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News Article | February 15, 2017
Site: www.eurekalert.org

OTTAWA, ON ¬- Feb. 15, 2017 -- A promising combination of immunotherapies delivers a one-two punch to brain cancer tumours with high cure rates in mice, scientific evidence published in Nature Communications today says. Researchers at the Children's Hospital of Eastern Ontario (CHEO) in Ottawa found that a combination of drugs known as SMAC Mimetics and immune checkpoint inhibitors (ICIs) amplifies kill rates of cancer tumour cells in laboratory testing. Researchers also discovered a new mechanism by which the combination promotes long-term immunity against glioblastoma tumours. The combination therapy also proved to be highly effective against breast cancer and multiple myeloma. "These findings represent a significant evolution in our research and the field of immunotherapy. We are the first in the world to show the synergistic tumour-killing impact of combining SMAC Mimetics with immune checkpoint inhibitors for glioblastoma," said Dr. Robert Korneluk, distinguished professor at the University of Ottawa and senior scientist at the CHEO Research Institute. "You could say it takes two to tango. We believe that it takes a combination strategy to impact cancer cure rates." In 2014, a team of scientists led by Dr. Korneluk discovered that combining SMAC Mimetics with immune stimulators or live virus therapies had a synergistic or amplified tumour-killing effect that was greater than either agent on its own. Today's news shows that SMAC Mimetics also have a powerful synergistic effect with ICIs, relatively new drugs that are showing great promise in the clinic. SMAC Mimetics known as LCL161 and Birinapant were combined with ICI antibodies targeting PD-1 and CTLA-4 immune checkpoints. Eric Lacasse, a scientist at the CHEO Research Institute, said: "Two drug companies have initiated human clinical trials this year to assess the impact of this combination of SMAC Mimetics and ICIs on patients with a variety of cancers. Although it could be years before any clinical trials begin for adults or children with the deadly brain cancer, glioblastoma, we're looking forward to seeing how scientific evidence from these experimental treatments adds to our knowledge. It's an exciting, exploratory field and we hope we've hit a home run." Shawn Beug, lead author of the 2014 and 2017 papers, said: "This research heightens our understanding of the mechanics behind this double-whammy effect, which both enhances the immune response and weakens tumour cells to immune attack. We're hoping that more oncologists and biotech companies test out this combination in clinical trials as we continue to decipher how SMAC Mimetics encourage the immune system to kill cancer cells." The research was funded by the Canadian Cancer Society Research Institute, Brain Canada (with financial support from Health Canada through the Canada Brain Research Fund) and the Canadian Institutes of Health Research. In addition, the work was supported by donations to the Ottawa Regional Cancer Foundation, the Kiwanis Medical Foundation and the CHEO Foundation. The University of Ottawa--A crossroads of cultures and ideas The University of Ottawa is home to over 50,000 students, faculty and staff, who live, work and study in both French and English. Our campus is a crossroads of cultures and ideas, where bold minds come together to inspire game-changing ideas. We are one of Canada's top 10 research universities--our professors and researchers explore new approaches to today's challenges. One of a handful of Canadian universities ranked among the top 200 in the world, we attract exceptional thinkers and welcome diverse perspectives from across the globe. The CHEO Research Institute coordinates the research activities of the Children's Hospital of Eastern Ontario (CHEO) and is affiliated with the University of Ottawa. Its three programs of research include molecular biomedicine, health information technology, and evidence to practice research. Key themes include cancer, diabetes, obesity, mental health, emergency medicine, musculoskeletal health, electronic health information and privacy, and genetics of rare disease. The CHEO Research Institute makes discoveries today for healthier kids tomorrow. For more information, visit http://www.

News Article | November 2, 2016
Site: www.eurekalert.org

The Ottawa Hospital, the Children's Hospital of Eastern Ontario (CHEO), the University of Ottawa (uOttawa) and McMaster University congratulate Turnstone Biologics Inc. (Turnstone) on securing US$ 41.4 million in new private investments. Turnstone was founded in 2015 to advance the development of novel oncolytic viral immunotherapies for cancer. Its technology is based on research led by Dr. John Bell (from The Ottawa Hospital and uOttawa), Dr. Brian Lichty (from McMaster University) and Dr. David Stojdl (from CHEO and uOttawa). Turnstone's most advanced product is an oncolytic Maraba virus that is engineered to express melanoma-associated antigen A3 (MAGEA3). This is currently being tested in a clinical trial led by The Ottawa Hospital, sponsored by the Canadian Cancer Trials Group, and funded by the Ontario Institute for Cancer Research. Full results are expected to be released in 2017. More information for patients is available here. Dr. David Stojdl, senior scientist, Children's Hospital of Eastern Ontario; associate professor, University of Ottawa: "This financing is incredible validation that we're on the right track. We all want to be part of a scientific narrative that changes lives, and I believe that our immunotherapy approach is it." Dr. Brian Lichty, associate professor at McMaster University: "We have had tremendous success with our technology so far, but this financial support as a commercial venture is essential in enhancing our ability to bring it to the bedside. We know there is so much potential." Dr. John Bell, senior scientist, The Ottawa Hospital; professor, University of Ottawa: "Community support has been and will continue to be crucial for our research. However developing new therapies is extremely costly, so we also need to engage the private sector to take our research to the next level. I want to express my deep gratitude to all the people who have helped get us to this exciting place." Dr. Derek Jonker, Principal Investigator for the Maraba trial; medical oncologist, The Ottawa Hospital; professor, University of Ottawa: "We are pleased with the progress of the clinical trial so far and now have a better understanding of how patients do after receiving the dual virus vaccine therapy. We anticipate moving to phase II for patients with lung, breast and esophagogastric cancers in the near future." Dr. Martin Osmond, CEO and Scientific Director, CHEO Research Institute: "CHEO is proud that the Stojdl lab was involved in the initial discovery and development of the Maraba virus! Today it's the lead asset in Turnstone's impressive portfolio, which is nothing short of inspiring. My heartfelt congratulations to the entire team at Turnstone for this major funding milestone which boosts the trajectory towards improved patient outcomes through research." Dr. Duncan Stewart, Executive Vice-President of Research, The Ottawa Hospital; professor, University of Ottawa: "It is incredibly challenging for academic researchers to take a discovery all the way from the lab bench to the patient's bedside, so I want to offer my heartfelt congratulations to Dr. Bell and his colleagues. Their success has helped to create a culture of translational research at The Ottawa Hospital that has huge potential for patients as well as the economy." Dr. Mona Nemer, Vice-President of Research, University of Ottawa "This investment represents a major milestone in the development and translation of academic research discoveries into the clinic. The University of Ottawa congratulates Turnstone and our researchers on their success. We look forward to working with Turnstone and the research team to advance this technology further." Dr. Paul O'Byrne, Dean and Vice-President, Faculty of Health Sciences, McMaster University "Commercialization of discoveries in our academic laboratories is an important move forward to a healthy society, both economically and physically. We are extremely thrilled by the work of Dr. Lichty and other McMaster scientists, and the collaboration on this project with CHEO, The Ottawa Hospital, University of Ottawa, other supporters and now, Turnstone. This significant investment being made in Turnstone is much appreciated." Dr. Lincoln Stein, Interim Scientific Director of The Ontario Institute for Cancer Research: "The Ontario Institute for Cancer Research is proud to stimulate the groundbreaking multi-institutional research behind Turnstone, including significant financial and in-kind support enabling the current clinical trial. We congratulate the Turnstone team on attracting further investment to the benefit of both patients with cancer and the innovation economy of Ontario." Dr. Stéphanie Michaud, President and CEO, BioCanRx "On behalf of BioCanRx, I wish to extend my congratulations to Turnstone Biologics on the significant investment announced today. This announcement not only reflects the accomplishments of Turnstone but also of the advancements in the oncolytic virus platform in Canada, and around the world. These novel therapies potentially offer a unique opportunity to change the way we treat cancer patients. We are delighted to continue working with Turnstone in transitioning these important new discoveries out of the lab and into the clinic."

Samia Y.,The University of Ottawa | Kealey A.,Kingston University | Smith R.J.,The University of Ottawa
Mathematical Population Studies | Year: 2016

Human African sleeping sickness is found throughout sub-Saharan Africa. It affects up to 70,000 individuals per year, primarily the poor. Existing treatments are limited, costly, and often toxic. Recent evidence suggests that a vaccine may be viable. Potential vaccines against Rhodesian sleeping sickness may be imperfect, may only be delivered to some proportion of the population, may wane over time, and may not always mount an immunogenic response in the individual receiving it. The potential effects of such a vaccine are addressed and compared to vector control. The basic reproductive ratio for both unvaccinated and vaccinated individuals is derived. The fitness ratio is used to show that vaccines that grant longer life must be accompanied by a corresponding reduction in transmissibility. A sensitivity analysis shows that control of tsetse flies through insecticide is superior to an idealized vaccine. Such a vaccine is unlikely to eradicate the disease, even if delivered to 100% of the population. Consequently, efforts to control sleeping sickness that do not incorporate vector control may be flawed. © 2016 Taylor & Francis.

Miron R.E.,The University of Ottawa | Giordano G.A.,The University of Ottawa | Kealey A.D.,Kingston University | Smith R.J.,The University of Ottawa
Mathematical Population Studies | Year: 2016

Rift Valley fever is a vector-borne disease, primarly found in West Africa, that is transmitted to humans and domestic livestock. Its similarities to the West Nile virus suggest that establishment in the developed world may be possible. Rift Valley fever has the potential to invade North America, where seasons play a role in disease persistence. The values for the basic reproductive number show that, in order to eradicate the disease, the survival time of mosquitoes must decrease below 8.67 days. Mechanisms such as aggressive spraying that decreases the mosquito population can contain an outbreak. Otherwise, Rift Valley fever is likely to establish itself as a recurring seasonal outbreak. Rift Valley fever poses a potential threat to North America that would require aggressive interventions in order to prevent a recurring seasonal outbreak. © 2016 Taylor & Francis.

PubMed | The University of Ottawa
Type: Comparative Study | Journal: Journal of otolaryngology - head & neck surgery = Le Journal d'oto-rhino-laryngologie et de chirurgie cervico-faciale | Year: 2012

The use of the DynaClose topical tissue expansion device for closure of radial forearm free flap (RFFF) donor sites has been demonstrated to significantly reduce healing time and postoperative pain compared to the traditional use of a split-thickness skin graft. However, long-term cosmetic and functional outcomes are not known.The objective of this study was to test the hypothesis that using a new method of donor site management will result in improved cosmesis of RFFF donor sites as assessed by both patients and expert observers without resulting in a reduction in the function of the patients forearm.A cohort of 25 patients previously randomized to either the treatment (tissue expansion) or the control group were assessed at 10 months. The Patient and Observer Scar Assessment Scale (PAOSAS) was used to assess forearm scars, whereas the Michigan Hand Outcomes Questionnaire assessed hand function.Expert observers noted improved scar cosmesis in the treatment group (p = .013), with primary closure having the best cosmetic outcome, followed by local full-thickness skin graft closure (p < .001). There was no statistically significant improvement in cosmesis as assessed by patients (p = .03) or differences in Michigan Hand Outcomes Questionnaire scores between treatment groups (p = .57).Using an inexpensive, noninvasive preoperative tissue expansion device safely results in improved cosmetic outcomes as assessed by expert observers, without any significant functional forearm and hand deficits.

PubMed | The University of Ottawa
Type: | Journal: Journal of otolaryngology - head & neck surgery = Le Journal d'oto-rhino-laryngologie et de chirurgie cervico-faciale | Year: 2011

The objective of this study is to test the hypothesis that using a simple and inexpensive preoperative tissue expansion device for radial forearm free flap donor sites will result in a significant reduction in healing time and reduced postoperative pain compared to unexpanded radial forearm free flap donor site skin.Twenty-nine patients were enrolled and randomized to either the treatment (tissue pre-expansion) or the control group. An intention-to-treat analysis was used. Healing time was recorded for all patients. The Short Form McGill Pain Questionnaire was used to record arm pain and overall surgical pain 1 week postsurgery.The mean (95% CI) healing time was 5.7 (3.9-7.6) days for the treatment group and 32.5 (12.2-53.0) days for the control group (p < .001). Overall surgical pain (p < .001) was significantly lower in the treatment group. There was no significant difference in donor site arm pain (p < .2).Using a simple, noninvasive method of preoperative tissue expansion results in both clinically and statistically significant reductions in healing time and postoperative pain.

PubMed | University of California at San Diego and The University of Ottawa
Type: | Journal: Clinical cancer research : an official journal of the American Association for Cancer Research | Year: 2016

Following the approval of bevacizumab, an antibody targeting vascular endothelial growth factor-A (VEGF-A), for advanced non-squamous non-small cell lung cancer (NSCLC) in 2006, intensive efforts were put into the clinical development of antiangiogenic agents for NSCLC. Currently, the other antiangiogenic agents approved for NSCLC are ramucirumab, a VEGF receptor-2 (VEGFR-2)-targeting antibody indicated for both squamous and non-squamous NSCLC in the United States, and nintedanib, an anti-VEGFR-/3, platelet-derived growth factor receptor (PDGFR)-/, fibroblast growth factor receptor (FGFR)-/3 angiokinase inhibitor indicated for adenocarcinoma of the lung in the European Union. Many other antiangiogenic agents are being evaluated in phase III trials for NSCLC, including aflibercept, sunitinib, sorafenib, cediranib, and vandetanib. Although many of the same signaling pathways are targeted by these novel agents, mixed efficacy results have been observed in these trials. Moreover, safety issues have raised concerns about using antiangiogenic agents in this patient population, and fatal bleeding events have been reported. Importantly, although no biomarker has yet been validated for antiangiogenic agents in NSCLC, biomarkers that show potential include circulating levels of short VEGF-A isoforms, expression of neuropilin-1 and VEGFR-1 in tumors and plasma, genetic variants in VEGF-A and VEGFR, and TP53 mutations (with the latter having been shown to correlate with increased levels of VEGF-A transcripts). This review provides an overview of the clinical benefit and risk associated with the use of antiangiogenic agents for NSCLC, and summarizes the research to date on the identification of predictive biomarkers for antiangiogenic therapies.

PubMed | The University of Ottawa
Type: | Journal: Journal of otolaryngology - head & neck surgery = Le Journal d'oto-rhino-laryngologie et de chirurgie cervico-faciale | Year: 2012

To test the hypothesis that using Listerine mouthwash prior to administration of topical nasal lidocaine will result in improved pain and comfort outcomes during flexible nasolaryngoscopy (FNL).Randomized, controlled trial.A total of 120 patients were randomized to receive a combination of either treatment or placebo mouthwash followed by treatment or placebo nasal spray prior to an FNL examination.Pain and discomfort using a 100 mm visual analogue scale.The use of lidocaine significantly reduced pain (p = .011) and discomfort (p = .008) compared to placebo nasal spray. Using Listerine prior to administration of lidocaine resulted in the largest reductions. Patients having an extended nasal examination reported more pain (p = .001) and discomfort (p = .03) levels while demonstrating a greater benefit of topical lidocaine compared to those undergoing a primary laryngeal examination (p < .001).Using Listerine prior to application of lidocaine nasal spray reduces the pain and discomfort of FNL. This effect was most clinically significant in patients undergoing an extended or full bilateral nasal examination.

PubMed | The University of Ottawa and University of Montréal
Type: Editorial | Journal: Canadian journal of anaesthesia = Journal canadien d'anesthesie | Year: 2016

Lvaluation ditoriale par des pairs est un processus trs important qui dtermine quels manuscrits sont publis dans les revues dotes de comit dvaluation par des pairs, tout en ayant une influence majeure sur la qualit des articles publis. Alors que la science de lvaluation par les pairs continue dvoluer, le processus devrait tre transparent et devrait intresser tous ceux qui contribuent la littrature mdicale et qui la lisent. Les publications scientifiques font progresser la pratique de la mdecine. En ce sens, nous sommes heureux de tenir les auteurs et notre lectorat au courant de la politique duJournal sur lvaluation par les pairs.

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