A5076512550- Glioma Diagnosis and Treatment
- Hedgehog Signaling Pathway Studies
- Cancer Mechanisms and Therapy
- Microtubule and mitosis dynamics
- Genomics and Chromatin Dynamics
- Cancer, Hypoxia, and Metabolism
- Epigenetics and DNA Methylation
- Genetic and Kidney Cyst Diseases
- Neurofibromatosis and Schwannoma Cases
- Teratomas and Epidermoid Cysts
- Hepatocellular Carcinoma Treatment and Prognosis
- Liver physiology and pathology
- MicroRNA in disease regulation
- Neuroblastoma Research and Treatments
University Medical Center Groningen
2014-2022
University of Groningen
2018-2022
Up to now, several clinical studies have been started investigating the relevance of receptor tyrosine kinase (RTK) inhibitors upon progression free survival in various pediatric brain tumors. However, single targeted inhibition failed, possibly due tumor resistance mechanisms. The present study will extend our previous observations that vascular endothelial growth factor (VEGFR)-2, platelet derived (PDGFR)β, Src, epidermal (ErbB) family, and hepatocyte (HGFR/cMet) are potentially drugable...
The brain cancer medulloblastoma consists of different transcriptional subgroups. To characterize at the phosphoprotein-signaling level, we performed high-throughput peptide phosphorylation profiling on a large cohort SHH (Sonic Hedgehog), group 3, and 4 medulloblastomas. We identified two major protein-signaling profiles. One profile was associated with rapid death post-recurrence resembled MYC-like signaling for which MYC lesions are sufficient but not necessary. second showed enrichment...
Medulloblastoma consists of different transcriptional subgroups. To characterize medulloblastoma at the phosphoprotein-signaling level, we performed high-throughput peptide phosphorylation profiling on a cohort SHH, Group 3 and 4 medulloblastomas. We identified two major protein-signaling profiles. One profile was associated with rapid death post-recurrence resembled MYC-like signaling for which MYC lesions are sufficient but not necessary. The second showed DNA damage, apoptotic neuronal...
While there has been significant progress in the molecular characterization of childhood brain cancer medulloblastoma, tumor proteome remains less explored. However, it is important to obtain a complete understanding medulloblastoma protein biology, since interactions between proteins represent potential new drug targets. Using previously generated phosphoprotein signaling-profiles large cohort primary we discovered that phosphorylation transcription factor CREB strongly correlates with...
Sonic hedgehog (SHH) medulloblastoma originates from the cerebellar granule neuron progenitor (CGNP) lineage, which depends on Hedgehog signaling for its perinatal expansion. Whereas SHH tumors exhibit overall deregulation of this pathway, they also show patient age-specific aberrations. To investigate whether developmental stage CGNP can account these lesions, we analyzed developing murine transcriptomes and observed highly dynamic gene expression as a function age. Cross-species comparison...
Recent clinical trials investigating receptor tyrosine kinase (RTK) inhibitors showed a limited response in medulloblastoma. The present study investigated the role of micro-environmental growth factors expressed brain, such as HGF and EGF, relation to effects hepatocyte factor (MET) epidermal family (ErbB1-4) inhibition medulloblastoma cell lines. Medulloblastoma lines were treated with crizotinib or canertinib, targeting MET ErbB1-4, respectively. Upon treatment, cells stimulated VEGF-A,...
Abstract Prognosis for recurrent medulloblastoma patients is extremely poor, with a median survival of 26.8 months. Treatment options are limited and ineffective due to resistance chemotherapeutic agents radiotherapy. Therefore, more research required address the high mortality that have therapy-resistant medulloblastoma. In previous, study, we showed cyclic-AMP responsive element binding protein (CREB1) was highly phosphorylated in primary specimens. CREB an important transcription factor...
Abstract Medulloblastoma is the most common malignant pediatric brain tumor. Unfortunately, conventional therapies have led to long-term side effects in majority of survivors. Therefore, novel inhibiting specific target molecules seem promising. However, efficacy these drug treatments targeting tyrosine kinases often hampered, leading tumor recurrence within several months treatment. The aim this study examine whether various growth factors, present micro-environment, are able influence...
Abstract Recent clinical trials investigating receptor tyrosine kinase (RTK) inhibitors showed limited responses in medulloblastoma. An emerging concept is the role of tumor microenvironment bypassing targeted therapies by producing ligands that can compensate for drug-inhibited RTK via alternative routes pathway activation. The aim this study to investigate well-known CNS expressed growth factors relation effects hepatocyte factor (MET) and epidermal family (EGFR, ErbB2-4) inhibition on...
Sonic Hedgehog (SHH) medulloblastoma originates from the cerebellar granule neuron progenitor (CGNP) population that depends on signaling for its expansion. While SHH tumors are characterized by an overall deregulation of this pathway, they also exhibit aberrations specific patient age. To investigate if developmental stage tumor cell-of-origin can account these age-specific lesions, we compared transcriptomes developing mouse CGNPs and observed highly dynamic gene expression changes as...
Summary Sonic Hedgehog (SHH) medulloblastoma originates from the cerebellar granule neuron progenitor (CGNP) lineage that depends on signaling for its perinatal expansion. While SHH tumors exhibit overall deregulation of this pathway, they also show patient age-specific aberrations. To investigate if developmental stage CGNP can account these lesions, we analyzed developing murine transcriptomes and observed highly dynamic gene expression as function age. Cross-species comparison with human...