Gene mutation linked with liver cancer

Presently, there is no effective treatment for the cancer found in the liver called fibrolamellar hepatocellular carcinoma, which is mainly found among children and young people. Operation of the tumour is the only treatment, some of the patients do not survive after five years.

Coupling of the two genes through a mutation causes a cancer tumour to develop in the liver. The researchers have made sure the genetic composition of the mutation in the mice is identical with the mutation found in human patients. This makes the researchers conclude that the gene mutation also leads to cancer in humans.

Sequencing the DNA of the patients tumour showed that all the patients suffering from the disease had the same mutation in their DNA. The researchers used the revolutionary technology CRISPR/Cas9 that makes it possible to 'edit' genetic material on mice.
They have produced CRISPR/Cas9 reagents, which would provoke precisely the desired fusion of the two genes.

The reagents were injected into the mice's tails and then transported through the bloodstream to the liver.
 In the liver they created a mutation identical with the human mutation, then the researchers were able to conclude that the mice developed the expected type of tumour in the liver.

In other studies, researchers deliberately damage the mice's liver to imitate a liver disease found among human patients or expose them to several different forms of mutations which may cause cancer. This was not necessary here. Because of our genetic design based on CRISPR/Cas9-technology we are certain that the main factor that can explain the cancer is the fusion of the two genes.

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Poliovirus therapy activates immune response against cancer

An investigational therapy using modified poliovirus to attack cancer tumors appears to unleash the body's own capacity to fight malignancies by activating an inflammation process that prevent cancer cells to evade the immune system.

Glioblastoma is a lethal form of brain cancer. The research team elucidated how the poliovirus works not only to attack cancer cells directly, but also activates longer-lasting immune response that appears to inhibit regrowth of the tumor.

Using human melanoma and breast cancer cell lines, and then validating the findings in mouse models, the researchers found that the modified poliovirus therapy starts by attaching to malignant cells, which have an abundance of CD155 protein.

The CD155 protein is a poliovirus receptor. The modified virus then begins to attack the tumor cells, directly killing many, but not all. This releases tumor antigens. The second phase of assault is more complicated, by killing the cancer cells, the modified poliovirus triggers an alarm within the immune system, alerting the body's defenses to attack.

This appears to occur when the modified poliovirus infects dendritic cells and macrophages. Dendritic cells then present tumor to T cells to launch an immune response. Once the immune system is activated against the poliovirus-infected tumor, the cancer cells can no longer hide and they remain vulnerable to ongoing immune attack.

Poliovirus killed tumor cells and infected the antigen-presenting cells, which allows them to function in such a way that they can raise a T-cell response that can recognize and infiltrate a tumor. Poliovirus stimulates an innate inflammatory response.
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