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Hannes Steiner

Publications and source records attributed to Hannes Steiner.

At least 37 records · Page 2Linked to original sources
PubMed2004

Molecular cytogenetic analysis of human spermatocytic seminomas.

We performed comparative genomic hybridization (CGH) on 8 formalin-fixed, paraffin wax-embedded primary spermatocytic seminomas (SS) from 7 patients, one of whom developed metastatic disease. In general, this tumour type is not associated with development of metastases. Since there are only few reported cases of metastatic SS in the literature, this study is the first report of chromosomal constitution in a patient with metastatic disease. Chromosomal imbalances were observed in all 8 tumours analysed by CGH. Frequent copy number alterations were enh(9), dim(16 or 16p), enh(20) and enh(X), each in 6 samples, followed by dim(7) in 4, and enh(1), enh(18) and dim(15), each in 3 samples. In addition to the CGH analysis, interphase fluorescence in situ hybridisation (I-FISH) was applied to evaluate the CGH results and to define the size of the aberrant cell population. Interphase cytogenetics showed gain of material on chromosomes 9 and X in all tumours analysed. Overall, the I-FISH results were in agreement with the CGH data. In conclusion, gain of chromosome 9 seems to be restricted to SS and point to an important role for this aberration in the development of this tumour type.

Adult↗
PubMed2004

An autocrine loop for vascular endothelial growth factor is established in prostate cancer cells generated after prolonged treatment with interleukin 6.

Concentrations of interleukin 6 (IL-6) and its receptor are increased in human prostate cancer. Prostate cancer LNCaP-IL-6+ cells, established after prolonged treatment with IL-6, have been found to acquire a growth advantage. Vascular endothelial growth factor (VEGF) may accelerate the growth of various tumours by stimulation of VEGF receptor 2 (VEGFR-2). To understand better the regulation of proliferation of LNCaP-IL-6+ cells, the expression of VEGF and VEGFR-2 was here investigated in the LNCaP-IL-6+ subline. VEGF was measured in cellular supernatants by enzyme-linked immunoassay. The expression of VEGFR-2 was assessed by Western blot. LNCaP-IL-6+ and control LNCaP-IL-6- cells were treated with a neutralising antibody against VEGFR-2. VEGF concentrations were 20-fold higher in LNCaP-IL-6+ than in LNCaP-IL-6- cells. The stimulatory effect of IL-6 on VEGF production was abolished by an inhibitor of the signalling pathway for phosphoinositol 3 kinase in LNCaP-IL-6+ and LNCaP-IL-6- cells. Exogenous VEGF did not stimulate proliferation in either LNCaP-IL-6+ cells or controls. VEGFR-2 was detected only in LNCaP-IL-6+ cells, in which the neutralising antibody caused a partial inhibition of cell proliferation. It was concluded that a VEGF autocrine loop is established in prostate cancer cells generated after chronic treatment with IL-6. Because of the upregulation of IL-6 in patients with prostate cancer, these findings might be clinically relevant.

Autocrine Communication↗
PubMed2004

Long-term results of laparoscopic retroperitoneal lymph node dissection: a single-center 10-year experience.

OBJECTIVES: To evaluate the feasibility, morbidity, and long-term oncologic efficacy of laparoscopic retroperitoneal lymph node dissection (L-RPLND) in patients with nonseminomatous germ cell tumor (NSGCT). METHODS: L-RPLND was performed 188 times in 185 patients; 114 procedures were performed for Stage I NSGCT and 6 procedures for tumor marker-negative clinical Stage IIA disease. In the case of positive lymph nodes, adjuvant cisplatin-based chemotherapy was administered. After chemotherapy, L-RPLND was performed for retroperitoneal Stage IIA (10 patients), IIB (43 patients), and IIC lesions (15 patients). RESULTS: The mean operative time was 256 minutes for Stage I and 243 minutes for Stage II; the conversion rate was 2.6%. The mean blood loss was 159 mL in patients with Stage I and 78 mL in those with Stage II disease. Active tumor was found in 19.5% of patients with Stage I lesions and in 50% of patients with tumor marker-negative clinical Stage IIA disease. After chemotherapy, active tumor was found in 1 patient with Stage IIC disease and mature teratoma in 38.2% of patients. The mean postoperative hospital stay for those with Stage I and II disease was 4.1 and 3.7 days, respectively. Antegrade ejaculation was preserved in 98.4% of patients. The mean follow-up was 53.7 months for those with Stage I and 57.6 months for those with Stage II disease. All but 6 patients have remained free of relapse, and no patient died of tumor progression. CONCLUSIONS: The rate of tumor control after L-RPLND and the diagnostic accuracy of L-RPLND were equal to the open procedure, and the morbidity was significantly lower. Therefore, L-RPLND for Stage I and low-volume retroperitoneal Stage II disease can be performed at centers with experience in urologic laparoscopy and oncology.

Combined Modality Therapy↗
PubMed2004

Safer transurethral resection of the prostate: coagulating intermittent cutting reduces hemostatic complications.

PURPOSE: Transurethral resection of the prostate (TURP) is still the gold standard for the surgical treatment of symptomatic benign prostatic hyperplasia. However, the associated morbidity and blood loss remain concerns. A coagulating intermittent cutting (CIC) device with constant voltage pulses and controlled pulse intervals was recently developed. The impact of CIC on bleeding and blood transfusion rates as well as the occurrence of the TUR syndrome were investigated. MATERIALS AND METHODS: From January 2000 to July 2002, 271 consecutive patients with symptomatic benign prostatic hyperplasia underwent TURP with the CIC device. In addition to blood transfusion rates, serum hemoglobin and electrolytes were determined in all patients immediately before and after TURP. RESULTS: The mortality rate in the 271 patients subjected to TURP was 0.0%. Mean decrease in hemoglobin after TURP was 1.08 mg/dl. Intraoperative and postoperative blood transfusions were required in 7 patients (2.6%), and clinical signs of the transurethral resection syndrome were noted in 1.1% of patients. CONCLUSIONS: Coagulating intermittent cutting dramatically improves the safety of TURP by decreasing intraoperative and postoperative blood loss, and the rate of blood transfusions. With this blood sparing device we anticipate a lower incidence of hemostatic complications from TURP.

Adult↗
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

Chemometric correction of drift effects in optical spectra.

All quantitative data evaluation techniques applied to spectroscopy are based on the assumption that the baseline is stable in time. If this prerequisite is violated, major concentration errors can result since drifts are evaluated along with true spectroscopic features. For handling baseline drifts two improved principal component regression (PCR) methods are presented and compared to conventional Savitzky-Golay preprocessing followed by conventional PCR. The proposed drift-correction methods take advantage of baseline drifts being rather broad compared to the absorption features. The only assumption made is that drift effects can be modeled sufficiently by polynomials of user-selectable order. One correction method modifies principal components such that drifts of polynomial shape are orthogonal to the calibration model and thus cannot influence the concentration result. The second method extends the calibration model by synthetic so-called pseudo-principal components. While the principal components model the true spectral features, the pseudo-principal components describe drifts simultaneously and independently. Hence, drifts are explicitly included into the calibration and cannot cause erroneous concentration results. It is demonstrated that both correction methods are equivalently as powerful as the conventional PCR in the absence of drifts and superior if drifts are present. The overall performance--in the absence and presence of baseline drifts--of the novel methods makes them more versatile and reliable than the conventional Savitzky-Golay data preprocessing. In almost all investigated cases, the average concentration errors were significantly smaller than those obtained by Savitzky-Golay preprocessing. Furthermore, polyPCR and pPCR do not need laborious optimizations as Savitzky-Golay does for preventing suppression of relevant signal components. polyPCR demands less computation expense than Savitzky-Golay, and pPCR extracts the drift spectrum as additional qualitative information not provided by Savitzky-Golay.

Algorithms↗
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

Model-based optimal design of polymer-coated chemical sensors.

A model-based methodology for optimal design of polymer-coated chemical sensors is developed and is illustrated for the example of infrared evanescent field chemical sensors. The methodology is based on rigorous and computationally efficient modeling of combined fluid mechanics and mass transfer, including transport of multiple analytes. A simple algebraic equation for the optimal size of the sensor flow cell is developed to guide sensor design and validated by extensive CFD simulations. Based upon these calculations, optimized geometries of the sensor flow cell are proposed to further improve the response time of chemical sensors.

Journal Article↗
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

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↗
PubMed2003

Periprostatic administration of local anesthesia during transrectal ultrasound-guided biopsy of the prostate: a randomized, double-blind, placebo-controlled study.

OBJECTIVES: To evaluate the effect of periprostatic infiltration with local anesthesia on the level of discomfort associated with transrectal ultrasound-guided needle biopsy of the prostate. Transrectal ultrasound-guided needle biopsy of the prostate is the standard procedure to diagnose prostate cancer. METHODS: A prospective, randomized, double-blind study was performed on 100 men referred for biopsy of the prostate. Fifty subjects were randomized to periprostatic injection of 10 mL of 2% lidocaine solution without epinephrine, and 50 were randomized to injection of placebo (10 mL of 0.9% NaCl). Each subject completed three 10-point visual analog scales for pain after a series of 15 needle biopsies. Pain was rated during the biopsy, diagnostic investigation, and injection of lidocaine. RESULTS: Patients who received local anesthesia had significantly lower visual analog scale scores compared with the group without lidocaine during the biopsy (mean score 0.76 versus 3.62, P <0.001) and diagnostic examination (mean score 1.08 versus 1.86, P = 0.025). Lidocaine injection caused no adverse effects. CONCLUSIONS: Periprostatic injection of lidocaine represents a simple and safe procedure that significantly reduces discomfort during probe manipulation and biopsy. We recommend this procedure in men undergoing transrectal ultrasound-guided prostate biopsy.

Aged↗
PubMed2003

Late penile metastasis from primary bladder carcinoma.

We report a case of late penile metastasis from primary bladder carcinoma. Penile metastases are an extremely rare occurrence. The most striking feature of this case was that lung metastasis was diagnosed 7.5 years after the patient presented with primary bladder carcinoma and that metastasis to the penis was detected another 2.5 years later. No further urothelial carcinoma recurrence was observed during follow-up until the patient died of lung cancer 6 years after the occurrence of penile metastasis. The case is discussed with reference to published reports.

Carcinoma, Bronchogenic↗
PubMed2003

Frozen section analysis-guided organ-sparing approach in testicular tumors: technique, feasibility, and long-term results.

OBJECTIVES: To evaluate retrospectively the indications, surgical technique, feasibility, and follow-up data of our frozen section analysis-guided organ-sparing approach to small testicular tumors. Removal of a solitary testis or bilateral orchiectomy for testicular neoplasm results in androgen deprivation and infertility. Moreover, removal of a testis for benign lesions is to be avoided. Organ-sparing surgery aims at preserving enough testicular parenchyma to maintain physiologic endocrine function and, if possible, fertility. METHODS: Tumors of 25 mm or less in diameter were managed by an organ-sparing approach. Normal preoperative plasma levels of luteinizing hormone and testosterone were a prerequisite. After localization of the tumor by ultrasonography and accurate staging, organ-sparing surgery was performed under cold ischemia. Frozen section analyses of the tumor and tumor bed biopsies were obtained. In the case of malignant germ cell tumor with a normal contralateral testis, ablation of the tumor-bearing testis was performed. RESULTS: A total of 32 organ-preserving procedures were performed in 30 patients without any complications. Local recurrence was observed in 1 patient who refused to undergo local radiotherapy for concomitant testicular intraepithelial neoplasia; repeat organ-sparing surgery was performed in this patient. After organ-sparing surgery, ablation of the remaining testis was performed in 1 patient because of positive margins on final histologic analysis and in another patient because of endocrine insufficiency. In all other patients, the serum testosterone levels remained within normal limits. No retroperitoneal, pulmonary, or other recurrences were encountered; all patients were free of disease at a mean follow-up of 46.3 months. CONCLUSIONS: The organ-sparing frozen section analysis-guided approach to testicular masses represents a promising treatment alternative to orchiectomy in selected patients with bilateral malignant testicular tumors, tumors in a solitary testis, or unilateral or bilateral benign tumors. The technique is oncologically efficient, lifelong hormonal substitution can be prevented, and, in some patients, even fertility may be preserved, provided certain criteria concerning patient selection and surgical technique are observed.

Adolescent↗
PubMed2003

Transurethral microwave thermotherapy (TUMT) with the Targis System: a single-centre study on 78 patients with acute urinary retention and poor general health.

OBJECTIVES: To evaluate the Targis System in men presenting with acute urinary retention, high prostate volume and high operative risk. MATERIALS AND METHODS: Between August 1997 and March 2001, a total of 78 patients in poor general health status presenting with large prostate glands and acute urinary retention secondary to BPH were treated with the Targis TUMT device. Mean age, mean prostate volume, and the percentage of patients who were able to urinate spontaneously after the procedure as well as mean peak and average flow rates and mean residual urine volume were evaluated. RESULTS: 68 (87.1%) of the 78 patients were able to urinate spontaneously three months after the procedure. In 5 (7.3%) of the 68 patients urinary retention recurred within two years. Following treatment, the mean peak flow rate in the 68 successfully treated patients was 11.1 ml/s, while the mean postvoid residual volume was 46 ml. CONCLUSION: Based on these data we recommend transurethral thermotherapy using the Targis System for patients in poor general health presenting with urinary retention and prostate volumes of more than 35 cc in whom TURP is not possible.

Aged↗
PubMed2003

Management of adult Leydig-cell testicular tumors: assessing the role of laparoscopic retroperitoneal lymph node dissection.

BACKGROUND AND PURPOSE: Leydig-cell tumors represent <5% of malignant testicular tumors in adults. Orchiectomy is curative in approximately 90% of cases; however, the remaining men can develop metastases refractory to chemotherapy and radiation. We evaluated the role of laparoscopic retroperitoneal lymph node dissection (RPLND) in adult Leydig-cell tumors. PATIENTS AND METHODS: Between 1999 and 2001, laparoscopic RPLND was performed with four transperitoneal ports within a unilateral template for six patients with pure Leydig-cell tumors. Presenting signs and symptoms, operative time, blood loss, intraoperative complications, postoperative complications, length of hospitalization, pathology reports, ejaculatory function, and survival were reviewed retrospectively. RESULTS: Laparoscopic RPLND was successful, without open conversions or reinterventions. Two vascular injuries occurred during dissection; additional intraoperative complications were not observed. Postoperatively, one patient developed erysipelas, but no other postoperative complications were recorded. The mean operative time was 190 minutes, and the mean length of hospitalization was 4.3 days. Pathologic analysis of lymph nodes revealed no evidence of metastatic Leydig-cell tumor. At 12 months' mean follow-up (range 3-29 months), no recurrences have been identified. CONCLUSIONS: Laparoscopic RPLND is a safe, minimally invasive procedure for Leydig-cell tumors. Additional clinical experience is required to evaluate its effectiveness for pathologic stage II tumors and to determine if a therapeutic advantage can be realized with a protocol employing laparoscopic RPLND for adult Leydig-cell tumors.

Adult↗
PubMed2003

Androgen receptors in prostate cancer.

PURPOSE: Androgen receptor (AR) is expressed in the majority of human prostate cancers. For a better understanding of prostate carcinoma events it is necessary to present findings on the regulation of AR target genes, AR interaction with associated proteins, ligand independent activation and point mutations. MATERIALS AND METHODS: A comprehensive literature review of manuscripts published on AR in prostate cancer was performed using PubMed. RESULTS: AR regulates the expression of genes involved in the proliferation and differentiation of prostate cancer cells. Due to differential interactions with coactivators and corepressors AR activation results in the stimulation of a mitogenic response or in the expression of secretory proteins. AR is functional in advanced carcinoma of the prostate, as evidenced in studies of mutant receptors and ligand independent activation. AR point mutations appear in advanced prostate cancer more frequently than in organ confined disease. CONCLUSIONS: Current therapy options aimed to inhibit AR function in prostate cancer are limited. Antiandrogenic drugs frequently acquire agonistic properties in the presence of mutated ARs. In addition, androgen signaling pathway activity increases during long-term androgen ablation. AR coactivator complexes might be a target for novel therapies for prostate cancer.

Cell Division↗