0000000000636894
AUTHOR
Tobias Pukrop
showing 5 related works from this author
Effects on Survival and Neurocognitive Functions of Whole-Brain Radiotherapy (WBRT) and Autologous Stem Cell Transplantation (ASCT) as Consolidation …
2016
Abstract Introduction: IELSG32 is an international randomized phase II trial with 2 key clinical questions in pts with PCNSL. The first question focused on optimal induction therapy, and results of the 1st randomization have demonstrated that MATRix combination (methotrexate (MTX), cytarabine (ARAC), thiotepa, rituximab (R)) is associated with significantly better outcome [Ferreri AJ, et al. Lancet Haematol 2016]. The second question addresses the efficacy and neurotolerability of ASCT, as an alternative to WBRT as consolidation. Herein, we report the results of the 2nd randomization (NCT01011920). Methods: HIV-neg pts 18-70 ys and ECOG PS ≤3 with new histology-proven PCNSL and measurable d…
CD14 is a key organizer of microglial responses to CNS infection and injury
2015
Microglia, innate immune cells of the CNS, sense infection and damage through overlapping receptor sets. Toll-like receptor (TLR) 4 recognizes bacterial lipopolysaccharide (LPS) and multiple injury-associated factors. We show that its co-receptor CD14 serves three non-redundant functions in microglia. First, it confers an up to 100-fold higher LPS sensitivity compared to peripheral macrophages to enable efficient proinflammatory cytokine induction. Second, CD14 prevents excessive responses to massive LPS challenges via an interferon β-mediated feedback. Third, CD14 is mandatory for microglial reactions to tissue damage-associated signals. In mice, these functions are essential for balanced …
Whole-brain radiotherapy or autologous stem-cell transplantation as consolidation strategies after high-dose methotrexate-based chemoimmunotherapy in…
2017
Background The International Extranodal Lymphoma Study Group-32 (IELSG32) trial is an international randomised phase 2 study that addresses two key clinical questions in the treatment of patients with newly diagnosed primary CNS lymphoma. Results of the first randomisation have demonstrated that methotrexate, cytarabine, thiotepa, and rituximab (called the MATRix regimen) is the induction combination associated with significantly better outcome compared with the other induction combinations tested. Here, we report the results of the second randomisation that addresses the efficacy of myeloablative chemotherapy supported by autologous stem-cell transplantation (ASCT), as an alternative to wh…
Chemoimmunotherapy with methotrexate, cytarabine, thiotepa, and rituximab (MATRix regimen) in patients with primary CNS lymphoma: results of the firs…
2016
BACKGROUND: Standard treatment for patients with primary CNS lymphoma remains to be defined. Active therapies are often associated with increased risk of haematological or neurological toxicity. In this trial, we addressed the tolerability and efficacy of adding rituximab with or without thiotepa to methotrexate-cytarabine combination therapy (the MATRix regimen), followed by a second randomisation comparing consolidation with whole-brain radiotherapy or autologous stem cell transplantation in patients with primary CNS lymphoma. We report the results of the first randomisation in this Article.METHODS: For the international randomised phase 2 International Extranodal Lymphoma Study Group-32 …
Tyrphostin AG126 exerts neuroprotection in CNS inflammation by a dual mechanism
2015
The putative protein tyrosine kinase (PTK) inhibitor tyrphostin AG126 has proven beneficial in various models of inflammatory disease. Yet molecular targets and cellular mechanisms remained enigmatic. We demonstrate here that AG126 treatment has beneficial effects in experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. AG126 alleviates the clinical symptoms, diminishes encephalitogenic Th17 differentiation, reduces inflammatory CNS infiltration as well as microglia activation and attenuates myelin damage. We show that AG126 directly inhibits Bruton's tyrosine kinase (BTK), a PTK associated with B cell receptor and Toll-like receptor (TLR) signaling. However, BTK …