Malignant glioblastomas are the most common primary brain tumors, causing more than 13,000 deaths each year, said Anthony van den Pol, professor of neurosurgery at Yale School of Medicine and senior author of the study. There are currently no known medical or surgical approaches that constitute an effective cure for glioblastoma, and most patients diagnosed with this type of brain tumor live less than a year.
Van den Pol ™s team put nine different DNA and RNA viruses through a series of tests to determine which infect, slow down, or kill brain tumor cells. The researchers then took the viruses that were most effective at killing tumor cells, cultivated viruses for many generations on brain tumor cells, and selected virus clones with improved tumor “killing capacity and reduced capacity to infect non “tumor cells. The winning candidate was a strain of vesicular stomatitis virus (VSV) that replicates quickly. Whereas humans and other mammals use DNA to carry their genetic code, the viral genome of VSV is encoded by RNA, van den Pol said.
To track the virus as it invaded tumor cells, a recombinant VSV was used that contained a reporter gene isolated from jellyfish that turns infected tumor cells green.
Virus particles that cannot replicate have been used to kill cancer cells, but they can only infect a relatively small number of tumor cells. Van den Pol ™s group theorized that if the replication “competent virus encounters a tumor cell, it will infect the cell, replicate in the tumor cell, and, as the tumor cells die, more viruses will be released that then target more tumor cells. Van den Pol said the current project is the first stage and more work is needed to ensure the safety of the virus before it can be considered for use in clinical trials.
The first author was Guido Wollmann, postdoctoral associate. Peter Tattersall, professor of genetics and laboratory medicine, was co “author. The study was funded by the National Institutes of Health and the National Cancer Institute.
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Rossi, along with Hermann Ziltener, a UBC professor of pathology and laboratory medicine, found that a molecule called P-selectin increases if the thymus is ready and able to accept migrating T-cells. Scientists refer to successful migration as passing through the thymic gate. By tracking P-selectin, scientists can now detect if thymic gates are open or closed.
This research marks the first description of the thymic gate mechanism and was published recently in Nature Immunology. Rossi and Ziltener work at UBC ™s Biomedical Research Centre.
There are approximately 150 blood stem cell transplants in B.C. every year. The survival rate ranges from 25-75 per cent, according to the Leukemia/BMT Program of British Columbia.
Researchers estimate that it would be at least five years before the discovery can be translated into a clinical test.
For more information about bone marrow transplants, visit www.bloodservices.
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