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News Article | November 10, 2015
Site: www.scientificcomputing.com

Adaptive Computing worked with High Performance Computing for Health Sciences (HPC4Health) — which consists of The Hospital for Sick Children (SickKids), University Health Network’s (UHN) Princess Margaret Cancer Center, Compute Canada and Compute Ontario — to create a converged HPC, cloud and big data environment that was capable of bringing multiple organizations together to share resources dynamically, securely and equitably. Together, we are building the engine that will help make personalized medicine and diagnostics a reality. To help bring these organizations together, Moab HPC Suite - Enterprise Edition 8.1 (Moab) was chosen for its elastic computing, advanced policies and accounting capabilities. HPC4Health has been an amazing project. We loved working with the HPC4 Health teams. They were so creative and dedicated to creating an environment that would really make a difference. Everyone knew they needed the power of HPC to analyze the massive data they were collecting and to extract the necessary data fast to make life-changing decisions. By coupling HPC with cloud, and its inherent sharing capabilities, you have this really cool, dynamic, scalable, powerful environment that can serve multiple organizations and deliver the necessary resources when each organization needs it. By creating this converged infrastructure of cloud, HPC and big data with Moab, SickKids and UHN’s Princess Margaret Cancer Center have the resources necessary to save lives! Adaptive was there from the beginning to help create technology that did not exist to make HPC4Heath’s vision a reality. We helped them build a converged data center that dynamically shared resources securely and allowed them to account for the workloads used by each organization involved in HPC4Health. The HPC4Health IT Infrastructure is configured as a single pool of resources, with each organization having dedicated resources, plus a common communal pool of resources. Each organization and their Admins manage their dedicated resources just as if it were a private data center. As workloads increase, Moab automates each organization’s growth requirements and dynamically obtains additional resources from the communal pool to handle the peak loads, and then relinquishes those resources back to the communal pool for the next peak workload requirement from any organization. All workloads are tracked per user/organization and accounted for with extensive reporting capabilities. Here are a few more details about elastic computing, advanced policies and accounting capabilities to better understand how HPC4Health is able to orchestrate their workloads and resources. Administrators from both SickKids and UHN’s Princess Margaret Cancer Centre must ensure that regularly scheduled workloads are completed, particularly during peak times. Each organization manages many users with countless needs, and the requirement to be responsive to those needs is imperative; therefore, the ability to burst workloads to other resources is extremely important. Moab tackles these challenges with elastic computing, which allows Admins to efficiently manage resource expansion by bursting to private clouds or other data center resources utilizing OpenStack. Elastic computing is triggered when a threshold set in Moab is exceeded. To determine this threshold, Moab surveys the system workload and calculates the combined completion time of these burstable workloads if no other workloads are running. Elastic computing bursts workloads, on an as-needed basis, into a communal pool of data center resources and then relinquishes these resources back to the shared pool. Using Openstack, Moab completely wipes each resource after use to help comply with Canadian privacy regulations. This added flexibility enables Admins to expand their own cluster while taking advantage of the elasticity of resources and scalability of the cloud. Some advanced policies, such as auto enforcement of Service Level Agreements (SLAs), dynamic provision of virtual resources, and job arrays, are key to the success of HPC4Health’s converged infrastructure. Usage accounting and budget enforcement enables tracking of resource usage, as well as the setting and enforcement of usage budgets by user, group, project or any custom organizational hierarchy. Resources are scheduled against that budget for a given period of time, including dynamic usage reports and a flexible conditional usage cost/charge structure. This allows HPC4Health to track usage for each organization and then each organization can further track internal usage by user, department or group. To hear more about HPC4Health, join us at SC15 in Austin, TX. Jorge Gonzalez-Outeirino, Ph.D., Facility Manager at the Centre for Computational Medicine at SickKids will be speaking in booth #833 on November 17 at 10:30 am. Also you can visit the Adaptive Computing Web site for additional information on the HPC4Health deployment.


News Article | December 23, 2016
Site: www.eurekalert.org

In findings they call counterintuitive, a team of UCLA-led researchers suggests that blocking a protein, which is crucial to initiating the immune response against viral infections, may actually help combat HIV. Findings from a study in animals appear to demonstrate that temporarily blocking a type of protein, called type I interferon, can restore immune function and speed up viral suppression during treatment with anti-viral drugs for people with chronic infection of the virus that causes AIDS. This is the first study to show the role that type I interferon plays in driving the body's immune destruction during HIV infection, said Scott Kitchen, associate professor of medicine in the division of hematology/oncology at the David Geffen School of Medicine at UCLA and senior author of the study published in the peer-reviewed Journal of Clinical Investigation. "This finding is completely counterintuitive, because many believe that the more interferon at work, the better," said Kitchen, a member of the UCLA AIDS Institute. "We show that the type of interferon being produced during chronic stages of HIV infection has detrimental effects on the body's ability to fight off HIV and other types of infection or cancer and could actually be contributing to accelerated HIV disease." HIV cripples the immune system by destroying immune cells called CD4 T cells, which are activated during early HIV infection by type I interferon. CD4 T cells are also known as "helper" cells because they signal another type of T cell, the CD8, to destroy HIV-infected cells. Also, HIV evades the body's CD8 cells by constantly mutating, escaping recognition by CD8 cells and making them ineffective. The chronically heightened state of inflammation and activation eventually leads to what is known as immune exhaustion when the immune cells can no longer function properly to clear infected cells. This, along with the loss of CD4 T cells ultimately leads to the destruction of the immune system. The researchers' idea is to block type I interferon to reduce chronic activation of the immune cells, which could give the exhausted CD8 T cells the opportunity to restore their abilities to fighting strength. Combine that with antiretroviral therapy and it may be possible to both restore immune function and eradicate HIV throughout the body. The researchers used "humanized mice," which have had their immune systems replaced with human immune system cells, thymus tissue and bone marrow. They treated HIV-infected mice with antibodies that blocked type I interferons, which allowed the mice's immune systems to revert from the state of exhaustion. This made it possible for their immune systems to produce sufficient amounts of CD8 T cells that were primed to attack and kill HIV-infected cells. When combined with antiretroviral therapy, the treatment accelerated the effect of antiretroviral therapy in suppressing HIV. "We found -- counterintuitively -- that blocking this immune response against the virus had beneficial effects in lowering the amounts of virus and increasing the ability of the immune response to clear out the virus," said Kitchen, who is also director of the UCLA Humanized Mouse Core Laboratory. Kitchen noted that these findings offer a proof of principle in a humanized mouse system and are not definitive. More experiments are needed in non-human primates before moving on to human clinical trials to determine whether the researchers' theory holds up and this treatment is safe in humans. But the findings offer a new perspective into the function of type I interferon during untreated and treated HIV chronic infection, said Anjie Zhen, a postdoctoral scholar and member of the UCLA AIDS Institute who led the study. "This could have profound implications for the development of therapies that include such approaches as interferon alpha therapy," Zhen said. "This shows that a proper balance is required when administering this type of therapy, where too much can have detrimental effects in suppressing important immune responses." Study co-authors are Valerie Rezek, Cindy Youn, Brianna Lam, Nelson Chang, Jonathan Rick, Mayra Carrillo, Heather Martin, Saro Kasparian, Philip Syed, and Nicholas Rice of UCLA, and David Brooks of the Princess Margaret Cancer Center in Toronto, Canada and of the University of Toronto. Grants from the National Institutes of Health (AI078806, AI110306-01, AI085043, T32AI060567), the UCLA AIDS Institute (P30AI28697), the California Center for Regenerative Medicine (TR4-06845), the UC Multicampus Research Program and Initiatives, the California Center for Antiviral Drug Discovery, the California HIV/AIDS Research Program (F12-LA-215) and the UCLA Center for AIDS Research (AI28697) funded this study.


Pechoux C.L.,Gustave Roussy University Hospital | Sun A.,Princess Margaret Cancer Center | Slotman B.J.,VU University Amsterdam | De Ruysscher D.,Maastricht University | And 3 more authors.
The Lancet Oncology | Year: 2016

The incidence of brain metastases in patients with lung cancer has increased as a result of improved local and systemic control and better diagnosis from advances in brain imaging. Because brain metastases are responsible for life-threatening symptoms and serious impairment of quality of life, resulting in shortened survival, prophylactic cranial irradiation has been proposed in both small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) to try to improve incidence of brain metastasis, survival, and eventually quality of life. Findings from randomised controlled trials and a meta-analysis have shown that prophylactic cranial irradiation not only reduces the incidence of brain metastases in patients with SCLC and with non-metastatic NSCLC, but also improves overall survival in patients with SCLC who respond to first-line treatment. Although prophylactic cranial irradiation is potentially associated with neurocognitive decline, this risk needs to be balanced against the potential benefit in terms of brain metastases incidence and survival. Several strategies to reduce neurotoxicity are being investigated. © 2016 Elsevier Ltd


News Article | December 14, 2016
Site: marketersmedia.com

The presentations were delivered by Dr. Lothar Lilge, Senior Scientist, Princess Margaret Cancer Center, University Health Network ("UHN") and Dr. Girish Kulkarni, Uro-Oncologist, also from UHN. The video of the presentations may be viewed at: Roger Dumoulin-White, President and CEO of Theralase stated that, "Theralase has made significant advances in 2016 in both of its divisions. In the TLT division, Theralase has successfully commercialized its next generation TLC-2000 therapeutic laser system in both Canada and the US. In the PDT division, Theralase has achieved its primary objective of commencing a Phase Ib clinical trial for Non-Muscle Invasive Bladder Cancer, using its lead, light-activated PDC, TLD-1433." Theralase Technologies Inc. ("Theralase®" or the "Company") (TSXV: TLT) (OTC: TLTFF) in its Therapeutic Laser Technology ("TLT") division designs, manufactures, markets and distributes patented super-pulsed laser technology indicated for the treatment of chronic knee pain and in off-label use the elimination of pain, reduction of inflammation and dramatic acceleration of tissue healing for numerous nerve, muscle and joint conditions. Theralase's Photo Dynamic Therapy ("PDT") division researches and develops specially designed molecules called Photo Dynamic Compounds ("PDCs"), which are able to localize to cancer cells and then when laser light activated, effectively destroy them. Additional information is available at www.theralase.com and www.sedar.com. This news release contains "forward-looking statements" which reflect the current expectations of management of the Corporation's future growth, results of operations, performance and business prospects and opportunities. Such statements include, but are not limited to, statements regarding the proposed use of proceeds.. Wherever possible, words such as "may", "would", "could", "should", "will", "anticipate", "believe", "plan", "expect", "intend", "estimate", "potential for" and similar expressions have been used to identify these forward-looking statements. These statements reflect management's current beliefs with respect to future events and are based on information currently available to management. Forward-looking statements involve significant risks, uncertainties and assumptions. Many factors could cause the Corporation's actual results, performance or achievements to be materially different from any future results, performance or achievements that may be expressed or implied by such forward-looking statements; including, without limitation, those listed in the filings made by the Corporation with the Canadian securities regulatory authorities (which may be viewed at www.sedar.com). Should one or more of these risks or uncertainties materialize, or should assumptions underlying the forward looking statements prove incorrect, actual results, performance or achievements may vary materially from those expressed or implied by the forward-looking statements contained in this news release. These factors should be considered carefully and prospective investors should not place undue reliance on the forward-looking statements. Although the forward-looking statements contained in the news release are based upon what management currently believes to be reasonable assumptions, the Corporation cannot assure prospective investors that actual results, performance or achievements will be consistent with these forward-looking statements. The Corporation disclaims any intention or obligation to revise forward-looking statements whether as a result of new information, future developments or otherwise except as required by law. All forward-looking statements are expressly qualified in their entirety by this cautionary statement. Neither TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in the policies of the TSX Venture Exchanges) accepts responsibility for the adequacy or accuracy of this release.


News Article | December 14, 2016
Site: www.accesswire.com

TORONTO, ON / ACCESSWIRE / December 14, 2016 / Theralase Technologies Inc. ("Theralase" or the "Company") (TSXV: TLT) (OTC: TLTFF), a leading biotech company focused on the commercialization of medical devices to eliminate pain and the development of Photo Dynamic Compounds ("PDCs") to destroy cancer, announced today that it has released the video presentations conducted at the end of its Annual General and Special Meeting held on December 9, 2016 in Toronto, Canada. The presentations were delivered by Dr. Lothar Lilge, Senior Scientist, Princess Margaret Cancer Center, University Health Network ("UHN") and Dr. Girish Kulkarni, Uro-Oncologist, also from UHN. The video of the presentations may be viewed at: Roger Dumoulin-White, President and CEO of Theralase stated that, "Theralase has made significant advances in 2016 in both of its divisions. In the TLT division, Theralase has successfully commercialized its next generation TLC-2000 therapeutic laser system in both Canada and the US. In the PDT division, Theralase has achieved its primary objective of commencing a Phase Ib clinical trial for Non-Muscle Invasive Bladder Cancer, using its lead, light-activated PDC, TLD-1433." Theralase Technologies Inc. ("Theralase®" or the "Company") (TSXV: TLT) (OTC: TLTFF) in its Therapeutic Laser Technology ("TLT") division designs, manufactures, markets and distributes patented super-pulsed laser technology indicated for the treatment of chronic knee pain and in off-label use the elimination of pain, reduction of inflammation and dramatic acceleration of tissue healing for numerous nerve, muscle and joint conditions. Theralase's Photo Dynamic Therapy ("PDT") division researches and develops specially designed molecules called Photo Dynamic Compounds ("PDCs"), which are able to localize to cancer cells and then when laser light activated, effectively destroy them. Additional information is available at www.theralase.com and www.sedar.com. This news release contains "forward-looking statements" which reflect the current expectations of management of the Corporation's future growth, results of operations, performance and business prospects and opportunities. Such statements include, but are not limited to, statements regarding the proposed use of proceeds.. Wherever possible, words such as "may", "would", "could", "should", "will", "anticipate", "believe", "plan", "expect", "intend", "estimate", "potential for" and similar expressions have been used to identify these forward-looking statements. These statements reflect management's current beliefs with respect to future events and are based on information currently available to management. Forward-looking statements involve significant risks, uncertainties and assumptions. Many factors could cause the Corporation's actual results, performance or achievements to be materially different from any future results, performance or achievements that may be expressed or implied by such forward-looking statements; including, without limitation, those listed in the filings made by the Corporation with the Canadian securities regulatory authorities (which may be viewed at www.sedar.com). Should one or more of these risks or uncertainties materialize, or should assumptions underlying the forward looking statements prove incorrect, actual results, performance or achievements may vary materially from those expressed or implied by the forward-looking statements contained in this news release. These factors should be considered carefully and prospective investors should not place undue reliance on the forward-looking statements. Although the forward-looking statements contained in the news release are based upon what management currently believes to be reasonable assumptions, the Corporation cannot assure prospective investors that actual results, performance or achievements will be consistent with these forward-looking statements. The Corporation disclaims any intention or obligation to revise forward-looking statements whether as a result of new information, future developments or otherwise except as required by law. All forward-looking statements are expressly qualified in their entirety by this cautionary statement. Neither TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in the policies of the TSX Venture Exchanges) accepts responsibility for the adequacy or accuracy of this release.


Matulonis U.A.,Dana-Farber Cancer Institute | Oza A.M.,Princess Margaret Cancer Center | Ho T.W.,Astrazeneca | Ledermann J.A.,University College London
Cancer | Year: 2015

Ovarian cancer patients are usually diagnosed at an advanced stage, experience recurrence after platinum-based chemotherapy, and eventually develop resistance to chemotherapy. Overall survival (OS), which has improved in recent years as more active treatments have been incorporated into patient care, is regarded as the most clinically relevant endpoint in ovarian cancer trials. However, although there remains a significant need for new treatments that prolong OS further without compromising quality of life, it has become increasingly difficult to detect an OS benefit for investigational treatments because of the use of multiple lines of chemotherapy to treat ovarian cancer. Progression-free survival (PFS), which measures the time to disease progression or death, is unaffected by postprogression therapies but does not evaluate the long-term impact of investigational treatments on tumor biology and responses to future therapies. Recent clinical trials of targeted agents in relapsed ovarian cancer have shown improvements in PFS but not OS, and this is possibly reflective of the long postprogression survival (PPS) period associated with this disease. Intermediate endpoints such as the time to second disease progression or death and the time to second subsequent therapy or death may provide supportive evidence for clinically meaningful PFS improvements and may be used to determine whether these improvements persist beyond the first disease progression and throughout subsequent lines of therapy. For clinical trials that have settings with a long PPS duration and/or involve multiple rounds of postprogression therapy, a primary endpoint of PFS supported by intermediate clinical endpoints and OS may provide a more comprehensive approach for evaluating efficacy. © 2014 American Cancer Society.


Saggar J.K.,University of Toronto | Fung A.S.,University of Toronto | Patel K.J.,University of Toronto | Tannock I.F.,University of Toronto | Tannock I.F.,Princess Margaret Cancer Center
Molecular Cancer Therapeutics | Year: 2013

Poor distribution of anticancer drugs within solid tumorsmaylimit their effectiveness. Here,wecharacterize the distribution within solid tumors of biomarkers of drug effect. γ-H2AX, cleaved-caspase-3 or -6, and Ki67 were quantified in tumor sections in relation to blood vessels (recognized by CD31) using monoclonal antibodies and immunohistochemistry. To validate their use, we compared their time-dependent distribution with that of (i) fluorescent doxorubicin and (ii) a monoclonal antibody that detects melphalan-induced DNA adducts. The biomarkers were then used to quantify the distribution of docetaxel in relation to tumor blood vessels. Activation of γ-H2AX was evaluated following in vitro exposure of tumor cells to multiple drugs. Distributions of doxorubicin in MDA-MB-231 and MCF-7 xenografts and of melphalan- inducedDNAadducts in MCF-7 and EMT-6 tumors decreased with distance from blood vessels, similar to the distributions of (i) γ-H2AX at 10 minutes, (ii) cleaved caspase-3 or -6, and (iii) change in Ki67 at 24 hours following treatment. The distribution of these biomarkers following treatment with docetaxel also decreased with increasing distance from tumor blood vessels. Activation of γ-H2AX occurred within 1 hour after exposure to several drugs in culture. Multiple anticancer drugs show a decrease in activity with increasing distance from tumor blood vessels; poor drug distribution is an important cause of drug resistance. The above biomarkers may be used in designing strategies to overcome therapeutic resistance by modifying or complementing the limited spatial distribution of drug activity in solid tumors. © 2013 American Association for Cancer Research.


Leung-Hagesteijn C.,Princess Margaret Cancer Center | Erdmann N.,Princess Margaret Cancer Center | Cheung G.,Princess Margaret Cancer Center | Keats J.J.,Translational Genomics Research Institute | And 6 more authors.
Cancer Cell | Year: 2013

Proteasome inhibitor (PI) resistance mechanisms in multiple myeloma (MM) remain controversial. We report the existence of a progenitor organization in primary MM that recapitulates maturation stages between Bcells and plasma cells and that contributes to clinical PI resistance. Xbp1s- tumor B cells and pre-plasmablasts survive therapeutic PI, preventing cure, while maturation arrest of MM before the plasmablast stage enables progressive disease on PI treatment. Mechanistically, suppression of Xbp1s in MM is shown to induce bortezomib resistance via de-commitment to plasma cell maturation and immunoglobulin production, diminishing endoplasmic reticulum (ER) front-loading and cytotoxic susceptibility to PI-induced inhibition of ER-associated degradation. These results reveal the tumor progenitor structure in MM and highlight its role in therapeutic failure. © 2013 Elsevier Inc.


Wilson M.K.,Princess Margaret Cancer Center | Karakasis K.,Princess Margaret Cancer Center | Oza A.M.,Princess Margaret Cancer Center
The Lancet Oncology | Year: 2015

Cancer treatment should allow patients to live better or longer lives, and ideally, both. Trial endpoints should show clinically meaningful improvements in patient survival or quality of life. Alternative endpoints such as progression-free survival, disease-free survival, and objective response rate have been used to identify benefit earlier, but their true validity as surrogate endpoints is controversial. In this Review we discuss the measurement, assessment, and benefits and limitations of trial endpoints in use for cancer treatment. Many stakeholders are affected, including regulatory agencies, industry partners, clinicians, and most importantly, patients. In an accompanying Review, reflections from individual stakeholders are incorporated into a discussion of what the future holds for clinical trial endpoints and design. © 2015 Elsevier Ltd.


Sahgal A.,Princess Margaret Cancer Center
Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2013

Vertebral compression fracture (VCF) is increasingly recognized as an adverse event after spine stereotactic body radiotherapy (SBRT). We report a multi-institutional study aimed at clarifying the risk and predictive factors associated with VCF. A total of 252 patients with 410 spinal segments treated with SBRT were included. The primary outcome was the development of VCF (a new VCF or progression of a baseline VCF). In addition to various patient-, treatment-, and tumor-specific factors, the Spinal Instability Neoplastic Scoring (SINS) system was applied to determine predictive value. The median follow-up was 11.5 months (range, 0.03 to 113 months). The median and mean overall survival rates were 16 and 26 months, respectively. We observed 57 fractures (57 of 410, 14%), with 47% (27 of 57) new fractures and 53% (30 of 57) fracture progression. The median time to VCF was 2.46 months (range, 0.03 to 43.01 months), and 65% occurred within the first 4 months. The 1- and 2-year cumulative incidences of fracture were 12.35% and 13.49%, respectively. Multivariable analysis identified dose per fraction (greatest risk for ≥ 24 Gy v 20 to 23 Gy v ≤ 19 Gy), in addition to three of the six original SINS criteria: baseline VCF, lytic tumor, and spinal deformity, as significant predictors of VCF. Caution must be observed when treating with ≥ 20 Gy/fraction, in particular, for patients with lytic tumor, spinal misalignment, and a baseline VCF. Frequent short-term follow-up is required, as nearly two thirds of all VCF occurred within the first 4 months. We also conclude that SINS may have utility in predicting patients at high risk of SBRT-induced VCF.

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