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Tag Archives: ischemia

Friday Science Review: February 26, 2010

A few medical research applications this week…

Personalized Medicine – for Lung Cancer: To develop a personalized medicine approach to treating non-small cell lung cancer (NSCLC), researchers generated a xenograft model where they implant human tumour tissue into the renal capsule of a host mouse.  As the tumour establishes itself, the mouse then becomes the platform for testing various chemotherapy regimes (cisplatin+vinorelbine; cisplatin+docetaxel; cisplatin+gemcitabine) to determine which one or combination therapy is the most effective against each of the different tumours.  They compared the results of the treatments in mice to retrospective patient outcomes and found significant correlation to consider the xenograft model a success.  Although it takes about 6-8 weeks for the results, they believe that it is quick enough to gain an insightful preliminary assessment of the potential therapeutic outcome.  Dr. Yuzhuo Wang led his team at the BC Cancer Agency and reports their work in Clinical Cancer Research.

HIV-1 Molecular Manipulations: HIV-1 infected patients exhibit a loss of CD4+ T cells, which are essential players in the defense against viral infections.  A new study reveals how the HIV-1 protein, Vpr, activates the Natural Killer (NK) cells by inducing the expression of stress-related proteins at the cell surface of CD4+ T cells.  The NK cells recognize the stress signals on CD4+ T cells and attacks and destroy these cells, leaving the patient with severely reduced CD4+ T cells.  Researchers also noticed that the continuous activation of NK cells eventually desensitizes them and they eventually lose their ability to perform their normal duties in attacking infected cells.  The molecular mechanisms of Vpr discovered in this study should help in future research leading to new therapeutic strategies.  Dr. Éric Cohen and his team at the Institut de recherches cliniques de Montréal describe their research in last week’s issue of Blood.

Protecting Your Heart: The blood pressure cuff you see in every doctor’s office can be used to limit the severity of heart attacks by triggering a molecular response in the body that protects the heart during an attack.  It is called remote ischemic preconditioning where the blood pressure cuff is used to intermittently cut off blood flow to the arm during an attack.  This triggers an innate response warning message throughout the body to release molecules to protect itself from the lack of blood flow.  In this particular study, the size of the heart attacks were reduced by 30-50% compared to control groups.  It is one of the most effective treatments and is relatively simple to administer.  Dr. Andrew Redington at The Hospital for Sick Children led the international study and is published in the The Lancet.

Friday Science Review: September 11, 2009

Two great medical discoveries…

Stayin’ Alive:  During a stroke, for example, neurons deprived of oxygen undergo cell death.  In a recent discovery lead by Dr. Michael Tymianski’s team at the Krembil Neuroscience Centre at Toronto Western Hospital, the protein TRPM7 was found to play a critical role in mediating this detrimental effect.   After suppressing TRPM7 expression in a localized region of a rat’s brain, they simulated a stroke by cutting off blood flow to the brain for 15 minutes.  The subsequent analysis revealed a complete lack of tissue damage compared to rat brains expressing TRPM7.  The resistance to death by cells lacking TRPM7 even preserved the brain’s cognitive function and memory performance following the ‘stroke’.  This may have tremendous implications for preventing further cell damage following ischemia in any tissue and is not necessarily limited to the brain, although it is yet to be tested elsewhere in the body

Details of the discovery are reported in the latest edition of Nature Neuroscience.

Insulin Resistance Gene Discovery: An international effort led by Dr. Robert Sladek and Dr. Constantin Polychronakos at McGill University performed a genome-wide comparison and identified a single nucleotide variation in the genetic region near the IRS1 gene that is associated with insulin resistance and hyperinsulinemia.

Dr. Sladek explains it best:

“It’s a single-nucleotide polymorphism (SNP, pronounced ‘snip’), a single letter change in your DNA,” said Sladek. “What’s interesting about this particular SNP is that it’s not linked genetically to the IRS1 gene in any way; it’s about half-a-million base-pairs away, in the middle of a genetic desert with no known genes nearby. In genetic terms, it’s halfway from Montreal to Halifax. And yet we can see that it causes a 40-per-cent reduction in the IRS1 gene, and even more important, a 40-per-cent reduction in its activity. Which means that even if insulin is present, it won’t work.”

IRS1 is known to be the key signalling protein involved in the cell’s initial response to insulin.  This recently discovered variant allele affects the level of IRS1 protein expressed and reduces the capacity of the cells to respond to insulin. Unlike other diabetes risk genes that affect insulin production in the body, this is the first that is known to suppress insulin stimulation in the cells.

The research article appears in the early online edition of Nature Genetics.

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