Prof. Dr. Grotzer Michael

Main Field(s) of Research, Abstract
Primitive neuroectodermal brain tumors (PNET) including medulloblastoma (PNET/MB) are the most common malignant childhood brain tumors. Because of the high risk of leptomeningeal dissemination, standard postoperative treatment for PNET includes not only local radiotherapy, but also craniospinal radiotherapy and chemotherapy. Such treatment causes long-term morbidity including endocrine and growth disturbances, as well as neurocognitive dysfunction, which is particularly severe in young children. To identify molecular prognostic markers of use for routine disease risk stratification of children with PNET/MB, we analyze prospectively the expression of c-MYC, TrkC, and other candidates by quantitative RT-PCR in a European multi-institution group effort. To understand the role(s) of Trk receptor function in PNET, we analyze the effects of neurotrophin addition and withdrawal on primary cultures of PNET and human PNET cell lines expressing different levels of TrkC, and examine radio-sensitivity and sensitivity to anti-tumor drugs. Ultimately, better knowledge about neurotrophins, Trk receptors, and c-MYC in PNET biology may lead to the development of individualized less toxic treatment regimens that increase the quality of life for many long-term survivors.

Central nervous system (CNS) atypical teratoid/rhabdoid tumors (ATT/RhT) are among the pediatric malignant tumors with the worst prognosis and fatal outcome. To date there are no explanations for their remarkable resistance to cytostatic drugs and radiotherapy. Insulin-like growth factor I receptor (IGF-IR) plays a critical role in cell survival, proliferation, transformation and regulation of apoptosis. We expect that our efforts to modulate the function of IGF-IR in ATT/RhT will form the basis of a better understanding of ATT/RhT biology and lead to novel therapeutic strategies.

The Swiss Pediatric Oncology Group (SPOG) Tumor Bank aims to create a national basis for research into the molecular, genetic, immunological and other characteristic features of children's tumors.

Main Fields of Research, Keywords
Brain tumor; medulloblastoma; primitive neuroectodermal tumor; ATT/RhT; neurotrophin-receptor TrkC; oncogene c-MYC; telomerase; apoptosis; tumor bank; experimental therapies

Special Techniques and Equipment
Quantitative real-time RT-PCR
Microarray Analysis
Methylation-specific PCR
Gene-Transfection
Cell Culture
Western
ELISA
Apoptosis assays
Telomerase assays

Education and Training
We have training opportunities for MD students and postdoctoral candidates to conduct translational research in the research topics mentioned above.