Asthma patients are at risk of potentially severe and sometimes lethal exacerbations. These exacerbations can be caused by a variety of triggers, such as infections or exposure to allergens. Diesel exhaust and other traffic-related constituents can also be inhaled along with the allergen. This multi-inhalant mixture results in immune reactions that are more complex than exposure to the allergen alone. Although it is well established that multi-inhalant mixtures of allergens and pollution contribute to asthma exacerbations, research in this area typically focuses on exposures to single agents, either diesel exhaust or allergens alone.
Dr. Francesco Sava is investigating the relationship and the synergies that exist between diesel exhaust and allergen-triggered asthma exacerbations using a live-patient model. His aim is to demonstrate that inhalation of diesel exhaust increases allergen-induced inflammation in the lungs of asthmatic patients. Using state-of-the-art equipment, he will expose patients to controlled diesel exhaust concentrations. A very small amount of allergen will be introduced into a segment of the patients’ lungs, and the resulting inflammation will be measured. This multi-inhalant exposure model reflects the real-life conditions that patients are likely to encounter. The experimental model he uses has been widely studied, is very safe, and allows researchers to test allergens on humans without triggering an overt asthma attack.
The research will help define the synergies between the real-world concentrations of inhaled diesel exhaust and allergen exposure in the asthmatic population. This information will likely lead to recommendations for air quality and strategies to protect vulnerable populations.
One in every eight Canadian men will be diagnosed with prostate cancer in their lifetime. Androgens, which are male sex hormones, are the primary driving force behind the development of prostate cancer and are synthesized in the testes, prostate, and in the prostate cancer tumour itself. Although once the standard of care, orchiectomy is rarely performed; continuous androgen deprivation is necessary when the cancer is very advanced. In these cases, the cancer becomes more aggressive and progresses to a stage called castration-resistant prostate cancer, which does not respond to hormonal agents. Dutasteride and abiraterone acetate are two current treatments for prostate cancer. The actions of these therapies are complementary, targeting different androgen metabolizing enzymes. Currently, dutasteride is successfully used for benign prostate hyperplasia, which is non-cancerous enlargement of the prostate. Abiraterone acetate, which was been approved in April 2011, is a promising treatment option for advanced prostate cancer patients. Clinical studies have shown that a subset of prostate cancer patients manifested resistance to abiraterone, and this suggests that there are compensatory mechanisms at work, either by supplying androgens via alternative biosynthetic pathways and/or by altering the signaling pathways involved in prostate cancer progression. The purpose of Dr. Subrata Deb’s research is to investigate the effects of abiraterone and dutasteride on pathways of androgen biosynthesis in castration-resistant prostate cancer. Mouse models of human prostate cancer, human prostate cancer cells, and human prostate tissues will be used to determine the effect of dutasteride and abiraterone acetate, either alone or in combination, on androgen formation during castration-resistant prostate cancer or in resistance to abiraterone. The aim of this research is to find the potential reasons for treatment failure in prostate cancer and aid in the development of potential treatment strategies.