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Heidelberg, Germany

Bell E.,Northumbria University | Bell E.,German Cancer Center | Ponthan F.,Northumbria University | Whitworth C.,Northumbria University | And 3 more authors.
Clinical and Experimental Metastasis | Year: 2014

COX2 is an inducible cyclooxygenase implicated in the metastasis and migration of tumour cells. In neuroblastoma, COX2 expression has been detected in both cell lines and tumours. The treatment of neuroblastoma cells in vitro with celecoxib, a COX2 inhibitor, induces apoptosis. The aim of this study was to investigate the role of COX2 in neuroblastoma tumour biology by creating a cell line in which COX2 could be conditionally expressed. Xenograft studies showed that the conditional expression of COX2 enhanced tumour growth and malignancy. Elevated COX2 expression enhanced the proliferation and migration of neuroblastoma cells in vitro. However, elevated COX2 expression or variation between cell lines did not affect sensitivity to the COX2 inhibitor celecoxib, indicating that celecoxib does not promote cell death through COX2 inhibition. These data show that increased COX2 expression alone can enhance the tumorigenic properties of neuroblastoma cells; however, high levels of COX2 may not be a valid biomarker of sensitivity to non-steroidal anti-inflammatory drugs such as celecoxib. © 2014 Springer Science+Business Media. Source

Abschuetz O.,German Cancer Research Center | Osen W.,German Cancer Center | Frank K.,German Cancer Research Center | Kato M.,Chubu University | And 2 more authors.
Cancers | Year: 2012

Poor response of human malignant melanoma to currently available treatments requires a development of innovative therapeutic strategies. Their evaluation should be based on animal models that resemble human melanoma with respect to genetics, histopathology and clinical features. Here we used a transgenic mouse model of spontaneous skin melanoma, in which the ret transgene is expressed in melanocytes under the control of metallothionein-I promoter. After a short latency, around 25% mice develop macroscopic skin melanoma metastasizing to lymph nodes, bone marrow, lungs and brain, whereas other transgenic mice showed only metastatic lesions without visible skin tumors. We found that tumor lesions expressed melanoma associated antigens (MAA) tyrosinase, tyrosinase related protein (TRP)-1, TRP-2 and gp100, which could be applied as targets for the immunotherapy. Upon peptide vaccination, ret transgenic mice without macroscopic melanomas were able to generate T cell responses not only against a strong model antigen ovalbumin but also against typical MAA TRP-2. Although mice bearing macroscopic primary tumors could also display an antigen-specific T cell reactivity, it was significantly down-regulated as compared to tumor-free transgenic mice or non-transgenic littermates. We suggest that ret transgenic mice could be used as a pre-clinical model for the evaluation of novel strategies of melanoma immunotherapy. © 2012 by the authors; licensee MDPI, Basel, Switzerland. Source

Urbich C.,Goethe University Frankfurt | Kaluza D.,Goethe University Frankfurt | Fromel T.,Goethe University Frankfurt | Knau A.,Goethe University Frankfurt | And 11 more authors.
Blood | Year: 2012

MicroRNAs (miRs) are small RNAs that regulate gene expression at the posttranscriptional level. miR-27 is expressed in endothelial cells, but the specific functions of miR-27b and its family member miR-27a are largely unknown. Here we demonstrate that overexpression of miR-27a and miR-27b significantly increased endothelial cell sprouting. Inhibition of both miR-27a and miR-27b impaired endothelial cell sprout formation and induced endothelial cell repulsion in vitro. In vivo, inhibition of miR-27a/b decreased the number of perfused vessels in Matrigel plugs and impaired embryonic vessel formation in zebrafish. Mechanistically, miR-27 regulated the expression of the angiogenesis inhibitor semaphorin 6A (SEMA6A) in vitro and in vivo and targeted the 3′-untranslated region of SEMA6A. Silencing of SEMA6A partially reversed the inhibition of endothelial cell sprouting and abrogated the repulsion of endothelial cells mediated by miR-27a/b inhibition, indicating that SEMA6A is a functionally relevant miR-27 downstream target regulating endothelial cell repulsion. In summary, we show that miR-27a/b promotes angiogenesis by targeting the angiogenesis inhibitor SEMA6A, which controls repulsion of neighboring endothelial cells. © 2012 by The American Society of Hematology. Source

Huy C.,11 Health | Steindorf K.,German Cancer Center | Litaker D.,11 Health | Thiel A.,University of Tubingen | Diehm C.,University of Heidelberg
European Journal of Sport Science | Year: 2011

Little is known about physical activity in adults at differing risk of cardiovascular disease (CVD). Here, we describe and compare the physical activity and patterns of association with physical activity by CVD risk status based on data from computer-assisted telephone interviews of 2002 men and women aged 50-70 years in Germany. Physical activity preferences, settings, and health-related attitudes were assessed and groups were compared using chi-square and non-parametric tests. Stratified multi-variable regression models identified factors associated with regular physical activity (at least once a week for 6 months). The proportion of respondents engaging in regular physical activity ranged from 53.8% to 60.6% across the groups (P=0.08). Respondents with and without CVD/CVD risk factors varied modestly regarding the type and settings for physical activity. However, models stratified by CVD risk demonstrated different patterns of association with regular physical activity. Socioeconomic status, for example, was important for respondents with CVD-related risk factors (odds ratio=2.30; 95%CI: 1.38 to 3.85 for high vs. low socioeconomic status), while internal health locus of control and other attitudes towards physical activity were important for respondents with CVD (odds ratio=1.20; 95%CI: 1.06 to 1.35 per unit increase at subscale score). Our data provide opportunities for developing physical activity interventions targeted at individuals with differing cardiovascular risk. © 2011 Copyright European College of Sport Science. Source

Andreotti G.,U.S. National Cancer Institute | Birmann B.,Brigham and Womens Hospital | De Roos A.J.,Fred Hutchinson Cancer Research Center | Spinelli J.,University of British Columbia | And 27 more authors.
Cancer Epidemiology Biomarkers and Prevention | Year: 2013

Background: Recent findings suggest that alcohol consumption may reduce risk of multiple myeloma. Methods: To better understand this relationship, we conducted an analysis of six case-control studies participating in the International Multiple Myeloma Consortium (1,567 cases, 7,296 controls). Summary ORs and 95% confidence intervals (CI) relating different measures of alcohol consumption and multiple myeloma risk were computed by unconditional logistic regression with adjustment for age, race, and study center. Results: Cases were significantly less likely than controls to report ever drinking alcohol (men: OR = 0.72; 95% CI, 0.59-0.89; women: OR = 0.81; 95% CI, 0.68-0.95). The inverse association with multiple myeloma was stronger when comparing current to never drinkers (men:OR=0.57; 95% CI, 0.45-0.72; women:OR=0.55; 95% CI, 0.45-0.68), but null among former drinkers. We did not observe an exposure-response relationship with increasing alcohol frequency, duration, or cumulative lifetime consumption. Additional adjustment for body mass index, education, or smoking did not affect our results; and the patterns of association were similar for each type of alcohol beverage examined. Conclusions: Our study is, to our knowledge, the largest of its kind to date, and our findings suggest that alcohol consumption may be associated with reduced risk of multiple myeloma. Impact: Prospective studies, especially those conducted as pooled analyses with large sample sizes, are needed to confirm our findings and further explore whether alcohol consumption provides true biologic protection against this rare, highly fatal malignancy. © 2013 AACR. Source

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