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- Kinhult, Sara, et al.
(author)
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Regional variation in usage of TTF (Optune) Regional variation i användningen av TTF vid glioblastombehandling : [Regional variation in usage of TTF (Optune)]
- 2023
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In: Läkartidningen. - : Sveriges läkarförbund. - 0023-7205 .- 1652-7518. ; 120
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Journal article (peer-reviewed)abstract
- The standard treatment of glioblastoma, an aggressive brain tumour, includes radiotherapy combined with temozolomide. Based on a randomised trial, showing five months increased survival, TTF has been introduced in the management of patients with good performance status. Data from the Swedish national quality registry for CNS tumours have been analysed for TTF usage. The results demonstrate that 65 percent of the patients accepted treatment with TTF. More than half of the treated patients interrupted treatment due to low compliance or their own wish. Median treatment time was 164 days, with a range from 0 to 774 days. There was a large variation between different regions in how many patients were offered TTF treatment. A non-significant trend to better survival was seen for the group of TTF-treated patients compared to individually matched controls. In summary, TTF is a new treatment for glioblastoma, with potential to prolong survival also in real world patients. Today, the treatment is not offered equally to all patients, despite national guidelines.
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- Sandström, Maria, et al.
(author)
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Effects of the VEGFR inhibitor ZD6474 in combination with radiotherapy and temozolomide in an orthotopic glioma model.
- 2008
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In: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 88:1, s. 1-9
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Journal article (peer-reviewed)abstract
- AIM OF THE STUDY:The extensive neovascularisation of malignant glioma is mainly influenced by vascular endothelial growth factor (VEGF). The effect of ZD6474, a potent inhibitor of VEGF-receptor-2, was evaluated in combination with either radiotherapy or temozolomide.METHODS:The effects on glioma growth were investigated in the intracerebral BT4C rat glioma model. ZD6474 30 mg/kg was given alone or in combination with radiotherapy 12 Gy x 1 or with temozolomide 100 mg/kg for 3 days. Two different experiments were performed comparing ZD6474 to radiotherapy or temozolomide. For each experiment 28 animals were randomized into four groups.RESULTS:ZD6474 in combination with radiotherapy significantly decreased tumour area by 66% compared with controls whereas the combination with temozolomide decreased tumour area by 74%.CONCLUSIONS:ZD6474 in combination with two standard modalities in the treatment of malignant glioma, radiotherapy and chemotherapy, markedly decreased the growth of an intracerebral experimental glioma. These results justify further investigations of these therapies in combination.
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- Sandström, Maria, 1969-
(author)
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Experimental therapies of malignant glioma : with emphasis on angiogenesis inhibition
- 2008
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Doctoral thesis (other academic/artistic)abstract
- Malignant glioma consists of a group of diseases where the localisation and the nature of the disease makes treatment an extreme challenge. Two important biological features of malignant glioma cells are their infiltrative growth and their ability to induce angiogenesis. Glioma cells migrate extensively behind the blood-brain barrier and infiltrate the surrounding brain making radical treatment with surgery and radiotherapy almost impossible. The aims of this thesis were to investigate factors of importance for glioma cell migration and angiogenesis and to evaluate if an anti-angiogenesis approach alone or in combination with current treatment modalities could inhibit glioma growth. For this purpose we used the BT4C orthotopic rat glioma model and investigated treatment effects of the vascular endothelial growth factor (VEGF) receptor-2 and epidermal growth factor (EGF) receptor tyrosine kinase inhibitor ZD6474 alone or in combination with temozolomide or radiotherapy. Altered protein expression pattern after anti-angiogenesis treatment was measured using a mass-spectrometric proteomic method, followed by multivariate data-analysis. The tissue plasminogen activator (tPA), urokinase plasminogen activator (uPA), plasminogen activator inhibitor-1 (PAI-1), and VEGF showed altered temporal and spatial mRNA expression during glioma progression. In early stages of tumour progression the expression was found throughout the tumour while in later stages, the expression was more predominant in the invasive tumour border. ZD6474 in monotherapy significantly inhibited tumour growth in the BT4C glioma model. The effect was further enhanced when combined with radiotherapy or temozolomide. Using mass-spectrometric methods an altered protein expression pattern after ZD6474 treatment was observed implicating the possibility to use proteomic methods for finding predictive biomarkers for anti-angiogenesis treatment. In conclusion, this thesis demonstrates a co-expression of factors important for glioma growth and angiogenesis and that treatment with an angiogenesis inhibitor has additive effects on glioma growth when combined with radiotherapy and chemotherapy. Finally, an altered protein expression pattern after anti-angiogenesis treatment is evident and detectable. Hopefully this work will contribute to and encourage further research to reach a better understanding of how to combine and evaluate different treatment approaches in malignant glioma.
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- Wibom, Carl, 1977-, et al.
(author)
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Vandetanib alters the protein pattern in malignant glioma and normal brain in the BT4C rat glioma model
- 2010
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In: International Journal of Cancer. - : Spandidos Publications. - 0020-7136 .- 1097-0215 .- 1019-6439 .- 1791-2423. ; 37:4, s. 879-890
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Journal article (peer-reviewed)abstract
- The treatment of glioblastoma is unsatisfactory. Improved understanding of the biological effects of treatment, together with development of new tools to predict outcome of the initiated treatment are therefore of great need. Vandetanib (ZD6474) is mainly a vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) receptor tyrosine kinase inhibitor. This study investigated the pattern of protein expression in brain tumor and normal brain tissue, following treatment with vandetanib in a rat glioma model. BT4C-cells were stereotactically implanted into the brain of BD IX rats. The rats were divided into three different experiments. The treatment schedule for experiments one and two consisted of daily, oral doses of vandetanib from day 6 until day 12 or 20 after implantation, respectively. In the third experiment, each animal received a single dose of vandetanib on day 19 after implantation and was then sacrificed 2, 8 or 24 h thereafter. The protein expression profiles were analyzed by SELDI-TOF-MS and evaluated with multivariate statistical methods. Following treatment with vandetanib, we found significantly altered protein expression pattern in malignant glioma and normal brain. Analyzing protein spectra is an interesting option to assess biological effects induced in brain tissue by signal transduction inhibitors such as vandetanib.
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