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Tag Archives: University of Ottawa

Friday Science Review: November 19, 2010

Mobile Phones Increase Patient Adherence in HIV Clinical Study

University of Nairobi ♦ University of Manitoba ♦ University of British Columbia

Published in Lancet, November 9, 2010

Researchers recently demonstrated the effectiveness of mobile phones as a tool to bolster patient adherence to an HIV treatment regime. Better adherence to treatment reduced HIV-1 RNA load and may improve patient outcome. Patients receiving anti-retroviral therapy (ART) in Kenya were placed into one of two treatment groups. Both treatment groups received ART but only one received SMS support from healthcare workers. Clinicians sent weekly reminders to patients in the SMS intervention group, upon which they had to reply to confirm adherence within 48h. Adherence to therapy was observed in 168 of 273 patients in the SMS intervention group, and 132 of 265 in the control group, confirming that communication between healthcare workers and patients increased adherence. Suppressed viral loads were documented in 156 of 273 and 128 of 265 patients in the SMS intervention and control groups respectively, providing clear evidence that mobile phone reminders can improve outcome in patients receiving ART. Mobile phone usage is expected to be a useful mechanism to promote ART adherence in resource limiting environments, such as Africa, and is also an important measure for program cost containment. UNAIDS, the Joint United Nations Program on HIV/AIDS, is supporting the use of mobile technologies for future AIDS response.

A Molecular Circuit of Congenital Heart Disease Revealed

University of Ottawa ♦ University of Montreal

Published in PNAS, November 9, 2010

Congenital heart disease (CHD) is the primary (non-infectious) cause of death in infants within the first year of life. The incidence of CHD is now estimated to be a shocking 5% of live births, with less severe undiagnosed cases leading to increased risk of mortality, stroke, and ischemic heart disease. By elucidating a pathway contributing to congenital heart defects, researchers are now closer to grasping the causes of these developmental mishaps. Normal heart development requires differentiation, proliferation, and communication between two adjacent layers of tissue composed of endocardial and myocardial cells. The transcription factors Tbx5 and GATA4 are key players in this process, ensuring that correct myocardial patterning and chamber specification occur. In this study led by Dr. Mona Nemer of the University of Ottawa, researchers implicate Tbx5 in normal heart development by showing that its deletion in mice causes severe atrial defects. After going on the hunt for modifiers of Tbx5 they later identified the gene Nos3. Interestingly, Nos3 is known to be regulated by several factors that increase risk of congenital heart disease including stress and diabetes. These findings illustrate a direct link between environmental cues and the development of atrial defects.

Cisplatin and ING4-carrying Adenovirus Elicit Synergistic Anticancer Activity

Soochow University ♦ University of Saskatchewan

Published in Cell Gene Therapy (npg), November 5, 2010

Combinatorial approaches to the treatment of cancer have been of great interest to the scientific and medical communities as they provide a means to sensitize cancer cells to small molecule drugs. The combination of sensitizing agents and conventional chemotherapeutics has been shown to reduce tumour size more rapidly, prevent cancer cell resistance, and reduce side effects by lowering the dose of cytotoxic small molecule drugs required for therapy. In a joint study between Soochow University, China; and the University of Saskatchewan, researchers have shown that the adenoviral delivery of the tumour supressor ING4 (Ad-ING4) along with cisplatin induces synergistic growth inhibition and apoptosis in a hepatocarcinoma cell line both in vitro and in vivo. In this study researchers reported the upregulation of several protein markers associated with apoptosis and down regulation of the oncogene Bcl-2 in the presence of the Ad-ING4 vector and cisplatin. Importantly, the combination of these agents did not elicit overlapping toxicities in in vivo normal liver tissues of mice suggesting that it could have potential as a future treatment for hepatocarcinoma.

Friday Science Review: October 29, 2010

One announcement to make this week before delving into the FSR – Gordon Ramsay and a handful of well known Canadian chefs, including Toronto’s Mark McEwan, Jamie Kennedy, and Lynn Crawford, will be attending Mount Sinai Hospital on November 20th for the Chef’s Challenge. Participants must raise $2500 to attend the event and the top 50 fundraisers get to go head to head with Ramsay in a kitchen battle. Proceeds raised will go towards funding breast and ovarian cancer research at the Samuel Lunenfeld Research Institute and the Marvelle Koffler Breast Centre both of Mount Sinai Hospital. Check it out.

Oxygen Sensors Down: Preeclampsia is a serious pregnancy disorder, affecting 5-10% of all pregnancies, and results from the dysregulation of oxygen sensing mechanisms during early formation of the placenta. Ultimately, this defective development leads to hypertension and drastic increases in urinary protein that can damage the kidney and liver of women who suffer from the disorder. The Hypoxia Inducible Factor (HIF) family transcription factors have a key role in physiological response to acute and chronic hypoxia. One member of this family, HIF-1, is important for healthy placental development and is found in abnormally high concentrations in preeclamptic placental tissue. By establishing cultures of villous explants derived from human placental tissue and growing them under varying oxygen tensions, researchers at the Samuel Lunenfeld Research Institute were able to demonstrate that HIF-1 accumulation results from the diminished function of the oxygen sensing molecules PHD2, FIH, and the SIAHs. Under normal circumstances, PHD2 controls the abundance of HIF-1 by marking it for degradation. In the absence of a functional oxygen sensing mechanism, HIF-1 accumulates beyond normal levels and alters the expression of molecules necessary for proper modeling of maternal arteries at the maternal-placental interface, leading to preeclamptic symptoms. The study was led by Dr. Isabella Caniggia, and is published in PloS ONE.

Microsatellites Need Repair: In a large-scale multi-center study, published in PLoS ONE, researchers describe how single nucleotide polymorphisms contribute to colorectal cancer (CRC).  Typically CRC arises either through abnormalities in the APC/wingless signaling pathway causing somatic mutations in oncogenes (~80% of the time), or results from deficiencies in a mismatch-repair (MMR) system causing genome-wide microsatellite instability (~20% of the time). Building on their previous work which identified several single nucleotide polymorphisms (SNPs) associated with microsatellite instability-colorectal cancer (MSI-CRC), researchers have elucidated a mechanism that explains how these SNPs contribute to the onset and formation of the disease. After removing lymphocytes from the blood of patients, researchers genotyped SNPs located in a specific region of chromosome 3 surrounding the mismatch repair gene MLH1. They were then able to use logistical regression to test for the association between these SNPs and MLH1 gene expression in CRC, and DNA methylation in CRC. Results of this analysis suggest that SNPs near or in the promoter of the MLH1 gene make this segment of DNA more susceptible to methylation, which reduces its expression causing mismatch-repair deficiency and eventually genome-wide instability. This study, led by Dr. Bharati Bapat of the Samuel Lunenfeld Research Institute, included large patient samples from Ontario, Newfoundland, and the Seattle metropolitan area.

Death by Synergy: Researchers have discovered yet another way to sensitize drug resistant cancer cells to chemotherapeutics. A group at the University of Ottawa, led by Dr. Mary-Ellen Harper, has found that a molecule known as genipin can sensitize drug-resistant cancer cells (MX2) to a number of cancer fighting small molecule drugs including menadione, doxorubicin, and epirubicin. How does it do this? Drug resistant cancer cells respond to oxidative stresses by activating uncoupling protein-2 (UCP2). This protein, a component of the mitochondrial membrane, is responsible for ushering reactive oxygen species (ROS) from the cytoplasm into the matrix of the mitochondria. By activating UCP2, drug-resistant cancer cells have a way of evading oxidative damage to essential cellular macromolecules by storing these ROS in the mitochondria. Genipin happens to be an inhibitor of UCP2 and its presence increases the concentration of ROS in the cytoplasm leading to increased cell death in the presence of cytotoxic drugs. Find the study in PLoS ONE.

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