MCGILL UNIVERSITY
Faculty of Medicine
Summer Research Bursary Program
APPLICATION / AGREEMENT
	
STUDENT INFORMATION – to be completed by Student	
SESSION 	SUMMER	Regular	X	Leukemia		Cardiology		
	WINTER		
Student Name	Margaret Aron	
Student ID	110228318	Present Address	
Faculty	Medicine	11 Oslo
D.D.O,  Quebec
H9A 2H4	
Program /Yr of Study	First year Medicine		
Social Insurance No.	282 226 331		
Date of Birth	July 29, 1983		
Foreign Students must supply the following info:	Phone (H)	(514) 421-0983	
Visa Number 	F-	Phone (W)		
Expiry Date		Email Address	maggiearon@hotmail.com	
Previous Research Experience:	
No previous research experience.  

	
I have read and I accept the conditions outlined in the Research Bursary Program Guidelines, describing the program.  I realize that if I do not fulfill the conditions, I may have to return the research bursary funds. 	
Student Signature	
	Date		
STUDENT-SUPERVISOR AGREEMENT – to be completed by McGill Faculty Member	
Supervisor	Dr. Miguel Bernier	Address	
Faculty ID	150931339	DuffBuilding-rm B216
3775 University St.
Montreal	
Telephone No.	(514) 843-1544		
Fax No.	(514) 843-1624		
Email Address	Miguel.bernier@mcgill.ca	Project Start Date	June 30, 2004	Project Finish Date	August 30, 2004	
Who will directly supervise the student’s research?	Dr. Miguel Bernier	
Title of Project	
Expression of phospho-AKT in human uveal melanoma animal model.
	
I have reviewed the above Student’s Research Project.  Approval from all appropriate Ethics Committees for research involving human subjects or animals has been obtained.  I have read and accept the conditions outlined in the Research Bursary Program Guidelines (pages 1 through 6), describing the program.  I realize that if my Student does not fulfill all of the conditions, he/she may have to return the research bursary funds.   	
Supervisor Signature	
	
Student Signature	
	
Date	

MCGILL UNIVERSITY
Faculty of Medicine
Summer Research Bursary Program
PROJECT PROPOSAL
	
SESSION 	SUMMER	Regular	x	Leukemia		Cardiology		
	WINTER		
Student Name	Margaret Aron	
Supervisor Name 	Dr. Miguel Bernier	
Note: Project Proposal to be written by the Student with guidance from the Supervisor	
Relevance of the project and hypothesis to be tested:	
Uveal melanoma is the most common primary intraocular tumor in adults with an incidence of 5 to 7 cases per million people per year. Despite successful local treatment with radiotherapy and/or surgery, systemic prognosis has not improved and 5-year survival rates were practically unchanged in the past decades. Tumor-related death is mainly due to liver metastasis, which is usually detected several years after diagnosis and treatment of the primary tumor. Once metastasis occurs, there is no effective treatment and the outcome is poor. Therefore, the search for new treatment strategies, especially those focusing on metastatic spread, continues. 
As with other tumors, several factors are implicated in the metastatic cascade of uveal melanoma. Protection from apoptosis is one of them, which is in turn related to a number of intracellular mediators and signaling pathways. These molecules and pathways represent important leads for the development of new therapeutic agents in cancer research. 
One example is Akt, an anti-apoptotic protein that has been shown to play a major role in cell survival and tumorigenesis. Akt is a serine/threonine kinase and an important component of the phosphatidylinositol 3’-kinase signaling pathway. Akt is activated by phosphorylation, becoming phospho-Akt. Phospho-Akt, in turn, phosphorylates and inactivates several proteins involved in apoptosis. 
Immunohistochemistry studies have been performed in other tumors, such as skin malignant melanoma, multiple myeloma, prostate cancer and renal cell carcinoma, showing a statistically significant association between positive phospho-Akt staining and high-grade tumors. 
The purpose of this study is to characterize the immunohistochemical expression of phospho-Akt in a human uveal melanoma animal model and its role as a prognostic factor of metastasis occurrence.
HYPOTHESIS
Phospho-Akt is expressed by uveal melanomas in the animal model and this expression correlates 

with the development of metastasis.

Methods:	

There are currently several animal models of ocular melanoma. Intraocular inoculation of cultured human uveal melanoma cells into the suprachoroidal space of immunosuppressed rabbits, the animal model that best resembles human disease, and is the one I will be using in this project.
Twenty-five immunosuppressed New Zealand albino rabbits will be injected with 1x106 human uveal melanoma cells into the suprachoroidal space. The 92.1 human uveal melanoma cell line will be used. All animals will receive the same cyclosporin A (CsA) dosing regimen during the 10-week experiment in order to prevent cell rejection. 
Autopsy and tissue collection (eyes, livers, lungs) will be performed at the end of the experiment on each rabbit. The specimens will be formalin-fixed, paraffin-embedded and sectioned.
Immunohistochemistry for phospho-Akt will be performed in the eye sections using an anti-phospho-Akt (Ser 473) rabbit antibody. Samples will be classified as negative or positive. 
Sections of the lungs and livers will be stained with hematoxilin-eosin and immunohistochemistry for HMB-45 will also be performed in order to confirm the presence of metastasis in these sites. 
Curves of cumulative metastasis according to phospho-Akt immunostaining will be plotted using Kaplan-Meier survival 

    analysis. The log-rank test will be used to assess statistically significant differences.	
The specific role of the student (including the student’s role in initiating the project) and possible problems in data collection and in relating the data to the hypothesis:	

STUDENT’S ROLE
-	Rabbit handling workshop;
-	Participate in the care of the animals during the experiment;
-	Perform immunohistochemistry for phospho-Akt and HMB-45;
-	Analyze and present the results as a scientific poster/ paper.

POSSIBLE PROBLEMS
Phospho-Akt is not expressed by human uveal melanoma cell lines; the rabbits do not develop tumor in the eye; the 

rabbits do not develop metastasis; immunohistochemistry for phospho-Akt does not work; phospho-Akt is expressed by 

human uveal melanoma cell lines in the animal model, however it is not able to be a predictor of metastasis development.

	
Student Signature	
	
Date