A novel polyarginine containing Smac peptide conjugate that mediates cell death in tumor and healthy cells.

The seven N-terminal amino acids AVPIAQK (SmacN7) of the mitochondrial protein Smac (second mitochondria-derived activator of caspase) promote caspase activation by binding specifically to inhibitor of apoptosis proteins (IAPs) and blocking their inhibitory activity. SmacN7 cannot pass through the cell membrane, but to be of therapeutic use it would be essential for it to enter the cell. To achieve transmembrane transport of SmacN7 we coupled it to a novel fluorescein isothiocyanate (FITC)-labelled transmembrane transport peptide RRRRK(FITC)RRRR via ss-alanine to produce the conjugate AVPIAQKssA RRRRK(FITC)RRRR. Because IAPs are much more strongly expressed in the cytoplasm of tumor cells, we expected this conjugate to produce staining of the cytoplasm, and for this to be stronger in tumor cells than in healthy cells. Surprisingly, we found strong nuclear uptake of the Smac conjugate and of the transport peptide alone without subsequent release in both tumor cells and healthy cells from the bladder, prostate, and brain. This was accompanied by cell death. In contrast to expectations, it appears that the apoptotic effects observed do not result from the SmacN7 cargo alone.

[Bioartificial urothelium generated from bladder washings. A future therapeutic option for reconstructive surgery]. / Bioartifizielles autologes Urothel etabliert aus Spülungen der Harnblase. Eine zukünftige Therapieoption für die rekonstruktive Urologie.

Reconstructive surgery of lower urinary tract disorders can be limited by a shortage of adequate autologous tissue. Tissue engineering is an option for surgical reconstruction with evolved biological substitutes. Urethral repair with bioartificial urothelial implants can be an innovative method for sustained urothelial regeneration in situ. The needed urothelial cells are commonly isolated from native urothelium requiring surgery.The aim of this study was to establish primary human urothelial cell cultures from bladder washings in serum-free media and to generate urothelial tissue without seeding of matrices in a feeder cell-free system. It could be demonstrated that under these conditions bioartificial urothelium can be developed successfully from bladder washings. Its multilayered cellular structure and the initial differentiation in vitro, similar to native-grown urothelial tissue, are promising with regard to intended clinical application. Current work focuses on establishing cell culture techniques according to legal regulations, terminal differentiation of the urothelial constructs in vitro, and techniques to surgically implant lab-grown bioartificial urothelium.

[Value of stem cell therapy for the treatment of stress incontinence. Current status and perspectives]. / Stellenwert der Stammzelltherapie für die Behandlung der Belastungsinkontinenz. Aktueller Stand und Ausblick.

Parallel to a fundamental change in the therapeutic approach to managing stress incontinence, an increasing number of patients ask for reconstruction of the outer, striated urethral sphincter as therapy for urinary stress incontinence. Regenerative medicine is starting to offer solutions using stem cells as a part of oncological therapy or in reconstructive surgery. In addition to the many auspicious experimental approaches, one published study reports the effective therapeutic use of myogenic stem cells in urinary stress incontinent patients. Before this procedure is adopted into general clinical practice, further studies with validated evaluations and a sound legal basis are needed.

[Tissue engineering and stem cell research in urology for a reconstructive or regenerative treatment approach]. / "Tissue engineering" und Stammzellforschung in der Urologie für den rekonstruktiven bzw. regenerativen Therapieansatz.

With the involvement of clinical reconstructive urology in the field of tissue engineering, outstanding results have been achieved in basic research as well as in some clinics. Stem cell research has even opened up possibilities for regenerative aspects. In close cooperation with various disciplines, the Department of Urology at the University of Tübingen investigates different clinical aspects with regard to reconstructive and regenerative urology. The regeneration of the external urethral sphincter requires functionally integrated muscle cells. In addition stricture reconstruction with multilayer urothelium should become less invasive and the re-stricture rate reduced. After the application of differentiating stem cells was proven, the clinical setting needed to be set for legal issues. In addition to the specification of culture media and verification in the animal model, the possibility to harvest omnipotent stem cells out of human testis and to differentiate those into the three germ layers was demonstrated. With the reduced invasiveness of harvesting the urothelium cells by a bladder wash using specific culture fluids, the cell culture was significantly improved enabling successful creation of urothelium by stratification. In addition urothelial cells in a matrix are further improved for endoscopic application. The close cooperation of different disciplines shortens the time to develop therapeutic approaches with a close clinical relationship in reconstructive and regenerative urology.

[Tumor marker tests in bladder cancer]. / Pruebas de marcadores tumorales en el cáncer de vejiga.

The gold standard for detecting bladder cancer is cystoscopy which identifies nearly all papillary and sessile lesions. However, it is an invasive procedure causing some discomfort for patients. Urine cytology is the standard non-invasive marker with very high specificity, but unfavourable poor sensitivity for Ta, G1, and T1 bladder tumors. To improve early detection of bladder cancer as well as to monitor treatment response and tumor recurrence, bladder tumor markers are eligible. An ideal bladder cancer test would have the potential to replace or delay cystoscopy in the follow-up of bladder cancer patients. In recent years, the FDA approved non-invasive tumor marker tests ImmunoCyt / uCyt+, BTA TRAK, BTA stat, NMP22, NMP22 BladderChek, and UroVysion have been investigated. The tests demonstrated higher sensitivity for diagnosis of bladder cancer compared to urine cytology. Overall, the mean sensitivity and mean specificity was 64-80% and 71-95% and the mean positive and negative predictive values to detect malignancy were 49-84% and 79-95%, respectively. BTA TRAK, BTA stat, NMP22, and NMP22 BladderChek assays are limited by false-positive results in patients with benign urological diseases such as hematuria, urocystitis, renal calculi or urinary tract infections. Due to low specificity BTA TRAK, BTA stat, NMP22, and NMP22 BladderChek should not be used without first ruling out benign or malignant genitourinary disease other than bladder cancer. With the exception of UroVysion achieving 80% sensitivity and 94% specificity, none of these non-invasive tests revealed a high sensitivity and specificity at the same time, which is a main demand to be made on an ideal tumor marker. Insufficient sensitivity along with limited specificity does not allow replacing cystoscopy in diagnosis of bladder cancer or treatment decisions based on a positive test result.

Correlation of bFGF expression in renal cell cancer with clinical and histopathological features by tissue microarray analysis and measurement of serum levels.

The prognostic value of bFGF for surgically treated renal cell cancer (RCC) patients was evaluated by immunohistochemistry (IHC) and the tissue microarray technique (TMA). Additionally, preoperative serum bFGF levels were correlated to tumour stage and the presence of metastases at initial diagnosis. Serum levels of bFGF were measured by ELISA in 39 healthy volunteers, in 37 patients with benign urologic diseases and in 74 RCC patients, 26 of whom revealed lymph node or distant metastases. bFGF expression as detected by IHC was investigated in 777 tissue cores from 259 different RCC patients [median follow-up: 138 (36-240) months]. Eighty eight patients died from tumour progression. For each patient, the TMA slides contained a tissue core from the primary tumour, its invasion front and the normal renal parenchyma. bFGF serum levels were higher in RCC patients vs healthy volunteers (P<0.01) and vs patients with benign urologic diseases (P<0.01). Metastasized patients revealed higher bFGF serum levels than organ-confined specimens (P<0.01). As detected by IHC only increased bFGF expression in the invasion front tissue correlated with the patients' long-term survival (log rank test) (P=0.03). In multivariate analysis regional LN metastases (P<0.01), the histological grading (P<0.01), and an increased bFGF expression in the invasion front (P=0.04) independently predicted the patients' clinical prognosis. Not the expression of bFGF in the primary tumour but in its invasion front reflects the aggressiveness of RCC, hereby indicating a different biological potential within both areas. The value of bFGF serum levels as indicators of systemic tumour dissemination remains to be determined.

[In vitro stratified urothelium and its relevance in reconstructive urology]. / In vitro stratifiziertes Urothelium und seine Bedeutung für die rekonstruktive Urologie.

There are two main objectives regarding tissue engineering in reconstructive urology: (1) to provide the surgeon with autologous tissue for urogenital reconstructive purposes and (2) to create the framework for experimental investigations to better understand the structure and function of the tissues involved. In the last years urothelial cell culture has become a routine laboratory technique. There is sufficient cellular output after isolation and propagation to seed cells as single cell suspensions on biodegradable matrices for the construction of cell-matrix implants. In recent publications attention was directed toward using established primary cell cultures for in vitro stratification of multilayered urothelial sheets. Urothelial sheets have been used quite successfully for covering acellular matrices for bladder augmentation in dog and minipig models. However, up to now there has been no clinical application in humans of urothelial sheets generated in vitro. Here we review facts about the different strategies for generating multilayered urothelial sheets.

Immunohistochemical examinations (Ki67, p53, nm23) and DNA cytophotometry in bladder cancer.

Bladder cancer is clinically characterized by a high recurrence rate for superficial tumours up to 70% and by the invasiveness of advanced bladder cancer. To learn more about the biological behaviour of an individual bladder cancer different tumour markers have been investigated. The aim of our study was to compare the potential of aggression of both superficial and invasive bladder tumours by means of the proliferation marker Ki67, the tumour suppressor gene p53, the non metastasizing protein nm23 and the evaluation of DNA ploidy. We examined 36 patients, 28 with a bladder tumour (Ta-T4) and 8 without as a control group. For immunohistochemistry (Ki67, p53, nm23) we took paraffin sections and scored semiquantitatively under a microscope. The DNA cytophotometry was done on bladder washings by evaluating the DNA ploidy of single cells. The results showed that benign tissues were negative for Ki67 and p53 but positive for nm23. The DNA diagnosis was diploid for all benign samples. The superficial bladder cancer (Ta, T1) showed, in comparison to the invasive tumours, significantly lower numbers of aneuploid cells and a higher rate of p53 mutations. On the other hand the invasive tumours (T2-4) were correlated to significantly higher proliferation rates and higher potencies for metastasizing. The combination of the investigated tumour markers allowed a graduation of the biological behavior of an individual bladder cancer. Especially a high p53 mutation rate and a non aneuploid DNA diagnosis were indicators for the recurrence of superficial bladder tumours. Invasive growth of bladder cancer was characterized by high Ki67 proliferation and low nm23 protein binding.

Molecular genetic methods in the diagnosis of invasive bladder cancer.

Development and progression of tumours is generally driven by an accumulation of genetic alterations. In this study we correlated chromosome 17 aneuploidy to invasiveness of bladder cancer by the method of fluorescence in situ hybridisation (FISH) in urinary cytospins. We investigated the value of FISH compared to DNA cytophotometry in the diagnosis of bladder cancer. 39 patients with or suspicious for bladder tumour were analyzed. 19 patients had a bladder tumor at the time of diagnosis, 14 superficial (Ta-T1) and 5 invasive (T2-3). The remaining 20 patients had no tumour at the time of diagnosis, however 9 of them had one in prehistory (Ta-T2). For FISH we used the DNA probe of HER-2/neu located on chromosome 17. DNA image cytometry was performed according to single cell interpretation of Böcking. Our results showed a correlation between HER-2/neu CEP 17 alterations and invasive bladder cancer to the extent of 10-70% aberrant cells for patients with current invasive bladder tumour as well as for patients who had been cured but with as invasive bladder cancer in prehistory. On the other hand, the percentage of aneuploid cells for negative biopsy and superficial tumour was 0-2%. The DNA cytophotometry brought an uniform aneuploidy only for present invasive tumours: negative biopsies, superficial cancer and invasive tumour just in prehistory, showed mixed diploid-aneuploid DNA patterns. Our results showed that for the detection of aberrant tumour cells the method of FISH is more sensitive than DNA cytometry. FISH could provide important information in the prognosis of bladder cancer.

Marker for renal cell carcinoma (RCC): the dimeric form of pyruvate kinase type M2 (Tu M2-PK).

OBJECTIVE: The evaluate a potential tumor marker for RCC. Tumor formation is generally linked to an expansion of glycolytic phosphometabolite pools and aerobic glycolyticflux rates. To achieve this, tumor cells generally overexpress a special glycolytic isoenzyme, termed pyruvate kinase type M2. To establish the expansion of phosphometabolite pools pyruvate kinase switches between a tetrameric form with high phosphoenol-pyruvate (PEP) affinity and a dimeric form with a lower PEP affinity. The dimeric form is predominant in all tumors that have been investigated and has been termed TuM2Pk. MATERIALS AND METHODS: We studied: a) the expression of TuM2Pk in RCC by immunohistochemistry using a monoclonal antibody recognizing only the mono- or dimeric form of pyruvate kinase, b) the stability of TuM2Pk in serum by measuring TuM2Pk in 3 patients at different times after taking blood with a two-site immunometric assay, c) the a circadiane rhythm of TuM2Pk in blood by measuring levels every 4 hours in 5 patients, d) TuM2Pk- expression in serum (see 2.) in 5 patients by taking blood from tumor-side vena renalis compared to peripherally blood, e) TuM2Pk (see point 2.) in 40 RCC-patients comparing the results with 39 healthy persons and clinical data of RCC, f) the influence of wound healing to TuM2Pk by measuring serum-levels during a period of more than 12 weeks in 6 patients, g) the individual follow up of 4 patients with RCC stage Robson III for more than 2 years. Comparing TuM2Pk-levels to findings of staging by computed tomography. RESULTS: The isoenzyme TuM2Pk could be demonstrated in RCC and their metastases by immunohistochemistry with a monoclonal antibody specific for pyruvate kinase type M2. In normal kidney cells pyruvate kinase type M2 is not detectable. The stability of TuM2Pk was studied in the serum within 30 minutes. No circadian rhythm was found. Most serum TuM2Pk comes from tumor. Serum evaluation in 39 healthy persons was used to determine normal values, with an upper concentration of 28 U/ml of TuM2Pk (95% percentile of normal healthy persons). Serum evaluation in 40 RCC showed a significant difference to healthy persons and a positive correlation with Robson stage and grading No correlation of TuM2Pk was found with histopathological cell type of tumor diameter. After radical nephrectomy normalization of TuM2Pk level was found within 11 weeks in all localized RCC. Continuously elevated serum levels were seen in metastatic RCC. Individual follow-up seems to be possible. CONCLUSION: Initial discrimination is not possible between localized and metastasized RCC using TuM2PK; however, it is possible to differentiate between benign and malignant renal processes; the specificity under these circumstances is 75%. After successful surgery of localized RCC, an elevated TuM2Pk will be normalized within 11 weeks, and will be remain elevated or will increase again in case of RCC-relapse or metastasis. Thus TuM2Pk would appear to be a useful marker for RCC detection and follow-up.

Immunohistological investigations of carcinoembryonic antigen (CEA) in urothelial carcinomas.

CEA is discussed as a potential tumour marker for carcinomas of the urothelium. However, investigations by means of polyclonal antibodies have shown various cross reactions which are not to be expected with monoclonal antibodies (MAb). Immunohistochemistry was done with the MAb anti-CEA BW 431/26 (Behring), N 1522 (Dako), and C 7292 (Sigma) on 37 carcinomas of the urothelium (grades 1-3). The MAb BW 431/26 showed the best results concerning specificity and sensitivity. In general, immunohistological investigations demonstrated negative or moderate staining reactions. Positive reactions were seen in 32% (12/37) of the carcinomas. Staining intensity for CEA correlated with differentiation grade. On the whole, a maximum of 5% of the tumour cells were CEA positive. Our results indicate that monoclonal anti-CEA antibodies are not usefull as a tumour marker for urothelial carcinomas. For the suitability of CEA for in vitro and for in vivo diagnosis a threshold of CEA positive tumour cells has to be defined.

Serologic angiogenesis factors and microvascular density in renal cell carcinoma: two independent parameters.

Renal Cell Carcinoma (RCC) is characterized by high intratumoral microvascular density (iMVD) and significantly elevated serologic titers of angiogenesis factors, basic fibroblast growth factor (bFGF), vascular endothelial growth factor (vEGF) and angiogenin (Ag). The goal of the present study was to find whether a correlation exists between any of these factors and intratumoral microvascular density (iMVD). Serologic angiogenesis factors were determined directly before nephrectomy of a tumorous kidney in 12 patients (average age: 67.6 years [49-78] with localized clear-cell RCC (Robson I-II) (Quantikine', R&D Systems Europe, Abington, UK). Sections were taken in each case from the microscopically most aggressive area of the tumorous kidney preparations. Staining was carried out with a primary antibody against CD31 (DAKO M 0823, Hamburg, Germany). iMVD was counted at 160x magnification at five "hot spots" 200 x 200 microns in size, and the individual factors were then correlated with the areas of maximum and average iMVD (iMVDmax, iMVD-d). Average concentrations of 38 pg/ml +/- 68 were found for bFGF, 712 pg/ml +/- 791 for vEGF, and 358 ng/ml +/- 97 for Ag. iMVDmax was 20 +/- 11 per area, iMVD-d was 410/mm2 +/- 243. No correlation was found between microvascular density and serologic angiogenesis factors for any parameter. Actual tumor vascularization, expressed as iMVD, was not correlated with the 3 angiogenesis parameters which were studied. On the one hand, this raises the question whether angiogenesis can be measured at all with these parameters; on the other, it remains nuclear whether the continuous process of angiogenesis can be registered at all by chronologic, specific factor analysis.

Control of hepatic parameters in renal cell carcinoma (RCC) by interleukin-6 (IL-6)?

RCC can go hand-in-hand with an elevation of various hepatic proteins. An interrelationship between the IL-6 titer, C-reactive protein (CRP) and the blood sedimentation rate (BSR) has already been proven. The aim of the present study was to study 1) the possibility of differentiating between healthy and RCC patients via IL-6 in the serum and 2) the relationship of IL-6 to hepatic parameters {alkaline phosphatase (AP), gamma-glutamyltransferase (gGT), serum proteins (E'p)} and the usual clinical prognostic parameters (tumor grading, staging). Serum analysis of 38 healthy patients via ELISA (DPC-Biermann, Germany) showed normal values of 1.2 ng/ml for IL-6, with a standards deviation of +/- 1.7 and a peak concentration of 3 ng/ml (specificity: 95%). In 20 RCCs there were IL-6 titers of 10.7 ng/ml +/- 6.56 in the pre-operative serum. The sensitivity of IL-6 was about 90%. The difference was statistically significant (p < 0.0001, Wilcoxon test). For IL-6 there was a positive correlation with the BSR (1-hour value: r = 0.7; 2-hour value: r = 0.6), CRP (r = 0.85), E'p (r = 0.6), and gGT (r = 0.6). No correlation was found between AP, the Robson stage, grading, and IL-6. IL-6 is potentially suitable for differentiating between healthy and RCC patients but is not tumor specific. IL-6 has a strong correlation with all laboratory values which were analyzed except AP thus there is considerable evidence for a cytokine (IL-6) control of the hepatic changes. Since some of the above-named laboratory parameters have prognostic relevance, IL-6 can be regarded as a cumulative prognostic parameter.

Renal cell carcinoma: immunohistological investigation of expression of the integrin alpha v beta 3.

alpha v beta 3 Integrin has been shown in various tumor entities to promote binding to superficial structures of the basement membrane during metastasis. The goal of the present paper was a structural demonstration of this Integrin in renal cell carcinoma (RCC). After removal of paraffin from formalin-fixed tissue, the cells were labelled with the antibody (VNR 147, H. Biermann, Bad Nauheim) using the peroxidase-antiperoxidase method (DAKO Diagnostical GmbH, Hamburg). Evaluation was carried out microscopically and semiquantitatively from missing (-) through moderate (+) to strong (+2) staining. A total of n = 79 RCCs and n = 53 healthy areas were examined. Semiquantitative staining results: there was a grading-dependent increase (+2) of stainability and thus alpha v beta 3 expression. Two of 53 benign specimens showed strong staining, 11 of 53, only weak staining. Four of 18 G1 RCCs showed strong staining, 11 of 18 only weak staining. Results for G2-RCCs: 11 with strong staining, 21 of 40 with weak staining. G3-RCCs: 4 with strong staining, 2 of 7 with weak staining. Of the metastases, on the other hand, 2 of 14 showed strong staining, another 8 of 14 only weak staining. There were no deviations within the histologic (clear-cell, chromophil, or chromophobe) subpopulations. This grading-dependent expression permits the conclusion that the probability of binding to the human basement membrane mediated by alpha v beta 3 Integrin rises with increasing grading, but the already metastatic cell exhibited this Integrin less strongly, since a basement membrane adhesion is no longer necessary for this cell group.

Renal cell carcinoma: relevance of angiogenetic factors.

Angiogenesis is essential for tumour growth. Mostly hypervasculariced renal cell carcinoma (RCC) usually express angiogenic factors, e.g. basic fibroblast factor (bFGF), vascular endothelial growth factor, and angiogenin (ag). This study was designed to evaluate the improvement of serological angiogenesis-factors, their prognostic relevance and correlation to tumour-grade, -stage and -volume. Measurement of bFGF, vEGF and ag was done with ELISA (Quantikine), R and D-Systems Europe Abbington, United Kingdom. The control group comprised 39 healthy blood donors, RCC-group were 35 patients with different RCC. Survival dates were presented with Kaplan-Meyer-curves, significance was tested with students-t-test. For all angiogenic factors a highly significant difference between the healthy and RCC-group was found. A strong correlation between angiogenic factors and tumor grade, -stage and -volume, was not found, but a trend for each of the angiogenic factors to correlate with grade was seen. No survival benefit was seen between patients with normal angiogenic factor over those with elevated angiogenic levels.

DNA cytophotometry in renal cell carcinoma: a significant prognostic factor?

We report on a prospective DNA cytophotometric study of 66 patients with renal tumors, 61 of whom had renal cell carcinoma (RCC) (pT1-pT4, G1-G3). 16 of the patients had a metastasis at the time of diagnosis. Cell material from 1-5 specimens of each tumor was analyzed for intratumoral heterogeneity. The aim of the study was to evaluate the prognostic value of the following DNA parameters: DNA ploidy, DNA grade of malignancy (DNA MG), mean DNA, DNA index, 2c deviation index (2cDI), and 5c exceeding rate (5cER). In this study 21% of the tumors were non-aneuploid, 79% were aneuploid; however, it proved possible to diagnose 38% of the total collective as aneuploid only by analyzing several tumor areas. In five of 61 RCC patients who died during an observation period of 42 months, at least one area of the primary tumor was aneuploid. Aneuploid primary tumors also accompanied the development of metastases and recurrent tumors in four of the 61 RCC patients. Only DNA 2cDI was found to have a significantly positive clinical correlation with metastasis (r = 0.261) during the clinical course. This was not true, however, for the histopathologic parameters. Significantly positive correlations were found between the tumor stages and the following DNA parameters: mean DNA, DNA index, and 5cER. Histopathologic tumor grading showed a significantly positive correlation with DNA MG, mean DNA, and 5cER. Statistically, the mean values of all evaluated parameters were significantly higher in metastasizing and recurrent RCCs than in non-metastasizing carcinomas (p < 0.05; t-test). DNA cytophotometry cannot substitute histopathologic prognosis. However, the analysis of various DNA parameters helps considerably in evaluating both the malignant potential of kidney tumors and the benign parenchyma of tumor-bearing kidneys.

Loss of chromosomes in clear cell renal cell carcinoma and in corresponding renal parenchyma.

Chromosome studies were done on six renal cell carcinomas (RCC) and on the corresponding renal parenchymas of the tumor bearing kidneys. Histopathologically, all tumors belonged to the clear cell subtype. All examined parenchymas were pathologically benign. None of the tumor cells showed the typical chromosomal aberrations described for (nonpapillary) RCC, i.e. deletions in the short arm of chromosome #3, or gains in the long arm of chromosome #5. In our series both the tumor and the benign kidney tissues were characterized by loss of chromosomes, especially of the chromosomes #6, #9, #16, #20, and of the Y chromosome. Trisomy of chromosome #7 was found frequently in benign parenchyma cells. The identical chromosomal changes in the tumor and in the parenchyma tissues might reflect rather in vivo mosaics rather than primary chromosomal aberrations in the oncogenetic process of clear cell RCC.

[Tissue engineering of the urethra and ureter]. / Tissue Engineering der Harnröhre und des Harnleiters.

Congenital or acquired disorders of the urethra or ureter often require adequate tissue transfer for reconstruction. A variety of biomaterials have proved to be useful in the reconstruction of the urethra or ureter in animal models and meanwhile even clinically. Innovative tissues such as acellular matrices can be placed in the host and function as a scaffold to allow the natural process of tissue regeneration. Biodegradable scaffolds can also be used as cell transplantation vehicles for the reconstruction of urethral or ureteral tissue. One of the limitations of cell-based tissue engineering techniques however is the difficulty of growing genitourinary-associated cells in large quantities in primary cultures. It can be speculated that stem cell research might help to overcome this specific problem in the future.

[Renal cell carcinoma. Immunohistological study to the expression of the inactive form of the pyruvate kinase]. / Nierenzellkarzinom. Immunhistologische Untersuchungen zur Expression der inaktiven Form der Pyruvatkinass.

PURPOSE: The inactive form of pyruvatekinase could be established in different tumours. Purpose of this study was to demonstrate the presence or absence of the inactive form of pyruvatekinase in renal cell carcinoma, metastases and benign renal tissue by immunohistology. METHOD: After deparaffinization of formaline-fixed tissue (5 original tumours, 2 metastases and 5 benign renal tissues) cells were stained (APAAP-method) with Clon DF4 (ScheBo Tech). RESULTS: All malign tissue showed a positive reaction, inside benign tissue we saw a positive reaction of endothelial cells however we saw no reaction with benign renal cells. CONCLUSION: Renal cell carcinoma and metastatic cells show a strong immunohistological reaction against the inactive form of pyruvatekinase, no reaction of benign renal cells. It should be possible to develop a serological tumour marker for renal cell carcinoma.

[Advantages of nerve-sparing pelvic surgery. Animal experiments and clinical results]. / Vorteile der nerverhaltenden Beckenchirurgie. Tier experimentelle und klinische Ergebnisse.

Traditionally, oncological factors have been the only ones used in the evaluation of treatment outcome for urological tumor patients. With increased diagnoses of early, curable tumors in younger individuals, health-related quality of life and functional aspects are gaining importance. Sexual and urinary function are significant aspects of quality of life, which are especially vulnerable in urological patients. New insights into the anatomy and physiology of the pelvic organs have resulted in an improvement in surgical therapy. In this article, we present the results of current experimental and clinical studies, which underline the importance of nerve sparing techniques for maintaining a satisfying urinary and sexual function in this patient population.