Cancer-killing viruses stimulate tumor blood-vessel growthJune 11th, 2008 - 2:09 pm ICT by ANI
Washington , June 11 (ANI): While viruses genetically designed to kill cancer cells offer a promising strategy for treating incurable brain tumors such as glioblastoma, a new study by an Indian-origin scientist has found that such viruses also stimulate the growth of new blood vessels to the tumor, thereby actually leading to regrowth of the tumor.
These vessels transport immune cells that eradicate the viruses and actually stimulate regrowth of the tumor.
Led by Balveen Kaur, a researcher with Ohio State ’s Comprehensive Cancer Center and the Dardinger Laboratory for Neuro-oncology and Neurosciences, the findings of this study could improve this therapy for brain cancer patients.
“This study points to an important side effect of oncolytic viral therapy that may limit its efficacy. Knowing this, we can now work on designing a combination therapy that will inhibit this effect and enhance the action of the viral therapy,” said Kaur.
It was also found that in infected tumor cells, the viruses changed the activity levels of three genes linked to blood-vessel growth in gliomas.
They short listed one of these genes, called CYR61, and said that it was nine times more active in virus-treated tumor cells than in uninfected tumors. It was also demonstrated that the higher the dose of virus used, the greater the gene’s activity.
In the study, researchers implanted human glioma cells into rodents with a working immune system, then injected the resulting tumors of some with a cancer-killing, or oncolytic, virus called hrR3.
They observed that the treated animals lived 17 days as against 14 days for the untreated controls. The virus-treated tumors had almost five times more blood vessels in them than the untreated tumors. Treated tumors also showed changes in gene activity for three of 11 genes thought to play a role in blood-vessel development in gliomas. Of these, CYR61 showing an 8.9-fold increase in activity 12 hours after treatment.
In the end, the researchers verified the virus-caused increase in CYR61 gene activity using several different glioma cell lines and glioma cells from patients, and several strains of active, replicating oncolytic viruses.
“In all cases, we observed a rise in CYR61 gene activity, which indicates that this change in gene activity may represent a host response to the viral infection,” said Kaur.
However, non-replicating viruses did not have any effect on the gene’s activity.
Kaur and her colleagues are now studying why cells turn on this gene when infected with oncolytic viruses and whether the protein that results from this gene activation might serve as a biomarker reflecting patients’ response to oncolytic virus therapy.
The study is published in the latest issue of the journal Molecular Therapy. (ANI)
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