{"entity": "journal", "iuid": "75711305cda24d93a797ab473c936303", "timestamp": "2026-08-09T08:04:13.487Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/Neuro-oncology.json"}, "display": {"href": "https://publications.scilifelab.se/journal/Neuro-oncology"}}, "title": "Neuro-oncology", "issn": "1523-5866", "issn-l": "1522-8517", "publications_count": 10, "publications": [{"entity": "publication", "iuid": "a638af5681c8450aa2d7be769b749cdb", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a638af5681c8450aa2d7be769b749cdb.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a638af5681c8450aa2d7be769b749cdb"}}, "title": "High-throughput neural stem cell-based drug screening identifies S6K1 inhibition as a selective vulnerability in sonic hedgehog-medulloblastoma.", "authors": [{"family": "Zhou", "given": "Leilei", "initials": "L"}, {"family": "van Bree", "given": "Niek", "initials": "N"}, {"family": "Boutin", "given": "Lola", "initials": "L"}, {"family": "Ryu", "given": "Jinhye", "initials": "J"}, {"family": "Moussaud", "given": "Simon", "initials": "S", "orcid": "0000-0002-6340-9511", "researcher": {"href": "https://publications.scilifelab.se/researcher/a5895fb4a9354936b14c330fa8835351.json"}}, {"family": "Liu", "given": "Mingzhi", "initials": "M"}, {"family": "Otrocka", "given": "Magdalena", "initials": "M"}, {"family": "Olsson", "given": "Magnus", "initials": "M"}, {"family": "Falk", "given": "Anna", "initials": "A"}, {"family": "Wilhelm", "given": "Margareta", "initials": "M", "orcid": "0000-0002-0516-9724", "researcher": {"href": "https://publications.scilifelab.se/researcher/fa0ccfc8178142e4954e05e25613d751.json"}}], "type": "journal article", "published": "2024-09-05", "journal": {"title": "Neuro-oncology", "issn": "1523-5866", "volume": "26", "issue": "9", "pages": "1685-1699", "issn-l": "1522-8517"}, "abstract": "Medulloblastoma (MB) is one of the most common malignant brain tumors in children. Current treatments have increased overall survival but can lead to devastating side effects and late complications in survivors, emphasizing the need for new, improved targeted therapies that specifically eliminate tumor cells while sparing the normally developing brain.\n\nHere, we used a sonic hedgehog (SHH)-MB model based on a patient-derived neuroepithelial stem cell system for an unbiased high-throughput screen with a library of 172 compounds with known targets. Compounds were evaluated in both healthy neural stem cells (NSCs) and tumor cells derived from the same patient. Based on the difference of cell viability and drug sensitivity score between normal cells and tumor cells, hit compounds were selected and further validated in vitro and in vivo.\n\nWe identified PF4708671 (S6K1 inhibitor) as a potential agent that selectively targets SHH-driven MB tumor cells while sparing NSCs and differentiated neurons. Subsequent validation studies confirmed that PF4708671 inhibited the growth of SHH-MB tumor cells both in vitro and in vivo, and that knockdown of S6K1 resulted in reduced tumor formation.\n\nOverall, our results suggest that inhibition of S6K1 specifically affects tumor growth, whereas it has less effect on non-tumor cells. Our data also show that the NES cell platform can be used to identify potentially effective new therapies and targets for SHH-MB.", "doi": "10.1093/neuonc/noae104", "pmid": "38860311", "labels": {"Chemical Biology Consortium Sweden": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC11376459"}, {"db": "pii", "key": "7690843"}], "notes": [], "created": "2025-09-03T08:06:58.068Z", "modified": "2025-10-17T13:04:27.249Z"}, {"entity": "publication", "iuid": "fd4181f5019c4a9ba309492cb432228a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/fd4181f5019c4a9ba309492cb432228a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/fd4181f5019c4a9ba309492cb432228a"}}, "title": "EDA2R reflects the acute brain response to cranial irradiation in liquid biopsies.", "authors": [{"family": "Lastra Romero", "given": "Alejandro", "initials": "A"}, {"family": "Seitz", "given": "Thea", "initials": "T"}, {"family": "Zisiadis", "given": "Georgios Alkis", "initials": "GA"}, {"family": "Jeffery", "given": "Holli", "initials": "H"}, {"family": "Osman", "given": "Ahmed M", "initials": "AM", "orcid": "0000-0002-5255-2136", "researcher": {"href": "https://publications.scilifelab.se/researcher/91eb7159bac6486e897aa8b65cef1b5a.json"}}], "type": "journal article", "published": "2024-09-05", "journal": {"title": "Neuro-oncology", "issn": "1523-5866", "volume": "26", "issue": "9", "pages": "1617-1627", "issn-l": "1522-8517"}, "abstract": "Cranial radiotherapy is standard of care for high-grade brain tumors and metastases; however, it induces debilitating neurocognitive impairments in cancer survivors, especially children. As the numbers of pediatric brain cancer survivors continue improving, the numbers of individuals developing life-long neurocognitive sequalae are consequently expected to rise. Yet, there are no established biomarkers estimating the degree of the irradiation-induced brain injury at completion of radiotherapy to predict the severity of the expected neurocognitive complications. We aimed to identify sensitive biomarkers associated with brain response to irradiation that can be measured in easily accessible clinical materials, such as liquid biopsies.\n\nJuvenile mice were subjected to cranial irradiation with 0.5, 1, 2, 4, and 8 Gy. Cerebrospinal fluid (CSF), plasma, and brains were collected at acute, subacute, and subchronic phases after irradiation, and processed for proteomic screens, and molecular and histological analyses.\n\nWe found that the levels of ectodysplasin A2 receptor (EDA2R), member of tumor necrosis factor receptor superfamily, increased significantly in the CSF after cranial irradiation, even at lower irradiation doses. The levels of EDA2R were increased globally in the brain acutely after irradiation and decreased over time. EDA2R was predominantly expressed by neurons, and the temporal dynamics of EDA2R in the brain was reflected in the plasma samples.\n\nWe propose EDA2R as a promising potential biomarker reflecting irradiation-induced brain injury in liquid biopsies. The levels of EDA2R upon completion of radiotherapy may aid in predicting the severity of IR-induced neurocognitive sequalae at a very early stage after treatment.", "doi": "10.1093/neuonc/noae077", "pmid": "38683135", "labels": {"Affinity Proteomics Stockholm": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11376461"}, {"db": "pii", "key": "7655324"}], "notes": [], "created": "2025-04-30T12:45:29.575Z", "modified": "2025-04-30T12:45:32.844Z"}, {"entity": "publication", "iuid": "0af2ba2133ef426695491e3b74eea850", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0af2ba2133ef426695491e3b74eea850.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0af2ba2133ef426695491e3b74eea850"}}, "title": "Small molecule-mediated disruption of ribosome biogenesis synergizes with FGFR inhibitors to suppress glioma cell growth", "authors": [{"family": "Zisi", "given": "Asimina", "initials": "A", "orcid": "0000-0002-4253-0275", "researcher": {"href": "https://publications.scilifelab.se/researcher/5cf82380ca6e4cd1985bc9dd23789539.json"}}, {"family": "Kanellis", "given": "Dimitris C", "initials": "DC", "orcid": "0000-0001-8690-2010", "researcher": {"href": "https://publications.scilifelab.se/researcher/0921ab7566514fb0a3cd0daf2baabe6e.json"}}, {"family": "Moussaud", "given": "Simon", "initials": "S", "orcid": "0000-0002-6340-9511", "researcher": {"href": "https://publications.scilifelab.se/researcher/a5895fb4a9354936b14c330fa8835351.json"}}, {"family": "Karlsson", "given": "Ida", "initials": "I"}, {"family": "Car\u00e9n", "given": "Helena", "initials": "H", "orcid": "0000-0002-8584-555X", "researcher": {"href": "https://publications.scilifelab.se/researcher/b31c235b05d54d5ab5d65b3e640c9f66.json"}}, {"family": "Br\u00e4utigam", "given": "Lars", "initials": "L"}, {"family": "Bartek", "given": "Jiri", "initials": "J", "orcid": "0000-0003-2013-7525", "researcher": {"href": "https://publications.scilifelab.se/researcher/cd0d4d98261f41268c76dd91345a1857.json"}}, {"family": "Lindstr\u00f6m", "given": "Mikael S", "initials": "MS", "orcid": "0000-0003-1148-8497", "researcher": {"href": "https://publications.scilifelab.se/researcher/5aa942fbfbee4257a129b3e7888f5b6d.json"}}], "type": "journal-article", "published": "2023-06-02", "journal": {"title": "Neuro-oncology", "issn": "1522-8517", "issn-l": null, "volume": "25", "issue": "6", "pages": "1058-1072"}, "abstract": "High-grade gliomas are malignant brain tumors characterized by aggressiveness and resistance to chemotherapy. Prognosis remains dismal, highlighting the need to identify novel molecular dependencies and targets. Ribosome biogenesis (RiBi), taking place in the nucleolus, represents a promising target as several cancer types rely on high RiBi rates to sustain proliferation. Publicly available transcriptomics data of glioma patients revealed a positive correlation between RiBi rates and histological grades. We, therefore, hypothesized that glioma cells could be susceptible to RiBi inhibition.\r\n\r\nTranscriptomics data from glioma patients were analyzed for RiBi-related processes. BMH-21, a small molecule inhibitor of RNA polI transcription, was tested in adult and pediatric high-grade glioma cell lines and a zebrafish transplant model. Cellular phenotypes were evaluated by transcriptomics, cell cycle analysis, and viability assays. A chemical synergy screen was performed to identify drugs potentiating BMH-21-mediated effects.\r\n\r\nBMH-21 reduced glioma cell viability, induced apoptosis, and impaired the growth of transplanted glioma cells in zebrafish. Combining BMH-21 with TMZ potentiated cytotoxic effects. Moreover, BMH-21 synergized with FGFR inhibitor Erdafitinib, a top hit in the chemical synergy screen. RiBi inhibition using BMH-21, POLR1A siRNA, or Actinomycin D revealed engagement of the FGFR-FGF2 pathway. BMH-21 downregulated FGFR1 and SOX2 levels, whereas FGF2 was induced and released from the nucleolus.\r\n\r\nThis study conceptualizes the implementation of RiBi inhibition as a viable future therapeutic strategy for glioma and reveals an FGFR connection to the cellular response upon RiBi inhibition with potential translational value.", "doi": "10.1093/neuonc/noac286", "pmid": "36583853", "labels": {"Chemical Biology Consortium Sweden": "Collaborative"}, "xrefs": [{"db": "pii", "key": "6965891"}], "notes": [], "created": "2023-01-04T09:27:34.964Z", "modified": "2025-10-17T13:04:27.661Z"}, {"entity": "publication", "iuid": "21d7e28b1789437a85310459cdaa7f7e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/21d7e28b1789437a85310459cdaa7f7e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/21d7e28b1789437a85310459cdaa7f7e"}}, "title": "Novel cancer gene discovery using a forward genetic screen in RCAS-PDGFB-driven gliomas.", "authors": [{"family": "Weishaupt", "given": "Holger", "initials": "H"}, {"family": "\u010can\u010der", "given": "Matko", "initials": "M"}, {"family": "Ros\u00e9n", "given": "Gabriela", "initials": "G"}, {"family": "Holmberg", "given": "Karl O", "initials": "KO"}, {"family": "H\u00e4ggqvist", "given": "Susana", "initials": "S"}, {"family": "Bunikis", "given": "Ignas", "initials": "I"}, {"family": "Jiang", "given": "Yiwen", "initials": "Y"}, {"family": "Sreedharan", "given": "Smitha", "initials": "S"}, {"family": "Gyllensten", "given": "Ulf", "initials": "U"}, {"family": "Becher", "given": "Oren J", "initials": "OJ"}, {"family": "Uhrbom", "given": "Lene", "initials": "L"}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}, {"family": "Swartling", "given": "Fredrik J", "initials": "FJ", "orcid": "0000-0002-8460-4367", "researcher": {"href": "https://publications.scilifelab.se/researcher/69679cebbc90496f9c5b32f56d966654.json"}}], "type": "journal article", "published": "2023-01-05", "journal": {"title": "Neuro-oncology", "issn": "1523-5866", "volume": "25", "issue": "1", "pages": "97-107", "issn-l": "1522-8517"}, "abstract": "Malignant gliomas, the most common malignant brain tumors in adults, represent a heterogeneous group of diseases with poor prognosis. Retroviruses can cause permanent genetic alterations that modify genes close to the viral integration site.\n\nHere we describe the use of a high-throughput pipeline coupled to the commonly used tissue-specific retroviral RCAS-TVA mouse tumor model system. Utilizing next-generation sequencing, we show that retroviral integration sites can be reproducibly detected in malignant stem cell lines generated from RCAS-PDGFB-driven glioma biopsies.\n\nA large fraction of common integration sites contained genes that have been dysregulated or misexpressed in glioma. Others overlapped with loci identified in previous glioma-related forward genetic screens, but several novel putative cancer-causing genes were also found. Integrating retroviral tagging and clinical data, Ppfibp1 was highlighted as a frequently tagged novel glioma-causing gene. Retroviral integrations into the locus resulted in Ppfibp1 upregulation, and Ppfibp1-tagged cells generated tumors with shorter latency on orthotopic transplantation. In human gliomas, increased PPFIBP1 expression was significantly linked to poor prognosis and PDGF treatment resistance.\n\nAltogether, the current study has demonstrated a novel approach to tagging glioma genes via forward genetics, validating previous results, and identifying PPFIBP1 as a putative oncogene in gliomagenesis.", "doi": "10.1093/neuonc/noac158", "pmid": "35738865", "labels": {"NGI Uppsala (Uppsala Genome Center)": "Collaborative", "National Genomics Infrastructure": "Collaborative", "NGI Short read": "Collaborative", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9825320"}, {"db": "pii", "key": "6615415"}], "notes": [], "created": "2022-11-21T10:37:55.157Z", "modified": "2024-01-16T13:48:34.197Z"}, {"entity": "publication", "iuid": "97858c5971a0490f893b3715a005a690", "links": {"self": {"href": "https://publications.scilifelab.se/publication/97858c5971a0490f893b3715a005a690.json"}, "display": {"href": "https://publications.scilifelab.se/publication/97858c5971a0490f893b3715a005a690"}}, "title": "Distinct metabolic hallmarks of WHO classified adult glioma subtypes.", "authors": [{"family": "Bj\u00f6rkblom", "given": "Benny", "initials": "B", "orcid": "0000-0001-9347-5790", "researcher": {"href": "https://publications.scilifelab.se/researcher/acf29b039dfc496fb33c0cf7cb1d587c.json"}}, {"family": "Wibom", "given": "Carl", "initials": "C"}, {"family": "Eriksson", "given": "Maria", "initials": "M"}, {"family": "Bergenheim", "given": "A Tommy", "initials": "AT"}, {"family": "Sj\u00f6berg", "given": "Rickard L", "initials": "RL"}, {"family": "Jonsson", "given": "P\u00e4r", "initials": "P"}, {"family": "Br\u00e4nnstr\u00f6m", "given": "Thomas", "initials": "T"}, {"family": "Antti", "given": "Henrik", "initials": "H"}, {"family": "Sandstr\u00f6m", "given": "Maria", "initials": "M"}, {"family": "Melin", "given": "Beatrice", "initials": "B"}], "type": "journal article", "published": "2022-09-01", "journal": {"title": "Neuro-oncology", "issn": "1523-5866", "volume": "24", "issue": "9", "pages": "1454-1468", "issn-l": "1522-8517"}, "abstract": "Gliomas are complex tumors with several genetic aberrations and diverse metabolic programs contributing to their aggressive phenotypes and poor prognoses. This study defines key metabolic features that can be used to differentiate between glioma subtypes, with potential for improved diagnostics and subtype targeted therapy.\n\nCross-platform global metabolomic profiling coupled with clinical, genetic, and pathological analysis of glioma tissue from 224 tumors-oligodendroglioma (n = 31), astrocytoma (n = 31) and glioblastoma (n = 162)-were performed. Identified metabolic phenotypes were evaluated in accordance with the WHO classification, IDH-mutation, 1p/19q-codeletion, WHO-grading 2-4, and MGMT promoter methylation.\n\nDistinct metabolic phenotypes separate all six analyzed glioma subtypes. IDH-mutated subtypes, expressing 2-hydroxyglutaric acid, were clearly distinguished from IDH-wildtype subtypes. Considerable metabolic heterogeneity outside of the mutated IDH pathway were also evident, with key metabolites being high expression of glycerophosphates, inositols, monosaccharides, and sugar alcohols and low levels of sphingosine and lysoglycerophospholipids in IDH-mutants. Among the IDH-mutated subtypes, we observed high levels of amino acids, especially glycine and 2-aminoadipic acid, in grade 4 glioma, and N-acetyl aspartic acid in low-grade astrocytoma and oligodendroglioma. Both IDH-wildtype and mutated oligodendroglioma and glioblastoma were characterized by high levels of acylcarnitines, likely driven by rapid cell growth and hypoxic features. We found elevated levels of 5-HIAA in gliosarcoma and a subtype of oligodendroglioma not yet defined as a specific entity, indicating a previously not described role for the serotonin pathway linked to glioma with bimorphic tissue.\n\nKey metabolic differences exist across adult glioma subtypes.", "doi": "10.1093/neuonc/noac042", "pmid": "35157758", "labels": {"Swedish Metabolomics Centre": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9435506"}, {"db": "pii", "key": "6528465"}], "notes": [], "created": "2022-12-05T08:06:53.788Z", "modified": "2025-10-17T13:03:14.695Z"}, {"entity": "publication", "iuid": "38139cec014548ceb9c9565608cf39c9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/38139cec014548ceb9c9565608cf39c9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/38139cec014548ceb9c9565608cf39c9"}}, "title": "Real-time evaluation of glioblastoma growth in patient-specific zebrafish xenografts.", "authors": [{"family": "Almstedt", "given": "Elin", "initials": "E", "orcid": "0000-0002-1946-9138", "researcher": {"href": "https://publications.scilifelab.se/researcher/c4414ac7f9284bf9bf0b52530ec19ee3.json"}}, {"family": "Ros\u00e9n", "given": "Emil", "initials": "E", "orcid": "0000-0002-1664-2257", "researcher": {"href": "https://publications.scilifelab.se/researcher/db0751a3a95e488bb849059c09c4fc7d.json"}}, {"family": "Gloger", "given": "Marleen", "initials": "M"}, {"family": "Stockgard", "given": "Rebecka", "initials": "R"}, {"family": "Hekmati", "given": "Neda", "initials": "N"}, {"family": "Koltowska", "given": "Katarzyna", "initials": "K", "orcid": "0000-0002-6841-8900", "researcher": {"href": "https://publications.scilifelab.se/researcher/06a8aeda504340c1af3ab893fd413a65.json"}}, {"family": "Krona", "given": "Cecilia", "initials": "C"}, {"family": "Nelander", "given": "Sven", "initials": "S"}], "type": "journal article", "published": "2022-05-04", "journal": {"issn": "1523-5866", "title": "Neuro-oncology", "volume": "24", "issue": "5", "pages": "726-738", "issn-l": "1522-8517"}, "abstract": "Patient-derived xenograft (PDX) models of glioblastoma (GBM) are a central tool for neuro-oncology research and drug development, enabling the detection of patient-specific differences in growth, and in vivo drug response. However, existing PDX models are not well suited for large-scale or automated studies. Thus, here, we investigate if a fast zebrafish-based PDX model, supported by longitudinal, AI-driven image analysis, can recapitulate key aspects of glioblastoma growth and enable case-comparative drug testing.\n\nWe engrafted 11 GFP-tagged patient-derived GBM IDH wild-type cell cultures (PDCs) into 1-day-old zebrafish embryos, and monitored fish with 96-well live microscopy and convolutional neural network analysis. Using light-sheet imaging of whole embryos, we analyzed further the invasive growth of tumor cells.\n\nOur pipeline enables automatic and robust longitudinal observation of tumor growth and survival of individual fish. The 11 PDCs expressed growth, invasion and survival heterogeneity, and tumor initiation correlated strongly with matched mouse PDX counterparts (Spearman R = 0.89, p < 0.001). Three PDCs showed a high degree of association between grafted tumor cells and host blood vessels, suggesting a perivascular invasion phenotype. In vivo evaluation of the drug marizomib, currently in clinical trials for GBM, showed an effect on fish survival corresponding to PDC in vitro and in vivo marizomib sensitivity.\n\nZebrafish xenografts of GBM, monitored by AI methods in an automated process, present a scalable alternative to mouse xenograft models for the study of glioblastoma tumor initiation, growth, and invasion, applicable to patient-specific drug evaluation.", "doi": "10.1093/neuonc/noab264", "pmid": "34919147", "labels": {"Genome Engineering Zebrafish": "Service"}, "xrefs": [{"db": "pii", "key": "6432157"}, {"db": "pmc", "key": "PMC9071311"}], "notes": [], "created": "2021-12-20T12:13:15.480Z", "modified": "2022-08-24T11:18:59.919Z"}, {"entity": "publication", "iuid": "f55246fcc918487698baf86ca73bf5f3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f55246fcc918487698baf86ca73bf5f3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f55246fcc918487698baf86ca73bf5f3"}}, "title": "An orthotopic glioblastoma animal model suitable for high-throughput screenings.", "authors": [{"family": "Pudelko", "given": "Linda", "initials": "L"}, {"family": "Edwards", "given": "Steven", "initials": "S"}, {"family": "Balan", "given": "Mirela", "initials": "M"}, {"family": "Nyqvist", "given": "Daniel", "initials": "D"}, {"family": "Al-Saadi", "given": "Jonathan", "initials": "J"}, {"family": "Dittmer", "given": "Johannes", "initials": "J"}, {"family": "Alml\u00f6f", "given": "Ingrid", "initials": "I"}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7256c271ea4adea404d4ff355f804e.json"}}, {"family": "Br\u00e4utigam", "given": "Lars", "initials": "L"}], "type": "journal article", "published": "2018-10-09", "journal": {"volume": "20", "issn": "1523-5866", "issue": "11", "pages": "1475-1484", "title": "Neuro-oncology", "issn-l": "1522-8517"}, "abstract": "Glioblastoma (GBM) is an aggressive form of brain cancer with poor prognosis. Although murine animal models have given valuable insights into the GBM disease biology, they cannot be used in high-throughput screens to identify and profile novel therapies. The only vertebrate model suitable for large-scale screens, the zebrafish, has proven to faithfully recapitulate biology and pathology of human malignancies, and clinically relevant orthotopic zebrafish models have been developed. However, currently available GBM orthotopic zebrafish models do not support high-throughput drug discovery screens.\n\nWe transplanted both GBM cell lines as well as patient-derived material into zebrafish blastulas. We followed the behavior of the transplants with time-lapse microscopy and real-time in vivo light-sheet microscopy.\n\nWe found that GBM material transplanted into zebrafish blastomeres robustly migrated into the developing nervous system, establishing an orthotopic intracranial tumor already 24 hours after transplantation. Detailed analysis revealed that our model faithfully recapitulates the human disease.\n\nWe have developed a robust, fast, and automatable transplantation assay to establish orthotopic GBM tumors in zebrafish. In contrast to currently available orthotopic zebrafish models, our approach does not require technically challenging intracranial transplantation of single embryos. Our improved zebrafish model enables transplantation of thousands of embryos per hour, thus providing an orthotopic vertebrate GBM model for direct application in drug discovery screens.", "doi": "10.1093/neuonc/noy071", "pmid": "29750281", "labels": {"Integrated Microscopy Technologies Stockholm": "Collaborative"}, "xrefs": [{"db": "pii", "key": "4994699"}, {"db": "pmc", "key": "PMC6176805"}], "notes": "Steven Edwards collaboration (Light-sheet)", "created": "2018-10-29T15:18:29.786Z", "modified": "2021-07-08T13:01:30.968Z"}, {"entity": "publication", "iuid": "42a1e90686e64d3283edb58f0af1ec60", "links": {"self": {"href": "https://publications.scilifelab.se/publication/42a1e90686e64d3283edb58f0af1ec60.json"}, "display": {"href": "https://publications.scilifelab.se/publication/42a1e90686e64d3283edb58f0af1ec60"}}, "title": "Primary glioblastoma cells for precision medicine: a quantitative portrait of genomic (in)stability during the first 30 passages.", "authors": [{"family": "Baskaran", "given": "Sathishkumar", "initials": "S"}, {"family": "Mayrhofer", "given": "Markus", "initials": "M"}, {"family": "Kultima", "given": "Hanna G\u00f6ransson", "initials": "HG"}, {"family": "Bergstr\u00f6m", "given": "Tobias", "initials": "T"}, {"family": "Elfineh", "given": "Lioudmila", "initials": "L"}, {"family": "Cavelier", "given": "Lucia", "initials": "L", "orcid": "0009-0003-8195-370X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f01226edb140436da0c9d166c1f5fe51.json"}}, {"family": "Isaksson", "given": "Anders", "initials": "A"}, {"family": "Nelander", "given": "Sven", "initials": "S"}], "type": "journal article", "published": "2018-07-05", "journal": {"volume": "20", "issn": "1523-5866", "issue": "8", "pages": "1080-1091", "title": "Neuro-oncology", "issn-l": "1522-8517"}, "abstract": "Primary glioblastoma cell (GC) cultures have emerged as a key model in brain tumor research, with the potential to uncover patient-specific differences in therapy response. However, there is limited quantitative information about the stability of such cells during the initial 20-30 passages of culture.\n\nWe interrogated 3 patient-derived GC cultures at dense time intervals during the first 30 passages of culture. Combining state-of-the-art signal processing methods with a mathematical model of growth, we estimated clonal composition, rates of change, affected pathways, and correlations between altered gene dosage and transcription.\n\nWe demonstrate that GC cultures undergo sequential clonal takeovers, observed through variable proportions of specific subchromosomal lesions, variations in aneuploid cell content, and variations in subpopulation cell cycling times. The GC cultures also show significant transcriptional drift in several metabolic and signaling pathways, including ribosomal synthesis, telomere packaging and signaling via the mammalian target of rapamycin, Wnt, and interferon pathways, to a high degree explained by changes in gene dosage. In addition to these adaptations, the cultured GCs showed signs of shifting transcriptional subtype. Compared with chromosomal aberrations and gene expression, DNA methylations remained comparatively stable during passaging, and may be favorable as a biomarker.\n\nTaken together, GC cultures undergo significant genomic and transcriptional changes that need to be considered in functional experiments and biomarker studies that involve primary glioblastoma cells.", "doi": "10.1093/neuonc/noy024", "pmid": "29462414", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Clinical Genomics Uppsala": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "4860173"}, {"db": "pmc", "key": "PMC6280139"}], "notes": [], "created": "2018-10-25T08:50:53.954Z", "modified": "2024-01-16T13:48:46.006Z"}, {"entity": "publication", "iuid": "a670ef31b8494b6c8b05f44412358c51", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a670ef31b8494b6c8b05f44412358c51.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a670ef31b8494b6c8b05f44412358c51"}}, "title": "Methylated RASSF1A in malignant peripheral nerve sheath tumors identifies neurofibromatosis type 1 patients with inferior prognosis.", "authors": [{"family": "Danielsen", "given": "Stine A", "initials": "SA"}, {"family": "Lind", "given": "Guro E", "initials": "GE"}, {"family": "Kolberg", "given": "Matthias", "initials": "M"}, {"family": "H\u00f8land", "given": "Maren", "initials": "M"}, {"family": "Bjerkehagen", "given": "Bodil", "initials": "B"}, {"family": "Sundby Hall", "given": "Kirsten", "initials": "K"}, {"family": "van den Berg", "given": "Eva", "initials": "E"}, {"family": "Mertens", "given": "Fredrik", "initials": "F"}, {"family": "Smeland", "given": "Sigbj\u00f8rn", "initials": "S"}, {"family": "Picci", "given": "Piero", "initials": "P"}, {"family": "Lothe", "given": "Ragnhild A", "initials": "RA"}], "type": "journal article", "published": "2015-01-00", "journal": {"volume": "17", "issn": "1523-5866", "issue": "1", "pages": "63-69", "title": "Neuro-oncology", "issn-l": "1522-8517"}, "abstract": "Malignant peripheral nerve sheath tumor (MPNST) is a rare and highly aggressive disease with no evidence of effect from adjuvant therapy. It is further associated with the hereditary syndrome neurofibromatosis type 1 (NF1). Silencing of the tumor suppressor gene RASSF1A through DNA promoter hypermethylation is known to be involved in cancer development, but its impact in MPNSTs remains unsettled.\n\nThe RASSF1A promoter was analyzed by methylation-specific PCR in 113 specimens, including 44 NF1-associated MPNSTs, 47 sporadic MPNSTs, 21 benign neurofibromas, and 1 nonneoplastic nerve sheath control.\n\nRASSF1A methylation was found only in the malignant samples (60%) and identified a subgroup among patients with NF1-associated MPNST with a poor prognosis. These patients had a mean 5-year disease-specific survival of 27.3 months (95% CI: 17.2-37.4) versus 47.4 months (95% CI: 37.5-57.2) for NF1 patients with unmethylated promoters, P = 0.014. In multivariate Cox regression analysis, methylated RASSF1A remained an adverse prognostic factor independent of clinical risk factors, P = .013 (hazard ratio: 5.2; 95% CI: 1.4-19.4).\n\nA considerable number of MPNST samples display hypermethylation of the RASSF1A gene promoter, and for these tumors, this is the first molecular marker that if validated can characterize a subgroup of patients with inferior prognosis, restricted to individuals with NF1.", "doi": "10.1093/neuonc/nou140", "pmid": "25038505", "labels": {"National Genomics Infrastructure": null, "NGI Stockholm (Genomics Applications)": null, "NGI Stockholm (Genomics Production)": null}, "xrefs": [{"db": "pii", "key": "nou140"}, {"db": "pmc", "key": "PMC4416132"}], "notes": [], "created": "2017-05-04T14:58:49.751Z", "modified": "2020-01-21T13:56:04.288Z"}, {"entity": "publication", "iuid": "e9c9a297dc294e8a9b7a9be667c54458", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e9c9a297dc294e8a9b7a9be667c54458.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e9c9a297dc294e8a9b7a9be667c54458"}}, "title": "Comparative drug pair screening across multiple glioblastoma cell lines reveals novel drug-drug interactions.", "authors": [{"family": "Schmidt", "given": "Linn\u00e9a", "initials": "L"}, {"family": "Kling", "given": "Teresia", "initials": "T"}, {"family": "Monsefi", "given": "Naser", "initials": "N"}, {"family": "Olsson", "given": "Maja", "initials": "M"}, {"family": "Hansson", "given": "Caroline", "initials": "C", "orcid": "0000-0001-6738-6495", "researcher": {"href": "https://publications.scilifelab.se/researcher/3f707f6560ae4e948196bf0f5abfa36f.json"}}, {"family": "Baskaran", "given": "Sathishkumar", "initials": "S"}, {"family": "Lundgren", "given": "Bo", "initials": "B"}, {"family": "Martens", "given": "Ulf", "initials": "U"}, {"family": "H\u00e4ggblad", "given": "Maria", "initials": "M", "orcid": "0000-0002-3857-1437", "researcher": {"href": "https://publications.scilifelab.se/researcher/c2b5f5d0486a4422b93a626a2cd1583f.json"}}, {"family": "Westermark", "given": "Bengt", "initials": "B", "orcid": "0000-0001-7153-5545", "researcher": {"href": "https://publications.scilifelab.se/researcher/dbaf3a1cdd7d48e5ba9e147bfb5055b6.json"}}, {"family": "Forsberg Nilsson", "given": "Karin", "initials": "K"}, {"family": "Uhrbom", "given": "Lene", "initials": "L", "orcid": "0000-0001-8595-5698", "researcher": {"href": "https://publications.scilifelab.se/researcher/67bb8672ad514a9bb5f86c8d6b494269.json"}}, {"family": "Karlsson-Lindahl", "given": "Linda", "initials": "L"}, {"family": "Gerlee", "given": "Philip", "initials": "P"}, {"family": "Nelander", "given": "Sven", "initials": "S", "orcid": "0000-0003-1758-1262", "researcher": {"href": "https://publications.scilifelab.se/researcher/1d684fc3b26d4741b850790ba0571c96.json"}}], "type": "journal article", "published": "2013-11-00", "journal": {"volume": "15", "issn": "1523-5866", "issue": "11", "pages": "1469-1478", "title": "Neuro-oncology", "issn-l": "1522-8517"}, "abstract": "Glioblastoma multiforme (GBM) is the most aggressive brain tumor in adults, and despite state-of-the-art treatment, survival remains poor and novel therapeutics are sorely needed. The aim of the present study was to identify new synergistic drug pairs for GBM. In addition, we aimed to explore differences in drug-drug interactions across multiple GBM-derived cell cultures and predict such differences by use of transcriptional biomarkers.\r\n\r\nWe performed a screen in which we quantified drug-drug interactions for 465 drug pairs in each of the 5 GBM cell lines U87MG, U343MG, U373MG, A172, and T98G. Selected interactions were further tested using isobole-based analysis and validated in 5 glioma-initiating cell cultures. Furthermore, drug interactions were predicted using microarray-based transcriptional profiling in combination with statistical modeling.\r\n\r\nOf the 5 \u00d7 465 drug pairs, we could define a subset of drug pairs with strong interaction in both standard cell lines and glioma-initiating cell cultures. In particular, a subset of pairs involving the pharmaceutical compounds rimcazole, sertraline, pterostilbene, and gefitinib showed a strong interaction in a majority of the cell cultures tested. Statistical modeling of microarray and interaction data using sparse canonical correlation analysis revealed several predictive biomarkers, which we propose could be of importance in regulating drug pair responses.\r\n\r\nWe identify novel candidate drug pairs for GBM and suggest possibilities to prospectively use transcriptional biomarkers to predict drug interactions in individual cases.", "doi": "10.1093/neuonc/not111", "pmid": "24101737", "labels": {"Drug Discovery and Development": "Collaborative"}, "xrefs": [{"db": "pii", "key": "not111"}, {"db": "pmc", "key": "PMC3813417"}], "notes": "Biochemical and Cellular Screening", "created": "2017-05-04T14:57:02.204Z", "modified": "2025-10-23T08:55:35.813Z"}], "created": "2017-05-09T09:12:15.705Z", "modified": "2020-11-27T13:14:04.510Z"}