How to Help a Virus Kill Cancer ? Profncampbell's Blog

How to Help a Virus Kill Cancer

Oncolysis stopped by CCN1 activation

Reviewed By: Chris Galloway, M.D.

By: Travis Giddings

Published:? Mar 30, 2012 06:54 am

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Glioblastoma (a form of aggressive brain cancer) has limited treatment options. Recently some studies have tried to make headway in treatment by examining the use of viruses to upload new DNA into the tumor cells, then using a secondary effect to kill the tumor.

Work in this field has been problematic, given the many defenses the human cell has against viral infection.

Researchers are trying to improve the results of the cancer-killing viral therapy by studying how the cells normally defend against a viral infection.

Ask your oncologist about immunotherapy.

Researchers from Ohio State University Comprehensive Cancer Center looked into increasing the effectiveness of these human-engineered cancer-killing viruses, known as oncolytic viruses. Specifically, the group found that the brain cancer cells signaled others with a protein called CCN1, sounding the alarm to the immune system to begin fighting back.

The protein CCN1 was known to be involved in immune signaling, but testing found that the primary role is to prevent viral infection.

?We found that, in the extracellular matrix, this protein orchestrates a striking cellular antiviral response that reduces viral replication and limits its cytolytic efficacy,? said principal investigator Balveen Kaur, who holds a doctorate in molecular biology.

?These findings are significant because they reveal a novel mechanism used by infected cells to fight viral infections and alert adjacent uninfected cells to prepare their defenses to fight off forthcoming viral attacks,? Kaur says.

The study found that the protein CCN1 is important in normal immune function, but in this case prevents the viral therapy from working to kill the cancer cells. Normally a good thing, this defense protein usually keeps cells from being infected, but scientists found that it is even more common than usual in these brain cancers, showing up in 68 percent of glioblastoma specimens.

The study builds on Kaur?s previous research on CCN1?s interactions with cancer cells and oncolytic viruses. Researchers experimented using animal models, planting glioma cells cultivated from human tumors, and injecting oncolytic viruses derived from human herpes virus type 1 (HSV-1).

The research was examining the use of viral infection of cancer cells, but the principals explored in viral infection have broad application in immunotherapy for preventing viral infection as well.

Lowering immune function after intentionally introducing viruses that alter DNA is not without controversy in scientific quarters, but researchers hope to further research in the field of immune therapy in general before beginning to test viral therapy in humans.

Researchers concluded that the protein CCN1 causes a category one immune response, and treatments are currently available to suppress the immune system to enhance the virus? effect on cancer cells. The possible complications and side effects demonstrated in the past few decades with viral therapy may keep this line research purely experimental for some time.

The study was published in a recent issue of the journal Cancer Research.

Full financial disclosure of conflicts of interests and funding was not made publicly available.

Brain Tumors

Each year in the United States, over 25,000 people will be newly diagnosed with some form of primary malignant brain tumor, and over 90,000 people are currently living with the disease and undergoing treatment. Approximately 13,000 of these patients will die from the disease, representing 2% of all cancer deaths.

Brain tumors encompass a wide variety of types of cancer, some more aggressive than others. They include:

• Glioblastoma multiforme (GBM) ? A deadly tumor forming in the white matter of the brain. Makes up 52% of all cerebral tumors and most common in white and Asian men over age 50. It is very difficult to treat and average survival after diagnosis is 14 months.
• Astrocytoma ? a tumor that forms from the glial cells in the brain (support cells for neurons). These can be benign or malignant (GBM is a form of astrocytoma) and appear in young children as well.
• Oligodendroglioma ? arise from the oligodendrocytes (insulating cells for axoms). They appear mostly in adults around age 35 and represent about 10% of all primary brain tumors and tend to recur after treatment.
• Ependymoma ? arises from tissues in the brain that surround the drainage system of the brain. They represent about 5% of adult brain tumors, and 10% of pediatric brain tumors, peaking at age 35 and earlier at age 5. Often they end up causing hydrocephalus, or ?water on the brain.?

• Brain tumors are caused by a change in genetics, much like any other cancer that causes cells to grow out of control. Some brain tumors are associated with specific chromosomal changes, but in most cases, the cause of a brain tumor is unknown, and due to some combination of genetic instability and environmental damage.
• Symptoms of a brain tumor depend mainly on the size of the tumor and where it is located in the brain. Because the brain is housed in the skull, a growing tumor will cause something called mass effect, where the enlarging tumor is taking up too much space and cause increased pressure in the brain. This can cause terrible headaches, nausea, vomiting, and changes in consciousness among other specific signs. In other cases, the growing tumor may encroach upon a part of the brain that has a specific function, and cause that function to cease. Depending on what part of the brain the tumor is in, language, motor coordination, vision, balance, and paralysis can occur. In both cases, a brain tumor can present immediately or after several years of growing.
• Diagnosis of a brain tumor will ultimately be made by CT scan and MRI. Treatment of brain tumors may involve surgery, radiation, and chemotherapy. Additionally, MRI-guided laser ablation is frequently used, a technique that involves placing a laser directly into the tumor, and then guiding the laser to destroy the tumor with heat while leaving the surrounding brain tissue undisturbed. Each modality presents its own risks and benefits. Surgery is sometimes not possible because of risk to damage of vital brain structures necessary for life.
• Prognosis for a brain tumor is entirely dependent on the type of tumor and its location. Some tumors grow very fast and are inoperable due to the cell type and location, and these patients have a poor prognosis. Other brain tumors can be lived with for years, or quickly and easily treated with surgery.
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