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Tag Archives: apoptosis

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 30, 2010

Maybe these primary research projects will lead to the next great “Dendreon” story…

Mirror-rorriM Movement Disorder: Defects in the proper connections between the left and right sides of the brain can lead to involuntary movements where one side of the body follows or mirrors the movement of the other side.  A study of two families affected by inherited cases of mirror movements led to the identification of mutations in the DCC gene (Deleted in Colorectal Carcinoma).  DCC is a receptor for netrin-1, which is a factor that is important for guiding neural axons across the midline to make the proper left-right connections.  This is a key finding in understanding the complexities of how our brains are wired.  Dr. Guy Rouleau (Université de Montréal) and Dr. Frédéric Charron (Institut de recherches cliniques de Montréal) collaborated on the study and is published in the prestigious Science journal.

Improving RNA Therapeutics: RNA interference based therapeutics is gaining traction in the biotech world (eg. Tekmira, Alnylam, MDRNA).  Enhancing the potency of siRNA is the focus of this research study published in Nucleic Acids Research journal.  The technology uses a combination of DNA and RNA analogs to increase the stability of the siRNA agent against nucleases and helps them to evade immune responses that often limit their effectiveness.  Dr. Masad Damha led his group at McGill University.

Also in Montreal, Drs. François Major and Gerardo Ferbeyre (Université de Montréal) announced the launch of the first ribonucleic acid (RNA) engineering laboratory in Canada.  They are using bioinformatics and biochemistry to come up with designer microRNAs that can control the behaviour of RNAs to control or cure cancers.

New Tumour Suppressor:  A recent study demonstrates the tumour suppressor properties of the Cdh11 gene.  The first hint of this function arose from studies showing a frequent loss Cdh11 in retinoblastoma cancers.  Using a series of animal models to determine the role of Cdh11, Dr. Brenda Gallie’s team (Ontario Cancer Institute) demonstrated the tumour suppressor properties of Cdh11 through a mechanism promoting cell death or apoptosis.  The full text article appears online in PLoS Genetics.

Lung Cancer Drug Target: CXCR4 may be the next therapeutic target for treating lung cancer.  Its overexpression in about 10% of lung cancers is associated with poor patient outcome (2.7 vs. 6.1 months survival), likely due to CXCR4’s support for the rapid growth and metastasis of tumours.  On the brighter side, anti-CXCR4 drugs, which are already in existence for the treatment of HIV/AIDS, may be “fast tracked” for testing in lung cancer patients.  Dr. Gwyn Bebb, from the University of Calgary, presented her data recently at the 2nd European Lung Cancer Conference.

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.

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