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HSIP 2010 Program

2010hsp

2010 HSIP Interns (Clockwise: Henry Barron, Nicole Crooks, Alicia Parker, Jason Wang)

Histology as a tool for Cancer Diagnosis and Research - Led by Researcher Katy Milne

The aim of the this project was to give the two selected HSIP students a chance to see how various histological techniques are used in the diagnosis of cancer and as a means of taking a closer look at the characteristics of the tumor microenvironment in research.   

In addition to performing histological work required by several research groups the students also had a chance to work on a couple side projects.  One project involved looking at immune cells in human ovarian cancer xenografts from mouse, comparing them to the primary tumour samples that they came from.  The information gained from the project will hopefully be built on as the Deeley Research Centre moves toward adopting xenograft models for immune infiltrate research to better understand how the immune system and cancer interact. 

The students were also responsible for the set-up, quality control and technical development of an automated staining system in the histology lab.  They were responsible for testing the equipment, setting protocols and selling the researchers on the benefits of automated staining over protocols currently used in the lab.  This piece of equipment was demonstrated to be superior to existing staining methods in terms of quality and cost and time savings and will have a lasting impact on the lab. 

The students had many opportunities to learn the different features of both normal and tumour tissue and got a chance to see how the Tumour Tissue Repository (TTR) plays a vital role in cancer research in obtaining tumour samples from patients undergoing surgery.  They were also involved in numerous other tasks including reorganizing the histology lab and updating the DRC chemical inventory. 

 

 Mouse Mammory Tumour Project - led by Researchers Dr. Michele Martin and Dr. Ron de Leeuw

Breast cancer is estimated to affect 1 in 10 women. While newer treatments have improved the 10-year survival rate, certain types of breast cancer still have a poor prognosis. 

Approximately 30% of breast cancers are classified as “HER2 positive”. HER2 is a transmembrane protein that is expressed at the surface of HER2 positive breast cancer cells and acts as a receptor for a growth factor. Over-expression of this protein is correlated to more aggressive breast tumours and consequently, a poor prognosis. While there are treatments that can effectively induce remission, HER2 positive tumours frequently recur and metastasize to distant sites. Thus, more effective therapies are needed for this type of breast cancer. 

We investigated the adoptive immunotherapy technique for treating this type of breast cancer. Adoptive immunotherapy involved the isolation of a patients’ own tumour reactive immune cells (“killer” T cells) followed by a massive in vitro expansion of these T cells. After expansion, this “army” of tumour reactive T cells was re-infused back into the patient, with the expectation that these T cells would recognize and destroy the tumour. While this technique has been used to successfully treat melanoma (a type of skin cancer), it has yet to be evaluated in the setting of human breast cancer. 

Using an innovative mouse model for HER2 breast cancer, we were able to develop breast cancer cell lines and test them for susceptibility to the adoptive immunotherapy technique. Using these cell lines, we determined that one cell line (NOP21CR) is completely responsive to adoptive immunotherapy and these tumours fully regress following treatment and do not recur. Another cell line (NOP23PR) is partially responsive to adoptive immunotherapy. T cells can initially induce regression of these tumours, but for some reason, these tumours recur and then continue to grow. A third cell line (NOP18PD) was completely unresponsive to adoptive immunotherapy; T cells are unable to affect the growth of these tumours. Therefore, a major question that we were interested in is: “why are some tumours resistant to T cells?” To answer this, we used an experimental gene expression technique (“Affymetrix”) to assess the entire gene expression profile of these three different tumours. In doing so, we have determined that there is a subset of genes that is differentially expressed by these tumours, and some of these genes may be responsible for the differing susceptibility to T cell therapy. By identifying the critical genes responsible for the different sensitivities to adoptive immunotherapy, we may be able to enhance the efficacy of this treatment. We may also be able to predict whether a patient’s tumour would respond to adoptive immunotherapy, or whether a different treatment option would be more beneficial. 

This summer, the interns were involved in further validation of our Affymetrix data using the quantitative polymerase chain reaction (QPCR) technique. To do this, our interns were involved with the isolation of messenger RNA (mRNA) from tumours, followed by the synthesis of complementary DNA (cDNA) and then assessed gene expression using QPCR. This also involved the hands-on design of QPCR primers, an important part of the experimental technique. Depending on the results, we may also validate our experimental findings at the protein level using the Western Blot technique.  

 

Meet the Interns

   

 

 

 

  henry 

Henry Barron, Esquimalt Secondary School

I look forward to exploring the cancer immunology research projects that are part of the HSIP.  Cancer is a disease that hits close to home for me, as it does for so many.  To be a part of the process of trying to find a cure is a truly exciting and inspiring prospect.  The opportunity to learn and work for experienced researchers and perform real science is another huge draw for me.  Here's looking forward to an excellent 8 weeks!

     

   

 

 

 

  nicole 

Nicole Crooks, Timberline Secondary School

I am interested in the differences between cancer cells and regular cells and the reasons cancer cells can survive for an extended period of time and adapt to different areas of the body.  

   

  

 

 


  alicia 

Alicia Parker, Cowichan Secondary School

While attending Cowichan Secondary School, right out of Grade 11, I know very little about the world of research and am learning more each day.  I am very interested in medicine, and searching for the answers of cancer, and how it can be prevented.  I am looking forward to learning new things throughout the summer, and really understanding what my interests are.

   

   

 

 

 

  jason 

Jason Wang, Dover Bay Secondary School

As part of the High School Internship Program, I will be working on the Mouse Mammary Tumour Project, led by Researchers Dr. Michele Martin and Dr. Ron de Leeuw.  We will be primarily investigating the adoptive immunotherapy technique for treating HER2 Positive tumours.  As an intern, I will be involved in further validation of the Affymetrix data by using the quantitative polymerase chain reaction (QPCR) technique.