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Tag Archives: interferon

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: April 23, 2010

Iron Man 2: Actually, this is about IRP2 – Iron Regulatory Protein 2.  Ok, not quite as exciting as the superhero movie but it is interesting/unexpected that overexpression of IRP2 promotes cancer cell growth.  In contrast, the very similar IRP1 protein suppresses tumour growth.  The difference seems to lie within a 73 amino acid sequence in IRP2 that is required for its growth promoting properties.  It is a long stretch to try to make any link between iron intake and cancer based on this preliminary study but it does warrant further research to understand the roles of IRP1 and IRP2.  Dr. Kostas Pantopoulos (McGill University) published his study in PLoS One.

Not All Herpes are the Same: There are many different strains of herpes viruses, each with slightly different properties and responses to drugs.  Human herpesvirus 6A and 6B (HHV-6A, HHV-6B) variants are prime examples of this.  Classic anti-viral drugs based on type 1 Interferon (IFN) are effective against HHV-6A infected cells but not cells infected with HHV-6B.  Dr. Louis Flamand’s group at Université Laval’s Centre de Recherche en Rhumatologie et Immunologie (CRRI) worked out some of the molecular details explaining this difference.    They mapped a 41 amino acid region in the IE1 protein that is present only in the HHV-6B strain, which acts to block any further genetic responses to the IFN drugs.  These small differences between herpes strains make it difficult to effectively treat infected patients but research such as this one are very important to identify how to better target each specific strain.  The study is reported in this week’s issue of the Proceedings of the National Academy of Sciences.

Hippos are Your (Kidney’s) Friend: Polycystic Kidney Disease (PKD) is a common genetic disease affecting an estimated 12.5 million people worldwide and is the forth leading cause of kidney failure.  Researchers are unraveling the key molecular players involved in PKD.  In this study, Dr. Liliana Attisano’s team (University of Toronto) took a closer look at the Hippo pathway and identified a new function for the transcriptional activator, TAZ. TAZ modulates the beta-Catenin/Wnt signalling pathway, which is important in development and morphogenetic events.  Mouse knockouts that do not express TAZ develop polycystic kidneys and demonstrate the role that these pathways play in kidney disease.  This study is reported in the latest edition of Developmental Cell.

Ovarian Cancer Cells Avoid Death: Researchers studying ovarian cancer determined the mechanism by which ovarian cancer cells thrive.  The sequence goes like this:  ovarian cancer ascites triggers an adhesion protein called alphavbeta5 integrin; this activates FAK phosphorylation and correlates with Akt activation; the Akt pathway inhibits the molecular events leading to cell death or apoptosis.  Thus, ovarian ascites confers protection against cell death.  This study reveals some possible key target points for therapeutic intervention in the treatment of ovarian cancer.  Dr. Alain Piche at the Université de Sherbrooke describes his work in the journal Oncogene.

Friday Science Review: January 22, 2010

Some really exciting research in this week’s review…

Special (RNAi) Delivery: One of the obstacles for RNAi based therapeutics is the difficulty in getting the RNAi into the cells efficiently to invoke a positive response.  Vancouver based Tekmira Pharmaceuticals (TSX: TKM.TO), in partnership with Alnylam Pharmaceuticals (Nasdaq: ALNY) and researchers at the University of British Columbia, Drs. Pieter Cullis and Marco Ciufolini, developed a new and improved RNAi delivery method that is 10X better than their standard delivery platform.  Using their knowledge of lipid structure and how specific features influences delivery into cells, they used a rational design approach to develop a new cationic lipid, DLin-KC2-DMA (KC2), that is used with their current SNALP system (stable nucleic acid-lipid particles) to achieve the remarkable results.  Details of the study are reported in this week’s issue of Nature Biotechnology.

Resolving Stem Cell Populations: The differentiation of stem cells is a complex multi-step process that is not fully understood.   With each step, the potential of that stem cell becomes more and more restricted.  Researchers performed a series of intricate detailed studies on cell populations to resolve distinct Intermediate Term Reconstituting Hematopoietic Stem Cells or ITRC (versus long- and short-term populations).  The significance of this key finding is that researchers who are interested in harnessing the potential of long-term reconstituting hematopoietic stem cells can more accurately study a pure population of true, self-renewing stem cells with homogeneous characteristics.  Prior to this new “intermediate-term” identification, the majority of “long-term” cells were actually comprised of intermediate-term cells.  Dr. Norman Iscove and his team at the University Health Network describe their work in the latest issue of Cell Stem Cell.

Fishing for New Drugs: A high-throughput behavioural monitoring system to observe the response of Zebrafish to neuroactive chemical compounds should help expedite the discovery of new drugs for neurological disorders.  Researchers setup a video system and applied “behavioural barcodes” that they say can track the effects of 14,000 chemicals on zebrafish behaviour.  The capacity of this large-scale screen is unique and the use of zebrafish is quite informative because they are transparent, genetically tractable, and more similar to humans than you might think.  In this platform, response to two strong light pulses after exposure to chemicals is monitored and the observations are translated into barcodes that make data analysis of this magnitude a lot more manageable.  Drs. Jennifer Bryan and Rick White at UBC collaborated with Harvard researchers and published their study in Nature Chemical Biology.

Intrinsic Stimulator of Muscle Regeneration: A new subpopulation of cells in muscle tissue that contribute to muscle injury repair has been identified.  The surprise is that these cells, called fibro/adipogenic progenitors (FAPs), are derived from a different developmental lineage as muscle cells.  These fat-lineage cells, which are resident in muscle tissue, are ‘activated’ in response to muscle damage but they do not become muscle cells.  Instead, they release factors that promote and enhance muscle progenitors in the myogenesis repair process.  The conundrum, however, is that too much of these FAPs can lead to fibrosis and contribute to muscle disorders.  The study, reported in Nature Cell Biology, was led by Dr. Fabio Rossi at the University of British Columbia.

Pharmacoviral Therapy for Gliomas: Oncolytic viruses (VSVs) are used in the treatment against malignant gliomas but are limited in efficacy due to the viral induced IFN (interferon) response – one of our body’s natural defense mechanism.  Knowledge of the molecular mechanisms involving the mTOR pathway in IFN production led researchers to investigate the use of rapamycin, an mTOR inhibitor, in conjunction with the VSVs.  This “pharmacoviral” combinatorial approach was very successful when tested in rats with malignant gliomas and represents a potentially new therapeutic strategy.  Dr. Nahum Sonenberg and his team at McGill University are experts in the mTOR pathway and describe their work in the Proceedings of the National Academy of Sciences.

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