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  • "Celebrate failure!" says TFRI’s leader in new book celebrating Chinese Canadians

    by Peter Mothe | Jun 12, 2018

    Celebration
    A new book on on Chinese Canadian legacies published by Province of British Columbia Ministry of Tourism, Arts and Culture highlights Dr. Ling's work at the Terry Fox Research Institute. 

    "TO BE SUCCESSFUL, ONE MUST LEARN TO TOLERATE AND EVEN CELEBRATE FAILURES,"
    remarks TFRI President and Scientific Director Dr. Victor Ling, who is among several prominent Chinese Canadians featured in a newly published 180-page, full-colour book titled Celebration: Chinese Canadian Legacies in British Columbia. “As a young person, I learned to imagine what success would be like and let that vision sustain me through the long dark periods of waiting and dealing with repeated failures.”

    Published by the Province of British Columbia Ministry of Tourism, Arts and Culture, the book evolved as part of a legacy following an apology by the British Columbia Legislature for the historical wrongs endured by Chinese Canadians. It highlights the contributions Chinese Canadians have made to this country and province – from serving in the military to playing an important part of its social, cultural and economic fabric. 

    Dr. Ling is described as iconic figure in the field of cancer research. He refers to his role at TFRI “as a matchmaker in bringing the best scientists from different institutions to work on collaborative research on more effective and larger-scale research studies.”  He attributes his successes to his father and those who mentored him in his scientific research.






  • Three top Canadian research teams receive $13 million to solve key cancer challenges

    by Peter Mothe | Jun 12, 2018
    TFRI_2018PPG_Photo

    From left to right: Drs. Greg Czarnota (Sunnybrook Health Sciences Centre), David Malkin (Hospital for Sick Children) and David Huntsman (BC Cancer, UBC).

    (Click here for French version)

    VANCOUVER - Three outstanding cancer research teams will receive nearly $13 million to continue their investigations into rare tumours, an inherited disorder (Li-Fraumeni Syndrome) and the use of magnetic resonance imaging (MRI) and ultrasound to improve treatments for breast cancer.

    Two teams primarily based in Ontario and the other in BC will receive the funding from the Terry Fox Research Institute (TFRI) as winners of its 2018 Terry Fox New Frontiers Program Project Grant (PPGs) competition.

    “These three teams have demonstrated that they are able to think outside the box and create really innovative projects that tackle some of the most challenging problems in cancer research. They bring together leading researchers with complementary skills to investigate different aspects of a given area of cancer research to find solutions that could yield positive results for patients in the short term,” says Dr. Victor Ling, TFRI president and scientific director.

    The projects were selected after a rigorous process that saw a committee of international experts visit six short-listed labs before making a final decision on the award recipients.

    Familiar faces, innovative approaches

    All three research teams have a proven track-record in cancer research and have received funding from the TFRI before.  With this new funding, the teams hope to continue building on previous discoveries with the hopes of beginning to transition their ground-breaking research out of the lab and into clinics.

    “The only way you can do this type of research is through a team grant,” says Dr. David Huntsman (UBC, BC Cancer), lead investigator for the renewed forme fruste program. “The New Frontiers Grant is Canada’s premiere grant for team science cancer research and has allowed us to take on a large challenge – something much greater than any of us would be able to tackle as individuals – and be able to deliver discoveries that would otherwise be impossible to find.”

    Learn more about the research of the 2018 Terry Fox New Frontiers Program Project Grant winners:

    About The Terry Fox Research Institute (TFRI) 

    Launched in October 2007, The Terry Fox Research Institute is the brainchild of The Terry Fox Foundation and today functions as its research arm. TFRI seeks to improve significantly the outcomes of cancer research for the patient through a highly collaborative, team-oriented, milestone-based approach to research that will enable discoveries to translate quickly into practical solutions for cancer patients worldwide. TFRI collaborates with over 70 cancer hospitals and research organizations across Canada. TFRI headquarters are in Vancouver, BC. www.tfri.ca 


    For more information, contact:
     
    Peter Mothe
    Communications Specialist
    604-675-8000 ext.7630
    C: 604-773-2827
    pmothe@tfri.ca 

  • Trois des meilleures équipes de recherche canadiennes reçoivent 13 millions de dollars pour résoudre les principaux problèmes liés au cancer

    by Peter Mothe | Jun 05, 2018

    TFRI_2018PPG_Photo
    Drs. Greg Czarnota (Sunnybrook Health Sciences Centre), David Malkin (Hospital for Sick Children) and David Huntsman (BC Cancer, UBC)

    (Click here for English version)


    VANCOUVER -
    Trois équipes exceptionnelles de recherche sur le cancer recevront près de 13 millions de dollars afin de poursuivre leurs recherches sur les tumeurs rares, un trouble héréditaire (syndrome de Li-Fraumeni), sur l'imagerie par résonance magnétique (IRM) ainsi que sur l'échographie pour améliorer les traitements du cancer du sein.

    Deux équipes, une basée en Ontario et l'autre en Colombie-Britannique, recevront le financement de l'Institut de recherche Terry Fox (IRTF) en tant que lauréats du concours de subventions de projet du Programme Terry Fox Nouvelles frontières (PPG) de 2018.

    “Ces trois équipes ont démontré qu'elles sont capables de sortir des sentiers battus et de créer des projets vraiment innovants qui s'attaquent à certains des problèmes les plus difficiles de la recherche sur le cancer. Ils réunissent des chercheurs chevronnés possédant des compétences complémentaires pour étudier différents aspects d'un domaine donné de la recherche sur le cancer afin de trouver des solutions qui pourraient conduire à des résultats positifs à court terme pour les patients ”, déclare le Dr Victor Ling, président et directeur scientifique de l'IRTF.

    Les projets ont été sélectionnés à la suite d’un processus rigoureux, notamment par la visite par un comité d'experts internationaux de six laboratoires présélectionnés avant que la décision finale sur les lauréats soit rendue.

    Visages familiers, approches innovantes

    Les trois équipes de recherche ont fait leurs preuves dans la recherche sur le cancer et ont déjà reçu des fonds de l'IRTF auparavant. Grâce à ce nouveau financement, ces équipes espèrent continuer à tirer parti des découvertes précédentes dans l'espoir de commencer à faire le transfert de leurs résultats de recherche vers la clinique.

    “La seule façon de faire ce genre de recherche est de subventionner une équipe”, affirme le Dr David Huntsman (UBC, BC Cancer), chercheur principal du programme renouvelé sur les formes frustes de cancer. “La subvention Nouvelles frontières est la première subvention canadienne pour la recherche scientifique sur le cancer en équipe et nous a permis de relever un grand défi - quelque chose de beaucoup plus grand qu'aucun d'entre nous ne pourrait atteindre en tant qu'individu - et de faire des découvertes autrement impossible à faire."

    Pour en apprendre davantage sur les lauréats du programme Nouvelles frontières 2018 Terry Fox :

    Au sujet de l’Instutut de recherche Terry Fox (IRTF)

    Lancé en octobre 2007, l'Institut de recherche Terry Fox est une idée originale de la Fondation Terry Fox et fonctionne aujourd'hui comme son bras de recherche. L'IRTF cherche à améliorer considérablement les résultats de la recherche sur le cancer pour le patient grâce à une approche de recherche hautement collaborative, axée sur l'équipe et sur les étapes, qui permettra aux découvertes de se traduire rapidement en solutions pratiques pour les patients atteints de cancer. L'IRTF collabore avec plus de 70 hôpitaux et organismes de recherche sur le cancer partout au Canada. Le siège de l'IRTF est à Vancouver, en Colombie-Britannique. www.tfri.ca 

    Pour de plus amples informations, veuillez contacter: 

    Peter Mothe
    Spécialiste des communications
    604-675-8000 poste 7630
    C: 604-773-2827
    pmothe@tfri.ca


  • Three top Canadian research teams receive $13 million to solve key cancer challenges

    by Peter Mothe | Jun 05, 2018
    TFRI_2018PPG_Photo

    From left to right: Drs. Greg Czarnota (Sunnybrook Health Sciences Centre), David Malkin (Hospital for Sick Children) and David Huntsman (BC Cancer, UBC).

    (Click here for French version)

    VANCOUVER - Three outstanding cancer research teams will receive nearly $13 million to continue their investigations into rare tumours, an inherited disorder (Li-Fraumeni Syndrome) and the use of magnetic resonance imaging (MRI) and ultrasound to improve treatments for breast cancer.

    Two teams primarily based in Ontario and the other in BC will receive the funding from the Terry Fox Research Institute (TFRI) as winners of its 2018 Terry Fox New Frontiers Program Project Grant (PPGs) competition.

    “These three teams have demonstrated that they are able to think outside the box and create really innovative projects that tackle some of the most challenging problems in cancer research. They bring together leading researchers with complementary skills to investigate different aspects of a given area of cancer research to find solutions that could yield positive results for patients in the short term,” says Dr. Victor Ling, TFRI president and scientific director.

    The projects were selected after a rigorous process that saw a committee of international experts visit six short-listed labs before making a final decision on the award recipients.

    Familiar faces, innovative approaches

    All three research teams have a proven track-record in cancer research and have received funding from the TFRI before.  With this new funding, the teams hope to continue building on previous discoveries with the hopes of beginning to transition their ground-breaking research out of the lab and into clinics.

    “The only way you can do this type of research is through a team grant,” says Dr. David Huntsman (UBC, BC Cancer), lead investigator for the renewed forme fruste program. “The New Frontiers Grant is Canada’s premiere grant for team science cancer research and has allowed us to take on a large challenge – something much greater than any of us would be able to tackle as individuals – and be able to deliver discoveries that would otherwise be impossible to find.”

    Learn more about the research of the 2018 Terry Fox New Frontiers Program Project Grant winners:

    About The Terry Fox Research Institute (TFRI) 

    Launched in October 2007, The Terry Fox Research Institute is the brainchild of The Terry Fox Foundation and today functions as its research arm. TFRI seeks to improve significantly the outcomes of cancer research for the patient through a highly collaborative, team-oriented, milestone-based approach to research that will enable discoveries to translate quickly into practical solutions for cancer patients worldwide. TFRI collaborates with over 70 cancer hospitals and research organizations across Canada. TFRI headquarters are in Vancouver, BC. www.tfri.ca 


    For more information, contact:
     
    Peter Mothe
    Communications Specialist
    604-675-8000 ext.7630
    C: 604-773-2827
    pmothe@tfri.ca 

  • Erectile dysfunction drugs and flu vaccine may work together to help immune system fight cancer after surgery, study finds

    by Peter Mothe | May 17, 2018

    Auer_Rebecca

    A new study led by Dr. Rebecca Auer, a member of TFRI's Oncolytic Virus project and former recipient of a TFRI New Investigator Award, suggests that a common treatment for erectile dysfunction combined with the flu vaccine may be able to help the immune system mop up cancer cells left behind after surgery. The study, published in OncoImmunology, shows that this unconventional strategy can reduce the spread of cancer by more than 90 percent in a mouse model. It is now being evaluated in a world-first clinical trial.  

    “Surgery is very effective in removing solid tumours,” said Dr. Auer, a surgical oncologist and head of cancer research at The Ottawa Hospital. “However, we’re now realizing that, tragically, surgery can also suppress the immune system in a way that makes it easier for any remaining cancer cells to persist and spread to other organs. Our research suggests that combining erectile dysfunction drugs with the flu vaccine may be able to block this phenomenon and help prevent cancer from coming back after surgery.”

    The current study investigated sildenafil (Viagra), tadalafil (Cialis) and an inactivated influenza vaccine (Agriflu) in a mouse model that mimics the spread of cancer (metastasis) after surgery. The researchers evaluated these treatments by counting the number of metastases in mouse lungs. They found an average of:

    • 37 metastases with cancer cells alone
    • 129 metastases with cancer cells and surgery
    • 24 metastases with cancer cells, surgery and one of the erectile dysfunction drugs
    • 11 metastases with cancer cells, surgery, one of the erectile dysfunction drugs and the flu vaccine

    Dr. Auer is now leading the first clinical trial in the world of an erectile dysfunction drug (tadalafil) and the flu vaccine in people with cancer. It will involve 24 patients at The Ottawa Hospital undergoing abdominal cancer surgery. This trial is designed to evaluate safety and look for changes in the immune system. If successful, larger trials could look at possible benefits to patients.  

    “We’re really excited about this research because it suggests that two safe and relatively inexpensive therapies may be able to solve a big problem in cancer,” said Dr. Auer. “If confirmed in clinical trials, this could become the first therapy to address the immune problems caused by cancer surgery.” 

    Using a variety of mouse and human models, Dr. Auer’s team has also made progress in understanding how erectile dysfunction drugs and the flu vaccine affect cancer after surgery. Normally, immune cells called natural killer (NK) cells play a major role in killing metastatic cancer cells. But surgery causes another kind of immune cell, called a myeloid derived suppressor cell (MDSC), to block the NK cells. Dr. Auer’s team has found that erectile dysfunction drugs block these MDSCs, which allows the NK cells to do their job fighting cancer. The flu vaccine further stimulates the NK cells.

    “Cancer immunotherapy is a huge area of research right now, but we’re still learning how best to use it in the time around surgery,” said first author Dr. Lee-Hwa Tai, former postdoctoral fellow in Dr. Auer’s lab and now assistant professor at the Université de Sherbrooke. “This research is an important step forward that opens up many possibilities.”

    Dr. Auer noted that although erectile dysfunction drugs and the flu vaccine are widely available, people with cancer should not self-medicate. Any changes in medication should be discussed with an oncologist.

    The work was funded by several agencies and organizations. 

    Full reference: “Phosphodiesterase-5 inhibition reduces postoperative metastatic disease by targeting surgery-induced myeloid derived suppressor cell-dependent inhibition of Natural Killer cell cytotoxicity.”  Lee-Hwa Tai, Almohanad A. Alkayyal, Amanda L. Leslie, Shalini Sahi, Sean Bennett, Christiano Tanese de Souza, Katherine Baxter, Leonard Angka, Rebecca Xu, Michael A. Kennedy & Rebecca C. Auer. OncoImmunology. Published Online: 01 Mar 2018. https://www.tandfonline.com/doi/full/10.1080/2162402X.2018.1431082


  • Breakthrough test uses ctDNA to determine treatment resistance in advanced prostate cancer patients

    by TFRI Admin | May 15, 2018
    Dr. Alex Wyatt Image

    Metastatic castration-resistant prostate cancer (mCRPC) patients are now one step closer to more personalized treatment, thanks to a new test that can distinguish who will respond well to standard therapies and who will become resistant to treatment.

    The simple blood test uses plasma circulating tumour DNA (ctDNA) to identify genetic markers that can indicate if a patient is either currently -- or likely to become -- resistant to widely-used treatments. Defects in BRCA2 and ATM were strongly linked to poor clinical outcomes in patients receiving standard therapy regimes, and somatic alterations in TP53 were also independently associated with tumour resistance.

    The present study was led by Drs. Kim Chi, Alexander Wyatt and Martin Gleave (Vancouver Prostate Centre), and results were published in Cancer Discovery (January 2018). Around 30 per cent of patients with advanced metastatic cancer do not respond to standard treatments. This test is the first of its kind to offer hope to these patients, allowing physicians to direct this demographic to alternative treatments or therapy intensification (combination approaches) that may be more effective in treating their metastatic disease.

    The paper builds on the team’s foundational June 2017 discovery (published in JNCI), which determined that plasma ctDNA was indeed accurately representative of metastatic prostate cancer biopsies. Prior to this discovery, the only method of collecting samples of metastases in advanced prostate cancer was by taking a biopsy of the bone, the most common location for tumour spread in this disease. This invasive procedure hindered the collection of metastases, and made developing more personalized patient management difficult.

    For the JNCI paper, researchers performed targeted sequencing across 72 clinically relevant genes in ctDNA samples from 45 different patients. The results showed that all somatic mutations identified in matched metastatic tissue biopsies were also present in ctDNA, suggesting that blood-based profiling is sufficient to guide mCRPC patient management.

    Study: Concordance of Circulating Tumor DNA and Matched Metastatic Tissue Biopsy in Prostate Cancer

     Authors: Alexander W. Wyatt, Matti Annala, Rahul Aggarwal, Kevin Beja, Felix Feng, Jack Youngren, Adam Foye, Paul Lloyd, Matti Nykter, Tomasz M. Beer, Joshi J. Alumkal, George V. Thomas, Robert E. Reiter, Matthew B. Rettig, Christopher P. Evans, Allen C. Gao, Kim N. Chi, Eric J. Small, Martin E. Gleave

    Study: Circulating Tumor DNA Genomics Correlate with Resistance to Abiraterone and Enzalutamide in Prostate Cancer

    Authors: Matti Annala, Gillian Vandekerkhove, Daniel Khalaf, Sinja Taavitsainen, Kevin Beja, Evan W. Warner, Katherine Sunderland, Christian Kollmannsberger, Bernhard J. Eigl, Daygen Finch, Conrad D. Oja, Joanna Vergidis, Muhammad Zulfiqar, Arun A. Azad, Matti Nykter, Martin E. Gleave, Alexander W. Wyatt, and Kim N. Chi

    Funding: Both studies were funded in part by a Terry Fox New Frontiers Program Project grant from The Terry Fox Research Institute.

     Links #6

  • Medulloblastoma leptomeningeal metastases can also occur through the bloodstream, study finds

    by TFRI Admin | May 15, 2018
    Dr. Michael Taylor

    Findings from a recent study published in Cell are breaking new ground in the pediatric brain cancer world, suggesting medulloblastoma cells can metastasize in an entirely different way than previously assumed.

    Medulloblastoma is a tumour of the cerebellum that frequently metastasizes to the leptomeninges of the central nervous system. It is the most common malignant childhood brain tumour, and metastasis is the leading cause of patient death.

     The scientific community has historically assumed this metastasis occurred exclusively when cancer cells detached from the tumour in the cerebellum, travelling in the cerebrospinal fluid to attach and grow on the leptomeninges. Yet a recent discovery led by Dr. Michael Taylor (SickKids Hospital, Toronto) and his TFRI-funded team has shown that medulloblastoma cells can also travel from the cerebellum to the bloodstream before entering the central nervous system and forming leptomeningeal metastases. The majority of other cancers also spread through a similar hematogenous route.

    With this information, new methods to detect recurrence can be devised by analyzing the circulating tumour cells in the blood of patients post-treatment. This could potentially enable clinicians to detect patients who are at higher risk of developing metastasis very early, and administer treatment more aggressively. Further, specific strategies to kill or block these cells from entering the central nervous system and forming metastasis can be designed by analyzing the circulating tumour cells.

    Importantly, the team has also identified a signalling pathway that increases the tendency of medulloblastoma cells to metastasize, the CCL2/CCR2 axis. Leptomeningeal metastases express high levels of the chemokine CCL2, and expression of CCL2 in medulloblastoma can stimulate dissemination. Looking forward, this information could be utilized to design metastasis-specific precision medicine approaches for medulloblastoma.

    Study: A Hematogenous Route for Medulloblastoma Leptomeningeal Metastases

    Authors: Livia Garzia, Noriyuki Kijima, A. Sorana Morrissy, Pasqualino De Antonellis, Ana Guerreiro-Stucklin, Borja L. Holgado, Xiaochong Wu, Xin Wang, Michael Parsons, Kory Zayne, Alex Manno, Claudia Kuzan-Fischer, Carolina Nor, Laura K. Donovan, Jessica Liu, Lei Qin, Alexandra Garancher, Kun-Wei Liu, Sheila Mansouri, Betty Luu, Yuan Yao Thompson, Vijay Ramaswamy, John Peacock, Hamza Farooq, Patryk Skowron, David J.H. Shih, Angela Li, Sherine Ensan, Clinton S. Robbins, Myron Cybulsky, Siddhartha Mitra, Yussanne Ma, Richard Moore, Andy Mungall, Yoon-Jae Cho, William A. Weiss, Jennifer A. Chan, Cynthia E. Hawkins, Maura Massimino, Nada Jabado, Michal Zapotocky, David Sumerauer, Eric Bouffet, Peter Dirks, Uri Tabori, Poul H.B. Sorensen, Priscilla K. Brastianos, Kenneth Aldape, Steven J.M. Jones, Marco A. Marra, James R. Woodgett, Robert J. Wechsler-Reya, Daniel W. Fults, and Michael D. Taylor.

     Funding: This study is supported in part by the Terry Fox Research Institute.

    Links #6

     

     

     

  • Researchers develop groundbreaking targeted sequencing pipeline to further precision medicine in lymphoid cancers

    by TFRI Admin | May 15, 2018
    Dr. Steidl

    A cancer research team funded partly by The Terry Fox Research Institute has identified the best method for sequencing gene mutations across several of the most common forms of lymphoid cancer.

     Dr. Christian Steidl (BC Cancer, Vancouver) led the groundbreaking study, published in The Journal of Molecular Diagnostics (March 2018). The paper established hybrid-capture sequencing as the method of choice for sequencing of actionable gene mutations in diffuse large B-cell lymphoma, follicular lymphoma, and chronic lymphocytic leukemia.

     Lymphoid cancers are the fourth most common cancer in Canada, and incidence rates have steadily increased over the last 50 years. Fully implemented targeted sequencing-based assays in routine-diagnostic pathology laboratories are currently lacking in lymphoid cancer care, and clinical implementation of precision medicine approaches is needed in the form of novel biomarker assays.

     In the present study, the team compared capture hybridization and amplicon sequencing approaches using tumour samples from lymphoma patients. A targeted sequencing pipeline using a 32-gene panel was developed for accurate detection of actionable mutations in tumour samples from the most common forms of lymphoid cancers. Hybrid-capture sequencing was found to be superior to the amplicon-based method when it comes to providing deep, more uniform coverage, as well as yielding higher sensitivity for variant calling. Further, at least one actionable mutation was identified in 91 per cent of tumours from 219 patients.

     This discovery has the potential to change the way future testing in this field is done, as amplicon-based methods have been preferentially used given their short preparation time and small DNA input amounts. Importantly, the team has developed and optimized a targeted sequencing assay and demonstrated successful application of this assay to prospectively collected tissue and blood samples of patients treated at BC Cancer over a three-year period.

    Looking forward, the scientists hope to implement these assays in accredited pathology labs and demonstrate clinical utility beyond pure outcome prognostication. This is a necessary step to offering sequencing-based biomarker assays to patients, in particular in the context of clinical trials testing novel cancer therapeutics and biomarker-driven clinical decision-making.

     Study: Assessment of Capture and Amplicon-Based Approaches for the Development of a Targeted Next-Generation Sequencing Pipeline to Personalize Lymphoma Management

     Authors: Stacy S. Hung, Barbara Meissner, Elizabeth A. Chavez, Susana Ben-Neriah, Daisuke Ennishi, Martin R. Jones, Hennady P. Shulha, Fong Chun Chan, Merrill Boyle, Robert Kridel, Randy D. Gascoyne, Andrew J. Mungall, Marco A. Marra, David W. Scott, Joseph M. Connors, and Christian Steidl.

     Funding: This study is supported in part by the Terry Fox Research Institute grant 1061.

     

     

     

     

     


  • Targeting hypoxia can, in turn, target cancer-initiating cells in colorectal tumours

    by TFRI Admin | May 15, 2018

    Targeting hypoxia can, in turn, target cancer-initiating cells (C-ICs) in colorectal cancer a study team in Toronto has found. Additionally, the team has discovered a biomarker for hypoxia to identify tumours that would most benefit from this innovative treatment method.

    C-ICs occur in many tumour types, and are known to be self-renewing. They also become resistant to chemotherapy and radiotherapy, and increase rapidly when exposed to hypoxia. Patients respond poorly to treatment if their tumours are hypoxic (oxygen deficient), and these tumours are more likely to grow and spread aggressively. Despite this, targeting hypoxia is not a standard treatment option.

    Dr. Catherine O’Brien (Princess Margaret Cancer Centre, Toronto) led the present study, published in Clinical Cancer Research (March 2018) and funded in part by TFRI. The paper demonstrated that a four-day course of 5-Fluorouracil (5-FU) could drive colorectal cancer cells to enter a hypoxic, cancer-initiating cell (C-IC) state. During this phase the cancer cells were extremely sensitive to the hypoxia-activated prodrug evofosfamide (Evo). Sequential treatment with either 5-FU or chemoradiotherapy (CRT) followed by Evo specifically targeted the colorectal C-ICs.

    The non-invasive biomarker (FAZA-PET) they found for hypoxia can predict if a colorectal cancer tumour would respond to this selective targeting. Using non-invasive FAZA-PET/CT imaging, it was found that tumours with higher baseline intratumoral hypoxia responded best to this innovative form of therapy.

    This form of novel combination therapy holds tremendous potential to improve patient outcomes. Colorectal cancer is the second most common cancer diagnosed in Canada, and is the second-leading cause of cancer death for men and the third for women. 

     Study: Administration of Hypoxia-Activated Prodrug Evofosfamide after Conventional Adjuvant Therapy Enhances Therapeutic Outcome and Targets Cancer-Initiating Cells in Preclinical Models of Colorectal Cancer

     Authors: Jennifer Haynes, Trevor D. McKee, Andrew Haller, Yadong Wang, Cherry Leung, Deena M. A. Gendoo, Evelyne Lima-Fernandes, Antonija Kreso, Robin Wolman, Eva Szentgyorgyi, Douglass C. Vines, Benjamin Haibe-Kains, Bradly G. Wouters, UrMetser, David A. Jaffray, Myles J. Smith, Catherine A. O’Brien.

     Funding: This work was supported in part by grants from The Terry Fox Research Institute.

     Links #6

  • Blocking donor T cell–mediated TNFα signaling can enhance positive effects of stem cell transplantation

    by TFRI Admin | May 15, 2018
    Drs. Zandstra & Weijia3
    Photo: Study author Dr. Weijia Wang


    A collaboration between Swiss and Canadian research institutes has shown an effective way to enhance human hematopoietic stem and progenitor cell engraftment after stem cell transplantation by blocking donor T cell-mediated TNFα signalling.

    The study, published in Science Translational Medicine (December 2017), was led by Dr. Peter Zandstra (University of Toronto) and Dr. Weijia Wang (formerly at the University of Toronto and now in collaborator Timm Schroeder’s lab at ETH Zürich) with collaboration from renowned TFRI-funded cancer researcher Dr. John Dick (Princess Margaret Cancer Centre). Results suggested that tumour necrosis factor-alpha (TNFα), which is produced by some of the differentiated cells after stem cell transplantation, is harmful for the survival of blood stem cells. Further, by using one of the clinically available drugs that block TNFα, higher numbers of blood stem cells and more diverse types of blood cells were found in the bone marrow after two weeks of transplant in a preclinical mouse model.    

     Allogeneic hematopoietic stem cell transplantation (HSCT) is a form of therapy for patients living with hematologic diseases including leukemia, and is potentially curative – yet up to 70 per cent of patients do not have a matched related donor. One cell source of stem cell transplantations is umbilical cord blood, but the number of stem cells available in individual umbilical cord blood units is often limiting. This can lead to delayed hematopoietic recovery and a higher risk of graft failure, both major complications that can lead to patient death post-transplant.

    The findings in the present study have the potential to dramatically improve patient outcomes after a transplant, and provide a strong basis for conducting clinical trials to see whether the use of TNFα blockers (which are used to treat auto-immune diseases like arthritis and psoriasis) could improve the outcomes of people who receive blood stem cell transplants. For example, if this strategy boosts the survival rate of blood stem cells in humans, smaller grafts could be used. This would vastly increase the pool of usable umbilical cord blood donations, making stem cell transplants more feasible – not only for blood cancers, but also for auto-immune diseases, like Crohn’s disease or even HIV.

    Study: Enhanced human hematopoietic stem and progenitor cell engraftment by blocking donor T cell-mediated TNFα signalling

    Authors: Weijia Wang, Hisaki Fujii, Hye Jin Kim, Karin Hermans, Tatiana Usenko, Stephanie Xie, Zhi-Juan Luo, Jennifer Ma, Cristina Lo Celso, John E. Dick, Timm Schroeder, Joerg Krueger, Donna Wall, R. Maarten Egeler, Peter W. Zandstra.

     Funding: This study was partially funded by a grant from the Terry Fox Research Institute.

    Links #6

     

     

     


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