The Cross-Border Biotech Blog

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Tag Archives: Marvelle Koffler Breast Centre

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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