TY  - JOUR
A1  - Scheer, Sebastian
A1  - Krempl, Christine
A1  - Kallfass, Carsten
A1  - Frey, Stefanie
A1  - Jakob, Thilo
A1  - Mouahid, Gabriel
A1  - Mone, Helene
A1  - Schmitt-Graeff, Anette
A1  - Staeheli, Peter
A1  - Lamers, Marinus C.
T1  - S-mansoni Bolsters Anti-Viral Immunity in the Murine Respiratory Tract
JF  - PLOS ONE
N2  - The human intestinal parasite Schistosoma mansoni causes a chronic disease, schistosomiasis or bilharzia. According to the current literature, the parasite induces vigorous immune responses that are controlled by Th2 helper cells at the expense of Th1 helper cells. The latter cell type is, however, indispensable for anti-viral immune responses. Remarkably, there is no reliable literature among 230 million patients worldwide describing defective anti-viral immune responses in the upper respiratory tract, for instance against influenza A virus or against respiratory syncitial virus (RSV). We therefore re-examined the immune response to a human isolate of S. mansoni and challenged mice in the chronic phase of schistosomiasis with influenza A virus, or with pneumonia virus of mice (PVM), a mouse virus to model RSV infections. We found that mice with chronic schistosomiasis had significant, systemic immune responses induced by Th1, Th2, and Th17 helper cells. High serum levels of TNF-alpha, IFN-gamma, IL-5, IL-13, IL-2, IL-17, and GM-CSF were found after mating and oviposition. The lungs of diseased mice showed low-grade inflammation, with goblet cell hyperplasia and excessive mucus secretion, which was alleviated by treatment with an anti-TNF-alpha agent (Etanercept). Mice with chronic schistosomiasis were to a relative, but significant extent protected from a secondary viral respiratory challenge. The protection correlated with the onset of oviposition and TNF-alpha-mediated goblet cell hyperplasia and mucus secretion, suggesting that these mechanisms are involved in enhanced immune protection to respiratory viruses during chronic murine schistosomiasis. Indeed, also in a model of allergic airway inflammation mice were protected from a viral respiratory challenge with PVM.
KW  - innate lymphoid cells
KW  - necrosis-factor-alpha
KW  - CD4(+) T-cells
KW  - helminth infection
KW  - pneumona virus
KW  - dendritic cells
KW  - TNF-alpha
KW  - in-vivo
KW  - cytokine responses
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-114723
SN  - 1932-6203
VL  - 9
IS  - 11
ER  - 
TY  - JOUR
A1  - Scheer, Monika
A1  - Vokuhl, Christian
A1  - Blank, Bernd
A1  - Hallmen, Erika
A1  - von Kalle, Thekla
A1  - Münter, Marc
A1  - Wessalowski, Rüdiger
A1  - Hartwig, Maite
A1  - Sparber-Sauer, Monika
A1  - Schlegel, Paul-Gerhardt
A1  - Kramm, Christof M.
A1  - Kontny, Udo
A1  - Spriewald, Bernd
A1  - Kegel, Thomas
A1  - Bauer, Sebastian
A1  - Kazanowska, Bernarda
A1  - Niggli, Felix
A1  - Ladenstein, Ruth
A1  - Ljungman, Gustaf
A1  - Jahnukainen, Kirsi
A1  - Fuchs, Jörg
A1  - Bielack, Stefan S.
A1  - Klingebiel, Thomas
A1  - Koscielniak, Ewa
T1  - Desmoplastic small round cell tumors: Multimodality treatment and new risk factors
JF  - Cancer Medicine
N2  - Background

To evaluate optimal therapy and potential risk factors.

Methods

Data of DSRCT patients <40 years treated in prospective CWS trials 1997-2015 were analyzed.

Results

Median age of 60 patients was 14.5 years. Male:female ratio was 4:1. Tumors were abdominal/retroperitoneal in 56/60 (93%). 6/60 (10%) presented with a localized mass, 16/60 (27%) regionally disseminated nodes, and 38/60 (63%) with extraperitoneal metastases. At diagnosis, 23/60 (38%) patients had effusions, 4/60 (7%) a thrombosis, and 37/54 (69%) elevated CRP. 40/60 (67%) patients underwent tumor resection, 21/60 (35%) macroscopically complete. 37/60 (62%) received chemotherapy according to CEVAIE (ifosfamide, vincristine, actinomycin D, carboplatin, epirubicin, etoposide), 15/60 (25%) VAIA (ifosfamide, vincristine, adriamycin, actinomycin D) and, 5/60 (8%) P6 (cyclophosphamide, doxorubicin, vincristine, ifosfamide, etoposide). Nine received high-dose chemotherapy, 6 received regional hyperthermia, and 20 received radiotherapy. Among 25 patients achieving complete remission, 18 (72%) received metronomic therapies. Three-year event-free (EFS) and overall survival (OS) were 11% (±8 confidence interval [CI] 95%) and 30% (±12 CI 95%), respectively, for all patients and 26.7% (±18.0 CI 95%) and 56.9% (±20.4 CI 95%) for 25 patients achieving remission. Extra-abdominal site, localized disease, no effusion or ascites only, absence of thrombosis, normal CRP, complete tumor resection, and chemotherapy with VAIA correlated with EFS in univariate analysis. In multivariate analysis, significant factors were no thrombosis and chemotherapy with VAIA. In patients achieving complete remission, metronomic therapy with cyclophosphamide/vinblastine correlated with prolonged time to relapse.

Conclusion

Pleural effusions, venous thrombosis, and CRP elevation were identified as potential risk factors. The VAIA scheme showed best outcome. Maintenance therapy should be investigated further.
KW  - C-reactive protein
KW  - desmoplastic small round cell tumor
KW  - maintenance therapy
KW  - soft tissue sarcoma
KW  - Trousseau's syndrome
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228444
VL  - 8
IS  - 2
ER  -