Igor Tsaur

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

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Publications (76)184.18 Total impact

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    ABSTRACT: Aims: Despite impressive survival benefits from new agents to treat metastasized prostate cancer (PCa), progressive drug resistance hinders long-term response and restricts the efficacy of subsequent therapy. Due to reported antitumor activity of amygdalin and growing popularity for complementary and alternative medicine the potential of this natural, widely used substance to exert antineoplastic effects on prostate cancer cells has been assessed. Main methods: LNCaP (castration-sensitive), DU-145 and PC3 cells (castration-resistant) were exposed to different concentrations of amygdalin for 24h or 2weeks. Cell growth was measured by the MTT test, clonal formation by the clonogenic assay. Flow cytometry served to investigate apoptosis and cell cycle phases. Cell cycle regulating proteins and the mTOR-akt signaling axis were analyzed by western blotting. Key findings: Amygdalin dose-dependently diminished tumor cell growth with maximum effects at 10mg/ml. Apoptosis of PC3 and LNCaP but not of DU-145 cells was reduced, whereas colony formation was suppressed in all cell lines. A decrease in the number of G2/M- and S-phase cells along with an elevated number of G0/G1-phase cells was recorded. The cell cycle proteins cdk 1, cdk 2 and cdk 4 as well as cyclin A, cyclin B and cyclin D3 were modulated by amygdalin after both 24h and 2weeks. Distinct effects on p19 and p27 expression and on Akt, Rictor and Raptor activation became evident only after 2weeks. Significance: Amygdalin exhibits significant antitumor activity in both castration-sensitive and castration-resistant PCa cell lines and merits further evaluation for therapeutic purposes.
    No preview · Article · Jan 2016 · Life sciences
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    ABSTRACT: In patients with leiomyosarcoma, beta-humane chorionic gonadotropin (b-hCG) expression is a rare condition with only a few reports so far. We present a casuistry of a 76-year old male with an unclear unilateral scrotal mass. Because of high serum levels of b-hCG and normal appearing testicular parenchyma on ultrasound, extragonadal germ cell tumor (EGCT) was considered as diagnosis. However, because of the following inability to further characterize the mass by magnetic resonance imaging (MRI) and two consecutive tissue biopsies, therapy of the patient was delayed. Finally, resection of the tumor including penectomy with perineal urethrostomy, bilateral orchiectomy and scrotectomy was performed. B-hCG normalized completely 6 weeks after surgery; however the patient developed hepatic metastasis 5 months after initial operation. In selected cases serum b-hCG should be taken into consideration in patients with leiomyosarcoma, since it might represent a useful marker for disease monitoring in selected cases. Treatment should be started immediately in order to provide complete tumor resection and avoid systemic dissemination.
    No preview · Article · Jan 2016 · Clinical Genitourinary Cancer
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    ABSTRACT: Information about the natural compound amygdalin, which is employed as an antitumor agent, is sparse and thus its efficacy remains controversial. In this study, to determine whether amygdalin exerts antitumor effects on renal cell carcinoma (RCC) cells, its impact on RCC metastatic activity was investigated. The RCC cell lines, Caki-1, KTC-26 and A498, were exposed to amygdalin from apricot kernels, and adhesion to human vascular endothelium, immobilized collagen or fibronectin was investigated. The influence of amygdalin on chemotactic and invasive activity was also determined, as was the influence of amygdalin on surface and total cellular α and β integrin expression, which are involved in metastasis. We noted that amygdalin caused significant reductions in chemotactic activity, invasion and adhesion to endothelium, collagen and fibronectin. Using FACScan analysis, we noted that amygdalin also induced reductions, particularly in integrins α5 and α6, in all three cell lines. Functional blocking of α5 resulted in significantly diminished adhesion of KTC-26 and A498 to collagen and also in decreased chemotactic behavior in all three cell lines. Blocking α6 integrin significantly reduced chemotactic activity in all three cell lines. Thus, we suggest that exposing RCC cells to amygdalin inhibits metastatic spread and is associated with downregulation of α5 and α6 integrins. Therefore, we posit that amygdalin exerts antitumor activity in vitro, and this may be linked to integrin regulation.
    No preview · Article · Jan 2016 · International Journal of Molecular Medicine
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    ABSTRACT: Although amygdalin is used by many cancer patients as an antitumor agent, there is a lack of information on the efficacy and toxicity of this natural compound. In the present study, the inhibitory effect of amygdalin on the growth of renal cell carcinoma (RCC) cells was examined. Amygdalin (10 mg/ml) was applied to the RCC cell lines, Caki-1, KTC-26 and A498, for 24 h or 2 weeks. Untreated cells served as controls. Tumor cell growth and proliferation were determined using MTT and BrdU tests, and cell cycle phases were evaluated. Expression of the cell cycle activating proteins cdk1, cdk2, cdk4, cyclin A, cyclin B, cyclin D1 and D3 as well as of the cell cycle inhibiting proteins p19 and p27 was examined by western blot analysis. Surface expression of the differentiation markers E- and N-cadherin was also investigated. Functional blockade by siRNA was used to determine the impact of several proteins on tumor cell growth. Amygdalin treatment caused a significant reduction in RCC cell growth and proliferation. This effect was correlated with a reduced percentage of G2/M-phase RCC cells and an increased percentage of cells in the G0/1-phase (Caki-1 and A498) or cell cycle arrest in the S-phase (KTC-26). Furthermore, amygdalin induced a marked decrease in cell cycle activating proteins, in particular cdk1 and cyclin B. Functional blocking of cdk1 and cyclin B resulted in significantly diminished tumor cell growth in all three RCC cell lines. Aside from its inhibitory effects on growth, amygdalin also modulated the differentiation markers, E- and N-cadherin. Hence, exposing RCC cells to amygdalin inhibited cell cycle progression and tumor cell growth by impairing cdk1 and cyclin B expression. Moreover, we noted that amygdalin affected differentiation markers. Thus, we suggest that amygdalin exerted RCC antitumor effects in vitro.
    No preview · Article · Dec 2015 · International Journal of Molecular Medicine
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    ABSTRACT: Background: Many patients diagnosed with prostate cancer search for information on robotic prostatectomy (RobP) on the Web. We aimed to evaluate the qualitative characteristics of the mostly frequented Web sites on RobP with a particular emphasis on provider-dependent issues. Materials and methods: Google was searched for the term "robotic prostatectomy" in Europe and North America. The mostly frequented Web sites were selected and classified as physician-provided and publically-provided. Quality was measured using Journal of the American Medical Association (JAMA) benchmark criteria, DISCERN score, and addressing of Trifecta surgical outcomes. Popularity was analyzed using Google PageRank and Alexa tool. Accessibility, usability, and reliability were investigated using the LIDA tool and readability was assessed using readability indices. Results: Twenty-eight Web sites were physician-provided and 15 publically-provided. For all Web sites, 88% of JAMA benchmark criteria were fulfilled, DISCERN quality score was high, and 81% of Trifecta outcome measurements were addressed. Popularity was average according to Google PageRank (mean 2.9 ± 1.5) and Alexa Traffic Rank (median, 49,109; minimum, 7; maximum, 8,582,295). Accessibility (85 ± 7%), usability (92 ± 3%), and reliability scores (88 ± 8%) were moderate to high. Automated Readability Index was 7.2 ± 2.1 and Flesch-Kincaid Grade Level was 9 ± 2, rating the Web sites as difficult to read. Physician-provided Web sites had higher quality scores and lower readability compared with publically-provided Web sites. Conclusion: Websites providing information on RobP obtained medium to high ratings in all domains of quality in the current assessment. In contrast, readability needs to be significantly improved so that this content can become available for the populace.
    No preview · Article · Dec 2015 · Clinical Genitourinary Cancer
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    ABSTRACT: Objectives: We aimed to investigate the contemporary usage rate and habits of the WHO Surgical Safety Checklist (SSC) in German urological departments. Methods: We designed a 26-item questionnaire that was sent to all urological departments in Germany. The primary aim of this study was to evaluate the usage rate of the SSC. Secondary aims were to compare perioperative characteristics of users vs. non-users of the SSC and to assess circumstances of the SSC application. Results: A total of 213 of 234 (91 %) urological departments were users of the SSC, and 21 (9 %) were non-users. SSC users had more often a standard protocol, took less time and had fewer people involved for checking perioperative patient data compared to non-users. Financial budgeting for the SSC existed in 55 (24 %) departments and for patient safety in 73 (32 %) departments. Conclusions: The usage rate of the SSC in urological departments in Germany is high despite restricted financial budgeting. Users of the SSC profit by saving time and manpower for checking perioperative patient data.
    Full-text · Article · Nov 2015 · Patient Safety in Surgery
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    ABSTRACT: Introduction: Twitter use has grown exponentially within the urological community. We aimed to determine the perceptions of the impact of Twitter on users' clinical practice, research, and other professional activities. Methods: We performed an 11-item online survey of Twitter contributors during two major urological meetings: the European Association of Urology (EAU) and the American Urological Association (AUA) annual meetings. During the EAU 2014 meeting, we distributed the survey via the meeting official Twitter feed. During the AUA 2014 meeting, we applied a new method by directly sending the survey to Twitter contributors. We performed a subset analysis for assessing the perceived impact of Twitter on the clinical practice of physicians. Results: Among 312 total respondents, the greatest perceived benefits of Twitter among users were for networking (97%) and disseminating information (96%), followed by research (75%), advocacy (74%) and career development (62%). In total, 65% of Twitter users have dealt with guidelines on online medical professionalism and 71% of physician users found that Twitter had an impact on their clinical practice, and 33% had made a clinical decision based on an online case discussion. Conclusions: Our results suggest that Twitter users in the urological community perceive important benefits. These benefits extend to multiple professional domains, particularly networking, disseminating information, remote conference participation, research, and advocacy. This is the first study that has been disseminated to targeted individuals from the urological community directly through tweets, providing a proof of principle for this research method.
    Full-text · Article · Oct 2015 · Canadian Urological Association journal = Journal de l'Association des urologues du Canada
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    ABSTRACT: Background: In patients with penile cancer and increased risk of inguinal lymphatic dissemination, inguinal lymphadenectomy (iLAD) offers a direct histological staging as the most reliable tool for assessment of nodal metastatic status and a definitive oncologic treatment at the same time. However, postoperative complications with persisting lymph edema, prolonged lymphorrhea and delayed wound healing are often observed. We report on clinical outcome and complications of a limited inguinal lymph node (LN) dissection. Methods: Our iLAD dissection field reached from the inguinal crease to 18 cm caudal of pubic tubercle and 20 cm caudal of anterior superior iliac spine, which outer limits being marked with perpendicular lines. A 10 cm wide transverse incision was made about 3 cm below inguinal crease. Clinical and histopathological data of all patients with penile cancer who underwent limited iLAD at our institution between 1986 and 2012 were collected from patient charts and analyzed retrospectively. Results: Mean operative time for one-sided iLAD was 89.0 ± 37.3 minutes with 8.1 ± 3.7 LNs removed. A complication rate of 54,4% (n=34), including 16 minor and 15 major complications was found in a total of 57 procedures. 4 patients with clinically positive LNs developed inguinal lymphatic recurrence within 9 months after surgery. Follow-up period of the study cohort was 49.5 ± 42.6 months. Conclusions: iLAD provided an acceptable complication rate without aggravating morbidity. We experienced no recurrences in clinically LN negative patients, so that the approach might be a reasonable option in this case. In patients with enlarged LNs, more extended surgery is required and the standard radical technique still appears to represent the gold standard.
    No preview · Conference Paper · Sep 2015
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    ABSTRACT: Many patients diagnosed with cancer search for health information on the Web. We aimed to assess the quality and reliability of online health information on prostate cancer. Google, Yahoo, and Bing were searched for the term "prostate cancer." After selecting the most frequented websites, quality was measured by DISCERN score, JAMA benchmark criteria, and presence of HONcode certification. Popularity was assessed by Alexa tool, while accessibility, usability, and reliability were investigated by LIDA tool. Readability was analyzed by Flesch-Kincaid Reading Grade Level and Automated Readability Index. All 13 selected websites were rated as being of high quality according to the DISCERN instrument (76.5 ± 2.6 out of 80 points). JAMA benchmark criteria were fulfilled by 87 % of websites, whereas only 37 % were certified by the HONcode. Median Alexa Traffic Rank was 2718 ranging from 7 to 679,038. Websites received 2.3 ± 0.5 daily pageviews per visitor and users spent an average of 2 min 58 s ± 39 sec on the website. Accessibility (92 ± 5 %) and usability (92 ± 3 %) scores were high and reliability (88 ± 8 %) moderate according to the LIDA tool. Flesch-Kincaid Grade Level was 7.9 ± 2.2, and Automated Readability Index was 7.5 ± 2.4, rating the websites as fairly difficult to read. In conclusion, quality, accessibility, and usability of websites on prostate cancer provided a high rating in the current analysis. These findings are encouraging in view of the growing frequency of patients' access of health information online.
    Full-text · Article · Aug 2015 · Journal of Cancer Education
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    ABSTRACT: In patients with penile cancer (PeCa) and increased risk of inguinal lymphatic dissemination, inguinal lymphadenectomy offers a direct histological staging as the most reliable tool for assessment of the nodal metastasic status and a definitive oncologic treatment simultaneously. However, peri- and/or postoperative mutilating sequalae often occurn. We report on clinical outcome and complications of a limited inguinal lymph node (LN) dissection. Clinical and histopathological data of all patients with PeCa who underwent limited inguinal lymphadenectomy (LIL) at our institution between 1986 and 2012 were comprehensively analyzed. Perioperative results were presented in relation to one-sided procedures, if appropriate, which were assessed without cross comparison with contralateral LILs. 29 consecutive patients with PeCa aged 60±10.3 years were included in the current study with 57 one-sided LIL performed. Mean operative time for one-sided LIL was 89.0±37.3 minutes with 8.1±3.7 LNs removed. A complication rate of 54.4% (n=31), including 16 minor and 15 major complications was found in a total of 57 procedures with leg oedema being the most prevalent morbidity (15.8%). 4 patients with clinically positive LNs developed inguinal lymphatic recurrence within 9 months after surgery. Our technique of limited inguinal LN dissection provided an acceptable complication rate without aggravating morbidity. We experienced no recurrences in clinically LN negative patients, so that the approach might be a reasonable option in this scenario. In patients with enlarged LNs, radical inguinal lymphadenectomy still appears to represent the gold standard.
    No preview · Article · Jul 2015 · International braz j urol: official journal of the Brazilian Society of Urology
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    ABSTRACT: Chronic inflammation as an important epigenetic and environmental factor for putative tumorigenesis and tumor progression may be associated with specific activation of Toll-like receptors (TLR). Recently, carcinogenesis has been suggested to be dependent on TLR7 signaling. In the present study, we determined the role of both TLR7 and TLR8 expression and signaling in tumor cell proliferation and chemoresistance in pancreatic cancer. Expression of TLR7/TLR8 in UICC stage I-IV pancreatic cancer, chronic pancreatitis, normal pancreatic tissue and human pancreatic (PANC1) cancer cell line was examined. For in vitro/in vivo studies TLR7/TLR8 overexpressing PANC1 cell lines were generated and analyzed for effects of (un-)stimulated TLR expression on tumor cell proliferation and chemoresistance. TLR expression was increased in pancreatic cancer, with stage-dependent upregulation in advanced tumors, compared to earlier stages and chronic pancreatitis. Stimulation of TLR7/TLR8 overexpressing PANC1 cells resulted in elevated NF-κB and COX-2 expression, increased cancer cell proliferation and reduced chemosensitivity. More importantly, TLR7/TLR8 expression increased tumor growth in vivo. Our data demonstrate a stage-dependent upregulation of both TLR7 and TLR8 expression in pancreatic cancer. Functional analysis in human pancreatic cancer cells point to a significant role of both TLRs in chronic inflammation-mediated TLR7/TLR8 signaling leading to tumor cell proliferation and chemoresistance.
    Full-text · Article · Jul 2015 · International Journal of Oncology
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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.
    Full-text · Article · May 2015 · Journal of Experimental & Clinical Cancer Research
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    Full-text · Conference Paper · Apr 2015
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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.
    Full-text · Article · Mar 2015 · Journal of Cellular and Molecular Medicine
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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.
    No preview · Article · Mar 2015 · Cancer biomarkers: section A of Disease markers
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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.
    No preview · Article · Dec 2014 · Journal of Cellular and Molecular Medicine
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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.
    Full-text · Article · Oct 2014 · PLoS ONE
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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.
    Full-text · Article · Oct 2014 · Cancer Research and Treatment
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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.
    No preview · Article · Oct 2014 · European Journal of Radiology
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    ABSTRACT: Purpose: 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. Methods: The human PCa cell line PC3 was stimulated with CCL2. Cell growth was investigated by MTT dye reduction assay. Cell adhesion was analyzed by measuring attachment to a human endothelial cell (HUVEC) monolayer and immobilized collagen. Cell migration was assessed by a chemotactic assay. Integrin expression on the cell surface was evaluated by Western blot. Blocking studies were performed with anti-integrin α3, anti-integrin α6 and anti-integrin β4 monoclonal antibodies. Results: PC3 cell growth 72 h after CCL2 exposure was significantly increased, compared to controls. Activation of tumor cells by CCL2 significantly enhanced tumor cell adhesion to HUVEC and immobilized collagen. CCL2, added for 4 or 24 h, elevated α6 and β4 (4 > 24 h) integrin expression. α3 was enhanced after 4 h, but reduced after 24 h. Blocking either α3, α6 or β4 led to significant suppression of tumor cell binding to immobilized collagen. Conclusions: CCL2 stimulates PCa cell adhesion and induces alterations in α3-, α6- and β4-integrin expression on the cell surface. Blocking these integrins leads to a significant reduction in cell adhesion.
    No preview · Article · Sep 2014 · World Journal of Urology

Publication Stats

302 Citations
184.18 Total Impact Points

Institutions

  • 2010-2016
    • Goethe-Universität Frankfurt am Main
      Frankfurt, Hesse, Germany
  • 2008-2016
    • University Hospital Frankfurt
      Frankfurt, Hesse, Germany
  • 2013
    • Hospital Frankfurt Hoechst
      Frankfurt, Hesse, Germany
  • 2011-2012
    • Universitätsklinikum Freiburg
      Freiburg an der Elbe, Lower Saxony, Germany