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  • 1
    Language: English
    In: Medical oncology (Northwood, London, England), December 2013, Vol.30(4), pp.705
    Description: Until today, there is no reliable prognostic or predictive parameter for the prognosis of patients with metastatic urothelial cancer of the bladder prior to chemotherapy. Recently, serum C-reactive protein (CRP) level has been shown to be associated with survival of patients with various malignancies including localized and metastatic renal cell carcinoma, upper urinary tract as well as penile cancer. The aim of this study was to evaluate the prognostic impact of the pretreatment CRP serum level in patients with metastatic urothelial cancer of the bladder. We retrospectively evaluated 34 patients with metastatic urothelial cancer of the bladder and information about the CRP level prior to chemotherapy. The CRP level was correlated with patient- and tumor-specific characteristics. Kaplan-Meier and log-rank analyses were employed to calculate progression-free (PFS) and overall survival (OS). Receiver operating characteristics (ROC) analysis was used to determine an optimal prognostic CRP cutoff value to predict cancer-specific death. The median PFS to first-line chemotherapy and the OS for the whole cohort were 3.3 and 24.3 months, respectively. Serum CRP in mg/l was significantly associated with patients' survival (HR 1.02, p 〈 0.001, univariate Cox-regression). ROC analysis identified a CRP value of 80 mg/l to be the optimal cutoff. The median PFS was 4.5 and 3.0 months (p = 0.08; Mann-Whitney test), and the calculated 1-year OS was 82.6 and 22.2 % for patients with a CRP 〈80 and ≥80 mg/l, respectively (log-rank, p 〈 0.001). In contrast, neither T-stage, tumor grade, sex, age nor the body mass index was related to the CRP level or associated with overall survival. This is the first analysis revealing that the CRP value prior to systemic treatment might be of prognostic significance and could enable better risk stratification for patients with metastatic urothelial cancer of the bladder.
    Keywords: C-Reactive Protein -- Metabolism ; Urinary Bladder Neoplasms -- Metabolism
    ISSN: 13570560
    E-ISSN: 1559-131X
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  • 2
    In: International Journal of Urology, June 2013, Vol.20(6), pp.585-592
    Description: Byline: Sandra Steffens, Kristina I Ringe, Katharina Schroeer, Rieke Lehmann, Julia Rustemeier, Gerd Wegener, Mark Schrader, Rainer Hofmann, Markus A Kuczyk, Andres J Schrader, Keywords: body mass index; body surface area; obesity; prognosis; renal cell carcinoma; risk factors; visceral fat Objectives To assess the impact of overweight on prognosis of renal cell carcinoma patients. Patients And Methods A total of 2030 patients who underwent surgery for renal cell carcinoma from 1990 to 2011 in three University Medical Centers were included in this retrospective analysis. For all patients, height and weight measurements at the time of diagnosis were available for review. The median (mean) follow up was 56.6 months (66.0 months). Results A low body mass index was significantly associated with poor tumor differentiation, histology, microscopic vascular invasion and metastatic disease at the time of diagnosis. A lower-than-average body surface area - stratified according to the European average for men (1.98m.sub.2) and women (1.74m.sub.2) - was significantly related to older age, poor tumor differentiation, the histological subtype and microscopic vascular invasion. In addition, a low visceral fat area calculated in a subgroup of 133 evaluable patients was associated with a higher risk of advanced disease (pT3-4 and/or N/M+) at diagnosis. The tumor-specific 5-year survival rate was 71.3, 78.7 and 80.1%, for patients with a body mass index of, 〈25, 25-30 and a[yen]30. Multivariate analysis confirmed body mass index as an independent prognostic factor. Conclusion Our findings suggest that overweight represents an independent prognostic factor in renal cell carcinoma patients. Further research should address the question of why obese people have a higher incidence of renal cell carcinoma, but at the same time a significantly better prognosis than other patients, particularly in the case of localized disease. Author Affiliation:
    Keywords: Body Mass Index ; Body Surface Area ; Obesity ; Prognosis ; Renal Cell Carcinoma ; Risk Factors ; Visceral Fat
    ISSN: 0919-8172
    E-ISSN: 1442-2042
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  • 3
    Language: English
    In: BMC cancer, 03 May 2013, Vol.13, pp.223
    Description: High levels of circulating C-reactive protein (CRP) have recently been linked to poor clinical outcome in various malignancies. The aim of this study was to evaluate the prognostic significance of the preoperative serum CRP level in patients with squamous cell carcinoma (SCC) of the penis. This retrospective analysis included 79 penile cancer patients with information about their serum CRP value prior to surgery who underwent either radical or partial penectomy at two German high-volume centers (Ulm University Medical Center and Hannover Medical School) between 1990 and 2010. They had a median (mean) follow-up of 23 (32) months. A significantly elevated CRP level (〉15 vs. ≤ 15 mg/l) was found more often in patients with an advanced tumor stage (≥pT2) (38.9 vs. 11.6%, p=0.007) and in those with nodal disease at diagnosis (50.0 vs. 14.6%, p=0.007). However, high CRP levels were not associated with tumor differentiation (p=0.53). The Kaplan-Meier 5-year cancer-specific survival (CSS) rate was 38.9% for patients with preoperative CRP levels above 15 mg/l and 84.3% for those with lower levels (p=0.001). Applying multivariate analysis and focusing on the subgroup of patients without metastasis at the time of penile surgery, both advanced local tumor stage (≥pT2; HR 8.8, p=0.041) and an elevated CRP value (〉15 mg/l; HR 3.3, p=0.043) were identified as independent predictors of poor clinical outcome in patients with penile cancer. A high preoperative serum CRP level was associated with poor survival in patients with penile cancer. If larger patient populations confirm its prognostic value, its routine use could enable better risk stratification and risk-adjusted follow-up of patients with SCC of the penis.
    Keywords: Biomarkers, Tumor -- Blood ; C-Reactive Protein -- Metabolism ; Carcinoma, Squamous Cell -- Blood ; Penile Neoplasms -- Blood
    E-ISSN: 1471-2407
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  • 4
    Language: English
    In: BMC urology, 22 October 2013, Vol.13, pp.53
    Description: The nodal status is a strong predictor for cancer specific death in patients with penile carcinoma, and the C-reactive protein (CRP) level at diagnosis has recently been shown to be associated with poor clinical outcome in various solid malignancies. Therefore, this retrospective study was performed to evaluate the association between preoperative CRP levels and the incidence of nodal metastasis in patients with squamous cell carcinoma (SCC) of the penis. The analysis included 51 penile cancer patients who underwent either radical or partial penectomy for pT1-4 penile cancer between 1990 and 2010. The nodal status was correlated with patient and tumor specific characteristics. Sixteen (31%) patients had lymph node metastasis at the time of penile cancer surgery. Nodal status was associated with tumor stage but did not correlate significantly with tumor grade. In contrast, high presurgical CRP levels were significantly associated with the diagnosis of nodal involvement (p = 0.04). The optimal CRP cut-off value to predict lymph node metastasis was set at 20 mg/l based on ROC analysis. Since a high preoperative serum CRP level was closely correlated with nodal disease, it could be used as an additional marker to help identify patients with penile cancer who may benefit from inguinal lymph node dissection.
    Keywords: Biomarkers, Tumor -- Blood ; C-Reactive Protein -- Metabolism ; Carcinoma, Squamous Cell -- Secondary ; Penile Neoplasms -- Blood
    E-ISSN: 1471-2490
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  • 5
    Book
    Book
    Berlin: Deutsche Schriftsteller-Genossenschaft
    Language: German
    Description: Microfiche. Erlangen : Harald Fischer Verlag GmbH, c2001. 1 fiche
    Keywords: Women -- Employment -- Germany ; Women -- Germany -- History -- Sources ; Women&Apos;S Rights -- Germany -- History -- Sources ; Women -- Germany -- Social Conditions -- Sources
    ISSN: 0940-5968 ;
    Source: Center for Research Libraries
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  • 6
    In: Anesthesia & Analgesia, 2012, Vol.114(6), pp.1217-1219
    Description: We report on seizures during anesthesia induction in animals treated with a cannabinoid receptor 1 (CB1R) antagonist for experimental sepsis. Animals received surgery for colon ascendens stent peritonitis–induced sepsis or sham surgery followed by treatment of CB1R antagonist, CB1R agonist, or placebo. Fourteen hours later, animals received pentobarbital or ketamine for anesthesia induction and animal behavior was observed. Tonic-clonic seizures were observed in 5 of 12 septic animals (42%) treated with CB1R antagonist after induction of anesthesia with pentobarbital. The data suggest that CB1R inhibition in combination with pentobarbital may increase the incidence of anesthetic-induced seizures in the case of sepsis.
    Keywords: Anesthesia -- Adverse Effects ; Epilepsy, Tonic-Clonic -- Etiology ; Hypnotics and Sedatives -- Toxicity ; Morpholines -- Toxicity ; Pentobarbital -- Toxicity ; Pyrazoles -- Toxicity ; Receptor, Cannabinoid, Cb1 -- Antagonists & Inhibitors ; Sepsis -- Complications;
    ISSN: 0003-2999
    E-ISSN: 15267598
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  • 7
    Language: English
    In: Critical Care, March 15, 2012, Vol.16, p.R47
    Description: Introduction Cannabinoid receptor 2 (CB2R) expression is upregulated during sepsis. However, there are conflicting results regarding the effects of CB2R modulation in the hyperinflammatory phase of the disease. The aim of this study was therefore to investigate the effects of CB2R manipulation on leukocyte activation within the intestinal microcirculation in two acute experimental sepsis models. Methods In the endotoxemia model we studied four groups of Lewis rats: controls, lipopolysaccharide (LPS), LPS + CB2R agonist HU308 (2.5 mg/kg), and LPS + CB2R antagonist AM630 (2.5 mg/kg). In the colon ascendens stent peritonitis (CASP)-induced sepsis model we also studied four groups: sham group, CASP and CASP + CB2R agonist (HU308, 2.5 or 10 mg/kg). Intravital microscopy was performed 2 hours following LPS/placebo administration or 16 hours following CASP/sham surgery to quantify intestinal leukocyte recruitment. Additionally, hemodynamic monitoring, histological examinations and measurements of inflammatory mediators were performed. Results HU308 administration significantly reduced intestinal leukocyte adhesion in both acute sepsis models. The systemic levels of inflammatory mediators were significantly reduced by 10 mg/kg HU308 treatment in CASP animals. Conclusion CB2R activation reduces leukocyte activation and systemic release of inflammatory mediators in acute experimental sepsis. Drugs targeting the CB2R pathway may have therapeutic potential in sepsis.
    Keywords: White Blood Cells -- Research ; White Blood Cells -- Analysis ; Cell Receptors -- Research ; Cell Receptors -- Analysis
    ISSN: 1364-8535
    Source: Cengage Learning, Inc.
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  • 8
    Language: English
    In: Critical Care, March 15, 2012, Vol.16, p.R47
    Description: Introduction Cannabinoid receptor 2 (CB2R) expression is upregulated during sepsis. However, there are conflicting results regarding the effects of CB2R modulation in the hyperinflammatory phase of the disease. The aim of this study was therefore to investigate the effects of CB2R manipulation on leukocyte activation within the intestinal microcirculation in two acute experimental sepsis models. Methods In the endotoxemia model we studied four groups of Lewis rats: controls, lipopolysaccharide (LPS), LPS + CB2R agonist HU308 (2.5 mg/kg), and LPS + CB2R antagonist AM630 (2.5 mg/kg). In the colon ascendens stent peritonitis (CASP)-induced sepsis model we also studied four groups: sham group, CASP and CASP + CB2R agonist (HU308, 2.5 or 10 mg/kg). Intravital microscopy was performed 2 hours following LPS/placebo administration or 16 hours following CASP/sham surgery to quantify intestinal leukocyte recruitment. Additionally, hemodynamic monitoring, histological examinations and measurements of inflammatory mediators were performed. Results HU308 administration significantly reduced intestinal leukocyte adhesion in both acute sepsis models. The systemic levels of inflammatory mediators were significantly reduced by 10 mg/kg HU308 treatment in CASP animals. Conclusion CB2R activation reduces leukocyte activation and systemic release of inflammatory mediators in acute experimental sepsis. Drugs targeting the CB2R pathway may have therapeutic potential in sepsis.
    Keywords: White Blood Cells -- Research ; White Blood Cells -- Analysis ; Cell Receptors -- Research ; Cell Receptors -- Analysis
    ISSN: 1364-8535
    Source: Cengage Learning, Inc.
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  • 9
    Language: English
    In: Critical care (London, England), 12 December 2012, Vol.16(2), pp.R47
    Description: Cannabinoid receptor 2 (CB2R) expression is upregulated during sepsis. However, there are conflicting results regarding the effects of CB2R modulation in the hyperinflammatory phase of the disease. The aim of this study was therefore to investigate the effects of CB2R manipulation on leukocyte activation within the intestinal microcirculation in two acute experimental sepsis models. In the endotoxemia model we studied four groups of Lewis rats: controls, lipopolysaccharide (LPS), LPS + CB2R agonist HU308 (2.5 mg/kg), and LPS + CB2R antagonist AM630 (2.5 mg/kg). In the colon ascendens stent peritonitis (CASP)-induced sepsis model we also studied four groups: sham group, CASP and CASP + CB2R agonist (HU308, 2.5 or 10 mg/kg). Intravital microscopy was performed 2 hours following LPS/placebo administration or 16 hours following CASP/sham surgery to quantify intestinal leukocyte recruitment. Additionally, hemodynamic monitoring, histological examinations and measurements of inflammatory mediators were performed. HU308 administration significantly reduced intestinal leukocyte adhesion in both acute sepsis models. The systemic levels of inflammatory mediators were significantly reduced by 10 mg/kg HU308 treatment in CASP animals. CB2R activation reduces leukocyte activation and systemic release of inflammatory mediators in acute experimental sepsis. Drugs targeting the CB2R pathway may have therapeutic potential in sepsis.
    Keywords: Inflammation Mediators -- Immunology ; Intestines -- Immunology ; Leukocytes -- Immunology ; Receptors, Cannabinoid -- Immunology ; Sepsis -- Immunology
    ISSN: 13648535
    E-ISSN: 1466-609X
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  • 10
    In: Journal of Leukocyte Biology, February 2017, Vol.101(2), pp.577-587
    Description: Traditionally, B cells have been best known for their role as producers of antibodies. However, in recent years, a growing body of evidence has accumulated showing that B cells fulfill a range of other immunologic functions. One of the functions that has attracted increasing attention is the capacity of B cells to induce antigen‐specific activation of T cells through presentation of antigens. However, the analysis of this B cell function has been hampered by the lack of a phenotypically well‐defined antigen‐presenting B cell subset. Here, we report the identification of a human antigen‐presenting B cell subset with strong immunostimulatory properties. This B cell subset is characterized by low expression of CD21 and high expression of the activation marker CD86 and exhibits strong T cell–stimulatory activity, as demonstrated by means of an autologous mixed‐lymphocyte reaction. Phenotypically, CD21CD86 immunostimulatory B cells (B) represented CD27 class‐switched IgMIgD B lymphocytes and displayed a higher expression of cell surface receptors, which mediate the migration from peripheral blood to sites of inflammation. Flow cytometric analysis of peripheral blood obtained from individuals with inflammatory conditions revealed that the B subset was expanded following vaccination and in patients with rheumatoid arthritis. Taken together, our work shows that B represents a strongly immunostimulatory B cell subset, which could be a promising target for immunotherapeutic intervention in inflammatory diseases.
    Keywords: Apc ; Rheumatoid Arthritis ; B Cell Subsets ; Inflammation
    ISSN: 0741-5400
    E-ISSN: 1938-3673
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