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Abstracts: Web Extra

The Sooner the Better: Study Says

Dr. Gregory Czarnota is using ultrasound imaging to measure cellular responses to chemotherapy and radiation therapy.

Photo credit: Doug Nicholson

Cancer treatments are not one size fits all. Many factors, including tumour type, genetics and stage of disease, contribute to how well a patient will respond to treatment.

A new study by researchers at Sunnybrook Research Institute (SRI) could pave the way for ultrasound to be adopted as a way to predict therapy response in women with breast cancer. Dr. Gregory Czarnota, director of the Odette Cancer Research Program, and colleagues demonstrated for the first time that quantitative ultrasound (QUS) imaging of breast tissue can predict a patient’s clinical and pathological response to treatment within days of starting chemotherapy.

The team used two different QUS parameters to measure changes in breast tissue at one and four weeks after the start of treatment. They found that patients who did not respond to treatment showed very little change in both parameters, while responding patients showed dramatic changes. The difference between responders and non-responders was statistically significant as early as one week after beginning treatment. To validate their results, the researchers analyzed tissue biopsies from responders and non-responders. Looking at the biopsies under a microscope, they found that non-responders still had large areas of disease in their breast tissue, whereas in responders, minimal amounts of tumour remained.

The results, published in Oncotarget, highlight the potential of QUS as a tool to help predict treatment response early during chemotherapy treatment. Compared with tissue biopsies and other methods that rely on DNA screening or imaging, QUS is noninvasive, cheap and capable of detecting changes much sooner. Early prediction of treatment response offers physicians more opportunities to switch from an ineffective treatment to a more effective one, thereby improving the chances of success for patients resistant to therapy.

Worth the Wait

A new stroke prevention strategy is on the horizon. Atrial fibrillation, a type of abnormal heartbeat, is a leading risk factor for stroke. It allows blood to pool in the heart, which can lead to clots that can travel to the brain. Stroke patients usually receive 24-hour monitoring to screen for atrial fibrillation, but the diagnosis can be missed because the condition is sometimes intermittent and asymptomatic. Detecting atrial fibrillation is important because it can be treated with anti-clotting drugs, which slash the risk of strokes by two-thirds.

Dr. David Gladstone, a scientist in the Hurvitz Brain Sciences Research Program at Sunnybrook Research Institute, led a national, multicentre study showing the benefit of prolonged heart monitoring to diagnose atrial fibrillation in people who have unexplained strokes.

The researchers studied 572 people, aged 55 years and older, who experienced a recent stroke or mini-stroke that was of unknown origin. Of the 280 patients who had noninvasive heart monitoring at home for 30 days, 16% were diagnosed with atrial fibrillation, compared with just 3% of the 277 patients who received standard monitoring. Improved detection of atrial fibrillation led to significantly more patients being prescribed anti-clotting medication to prevent recurrent strokes. The findings, published last year in the New England Journal of Medicine, provide evidence that extended monitoring can lead to detection and treatment of a common and modifiable risk factor for recurrent stroke.

Toning Fatty Liver

Dr. Burton Yang studies the role of microRNAs in angiogenesis and vascular diseases.

Photo credit: Doug Nicholson

Dexamethasone is a steroid medication with potent anti-inflammatory and immunosuppressive effects. It is widely prescribed to treat many autoimmune and inflammatory conditions like rheumatoid arthritis, psoriasis and lupus, and helps to manage the adverse effects of some cancer treatments. One of the side effects of dexamethasone is steatosis of the liver, when liver cells retain too much fat, which can lead to non-alcoholic fatty liver disease.

New research led by Dr. Burton Yang, asenior scientist in the Odette Cancer Research Program at Sunnybrook Research Institute, has helped identify factors that can mitigate the harmful effects of dexamethasone on liver health. Yang specializes in microRNAs, a class of ribonucleic acid that can alter gene expression by having a direct impact on protein synthesis. In a paper published in May 2015 in Molecular Therapy, Yang and his colleagues demonstrated that exposure to dexamethasone increased the levels of a microRNA called miR-17-5p, which, in turn, reduced the amount of a protein called PPAR-alpha. This protein is important in the prevention of fatty liver disease because it turns on numerous pathways to take up and metabolize fat. When the dexamethasone was given along with an inhibitor of miR-17-5p or an activator of PPAR-alpha, the livers were less fatty than when dexamethasone was given alone.

The scientists also identified several drugs that simultaneously decreased miR-17-5p levels while increasing the amount of PPAR-alpha in the presence of dexamethasone. They noted that for patients taking dexamethasone, these drugs, many of which are already widely used in clinic, could be taken in combination with dexamethasone to help prevent drug-induced development of fatty liver.