Igor Tsaur

Goethe-Universität Frankfurt am Main, Frankfurt, Hesse, Germany

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Publications (63)153.98 Total impact

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    ABSTRACT: Measurement of prostate-specific antigen (PSA) advanced the diagnostic and prognostic potential for prostate cancer (PCa). However, due to PSA's lack of specificity, novel biomarkers are needed to improve risk assessment and ensure optimal personalized therapy. A set of protein molecules as potential biomarkers was therefore evaluated in serum of PCa patients. Serum samples from patients undergoing radical prostatectomy (RPE) for biopsy-proven PCa without neoadjuvant treatment were compared to serum samples from healthy subjects. Preliminary screening of 119 proteins in 10 PCa patients and 10 controls was carried out by the Proteome Profiler Antibody Array. Those markers showing distinct differences between patients and controls were then further evaluated by ELISA in the serum of 165 PCa patients and 19 controls. Uni- and multivariate as well as correlation analysis were performed to test the capability of these molecules to detect disease and predict pathological outcome. Screening showed that soluble (s)E-cadherin, E-selectin, MMP2, MMP9, TIMP1, TIMP2, Galectin and Clusterin warranted further evaluation. sE-Cadherin, TIMP1, Galectin and Clusterin were significantly over- and MMP9 under-expressed in PCa compared to controls. The concentration of sE-cadherin, MMP2 and Clusterin correlated negatively and that of MMP9 and TIMP1 positively with the Gleason Sum at prostatectomy. Only sE-cadherin significantly correlated with the highest Gleason pattern. Compared to serum PSA, sE-cadherin provided an independent and better matching predictive ability for discriminating PCas with an upgrade at RPE and aggressive tumors with a Gleason Sum ≥7. sE-cadherin performed most favorably from a large panel of serum proteins in terms of diagnostic and predictive potential in curatively treatable PCa. sE-cadherin merits further investigation as a biomarker for PCa.
    Journal of Experimental & Clinical Cancer Research 05/2015; 34(1):43. DOI:10.1186/s13046-015-0161-6 · 3.27 Impact Factor
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    ABSTRACT: A significant proportion of men diagnosed with prostate cancer (PCa) eventually develop metastatic disease, which progresses to castration resistance, despite initial response to androgen deprivation. As anticancer therapy has become increasingly effective, acquired drug resistance has emerged, limiting efficacy. Combination treatment, utilizing different drug classes, exemplifies a possible strategy to foil resistance development. The effects of the triple application of the histone deacetylase (HDAC) inhibitor valproic acid (VPA), the mammalian target of rapamycin inhibitor everolimus and low dosed interferon alpha (IFNα) on PCa cell growth and dissemination capacity were investigated. For that purpose, the human PCa cell lines, PC-3, DU-145 and LNCaP were treated with the combined regimen or separate single agents. Cell growth was investigated by the MTT dye reduction assay. Flow cytometry served to analyse cell cycle progression. Adhesion to vascular endothelium or immobilized collagen, fibronectin and laminin was quantified. Migration and invasion characteristics were determined by the modified Boyden chamber assay. Integrin α and β subtypes were investigated by flow cytometry, western blotting and RT-PCR. Integrin related signalling, Epidermal Growth Factor Receptor (EGFr), Akt, p70S6kinase and extracellular signal-regulated kinases (ERK)1/2 activation were also assessed. The triple application of VPA, everolimus and low dosed IFNα blocked tumour cell growth and dissemination significantly better than any agent alone. Antitumour effects were associated with pronounced alteration in the cell cycle machinery, intracellular signalling and integrin expression profile. Combining VPA, everolimus and low dosed IFNα might be a promising option to counteract resistance development and improve outcome in PCa patients. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
    Journal of Cellular and Molecular Medicine 03/2015; DOI:10.1111/jcmm.12583 · 3.70 Impact Factor
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    ABSTRACT: Extent of pelvic lymph node (LN) dissemination is a critical prognostic feature for patients with prostate cancer (PCa) maintaining extended pelvic lymphadenectomy (LAD) as the gold standard for LN-staging. Unfortunately, conventional histopathological assessment may miss micrometastasis and recently presented immunocytochemical approach of the single cell analysis is still intricate. To comparatively assess the potential of Prostate cancer gene 3 (PCA3) and prostate specific antigene (PSA) to perform as markers for tumor cell load. Patients with high risk PCa for LN metastasis undergoing either a sentinel LN-guided staging LAD or retropubic radical prostatectomy with sentinel-guided pelvic LN dissection were included. LNs were investigated by routine histopathology. Tumor cell load was quantified by immunocytochemistry. Gene activity was determined by qRT-PCR. Twenty four out of 226 LNs were positive in routine histopathology and 51 in single cell analysis. PSA mRNA level correlated with tumor cell density in patients with a positive immunocytochemistry. Gene activity of PCA3 was upregulated in metastatic LNs and correlated with tumor cell density in patients with tumor-invaded LNs as detected by immunocytochemistry. PCA3 gene expression discriminates LN metastasis and might outperform PSA gene activity in reflecting tumor cell burden in pelvic LNs of PCa patients.
    Cancer biomarkers: section A of Disease markers 03/2015; DOI:10.3233/CBM-150461 · 1.19 Impact Factor
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    ABSTRACT: Sequential application of target drugs is standard procedure after renal cell carcinoma (RCC) patients develop resistance. To optimize the sequence, antitumour effects of the mTOR inhibitor RAD001 or the tyrosine kinase inhibitor (TKI) sorafenib on RCC cells with acquired resistance to the TKI sunitinib was evaluated. RCC cells were exposed to 1 μM sunitinib for 24 hrs (as control) and for 8 weeks (to induce resistance) and then switched to RAD001 (5 nM) or sorafenib (5 μM) for a further 8 weeks. Tumour cell growth, cell cycle progression, cell cycle regulating proteins and intracellular signalling were then investigated. Short-term application of sunitinib (24 hrs) induced cell growth blockade with accumulation in the G2/M phase. RCC cells became resistant to sunitinib after 8 weeks, demonstrated by accelerated cell growth along with enhanced cdk1, cdk2, loss of p27, activation of Akt, Rictor and Raptor. Switching to sorafenib only slightly reduced growth of the sunitinib resistant RCC cells and molecular analysis indicated distinct cross-resistance. In contrast, full response was achieved when the cancer cells were treated with RAD001. p19 and p27 strongly increased, phosphorylated Akt, Rictor and Raptor decreased and the tumour cells accumulated in G0/G1. It is concluded that an mTOR-inhibitor for second-line therapy could be the strategy of choice after first-line sunitinib failure. © 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
    Journal of Cellular and Molecular Medicine 12/2014; 19(2). DOI:10.1111/jcmm.12471 · 3.70 Impact Factor
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    ABSTRACT: The cyanogenic diglucoside amygdalin, derived from Rosaceae kernels, is employed by many patients as an alternative anti-cancer treatment. However, whether amygdalin indeed acts as an anti-tumor agent is not clear. Metastasis blocking properties of amygdalin on bladder cancer cell lines was, therefore, investigated. Amygdalin (10 mg/ml) was applied to UMUC-3, TCCSUP or RT112 bladder cancer cells for 24 h or for 2 weeks. Tumor cell adhesion to vascular endothelium or to immobilized collagen as well as tumor cell migration was examined. Effects of drug treatment on integrin α and β subtypes, on integrin-linked kinase (ILK) and total and activated focal adhesion kinase (FAK) were also determined. Integrin knock-down was carried out to evaluate integrin influence on migration and adhesion. A 24 h or 2 week amygdalin application distinctly reduced tumor cell adhesion and migration of UMUC-3 and RT112 cells. TCCSUP adhesion was also reduced, but migration was elevated under amygdalin. Integrin subtype expression was significantly and specifically altered by amygdalin depending on the cell line. ILK was moderately, and activated FAK strongly, lost in all tumor cell lines in the presence of amygdalin. Knock down of β1 integrin caused a significant decrease in both adhesion and migration of UMUC-3 cells, but a significant increase in TCCSUP adhesion. Knock down of β4 integrin caused a significant decrease in migration of RT112 cells. Since the different actions of amygdalin on the different cell lines was mirrored by β1 or β4 knock down, it is postulated that amygdalin influences adhesion and migratory properties of bladder cancer cells by modulating β1 or β4 integrin expression. The amygdalin induced increase in TCCSUP migratory behavior indicates that any anti-tumor benefits from amygdalin (seen with the other two cell lines) may depend upon the cancer cell type.
    PLoS ONE 10/2014; 9(10):e110244. DOI:10.1371/journal.pone.0110244 · 3.53 Impact Factor
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    ABSTRACT: Prostate specific antigen is not reliable in diagnosing prostate cancer (PCa), making the identification of novel, precise diagnostic biomarkers important. Since chemokines are associated with more aggressive disease and poor prognosis in diverse malignancies, we aimed to investigate the diagnostic relevance of chemokines in PCa. Preoperative and early postoperative serum samples were obtained from 39 consecutive PCa patients undergoing radical prostatectomy. Serum from 15 healthy volunteers served as controls. Concentrations of CXCL12, CXCL13, CX3CL1, CCL2, CCL5, and CCL20 were measured in serum by Luminex. The expression activity of CXCR3, CXCR4, CXCR5, CXCR7, CXCL12, CXCL13, CX3CR1, CXCL1, CCR2, CCR5, CCR6, CCR7, CCL2, and CCL5 mRNA was assessed in tumor and adjacent normal tissue of prostatectomy specimens by quantitative real-time polymerase chain reaction. The associations of these chemokines with clinical and histological parameters were tested. The gene expression activity of CCL2 and CCR6 was significantly higher in tumor tissue compared to adjacent normal tissue. CCL2 was also significantly higher in the blood samples of PCa patients, compared to controls. CCL5, CCL20, and CX3CL1 were lower in patient serum, compared to controls. CCR2 tissue mRNA was negatively correlated with the Gleason score and grading. Chemokines are significantly modified during tumorigenesis of PCa, and CCL2 is a promising diagnostic biomarker.
    Cancer Research and Treatment 10/2014; DOI:10.4143/crt.2014.015 · 2.98 Impact Factor
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    ABSTRACT: Background To evaluate the effectiveness of lymphography as a minimally invasive treatment option of lymphatic leakage in terms of local control and to investigate which parameters influence the success rate Method This retrospective study protocol was approved by the ethic committee. Patient history, imaging data, therapeutic options and follow-up were recorded and retrospectively analysed. Between June 1998 and February 2013, 71 patients (m:w= 42:29, mean age, 52.4; range 42-75 years) with lymphatic leakage in form of lymphatic fistulas (n=37), lymphocele (n=11), chylothorax (n=13) and chylous ascites (n=10) underwent lymphography. Sixty-four patients (90.1%) underwent successful lymphography while lymphography failed in 7 cases. Therapeutic success was evaluated and correlated to the volume of lymphatic leakage and to the volume of the applied iodized oil. Result Signs of leakage or contrast extravasation were directly detected in 64 patients. Of 64 patients, 45 patients (70.3%) were treated and cured after lymphography. Based on the lymphography findings, 19 Patients (29.7%) underwent surgical intervention with a completely occlusion of lymphatic leakage. The lymphatic leak could be completely occluded in 96.8% of patients when the lymphatic drainage volume was less than 200 mL/day (n=33). Even when lymphatic drainage was higher than 200 mL/day (n=31), therapeutic lymphography was still successful in 58.1% of the patients. Conclusion Lymphography is an effective, minimally invasive method in the detection and treatment of lymphatic leakage. The volume of lymphatic drainage per day is a significant predictor of the therapeutic success rate.
    European Journal of Radiology 10/2014; DOI:10.1016/j.ejrad.2014.09.013 · 2.16 Impact Factor
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    ABSTRACT: Chemokines undergo alterations during neoplasia. However, knowledge about their functional significance in prostate cancer (PCa) progression is still sparse. Since chemokine (C-C motif) ligand 2 (CCL2) is significantly up-regulated in patients with PCa, aim of the current study was to assess whether CCL2 contributes to invasive behavior of prostate cancer cells in vitro.
    World Journal of Urology 09/2014; 14(2). DOI:10.1007/s00345-014-1389-z · 3.42 Impact Factor
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    ABSTRACT: Amygdalin, a natural compound, has been used by many cancer patients as an alternative approach to treat their illness. However, whether or not this substance truly exerts an anti-tumor effect has never been settled. An in vitro study was initiated to investigate the influence of amygdalin (1.25-10 mg/ml) on the growth of a panel of bladder cancer cell lines (UMUC-3, RT112 and TCCSUP). Tumor growth, proliferation, clonal growth and cell cycle progression were investigated. The cell cycle regulating proteins cdk1, cdk2, cdk4, cyclin A, cyclin B, cyclin D1, p19, p27 as well as the mammalian target of rapamycin (mTOR) related signals phosphoAkt, phosphoRaptor and phosphoRictor were examined. Amygdalin dose-dependently reduced growth and proliferation in all three bladder cancer cell lines, reflected in a significant delay in cell cycle progression and G0/G1 arrest. Molecular evaluation revealed diminished phosphoAkt, phosphoRictor and loss of Cdk and cyclin components. Since the most outstanding effects of amygdalin were observed on the cdk2-cyclin A axis, siRNA knock down studies were carried out, revealing a positive correlation between cdk2/cyclin A expression level and tumor growth. Amygdalin, therefore, may block tumor growth by down-modulating cdk2 and cyclin A. In vivo investigation must follow to assess amygdalin's practical value as an anti-tumor drug.
    PLoS ONE 08/2014; 9(8):e105590. DOI:10.1371/journal.pone.0105590 · 3.53 Impact Factor
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    ABSTRACT: Targeted therapies have improved therapeutic options of treating renal cell carcinoma (RCC). However, drug response is temporary due to resistance development.
    Molecular Cancer 06/2014; 13(1):152. DOI:10.1186/1476-4598-13-152 · 5.40 Impact Factor
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    ABSTRACT: Molecular tumour targeting has significantly improved anti-cancer protocols. Still, the addition of molecular targeting to the treatment regime has not led to a curative breakthrough. Combined mammalian target of Rapamycin (mTOR) and histone deacetylase (HDAC) inhibition has been shown not only to enhance anti-tumour potential, but also to prevent resistance development seen under mono-drug therapy. This investigation was designed to evaluate whether cross-communication exists between mTOR signalling and epigenetic events regulated by HDAC. DU-145 prostate cancer cells were treated with insulin-like growth factor (IGF) to activate the Akt-mTOR cascade or with the HDAC-inhibitor valproic acid (VPA) to induce histone H3 and H4 acetylation (aH3, aH4). Subsequently, mTOR, Rictor, Raptor, p70s6k, Akt (all: total and phosphorylated), H3 and H4 (total and acetylated) were analysed by western blotting. Both techniques revealed a link between mTOR and the epigenetic machinery. IGF activated mTOR, Rictor, Raptor, p70s6k and Akt, but also enhanced aH3 and aH4. Inversely, IGFr blockade and knock-down blocked the Akt-mTOR axis, but simultaneously diminished aH3 and aH4. VPA treatment up-regulated histone acetylation, but also activated mTOR-Akt signalling. HDAC1 and 2 knock-down revealed that the interaction with the mTOR system is initiated by histone H3 acetylation. HDAC-mTOR communication, therefore, is apparent whereby tumour-promoting (Akt/mTORhigh, aH3/aH4low) and tumour-suppressing signals (Akt/mTORlow, aH3/aH4high) are activated in parallel. Combined use of an HDAC- and mTOR inhibitor might then diminish pro-tumour effects triggered by the HDAC- (Akt/mTORhigh) or mTOR inhibitor (aH3/aH4low) alone.
    Journal of Cellular and Molecular Medicine 04/2014; DOI:10.1111/jcmm.12299 · 3.70 Impact Factor
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    ABSTRACT: Inhibitors of the mammalian target of rapamycin (mTOR) have improved the treatment of renal cell carcinoma (RCC). However, chronic drug exposure may trigger resistance, limiting the utility of these agents. The metastatic behavior of RCC cells, susceptible (RCC(par)) or resistant (RCC(res)) to the mTOR inhibitor temsirolimus, was investigated. Adhesion to vascular endothelium or immobilized collagen and fibronectin was quantified. Chemotactic motility was evaluated with a modified Boyden chamber assay. Integrin α and β subtype receptors were analyzed by flow cytometry and Western blot analysis. The physiological relevance of the integrins was then determined by blocking studies and small interfering RNA knockdown. Adhesion to endothelial cells and to fibronectin (not to collagen) and chemotaxis were enhanced in RCC(res) compared to RCC(par). RCC(res) detached from fibronectin and motile activity further increased under retreatment with low-dosed temsirolimus. α5 integrin was diminished inside the cell and at the cell surface, whereas the β3 subtype was reduced intracellularly but elevated at the plasma membrane. In RCC(par), blocking α5 surface receptors enhanced RCC-collagen but reduced RCC-fibronectin interaction, whereas the opposite was true for RCC(res). Chemotaxis of RCC(par) but not of RCC(res) was strongly diminished by the α5 antibody. Blocking β3 significantly lowered chemotaxis with stronger effects on RCC(res), compared to RCC(par). Importantly, β3 knockdown reduced chemotaxis of RCC(par) but upregulated the motile behavior of RCC(res). Temsirolimus resistance is characterized by quantitative alterations of integrin α5 and β3 expression, coupled to functional changes of the integrin molecules, and forces a switch from RCC adhesion to RCC migration.
    Neoplasia (New York, N.Y.) 04/2014; 16(4):291-300. DOI:10.1016/j.neo.2014.03.011 · 5.40 Impact Factor
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    ABSTRACT: The prevention of postprostatectomy incontinence has always been a challenge for urologists. Improved understanding of male continence and changes in pelvic anatomy after radical prostatectomy and the implementation of new surgical techniques raised hope of reduced incontinence rates. Despite using the full potential of continence-sparing techniques and atraumatic robot-assisted surgery, postprostatectomy incontinence still occurs in 5-20 % of cases. Recently published data showed a trend of improved early return to continence using anterior suspension or posterior reconstruction in robot-assisted prostatectomy. Postprostatectomy incontinence has a negative impact on quality of life and causes high costs of treatment. Therefore, further research in the amelioration of postoperative continence is mandatory.
    Der Urologe 02/2014; · 0.44 Impact Factor
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    ABSTRACT: Inhibitors of the mammalian target of rapamycin (mTOR) have improved the treatment of renal cell carcinoma (RCC). However, chronic drug exposure may trigger resistance, limiting the utility of these agents. The metastatic behavior of RCC cells, susceptible (RCCpar) or resistant (RCCres) to the mTOR inhibitor temsirolimus, was investigated. Adhesion to vascular endothelium or immobilized collagen and fibronectin was quantified. Chemotactic motility was evaluated with a modified Boyden chamber assay. Integrin α and β subtype receptors were analyzed by flow cytometry and Western blot analysis. The physiological relevance of the integrins was then determined by blocking studies and small interfering RNA knockdown. Adhesion to endothelial cells and to fibronectin (not to collagen) and chemotaxis were enhanced in RCCres compared to RCCpar. RCCres detached from fibronectin and motile activity further increased under retreatment with low-dosed temsirolimus. α5 integrin was diminished inside the cell and at the cell surface, whereas the β3 subtype was reduced intracellularly but elevated at the plasma membrane. In RCCpar, blocking α5 surface receptors enhanced RCC-collagen but reduced RCC-fibronectin interaction, whereas the opposite was true for RCCres. Chemotaxis of RCCpar but not of RCCres was strongly diminished by the α5 antibody. Blocking β3 significantly lowered chemotaxis with stronger effects on RCCres, compared to RCCpar. Importantly, β3 knockdown reduced chemotaxis of RCCpar but upregulated the motile behavior of RCCres. Temsirolimus resistance is characterized by quantitative alterations of integrin α5 and β3 expression, coupled to functional changes of the integrin molecules, and forces a switch from RCC adhesion to RCC migration.
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    ABSTRACT: Die Vermeidung der Postprostatektomieinkontinenz (PPI) ist seit jeher eine Herausforderung für den operierenden Urologen. Die zurückliegenden Fortschritte im Verständnis der Anatomie und Physiologie des Kontinenzmechanismus des Mannes und das Etablieren neuer operativer Techniken ließen auf eine Verbesserung der Kontinenzraten hoffen. Unter Ausschöpfen kontinenzerhaltender Operationstechniken und schonendem robotisch assistiertem Zugang tritt dennoch in 5–20 % der Fälle Inkontinenz auf. Unlängst konnte jedoch in mehreren Publikationen ein Trend zur verbesserten Frühinkontinenz bei robotisch assistiertem Vorgehen mit anteriorer oder posteriorer Rekonstruktion beschrieben werden. Angesichts des negativen Einflusses der PPI auf die Lebensqualität und der Therapiekosten ist weitere Forschung zur Verbesserung des Kontinenzerhalts geboten.
    Der Urologe 01/2014; 53(3). DOI:10.1007/s00120-013-3348-5 · 0.44 Impact Factor
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    ABSTRACT: To reliably compare the results of gene expression studies, the expression of the target gene should be normalized to the expression of a reference gene. For lymph node metastases of prostate cancer, no data on polymerase chain reaction (PCR) normalization have yet been reported. We aimed to determine the most reliable reference gene combination for this purpose in patients with prostate cancer. Ten histologically- positive and ten negative lymph nodes of patients with prostate cancer were analyzed respectively. Expression of six candidate reference genes was comparatively assessed with quantitative Real-time PCR. The most stably-expressed gene combination was determined with geNorm software version 3.4. Hypoxanthine phosphoribosyltransferase-1 (HPRT1) and TATA box binding protein (TPB) were found to be the most stably expressed genes, with their combination having an expression stability value of M=0.17. Gene combination HPRT1 and TPB has the potential to be utilized for normalization in gene profiling assessment of metastatic and non-metastatic pelvic lymph node tissue from patients with prostate cancer.
    Anticancer research 12/2013; 33(12):5243-8. · 1.87 Impact Factor
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    ABSTRACT: Die traditionelle chinesische Medizin (TCM) ist eine Jahrtausende alte ganzheitliche Körperheilkunde und beruht auf der Lehre von tao und qi. Tao (das „Eine“) steht für den Wandel, aus dem die Polarität von yin und yang hervorgeht. Qi ist die Lebensenergie, die durch den Körper zirkuliert. Die Therapien der TCM umfassen Akupunktur, Phytotherapie, Ernährungsprinzipien sowie Tuina, eine spezielle Massagetechnik. In der westlichen Welt findet sie derzeit als alternative respektive komplementäre Medizin zunehmende Akzeptanz. Anwendung in der Urologie findet die TCM dabei v. a. in Form der Akupunktur als auch der Phytotherapie.
    Der Urologe 11/2013; DOI:10.1007/s00120-013-3205-6 · 0.44 Impact Factor
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    ABSTRACT: Traditional Chinese medicine (TCM) is an ancient holistic medicine based on the doctrine of Tao and Qi. Tao represents an alteration from which the polarity of Yin and Yang arises and Qi is the vitality which circulates through the body. Therapeutic concepts of TCM include acupuncture, herbal therapy, nutrition and Tuina, a form of manual therapy. TCM is now gaining increased acceptance in the Western society as a complementary therapy. Acupuncture and herbal therapy are the main forms of implementation of TCM in urology.
    Der Urologe 06/2013; · 0.44 Impact Factor
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    ABSTRACT: Das Blasenkarzinom kommt v. a. bei Patienten zwischen dem 70. und 80. Lebensjahr vor. Die radikale Zystektomie stellt derzeit den Goldstandard bei der Therapie des muskelinvasiven Blasenkarzinoms dar. In diesem Beitrag wurden die verschiedensten Aspekte der radikalen Zystektomie im Alter untersucht. In der Datenbank von Pubmed-MEDLINE wurde nach Publikationen mit folgenden Schlüsselwörtern gesucht: „radical“, „cystectomy“, „elderly“, „age“.
    Der Urologe 06/2013; 52(6). DOI:10.1007/s00120-013-3196-3 · 0.44 Impact Factor

Publication Stats

188 Citations
153.98 Total Impact Points

Institutions

  • 2010–2015
    • Goethe-Universität Frankfurt am Main
      • Klinik für Urologie und Kinderurologie
      Frankfurt, Hesse, Germany
  • 2008–2015
    • University Hospital Frankfurt
      Frankfurt, Hesse, Germany
  • 2013
    • Hospital Frankfurt Hoechst
      Frankfurt, Hesse, Germany