2005 Research Grants

In 2005, the following researchers received funding to support the research into the causes of and cures for brain tumours.

Dr. Sultan Darvesh

Associate Professor, Faculty of Medicine
Dalhousie University
Halifax, Nova Scotia

Title of Project:
Butyrylcholinesterase and primary brain tumours: mechanisms and treatment options.

This project is directed at gaining a better understanding of the roles that the enzymes butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE) play in brain tumorigenesis and how altering their activity might affect tumour growth. We will conduct several experiments to accomplish this goal. First, we will investigate BuChE and AChE activity in brain tumour cell lines. Second, we will study how increasing the concentration of each enzyme (BuChE or AChE) affects tumour proliferation and growth. Finally, we will explore what affect our synthetic cholinesterase modulators have on tumour cell proliferation and growth. It is our expectation that the results from these experiments will give us a greater understanding of the roles BuChE and AChE play in tumour growth and possibly provide a novel approach to treat brain tumours.


Dr. Rolando Del Maestro

Director, Brain Tumour Research Center
Montreal Neurological Institute
Montreal, Quebec

Title of Project:
Sodium alginate bead bioreactor technology for the sustained delivery of anti-invasive compounds in an in vivo medulloblastoma model.

Malignant central nervous system tumours rapidly invade the brain and make complete surgical removal difficult. Medulloblastoma is the most common malignant brain tumour in children, and recent studies placing brain tumours in the context of neurodevelopment have led to the recognition of new tumour suppressors and oncogenes involved in tumour progression. Slit and its receptor Roundabout (Robo) have been shown to play roles in the motility of cells as distinct as neurons and leukocytes. Recent evidence suggests that Slit2-Robo1 signaling inhibits medulloblastoma invasion using methods such as sodium alginate bead bioreactor technology. These results can be expanded to developing a reproducible in vivo system to investigate the effect of continuous, sustained delivery of anti-invasive compounds such as Slit on medulloblastoma invasion. Using this system, tumours can be examined using standard histology techniques and imaged using by magnetic resonance imaging (MRI). If sodium alginate bead bioreactor technology is successful at decreasing tumour growth, it may provide a mechanism for sustained anti-tumour and anti-invasive molecular release into the bed of resected tumours.

Research Outcome: The main objective of this research was to study an in vitro system to investigate the effects of continuous, sustained delivery of the anti-invasive Slit2 on medulloblastoma invasion.

Upon completion of research, this study indicated that Slit2 inhibit medulloblastoma invasion as evidenced in a number of in vitro models. Videomicroscopy demonstrates the reduction of invasion rate by Slit2, without affecting cell direction or proliferation. 

The study also found that both medulloblastoma and glioma tumours express Robo1 and Slit2 proteins, however medulloblastoma invasion is inhibited by Slit2. The study suggests the down-regulation of Cdc42 may contribute to the difference in response. Results help to validate the use of neurodevelopment cues in understanding brain tumour invasion. 

Dr. Brian K. Rutt

Scientist, Imaging Group
Robarts Research Institute
London, Ontario

Title of Project:
Visualizing invading glioma cells with magnetic resonance imaging (MRI).

The main objective of this research was focused on developing MRI and labelling techniques for imaging glioma cells in an in vitro model, and to study the factors that influence the detectability of labelled cells in a 3D model of cell invasion.

The migration and invasion of glioma cells has not yet been observed in vivo over time and thus, it is still unknown at which state in the cancer process the cells leave the primary tumour. Until recently, the imaging of single cells in vivo had not been possible. However, single cells have been detected in vitro with magnetic resonance imaging (MRI) using special cell labeling techniques by several groups including our own, and the role of factors contributing to their detection are being investigated and characterized. The underlying hypothesis for this work is that single invading glioma cells can be visualized and studied using MRI. Our objectives are to develop MRI and labeling techniques for imaging glioma cells in an in vitro model, and to study the factors that influence the detect ability of labeled cells in a 3-dimensional model of cell invasion.

Research Outcome: Upon completion of research this study indicates that the methods developed have the potential to allow for the detection of cell invasion away from a bulk tumour and may also have application to other models that require high sensitivity to iron.


Dr. Penelope C. Costello

Adjunct Professor, Department of Pathology
University of Western Ontario
London, Ontario

Title of Project:
Determination of human brain tumour therapy response using an Ex Vivo invasion assay - a potential step toward individualized treatment.

Surgical tissue specimens can be used to obtain valuable information regarding sensitivity to therapies. A tiny tumour specimen obtained immediately after surgical removal can be placed in a nutrient-rich gelatine mixture or matrix. If the tissue specimen is kept at body temperature, the tumour cells will remain active and will invade into the surrounding 3-dimensional gelatine matrix. This invasion mimics the tumour spreading in the body. Tumour movement and invasion can be monitored using a microscope and measured using a video camera that has been attached to the microscope. Potential chemo and radiation therapies can be administered to the tumour specimen right in the gelatine matrix. The relative effectiveness of therapies can be assessed for a patient’s individual tumour response within 5-10 days. Patients normally begin chemotherapy and/or radiation therapy 4 weeks after surgery. This provides a small window of opportunity to pre-evaluate clinical tumour response to a number of potential therapies.

Initially, the focus of the tissue testing will be malignant brain tumours. Tumour specimens from each patient will be evaluated by mimicking the chemotherapy and radiation treatment patterns that they may receive in the clinic. The predictive value and clinical significance of data from the surgical tissue 3-dimensional invasion assay can then be evaluated by correlating this data with patient outcome. The assays can be adapted to accommodate a large number of specimens per patient and will allow for a statistically significant amount of data for each therapy being tested.

The main goal of this project is to test individual patient tumours with existing and newly developed therapeutic treatment modalities in a well-established model of invasion and growth. The response data is intended to provide the neuro-oncology team with additional information about the patient’s tumour responsiveness to a variety of therapies. The project is unique in that it represents a mutual interest and collaboration by the surgeons, pathologists, oncologists and scientists dedicated to improving care for brain tumour patients. There is potential for the information obtained from this surgical tissue invasion assays to lead to more individualized and therefore more successful treatment of each patient.

In vivo - An experiment in a living organism rather than in a test tube, using human or animal subjects. Latin translation: "in life".
Ex vivo – Tissues or cells removed from within the living body for analysis. Latin translation: "out of or from life"
In vitro - In an artificial environment, especially test tube experiments involving a reaction of human tissue. Latin translation: "in glass".

Research Outcome: The main goal of this project was to test individual patient tumours with existing and newly developed therapeutic treatment modalities in a well-established model of invasion and growth. Results from Dr. Costello's research indicated that individual response to chemotherapy is highly variable both clinically and in the ex vivo assessment. Pre-screening responsiveness to chemotherapies could lead to more individualized and more effective treatment of brain tumours.

Dr. Costello is Adjunct Professor, Department of Pathology the University of Western Ontario and Co-Founder of Onco-Screen Inc. at the London Health Sciences Centre – South Street Hospital

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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