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Archive for the ‘Researcher’s Blog’ Category

Using MRI to detect TAM cells

posted by:
Makela

Ashley Makela, PhD candidate

Hi! My name is Ashley Makela and I’m a PhD candidate in the Department of Medical Biophysics at Western University. I’m working at Robarts Research Institute in Dr. Paula Foster’s lab where MRI cell tracking is a main focus.

My research involves using MRI to detect and quantify specific cells called tumour associated macrophages (TAMs), which are associated with cancer. The presence of these cells in breast cancer correlates with an aggressive tumour, metastasis (the spread of the primary tumour to distant sites in the body) and a poor patient prognosis.

We’re excited because our imaging has been telling us a lot about the breast cancer tumour microenvironment – for instance, we can visualize these cells within a mouse model of breast cancer. The ability to do this may produce important information about the influence of TAMs on tumour growth and metastatic spread, and give insight on how to use this information to aid in detection, prognosis and treatment evaluation.

The next few months will be exciting ones! I’ll be busy writing a research paper and will be presenting my research at the International Society for Magnetic Resonance in Medicine conference in Singapore this May.

Thank you to BCSC for your trainee support!
Ashley Makela, PhD Candidate
Pamela Greenaway-Kohlmeier Translational Breast Cancer Research Unit, London Health Sciences Centre

Examining how breast cancer tumour ‘seeds’ travel to other organs

posted by:
Mauricio Rodriguez-Torres

Mauricio Rodriguez-Torres

Hello! I’m Mauricio Rodriguez-Torres and I’m a PhD student in the Department of Anatomy and Cell Biology at Western University, working under the supervision of Dr. Alison Allan.

Most breast cancer deaths occur as a result of metastasis, the process whereby tumour cells leave the breast through the bloodstream and establish themselves in other organs. These metastatic tumours are often difficult to find and have an increased capacity for therapy resistance.

Furthermore, there is strong scientific evidence indicating that not all tumour cells have an equal ability to seed themselves in distant organs. In particular, a very aggressive group of breast tumour cells, also known as breast cancer stem cells, have been found to display an increased ability to form metastasis.

We’re identifying the molecular factors utilized by these tumour seeds to enter, be planted and thrive in distant organs. The identification and subsequent interference of the action of these factors with new drugs has the potential to improve breast cancer treatment by blocking the lethal seeding activity of breast cancer to distant vital organs, such as the lung.

Because so many breast cancer patients die from metastasis affecting their vital organs, we’re aiming to identify and control the tumour cells responsible for metastatic behavior.

Thank you to BCSC for your trainee support!
Mauricio Rodriguez-Torres, PhD student
Pamela Greenaway-Kohlmeier Translational Breast Cancer Research Unit, London Health Sciences Centre

A potential tool to differentiate between malignant tumours and benign tissue in MRI

posted by:

Yonathan ArayaHello! My name is Yonathan Araya and I’m a PhD candidate in the Department of Medical Biophysics at Western University. I work in the Imaging Research Laboratories at Robarts Research Institute under the supervision Dr. Timothy Scholl.

One of the disadvantages of Magnetic Resonance Imaging (MRI) is the lack of specificity and sensitivity to distinguish between malignant tumours and benign tissue, and the different stages of tumour progression. One way to address this shortcoming is targeted magnetic resonance contrast-agent approaches, whereby a contrast agent binds to specific proteins or receptors.

I’ve been imaging the specific magnetic field dependence of tissues and quantifying their intrinsic magnetic resonance properties using our fast field-cycling magnet. This work is ongoing at the University Hospital 1.5 Tesla MRI suite. The application of a fast field-cycling MRI allows us to observe the targeted contrast agent when it binds to the protein/receptor, suppressing the untargeted agent and background tissue. This is a potential tool to differentiate between normal and cancerous breast tissues.

Our preliminary findings have shown an inherent weak magnetic field dependence of healthy tissues. This is important as we study atypical or cancerous tissues, which may have a significantly greater magnetic field dependence and may be highlighted by a targeted contrast agent.

Thank you for your trainee support!
Yonathan Araya, PhD candidate
Pamela Greenaway-Kohlmeier Translational Breast Cancer Research Unit, London Health Sciences Centre

How do breast cancer cells move through the body?

posted by:
Drs. Desnoyer and Lewis

Drs. Desnoyer and Lewis at the Atlantic Cancer Research Institute in Moncton, NB

Drs. Desnoyers and Lewis are working to understand how breast cancer cells can move throughout the body. Breast cancer becomes more aggressive when normal breast cells change to become invasive by a process called epithelial-to-mesenchymal transition (EMT). Following EMT, breast cancer cells can move throughout the body and spread the tumor, an event known as metastasis. In recent years, small molecules called miRNA have been shown to be important in the regulation of EMT and the formation of metastases. Given that miRNAs are fairly easy to detect from biological fluids, they are currently employed as cancer biomarkers.

Drs. Desnoyers and Lewis want to characterize the way these miRNAs contribute to EMT to provide a better understanding of how breast cancer metastasis is regulated, with the goal of identifying novel miRNAs involved in the regulation of EMT and breast cancer metastasis.

Through their research, Drs. Desnoyers and Lewis hope to gain a better understanding of EMT and the metastatic process, which may lead to the identification of novel therapeutic targets for the treatment of metastatic breast cancer. In addition, the novel miRNAs that they identify in their study could be suitable biomarkers to help in the early detection of metastatic breast cancer.

 

Dr. Guillaume Desnoyers and Dr. Stephen Lewis at the Atlantic Cancer Research Institute in Moncton, New Brunswick received funding from the Breast Cancer Society of Canada through a partnership with the QEll Foundation and the Beatrice Hunter Cancer Research Institute.

Attempting to inhibit breast cancer proliferation

posted by:
Hauser-Kawaguchi

Alexandra Hauser-Kawaguchi in the lab

Hi everyone! My name is Alexandra Hauser-Kawaguchi and I’m a PhD candidate in the Department of Chemistry at Western University. I work in Dr. Len Luyt’s lab at London Health Sciences Centre’s London Regional Cancer Program.

You may remember seeing my blog post last year.

Since then, I’ve continued to study the interactions between the mini-protein known as 7 kDa RHAMM and the molecules called peptide ligands. If we can discover a peptide that has better binding to 7 kDa RHAMM than the natural ligand, we can potentially inhibit the actions that lead to breast cancer proliferation.

It’s taken a while, but we’ve finally found that the best way to study these interactions is by using the technique called surface plasmon resonance, which studies the binding interactions in real time.

This past year has been an exciting one outside the lab as well. I presented my work at the Boulder Peptide Symposium in September, where I also learned about some interesting new techniques. I’ve already started using some of them in the lab … updates to come in my next blog post!

Thank you to BCSC for your trainee support!
Alexandra Hauser-Kawaguchi, PhD candidate
Pamela Greenaway-Kohlmeier Translational Breast Cancer Research Unit, London Health Sciences Centre

Helping breast surgeons increase the success rate of breast-conserving surgery

posted by:

Hi! My name is Ivan Kosik and I’m a PhD student in the Department of Medical Biophysics at Western University, working in the lab of Jeff Carson, PhD.  You might have seen my first blog in January 2015 where I outlined our strategy to increase the success rate of breast-conserving surgery by developing an imaging system that can help surgeons ensure that complete tumour removal was achieved on the first try.

Ivan Kosik, student researcher

Ivan Kosik, student researcher

I’m pleased to say we’ve made great strides in the effort to translate our technology from bench to bedside, accelerating towards the day when we can directly impact patients’ lives.  We’ve adapted our imager to fit within the OR and have been actively working with Dr. Muriel Brackstone.  To date we’ve imaged 80 specimens with very encouraging results, and have even attracted the attention of a medical device company interested in commercializing our technology.  This is very exciting because it represents a potential leap towards improving the standard of care for all breast cancer patients.

In the near future I hope to bring attention to our technology through conference presentations where I can reach a broader audience of surgeons and medical professionals.

Thank you to BCSC for your trainee support!
Ivan Kosik, PhD student
Pamela Greenaway-Kohlmeier Translational Breast Cancer Research Unit, London Health Sciences Centre

Why do some early breast cancers progress to deadly cancer and others do not?

posted by:
milica krstic

Milica Krstic in the TBCRU Lab

Hi! My name is Milica Krstic. I’m a PhD student in the Department of Pathology and Laboratory Medicine at Western University. I work at London Regional Cancer Program under the supervision of Ann Chambers, PhD, and Alan Tuck, MD/PhD.

I’m studying a protein called TBX3 and its role in early stages of breast cancer. It has been shown that TBX3 levels are higher in several types of cancer, but its role in breast cancer progression is not yet understood.

I’ve shown that elevating TBX3 levels in early breast cancer cells causes them to become more aggressive in cell lines and animal models. Women with early breast cancers (termed DCIS or ductal carcinoma in situ) have a 10-times-higher risk for developing invasive cancer than woman without DCIS history. However, why some lesions progress and others don’t is not yet understood.

I’ve studied expression of this protein in 200 breast cancer patient samples to see if TBX3 levels predict for whether these tumours will progress. I’m also studying the mechanism by which TBX3 promotes cancer progression.

Understanding this mechanism may lead to new treatment targets to inhibit TBX3 signaling pathways for breast cancer therapy, with the aim of stopping early breast cancers from progressing to deadly cancers.

Thank you to BCSC for your trainee support!
Milica Krstic
Pamela Greenaway-Kohlmeier Translational Breast Cancer Research Unit, London Health Sciences Centre

Identifying how the estrogen receptor drives tumour growth

posted by:
PhD candidate Bart Kolendowski

PhD candidate Bart Kolendowski

Hi! My name is Bart Kolendowski and I’m a PhD candidate in the Department of Biochemistry at Western University. I work in Dr. Joe Torchia’s lab located at London Health Sciences Centre’s London Regional Cancer Program.

Our lab is interested in the basic mechanisms of nuclear hormone signalling and gene regulation, and how these signalling pathways relate to cancer. My research is dedicated to understanding a receptor protein for the hormone estrogen called the estrogen receptor, which is found in many breast cancers and is often the target of breast cancer therapies.

Using powerful techniques from modern biology such as next-generation sequencing, as well as computational sciences, I’ve been able to identify a new mechanism by which the estrogen receptor causes changes in gene expression and drives tumour growth. The current work we’re doing will provide us with new information that is important for understanding estrogen receptor function and the connection between hormone-regulated gene expression and breast cancer.

Recently, my research was selected for a presentation at the Keystone Symposia on Nuclear Receptors held in Snowbird, Utah. Presenting my work at this prestigious conference will be a great opportunity to share with academic and industry leaders the innovative research being supported by the BCSC.

Thank you for your trainee support!
Bart Kolendowski, PhD candidate
Pamela Greenaway-Kohlmeier Translational Breast Cancer Research Unit, London Health Sciences Centre

What role do bacteria play in breast cancer?

posted by:
camilla

Camilla Urbaniak, PhD student

Hello! I’m Camilla Urbaniak, a PhD student in the Department of Microbiology & Immunology at Western University. I’m studying the bacteria that grow in breast tissue so I can determine which bacteria may protect against breast cancer development, and which may promote cancer development. We’re also studying whether these breast bacteria can affect a woman’s response to chemotherapy.

In February 2015, I was invited to give a talk at the 8th International Symposium on the Breast, hosted by the Dr. Susan Love Research Foundation. The enthusiasm and passion emanating from all the speakers and attendees (including clinicians, basic scientists and breast cancer survivors) was infectious, and I was touched by the collaborative spirit and desire to work together to put an end to this devastating disease.

One unique part of the conference was the formation of consortia, in which we developed projects (over the span of three days) that were then presented to a panel of judges for grants. One consortium winner proposed the use of bacterial proteins, administered intraductally into women with breast cancer, in order to boost the anti-tumour immune response so as to prevent invasive breast cancer from developing.

This meeting has been the highlight of my year and I’m already hoping to be able to attend again in two years’ time.

Thank you to BCSC for your trainee support!
– Camilla Urbaniak
Pamela Greenaway-Kohlmeier Translational Breast Cancer Research Unit, London Health Sciences Centre

Studying why some breast cancer patients are Herceptin-resistant

posted by:
Xuguang

PhD student Xuguang Liu

Greetings! I’m Xuguang Liu, a fourth-year PhD student in the Biochemistry Department at Western University. My current research project is focused on the development of Herceptin resistance in HER2-positive breast cancer. Particularly, we’re trying to establish a diagnostic technique that might be able to further classify this cancer type.

HER2-positive breast cancer is diagnosed as over-activity of the HER2 gene. Two target therapeutics, Tykerb and Herceptin, have been clinically approved and both are designed to reduce HER2 activity.

A common problem for the target therapeutics is drug resistance. For instance, only 30 per cent of patients diagnosed as HER2-positive respond to Herceptin in the beginning, which is defined as “intrinsic resistance.” In this 30 per cent of patients, many develop “acquired resistance” as soon as several months after treatment. The mechanism of resistance is complicated, but it’s well accepted that many HER2-like players can be over-activated during treatment, which in turn compensate for the loss of HER2 activity.

We’re trying to establish a strategy to define the activation status of all these players from a single test on a biopsy sample. In a preliminary test, we’ve successfully isolated the activity-deciding fragments of these players from a tiny amount of lab-cultured cells, and made them analyzable in the mass-spectrometry instrument.

Future work will aim to establish a standard operating procedure in biopsy-sample diagnosis. Finding these co-players will facilitate a further classification of HER2-positive breast cancer and the design of precision treatment for each breast cancer patient.

Thank you to BCSC for your trainee support!
 – Xuguang Liu, PhD Student
Pamela Greenaway-Kohlmeier Translational Breast Cancer Research Unit, London Health Sciences Centre