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The tyrosine kinase inhibitor ZD6474 inhibits tumour growth in an intracerebral rat glioma model
Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi. Patologi.
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2004 (Engelska)Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 91, nr 6, s. 1174-1180Artikel i tidskrift (Refereegranskat) Published
Ort, förlag, år, upplaga, sidor
2004. Vol. 91, nr 6, s. 1174-1180
Nyckelord [en]
glioma, ZD6474, angiogenesis, VEGF, tyrosine kinase inhibitor
Identifikatorer
URN: urn:nbn:se:umu:diva-15551DOI: doi:10.1038/sj.bjc.6602108PubMedID: 15305185OAI: oai:DiVA.org:umu-15551DiVA, id: diva2:155223
Tillgänglig från: 2007-11-23 Skapad: 2007-11-23 Senast uppdaterad: 2018-06-09Bibliografiskt granskad
Ingår i avhandling
1. Experimental therapies of malignant glioma: with emphasis on angiogenesis inhibition
Öppna denna publikation i ny flik eller fönster >>Experimental therapies of malignant glioma: with emphasis on angiogenesis inhibition
2008 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

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.

Ort, förlag, år, upplaga, sidor
Umeå: Umeå universitet, 2008. s. 76
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 1219
Nyckelord
glioma, angiogenesis, VEGF, tyrosinekinaseinhibitor, ZD6474, plasminogenactivator, tPA, uPA, proteomics
Nationell ämneskategori
Cancer och onkologi
Identifikatorer
urn:nbn:se:umu:diva-1955 (URN)978-91-7264-667-4 (ISBN)
Disputation
2009-01-23, Betula, 6M, Norrlands Universitets Sjukhus, Umeå, 13:00 (Engelska)
Opponent
Handledare
Tillgänglig från: 2009-01-07 Skapad: 2009-01-07 Senast uppdaterad: 2018-06-09Bibliografiskt granskad

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Sandström, MariaJohansson, MikaelAndersson, UlrikaBergh, AndersBergenheim, A TommyHenriksson, Roger

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Sandström, MariaJohansson, MikaelAndersson, UlrikaBergh, AndersBergenheim, A TommyHenriksson, Roger
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OnkologiPatologiInstitutionen för farmakologi och klinisk neurovetenskap
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