A5078378771- Neuroblastoma Research and Treatments
- Cancer, Hypoxia, and Metabolism
- Neuroendocrine Tumor Research Advances
- Cancer therapeutics and mechanisms
- Lung Cancer Research Studies
- Virus-based gene therapy research
- Receptor Mechanisms and Signaling
- Cancer, Stress, Anesthesia, and Immune Response
- Ubiquitin and proteasome pathways
- Inflammatory mediators and NSAID effects
- Cancer Mechanisms and Therapy
- Neuropeptides and Animal Physiology
- Epigenetics and DNA Methylation
- Glioma Diagnosis and Treatment
- Eicosanoids and Hypertension Pharmacology
- Immune cells in cancer
- Cell death mechanisms and regulation
- Protein Degradation and Inhibitors
- Retinoids in leukemia and cellular processes
- Adrenal and Paraganglionic Tumors
- Childhood Cancer Survivors' Quality of Life
- Neurofibromatosis and Schwannoma Cases
- Signaling Pathways in Disease
- Cancer-related gene regulation
- Cancer-related Molecular Pathways
Karolinska University Hospital
2016-2025
Karolinska Institutet
2016-2025
Svenska Örtmedicinska Institute
2012-2024
Weatherford College
2021
Stockholm Health Care Services
2013-2017
Université Paris Cité
2014
University of Gothenburg
1996-2014
Sahlgrenska University Hospital
1998-2014
Moffitt Cancer Center
2014
Ludwig Cancer Research
2014
PR-39, a proline/arginine-rich peptide antibiotic, has been purified from pig intestine and later shown to originate in the bone marrow. Intending isolate clone for human counterpart we synthesized PCR probe derived PR-39 gene. However, when this was used screen marrow cDNA library, eight clones were obtained with information another putative designated FALL-39 after first four residues. is 39-residue lacking cysteine tryptophan. All antibiotics previously isolated (or predicted) belong...
The MYC genes are the most frequently activated oncogenes in human tumors and hence attractive therapeutic targets. MYCN amplification leads to poor clinical outcome childhood neuroblastoma, yet strategies modulate function of do not exist. Here we show that 10058-F4, a characterized c-MYC/Max inhibitor, also targets MYCN/Max interaction, leading cell cycle arrest, apoptosis, neuronal differentiation -amplified neuroblastoma cells increased survival transgenic mice. We report discovery...
Abstract The DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) is commonly overexpressed in cancers and implicated the development of chemoresistance. use drugs inhibiting MGMT has been hindered by their haematologic toxicity inefficiency. As a different strategy to inhibit we investigated cellular regulators expression multiple cancers. Here show significant correlation between Wnt signalling with origin confirm findings bioinformatic analysis immunofluorescence. We...
Purpose In neuroblastoma, the ALK receptor tyrosine kinase is activated by point mutations. We investigated potential role of mutations in neuroblastoma clonal evolution. Methods analyzed 54 paired diagnosis–relapse samples using Sanger sequencing. When an mutation was observed one sample, a minor mutated component other sample searched for more than 100,000× deep sequencing relevant hotspot, with sensitivity 0.17%. Results All nine ALK-mutated cases at diagnosis demonstrated same relapse,...
Abstract Telomerase-negative tumors maintain telomere length by alternative lengthening of telomeres (ALT), but the underlying mechanism behind ALT remains poorly understood. A proportion aggressive neuroblastoma (NB), particularly relapsed tumors, are positive for (ALT+), suggesting that a better dissection could lead to novel therapeutic opportunities. TERRA, long non-coding RNA (lncRNA) derived from ends, localizes in R-loop-dependent manner and plays crucial role maintenance. Here we...
ALK (anaplastic lymphoma kinase) is oncogenic in several tumours and has recently been identified as a predisposition gene for familial NB (neuroblastoma) harbouring mutations the TKD (tyrosine kinase domain). We have analysed large set of sporadic human primary all clinical stages chromosomal re-arrangements using CGH (comparative genomic hybridization) array (n=108) (n=90), expression related genes (n=19). amplification or in-gene were found 5% 11%, including two novel not previously...
Analysis of chromosomal aberrations is used to determine the prognosis neuroblastomas (NBs) and aid treatment decisions. MYCN amplification (MNA) alone an incomplete poor prognostic factor, chromosome 11q status has recently been included in risk classification. We analyzed 165 NB tumors using high-density SNP microarrays specifically compared high-risk groups defined by MNA ( n = 37) 11q-deletion 21). Median patient age at diagnosis was 21 months for 42 tumors, median survival time after 16...
Medulloblastomas are the most common malignant brain tumors in children. They express high levels of COX-2 and produce PGE2, which stimulates tumor cell proliferation. Human cytomegalovirus (HCMV) is prevalent human population encodes proteins that provide immune evasion strategies promote oncogenic transformation oncomodulation. In particular, HCMV induces expression; STAT3 phosphorylation; production vascular endothelial growth factor, IL-6; formation vivo. Here, we show a large proportion...
Antimicrobial peptides have been shown to exert cytotoxic activity towards cancer cells through their ability interact with negatively charged cell membranes. In this study the effect of antimicrobial peptide, LfcinB was tested in a panel human neuroblastoma lines. displayed selective against both MYCN-amplified and non-MYCN-amplified Non-transformed fibroblasts were not substantially affected by LfcinB. Treatment induced rapid destabilization cytoplasmic membrane formation blebs....
Activation of the beta-catenin and receptor kinase pathways occurs often in medulloblastoma, most common pediatric malignant brain tumor. In this study, we show that molecular cross-talk between phosphatidylinositol 3-kinase (PI3K)/Akt signaling is crucial to sustain medulloblastoma pathophysiology. Constitutive activation phosphoinositide-dependent protein 1 (PDK1), Akt, phosphorylation [corrected] glycogen synthase 3beta (GSK-3beta) was detected by immunohistochemistry all primary...
Abstract Purpose: Neuroblastoma is the most common extracranial solid cancer type in childhood, and high-risk patients have poor prognosis despite aggressive multimodal treatment. Neuroblastoma-driven inflammation contributes to induction of suppressive myeloid cells that hamper efficient antitumor immune responses. Therefore, we sought enhance immunity by removing immunosuppression mediated cells. Experimental Design: The prognostic values are demonstrated analyzing genomic datasets...
Abstract Hedgehog (HH) signaling is an important regulator of embryogenesis that has been associated with the development several types cancer. HH characterized by Smoothened (SMO)‐dependent activation GLI transcription factors, which regulate expression critical developmental genes. Neuroblastoma, embryonal tumor sympathetic nervous system, was recently shown to express high levels key molecules in this cascade. Using compounds blocking SMO (cyclopamine and SANT1) or GLI1/GLI2 (GANT61)...
Significance Cancer-related inflammation promotes progression and therapy resistance in tumors of adulthood. Knowledge concerning the significance childhood malignancies has been limited. Neuroblastoma is an embryonal tumor early with poor prognosis despite intensified therapy, biological understanding necessary to develop novel therapies. We found high-risk neuroblastoma, particular therapy-resistant subset chromosome 11q-deletion, be inflammatory driven characterized by high expression...
Childhood neuroblastoma has a remarkable variability in outcome. Age at diagnosis is one of the most important prognostic factors, with children less than 1 year old having favorable outcomes. Here we study single-cell and single-nuclei transcriptomes different clinical risk groups stages, including healthy adrenal gland. We compare tumor cell populations embryonic mouse sympatho-adrenal derivatives, post-natal human provide evidence that low high-risk have identities, representing two...
In neuroblastoma (NB), the ALK receptor tyrosine kinase can be constitutively activated through activating point mutations or genomic amplification. We studied genetic alterations in high-risk (HR) patients on HR-NBL1/SIOPEN trial to determine their frequency, correlation with clinical parameters, and prognostic impact.Diagnostic tumor samples were available from 1,092 amplification status (n = 330), mutational profile 191), both 571).Genomic (ALKa) was detected 4.5% of cases (41 out 901),...
Understanding the complete immune cell composition of human neuroblastoma (NB) is crucial for development immunotherapeutics. Here, we perform single-cell RNA sequencing (scRNA-seq) on 19 NB samples coupled with multiplex immunohistochemistry, survival analysis, and comparison normal fetal adrenal gland data. We provide a comprehensive landscape characterize cell-state changes from tissue to NB. Our analysis reveals 27 subtypes, including distinct subpopulations myeloid, NK, B, T cells....
Neuroblastoma is an aggressive pediatric cancer with a high rate of metastasis to the bone marrow. Despite intensive treatments including high-dose chemotherapy, overall survival for children metastatic neuroblastoma remains dismal. Understanding cellular and molecular mechanisms tumor microenvironment crucial developing new therapies improving clinical outcomes. Here, we used single-cell RNA-sequencing characterize immune cell alterations in marrow metastases by comparative analysis...