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  • Article  (18)
  • Vogel, Ulrich  (18)
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  • Article  (18)
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  • 1
    Language: English
    In: The Journal of Urology, April 2012, Vol.187(4), pp.e535-e535
    Keywords: Medicine
    ISSN: 0022-5347
    E-ISSN: 1527-3792
    Source: ScienceDirect Journals (Elsevier)
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  • 2
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  • 4
    In: BJU International, February 2012, Vol.109(4), pp.634-638
    Description: To authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1464-410X.2011.10392.x Keywords: renal cell carcinoma (RCC); XPA-210; proliferation; oncocytoma; biomarker; thymidine kinase 1 Abstract: What's known on the subject? and What does the study add? The exposed proliferation antigen 210 (XPA-210) of the proliferation marker thymidine kinase 1 (TK1) showed higher expression levels in metastatic renal cell carcinoma. The current study used a new XPA-210 antibody to clarify the role of TK1 tissue expression in the largest reported cohort of different renal cell carcinoma types and oncocytomas. OBJECTIVE To determine the clinical role of the exposed proliferation antigen 210 (XPA-210) of the proliferation marker thymidine kinase 1 (TK1) in a large cohort of different renal cell carcinoma (RCC) types, oncocytomas and normal renal tissues samples, as TK1 is reported to be of clinical significance in several cancer entities and is suggested as a prognostic serum biomarker for RCC. PATIENTS AND METHODS Expressions of XPA-210 were determined immunohistochemically in 40 clear cell RCCs (ccRCC), 25 papillary RCCs (papRCC), 17 chromophobe RCC (chRCC), 27 oncocytomas and 64 normal renal parenchyma paraffin-embedded specimens. Immunohistochemistry was performed with a monoclonal anti-XPA-210 antibody. Staining was measured by the percentage of positive cells. Expression was compared between subgroups and correlated with respective clinical data using one-way analysis of variance with post hoc Tukey-Kramer analyses. RESULTS XPA-210 staining in the RCC subgroup was significantly different from the oncocytomas (mean [ sem] 4.1 [0.4] vs 2.2 [0.4]; P = 0.004) and from normal renal tissue (1.0 [0.1]; P 〈 0.001], whereas oncocytomas did not differ from normal renal parenchyma staining (P = 0.18). Subdivided into RCC groups, only ccRCC (mean [ sem] 5.1 [0.6]; P 〈 0.001) and papRCC (4.4 [0.6]; P 〈 0.001) varied from normal renal parenchyma, whereas chRCC (1.4 [0.3]; P = 0.99) did not. RCC XPA-210 staining was significantly associated with higher tumour stage (T = 3, P = 0.002) and grade (G = 3, P = 0.001). CONCLUSIONS The malignant character of RCC is reflected by higher XPA-210 expression as compared with oncocytomas and normal kidney. The ccRCC and papRCC subgroups had higher XPA-210 levels. XPA-210 could be considered a potential marker for the assessment of the proliferative activity in primary RCC. Author Affiliation: (1)Departments of Urology (*)Pathology, Eberhard-Karls University, Tuebingen, Germany ([dagger])Alere North America, Inc., San Diego, CA, USA Article History: Accepted for publication 16 March 2011 Article note: Christian Schwentner, Department of Urology, Eberhard-Karls University Tuebingen, Hoppe-Seyler Strasse 3, 72076 Tuebingen, Germany. e-mail: Christian.schwentner@med.uni-tuebingen.de
    Keywords: Renal Cell Carcinoma Rcc ; Xpa‐210 ; Proliferation ; Oncocytoma ; Biomarker ; Thymidine Kinase 1
    ISSN: 1464-4096
    E-ISSN: 1464-410X
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  • 5
    Language: English
    In: Anticancer research, November 2011, Vol.31(11), pp.3783-8
    Description: To investigate the protein kinase B (Akt) signalling proteins phosphatase and tensin homolog (PTEN), phosphorylated-Akt (p-Akt) and cyclin-dependent kinase inhibitor 1B (p27(Kip1)) in non-seminomatous germ cell tumors (NST) with a view to future investigative approaches. The expressions of PTEN, p-Akt and p27(Kip1) were immunohistochemically assessed in 17 teratomas, 27 embryonal cell carcinomas, 6 yolk sac tumors and 24 benign testicular parenchymas. The cytoplasmic and corresponding nuclear expressions were compared and correlated to tumor entity. PTEN was dramatically reduced in all the NST subgroups. Concentrated nuclear p27(Kip1) and loss of the cytoplasmic form was found in teratomas and embryonal cell carcinomas. Neither altered expression nor negative Akt regulation was found. The yolk sac tumors showed late cytoplasmic shift of PTEN and p27(Kip1). Both, the absence of overexpression of p-Akt and of negative correlations to PTEN and p27(Kip1) suggest that signalling of these parameters in NST might include additional mechanisms such as crosstalk to other pathways rather than classical Akt activation.
    Keywords: Cyclin-Dependent Kinase Inhibitor P27 -- Metabolism ; Neoplasms, Germ Cell and Embryonal -- Metabolism ; Pten Phosphohydrolase -- Metabolism ; Proto-Oncogene Proteins C-Akt -- Metabolism ; Testicular Neoplasms -- Metabolism
    E-ISSN: 1791-7530
    Source: MEDLINE/PubMed (U.S. National Library of Medicine)
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  • 6
    Language: English
    In: European Journal of Radiology, 2011, Vol.79(2), pp.189-195
    Description: To evaluate the value of T2w endorectal MRI (eMRI) for correct detection of tumor foci within the prostate regarding tumor size. 70 patients with histologically proven prostate cancer were examined with T2w eMRI before radical prostatectomy at a 1.5 T scanner. For evaluation of eMRI, two radiologists evaluated each tumor focus within the gland. After radical prostatectomy, the prostates were prepared as whole-mount sections, according to transversal T2w eMRI. For each slice, tumor surroundings were marked and compared with eMRI. Based on whole-mount section, 315 slices were evaluated and 533 tumor lesions were documented. Based on the T2w eMRI, 213 tumor lesions were described. In 137/213, histology could prove these lesions. EMRI was able to visualize 0/56 lesions with a maximum size of 〈0.3 cm (detection rate 0%), between 0.3 and 0.5 cm 4/116 (3%), between 1 and 0.5 cm 22/169 (13%), between 2 and 1 cm 61/136 (45%) and for 〉2 cm 50/56 (89%). False positive eMRI findings were: 〈0.3 cm = 0, 0.5–0.3 cm = 12, 0.5–1 cm = 34, 1–2 cm = 28 and 〉2 cm = 2. T2w eMRI cannot exclude prostate cancer with lesions smaller 10 mm and 0.4 cm respectively. The detection rate for lesions more than 20 mm (1.6 cm ) is to be considered as high.
    Keywords: Endorectal Mri ; Detection Rate ; Prostate Cancer ; T2w Mri ; Tumor Size ; Whole-Mount Specimens ; Medicine
    ISSN: 0720-048X
    E-ISSN: 1872-7727
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  • 7
    Language: English
    In: World Journal of Urology, 2013, Vol.31(2), pp.351-358
    Description: BACKGROUNDGalactin-3 is a cell adhesion molecule involved in tumor progression. Our aim was to examine Gal-3 expression in tumor, benign tissue adjacent to the tumor (adjacent-benign) and benign prostate specimens and correlated it with biochemical recurrence. MATERIALS AND METHODSTissue microarrays were prepared from 83 tumor, 78 adjacent-benign and 75 benign tissues obtained from 83 patients undergoing prostatectomy for clinically localized prostate cancer. Tissues were stained using a Gal-3 antibody and immunohistochemistry. The staining was graded between 0 and 300 depending upon staining intensity and the area of staining. In 37 patients on whom there was follow-up (Mean: 57.8 months; Median: 68 months), staining intensity was correlated with biochemical recurrence. RESULTSGal-3 showed both nuclear and cytoplasmic localization in benign, adjacent-benign and tumor tissues. Median Gal-3 staining scores significantly decreased from benign (192.5) to adjacent-benign (148.8 p = 0.007) and to tumor (108.8; p 〈 0.0001) tissues. In univariate analysis, age (p = 0.028), Gleason sum (p = 0.007), T stage (p = 0.011), seminal vesicle invasion (p = 0.009), pre-operative prostate-specific antigen (p = 0.045) and Gal-3 staining in tumor tissues (0.018) significantly correlated with biochemical recurrence. In multivariate analysis, Gal-3 expression in tumor (p = 0.04), adjacent-benign (p = 0.037) and benign (p = 0.005) tissues significantly correlated with biochemical recurrence. Gal-3 staining in tumor tissues had 91.7 % sensitivity, 64 % specificity and 73 % accuracy in predicting biochemical recurrence. CONCLUSIONSThis is the first study that showed a decreasing gradient of Gal-3 expression in benign, adjacent-benign and tumor tissues. Gal-3 expression may be useful in predicting biochemical recurrence.
    Keywords: Galectin-3 ; Biochemical recurrence ; Prostate cancer ; Tissue microarray
    ISSN: 0724-4983
    E-ISSN: 1433-8726
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  • 8
    Language: English
    In: Anticancer research, October 2012, Vol.32(10), pp.4339-45
    Description: To investigate the expression of the KIT/stem cell factor (SCF) axis in different renal cell carcinoma subtypes with regard to targeted therapies. The expression of KIT and SCF were immunhistochemically assessed in 40 clear cell (ccRCC), 25 papillary (pRCC) and 19 chromophobe carcinomas (chRCC); 27 oncocytomas and 32 benign kidney parenchyma specimens differentiated into distal tubules (DT) and proximal tubules (PT). The expression of KIT was significantly higher in chRCC and oncocytoma compared to ccRCC and pRCC. All tumours exhibited a significant increase of membranous to cytoplasmic KIT expression, with the highest in ccRCC and pRCCs. SCF was expressed in all tumour subgroups, with the highest in oncocytomas and pRCC. SCF correlated positively with the cytoplasmic expression of KIT. A higher tumour stage correlated to lower KIT expression in ccRCC. Simultaneous expression of SCF and KIT in renal tumours, which seems to undergo a shift from the cytoplasm to the cell membrane, suggests paracrine and autocrine mechanisms in KIT activation, with different, as yet unknown, regulatory mechanisms in the different tumour entities.
    Keywords: Carcinoma, Renal Cell -- Pathology ; Kidney Neoplasms -- Pathology ; Proto-Oncogene Proteins C-Kit -- Metabolism ; Stem Cell Factor -- Metabolism
    E-ISSN: 1791-7530
    Source: MEDLINE/PubMed (U.S. National Library of Medicine)
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  • 9
    Language: English
    In: World Journal of Urology, 2012, Vol.30(4), pp.547-552
    Description: XPA-210 is a proliferation marker derived from Thymidine kinase-1. It is of clinical significance in kidney, breast, and bladder cancer. There are no data available for XPA-210 in prostate cancer (PC). Herein, we aim to determine the clinical usefulness of XPA-210 in PC.In a retrospective study, cancer and benign tissue samples of 103 patients (median age 65 years, median PSA 9.04 ng/ml, median Gleason score 6) who underwent prostatectomy were constructed to a tissue micro array and stained for XPA-210. Semi-quantitative results were correlated with pathological and clinical data by Wilcoxon–Kruskall–Wallis and linear regression analysis. Expression levels in PC were correlated between the time of biochemical recurrence and the time to development of metastasis by the Kaplan–Meier method. Multivariate analysis was done to correlate those with the resection status.Mean staining score was 0.51–0.14 for tumor and benign tissue (P 〈 0.0001). Tumor staining score was significantly associated with Gleason score 〈6/≥6 (P 〈 0.0001) and T2/T 〉2 (P = 0.0007). When dividing the tumor score by the mean value, higher expression of XPA-210 was associated with a shorter time to biochemical recurrence (P = 0.003) and time to development of metastasis (P = 0.0061). Tumor staining (P = 0.0371) was an independent prognostic factor for biochemical relapse regardless of resection status.XPA-210 is a new tissue-based prognostic marker for prostate cancer histopathology. It reliably differentiates tumor and normal prostatic tissue predicting biochemical relapse and onset of metastatic disease. XPA-210 might be clinically useful for individual decision-making in PC-treatment.
    Keywords: Prostate cancer ; XPA-210 ; Biochemical recurrence ; Metastatic disease ; Proliferation
    ISSN: 0724-4983
    E-ISSN: 1433-8726
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  • 10
    Language: English
    In: World Journal of Urology, 2013, Vol.31(2), pp.345-350
    Description: BACKGROUND: Preclinical studies demonstrated effects of drugs inhibiting the mevalonate pathway including nitrogen-containing bisphosphonates (N-BPs) and statins on tumor growth and progression. The exact role of this pathway in prostate cancer (PC) has not been identified yet. Herein, we evaluate the expression of farnesyl pyrophosphate synthase (FPPS), the key enzyme of the mevalonate pathway, in PC.PATIENTS AND METHODS: Prostate cancer (PC) and benign prostate tissue of 114 men who underwent radical prostatectomy were constructed to a tissue microarray. Immunohistochemical staining of FPPS was quantified by the Remmele/Stegner immunoreactivity-score. Patients' clinical follow-up was assessed. IRS was correlated to pathological and clinical data. The impact of FPPS expression on clinical course was assessed univariate and multivariate.RESULTS: Mean IRS in PC and benign tissue was 5.7 (95% CI 5.0-6.5) and 2.6 (2.1-3.0, p〈0.0001). Mean IRS in PC tissue of patients with organ-confined and locally advanced disease (pT≥3) was 5.09 (4.22-5.96) and 6.87 (5.57-8.17, p=0.035). IRS of PC tissue significantly correlated with Gleason score (p=0.03). Patients with PC tissue IRS 〉3 showed shorter recurrence-free survival compared to the remaining (p=0.01). Increased FPPS expression is an independent risk factor for early biochemical recurrence (p=0.032).CONCLUSIONS: This is the first study on FPPS in PC specimens. The association of FPPS with established histopathological risk parameters and biochemical recurrence implicates a contribution of the mevalonate pathway to PC progression. Further functional analysis is required to explore the role of this pathway in PC and to investigate whether FPPS expression affects the response of PC cells to N-BPs.
    Keywords: Prostate cancer ; Bisphosphonates ; Farnesyl pyrophosphate synthase ; Zoledronic acid ; Mevalonate pathway
    ISSN: 0724-4983
    E-ISSN: 1433-8726
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