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Archive for the ‘Researcher’s Blog’ Category

Targeting tumours the FAST way

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Hello! We are Brent Johnston and Roy Duncan, Professors in the Department of Microbiology & Immunology at Dalhousie University. We have received funding from the Breast Cancer Society of Canada and the QEII Foundation through the Beatrice Hunter Cancer Research Institute, to investigate the use of viruses to target advanced and metastatic breast cancer.

Targeting tumours the FAST way, Breast Cancer Society of CanadaOncolytic viruses are engineered to selectively infect cancer cells by taking advantage of altered signalling pathways that result from cancer cell mutations. Oncolytic viruses not only kill tumour cells directly, they also stimulate the immune system to recognize and target the remaining cancer cells. Dr. Duncan has generated a novel oncolytic virus expressing a Fusion-Associated Small Transmembrane (FAST) protein. This protein helps the virus spread between tumour cells better, leading to greater infection and killing of cultured cancer cells. We are investigating how well FAST oncolytic viruses target breast cancer tumours and whether modified viruses can enhance stimulation of the immune system to target metastatic cancer cells. FAST viruses are also being combined with other therapeutic approaches that boost the function of the immune system further.

We are very excited that our approaches are generating promising results, and hope that his research will help establish new therapies to target advanced and metastatic breast cancer.

We thank the Breast Cancer Society of Canada, the QEll Foundation, and the generous donors for giving us the opportunity to do this work.

Towards breast cancer detection with nanoprobes

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Greetings! My name is Antonio Benayas. As some of you can perhaps remember from a previous post , I am a postdoc at Institut National de la Recherche Scientifique, working to develop novel near infrared nanoprobes part of Professor Fiorenzo Vetrone’s group. It is the right time to summarize what has been accomplished during my term as CIHR-BCSC fellow.

Nanoparticles researchers at CSACS

Nanoparticles-related researchers at CSACS meeting http://csacs.mcgill.ca (Montreal, QC May 2016). From left to right: INRS PhD student Artiom Skripka, myself, INRS-Venice U. PhD Student Riccardo Marin, and our colleague Concordia U. PhD student Paola Rojas.

Accordingly to our job at the academic research stage, my contribution is to develop a pool of … let us call them “discreet spies”! Ultra-small entities (nanoparticles) adapted to inject in to humans and can effectively navigate through the blood stream. They will be able to report the presence and evolution of tumors, in a non-invasive way (harmlessly emitting light). In this multi-lane “assembly line” inside the nanomedicines´ factory, the multidisciplinary group led by Prof. Vetrone is setting the chassis, transmission, and wheels. All those pieces are not called upon in a “common car”, but in a very customized one for cancer imaging and detection.

When our role is done, we passed the vehicle to the next workstation (in other words, communicating it to the scientific community). Then is the time of physicians/oncologists to test the different vessels provided, and to pick up the best among them to move ahead to clinical implementation, step by step. Although my combat takes place in a battleground far away from the bedside of cancer patients, I firmly believe it is very important to keep digging at the basic science level. That way, we provide those closer-to-the-cancer-patient researchers with the best possible weapons to map the extinction of the disease, advancing the fight against it. I am glad to inform you that our published results has advanced the state-of-the-art towards low-dose in vivo nanoprobes successfully tested in mice. Moreover, several kinds of “spies” also show the capacity to measure the temperature of their surroundings. That key feature has indeed allowed our best nanoprobes to carry out a real-time monitoring of heat-based eradication of superficial tumors on live specimens, thus avoiding any damage to healthy tissues around the tumor.

But there are other kinds of assets and progress that I would like to share with you. First, throughout my BCSC-funded term, I devoted my best efforts to set up a cutting-edge microscopy facility* in the relatively young group of Prof. Vetrone at INRS. That in-house tool expands the possibility to test at the cellular level our nano-spies right after we synthesize them. Like in any other human endeavor, workflow efficiency is important. In a different note, we have created new forums to share with the pure Materials Science community, the relevance of body-penetrating near-infrared wavelengths. We are bringing additional minds and resources to the joint venture of pursuing a better non-invasive imaging of breast cancer and other diseases.

Finally, my aim guiding these few lines is to also emphasize what will remain after my departure. In fact, the team I helped to assembly will work further on getting better nanoprobes “to spy” for the appearance of (breast) cancer tumors. In that regard, I have been fortunate enough to mentor and work, shoulder to shoulder, with well-trained and highly motivated young scientists such as Riccardo Marin and Artiom Skripka (picture above). They now carry the torch, and I foresee more exciting results to come that will help the crusade against breast cancer.
Thank you to BCSC for your trainee support!
– Antonio Benayas (Ph.D.),
Postdoctoral Researcher (Eileen Iwanicki Fellow 12/2013-11/2016; CIHR-BCSC)

(*) That venture was undergone in close cooperation with a small but very ambitious Canadian optics company (Photon Etc.).

Receptor for Hyaluronan-Mediated Motility or RHAMM

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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.

Alexandra Hauser-Kawaguchi - BCSC Breast Cancer ResearcherFor the past few years, I have been studying the protein RHAMM (Receptor for Hyaluronan-Mediated Motility). RHAMM levels increase in response to fragmentation of the compound hyaluronan (HA), which ultimately results in the spread of cancer and thus poorer outcomes for breast cancer patients.

We have recently been developing stapled peptides as RHAMM mimics. “Stapled” peptides are compounds that have been partially cyclized, giving them the appearance of having a “stapled” backbone. This “stapling” allows the peptide to circulate through the body longer than it would otherwise. This is ideal, as our RHAMM mimics are part of a drug discovery initiative, in which we have shown that they are able to block inflammation associated with breast cancer relating to fragmented HA. The RHAMM mimics could also help stop the disease from spreading to other parts of the body.

In September of 2016, I had the opportunity to attend the 34th European Peptide Symposium and 8th International Peptide Symposium in Leipzig, Germany. I was one of eight chosen to give an oral presentation in front of 700 scientists. This experience was frightening but also thrilling, and the high point of my graduate student career to date. After meeting with and learning from experts in the field, I returned to the lab full of new ideas on how to make our compounds better drugs for treating breast cancer.

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

Understanding how the estrogen receptor impacts breast cancer

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Hello! 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 Regional Cancer Program.
Bart KolendowskiDuring my tenure as a Pamela Greenaway-Kohlmeier Translational Breast Cancer Research Unit (TBCRU) scholarship recipient, I have focused my research on understanding how the estrogen receptor, a common target during breast cancer therapy, impacts breast cancer. By developing our understanding of how the estrogen receptor functions, we not only learn about how certain breast cancer therapies work but also why they may fail. With the support of TBCRU funding I have been able to advance our understanding of estrogen-mediated gene-expression, identifying previously unknown mechanisms that drive breast cancer development.

This work has been well received and has given me the opportunity to present my findings at prestigious conferences, including the Canadian Institutes of Health Research National Student Research Competition held at the University of Winnipeg. I was also selected for an oral presentation at the international Keystone Symposia on Nuclear Receptors held in Snowbird, Utah. I am excited as my research is currently being compiled into a manuscript for submission to an academic journal to be shared with a broader audience.

In addition to helping advance my research, the TBCRU scholarship has promoted researchers’ engagement with the community through events like the Breast Cancer Society of Canada’s Mother’s Day Walk. These events allow researchers to meet and hear the stories of survivors and their families while also giving us an opportunity to share our work with them, successfully bridging the world of research with the people it impacts.

Imaging biomarkers in treatment of breast cancer with high-dose radiation therapy

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My name is Matthew Mouawad. I am a third-year PhD student in the department of Medical Biophysics at Western University working under the supervision of Drs. Stewart Gaede and Neil Gelman.

Matthew Mouawad, CAMPEP PhD candidate Pamela Greenaway-Kohlmeier Translational Breast Cancer Research Unit, London Health Sciences Centre

With the high prevalence of breast cancers (1 in 9 women) in North America, we need to find ways to minimize the emotional and physical burden on patients and explore more efficient treatment techniques. Currently, breast-conserving therapies will often include five weeks of post-surgery radiotherapy, which can be prohibitively long for many patients. Furthermore, we currently do not have methods to non-invasively evaluate tumour control at an early stage.

To address these two limitations, London Regional Cancer Program is conducting a clinical trial headed by Drs. Muriel Brackstone, Michael Lock, and Brian Yaremko that is looking to reduce treatment time from five weeks to a single session, using high-dose radiotherapy. My role in this project is to use imaging we acquire from the hybrid PET-MRI at St. Joseph’s hospital to assess tumour control within seven days of treatment! The treatment technique would minimize patient burden significantly and the imaging would allow us to explore alternative ways to treat patients and potentially allow for adaptive patient treatment techniques.

We have successfully treated 14 patients using the new high-dose radiotherapy technique and have developed an imaging protocol that will allow us to investigate various tumour biomarkers. I look forward to presenting the most recent results in an manuscript within the next few months.

Thank you to BCSC for your trainee support!

– Matthew Mouawad, CAMPEP PhD candidate

Pamela Greenaway-Kohlmeier Translational Breast Cancer Research Unit, London Health Sciences Centre

 

Retinoic Acid maybe an effective therapy

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Dr Paola MarcatoI am Dr. Paola Marcato, Assistant Professor in the Department of Pathology at Dalhousie University. the Canadian Breast Cancer Society, the Beatrice Hunter Cancer Research Institute and the QEII Foundation, have funded my research lab and colleagues: Drs. Carman Giacomantonio, Lucy Helyer and Ian Weaver.

Our research is to  investigate if a vitamin A metabolite, retinoic acid may be an effective therapy for certain triple-negative breast cancer patients. Retinoic acid is a highly effective treatment for acute promyelocytic leukemia; however, when retinoic acid was applied generally to treat other cancers, including breast cancer it was not effective.

Our data suggests that retinoic acid-based therapy was not successful in the treatment of breast cancer because it was applied to all cancer patients, without considering key differences between individual patient tumors. Our data suggests that there are specific and measurable criteria that can predict if a triple-negative breast cancer tumor will respond well to retinoic acid treatment.

We propose experiments that will identify and measure these qualities in triple-negative breast cancer patients. Furthermore, we will use a pre-clinical model to test how effective our prediction tools are in determining tumor response to retinoic acid.

Completion of this project will lead to improved treatment for triple-negative breast cancer patients and hence the improved survival of these patients currently lacking targeted therapy options.

 

A Student Exchange Program: Understanding breast cancer using laboratory models

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Vasuveda Bhat and Dr. Alison Allan, in Dr. Allan’s lab at the London Regional Cancer Program.

Hello! My name is Vasudeva Bhat, PhD candidate in the Department of Immunology, under the guidance of Dr. Afshin Raouf at Regenerative Medicine Program/Cancercare Manitoba

Our lab is interested in investigating the molecular mechanisms involved in regulating the regenerative potential of normal mammary stem cells and how alterations in them produce tumors. In short we want to understand NORMAL to define ABNORMAL. Our studies have identified a key molecule which plays an important role in regulating cells fate during breast tissue regeneration and we believe that altered function of this molecule could potentially lead to breast cancer.

In order to further explore my interest in breast cancer I was given the opportunity to visit Dr. Alison Allan’s lab at London Regional Cancer Program in Ontario to better understand breast cancer using novel laboratory models.

Under Dr. Allan’s supervision I was able to learn techniques to decipher the ability of breast cancer cells to acquire stem-like characteristics. In addition, I also gained expertise in 2D and 3D ex vivo models to elucidate the potential of these cancer cells in promoting tumor development and spread.

I believe that the experience gained here will help in better understanding of breast cancer as a disease and design therapeutic strategies to treat patients.

Thank you Breast Cancer Society of Canada for your generous support of this trainee exchange program.

Vasudeva Bhat, PhD Candidate
Dr. Raouf Lab, University of Manitoba

Dr. Alison Allan (exchange program supervisor)
London Regional Cancer Program

3rd Biennial International Cancer Research Conference

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3rd Biennial International Cancer Research Conference

Hi all! My name is Milica Krstic and I am a PhD student within the department of Pathology and Laboratory Medicine at Western University. I work in Dr. Ann Chambers’ and Dr. Alan Tuck’s lab located at London Health Sciences Centre’s London Regional Cancer Program.

You may have seen my previous blog posts where I discussed my work studying how and why early breast cancer lesions progress to invasive cancer.

On November 19th, I travelled to my hometown of Windsor, Ontario to attend the 3rd Biennial International Cancer Research Conference hosted by the Windsor Cancer Research Group. I was invited to give an oral presentation about my research, focusing on a protein called TBX3 and the molecular mechanisms by which it promotes breast cancer progression [picture shown above]. In the audience were several experts across multiple disciplines, including research scientists (from both biology and chemistry-related fields), pathologists, oncologists, industry professionals and so on. The oral presentations and poster presentations were fascinating and great at fostering scientific discussion. I’m glad that I attended this conference and would suggest it to others as well!

The goal of my research project is to be able to predict which early breast cancer lesions will progress to invasion – this would allow us to stratify patients into risk groups, which would ultimately influence treatment strategies. I have begun the fourth year of my PhD training and work towards this goal every day!

Previous blog posts from Milica Krstic

 

Alyssa, a reason to give!

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Alyssa Vito Giving Tuesday Story

On November 29th, The Breast Cancer Society of Canada will partner with the Giving Tuesday Canada initiative to encourage Canadians across the country to fund life-saving breast cancer research.

Alyssa Vito is a breast cancer survivor, whose journey led her to cancer research. Alyssa’s story inspires the kind of work the Breast Cancer Society is funding. We hope you will also find inspiration in her story and take part in Giving Tuesday on November 29th, by giving to help those in need!

Alyssa’s Story

Six-time Ironman World champion Mark Allen once said, “Until you face your fears, you don’t move to the other side, where you find the power.” As someone who has been an athlete my entire life, I relate deeply to this quote. Overcoming fear is a crucial step to any athletic success. But athleticism aside, the cancer survivor inside me relates to this even deeper. Because there can be nothing scarier to an athlete than your body being devoured by cancer. And it’s only when you step up and face that fear head on that you can move to the other side and find a power so strong you never even knew it existed.

After finishing my B.Sc. and moving back to Toronto I was in top physical form. I had just finished rowing four years on a division one rowing team in the USA and was in the best shape of my life. I ran. I cycled. I worked out every day. Twice a day. I felt invincible. But one night when I was going to bed, I found a lump in my breast. And no matter how many people told me that I was “too young to have breast cancer”, on July 23rd, 2011,  I was diagnosed with invasive ductal carcinoma in the right breast.

With no family history and essentially no risk factors, it was a shocking diagnosis to anyone and everyone who heard it. But family history and risk factors aside, what was even more shocking was how healthy I was. I looked like someone capable of running a marathon… and I was.

I was twenty-three years old, working in the medical field and aspiring to become an oncologist. I had been a competitive athlete my entire life and lived as healthy and active as I could. I spent years volunteering in the cancer centre at Credit Valley Hospital and imagined one day transitioning from volunteer to doctor, but never considered the possibility that I could wind up a patient there myself.

Pathology showed that my tumour was stage two, triple negative and as such I was given an aggressive treatment regimen. I underwent surgery, chemo and radiation therapy and have now been in remission for four years and eight months.

After finishing treatment, I decided to go back to school and work in the field of cancer research. I wanted to see firsthand what was being done to prevent what I had gone through, from happening to someone else like me. I went to McMaster University and did my M.Sc. degree in chemical biology. My thesis sought to develop and evaluate molecular imaging probes for breast cancer detection. While I cannot say that I developed anything in my time there that is actually being used in the clinic today, I can say that we have made progress. We are making progress. One small step at a time.

This year I returned to McMaster to pursue my PhD, again in the field of cancer research. My PhD thesis is focused on an exciting new field, exploring immunotherapies for breast cancer treatment. These immunotherapies offer a way to use a patient’s own immune system to kill the malignant cells within them.

The field of oncology research is ever evolving. Ever changing. Ever growing. And it is no easy feat. As someone who works in this field, I can tell you that for every 100 experiments and hypotheses done in the lab, maybe 10 work. It is a constant battle to tackle such a devastating disease and work towards some way of better detecting it, fighting it, treating it.

Breast cancer mortality rates have decreased by 44% since the peak in 1986. This decrease is directly linked to research efforts like those I just mentioned. And even with that vast decrease, we still have a long way to go. This is precisely why organizations like the Breast Cancer Society of Canada and days like Giving Tuesday are so incredibly important. Though you may have heard it over and over again, I want to tell you that every dollar counts. Research works. I am living proof of this. But… research is expensive. The process of taking an idea, curating it, funding it and taking it from bench-to-bedside is no cheap or easy feat. No matter what your reason is for being connected to the cancer community, you need to remember that every dollar you donate puts us one step closer to a life in which no person fears cancer.

I never thought I would get into research. I never thought I would get breast cancer. Often in life, things happen that we weren’t expecting. It disrupts our daily flow and throws a fork into the straight road we thought we were traveling. But at the end of the day, it’s these divergent paths that guide us to new, typically better outcomes. It is these disruptions that carve out our lives. Our stories. It is these exact disruptions that have made me a wife, a mother, a survivor, a researcher and an overall better person… and I wouldn’t change one inch of it given the chance.

Your donation to The Breast Cancer Society of Canada will help fund breast cancer research. Give today and help save lives.

 

Where are they now? Former TBCRU Trainee Donna Murrell

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We thought it would be interesting to track the career development of trainees previously supported by studentships from Translational Breast Cancer Research Unit (TBCRU) in London.Donna Murrell, PhD 

Hello!  My name is Donna Murrell and I was supported by a TBCRU studentship, funded by the Breast Cancer Society of Canada, from 2012-2014. I then successfully competed for a national Canadian Breast Cancer Foundation Fellowship for 2014-2016.  You may have read some of my previous blog entries in 2014 and 2015.  I studied in Dr. Paula Foster’s lab at Robarts Research Institute and I recently earned my PhD in Medical Biophysics and Molecular Imaging from Western University.  My research project used magnetic resonance imaging (MRI) to study the development of breast cancer brain metastasis and dormant cancer cells to better understand how they are affected by radiation therapy.

My career goal is to become a clinical medical physicist and help to treat people who have cancer using radiation therapy.  To prepare for this career, I completed a CAMPEP-accredited (Commission on Accreditation of Medical Physics Education Programs) course-based Masters Degree concurrently with my PhD.  I am now working as a Physics Resident at the London Regional Cancer Program (LRCP) and will complete two years of clinical training in radiation oncology physics.  I am really enjoying residency and am learning a lot very quickly!
Thank you to BCSC for your support of the TBCRU program and helping me to launch my career.

Donna Murrell, PhD –  (pictured above in a radiation treatment room at the LRCP, with a linear accelerator that is used to deliver radiation treatment.)