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  • 11
    Keywords: CANCER ; EXPRESSION ; proliferation ; SURVIVAL ; carcinoma ; DISEASE ; GENE ; microarray ; MARKER ; BREAST ; DOUBLE-BLIND ; CELL CARCINOMA ; PREDICT ; PHASE-III TRIAL ; GROUP PROTEIN EZH2 ; ENHANCER-OF-ZESTE-HOMOLOG-2 GENE ; METASTATIC PROSTATE-CANCER
    Abstract: Background: The enhancer of zeste homolog 2 (EZH2) gene exerts oncogene-like activities and its (over) expression has been linked to several human malignancies. Here, we studied a possible association between EZH2 expression and prognosis in patients with renal cell carcinoma (RCC). Methods: EZH2 protein expression in RCC specimens was analyzed by immunohistochemistry using a tissue microarray (TMA) containing RCC tumor tissue and corresponding normal tissue samples of 520 patients. For immunohistochemical assessment of EZH2 expression, nuclear staining quantity was evaluated using a semiquantitative score. The effect of EZH2 expression on cancer specific survival (CSS) was assessed by univariate and multivariate Cox regression analyses. Results: During follow-up, 147 patients (28%) had died of their disease, median follow-up of patients still alive was 6.0 years (range 0-16.1 years). EZH2 nuclear staining was present in tumor cores of 411 (79%) patients. A multivariate Cox regression analysis revealed that high nuclear EZH2 expression was an independent predictor of poor CSS (〉 25-50% vs. 0%: HR 2.72, p = 0.025) in patients suffering from non-metastatic RCC. Apart from high nuclear EZH2 expression, tumor stage and Fuhrman's grading emerged as significant prognostic markers. In metastatic disease, nuclear EZH2 expression and histopathological subtype were independent predictive parameters of poor CSS (EZH2: 1-5%: HR 2.63, p = 0.043, 〉 5-25%: HR 3.35, p = 0.013, 〉 25%-50%: HR 4.92, p = 0.003, all compared to 0%: HR 0.36, p = 0.025, respectively). Conclusions: This study defines EZH2 as a powerful independent unfavourable prognostic marker of CSS in patients with metastatic and non-metastatic RCC
    Type of Publication: Journal article published
    PubMed ID: 20920340
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  • 12
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    German Medical Science; Düsseldorf, Köln
    In:  50. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie (gmds), 12. Jahrestagung der Deutschen Arbeitsgemeinschaft für Epidemiologie; 20050912-20050915; Freiburg im Breisgau; DOC05gmds300 /20050908/
    Publication Date: 2005-09-09
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 13
    Keywords: ADULT, adverse effects, Aged, AGREEMENT, albumin, BLOOD, BODY-WEIGHT, brain, brain neoplasms, brain
    Abstract: OBJECTIVE: The newly developed conjugate 5-aminofluorescein (AFL)-human serum albumin (HSA) was investigated in a clinical trial for fluorescence-guided surgery of malignant brain tumors to assess its efficacy and tolerability. METHODS: AFL, covalently linked to human serum albumin at a molar ratio of 1:1, was administered intravenously 0.5 to 4 days before surgery at 0.5 or 1.0 mg/kg of body weight to 13 patients aged 38 to 71 years who were suspected of having malignant gliomas. Fluorescence guidance using a 488-nm argon laser was performed during surgery at will. The extent of tumor resection was verified by early postoperative magnetic resonance imaging. Fluorescent and nonfluorescent samples were collected for neuropathology. Blood samples for laboratory and pharmacokinetic analyses were taken over the course of 4 weeks. RESULTS: Fluorescence staining of tumor tissue was bright in 11 patients (84%), resulting in complete resection of fluorescent tumor tissue in 9 patients (69%). In 2 patients, residual fluorescent tumor tissue was also confirmed by magnetic resonance imaging. Neither bleaching nor penetration of AFL-HSA into the surrounding brain edema or into necrotic tissue was seen. The agreement between fluorescence and histopathology in tumor samples and samples of the tumor border was 83.3%. There were no toxic side effects. The quality of fluorescence was independent of the dose administered. The optimal time for surgery is between 1 and 4 days after AFL-HSA administration. CONCLUSION: Tumor fluorescence using AFL-HSA made fluorescence-guided brain tumor resection possible, demonstrating that albumin is a suitable carrier system for selective targeting of aminofluorescein into malignant gliomas
    Type of Publication: Journal article published
    PubMed ID: 19240573
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  • 14
    Keywords: EXPRESSION ; SURVIVAL ; DISEASE ; BONE-MARROW ; PROSTATE-CANCER ; tumor-infiltrating lymphocytes ; PERIPHERAL-BLOOD ; UROTHELIAL CARCINOMA ; TELOMERASE ACTIVITY ; immune cells
    Abstract: Regulatory T cells (Tregs) play a key role in cancer immune escape. We identified target antigens of spontaneous tumor-specific T cell responses in urothelial carcinoma (UC) and evaluated their modulation by treatment and Treg. We determined Treg target antigens in UC. Fifty-six UC and 13 control patients were prospectively enrolled. Blood was drawn before and after routine treatment. Changes in Treg frequency were measured by fluorescence cytometry and the T effector cell (Teff) response against a set of nine tumor-associated antigens (TAAs) was monitored with an interferon-gamma ELISpot. Antigen specificity of Treg was determined by their increased capacity to inhibit after TAA-specific activation the proliferation of an autologous T cell population. The highest difference in the overall response rate for the total T cell population was observed for epidermal growth factor receptor (EGFR) (UC: 23% and controls: 0%). After depleting Treg, also new york esophageal (NYES)O1 (19 and 0%) and MUC20 (27 and 0%) were more frequently recognized in UC patients. In metastasized patients, the TAA-directed T cell response was augmented by Treg depletion. Tumor resection seemed to diminish Treg suppression of TAA-specific immunity, whereas chemotherapy had no effect. We demonstrated the existence of TAA-specific Treg in UC, which share antigen specificities with Teff. The coexistence of TAA-specific Treg and Teff was very rare. Treg frequencies in the peripheral blood were not changed by therapy. In summary, we identified potentially immunologically relevant TAA in UC. TAA-specific T cell responses against these antigens are suppressed by Treg. We identified TAA-specific Treg in UC patients, which do not cooccur with TAA-specific Teff.
    Type of Publication: Journal article published
    PubMed ID: 23625723
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  • 15
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  53. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie (gmds); 20080915-20080919; Stuttgart; DOCMI21-3 /20080910/
    Publication Date: 2008-09-11
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 16
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  53. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie (gmds); 20080915-20080919; Stuttgart; DOCMI21-4 /20080910/
    Publication Date: 2008-09-11
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 17
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    German Medical Science; Düsseldorf, Köln
    In:  68. Jahrestagung der Deutschen Gesellschaft für Unfallchirurgie, 90. Tagung der Deutschen Gesellschaft für Orthopädie und Orthopädische Chirurgie und 45. Tagung des Berufsverbandes der Fachärzte für Orthopädie; 20041019-20041023; Berlin; DOC04dguK6-1320 /20041019/
    Publication Date: 2004-10-20
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 18
    ISSN: 1432-1041
    Keywords: Lisinopril ; Dose adjustment ; ACE inhibitors ; pharmacokinetics ; pharmacodynamics ; renal failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract To prevent drug accumulation and adverse effects the dose of hydrophilic angiotensin-converting enzyme (ACE) inhibitors, e. g. lisinopril, must be reduced in patients with renal failure. To obtain a rational basis for dose recommendations, we undertook a prospective clinical trial. After 15 days of lisinopril treatment pharmacokinetic and pharmacodynamic parameters were determined in patients with advanced renal failure (n=8; endogenous creatinine clearance [CLCR]: 18 ml·min−1·1.73m−2) and in healthy subjects with normal renal function (n=16; CLCR: 107 ml·min−1·1.73m−2). The volunteers received 10 mg lisinopril once daily, the daily dose in patients (1.1–2.2 mg) was adjusted to the individual CLCR according to the method of Dettli [13]. After 15 days of lisinopril treatment the mean maximal serum concentration (C max) in patients was lower than in volunteers (30.7 vs 40.7 ng·ml−1, while the mean area under the concentration-time curve (AUC 0–24 h) was higher (525 vs 473 ng·h−1·ml−1). ACE activity on day 15 was almost completely inhibited in both groups. Plasma renin activity, angiotensin I and angiotensin II levels documented marked inhibition of converting enzyme in volunteers and patients. Furthermore, average mean arterial blood pressure in patients decreased by 5 mmHg and proteinuria from 3.9–2.7 g per 24 h after 15 days of treatment with the reduced dose of lisinopril. Adjustment of the dose of lisinopril prevents significant accumulation of the drug in patients with advanced renal failure during chronic therapy. Mean serum levels did not exceed this in subjects with normal renal function receiving a standard dose. Despite substantial dose reduction, blood pressure and proteinuria decreases were observed.
    Type of Medium: Electronic Resource
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  • 19
    Electronic Resource
    Electronic Resource
    Springer
    Zoomorphology 108 (1989), S. 309-313 
    ISSN: 1432-234X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Germ cell clusters are found in the germarial region of ovarioles of Parthenothrips dracenae. Cluster mitoses are synchronized, at least initially. The intercellular bridges are filled with fusomal material, which can fuse to form polyfusomal aggregates which in turn form small rosettes. All cells develop into oocytes. Oocytes become isolated by a secondary detachment process. Intercellular bridges, together with fusomal material and cell membranes, survive for some time as isolated bodies. Phylogenetic consequences are discussed. The data provide strong evidence for a secondary panoistic ovary in thysanopterans, since cluster formation in ovaries of primary panoists has not been shown.
    Type of Medium: Electronic Resource
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  • 20
    ISSN: 1434-3916
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die Problematik der residivierenden Schulterluxationen ist seit langem bekannt. Zu ihrer Behandlung sind bisher mehr als 100 verschiedene Operationen beschrieben worden. Dieser Überblick beschreibt 113 Patienten, die wegen rezidivierender Schulterluxationen ausnahmslos nach der Putti-Platt-Operationstechnik operiert wurden. Der signifikante Befund in der Vorgeschichte war eine mangelhafte Ruhigstellung des Gelenkes nach der ersten Luxation (bei 62% der Patienten). Nach dem operativen Eingriff wurden nur wenig Reluxationen (1%) aber eine relativ ausgeprāgte Bewegungseinschränkung beobachtet, die sich jedoch allmählich, bis zur annähernd vollen Beweglichkeit verbesserte.
    Notes: Summary Recurrent dislocation of the shoulder has long been recognized, and more than 100 techniques for repair of the injury are described. This survey describes 113 patients who suffered from recurrent anterior dislocation of the shoulder and were operated upon in accordance with the Putti Platt technique. The most significant preoperative finding was inadequate immobilization after the primary dislocation (62% of the patients). Postoperative recurrence was uncommon (1%) and a relative increased limitation of motion in the postoperative period improved gradually to almost a full range of movement.
    Type of Medium: Electronic Resource
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