Malignant Glioma: Chemosensitivity testing and Biomarkers

Lekka, Elvira (2012) Malignant Glioma: Chemosensitivity testing and Biomarkers. Masters thesis, University of Central Lancashire.

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Chemosensitivity testing and molecular biomarkers are commonly used methods during the management of several types of malignant tumours in routine clinical practice. The present work attempts to transfer the use of these two concepts to the management of malignant gliomas.
Chemosensitivity testing was performed on twelve primary malignant glioma cultures at passage 0. The drugs tested were Temozolomide, Cisplatin and Carmustine, which are commonly administered chemotherapeutic agents in clinical practice in our institution. The results revealed that cultures derived from females or from patients under 65 years of age were more sensitive to the drugs used. More importantly, the chemosensitivity in vitro results were predictive of the clinical outcome of the donor patient. During chemosensitivity testing, Temozolomide was found to have poor in vitro effect. Increased frequency of application as well as cell cycle synchronisation of glioma cell lines were found to improve the kill efficiency of Temozolomide.
Six molecules were considered as potential biomarkers. All of them were found to be effective at predicting the presence of malignant gliomas. With the exception of VEGF and PDGF-BB, this is the first report of Follistatin, IL-6, IL-8 and IL-10 as biomarkers for malignant gliomas. Overall age and gender of patients did not affect the biomarker results.
Brain tumours represent 2% of all cancers in the UK. Early detection and treatment of glioblastoma is challenging and little progress has been made so far. This imposes a clear need for improving the diagnosis and management of malignant gliomas. This study aims to address both challenges and proposed ways of improvement.

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