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Biomedical subjects

Georg Bartsch

Publications and source records attributed to Georg Bartsch.

At least 19 recordsLinked to original sources
PubMed2007

Gain of chromosome X in prostatic atrophy detected by CGH and FISH analyses.

BACKGROUND: Focal atrophy is presumed to be an indirect forerunner of prostate cancer. The aim of this study was to examine genetic alterations in prostate epithelia deriving from atrophic areas and compare these findings with those of cells deriving from paired prostate cancer in the same patient. METHODS: Formalin fixed paraffin wax-embedded prostatectomy specimens from 20 prostate cancer patients were utilized in this study. Comparative Genomic Hybridization (CGH) was performed on atrophic areas. To validate the CGH results, Fluorescence in Situ Hybridization (FISH) analysis was performed on atrophic areas and paired cancer tissue. RESULTS: Gain of the whole chromosome X was found as sole aberration in seven (70%) atrophic tissues by CGH. A gain of centromere X was observed in 13 (68.4%) atrophic areas and in 18 (90%) cancer tissues using FISH. CONCLUSIONS: Our investigation reconfirms the genetical instability of cells of the atrophic acini and attention of relevance of gain of chromosome X in atrophic areas.

Adult↗
PubMed2007

Isolation of amniotic stem cell lines with potential for therapy.

Stem cells capable of differentiating to multiple lineages may be valuable for therapy. We report the isolation of human and rodent amniotic fluid-derived stem (AFS) cells that express embryonic and adult stem cell markers. Undifferentiated AFS cells expand extensively without feeders, double in 36 h and are not tumorigenic. Lines maintained for over 250 population doublings retained long telomeres and a normal karyotype. AFS cells are broadly multipotent. Clonal human lines verified by retroviral marking were induced to differentiate into cell types representing each embryonic germ layer, including cells of adipogenic, osteogenic, myogenic, endothelial, neuronal and hepatic lineages. Examples of differentiated cells derived from human AFS cells and displaying specialized functions include neuronal lineage cells secreting the neurotransmitter L-glutamate or expressing G-protein-gated inwardly rectifying potassium channels, hepatic lineage cells producing urea, and osteogenic lineage cells forming tissue-engineered bone.

Amniotic Fluid↗
PubMed2007

Value of contrast-enhanced ultrasound and elastography in imaging of prostate cancer.

PURPOSE OF REVIEW: Prostate cancer is the most commonly diagnosed malignancy in men. Gray-scale ultrasound-guided systematic biopsy is the standard of care for prostate cancer detection in men with an elevated prostate-specific antigen or an abnormal digital rectal examination. Systematic biopsy may miss up to 35% of clinically relevant cancers. Color and power Doppler ultrasound, ultrasound contrast agents, and elastography have and will dramatically change the role of ultrasound in prostate cancer diagnosis. RECENT FINDINGS: Several reports have demonstrated that contrast-enhanced ultrasound investigations of the blood flow of the prostate allow for prostate cancer visualization and therefore, for targeted biopsies. Comparisons between systematic and contrast-enhanced ultrasound-targeted biopsies have shown that the targeted approach detects more cancers with a lower number of biopsy cores. Furthermore, contrast-enhanced ultrasound has been shown to detect cancers with higher Gleason scores compared with the systematic approach, which seems to improve prostate cancer grading. In addition, elastography is a new ultrasound technique that allows for the assessment of tissue elasticity. SUMMARY: Contrast-enhanced ultrasound and elastography improve prostate cancer detection and may be useful for prostate cancer grading and staging. Future clinical trials will be needed to determine the promise of these new advances for ultrasound of the prostate evolving into clinical applications.

Humans↗
PubMed2007

The association between local atherosclerosis and prostate cancer.

OBJECTIVE: To morphometrically compare local atherosclerotic changes in cancerous prostate with those in noncancerous prostate specimens, as epidemiological studies report a positive association between the prevalence of general atherosclerosis and prostate cancer. MATERIALS AND METHODS: The intima-to-media-ratio (IMR) of 538 prostate capsular tissue arteries was measured in 50 prostate cancer-positive and 29 prostate cancer-negative specimens (including 26 with benign prostatic hyperplasia and three with normal prostatic tissue). RESULTS: An IMR of >1 was significantly associated with prostate cancer and a greater risk of prostate cancer (odds ratio 2.28). The IMR was >1 in cancer-positive specimens about twice as often as in cancer-negative tissue. CONCLUSION: Local atherosclerosis (measured by the IMR) was more pronounced in prostate cancer-positive than in prostate cancer-negative specimens. The results support the view that men with local atherosclerotic lesions are at higher risk of prostate cancer.

Atherosclerosis↗
PubMed2007

Value of 3-dimensional transrectal/transvaginal sonography in diagnosis of distal ureteral calculi.

OBJECTIVE: In a prospective study, the feasibility of 3-dimensional (3D) transrectal/transvaginal sonography in comparison with transabdominal sonography and intravenous urography (IVU) in identifying distal ureteral calculi was evaluated. METHODS: Sixty-two patients in the urologic clinic with clinical suspicion of distal ureteral calculi were included. The patients consisted of 44 men and 18 women with a mean age +/- SD of 44 +/- 17 years. These patients underwent 3D transrectal/transvaginal sonography, transabdominal sonography with IVU, and, finally, ureterorenoscopy. RESULTS: Fifty-nine patients were confirmed to have distal ureteral calculi on the basis of urologic intervention (ureterorenoscopy). Three patients had a spontaneous stone passage immediately after imaging completion. The median size of the calculi was 3.7 +/- 2.00 mm. Transabdominal sonography detected 34 of the 62 patients with calculi (sensitivity, 55%). The median size of the calculi was calculated as 5.0 +/- 2.4 mm. The examination time was 6.5 +/- 2.7 minutes. Intravenous urography detected 44 of the 62 patients with ureterolithiasis (sensitivity, 71%). Herein, the median stone size was measured as 3.9 +/- 1.9 mm, and the examination time was 38 +/- 17 minutes. The combination of transabdominal sonography and IVU in visualization of ureterolithiasis raised the sensitivity to 81% (50 of 62 patients). Three-dimensional transrectal/transvaginal sonography showed ureterolithiasis in all 62 patients confirmed to have distal ureteral calculi (sensitivity and specificity, 100%). The median size of the calculi was calculated as 4.4 +/- 2.2 mm, and the examination took 1.9 +/- 0.6 minutes. CONCLUSIONS: The data in our prospective study show that transrectal/transvaginal sonography with 3D image assessment is superior to IVU and abdominal sonography for diagnosing distal ureteral calculi.

Adult↗
PubMed2006

Antigen-independent immune responses after dendritic cell vaccination.

The ability of cultured, antigen-loaded dendritic cells (DCs) to induce antigen-specific T cell immunity in vivo has previously been demonstrated and confirmed. Immune monitoring naturally focuses on immunity against vaccine antigens and may thus ignore other effects of DC vaccination. Here we therefore focused on antigen-independent responses induced by DC vaccination of renal cell carcinoma patients. In addition to the anticipated response against the vaccine antigen KLH, vaccination with CD83(+) monocyte-derived DCs resulted in a strong increase in the ex vivo proliferative and cytokine responses of PBMCs stimulated with LPS or BCG. In addition, LPS strongly enhanced the KLH-induced proliferative and cytokine response of PBMCs. Moreover, proliferative and cytokine responses of PBMCs stimulated with the homeostatic cytokines IL-7 and IL-15 were also clearly enhanced after DC vaccination. In contrast to LPS induced proliferation, which is well known to depend on monocytes, IL-7 induced proliferation was substantially enhanced after monocyte depletion indicating that monocytes limit IL-7 induced lymphocyte expansion. Our data indicate that DC vaccination leads to an increase in the ex vivo responsiveness of patient PBMCs consistent with a DC vaccination induced enhancement of T cell memory. Our findings also suggest that incorporation of bacterial components and homeostatic cytokines into immunotherapy protocols may be useful in order to enhance the efficacy of DC vaccination and that monocytes may limit DC vaccination induced immunity.

Cancer Vaccines↗
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

Microbubble-enhanced ultrasound to deliver an antisense oligodeoxynucleotide targeting the human androgen receptor into prostate tumours.

We have shown recently that downregulation of the androgen receptor (AR), one of the key players in prostate tumor cells, with short antisense oligodeoxynucleotides (ODNs) results in inhibition of prostate tumor growth. Particularly with regard to an application of these antisense drugs in vivo, we now investigated the usefulness of microbubble-enhanced ultrasound to deliver these ODNs into prostate cancer cells. Our short antisense AR ODNs were loaded onto the lipid surface of cationic gas-filled microbubbles by ion charge binding, and delivered into the cells by bursting the loaded microbubbles with ultrasound. In vitro experiments were initially performed to show that this kind of delivery system works in principle. In fact, transfection of prostate tumor cells with antisense AR ODNs using microbubble-enhanced ultrasound resulted in 49% transfected cells, associated with a decrease in AR expression compared to untreated controls. In vivo, uptake of a digoxigenin-labelled ODN was found in prostate tumour xenografts in nude mice following intratumoral or intravenous injection of loaded microbubbles and subsequent exposure of the tumour to ultrasound, respectively. Our results show that ultrasound seems to be the driving force of this delivery system. Uptake of the ODN was also observed in tumors after treatment with ultrasound alone, with only minor differences compared to the combined use of microbubbles and ultrasound.

Androgen Receptor Antagonists↗
PubMed2006

Growth curves of the fetal prostate based on three-dimensional reconstructions: a correlation with gestational age and maternal testosterone levels.

OBJECTIVE: To create a nomogram of the fetal growth of the human prostate corresponding to gestational age, and to investigate the relationship between the expansive growth of the fetal prostate and the maternal testosterone surge during pregnancy. MATERIALS AND METHODS: In all, 27 fetal prostates at 11-40 weeks of gestation, and seven neonatal specimens at 1-20 weeks after birth, were analysed. Serial sections of prostates were immunostained and examined using light microscopy. After modular image acquisition the volumes were calculated using three-dimensional reconstruction. The prostate volumes were correlated with gestational age, and related to reference testosterone levels during pregnancy. RESULTS: There was exponential growth of the fetal prostate with gestational age. The increasing volume of the prostate during the fetal period corresponded with maternal testosterone levels. In the second trimester there was a significant increase in prostate volume in relation to the bladder. In infants, macroscopically there was an inverse proportion between bladder size and prostate volume. CONCLUSIONS: Starting from the second trimester there is distinct growth of the fetal prostate, obviously triggered by the maternal testosterone surge. In neonates there is an inversion of the dimensions between bladder and prostate. These results indicating exponential growth of the fetal prostate provide evidence of a gender-related transient infravesical obstruction in human fetuses.

Female↗
PubMed2006

Three-dimensional ultrasonography of the urinary bladder: preliminary experience of assessment in patients with haematuria.

OBJECTIVE: To assess the value of three-dimensional (3D) vs two-dimensional (2D) ultrasonography (US) in the diagnostic evaluation of the urinary bladder in patients with haematuria. PATIENTS AND METHODS: In all, 42 patients with painless haematuria and/or irritative voiding symptoms were examined with 2D- and 3D-US. US was done with an Acuson Sequoia unit (Siemens Medical Sol. Mountain View, CA, USA) and the Perspective(R) 3D technique, to assess the presence of bladder lesions, including bladder cancer, bladder wall hypertrophy with trabeculation and diverticula, mucosal bladder folds or re-growth of the prostate mimicking a bladder tumour. The imaging findings were compared with cystoscopy and/or bladder biopsy. RESULTS: In 21 of the 42 patients (50%) cystoscopy with bladder biopsy revealed bladder cancer. Overall, 3D-US gave a correct diagnosis for 36 of 42 patients (86%). All 21 bladder cancers were correctly diagnosed, and 15 (71%) of the 21 benign bladder lesions were correctly identified. By contrast, 2D-US findings gave suspected bladder cancer in all patients. CONCLUSIONS: 3D-US is significantly more accurate than standard 2D-US in the diagnostic evaluation of patients with haematuria. Thus, this diagnostic technique might be useful for routine evaluation of the urinary bladder.

Aged↗
PubMed2006

Androgen axis in prostate cancer.

Endocrine therapy for advanced prostate cancer is based on androgen ablation or blockade of the androgen receptor (AR). AR action in prostate cancer has been investigated in a number of cell lines, their derivatives, and transgenic animals. AR expression is heterogenous in prostate cancer in vivo; it could be detected in most primary tumors and their metastases. However, some cells lack the AR because of epigenetic changes in the gene promoter. AR expression increases after chronic androgen ablation in vitro. In several xenografts, AR upregulation is the most consistent change identified during progression towards therapy resistance. In contrast, the AR pathway may be by-passed during chronic treatment with a nonsteroidal anti-androgen. AR sensitivity in prostate cancer increases as a result of activation of the Ras/mitogen-activated protein kinase pathway. One of the major difficulties in endocrine therapy for prostate cancer is acquisition of agonistic properties of AR antagonists observed in the presence of mutated AR. Enhancement of AR function by associated coactivator proteins has been extensively investigated. Cofactors SRC-1, RAC3, p300/CBP, TIF-2, and Tip60 are upregulated in advanced prostate cancer. Most studies on ligand-independent activation of the AR are focused on Her-2/neu and interleukin-6 (IL-6). On the basis of studies that showed overexpression and activation of the AR in advanced prostate cancer, it was suggested that novel therapies that reduce AR expression will provide a benefit to patients. There is experimental evidence showing that prostate tumor growth in vitro and in vivo is inhibited following administration of chemopreventive drugs or antisense oligonucleotides that downregulate AR mRNA and protein expression.

Androgen Antagonists↗
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

Bee venom secretory phospholipase A2 and phosphatidylinositol-homologues cooperatively disrupt membrane integrity, abrogate signal transduction and inhibit proliferation of renal cancer cells.

Bee venom secretory phospholipase A2 (bv-sPLA2) and phosphatidylinositol-(3,4)-bisphosphate (PtdIns(3,4)P2) act synergistically to induce cell death in tumour cells of various origins with concomitant stimulation of the immune system. Here, we investigated the mechanisms involved in such actions and examined structural requirements of PtdIns-homologues to inhibit tumour cells in combination with bv-sPLA2. Renal cancer cells were treated with bv-sPLA2 alone or in combination with PtdIns-homologues. Inhibitory effects on [(3)H] thymidine incorporation and intracellular signal transduction pathways were tested. Reaction products generated by bv-sPLA2 interaction with PtdIns(3,4)P2 were identified by mass spectrometry. Among the tested PtdIns-homologues those with a phosphate esterified to position 3 of the inositol head group, were most efficient in cooperating with bv-sPLA2 to block tumour cell proliferation. Growth inhibition induced by the combined action of bv-sPLA2 with either PtdIns(3,4)bisphosphate or PtdIns(3,4,5)trisphosphate were synergistic and accompanied by potent cell lysis. In contrast, PtdIns, which lacked the phosphate group at position 3, failed to promote synergistic growth inhibition. The combined administration of PtdIns(3,4)P2 and bv-sPLA2 abrogated signal transduction mediated by extracellular signal regulated kinase 1 and 2 and prevented transduction of survival signals mediated by protein kinase B. Surface expression of the epidermal growth factor (EGF)-receptor was reduced after PtdIns(3,4)P2-bv-sPLA2 administration and associated with a blockade of EGF-induced signalling. In addition, mass spectroscopy revealed that bv-sPLA2 cleaves PtdIns(3,4)P2 to generate lyso-PtdIns(3,4)P2. In conclusion, we suggest that the cytotoxic activity mediated by PtdIns(3,4)P2 and bv-sPLA2 is due to cell death that results from disruption of membrane integrity, abrogation of signal transduction and the generation of cytotoxic lyso-PtdIns(3,4)P2.

Animals↗
PubMed2006

The use of three-dimensional computed tomography for assessing patients before laparoscopic adrenal-sparing surgery.

OBJECTIVE: To evaluate the efficacy of three-dimensional computed tomography (3D-CT) in delineating the relationship of the adrenal mass to adjacent normal structures in preparation for laparoscopic partial adrenalectomy. PATIENTS AND METHODS: Multislice CT (1 mm slices, 0.5 s rotation time) was used to evaluate 12 patients before adrenal-sparing surgery for aldosterone-producing adenoma or phaeochromocytoma. The CT data were reconstructed using two rendering techniques; (i) volume rendering with the modified VOLREN software (Johns Hopkins Hospital, Baltimore, MD, USA) which allowed interactive 3D examination of the whole data volume within a few minutes; (ii) surface representations only of the interesting structures (kidney, adrenal tumour, vessels) represented in different colours and depicted together in a 3D scene using the software package 3DVIEWNIX. RESULTS: In all, 14 adrenal masses in 12 patients were evaluated with 3D-CT; the number and location of lesions was accurate in all cases with both rendering techniques. The coloured surface-rendered images showed a consistently better delineation of the adrenal tumour from the normal tissue than did the volume-rendering technique. From this information all laparoscopic partial adrenalectomies could be completed as planned. CONCLUSIONS: Interactive visualization of volume-rendered CT images was helpful for the planning and successful performance of the procedure, but coloured surface-rendered CT provided more convenient, immediate and accurate intraoperative information.

Adenoma↗
PubMed2006

Atherosclerosis as a risk factor for benign prostatic hyperplasia.

OBJECTIVES: To evaluate the relationship between clinical benign prostatic hyperplasia (BPH) and atherosclerosis, using colour Doppler ultrasonography (CDUS) and symptom scores. PATIENTS, SUBJECTS AND METHODS: CDUS was used to evaluate prostatic vascularity in four groups of men, comprising young healthy subjects, patients presenting with coronary artery disease (CAD), diabetes mellitus, or peripheral arterial occlusive disease (PAOD). Resistive index (RI) measurements and computer-assisted quantification of colour pixel density (CPD) were used to objectively evaluate perfusion. The International Prostate Symptom Score (IPSS) and the International Index of Erectile Function were used to quantify symptoms. RESULTS: In diabetic patients and men with PAOD, perfusion of the transition zone (TZ) of the prostate was significantly lower (P < 0.001) and the RI of the TZ was significantly higher (P < 0.001) than in healthy controls and men with CAD. In diabetics and men with PAOD, the mean prostate volume was greater than in healthy controls and men with CAD. The IPSS in patients with vascular damage (diabetes, PAOD) was significantly worse than in the control group. CONCLUSIONS: The significantly lower CPD and higher RI values of the TZ in patients with vascular disease than in healthy subjects support the hypothesis that an age-related impairment of blood supply to the prostate has a key role in the development of BPH.

Aged↗
PubMed2006

Reduction of prostate cancer mortality in Tyrol, Austria, after introduction of prostate-specific antigen testing.

The objective of this study was to analyze in detail the time trend in prostate cancer mortality in the population of Tyrol, Austria. In Tyrol, prostate-specific antigen tests were introduced in 1988-1989 and, since 1993, have been offered to all men aged 45-74 years free of charge. More than three quarters of all men in this age group had at least one such test in the last decade. The authors applied the age-period-cohort model by Poisson regression to mortality data covering more than three decades, from 1970 to 2003. For Tyrol, the full model with age and period and cohort terms fit fairly well. Period terms showed a significant reduction in prostate cancer mortality in the last 5 years, with a risk ratio of 0.81 (95% confidence interval: 0.68, 0.98) for Tyrol; for Austria without Tyrol, no effect was seen, with a risk ratio of 1.00 (95% confidence interval: 0.95, 1.05). Each was compared with the mortality rate in the period 1989-1993. Although the results of randomized screening trials are not expected until 2008-2010, these findings support the evidence that prostate-specific antigen testing offered to a population free of charge can reduce prostate cancer mortality.

Aged↗
PubMed2006

Material-enhanced laser desorption/ionization (MELDI)--a new protein profiling tool utilizing specific carrier materials for time of flight mass spectrometric analysis.

Over the past couple of years, proteomics pattern analysis has emerged as an effective method for the early diagnosis of diseases such as ovarian, breast, or prostate cancer, without identification of single biomarkers. MALDI-TOF MS, for example, offers a simple approach for fast and reliable protein profiling, especially by using carrier materials with various physical and chemical properties, in combination with a MALDI matrix. This approach is referred to as material-enhanced laser desorption/ionization (MELDI). In this paper, we report the development and application of derivatized carrier materials [cellulose, silica, poly(glycidyl methacrylate/divinylbenzene) (GMA/DVB) particles, and diamond powder] for fast and direct MALDI-TOF MS protein profiling. The applicability of MELDI for rapid protein profiling was evaluated with human serum samples. These carriers, having various hydrophobicities, resulted in characteristic mass fingerprints, even if all materials were derivatized with iminodiacetic acid (IDA) to yield an immobilized metal affinity chromatography (IMAC) functionality. Our study demonstrates that analyzing complex biological samples, such as human serum, by employing different MELDI carrier materials yielded type- and size-dependent performance variation.

Indicators and Reagents↗