2004 Research Grants

In 2004, the following researchers received funding to support the research into the causes of and cures for brain tumours.

Dr. Robert Griebel

Head of Neurosurgery, Royal University Hospital
Professor, University of Saskatchewan
Saskatoon, Saskatchewan

Title of Project:
Increasing the recurrence-free interval for patients with malignant brain tumours by decreasing glutathione-mediated resistance to radiotherapy.

Publication Summary:
Therapeutic success of radiotherapy, a standard treatment for patients with malignant brain tumours, is frequently limited by radioresistance of the tumour. We will test a novel method to increase the susceptibility of malignant brain tumours to radiotherapy. If successful, we would be able to increase the recurrence-free interval, and therefore the quality of life for patients with malignant brain tumours.

Dr. Annie Huang

Clinician Scientist, Div. of Hematology Oncolocy
Cancer Research Program
Labatt's Brain Tumour Research Centre
Hospital for Sick Children, Toronto, Ontario

Title of Project:
Identification of Genetic Markers of Chemosensitivity in Medulloblastoma Tumours.

Publication Summary:
Medulloblastoma is one of the most common malignant brain tumours of childhood and is one of the few malignant tumours where modest survival has been achieved with a combination of surgery, radiation and chemotherapy. Many survivors of medulloblastoma have significant neurological deficits largely as a result of their treatment with radiation therapy. It is known that a small but significant number of medulloblastoma tumours are very chemo-responsive and can be cured without radiation. We are interested in studying the genetic features of such tumours with the aim of using knowledge gained to identify patients that can be spared radiotherapy, and to gain more information regarding pathways of drug resistance in medulloblastoma tumours that may be targeted for therapy.

Dr. Robert Hammond

Neuropathologist, London Health Sciences
Professor, University of Western Ontario
London, Ontario

Title of Project:
Expression of angiopoietins 1 and 2 as indicators of angiogenesis in brain tumours.

Publication Summary:
Each year approximately 10,000 people in Canada are diagnosed with a primary or metastatic brain tumour. Primary brain tumours are the leading cause of death from solid tumours in children and adolescents. The growth of tumours depends on their ability to induce the development of new blood vessels. It has been postulated that the strength of a tumour to recruit new blood vessels is directly proportional to its aggressiveness. Unfortunately, tumour-induced angiogeneses is not completely understood. However, a number of tumour cell genes have been implicated in increased tumour blood vessel growth such as antiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2).

During angiogenesis blood vessels are established and remodeled by secreted proteins that include Ang-1, Ang-2 and Vascular Endothelial Growth Factor (VEGF). These proteins act on receptors expressed on the surface of endothelial cells that line the inside of blood vessels. Ang-1 promotes vessel integrity by stabilizing interactions between endothelial cells and the surrounding matrix, preventing the development of new vessels and capillaries. In contrast, Ang-2 blocks the action of Ang-1, interfering with the blood vessel stabilization. It is believed that in the presence of VEGF, Ang-2 ultimately leads to the development of new blood vessels.

This research is designed to determine the correlation between Ang-1 and Ang-2 expression and the pathological grade of human glioma specimens obtained from the Brain Tumour Tissue Bank at London Health Sciences Centre in London, Ontario. We hypothesize that more aggressive tumour types will express more Ang-2 and less Ang-1. The relative output of these genes in different tumour sets will be measured at the protein and gene transcription (mRNA) levels. Protein levels of Ang-1 and Ang-2 will be measured with immunohistochemistry and mRNA levels will be evaluated by the reverse polymerase chain reaction.

Preliminary studies have revealed a strong correlation between Ang-2 mRNA and increasing tumour grades, but no correlation between Ang-1 mRNA and tumour grade. Similarly, immmunohistochemistry revealed higher Ang-2 protein expression in higher grade gliomas. However, results in lower and mid-grade tumours were variable. Future studies are needed to further examine and confirm these trends. Furthermore, we will extend the analysis to relate Ang-1 and Ang-2 expression in resected tumours to patient prognosis. This type of research has clinical relevance representing a potential prognostic tool and therapeutic target for patients with brain tumours.

Research Outcome: Upon completion of research it was found that from 18 human glioma specimens varying in type Immunohistochemistry was used to identify and qualify Ang-1 and Ang-2 protein expressions. Both rtPCR and immunohistochemistry revealed an increase in Ang-2 expression correlating with increasing tumour grade. Ang-1 protein expression was also significantly increased in glioblastomas in comparison to oligodendrogliomas and anaplastic oligodendrogliomas.

Dr. Hammond is Associate Professor, University of Western Ontario, Neuropathologist, London Health Sciences Centre, received a 2004 Brain Tumour Foundation of Canada Research Grant.

Dr. Christopher Watling

Assistant Professor
Department of Clinical Neurological Sciences & Oncology
University of Western Ontario, London Regional Cancer Centre, Robarts Research Institute
London, Ontario

Title of Project:
Metabolic imaging of human malignant gliomas using 4.0 Tesla magnetic resonance spectroscopy.

Publication Summary:
No two malignant gliomas are the same. Even tumours which look identical on an MRI scan and under the microscope may behave in very different ways. Finding additional tools to help predict which tumours will respond best to which treatments is therefore essential. Magnetic Resonance Spectroscopy (MRS) potentially represents one such tool. This technique, done using an MRI scanner, provides information about tumour metabolism, and this information about what tumour cells are doing metabolically may be important to understanding their likely behaviour. This study will use MRS to create metabolic profiles for malignant brain tumours and to correlate these profiles with treatment response and outcome in a group of brain tumour patients. Hopefully, specific metabolic predictors of tumour behaviour will be identified, refining our ability to predict which treatments will help which tumours. The goal is a more intelligent and tailored approach to treating individuals with brain tumours.

Research findings from this project were published in the American Journal of Neuroradiology in March 2008. The study concluded that Low-grade glioma was characterized with low levels of NAA and Glu, high levels of mIns, and high levels of 23Na, whereas the ratio of NAA/23Na most clearly differentiated glioma tissue from normal tissue. To view the article in full published by Dr. Robert Bartha, Dr. Chris Watling, & Dr. Joseph Megyesi, click here.

Dr. Brian Thiessen

Clinical Assistant Professor, Division of Neurology
Vancouver General Hospital & Department of Medical Oncology, BC Cancer Agency,
Vancouver, B.C.

Title of Project:
Molecular Genetic Analysis of Tumour progression in Oligodendrogliomas.

Publication Summary:
Oligodendrogliomas often show deletions of chromosome arms 1p and 19q. Tumours with this molecular signature typically have a better prognosis and show good responses to chemotherapy. Nonetheless, these tumours still progress and become refractory to treatment. By using advanced molecular genetic analysis, we will examine several cases of oligodendrogliomas that have had more than one surgical procedure through the course of their illness. We hope to identify the key molecular changes that occur as these tumours progress from treatment responsive to treatment refractory stages. This may help identify which patients should be treated with cytotoxic chemotherapy and which tumours should be treated with novel molecular targeted therapies.

Any questions in regards to the Research Program, please call or e-mail the Research and Education Specialist:

Sue Ruypers
Research Program Specialist
(519) 642-7755 or 1-800-265-5106 ext. 240

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