS). PATIENTS, SUBJECTS AND METHODS: Transrectal CDUS and quantitative measurement of colour pixel intensity (CPI) are excellent minimally invasive techniques for assessing normal and pathological blood flow. CDUS was performed using the microbubble-based ultrasound enhancer for evaluating prostate, bladder neck and corpus cavernosum vascularity in young healthy men, men with BPH, and men with severe vascular damage (diabetes mellitus type 2). Resistive index measurements and computer-assisted quantification of CPI were used to objectively evaluate perfusion. The International Prostate Symptom Score (IPSS) and the International Index of Erectile Function (IIEF) were applied to quantify the symptoms. RESULTS: In patients with BPH, perfusion of the transition zone (TZ) of the prostate was significantly lower and the resistive index of the TZ significantly higher (both P < 0.001) than in healthy controls. The perfusion patterns of men with BPH and those who also had severe vascular damage (diabetes mellitus type 2) showed that vascularity in the latter group was lower in the prostatic TZ and the corpora cavernosa. In patients with BPH the IPSS, quality-of-life and IIEF scores were significantly worse than in the control group. Men with concomitant atherosclerosis had even worse symptom scores. CONCLUSION: These results strongly support the hypothesis that age-related impairment of blood supply to the lower urinary tract is important in the development of BPH and ED. Vascular damage may cause chronic ischaemia and thus be a contributing factor in the pathogenesis of BPH and ED.

Adult↗
PubMed2004

Expression and function of androgen receptor coactivators in prostate cancer.

Human androgen receptor (AR) associates with coactivator or corepressor proteins that modulate its activation in the presence of ligand. Early studies on AR coactivators in carcinoma of the prostate were hampered because of lack of respective antibodies. Investigations at mRNA level revealed that most benign and malignant prostate cells express common coactivators. AR coactivators SRC-1 and TIF-2 are up-regulated in tissue specimens obtained from patients who failed prostate cancer endocrine therapy. Increased expression of these coactivators is associated with enhanced activation of the AR by the adrenal androgen dehydroepiandrosterone. Similar association between AR coactivator expression and high prostate cancer grade and stage was reported for RAC-3 (SRC-3). The transcriptional integrator CBP was detected in clinical specimens representing organ-confined prostate cancer, lymph node metastases and tumour cell lines. Agonistic effect of the nonsteroidal antiandrogen hydroxyflutamide was strongly potentiated in prostate cells transfected with CBP cDNA. A functional homologue of CBP, p300, is implicated in ligand-independent AR activation by interleukin-6. The AR coactivator Tip60, which is up-regulated by androgen ablation, is recruited to the promoter of the prostate-specific antigen gene in the absence of androgen in androgen-independent prostate cancer sublines. It was proposed that the cofactor ARA70 is a specific enhancer of AR action. However, research from other laboratories has demonstrated interaction between ARA70 and other steroid receptors. Although in some cases dominant-negative coactivator mutants inhibited proliferation of prostate cancer cells in vitro, confirmation from in vivo tumour models is missing. In summary, several abnormalities in AR coactivator expression and function are associated with prostate cancer progression.

Acetyltransferases↗
PubMed2004

Clinical and pathologic features of prostate cancer detected after repeat false-negative biopsy in a screening population.

BACKGROUND: The present study was designed to investigate whether the clinical or pathologic features of prostate cancer (PCa) are related to the number of repeat biopsies required to establish the diagnosis of PCa. METHODS: Between February 1993 and August 2000, 653 patients were evaluated in this retrospective study. All patients underwent transrectal ultrasound-guided biopsy of the prostate prior to radical retropubic prostatectomy. The pathologic findings of specimens obtained at radical prostatectomy and pelvic lymph node dissection as well as PSA levels, findings on DRE, prostate volumes, transition zone volumes, and age were analyzed separately for all PCa patients diagnosed at the first set of biopsies (group A) and compared with the data of those diagnosed at the 2nd-5th set of biopsies (group B). In a second step, we compared the results obtained from patients diagnosed at the 2nd set of biopsies (group B1) with those of patients diagnosed at the 3rd to 5th set of biopsies (group B2). RESULTS: Gleason scores, pathologic tumor stages, and tumor volumes in group B were found to be significantly decreased compared to group A. But from the 2nd to 5th serial biopsy no further decrease in pathologic stage, Gleason score, or tumor volume was observed. On the contrary, there was a tendency towards higher tumor stages and Gleason scores. Of the tumors detected after the second false-negative set of biopsies almost 70% were lesions with Gleason scores of 6 or higher. CONCLUSIONS: False-negative results at the first needle biopsy are predictive of a lower pathologic stage and grade as well as smaller tumor volumes of PCa diagnosed at repeat sets of biopsies. False-negative results on repeat biopsy, however, have no prognostic significance for the tumor stage of PCas detected at subsequent sets of biopsies.

Aged↗