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Georg Bartsch

Publications and source records attributed to Georg Bartsch.

At least 55 records · Page 3Linked to original sources
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↗
PubMed2006

Dynamic transurethral sonography and 3-dimensional reconstruction of the rhabdosphincter and urethra: initial experience in continent and incontinent women.

OBJECTIVE: The purpose of this study was to evaluate the female urethra and the striated urinary sphincter, the rhabdosphincter (RS), by means of dynamic transurethral sonography and sonographic 3-dimensional (3D) reconstructions. METHODS: In 15 female patients with urinary stress incontinence (mean age, 67.5 years) and 5 continent women (mean age, 48.3 years), morphologic characteristics and function of the RS and urethra were examined with a 10-MHz transurethral ultrasound transducer. With the help of a mechanical pullback system, the transducer was slowly retracted to scan the whole urethra and the RS from the bladder neck to the urethral orifice. Subsequently, 3D reconstructions of the urethra using an integrated computer system were performed. The RS as well as the length of the urethra were investigated under contracted and noncontracted conditions to measure contractility of the RS and dynamic changes of the lower urinary tract. RESULTS: Partial or complete loss of RS function was detected in patients with stress incontinence. The findings on sonography were found to correlate well with the grade of incontinence. Furthermore, under contraction of the RS, a median increase in urethral length was observed. In incontinent patients, the increase in the urethral length was statistically significantly less (P = .04), which was related to the reduced contractility of the RS. CONCLUSIONS: Dynamic transurethral sonography with subsequent 3D reconstructions allows for assessment of function and morphologic characteristics of the RS and urethra. Normal contraction of the RS results in an elongation of the urethra.

Adolescent↗
PubMed2006

Akacid-medical-formulation, a novel biocidal oligoguanidine with antitumor activity reduces S-phase in prostate cancer cell lines through the Erk 1/2 mitogen-activated protein kinase pathway.

Oligomeric guanidines are highly efficient biocides against a broad spectrum of microorganisms. However, their antitumor effects have not been studied so far. We investigated an antiproliferative effect of Akacid-medical-formulation (AMF), a member of the oligoguanidine family of biocides, against solid cancer cell lines and primary cells by measuring [3H]-thymidine incorporation. Additionally, we examined cell cycle distribution in two AMF-sensitive prostate cancer cell lines (DU-145, LNCaP) using flow cytometry. Finally, the influence of AMF on cell cycle regulatory molecules and intracellular kinase cascade-related signaling molecules was assessed. We found that AMF has variable antiproliferative effects on all tested cells. In DU-145 and LNCaP cells, flow cytometric studies showed a reduction of S-phase with a maximum extent of 24 and 58%, respectively. This was associated with a decrease in expression of cyclin D1, cyclin-dependent kinases 2 and 4, while having varying effects on expression of cyclin E and p27. Additionally, reduced phosphorylation of Erk1 and Erk2 was found, whereas expression of phospho-Akt1 remained unchanged. Herein we report for the first time that AMF exerts potent antiproliferative activity against various malignant cell lines, including those of prostate. We therefore recommend further investigation of the anticancer activity of this biocidal oliguanidine.

Antineoplastic Agents↗
PubMed2005

Effect of a pT0 cystectomy specimen without neoadjuvant therapy on survival.

BACKGROUND: In some cases of radical cystectomy for bladder cancer, no residual tumor is found in the cystectomy specimen (the pT0 classification). The aim of this study was to evaluate the outcome of such patients in a large cystectomy series. METHODS: All 900 patients with radical cystectomy and pelvic lymphadenectomy for TCC of the bladder in the period January 1986 to September 2003 who received no neoadjuvant therapy were included. Cystectomy specimens from 181 (20.1%) patients were graded as pT0. Complete follow-up was obtained in all cases. Tumor-specific survival (pT0 vs. pT+) was calculated with the Kaplan-Meier method and compared with the log-rank test. RESULTS: The rate of lymph node metastases in the pT0 group was 6.6%. pT0 status was found with Ta/is/1 in 36.8%, T2a in 41.8%, and T2b in 10.9%. The 169 patients with pT0pN0 tumors had 10-year tumor-specific survival rates of 91.0. There was no statistically significant survival benefit for pT0pN0 tumors compared with pT+pN0 tumors for maximal tumor classifications of pTa/pTis/pT1 and pT2b, but patients with a pT0T2apN0 tumor had a statistically significantly better tumor-specific survival than those with a pT2apN0 tumor (P = 0.002). No patient with a pT0pN0 tumor had a local recurrence. The rate of incidental second primary malignancies in a specimen was 15.5%. CONCLUSIONS: A pT0pN0 cystectomy specimen indicates a curative therapy, but there is a substantial risk of tumor recurrence. In the group of tumors with a maximal classification of pT2a, the pT0 tumors constitute a subgroup with a significantly higher likelihood of survival.

Combined Modality Therapy↗
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

Small G-protein RhoE is underexpressed in prostate cancer and induces cell cycle arrest and apoptosis.

BACKGROUND: RhoE/Rnd3, a recently described novel member of the Rho GTPases family, was discussed as a possible antagonist of the RhoA protein that stimulates cell cycle progression and is overexpressed and/or overactivated in prostate cancer. We investigated the expression of RhoE and its role in cell cycle regulation and apoptosis in the human prostate. METHODS: RhoE expression in cell lines and tissue specimens was assessed by immunoblot analysis, real-time PCR (RT-PCR), and immunohistochemistry. To elucidate RhoE effects on the prostate, RhoE was cloned and overexpressed in DU-145 prostate cancer. Cell cycle modulation and apoptosis was investigated by immunoblot and FACS analysis. RESULTS: Immunoblot analysis showed a strong RhoE signal in both, benign epithelial and stromal cells. In contrast, almost no protein was detected in various prostate cancer cells. On RT-PCR and microarray analysis, RhoE mRNA expression was significantly reduced in malignant tissue when compared to benign samples. RhoE immunostaining was strong in benign tissue, especially in prostate epithelial cells, whereas it was minimal or absent in malignant tissue. Forced RhoE overexpression in a prostate cancer cell line inhibits the expression of two proteins essential for G2/M transition, namely CDC2 and cyclin B1, and induces G2/M arrest. In addition, apoptotic cell death as measured by a cleavage product of caspase 3 is significantly increased in RhoE-overexpressing cells. CONCLUSION: In conclusion, our findings suggest RhoE as a tumor suppressor gene that is downregulated early in the development of prostate cancer.

Apoptosis↗
PubMed2005

Are transition zone biopsies still necessary to improve prostate cancer detection? Results from the tyrol screening project.

OBJECTIVES: The present retrospective study was designed to investigate the value of transition zone (TZ) biopsies for prostate cancer (PC) detection rate in a combined contrast enhanced color Doppler targeted (CECD) and gray-scale systematic biopsy (SB) approach. METHODS: PSA screening participants totalling 1475 with tPSA of >1.25 ng/ml (fPSA< or =18%) were assessed. Ten SB and additionally 5 or fewer CECD were performed. The impact of TZ biopsies on the PC detection rate and the biological significance of the detected TZ-cancers were analyzed. RESULTS: Out of 1475 biopsied patients, 395 (26.8%) were identified as PC patients; 5925 biopsy cores from these patients were analyzed. In 86 patients (21.8% of PC), we found 102 PC- positive cores in the TZ, and only in 9 of them solitary TZ-cancers without any other PC-location (2.3% of PC or 0.6% of all investigated patients). Pathologic findings after retropubic prostatectomy (RPE) revealed multifocal adenocarcinoma including involved peripheral zone (PZ) in eight of these nine patients, and solitary TZ-cancer in one patient. There was no positive correlation between prostate volume and TZ-detection rate and no patient with solitary TZ-PC after rebiopsy. CONCLUSION: Biopsy revealed 9 solitary TZ cancers (1.8%) and RPE revealed only one of them to be truly TZ-confined cancer (0.6%). Furthermore PC-detection did not improve, even in patients with rebiopsy, and there was no correlation between detection of TZ-cancers and prostate volume. A combined use of CECD and SB to investigate participants of a PSA-screening program suggests that TZ-biopsies do not improve PC detection rate and are therefore unnecessary.

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

Up-regulation of functional chemokine receptor CCR3 in human renal cell carcinoma.

There is increasing evidence that chemokines and chemokine receptors are causally involved in tumorigenesis by facilitating tumor proliferation and metastasis. Little is known about the possible function of chemokine receptors in the development and progression of renal cell carcinoma (RCC). We, therefore, analyzed the expression of chemokine receptors in tumor specimens and adjacent healthy kidney tissues [normal kidney cell (NKC)] from 10 RCC patients. We also characterized the permanent RCC cell line A-498. CCR6, CXCR2, and CXCR3 were consistently expressed by both malignant cells and NKCs. A-498 displayed additional expression of CXCR4. Importantly, the expression of CCR3 was almost absent on NKCs but clearly enhanced in a substantial proportion of RCC specimens. The primary CCR3 ligand, eotaxin-1/CCL11, induced intracellular Ca2+ mobilization, receptor internalization, and proliferation in A-498 cells confirming signaling competence of RCC-associated CCR3. In addition, we screened tumor tissue sections of 219 patients and found that 28% (62 of 219) expressed the CCR3 receptor. The presence of CCR3 in tumor samples seemed to correlate with the grade of malignancy. Previous work has established that eotaxin-1 expression is induced by tumor necrosis factor-alpha, a cytokine known to be present in RCC tissue. Our data, therefore, supports a scenario in which eotaxin-1 as part of tumor-associated inflammation promotes progression and dissemination of CCR3-positive RCC.

Biological Transport↗
PubMed2005

Fetal development of striated and smooth muscle sphincters of the male urethra from a common primordium and modifications due to the development of the prostate: an anatomic and histologic study.

BACKGROUND: The aim of the study was to investigate the development of the human urethral sphincter complex during fetal development. METHODS: 23 human male fetal specimens were investigated. The histological sections were processed according to the epoxy resin-based plastination technology. RESULTS: At 9th week of gestation, a combined sphincteric primordium of the rhabdosphincter and the lissosphincter is situated at the anterior and lateral aspects of the membranous and prostatic urethra. Both muscular components assume an omega-shaped configuration due to the presence of a constant connective tissue raphe posterior to the urethra that anchors the rhabdosphincter in the perineal body. Development of the prostate laterally and posteriorly does not modify the growth of the urethral sphincter complex anteriorly but inhibits its development laterally and posteriorly. CONCLUSIONS: The important morphological characteristics of the male adult rhabdosphincter and lissosphincter can be seen very early in fetal development.

Fetal Development↗
PubMed2005

Ability of PSA-positive circulating macrophages to detect prostate cancer.

BACKGROUND: Prostate-specific antigen (PSA) is a widely used serum marker for prostate cancer, but has a poor specificity for early detection at levels below 10 ng/ml, because it can also result from benign conditions. Our aim was to determine the frequencies of circulating PSA+ macrophages in a blinded study and to examine the suitability of this new method for differentiating between benign and malignant prostate disease. METHODS: Between October 2002 and February 2003, 126 patients undergoing transrectal biopsy were enrolled in this study. Peripheral blood macrophages were stained for intracellular content of PSA in all patients. Ten patients' peripheral blood mononulear cells (PBMCs) were also supplementarily stained for cytokeratin (CK) and epithelial membrane antigen (EMA). Macrophages were analysed by flow cytometry. Patients were grouped according to their biopsy histology and bone scan results. FINDINGS: Based on histological data, patients were classified as having no evidence of malignancy (NEM) (n = 59), prostatitis (n = 20), or localised prostate cancer (n = 37). Significantly higher levels of circulating PSA+ macrophages were found in prostate cancer compared to benign conditions. Calculating a 2% cut-off level enabled the detection of localised prostate cancer with 89% sensitivity and 80% specificity. In a subset of patients (65%) with a serum PSA below 4 ng/ml and confirmed prostate cancer, the percentage of PSA+ macrophages was significantly higher compared to NEM and prostatitis. Macrophages of ten patients tested with prostate cancer contained significantly higher amounts of PSA, EMA, and CK compared to ten with NEM. INTERPRETATION: Intracellular PSA in combination with CK and EMA can be found in permeabilized blood macrophages, indicating phagocytosis of complete cancer cells. This study further suggests, that this new method might be suitable for differentiating between prostate cancer and benign conditions especially in patients with low serum PSA.

Aged↗
PubMed2005

Access of tumor-derived macromolecules and cells to the blood: an electron microscopical study of structural barriers in microvessel clusters in highly malignant primary prostate carcinomas.

BACKGROUND: The neo-angiogenetic microvessels forming a major reactive stromal element in highly malignant prostate neoplasms may exhibit fine-structural features relevant to our understanding of the passage of macromolecules from tumor to blood, on the one hand, and of events facilitating the metastatic cascade, on the other hand. METHODS: Ensuring rapid, optimal fixation in buffered glutaraldehyde was a foremost concern. Thin parings from radical prostatectomy specimens of Gleason scores (GS) 5-9 were taken from the tumor and from the contralateral side of the gland, glutaraldehyde-fixed, diced to smaller than 1 mm(3), postfixed in osmium tetroxide, embedded in Epon, ultrathin-sectioned, contrasted with lead and uranyl salts, and viewed in a transmission electron microscope. RESULTS: In dysplastic tissue areas, intraductal microvessels located in gland ducts were occasionally observed, and found to be aggressively invasive and highly active in producing neo-angiogenetic sprouts. Closely spaced microvessel clusters contained almost exclusively neo-angiogenetic microvessels, which were in cell-cell contact with numerous ameboid migratory cells, some of which were likely to be tumor cells. In these microvessel clusters, all structural barriers hindering passage of tumor-derived molecules or cells to the blood were eliminated. CONCLUSION: In microvessel clusters, the ultrastructural equivalent of microvascular hotspots, tumor invasion of microvessels is facilitated, but equally microvessels are observed invading the gland duct epithelial walls. This reciprocal invasivity of tumor cells and microvascular endothelial cells generates ideal conditions for tumor products and metastatic cells to enter the blood.

Aged↗
PubMed2005

Cancer of the prostate.

Prostate carcinoma, with about 190,000 new cases occurring each year (15% of all cancers in men), is the most frequent cancer among men in northern and western Europe. Causes of the disease are essentially unknown, although hormonal factors are involved, and diet may exert an indirect influence; some genes, potentially involved in hereditary prostate cancer (HPC) have been identified. A suspect of prostate cancer may derive from elevated serum prostate-specific antigen (PSA) values and/or a suspicious digital rectal examination (DRE) finding. For a definitive diagnosis, however, a positive prostate biopsy is requested. Treatment strategy is defined according to initial PSA stage, and grade of the disease and age and general conditions of the patient. In localized disease, watchful waiting is indicated as primary option in patients with well or moderately differentiated tumours and a life expectancy <10 years, while radical prostatectomy and radiotherapy (with or without hormone-therapy) could be appropriate choices in the remaining cases. Hormone-therapy is the treatment of choice, combined with radiotherapy, for locally advanced or bulky disease and is effective, but not curative, in 80-85% of the cases of advanced disease. Patients who develop a hormone-refractory prostate cancer disease (HRPC) have to be evaluated for chemotherapy because of the recent demonstration of improved overall survival (2-2.5 months) and quality of life with docetaxel in more than 1,600 cases.

Antineoplastic Protocols↗
PubMed2005

Are repeat biopsies required in men with PSA levels < or =4 ng/ml? A Multiinstitutional Prospective European Study.

OBJECTIVES: Pathological and biochemical features of prostate cancers detected on repeat biopsies in men with total PSA level between 2.0 and 4 ng/ml were evaluated and compared to those cancers detected on first biopsy. METHODS: 315 men with PSA level between 2.0 and 4 ng/ml underwent transrectal ultrasound guided sextant biopsy and two additional transition zone biopsies (Octant Biopsy). All subjects whose biopsy samples were negative for prostate cancer underwent a repeat biopsy after 6 weeks. Those with clinically localized cancers were offered surgery or radiation therapy. Pathological and clinical features of patients diagnosed with prostate cancer on initial and repeat biopsy were compared. RESULTS: Cancer detection rates on first and second biopsy were 24% (75/315) and 13% (29/224), respectively. Overall, of patients with clinically localized disease (83% of cancers detected), 87% underwent radical prostatectomy, 11% opted for radiation therapy and 2% opted for watchful waiting. Cancers found in the first biopsy group were more multifocal (p = 0.01) while cancers found on second biopsy were more located in the apical-dorsal region (p = 0.003). No significant differences were noted with respect to extracapsular extension, seminal vesical invasion, positive margins, final pathological stage, Gleason score, percentage Gleason grade 4/5, serum PSA and patient age between first and second biopsy. CONCLUSIONS: With an octant biopsy regime, biochemical and pathological features of cancers detected on initial and repeat biopsy in the PSA range 2.0 to 4 ng/ml are comparable in terms of PSA, grade, stage and cancer volume suggesting identical cancer characteristics, thus advocating for a repeat prostate biopsy in case of a negative finding on initial biopsy.

Aged↗