Abstract:
:Medulloblastomas are the most common malignant brain tumors in childhood. Emerging evidence suggests that medulloblastoma comprises at least four distinct diseases (WNT, SHH, Group 3 and 4) with different biology, clinical presentation, and outcome, with especially poor prognosis in Group 3. The tight connection of biology and clinical behavior in patients emphasizes the need for subgroup-specific preclinical models in order to develop treatments tailored to each subgroup. Herein we report on the novel cell line HD-MB03, isolated from tumor material of a patient with metastasized Group 3 medulloblastoma, and preclinical testing of different histone deacetylase inhibitors (HDACis) in this model. HD-MB03 cells grow long term in vitro and form metastatic tumors in vivo upon orthotopic transplantation. HD-MB03 cells reflect the original Group 3 medulloblastoma at the histological and molecular level, showing large cell morphology, similar expression patterns for markers Ki67, p53, and glial fibrillary acidic protein (GFAP), a gene expression profile most closely matching Group 3 medulloblastomas, and persistence of typical molecular alterations, i.e., isochromosome 17q [i(17q)] and MYC amplification. Protein expression analysis of HDACs 2, 5, 8, and 9 as well as the predictive marker HR23B showed intermediate to strong expression, suggesting sensitivity to HDACis. Indeed, treatment with HDACis Helminthosporium carbonum (HC)-toxin, vorinostat, and panobinostat revealed high sensitivity to this novel drug class, as well as a radiation-sensitizing effect with significantly increased cell death upon concomitant treatment. In summary, our data indicate that HD-MB03 is a suitable preclinical model for Group 3 medulloblastoma, and HDACis could represent a therapeutic option for this subgroup.
journal_name
J Neurooncoljournal_title
Journal of neuro-oncologyauthors
Milde T,Lodrini M,Savelyeva L,Korshunov A,Kool M,Brueckner LM,Antunes AS,Oehme I,Pekrun A,Pfister SM,Kulozik AE,Witt O,Deubzer HEdoi
10.1007/s11060-012-0978-1subject
Has Abstractpub_date
2012-12-01 00:00:00pages
335-48issue
3eissn
0167-594Xissn
1573-7373journal_volume
110pub_type
杂志文章abstract::Diffuse invasion of the brain by tumor cells is a hallmark of human glioblastomas and a major cause for the poor prognosis of these tumors. This phenomenon is only partially reproduced by rodent models of gliomas that display a very high rate of proliferation and limited cell migration. We have analyzed the developmen...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1023/a:1010620420241
更新日期:2001-05-01 00:00:00
abstract::A pilot study was performed combining cis-diamminedichloroplatinum (CDDP) and radiation therapy to treat patients with high-grade astrocytomas. CDDP at a dose of 40 mg/m2/week intravenously was given during the course of cranial irradiation. Following irradiation, CDDP was given every three weeks on a schedule of 35-4...
journal_title:Journal of neuro-oncology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00182955
更新日期:1983-01-01 00:00:00
abstract:PURPOSE:Diffuse pontine tumors are highly lethal, and there are few long-term survivors with the standard treatment of external beam irradiation. We investigated the effectiveness of high-dose thiotepa and etoposide-based chemotherapy regimens with autologous bone marrow rescue (ABMR) in children with pontine tumors. ...
journal_title:Journal of neuro-oncology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1023/a:1005874508975
更新日期:1998-03-01 00:00:00
abstract::Ewing's sarcoma/primitive neuroectodermal tumor (EWS/PNET) has a characteristic chimeric oncogene EWS-FLI1, which results from chromosomal translocation t (11; 22), that is believed to initiate tumorigenesis of EWS/PNET. However, the specific details of EWS/PNET oncogenesis and exact role of EWS-FLI1 remain largely un...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-008-9646-x
更新日期:2008-11-01 00:00:00
abstract::Intracranial Hodgkin's lymphoma (ICHL) in the HIV positive population is a rarely reported event with only three prior cases reported in the literature. In these prior reports, the outcome of the patients was uncertain or very poor. We report here the case of an HIV seropositive patient with an isolated intracranial r...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-008-9587-4
更新日期:2008-08-01 00:00:00
abstract::The determination of optimal therapy for ependymoma (EP) in infants is ongoing. We describe the incidence, management and outcomes of Canadian infants with EP to discern potential future research questions. Of 579 cases registered in a national database of children <36 months of age diagnosed with a brain tumor from 1...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-014-1396-3
更新日期:2014-04-01 00:00:00
abstract::Pediatric glial tumors differ from adult gliomas in several ways that are of major therapeutic importance. First, the value of extensive tumor resection, which is controversial for malignant intrinsic brain tumors in adults, has been confirmed for a variety of childhood brain tumors, such as supratentorial high-grade ...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,评审
doi:10.1023/a:1006107227856
更新日期:1999-05-01 00:00:00
abstract::Primary germinomas in the spinal cord are very rare with only 15 cases published previously. In this case a 22-year-old woman with urinary incontinence, lumbago, and bilateral leg pain and weakness was found to have a solid tumor in the conus medullaris between the L1 and L2 vertebral bodies. Serum HCG was elevated wi...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-005-3092-9
更新日期:2006-01-01 00:00:00
abstract:OBJECT:Although atypical teratoid/rhabdoid tumor (AT/RT) is known to generate through inactivation of the hSNF5/INI1 gene on chromosome 22q, the downstream molecular mechanism remains unclear. We histologically and molecularly reviewed our pediatric brain tumors for unrecognized AT/RTs and evaluated the role of cyclin ...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-004-4276-4
更新日期:2005-06-01 00:00:00
abstract::Long non-coding RNAs (lncRNAs) are important modulators of various cellular and molecular events, including cancer-associated pathways. The Anti-differentiation ncRNA (ANCR) is a key regulator of keratinocyte differentiation, where its expression is necessary to maintain epidermal progenitor's cells. Herein, we invest...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-018-2809-5
更新日期:2018-06-01 00:00:00
abstract::The antiproliferative effect of IFNalpha was tested on the human glioblastoma cell lines, U-373MG and T98G. IFNalpha significantly inhibited the growth of both cell lines, but was more effective in retarding the growth of U-373MG cells. Flow cytometry analysis indicated that synchronized IFNalpha-treated U-373MG cells...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1023/a:1006476408190
更新日期:2000-07-01 00:00:00
abstract:BACKGROUND:Tumor treating fields (TTFields) are anti-mitotic, non-invasive loco-regional cancer therapy comprising low intensity, intermediate frequency alternating electric fields. TTFields plus Temozolomide (TTFields/TMZ) extended survival versus TMZ alone in newly diagnosed glioblastoma (GBM) patients in the EF-14 t...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s11060-019-03361-2
更新日期:2020-02-01 00:00:00
abstract::In this retrospective, IRB-exempt study, we analyzed data from 68 patients diagnosed with glioblastoma (GBM) in two institutions and investigated the relationship between tumor shape, quantified using algorithmic analysis of magnetic resonance images, and survival. Each patient's Fluid Attenuated Inversion Recovery (F...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,多中心研究
doi:10.1007/s11060-016-2359-7
更新日期:2017-03-01 00:00:00
abstract::The biodistributions of carborane-containing copper porphyrins, CuTCP and CuTCPH, have been studied previously in mice bearing subcutaneously implanted mammary carcinomas. We now report biodistributions of those porphyrins in Fischer 344 rats bearing intracranial and/or multiple subcutaneous isogeneic 9L gliosarcomas ...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1023/a:1010622319892
更新日期:2001-04-01 00:00:00
abstract:PURPOSE:The highly vascular malignant brain tumor glioblastoma (GBM) appears to be an ideal target for anti-angiogenic therapy; however, clinical trials to date suggest the VEGF antibody bevacizumab affects only progression-free survival. Here we analyze a group of patients with GBM who received bevacizumab treatment a...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-019-03102-5
更新日期:2019-04-01 00:00:00
abstract::Antiangiogenic therapies for malignant gliomas often result in transient response, and recurrent disease is characterized by adoption of invasive and hypoxic phenotype. The notch signaling pathway is activated in gliomas, and augments cell migration and hypoxic response. Here we report a clinical study of the combinat...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-016-2263-1
更新日期:2016-12-01 00:00:00
abstract::The stable isotope 10B has a peculiarly marked avidity to capture slow neutrons whereupon it disintegrates into a lithium and a helium atom. These give up the 2.4 MeV of disintegration energy which they share within 5 and 9 microns of the 10B atom respectively. This means that the cell closest to the 10B atom bears th...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,评审
doi:10.1023/a:1005752827194
更新日期:1997-05-01 00:00:00
abstract::NF1, NF2, and Schwannomatosis are incurable tumor suppressor syndromes associated with poor quality of life. The aim of this study was to determine the feasibility, acceptability, and preliminary efficacy of an NF adapted, 8-week group mind body skills based intervention, the relaxation response resiliency program (3R...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-014-1522-2
更新日期:2014-10-01 00:00:00
abstract::O(6)-methylguanine-DNA-methyltransferase (MGMT) is mainly regulated by cytosine-guanine island promoter methylation that is believed to occur only in neoplastic tissue. The present study was undertaken to investigate whether methylation occurs also in non-neoplastic brains by collecting 45 non-neoplastic brains from a...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-014-1663-3
更新日期:2015-02-01 00:00:00
abstract::Glioblastoma stands out as the most frequent central nervous system neoplasia, presenting a poor prognosis. The aim of this study was to verify the frequency and clinical significance of the aneuploidy of chromosomes 7 and 10, EGFR amplification, PTEN and TP53 deletions and 1p/19q deficiency in adult patients diagnose...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-017-2606-6
更新日期:2017-12-01 00:00:00
abstract::When SK-N-BE(2) human neuroblastoma cells were exposed for 1h to growth medium supplemented with [14C]arachidonic acid (AA) at final concentrations ranging from 1 microM to 100 microM, an amount of this fatty acid was uptaken ranging form a 2% to a 120% of that present in cells at steady state. As more [14C]AA was upt...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1023/a:1005714320865
更新日期:1997-01-01 00:00:00
abstract:INTRODUCTION:High hospital case volumes are associated with improved treatment outcomes for numerous diseases. We assessed the association between academic non-profit hospital case volume and survival of adult glioblastoma patients. METHODS:From the nationwide Finnish Cancer Registry, we identified all adult (≥ 18 yea...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-020-03428-5
更新日期:2020-04-01 00:00:00
abstract::Treatment options and prognosis remains poor for patients with recurrent glioblastoma multiforme. These tumors are highly vascularised and over express angiogenic factors such as vascular endothelial growth factor and may potentially be responsive to antiangiogenic therapies. We present the results of a phase II trial...
journal_title:Journal of neuro-oncology
pub_type: 临床试验,杂志文章
doi:10.1023/a:1012554328801
更新日期:2001-08-01 00:00:00
abstract::Degradation and remodelling of the extracellular matrix has been investigated, with the main focus on the balance between matrix metalloproteinases (MMP) and tissue inhibitor of metalloproteinases (TIMP). Recent reports disclose the presence of a novel MMP-inhibiting cell membrane-anchored glycoprotein designated 'rev...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-008-9606-5
更新日期:2008-09-01 00:00:00
abstract::Previous studies have shown an inverse association between allergies and glioma risk; however, results for associations between single nucleotide polymorphisms (SNPs) of allergy-related genes and glioma risk have been inconsistent and restricted to a small number of SNPs. The objective of this study was to examine the...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s11060-013-1122-6
更新日期:2013-06-01 00:00:00
abstract::Meningiomas of the anterior skull base account for 40% of all intracranial meningiomas. Of these, almost half are sphenoid wing meningiomas; the other half are tuberculum sella tumors or olfactory groove tumors. Anterior clinoidal (medial sphenoid wing) meningiomas are a subcategory of the sphenoid wing meningiomas; t...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,评审
doi:10.1007/BF00165654
更新日期:1996-09-01 00:00:00
abstract:BACKGROUND:Despite aspirations to achieve equality in healthcare we know that socioeconomic differences exist and may affect treatment and patient outcome, also in serious diseases such as cancer. We investigated disparities in neurosurgical care and outcome for patients with low-grade glioma (LGG). METHODS:In this na...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-019-03378-7
更新日期:2020-01-01 00:00:00
abstract::Radiotherapy (RT) and concomitant/adjuvant therapy with temozolomide (Temodar) is a common treatment regimen for children and adults with glioma. Although temozolomide is generally well tolerated with temporary myelosuppression as the primary dose-limiting toxicity, irreversible bone-marrow aplasia after treatment wit...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-008-9704-4
更新日期:2009-01-01 00:00:00
abstract:BACKGROUND:Macroautophagy/autophagy is considered to play key roles in tumor cell evasion of therapy and establishment of metastases in breast cancer. High expression of LC3, a residual autophagy marker, in primary breast tumors has been associated with metastatic disease and poor outcome. FIP200/Atg17, a multi-functio...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-018-2959-5
更新日期:2018-11-01 00:00:00
abstract::New genetic models provide better biological mimics of human tumors. The new models can give deeper insight into tumorigenesis and provide better targets for testing therapies. To use the new models most successfully, it is useful to keep in mind limitations that are harder to overcome by genetic manipulation. These i...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,评审
doi:10.1023/a:1012230113527
更新日期:2001-07-01 00:00:00