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Vinzon S.E.,German Cancer Research Center | Braspenning-Wesch I.,German Cancer Research Center | Muller M.,German Cancer Research Center | Geissler E.K.,University of Regensburg | And 4 more authors.
PLoS Pathogens | Year: 2014

Certain cutaneous human papillomaviruses (HPVs), which are ubiquitous and acquired early during childhood, can cause a variety of skin tumors and are likely involved in the development of non-melanoma skin cancer, especially in immunosuppressed patients. Hence, the burden of these clinical manifestations demands for a prophylactic approach. To evaluate whether protective efficacy of a vaccine is potentially translatable to patients, we used the rodent Mastomys coucha that is naturally infected with Mastomys natalensis papillomavirus (MnPV). This skin type papillomavirus induces not only benign skin tumours, such as papillomas and keratoacanthomas, but also squamous cell carcinomas, thereby allowing a straightforward read-out for successful vaccination in a small immunocompetent laboratory animal. Here, we examined the efficacy of a virus-like particle (VLP)-based vaccine on either previously or newly established infections. VLPs raise a strong and long-lasting neutralizing antibody response that confers protection even under systemic long-term cyclosporine A treatment. Remarkably, the vaccine completely prevents the appearance of benign as well as malignant skin tumors. Protection involves the maintenance of a low viral load in the skin by an antibody-dependent prevention of virus spread. Our results provide first evidence that VLPs elicit an effective immune response in the skin under immunocompetent and immunosuppressed conditions in an outbred animal model, irrespective of the infection status at the time of vaccination. These findings provide the basis for the clinical development of potent vaccination strategies against cutaneous HPV infections and HPV-induced tumors, especially in patients awaiting organ transplantation. © 2014 Vinzón et al.

Antonsson A.,Queensland Institute of Medical Research | Pawlita M.,German Cancer Research Center | Feltkamp M.C.,Leiden University | Bouwes Bavinck J.N.,Leiden University | And 7 more authors.
Journal of Medical Virology | Year: 2013

The human polyomaviruses BKV and JCV cause mostly subclinical infections in childhood. Systemical immunosuppression after organ transplantation can lead to reactivation of persistent polyomavirus infections which may cause rejection of the transplanted organ. BKV and JCV seroprevalence and serostability was measured in 441 European solid organ transplanted recipients. Baseline samples were collected on average 24 days post-transplantation and sera were then collected over an 18 months follow-up period on up to six different time points. The overall seroprevalence at baseline for BKV was 97% with very little change over time. Prevalence for JCV was 76% at baseline and increased to 80% at the end of follow-up. BKV seroprevalence was highest in the youngest age group (100%) and decreased with increasing age (92% in the oldest age group; P<0.0001), while JCV increased with age (69% vs. 81%; P=0.020). Antibody reactivities for both BKV and JCV increased significantly with time (P=0.0002 and P<0.0001, respectively). Among the 406 patients with several samples, 94% were stably seropositive for BKV and 1% remained seronegative during the follow-up. JCV antibody stability was somewhat lower: 67% remained stably seropositive and 13% seronegative. While seroprevalence of BKV and JCV decrease and increase with age, respectively, both polyomaviruses showed significant increasing antibody reactivity over time in organ transplanted recipients at the onset of immunosuppression. J. Med. Virol. 85:327-335, 2013. © 2012 Wiley Periodicals, Inc. Copyright © 2012 Wiley Periodicals, Inc.

Simon D.,Albert Ludwigs University of Freiburg | Kriston L.,University of Hamburg | Loh A.,Albert Ludwigs University of Freiburg | Spies C.,University Hospital of Berlin | And 4 more authors.
Health Expectations | Year: 2010

Objective Validation of the German version of the Autonomy-Preference-Index (API), a measure of patients' preferences for decision making and information seeking. Methods Stepwise confirmatory factor analysis was conducted on a sample of patients (n = 1592) treated in primary care for depression (n = 186), surgical and internal medicine inpatients (n = 811) and patients with minor trauma treated in an emergency department (n = 595). An initial test of the model was done on calculation and validation halves of the sample. Both local and global indexes-of-fit suggested modifications to the scale. The scale was modified and re-tested in the calculation sample and confirmed in the validation sample. Subgroup analyses for age, gender and type of treatment setting were also performed. Results The confirmatory analysis led to a modified version of the API with better local and global indexes-of-fit for samples of German-speaking patients. Two items of the sub-scale, 'preference for decision-making', and one item of the sub-scale, 'preference for information seeking', showed very low reliability scores and were deleted. Thus, several global indexes-of-fit clearly improved significantly. The modified scale was confirmed on the validation sample with acceptable to good indices of fit. Results of subgroup analyses indicated that no adaptations were necessary. Discussion and conclusions This first confirmatory analysis for a German-speaking population showed that the API was improved by the removal of several items. There were theoretically plausible explanations for this improvement suggesting that the modifications might also be appropriate in English and other language versions. © 2010 The Authors. Journal compilation © 2010 Blackwell Publishing Ltd.

Kavvadias T.,Cantonal Hospital of Lucerne | Baessler K.,University Hospital of Berlin | Schuessler B.,Cantonal Hospital of Lucerne
International Urogynecology Journal and Pelvic Floor Dysfunction | Year: 2012

Therapeutic options for chronic pelvic pain in women offer only a limited symptom relief. Especially in the patient with lower urinary tract symptoms (LUTS), where overlap of pain, storage and voiding symptoms is common, data on the efficacy of treatment of pain are limited. We conducted a literature review to detect articles which pertained to female patients with LUTS and pelvic pain and we included articles which evaluated the efficacy of the treatment of pelvic pain. Forty-one articles were detected, which included nerve stimulation (sacral and pudendal), intravesical instillations and injections, oral pharmacological treatments, periurethral injections as well as physical and manual therapy as treatment options. Only five controlled trials were found, which did not show superiority of the active treatment versus placebo. Although some treatment options show promising results in the treatment of pelvic pain in patients with LUTS, more randomised controlled trials are needed to confirm these results. © The International Urogynecological Association 2012.

Esgueva R.,New York Medical College | Perner S.,University Hospital of Tuebingen | J Lafargue C.,New York Medical College | Scheble V.,University Hospital of Tuebingen | And 6 more authors.
Modern Pathology | Year: 2010

The majority of prostate cancers harbor recurrent gene fusions between the hormone-regulated TMPRSS2 and members of the ETS family of transcription factors, most commonly ERG. Prostate cancer with ERG rearrangements represent a distinct sub-class of tumor based on studies reporting associations with histomorphologic features, characteristic somatic copy number alterations, and gene expression signatures. This study describes the frequency of ERG rearrangement prostate cancer and three 5 prime (5′) gene fusion partners (ie, TMPRSS2, SLC45A3, and NDRG1) in a large prostatectomy cohort. ERG gene rearrangements and mechanism of rearrangement, as well as rearrangements of TMPRSS2, SLC45A3, and NDRG1, were assessed using fluorescence in situ hybridization (FISH) on prostate cancer samples from 614 patients treated using radical prostatectomy. ERG rearrangement occurred in 53% of the 540 assessable cases. TMPRSS2 and SLC45A3 were the only 5′ partner in 78% and 6% of these ERG rearranged cases, respectively. Interestingly, 11% of the ERG rearranged cases showed concurrent TMPRSS2 and SLC45A3 rearrangements. TMPRSS2 or SLC45A3 rearrangements could not be identified for 5% of the ERG rearranged cases. From these remaining cases we identified one case with NDRG1 rearrangement. We did not observe any associations with pathologic parameters or clinical outcome. This is the first study to describe the frequency of SLC45A3-ERG fusions in a large clinical cohort. Most studies have assumed that all ERG rearranged prostate cancers harbor TMPRSS2-ERG fusions. This is also the first study to report concurrent TMPRSS2 and SLC45A3 rearrangements in the same tumor focus, suggesting additional complexity that had not been previously appreciated. This study has important clinical implications for the development of diagnostic assays to detect ETS rearranged prostate cancer. Incorporation of these less common ERG rearranged prostate cancer fusion assays could further increase the sensitivity of the current PCR-based approaches. © 2010 USCAP, Inc. All rights reserved.

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