TY  - JOUR
A1  - Moll, Heidrun
A1  - Müller, Christoph
A1  - Gillitzer, Reinhard
A1  - Fuchs, Harald
A1  - Röllinghoff, Martin
A1  - Simon, Markus M.
A1  - Kramer, Michael D.
T1  - Expression of T-cell-associated serine proteinase-1 during murine Leishmania major infection correlates with susceptibility to disease
N2  - The expression of T-cell-associated serine proteinase 1 (MTSP-1) in vivo during Leishmania major infection was analyzed in genetically resistant C57BL/6 mice and in genetically susceptible BALB/c mice. Using a monoclonal antibody as well as an RNA probe specific for MTSP-1 to stain tissue sections, we found T cells expressing MTSP-1 in skin lesions and spleens of mice of both strains. In skin lesions, MTSP-1-positive T cells could be detected as early as 3 days after infection. Most importantly, the frequency of T cells expressing MTSP-1 was significantly higher in susceptible BALB/c mice than in resistant C57BL/6 mice. These findings suggest that MTSP-1 is associated with disease-promoting T cells and that it may be an effector molecule involved in the pathogenesis of cutaneous leishmaniasis.
KW  - Biologie
KW  - Immunologie
Y1  - 1991
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61311
ER  - 
TY  - JOUR
A1  - Nemes, Karolina
A1  - Johann, Pascal D.
A1  - Steinbügl, Mona
A1  - Gruhle, Miriam
A1  - Bens, Susanne
A1  - Kachanov, Denis
A1  - Teleshova, Margarita
A1  - Hauser, Peter
A1  - Simon, Thorsten
A1  - Tippelt, Stephan
A1  - Eberl, Wolfgang
A1  - Chada, Martin
A1  - Lopez, Vicente Santa-Maria
A1  - Grigull, Lorenz
A1  - Hernáiz-Driever, Pablo
A1  - Eyrich, Matthias
A1  - Pears, Jane
A1  - Milde, Till
A1  - Reinhard, Harald
A1  - Leipold, Alfred
A1  - van de Wetering, Marianne
A1  - Gil-da-Costa, Maria João
A1  - Ebetsberger-Dachs, Georg
A1  - Kerl, Kornelius
A1  - Lemmer, Andreas
A1  - Boztug, Heidrun
A1  - Furtwängler, Rhoikos
A1  - Kordes, Uwe
A1  - Vokuhl, Christian
A1  - Hasselblatt, Martin
A1  - Bison, Brigitte
A1  - Kröncke, Thomas
A1  - Melchior, Patrick
A1  - Timmermann, Beate
A1  - Gerss, Joachim
A1  - Siebert, Reiner
A1  - Frühwald, Michael C.
T1  - Infants and newborns with atypical teratoid rhabdoid tumors (ATRT) and extracranial malignant rhabdoid tumors (eMRT) in the EU-RHAB registry: a unique and challenging population
JF  - Cancers
N2  - Introduction: Malignant rhabdoid tumors (MRT) predominantly affect infants and young children. Patients below six months of age represent a particularly therapeutically challenging group. Toxicity to developing organ sites limits intensity of treatment. Information on prognostic factors, genetics, toxicity of treatment and long-term outcomes is sparse. Methods: Clinical, genetic, and treatment data of 100 patients (aged below 6 months at diagnosis) from 13 European countries were analyzed (2005–2020). Tumors and matching blood samples were examined for SMARCB1 mutations using FISH, MLPA and Sanger sequencing. DNA methylation subgroups (ATRT-TYR, ATRT-SHH, and ATRT-MYC) were determined using 450 k / 850 k-profiling. Results: A total of 45 patients presented with ATRT, 29 with extracranial, extrarenal (eMRT) and 9 with renal rhabdoid tumors (RTK). Seventeen patients demonstrated synchronous tumors (SYN). Metastases (M+) were present in 27% (26/97) at diagnosis. A germline mutation (GLM) was detected in 55% (47/86). DNA methylation subgrouping was available in 50% (31 / 62) with ATRT or SYN; for eMRT, methylation-based subgrouping was not performed. The 5-year overall (OS) and event free survival (EFS) rates were 23.5 ± 4.6% and 19 ± 4.1%, respectively. Male sex (11 ± 5% vs. 35.8 ± 7.4%), M+ stage (6.1 ± 5.4% vs. 36.2 ± 7.4%), presence of SYN (7.1 ± 6.9% vs. 26.6 ± 5.3%) and GLM (7.7 ± 4.2% vs. 45.7 ± 8.6%) were significant prognostic factors for 5-year OS. Molecular subgrouping and survival analyses confirm a previously described survival advantage for ATRT-TYR. In an adjusted multivariate model, clinical factors that favorably influence the prognosis were female sex, localized stage, absence of a GLM and maintenance therapy. Conclusions: In this cohort of homogenously treated infants with MRT, significant predictors of outcome were sex, M-stage, GLM and maintenance therapy. We confirm the need to stratify which patient groups benefit from multimodal treatment, and which need novel therapeutic strategies. Biomarker-driven tailored trials may be a key option.
KW  - atypical teratoid rhabdoid tumors
KW  - extracranial malignant rhabdoid tumor
KW  - RTPS1
KW  - RTPS2
KW  - germline mutation
KW  - EU-RHAB registry
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-270730
SN  - 2072-6694
VL  - 14
IS  - 9
ER  -