Thursday, May 22, 2008

Senator Kennedy, Gliomas and Vesicular Stomatitis Virus (VSV)

Some Bugs May Be Useful

In The Cockroach Catcher:

“……Nature is of course not about beauty or beauty alone. Beauty is both deceptive and subjective. To love only the beautiful and good and dislike the ugly and bad is missing the point ……
Wildlife is just wildlife. Not good. Not bad.”

As most now know, American Senator Edward Kennedy has been diagnosed with

From the
New York Times:

“Mr. Kennedy’s glioma is in the parietal area in the upper part of the left side of his brain, above the ear. This area of the brain involves motor control and ability to understand language, among other functions.

Malignant brain tumors rarely spread elsewhere in the body. But like the root of a plant, cancerous brain tumors can invade nearby areas in the brain.

Gliomas are categorized by subtypes and by a numerical gradation based on how aggressive they appear. But the doctors did not provide these details or the tumor’s size, saying only that the diagnosis was made by removing a small piece of the cancer in a biopsy, which followed a series of other tests that began after Mr. Kennedy suffered a seizure on Saturday morning.”

A viral view: Researchers at Yale University have genetically engineered a virus (green) that specifically attacks brain tumors in mice (red). The virus kills the primary tumor masses (B) and migrating tumor cells (E), while leaving healthy tissue intact. Credit: Van den Pol/Yale University

I read about this in MIT’s Technology Review

Systemic Vesicular Stomatitis Virus Selectively Destroys Multifocal Glioma and Metastatic Carcinoma in Brain

The Journal of Neuroscience, February 20, 2008, 28(8):1882-1893

Here is a relevant extract from the MIT review:

“.....Now researchers at Yale University have found that a virus that's in the same family as rabies effectively kills an aggressive form of human brain cancer in mice. Using time-lapse laser imaging, the team watched
vesicular stomatitis virus (VSV) rapidly home in on brain tumors, selectively killing cancerous cells in its path, while leaving healthy tissue intact. What's more, Anthony Van den Pol, lead researcher and professor of neurosurgery and neurobiology at Yale, says that VSV is able to self-replicate and produce secondary lines of defense.
A metastasizing tumor is fairly mobile, and a surgeon's knife can't get out all of the cells," says Van den Pol. "A virus might be able to do that, because as a virus kills a tumor cell, it could also replicate, and you could end up with a therapy that's self-amplifying.
His search for a virus candidate began six years ago, when he and his colleagues tested the effect of different viruses on brain tumors in culture. Repeatedly, VSV came out "at the top of the heap." The team grew the virus through many generations, isolating strains that infected cancer cells quickly while having a slow effect on healthy cells. The researchers recently ran the most effective strain through a number of tests in live mice, and they've published their results in a recent issue of the Journal of Neuroscience.
In its experiment, the team transplanted glioblastoma--the most common and aggressive form of human brain cancer--into the brains of mice. Prior to transplantation, researchers genetically engineered the tumor cells to express a red marker, which, once inside the brain, would show up in laser microscopy scans. Similarly, Van den Pol inserted a green marker in VSV cells and injected the virus intravenously through the tail. Within a few days, researchers observed that the green virus found its way to the brain and selectively infiltrated red tumor masses and individual tumor cells, while avoiding normal cells. Van den Pol says that as the virus infects tumors, cancerous cells start to turn green, swelling up until they eventually burst.
…… It's not yet clear why VSV is such an effective tumor killer, although Van den Pol has several theories. One possible explanation may involve a tumor's weak vascular system. Vessels that supply blood to tumors tend to be leaky, allowing a virus traveling through the bloodstream to cross an otherwise impermeable barrier into the brain, directly into a tumor.
Van den Pol says that VSV may also target cancer cells because of inherent defects in a tumor's immune system. Typically, in the presence of a virus, normal cells launch an immune response by producing interferon, proteins that prevent viral infection in healthy cells. Tumors lack such strong viral defenses, providing an easy target for viruses.”

As this is still in the early experimental stage, it may not be an option for Senator Kennedy right now. Vesicular stomatitis virus (VSV) belongs to the Rhabdoviridae family, as does the well-known Rabies virus. It is worth remembering that in nature there is no bad or good, and biodiversity is going to prove important to our future health. There is every reason to preserve the most virulent bug on planet Earth and perhaps in the whole universe. Cockroaches, on the other hand, require no preservation. They just survive!


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