Biomedical subjects

Georg Bartsch

Publications and source records attributed to Georg Bartsch.

At least 91 records · Page 5Linked to original sources

PubMed2005

Racial differences in serum prostate-specific antigen (PSA) doubling time, histopathological variables and long-term PSA recurrence between African-American and white American men undergoing radical prostatectomy for clinically localized prostate cancer.

OBJECTIVE: To determine if there are significant differences in biochemical characteristics, biopsy variables, histopathological data, and rates of prostate-specific antigen (PSA) recurrence between African-American (AA) and white American (WA) men undergoing radical prostatectomy (RP), as AA men are twice as likely to die from prostate cancer than their white counterparts. PATIENTS AND METHODS: We established a cohort of 1058 patients (402 AA, 646 WA) who had RP and were followed for PSA recurrence. Age, race, serum PSA, biopsy Gleason score, clinical stage, pathological stage, and PSA recurrence data were available for the cohort. The chi-square test of proportions and t-tests were used to assess basic associations with race, and log-rank tests and Cox regression models for time to PSA recurrence. Forward stepwise variable selection was used to assess the effect on the risk of PSA recurrence for race, adjusted by the other variables added one at a time. RESULTS: The AA men had higher baseline PSA levels, more high-grade prostatic intraepithelial neoplasia (HGPIN) in the biopsy, and more HGPIN in the pathology specimen than WA men. The AA men also had a shorter mean (sd) PSA doubling time before RP, at 4.2 (4.7) vs 5.2 (5.9) years. However, race was not an independent predictor of PSA recurrence (P = 0.225). Important predictors for PSA recurrence in a multivariable model were biopsy HGPIN (P < 0.014), unilateral vs bilateral cancer (P < 0.006), pathology Gleason score and positive margin status (both P < 0.001). CONCLUSIONS: This study indicates that while there are racial differences in baseline serum PSA and incidence of HGPIN, race is not an independent risk factor for PSA recurrence. Rather, other variables such as pathology Gleason score, bilateral cancers, HGPIN and margin positivity are independently associated with PSA recurrence. The PSA doubling time after recurrence may also be important, leading to the increased mortality of AA men with prostate cancer.

Black or African American↗

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↗

PubMed2005

The effect of percentage free prostate-specific antigen (PSA) level on the prostate cancer detection rate in a screening population with low PSA levels.

OBJECTIVE: To evaluate the prostate cancer detection rate at low total prostate-specific antigen (tPSA) ranges of 2.6-4 and 4.1-10 ng/mL, according to different percentage free (f/t) PSA levels in a screening population. SUBJECTS AND METHODS: In all, 1809 consecutive screening volunteers with a tPSA level of 2.6-10.0 ng/mL were assessed. Ten systematic ultrasonography-guided prostate biopsies and, since 2000, an additional five Doppler-enhanced targeted biopsies were taken on the basis of age-specific tPSA reference ranges. We analysed the detection rate of prostate cancer according to f/tPSA ranges of 0-9%, 10-14%, 15-18% and >18%. RESULTS: The detection rates for the subgroups with tPSA levels of 2.6-4.0 and 4.1-10.0 ng/mL were 20.2% and 27.0%, respectively. The cancer detection rate in the first group (2.6-4.0 ng/mL) at 0-10% fPSA was 22.9%, and that in the second group (4.1-10.0 ng/mL) at 0-10% was 36.9%. There were significant differences between these groups. If the f/tPSA was 10-15%, the cancer detection rate for the two groups were 22.6% and 32.5%, respectively (P < 0.05). There was no statistically significant difference in the cancer detecting rates at an f/tPSA of 15-18% or >18%. CONCLUSION: There is a statistically significantly higher cancer detection rate when the f/tPSA is <15% than in groups of men with a f/tPSA of >15% in screening population assessed primarily using tPSA level.

Adult↗

PubMed2005

Giant cystine stone in an infant bladder with no evidence of cystinuria--valence of possible pathomechanisms.

Bladder calculi account for approximately 5% of all urinary calculi. Children are at high risk in endemic areas whereas otherwise the entity is rare. Diet, voiding dysfunction and uncorrected anatomical abnormalities predispose to bladder stone formation. We report the case of a 2-year-old girl with a giant cystine bladder stone without relevant cystinuria and a small left kidney. Suprapubic cystolithotomy was performed for stone removal. We discuss possible associations of cystine calculi with unilateral genitourinary pathologies in the absence of persistent excess cystinuria.

Child, Preschool↗

PubMed2005

Generation of clinical-grade monocyte-derived dendritic cells using the CliniMACS system.

We describe the generation of monocyte-derived dendritic cells (MoDC) from leukapheresis products using the CliniMACS system from Miltenyi Biotec. In a clinical setting, the method turned out to be feasible for the generation of clinical-grade MoDC from patients with metastatic renal-cell carcinoma. MoDC generated with this system exhibited a fully mature phenotype as well as high migratory and T-cell stimulatory capacity.

Cell Differentiation↗

PubMed2005

Targeting the androgen receptor in hormone-refractory prostate cancer--new concepts.

The androgen receptor (AR) plays a key regulatory role in hormone-naive, as well as in advanced, therapy-resistant prostate cancer. Therefore, the development of novel treatment strategies using new means for targeting AR function in prostate tumors aims at providing better options for control of progression and progressive disease. This review summarizes recent attempts in this field with a critical view on their clinical usefulness. In addition to classic endocrine therapy by surgical and/or chemical castration, there are concepts to inhibit the AR directly through anti-androgens, selective AR modulators, naturally occurring AR inhibitors, neutralizing antibodies and dominant-negative peptides. A unique possibility to prevent AR expression at the transcriptional level represents the use of antisense technology. The advantage of this method is that AR expression, and thus any aberrant route of its activation is prevented. Furthermore, there are several approaches by which AR signaling is inactivated indirectly. Degradation of heat-shock proteins, which direct appropriate AR protein folding, or modulation of various growth factor signaling cascades, which are thought to contribute to AR activation in the androgen-deprived patient, have been investigated.

Androgen Receptor Antagonists↗

PubMed2005

Gene therapy strategies in prostate cancer.

Androgen ablation is the choice of treatment for patients with advanced prostate cancer. Although untreated tumors are mostly androgen-dependent, hormone withdrawal is only palliative. The major problem in prostate cancer treatment represents the progression to androgen-independent growth during therapy, rendering current strategies inefficient. Thus, there is an urgent need to develop novel treatments to combat therapy-resistant prostate cancer. Intensive research strongly improved the knowledge about the molecular changes, which are believed to occur during prostate carcinogenesis and progression to androgen-independence. This in turn led to the identification of several interesting genes, which may be useful as targets for prostate cancer gene therapy. In fact, there is a broad range of different gene therapy approaches in the field of prostate cancer, some of which have already progressed to clinical evaluation in patients. Promising data and best benefit for patients currently provide studies where gene therapy strategies are combined with conventional treatments like chemotherapy or radiation. In this review we will give an overview of several interesting gene therapy concepts and delivery systems in prostate cancer and discuss their usefulness in the clinic.

Animals↗

PubMed2005

Molecular effects of the isoflavonoid genistein in prostate cancer.

Differences in diet have been proposed to be at least partially responsible for the low rate of prostate cancer in Asian populations compared with men in Western countries. One of the compounds that occurs in a greater quantity in the Eastern diet is genistein, an isoflavonoid found in high concentrations in serum after ingestion of soy-rich foods. Extensive molecular studies have been performed to determine its potential health benefits. The mechanism of action of genistein is complex and includes several cellular pathways. In addition to its estrogenic and/or antiestrogenic activities, genistein has been reported to inhibit steroidogenesis and block several protein tyrosine kinases, including epidermal growth factor receptor and src tyrosine kinases. Moreover, it arrests the cell cycle, induces apoptosis, and has antiangiogenic and antimetastatic properties and antioxidant activity. Herein, we review the current literature on the molecular mechanisms of genistein in relation to its effects on prostate cancer cells.

Animals↗

PubMed2005

Screening for prostate cancer: updated experience from the Tyrol study.

OBJECTIVES: The aim of this study was to monitor the impact of prostate cancer screening in a natural experiment by comparing prostate cancer mortality in Tyrol, Austria, where prostate-specific antigen (PSA) testing was made available at no charge, with the rest of Austria, where this screening was not introduced. METHODS: In 1993, PSA testing was made freely available to men aged 40 to 79 years old living in the Federal State of Tyrol, Austria. In the first 10 years of this study, at least 70% of all men in this age range had PSA tests done at least once. Initially, only total PSA was measured, but free PSA measurement was added in 1995, and complexed PSA was added in 2001. Digital rectal examination (DRE) was not part of the screening examination. RESULTS: Significant migration to lower clinical as well as pathological prostate cancer stages has been observed in patients undergoing radical prostatectomy since the introduction of this screening program. A reduction in mortality rates from prostate cancer in Austria occurred from 1993 onward, with a much greater reduction in Tyrol; mortality remained fairly constant between 1993 and 1995 and subsequently fell. From 1993 to 2000 (the most recent data), there was a significantly greater decrease in the rate of prostate cancer mortality in Tyrol compared to the rest of Austria (P value = 0.006). Based on age-specific death rates for men aged 40 to 79, the difference between the number of expected and observed deaths from prostate cancer in Tyrol was 22 in 1998 (a 42% decrease), 18 in 1999 (a 33% decrease) and 25 in 2000 (a 44% decrease). CONCLUSIONS: These findings are consistent with the hypothesis that a policy of making PSA testing freely available, and wide acceptance by men in the population, is associated with a reduction in prostate cancer mortality in an area in which urology services and radiotherapy are available freely to all patients. It is our opinion that most of this decline in mortality is likely to be due to aggressive downstaging and successful treatment and that any contribution from detecting and treating early cancers will only become apparent in the years to come.

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

Allogeneic dendritic cell vaccination against metastatic renal cell carcinoma with or without cyclophosphamide.

In this phase I/II study, we evaluated the feasibility, safety and efficacy of allogeneic dendritic cells (DCs) with or without cyclophosphamide in the treatment of patients with metastatic renal cell carcinoma (RCC). Immunomagnetic beads were used to isolate CD14(+) monocytes from healthy donor leukapheresis products, and CD83(+) antigen-pulsed monocyte-derived DCs (moDCs) loaded with tumor lysate and keyhole limpet hemocyanin (KLH) were generated. Twelve patients were treated with allogeneic moDCs alone, while ten patients also received cyclophosphamide on days 4 and 3 prior to vaccination. Of the 22 patients enrolled, 20 received full treatment consisting of at least three vaccinations at monthly intervals. Two mixed responses with substantial tumor regression were observed. In 3 patients, disease stabilization occurred, in 13 patients disease progressed and 4 patients were lost to follow-up. Overall, immune responses against KLH and tumor lysate were weak or absent; however, the strongest increases in antigen-independent and KLH-specific responses were observed in the 2 patients with mixed responses. In addition, 1 of them showed a substantial increase in oncofetal antigen (OFA)-specific IFN-gamma production. Importantly, the 2 mixed responders and 1 patient with stable disease belonged to the cyclophosphamide group. Median overall survival in the cyclophosphamide group was 23.2 and 20.3 months in the group that received allogeneic moDCs alone. Allogeneic immunotherapy with moDCs is feasible and well tolerated. However, the immunogenicity of allogeneic moDCs is clearly less pronounced than that of autologous moDC immunotherapy. Cyclophosphamide may have the capacity to augment DC-induced antitumor immunity.

Adult↗

PubMed2004

Dendritic-cell activation by secretory phospholipase A2.

Dendritic cells (DCs), also referred to as the sentinels of the immune system, induce and coordinate important functions of immune surveillance. DCs acquire immunity-initiating capacity only after a process of maturation usually induced by ligands that bind to members of the tumor necrosis factor (TNF) or toll-like receptor families. Secretory phospholipase A2 (sPLA2), which hydrolyzes the sn-2 ester bond of glycerophospholipids, regulates a variety of cellular functions including migration of endothelial cells and neurite outgrowth. In the present study we investigated the role of sPLA2 in DC biology. We report that human monocyte-derived DC cultures lack sPLA2 activity but respond to exogenous sPLA2. sPLA2 alone and in cooperation with TNF-alpha and interleukin 1 beta (IL-1beta) induced fatty acid release from DC membranes, which was accompanied by upregulation of surface markers and by an increase in the migratory and immunostimulatory capacity of the DCs. Our findings indicate that secreted enzymes such as sPLA2 can contribute to DC maturation and emphasize the role of lipid mediators in the regulation of immune responses. This observation may also have implications for DC-based vaccine development.

Animals↗

PubMed2004

High-flow priapism: colour-Doppler ultrasound-guided supraselective embolization therapy.

High flow priapism is mainly caused by traumatic arteriocavernous fistulas. The standard therapy is a transcatheter embolization of the fistula. This study analyzes the combined approach of arteriography and color Doppler ultrasound during the embolization procedure. During the arteriography procedure, a perineal color Doppler ultrasound examination of the fistula was performed to achieve an optimal positioning of the catheter tip in the fistula with a minimum of radiation exposure. To visualize the correct localization, ultrasound contrast medium or saline solution was injected through the catheter. The flow-pattern of the contrast medium allowed evaluation of the successful occlusion of the fistula and preservation of the unaffected penile arteries. In six patients (unilateral fistula: three, bilateral fistulas: three) with a posttraumatic high-flow priapism, this technique was performed for embolization of the fistulas. A total of nine embolization sessions were performed. Only one case required a second session due to dislocation of a microcoil. In all cases, the priapism disappeared immediately after the final session while erectile function was restored within 4 weeks after embolization. The combined approach of x-ray and ultrasound imaging facilitates the supraselective embolization of the arteriocavernous fistula, leading to an optimal success rate, while reducing the radiation exposure and the applied dose of contrast medium.

Embolization, Therapeutic↗

PubMed2004

Prostate cancer cells generated during intermittent androgen ablation acquire a growth advantage and exhibit changes in epidermal growth factor receptor expression.

BACKGROUND: Intermittent androgen ablation is a palliative treatment option for advanced prostate cancer which is associated with less side effects, improved quality of life of patients, and reduced costs. Regulation of growth and survival of prostate cancer cells during intermittent androgen withdrawal has not been studied in appropriate models yet. METHODS: Two cycles of androgen withdrawal and supplementation were performed in human prostate cancer cells LNCaP in vitro. Proliferation of prostate cancer cell sublines established after intermittent androgen withdrawal was assessed in the absence or presence of epidermal growth factor (EGF) by protein determination. Cell cycle was analyzed with a flow cytometer. EGF was measured in the supernatants of LNCaP sublines with a commercial ELISA. EGF receptor mRNA and protein were determined by real-time PCR and Western blot, respectively. RESULTS: Basal proliferation rate of all newly generated LNCaP sublines increased over that of the parental LNCaP cell line. The highest stimulation of proliferation by exogenous EGF was observed in parental LNCaP cells. In each LNCaP derivative established during intermittent androgen withdrawal, the percentage of cells in the S phase of cell cycle was higher than that in parental LNCaP cells. EGF levels did not increase during intermittent androgen ablation. The expression of EGF receptor protein decreased following each cycle of androgen ablation and increased subsequently after androgen supplementation. EGF receptor (EGFR) mRNA was regulated in a similar manner in LNCaP derivatives established during the second cycle of intermittent withdrawal. CONCLUSIONS: Changes in the expression of the EGF receptor occur during intermittent androgen ablation but they cannot be solely responsible for increased basal proliferation. Alternatively, other ligands and receptors of the EGF system may become overexpressed during prolonged withdrawal and supplementation of androgenic hormones in prostate cancer therapy.

Androgen Antagonists↗

PubMed2004

Genetic aberrations in prostate carcinoma detected by comparative genomic hybridization and microsatellite analysis: association with progression and angiogenesis.

BACKGROUND: In spite of increasing knowledge about the tumor biology of prostate cancer (PC), molecular events involved in tumor progression are not well characterized. There is evidence that a number of genetic alterations play a role in tumor progression and in addition, angiogenesis also contributes. In this study, comparative genomic hybridization (CGH), a sensitive method for detecting regional DNA copy number abnormalities, and microsatellite analysis was used to identify frequent genome changes in PC. Correlation of these data with microvessel density (MVD) and clinical follow-up data was performed to determine genetic alterations that are associated with angiogenesis and subsequent tumor progression. METHODS: Fifty-seven paraffin embedded radical prostatectomy (RP) specimens were microdissected. DNA from the microdissected PC tissue was amplified by degenerate oligonucleoitide primed (DOP)-polymerase chain reaction (PCR), and CGH was performed on the PCR product. Quantitative analyses of the CGH profiles were performed using a t-statistic. Additionally, a microsatellite analysis of chromosome 13q was performed on a subgroup of 31 of the tumors. Using a polyclonal antibody against factor VIII, MVD was determined for all RP specimens. The results of CGH and microsatellite analysis were correlated with the clinical data of the patients and with MVD. RESULTS: Forty-two of the tumors (75%) showed one or more gains while 39 (70%) showed one or more losses per tumor. The most frequent DNA copy number gains were on chromosome 3, 4, 7, 8, 10, 11, 12, 13, and X. The most frequent losses were on chromosomes 2, 5, 6, 8, 10, 13, 15, and 16. Cancer recurrence occurred in 15 patients. The total number of DNA copy number losses was significantly higher in patients with this progression (86%) than without (52%) (P < 0.001). There was no significant difference in the number of gains in patients with or without progression. Contingency table analysis showed a significant correlation between progression and losses in regions of chromosomes 6q and 13q and a gain of chromosome 7q. In multivariate analysis, only loss of chromosome 6 was independently prognostic. The gains that correlated most closely with MVD > 35 were on chromosomes 2q, 7q, and Xq, while the losses most closely associated with MVD > 35 were on chromosomes 8q, 10q, and 13q. However, only the association between loss of chromosome 13q and MVD > 35 was statistically significant. Microsatellite analysis revealed a statistically significant correlation between MVD and instability of locus 171. CONCLUSIONS: This study indicates that the frequency of genetic alterations in PC as detected by CGH correlates with clinical outcome, and that losses of DNA from chromosomes 6q and 13q are important events that correlate with tumor progression, with loss of 13q, especially instability of locus 171, also associated with angiogenesis.

Chromosome Aberrations↗

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↗

PubMed2004

Long-term androgen-ablation causes increased resistance to PI3K/Akt pathway inhibition in prostate cancer cells.

BACKGROUND: In advanced stages of prostate cancer, the phosphatidylinositol-3' kinase (PI3K)/Akt signaling cascade, one of the major survival pathways in the cell, is frequently constitutively activated due to mutation or loss of the tumor suppressor protein phosphatase and tensin homolog deleted on chromosome 10 (PTEN). Using cell culture models representing different tumor stages, we explored the effect of inhibition of this survival pathway on the induction of apoptosis. METHODS: Inhibition of the survival kinase Akt and induction of apoptosis was analyzed in androgen-insensitive DU145 and PC-3 cells, in androgen-responsive LNCaP, and in androgen-independent long-term androgen-ablated LNCaP-abl cells representing therapy-resistant prostate cancer cells. Activated Akt was determined by immunoblotting using a phospho-Akt specific antibody. Induction of apoptosis was analyzed employing annexing V and propidium iodide staining and flow cytometry and measurement of cleavage of the caspases substrate poly-ADP-ribose polymerase (PARP). RESULTS: IGF-1, EGF, and heregulin but not PDGF or activators of protein kinase A induced phosphorylation of Akt in DU145 cells and activation was completely blocked by the PI3K inhibitor LY294002. In the hormone-responsive prostate cancer cell line LNCaP that has a constitutively switched-on Akt kinase, LY294002 caused a dose- and time-dependent Akt inhibition, which was absent in long-term androgen-ablated LNCaP sublines. In agreement with the resistance to inhibition of the PI3K/Akt pathway, long-term androgen-ablated LNCaP sublines remained relatively resistant to induction of cell death by LY294002 or the cytotoxic drug etoposide. Inhibition of the PI3K/Akt pathway restored the sensitivity of long-term androgen-ablated cells to induction of apoptosis by a cytotoxic drug almost completely. CONCLUSION: These results suggest that long-term androgen ablation therapy for prostate cancer reinforces the PI3K/Akt pathway and impedes its inhibition thus contributing to increased resistance of tumor cells to induction of apoptosis. With regard to treatment of therapy-refractory prostate cancer, these findings suggest effectiveness of a combination of cytotoxic treatment and inhibition of the PI3K-Akt survival pathway in tumor cells after failure of androgen-ablation therapy.

Androgen Antagonists↗

PubMed2004

Membrane properties of single muscle cells of the rhabdosphincter of the male urethra.

BACKGROUND: The electrophysiological properties of myoblast cultures established from the human and porcine rhabdosphincter (RS) and porcine lower limb muscle (LLSKM) were studied to elucidate their potential for tissue engineering applications in the lower urinary tract. METHODS: Muscle biopsies were collected from the prostatic part of the RS, the RS of male pigs, and the porcine LLSKM. Ion channels were studied by means of the patch-clamp technique. RESULTS: Only one subtype each of voltage gated Na+ and Ca2+ channels was observed in porcine RS and LLSKM. Two types of voltage gated Ca2+ channels were identified in human RS cells. The porcine RS and LLSKM myoblasts displayed similar fusion competence. CONCLUSIONS: Porcine RS and LLSKM myoblasts and human RS and human skeletal muscle cells show a high degree of similarity. Injection of autologous skeletal muscle myoboblasts in the lower urinary tract might, therefore, represent a promising approach to treat stress incontinence after radical prostatectomy.

Animals↗