Biomedical subjects

Lutz Trojan

Publications and source records attributed to Lutz Trojan.

At least 19 recordsLinked to original sources

PubMed2007

Correlation between motor function and lower urinary tract dysfunction in patients with infantile cerebral palsy.

AIMS: The aim of this study was to evaluate urodynamic findings in patients with infantile cerebral palsy (CP) and to correlate the findings with impaired motor function. METHODS: We conducted a videourodynamic investigation on a highly select group of 29 patients (3-53 years). Motor function was assessed in each patient by the Gross Motor Function Classification System for CP (GMFCS). With this system, motor function is divided into five levels: patients in Level I have the most independent motor function and patients in Level V the least. The patients were divided into Group 1 (23 symptomatic patients with recurrent urinary tract infection or urinary incontinence) and Group 2 (6 asymptomatic patients). RESULTS: In Group 1, 21 patients (91%) had reduced compliance (0.6-16.4 ml/cmH(2)O) and 16 patients (70%) had increased DLPP (>40 cmH(2)O). Detrusor overactivity and pelvic floor overactivity were found in all 23 patients. In Group 2, two patients (33%) had reduced compliance (0.7 and 5.8 ml/cmH(2)O) and four (67%) had increased DLPP (>40 cm H(2)O). Detrusor overactivity and pelvic floor overactivity were observed in five patients (83%). Symptomatic patients showed higher GMFCS levels than asymptomatic patients. In the group of asymptomatic patients, there was no one classified as Levels IV or V, while there were no symptomatic patients classified as Level I. CONCLUSIONS: We conclude that urinary symptoms and pathological urodynamic findings increase along with the degree of motor function impairment shown by the GMFCS. Pathologic urodynamic findings can be found in both symptomatic and in asymptomatic patients.

Adolescent↗

PubMed2006

Complications in percutaneous nephrolithotomy.

OBJECTIVE: This review focuses on a step-by-step approach to percutaneous nephrolithotomy (PNL) and its complications and management. METHODS: Based on institutional and personal experience with >1000 patients treated by PNL, we reviewed the literature (Pubmed search) focusing on technique, type, and incidence of complications of the procedure. RESULTS: Complications during or after PNL may be present with an overall complication rate of up to 83%, including extravasation (7.2%), transfusion (11.2-17.5%), and fever (21.0-32.1%), whereas major complications, such as septicaemia (0.3-4.7%) and colonic (0.2-0.8%) or pleural injury (0.0-3.1%) are rare. Comorbidity (i.e., renal insufficiency, diabetes, gross obesity, pulmonary disease) increases the risk of complications. Most complications (i.e., bleeding, extravasation, fever) can be managed conservatively or minimally invasively (i.e., pleural drain, superselective renal embolisation) if recognised early. CONCLUSIONS: The most important consideration for achieving consistently successful outcomes in PNL with minimal major complications is the correct selection of patients. A well-standardised technique and postoperative follow-up are mandatory for early detection of complications.

Adolescent↗

PubMed2006

The role of the lymphatic system and its specific growth factor, vascular endothelial growth factor C, for lymphogenic metastasis in prostate cancer.

OBJECTIVE: To compare prostate carcinoma, with and with no lymph node metastasis, to benign prostatic hyperplasia (BPH) tissue for lymphatic vessel density (LVD) and the expression of the lymph-endothelial specific growth factor, vascular endothelial growth factor C (VEGF-C), to determine their role in lymphogenic metastasis. PATIENTS, MATERIALS AND METHODS: Lymphatic vessels were stained using lymphatic vessel endothelial hyaluronan receptor 1 and assessed in standard areas. The expression of VEGF-C was assessed by the number of positive epithelial cells. The data were compared with the clinical staging. RESULTS: The lowest LVD was found in tumorous areas as opposed to periphery and nontumorous tissue (P = 0.007; P < 0.001). The highest LVD was in BPH tissue (P < 0.001). There was no correlation with clinical staging. There was more VEGF-C staining in pN1 than in pN0 and in BPH specimens (P = 0.002). CONCLUSION: LVD is not a prognostic variable for the process of lymphogenic metastasis in prostate cancer. VEGF-C is up-regulated in prostate cancer and its correlation with lymph node status suggests a role for the development of lymph node metastasis, e.g. via an increased permeability of lymphatic vessels.

Aged↗

PubMed2006

Intravenous contrast media in uroradiology: evaluation of safety and tolerability in almost 50,000 patients.

OBJECTIVE: To evaluate the frequency of adverse events and possible risk factors after the administration of an intravenous contrast medium (CM), iobitridol, in a large multicentre postmarketing surveillance study. SUBJECTS AND METHODS: A total of 49,975 patients undergoing intravenous urography were included in this study. A water-soluble, non-ionic CM (iobitridol, 1 ml/kg body weight) was administered. Age, sex, indication for the actual examination and adverse events were documented. Also, high-risk patients were identified. RESULTS: Of the 49,975 patients, 28,336 (56.7%) were males and 21,639 (43.3%) females. Indications for urography were mainly urolithiasis (39.1%), inflammatory diseases (25.6%) and tumours (13.9%). Additionally, 7.4% were risk patients: 1.9% with creatinine >1.5 mg/dl (0.1% were on haemodialysis); 0.8% had a history of previous allergic reactions to CM, 3.7% pre-existing asthma or allergies and 2% other risk factors against CM examination. Only 0.9% of the patients experienced acute adverse events that were non-serious and transient. Less than 0.1% of the patients experienced vomiting, dizziness or cardiovascular problems. Only 1 patient developed an anaphylactic shock but recovered fully under treatment. A chi(2) analysis revealed that adverse reactions occurred in patients with pre-existing renal insufficiency or allergies. Significantly more females had contrast-agent-related symptoms compared to men. Patients undergoing urography for urolithiasis had significantly fewer symptoms compared to patients with other indications. CONCLUSION: Iobitridol is clinically safe and well tolerated in urography as demonstrated in this study of a large patient population, producing mainly minor symptoms as adverse events. However, caution is advised when administering iobitridol to high-risk patients.

Acute Disease↗

PubMed2006

Intravesical mitomycin C for superficial transitional cell carcinoma.

Intravesical instillation of mitomycin C after a transurethral resection of a bladder tumor constitutes a standard treatment modality in the management of superficial transitional cell carcinoma in the urinary bladder. An immediate instillation of mitomycin C after transurethral resection has been shown to reduce the recurrence rate of superficial transitional cell carcinoma. Intravesical mitomycin C is generally considered to be a safe treatment option, but the past few years have seen the publication of a number of case reports on severe complications following mitomycin C instillation. This article reports on the mode of action, as well as the intravesical effects and current indications for mitomycin C instillation. This review will summarize the oncological benefits of mitomycin C in comparison with other intravesical treatments, such as bacillus Calmette-Guérin, and elucidate the incidence and types of possible complications associated with intravesical mitomycin C chemotherapy.

Administration, Intravesical↗

PubMed2005

IGF-II serum levels increase discrimination between benign prostatic hyperplasia and prostate cancer and improve the predictive value of PSA in clinical staging.

PURPOSE: IGF-I serum levels have been demonstrated as being associated with prostate cancer (PCa) and can serve as a predictive factor for the risk of PCa development. However, the role of IGF-II in PCa and its importance as a predictive marker is still unclear. Our aim was to determine PSA and IGF-II serum levels in patients with PCa and benign prostatic hyperplasia (BPH) and to analyse the value of IGF-II as an additional predictive factor in the diagnostics of PCa. METHODS: 112 patients who underwent surgery for BPH or PCa (no hormonal treatment, no further malignancies) were included in this study ((I) 38 PCa, PSA < or = 15 ng/ml; (II) 34 PCa, PSA > 15 ng/ml; (III) 40 BPH). Preoperative serum levels of total PSA and total IGF-II were determined by ELFA and ELISA, respectively. RESULTS: PSA levels were (I) 5.7+/-1.9 ng/ml; (II) 25.0+/-11.5 ng/ml and (III) 4.0+/-2.8 ng/ml. (II) was statistically associated with a high grading (2b/3; p = 0.0182), a high Gleason sum score (7-10; p = 0.0049) and a non-organ confined tumor (T3/4; p = 0.0009) compared to (I), all Chi2 test. IGF-II levels were significantly higher in PCa (I+II) compared to BPH (833.8+/-238.9 ng/ml vs. 633.3+/-141.4 ng/ml, p < 0.0001, t-test). Both PSA and IGF-II were associated with tumor staging (p = 0.0097, p = 0.0308; t-test). No significant correlation was observed between PSA and IGF-II levels. Logistic regression analysis revealed that the combination of PSA and IGF-II improves the prediction of tumor staging in PCa (p = 0.0175 and p = 0.0459, Wald test). Additionally, the combination of PSA and IGF-II can significantly increase discrimination between BPH and PCa; each p < 0.0001, Wald test. CONCLUSIONS: This study provides evidence that IGF-II serum levels may serve as an additional parameter for (a) improved determination of tumor staging and (b) better discrimination between BPH and PCa.

Aged↗

PubMed2005

Up-regulation of insulin-like growth factor axis components in human primary prostate cancer correlates with tumor grade.

There is an evidence that components of the insulin-like growth factor (IGF)-signaling pathway are involved in the development and progression of prostate cancer. The aim of the present study was to provide a comprehensive analysis of the expression levels of proteins of the IGF axis in prostate cancer. We studied expression of the ligands IGF-I and IGF-II, the inhibitory IGF binding protein-3, the type I IGF receptor (IGF-IR), and the downstream mediator insulin receptor substrate-1 by immunohistochemistry in 56 tissue specimens (28 low-grade and 28 high-grade prostate adenocarcinomas). Protein expression in tumor areas, prostatic intraepithelial neoplasias (PINs), and adjacent benign prostatic tissue were evaluated regarding staining intensity and fraction of positive cells. An immunoreactivity score was established from staining intensity and fraction of positive cells, and correlated with the prognostic clinicopathologic parameters prostate-specific antigen serum levels, Gleason score, and TNM stage. The expression levels of all proteins investigated, except IGF binding protein-3, were up-regulated in PIN and in cancer. IGF-I and IGF-II expression showed a higher expression in high-grade compared with low-grade tumor areas. IGF-I and IGF-II and insulin receptor substrate-1 immunoreactivity was higher in tumors from patients with preoperative prostate-specific antigen serum levels 10 ng/mL or greater, and IGF-II expression was correlated with Gleason score. The data indicate significant alterations in the IGF system as prostate cancer develops. Differential expression of growth-stimulating components of the IGF system may be associated with the malignant phenotype and more aggressive tumor behavior. Expression of IGFs, especially IGF-II, may be predictors of the outcome of prostate cancer.

Biomarkers, Tumor↗

PubMed2005

Calcium-binding proteins S100A8 and S100A9 as novel diagnostic markers in human prostate cancer.

PURPOSE: S100 proteins comprise a family of calcium-modulated proteins that have recently been associated with epithelial tumors. We examined the expression of two members of this family, S100A8 and S100A9, together with the S100 receptor RAGE (receptor for advanced glycation end products) in human prostate adenocarcinomas and in prostatic intraepithelial neoplasia. EXPERIMENTAL DESIGN: Tissue specimens of 75 patients with organ-confined prostate cancer of different grades were analyzed by immunohistochemistry for expression of S100A8, S100A9, and RAGE. In addition, in situ hybridization of S100A8 and S100A9 was done for 20 cases. An ELISA was applied to determine serum concentrations of S100A9 in cancer patients compared with healthy controls or to patients with benign prostatic hyperplasia (BPH). RESULTS: S100A8, S100A9, and RAGE were up-regulated in prostatic intraepithelial neoplasia and preferentially in high-grade adenocarcinomas, whereas benign tissue was negative or showed weak expression of the proteins. There was a high degree of overlap of S100A8 and S100A9 expression patterns and of S100A8 or S100A9 and RAGE, respectively. Frequently, a gradient within the tumor tissue with an increased expression toward the invaded stroma of the prostate was observed. S100A9 serum levels were significantly elevated in cancer patients compared with BPH patients or healthy individuals. CONCLUSION: Our data suggest that enhanced expression of S100A8, S100A9, and RAGE is an early event in prostate tumorigenesis and may contribute to development and progression or extension of prostate carcinomas. Furthermore, S100A9 in serum may serve as useful marker to discriminate between prostate cancer and BPH.

Adenocarcinoma↗

PubMed2005

Influence of neuroendocrine tumor cells on proliferation in prostatic carcinoma.

Neuroendocrine (NE) tumor cells in prostatic carcinoma (PCa) may influence tumor proliferation by a paracrine stimulus. The role of NE tumor cells is discussed controversially. This study investigates the influence of NE tumor differentiation on proliferation in PCa. Neuroendocrine differentiation, Ki-67, and Polo-like kinase 1 were studied immunohistochemically in 73 consecutive prostatectomies. Polo-like kinase 1 (PLK1) expression was also studied by Western and Northern blot analysis. Tumors were classified as high NE (HNE) and low NE differentiated (LNE), and depending on the growth pattern, with solitary and clusters of NE tumor cells. Low NE differentiated tumors were defined as less than 30 and HNE as 30 or more NE tumor cells per hot spot. Patients were followed by serum prostate-specific antigen (PSA) analysis. Neuroendocrine differentiation was present at least focally in 70% of tumors; 57% were HNE and 43% LNE. Solitary NE tumor cells were more often found in low-grade PCa, whereas clusters of NE tumor cells were more frequent in high-grade PCa. PLK1 messenger RNA and protein as well as Ki-67 were overexpressed in tumor tissue compared with tumor-free tissue. A stronger proliferation as determined by Ki-67 and PLK1 expression was present in HNE tumors compared with LNE tumors and in tumors with clusters in contrast to tumors with solitary NE tumor cells. Analysis for PSA relapse-free survival showed an earlier progression in HNE than in LNE tumors and in PCa with clusters of NE tumor cells. A significant and clustered NE differentiation in PCa may lead to an increased proliferation and earlier tumor progression, whereas few and solitary NE tumor cells have no prognostic impact.

Biomarkers, Tumor↗

PubMed2005

Validation of computer-based training in ureterorenoscopy.

OBJECTIVES: To evaluate the outcome of training both urological novices and experts, using the recently developed UroMentor (Simbionix Ltd, Israel) trainer, that provides a realistic simulation of rigid and flexible ureterorenoscopy (URS). SUBJECTS AND METHODS: Twenty experienced urologists (total number of previous flexible URSs 21-153) were monitored during simulated flexible URS for treating a lower calyceal stone, and the outcome was correlated with individual experience. A score was compiled based on the variables recorded, including total operation time, stone contact time, complications such as bleeding or perforation, and treatment success. A further five urological residents with no endourological experience were trained on the UroMentor in rigid URS for ureteric stone treatment. Their acquired clinical skills were subsequently compared to those of five urological residents who received no simulator training. RESULTS: All 20 experienced urologists disintegrated the stone on the simulator, and the score achieved was related to their personal experience; there was a significant difference in performance in those with < 40 and > 80 previous flexible URSs. For the five urological residents with no endourological experience, simulator training improved their skills, and comparison with urological residents who had received no simulator training showed advantages for the trained residents. After being trained on the simulator, the group performed better in the first four URSs on patients. CONCLUSIONS: Individual experience correlates with individual performance on the simulator. Simulator training was helpful in improving clinical skills. Although the distribution of computer-based simulators is limited by high prices, virtual reality-based training has the potential to become an important tool for clinical education.

Clinical Competence↗

PubMed2004

Simple models improve the discrimination of prostate cancers from the peripheral gland by T1-weighted dynamic MRI.

Evaluation of the accuracy of descriptive and physiological parameters calculated from signal intensity-time curves using T1-weighted dynamic contrast enhanced MRI (DCE MRI) to differentiate prostate cancers from the peripheral gland. Twenty-seven patients with prostate cancers were examined with DCE MRI prior radical prostatectomy. Regions of interest were defined in tumors and non-affected areas in the peripheral zone. Dynamic data were parameterized in amplitude and exchange rate constant (kep) using a two-compartment model. Additionally, relative slope during 26, 39, 52 and 65 s, areas under the curve (AUC) and time to start of signal intensity increase (tlag) were determined. Vessel density (VD) of excised prostates was quantified in tumor areas using a CD34 stain. The parameter slope52 showed 20% higher values (P<0.001) in tumors than in the peripheral gland and compared with the other parameters the largest area under the ROC curve (0.81). The minimum total error rate was attained at a cut-point of 0.021, yielding a sample value of sensitivity and specificity of 70% and 88%, respectively, and a bias-corrected sum of sensitivity and specificity of 1.54. In addition, amplitude (P<0.001), kep (P=0.03) and AUC (P<0.001) were significantly higher in tumors. tlag did not discriminate carcinomas from glandular tissue. VD was higher in tumors than in the non-affected peripheral prostate (P=0.05). However, none of the dynamic parameters in carcinomas showed a significant correlation with VD or Gleason score. Although pharmacokinetic modeling in DCE MRI showed potential to discriminate prostate cancers from peripheral prostate tissue, descriptive parameters of the early signal enhancement after contrast media injection reached higher sensitivity and specificity.

Aged↗

PubMed2004

Impact of holmium:YAG and neodymium:YAG lasers on the efficacy of DNA delivery in transitional cell carcinoma.

New approaches in the treatment of transitional cell carcinoma (TCC) are using gene therapy to influence the disease at the genetic level. Technical advances in genomics, the availability of tissue-specific gene promoters and other developments have made this approach more realistic. Transporting the gene into the target cell is still the major problem. Several transfection techniques have been introduced. Transfection of naked DNA is one of the simplest to perform but transfection rates have been very poor. We investigated the influence of laser energy on transfection efficacy in urothelial cancer cells in vitro with two types of medical lasers. A suspension of human transitional cancer cells (UM-UC3; 3.5 million cells/ml) was mixed with 200 microg of plasmid DNA (pEGFP-N1). Two types of laser energy, neodymium:YAG (Nd:YAG) and holmium:YAG (Ho:YAG), were applied to the cell suspension in different energy settings. Twenty four hours after treatment, transfection rates were measured with FACS analysis. Energy setting parameters that determine the efficacy of laser were investigated. The significance of different transfection rates was estimated with the student's t-test. We demonstrated that the Nd:YAG laser was not suitable for achieving significant transfection of the reporter gene to the cells. In contrast, the Ho:YAG laser produced satisfactory transfection rates. There was an increase in transfection with increasing frequency of laser pulses, from 16% with 2 Hz up to 40% with 10 Hz (p < 0.0005). Pulse frequency was therefore stabilised at 10 Hz. Pulse energy (mJ) showed the same dependency: a transfection rate of 18.3% was achieved with 1,000 mJ and 53.8% with 2,000 mJ (p > 0.0005). Additionally, we investigated the impact of total pulse number (imp) with different pulse energies. At 1,000 mJ, a transfection rate of 18.3% was estimated with 200 imp and 48.56% with 750 imp, (p < 0.0005). At 2,000 mJ, a transfection rate of 53.8% was achieved with 200 imp and 58.26% with 500 imp. The optimal laser setting observed in this experiment was 10 Hz, 2,000 mJ and 500 imp. This study indicates that the efficacy of naked DNA delivery into TCC in vitro is improvable by application of Ho:YAG laser energy. The Nd:YAG laser did not increase transfection rates in our model. Our results with the Ho:YAG laser are encouraging for further studies to optimise DNA delivery. As TCC tissue is relatively easy to access, this method could become an effective and minimally invasive procedure in urothelial cancer treatment.

Carcinoma, Transitional Cell↗

PubMed2004

The influence of oxalate on renal epithelial and interstitial cells.

Most renal stones in humans are composed of calcium oxalate. An increase in urinary oxalate levels has been shown to result in renal epithelial cell injury and crystal retention. However, the underlying mechanisms are unclear. Although the localization of primary stone formation and the associated cells playing the pivotal role in stone formation are still unknown, renal epithelial cells and interstitial cells seem to be involved in this process. The aim of this study was to evaluate the effects of oxalate on distinct renal epithelial and endothelial cells as well as fibroblasts. The first part focused on the toxicity of oxalate on the cells and a potential time- and dose-dependency. In the second part, renal epithelial cells were cultured in a two-compartment model to examine the vulnerability of the tubular or basolateral side to oxalate. LLCPK1, MDCK, renal fibroblast and endothelial cell lines were cultured under standard conditions. In part 1, cells were grown in standard culture flasks until confluent layers were achieved. Sodium oxalate was delivered at final concentrations of 1, 2 and 4 mM to either the apical or basolateral side (plain medium was delivered to the contralateral side). Cell survival was assessed microscopically by trypan blue staining after 1, 2 and 4 h. The influence of oxalate on proliferation and apoptosis induction was also investigated. In the second part, MDCK and LLCPK1 cells were grown in 6-well plates until confluent layers were achieved. Sodium oxalate at the above concentrations was applied, to either the apical or basolateral side and plain medium was delivered to the opposite side. The same protocol was then followed as in part 1. Part 1: sodium oxalate led to a time- and concentration-dependent decline in cell survival that was comparable in LLCPK1 and MDCK. Non-tubular cell lines like fibroblasts and endothelial cells were significantly more vulnerable to oxalate. These observations were reflected by significant impairment to cell proliferation. We could not demonstrate an induction of apoptosis in any cell line. Part 2: both cell lines were more vulnerable to oxalate on the basolateral side. This effect was more pronounced in MDCK cells at high oxalate concentrations (4 mM). Cells are apparently more resistant on the apical (tubular) side. Our results show that sodium oxalate has a negative effect on the growth and survival of renal epithelial cells and, to a greater extent, also fibroblasts and endothelial cells. We could not demonstrate any induction of apoptotic processes which implies a direct induction of cell necrosis. The finding of interstitial calcification and the proximity of tubules, vessels and interstitial cells make involvement of non-tubular renal cells in tissue calcification processes possible. Renal epithelial cells are apparently more vulnerable to oxalate on their basolateral side. Therefore, calcification processes within the interstitium may exert pronounced toxic effects to these cells, leading to inflammation and necrosis. These observations further support the idea of the interstitium as a site of primary stone formation.

Animals↗

PubMed2004

In vitro and ex vivo gene delivery into proximal tubular cells by means of laser energy--a potential approach for curing cystinuria?

Cystinuria is the cause of 1-2% of stones observed in adults and about 10% of those occurring in children. Recurrent stone formation and multiple operations cause considerable morbidity. We investigated the transfection efficiency of naked plasmid DNA in porcine kidney cells by applying holmium laser (Ho:YAG) energy in vitro as well as ex vivo in a porcine kidney papilla model. In the in vitro experiments, naked plasmid DNA was added to LLC-PK1 cells suspended in a medium and Ho:YAG laser applied with varying pulses. The transfection efficiency was measured by the expression of EGFP reporter gene in the cells by FACScan analysis and fluorescence microscopy. Ex vivo, papilla from porcine kidney was excised and naked plasmid DNA was added to the tissue in the medium. The laser was then applied and the cryosectioned tissue observed under fluorescence microscope. The efficiency of transfection in vitro significantly improved with the increase in impulses (P<0.01). Transfection at 50 impulses averaged 0.7+/-0.3%, at 200 impulses 28.3+/-7.7%, and at 500 impulses 36.1+/-3.1%. The cell mortality rate increased with higher pulse rate up to 70%. Ex vivo trials showed transfection in extended regions of the tissue and also in the peripheral layers of the papilla. Our study indicates that the transfection of benign kidney cells by Ho:YAG is a promising new gene transfer strategy. The ex vivo trials showed that peripheral renal tissue layers are susceptible to transfection by Ho:YAG applied from the papillary surface.

Cystinuria↗

PubMed2004

Micelle delivery of doxorubicin increases cytotoxicity to prostate carcinoma cells.

The use of doxorubicin as a chemotherapeutic agent is hindered by its toxic side effects on the normal cells of the body. The objective of this study was to determine if micelle-delivered doxorubicin could increase the effectiveness of doxorubicin against prostate carcinoma cells. Rat prostate carcinoma cells (MatLu) were cultured under standard conditions. Phosphate-buffered saline (PBS), doxorubicin and/or micelle solution (Pluronic 10500 solution) was added to the cell suspensions and incubated for 3 h. After incubation, cells were washed twice. Analysis consisted of: 1) immediate cell count and 2) proliferation assay at 24 and 144 h. After 24 h, samples with micelle-incorporated doxorubicin had 75% (10% pluronic with 10 microg/ml doxorubicin) and 80% (1% pluronic with 10 microg/ml doxorubicin) cell proliferation results compared with the control group. After 144-h incubation, these same two groups demonstrated cell proliferation results of only 30 and 43% of the control group. The in vitro cytotoxicity of doxorubicin against prostate carcinoma cells was dramatically increased by incorporating the molecule with polymeric micelles.

Analysis of Variance↗

PubMed2004

Expression of pro-angiogenic growth factors VEGF, EGF and bFGF and their topographical relation to neovascularisation in prostate cancer.

The aim of the study was to quantify the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) in prostate cancer and adjacent non-tumorous tissue in a standardized experimental set-up and to evaluate the paracrine effects of three endothelial stimuli on neovascularisation. Immunohistochemical staining of prostate cancer (PCa) specimens for VEGF, bFGF, EGF and the endothelial marker CD31 was performed (n=56). Sections were analyzed for growth factor-positive cancer/epithelial cells as well as staining intensity in (I) malignant and (II) non-tumorous tissue. Within PCa the topographic relationship (TR) of maximum microvessel density (MWD) and maximum expression of each growth factor was assessed. The number of VEGF- and EGF-positive cells in PCa was significantly enhanced compared with non-tumorous tissue (p<0.0001), whereas there was no difference in staining intensity. In contrast, the staining intensity of bFGF sections revealed a stronger expression in non-tumorous tissue compared with PCa (p<0.0001). In benign glands, VEGF, EGF and bFGF expression is chiefly restricted to basal cells. VEGF and EGF displayed a close TR in 65 and 57% of cases, respectively, whereas bFGF revealed a close TR in only 43% of PCa specimens. The results outline the relationship of the investigated growth factors and angiogenesis in PCa, which is strongest for VEGF and EGF. The relevance of VEGF and EGF is underlined by the increased number of positive cancer cells. Although previously reported to be a pro-angiogenic growth hormone, bFGF appears to play an assimilably minor role in the angiogenesis of PCa.

Aged↗

PubMed2004

Lymph and blood vessel architecture in benign and malignant prostatic tissue: lack of lymphangiogenesis in prostate carcinoma assessed with novel lymphatic marker lymphatic vessel endothelial hyaluronan receptor (LYVE-1).

PURPOSE: Due to the lack of specific markers the analysis of lymphatic vessel density (LVD) has been almost impossible in the past. We report the novel specific marker for lymphatic endothelium, lymphatic vessel endothelial hyaluronan receptor (LYVE-1), in prostatic, benign prostatic hyperplasia (BPH) and prostate cancer (PCa) tissue. Normal blood vessels were additionally quantified in BPH and PCa. MATERIALS AND METHODS: LYVE-1 lymphatics (LVD) and CD34 blood vessels were assessed in 20 paraffin sections of BPH and 50 of PCa tissue by immunohistochemistry in a standardized experimental setting. The regions of PCa, periphery of the tumor and nontumorous regions of the PCa specimens, and BPH tissue were evaluated. Double staining was done (LYVE-1/CD34). Acquired data were interrelated and compared to the pathological parameters of the specimens. RESULTS: Double staining revealed numerous CD34 blood vessels but only a few LYVE-1 lymphatic vessels in BPH and PCa sections. Mean LVD +/- SD was distinctly lower (0.55 +/- 0.93) in PCa tissue than in tumor periphery (2.45 +/- 1.93) and nontumorous (3.16 +/- 2.23) tissue (p <0.0001). Maximum LVD was observed in BPH (7.17 +/- 3.61), which differed markedly from nontumorous areas of PCa specimens (p <0.001). In contrast to LVD, significantly more blood vessels were found in PCa (116.00 +/- 39.25) than in BPH (60.30 +/- 19.34) tissue (p <0.001). CONCLUSIONS: LYVE-1 is a specific lymphatic endothelial marker in benign and malignant prostate tissues. It is a useful new marker for the investigation of lymphatics. To our knowledge we report the immunohistochemical visualization and quantification of lymphatic vessels in prostatic tissue for the first time. In contrast to the stimulated angiogenesis of blood vessels in PCa, the destruction of lymphatic vessels occurs rather than lymphangiogenesis.

Antigens, CD34↗

PubMed2003

Increase of AKT/PKB expression correlates with gleason pattern in human prostate cancer.

AKT/PKB is a central signaling molecule related to stimulation of cell proliferation and inhibition of apoptosis. Perturbations of AKT expression and function play an important role in tumor development and progression. We wanted to determine (a) whether AKT is overexpressed in human prostatic tumors, (b) whether AKT expression is correlated with tumor grade, and (c) whether AKT expression correlates with clinicopathological parameters. AKT expression was investigated by immunohistochemistry in sections from 56 paraffin-embedded prostate specimens displaying benign prostatic tissue (BPT), prostatic intraepithelial neoplasia (PIN), and primary tumors graded 2-5 according to Gleason. The staining intensity for AKT was significantly more pronounced in tumors compared to BPT, with PIN ranging between BPT and carcinomas. Similarly, the fraction of AKT-positive cells was higher in tumors than in BPT. A score of AKT expression (calculated as product from intensity and fraction of positive cells) ranging from 0-6 was also significantly higher in tumors than in BPT. Furthermore, the intensity of AKT expression in tumors showed a positive correlation with high preoperative serum levels of prostate specific antigen (PSA >/= 10 ng/ml, p = 0.0325). These data show that AKT is upregulated in prostate cancer and that expression is correlated with tumor progression.

Adult↗