Search results for "GLIOMA"
showing 10 items of 230 documents
Transplantation of prodrug-converting neural progenitor cells for brain tumor therapy
2003
Since neural progenitor cells can engraft stably into brain tumors and differentiate along the neuronal and glial line, we tested the hypothesis that transplanted cytosine deaminase (CD)-expressing ST14A cells (an immortalized neural progenitor cell line) can convert locally 5-fluorocytosine (5-FC) into 5-fluorouracil (5-FU) and produce a regression of glioma tumors. ST14A, retrovirally transduced with the E. coli CD gene, showed a strong bystander effect on glioma cells as assessed by in vitro assay. Intracerebral injection of C6 glioma cells generated a rapidly growing tumoral mass. DiI prelabeled ST14A, coinjected into the rat brain with C6 glioma cells, survived in the tumoral mass up t…
Differential Sensitivity of Malignant Glioma Cells to Methylating and Chloroethylating Anticancer Drugs: p53 Determines the Switch by Regulating xpc,…
2007
Abstract Glioblastoma multiforme is the most severe form of brain cancer. First line therapy includes the methylating agent temozolomide and/or the chloroethylating nitrosoureas [1-(2-chloroethyl)-1-nitrosourea; CNU] nimustine [1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea; ACNU], carmustine [1,3-bis(2-chloroethyl)-1-nitrosourea; BCNU], or lomustine [1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea; CCNU]. The mechanism of cell death after CNU treatment is largely unknown. Here we show that ACNU and BCNU induce apoptosis in U87MG [p53 wild-type (p53wt)] and U138MG [p53 mutant (p53mt)] glioma cells. However, contrary to what we observed previously for temozolomide, chl…
Temozolomide- and fotemustine-induced apoptosis in human malignant melanoma cells: response related to MGMT, MMR, DSBs, and p53
2009
Malignant melanomas are highly resistant to chemotherapy. First-line chemotherapeutics used in melanoma therapy are the methylating agents dacarbazine (DTIC) and temozolomide (TMZ) and the chloroethylating agents BCNU and fotemustine. Here, we determined the mode of cell death in 11 melanoma cell lines upon exposure to TMZ and fotemustine. We show for the first time that TMZ induces apoptosis in melanoma cells, using therapeutic doses. For both TMZ and fotemustine apoptosis is the dominant mode of cell death. The contribution of necrosis to total cell death varied between 10 and 40%. The O(6)-methylguanine-DNA methyltransferase (MGMT) activity in the cell lines was between 0 and 1100 fmol m…
Oligodendroglioma cells shed microvesicles which contain TRAIL as well as molecular chaperones and induce cell death in astrocytes.
2011
Microvesicles (MVs) shed from G26/24 oligodendroglioma cells were previously reported to cause a reproducible, dose-dependent, inhibitory effect on neurite outgrowth, and eventually neuronal apoptosis, when added to primary cultures of rat cortical neurons. These effects were reduced but not abolished by functional monoclonal antibodies against Fas-L. In order to investigate whether MVs contain other factors able to induce cell death, we tested them for TRAIL and found clear evidence of its presence in the vesicles. This finding suggests the possibility that Fas-L and TRAIL cooperate in inducing brain cell death. Aimed at understanding the route through which the vesicles deliver their mess…
T-cell Receptor Therapy Targeting Mutant Capicua Transcriptional Repressor in Experimental Gliomas
2021
Abstract Purpose: Gliomas are intrinsic brain tumors with a high degree of constitutive and acquired resistance to standard therapeutic modalities such as radiotherapy and alkylating chemotherapy. Glioma subtypes are recognized by characteristic mutations. Some of these characteristic mutations have shown to generate immunogenic neoepitopes suitable for targeted immunotherapy. Experimental Design: Using peptide-based ELISpot assays, we screened for potential recurrent glioma neoepitopes in MHC-humanized mice. Following vaccination, droplet-based single-cell T-cell receptor (TCR) sequencing from established T-cell lines was applied for neoepitope-specific TCR discovery. Efficacy of intravent…
P08.76 Anti-EGFL7 treatment as an add-on for glioma therapy
2016
Glioblastoma multiforme (GBM) is one the most common and malignant forms of brain tumors. The median survival time of patients diagnosed with primary GBM is around 15 months. In spite of multimodal treatments GBMs remain essentially incurable. Therefore, alternative treatments targeting previously unexplored aspects of GBMs are required. However, the molecular mechanisms underlying the formation of brain tumors have only partially been defined. Especially Notch, a conserved developmental pathway, is promising in terms of GBM formation, as components of this signaling cascade are aberrantly expressed in gliomas. Studies reported that the inhibition of Notch decreased glioma cell proliferatio…
P01.039 Development of signaling questions assessing distress and quality of life in glioma patients - Results of 50 interviews and an expert analysis
2018
BACKGROUND: Due to cognitive or physical limitations, glioma patients might not be able to validly complete self-reporting tools assessing quality of life, distress, and unmet needs. This not only impairs individual patient care and therapy monitoring but also creates bias in studies applying patient reported outcome measures (PROMs). In our study, we searched for signaling questions implementable in patient-doctor consultations in order to optimize the assessment. METHODS: We performed 1) a literature research to find out the most important questions for glioma patients that are also covered by standard questionnaires. 2) After a pretest in n=10 patients, we performed structured interviews…
Occupational risk factors for low grade and high grade glioma: Results from an international case control study of adult brain tumours
2004
The majority of suspected occupational risk factors for adult brain tumours have yet to be confirmed as etiologically relevant. Within an international case-control study on brain tumours, lifelong occupational histories and information on exposures to specific substances were obtained by direct interviews to further investigate occupational risk factors for glioma. This is one of the largest studies of brain tumours in adults, including 1,178 cases and 1987 population controls from 8 collaborating study centres matched for age, gender and centre. All occupational information, was aggregated into 16 occupational categories. In a pooled analysis, odds ratios (OR), adjusted for education, wer…
Blood flow and metabolic microenvironment of brain tumors
1994
Summarizing thesein vivo data in the context of brain tumor therapy, the following aspects are of particular importance: Low and heterogeneous tumor blood flow may — in addition to the limiting effects of the blood-brain barrier — result in compromised delivery of drugs from blood to the tissue. Low tumor pO2 reduces sensitivity to standard radiation and ‘O2-dependent’ anticancer drugs. Treatment efficacy may be further altered by changes of tumor pH. Particularly acidosis can decrease radiation sensitivity and modulate the cytotoxicity of anticancer drugs. In the following presentations, these aspects will be discussed regardingin vivo data obtained with positron emission tomography.
In the literature: May 2016
2016
Radiotherapy as single modality was considered the standard of care for low-grade gliomas, a mixed population of low proliferative tumours including oligodendrogliomas, oligoastrocytomas and grade 2 astrocytomas. However, a recently reported trial in the New England Journal of Medicine indicates1 that the addition of procarbacine, lomustine (CCNU) and vincristine, a combination known by its acronym, PCV, significantly prolongs survival in patients with low-grade glioma. When this trial was initially reported in 2012, after a median follow-up of almost 6 years, according to the estimated number of events needed to analyse the results, a significant difference in progression-free survival (PF…