The Cross-Border Biotech Blog

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Tag Archives: metabolism

Friday Science Review: May 14, 2010

A Cure for Brain Cancer: An aggressive type of brain cancer called glioblastoma may be cured using the small molecule dichloracetate (DCA), a cheap and safe generic compound.  The drug works by altering the metabolism of the cancer cells, which is an emerging concept that exploits the different (higher) energy demand of cancer cells.  DCA’s target in the cells is the metabolic enzyme pyruvate dehydrogenase kinase II and it also promotes cell death in glioblastoma cancer cells and cancer stem cells.  In an 18-month study, some of the five patients’ tumours either regressed in size or did not grow any more.  Drs. Kenn Petruk and Evangelos Michelakis at the University of Alberta describe their study showing efficacy of DCA in humans for the first time in the journal Science Translational Medicine.  It is interesting to note that these and future studies are funded by government grants and private donations since the pharmaceutical industry is not interested in a compound that is readily available and without intellectual property protection (ie. no $cha-ching$).

Embryonic Cells Can Stop Viruses: Embryonic cells have a natural defence mechanism to limit the ability of viruses to express their genes and thereby prevent infection and further spread of the virus.  Researchers also determined that the different layers of cells in the developing embryo have different capacities to silence viral activation.  This “graphical abstract” published in Cell Stem Cell shows the outer layer of extraembryonic endoderm stem cells as the first line of defence with the strongest abilities to extinguish viral gene expression.  Several proteins including chromatin remodelling and repressor complex proteins were also identified to play key roles in this process.  The study was lead by Dr. Mellissa Mann at the University of Western Ontario.

If Only Mice Could Talk: This one is a bit strange.  It looks like mice express pain through facial expressions similar to the way humans do.  McGill University researchers developed the Mouse Grimace Scale to aid scientists working with lab animals to better ‘communicate’ with the animals.  Not only will this help to minimize and manage the stress that is inflicted on the animals but they can read the facial responses to determine whether a drug treatment is working or as an indicator of negative side effects.  Check out the study by Dr. Jeffrey Mogil in the issue of Nature Methods.

Pathogens Are Our Friends: Diphtheria Toxin (DT) is a potent cytotoxin that kills the cells that it binds to.  The DT385 is a recombinant version that is truncated and can be targeted to cancer cells to be used as a therapeutic agent.  In the present study, 15 of the18 human cancer lines tested were inhibited by DT385 as a result of increased apoptosis and decreased protein synthesis.  Dr. David Waisman at Dalhousie University published his study online in PLoS One.  Using pathogen proteins as therapeutic agents is not a new concept.  Oncolytics Biotech’s REOLYSIN® is derived from the Reovirus and Advaxis, Inc. exploits the Listeria bacterium to activate the immune system in an immunotherapy approach.

Studying Herpes Infection: Dr. Karen Mossman (McMaster University) investigated Herpes Simplex Virus-1 infection and how a viral protein, ICP0, is localized properly in the cell to block Interferon Regulatory Factor 3 (IRF3), the cell’s innate antiviral mechanism.  The study is described in PLoS One journal.

Friday Science Review: March 5, 2010

Missing Enzyme Improves Metabolism: Mice lacking the TGH gene for the enzyme triacylglycerol hydrolase showed an unexpected dramatic improvement in their metabolic profile.  TGH is an enzyme that helps to release stored fat or triglycerides into the blood stream where it circulates to be used as an energy source or, if in excess, ends up being stored at tissue sites that do not normally store fat depots.  This contributes to cardiovascular diseases, diabetes, and liver dysfunction.  Researchers were correct in hypothesizing that deleting TGH would prevent this from happening but they were surprised to discover global metabolic benefits.  These mice not only have better lipid profiles but they also burn more fat and are also more physically active compared to mice that have the enzyme.  Additional research is required but this study demonstrates the potential of TGH as a therapeutic target for lowering blood lipid levels and likely other related benefits in humans.  The study was led Dr. Richard Lehner and his team at the University of Alberta and is published in this month’s issue of Cell Metabolism.

Gene Duplication Causes Bleeding Disorder: The genetic cause of the rare blood clotting disorder, Quebec Platelet Disorder (QPD) was recently discovered by researchers at McMaster University.  QPD is caused by a mutation involving an extra copy of the gene encoding the enzyme urokinase plasminogen activator (uPA), resulting in an overproduction of the enzyme that accelerates blood clot breakdown.  This transforms blood platelets from clot forming to clot busters.   A genetic test for the mutation, the first gene duplication mutation causing a bleeding disorder, is in development and will be an invaluable diagnostic tool.  Dr. Catherine Hayward led the discovery team and their study is published in the journal Blood.

Blocking Metabolic Genes: Prox1 is the newest player in the control of our body’s energy balance.  It binds to and inhibits two well known transcription factors for metabolic genes, estrogen-related receptor alpha (ERRalpha) and proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha).  These are significant findings along the long road to understanding the complex regulation and homeostasis of our metabolic system.  Dr. Vincent Giguère and his team at McGill University’s new Goodman Cancer Centre describe their work in the latest issue of Genes and Development.

Molecular Clues to Chemotherapy Resistance: Scientists at The Campbell Family Institute for Breast Cancer Research knocked out a specific isoform of the p73 protein family, DeltaNp73, to try to delineate the specific function of this protein.  They discovered a novel function whereby the DeltaNp73 protein targets the DNA damage site and partners with another protein, 53BP1, to block the subsequent DNA damage molecular response pathway involving p53.  This has significance in explaining chemotherapy resistance in human tumors with high levels of DeltaNp73 expression.  Dr. Tak Mak reports the study in Genes and Development.

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