TY  - JOUR
A1  - Nolte, Thomas
A1  - Zadeh-Khorasani, Maryam
A1  - Safarov, Orkhan
A1  - Rueff, Franziska
A1  - Varga, Rita
A1  - Herbach, Nadja
A1  - Wanke, Rüdiger
A1  - Wollenberg, Andreas
A1  - Mueller, Thomas
A1  - Gropp, Roswitha
A1  - Wolf, Eckhard
A1  - Siebeck, Matthias
T1  - Induction of oxazolone-mediated features of atopic dermatitis in NOD-scid \(IL2Rγ^{null}\) mice engrafted with human peripheral blood mononuclear cells
JF  - Disease Models and Mechanisms
N2  - Animal models mimicking human diseases have been used extensively to study the pathogenesis of autoimmune diseases and the efficacy of potential therapeutics. They are, however, limited with regard to their similarity to the human disease and cannot be used if the antagonist and its cognate receptor require high similarity in structure or binding. Here, we examine the induction of oxazolone-mediated features of atopic dermatitis (AD) in NOD-scid IL2Rγnull mice engrafted with human peripheral blood mononuclear cells (PBMC). The mice developed the same symptoms as immunocompetent BALB/c mice. Histological alterations induced by oxazolone were characterized by keratosis, epithelial hyperplasia and influx of inflammatory cells into the dermis and epidermis. The cellular infiltrate was identified as human leukocytes, with T cells being the major constituent. In addition, oxazolone increased human serum IgE levels. The response, however, required the engraftment of PBMC derived from patients suffering from AD, which suggests that this model reflects the immunological status of the donor. Taken together, the model described here has the potential to evaluate the efficacy of therapeutics targeting human lymphocytes in vivo and, in addition, might be developed further to elucidate molecular mechanisms inducing and sustaining flares of the disease.
KW  - human diseases
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-124150
VL  - 6
ER  - 
TY  - JOUR
A1  - Rhiem, Kerstin
A1  - Engel, Christoph
A1  - Graeser, Monika
A1  - Zachariae, Silke
A1  - Kast, Karin
A1  - Kiechle, Marion
A1  - Ditsch, Nina
A1  - Janni, Wolfgang
A1  - Mundhenke, Christoph
A1  - Golatta, Michael
A1  - Varga, Dominic
A1  - Preisler-Adams, Sabine
A1  - Heinrich, Tilman
A1  - Bick, Ulrich
A1  - Gadzicki, Dorothea
A1  - Briest, Susanne
A1  - Meindl, Alfons
A1  - Schmutzler, Rita K.
T1  - The risk of contralateral breast cancer in patients from BRCA1/2 negative high risk families as compared to patients from BRCA1 or BRCA2 positive families: a retrospective cohort study
JF  - Breast Cancer Research
N2  - Introduction: While it has been reported that the risk of contralateral breast cancer in patients from BRCA1 or BRCA2 positive families is elevated, little is known about contralateral breast cancer risk in patients from high risk families that tested negative for BRCA1/2 mutations.
Methods: A retrospective, multicenter cohort study was performed from 1996 to 2011 and comprised 6,235 women with unilateral breast cancer from 6,230 high risk families that had tested positive for BRCA1 (n = 1,154) or BRCA2 (n = 575) mutations or tested negative (n = 4,501). Cumulative contralateral breast cancer risks were calculated using the Kaplan-Meier product-limit method and were compared between groups using the log-rank test. Cox regression analysis was applied to assess the impact of the age at first breast cancer and the familial history stratified by mutation status.
Results: The cumulative risk of contralateral breast cancer 25 years after first breast cancer was 44.1% (95%CI, 37.6% to 50.6%) for patients from BRCA1 positive families, 33.5% (95%CI, 22.4% to 44.7%) for patients from BRCA2 positive families and 17.2% (95%CI, 14.5% to 19.9%) for patients from families that tested negative for BRCA1/2 mutations. Younger age at first breast cancer was associated with a higher risk of contralateral breast cancer. For women who had their first breast cancer before the age of 40 years, the cumulative risk of contralateral breast cancer after 25 years was 55.1% for BRCA1, 38.4% for BRCA2, and 28.4% for patients from BRCA1/2 negative families. If the first breast cancer was diagnosed at the age of 50 or later, 25-year cumulative risks were 21.6% for BRCA1, 15.5% for BRCA2, and 12.9% for BRCA1/2 negative families.
Conclusions: Contralateral breast cancer risk in patients from high risk families that tested negative for BRCA1/2 mutations is similar to the risk in patients with sporadic breast cancer. Thus, the mutation status should guide decision making for contralateral mastectomy.
KW  - contralateral breast cancer
KW  - BRCA1/2 negative
KW  - BRCA1 positive
KW  - BRCA2 positive
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-135715
VL  - 14
IS  - 6
ER  -