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Angiogenesis and angiopoietins in human gliomas

PhD ceremony:drs. M. Wagemakers
When:May 13, 2015
Supervisors:prof. dr. G. (Ingrid) Molema, Prof. J.J.A. Mooij
Co-supervisor:dr. W.F.A. (Wilfred) den Dunnen
Where:Academy building RUG
Faculty:Medical Sciences / UMCG
Angiogenesis and angiopoietins in human gliomas

High grade gliomas are brain tumors that have dismal prognosis despite the various modalities that are available for treatment. Like other tumors, gliomas are known to induce the formation of new blood vessels by a process called “angiogenesis”. Targeting this process has been successful in the treatment of other tumors and similar attempts are made in gliomas. Angiogenesis is a complex process that can be divided into several phases and involves multiple growth factor systems and cell types. The Angiopoietin-Tie2 growth factor system is thought to be intimately involved in the early phases of angiogenesis known as the “angiogenic switch” and is the main subject of the thesis “Angiogenesis and Angiopoietins in Human Gliomas” by neurosurgeon Michiel Wagemakers. This thesis reviews the possibilities for the immunohistochemical assessment of angiogenesis in gliomas, compares the extent to which angiogenesis occurs in two different types of gliomas in patients, relates the activity of the Angiopoietin-Tie2 system to patient prognosis in high grade gliomas, and studies the distribution of the individual factors of this system within the tumor. Also, a study is presented in which treatment induced vascular changes are shown within murine gliomas that suggest an involvement of the tumor vasculature in the effect of the treatment. As a whole, the thesis underlines the involvement of the Angiopoietin-Tie2 system in human high grade glioma growth and supports attempts to target this system as a new treatment.