How protein breakdown causes leukemias and brain cancer

An enzyme that is responsible for the breakdown of specific amino acids in food plays a key role in the development of leukemias and brain cancer. The researchers have discovered a surprising link between energy metabolism and the epigenetic code. These labels in the DNA of cancer stem cells determine the activity of genes and many cellular functions.

Acute myeloid leukemia AML is an aggressive type of blood cancer that often relapses in the wake of successful initial treatment. Stem cells that are resistant to therapy are believed to be responsible. Reseachers examined patient samples by comparing the composition of proteins of AML stem cells and leukemia cells without stem cells properties.

The investigators found suspiciously high levels of an enzyme called BCAT1 in the stem cells. These levels rose even higher during a cancer recurrence. The researchers considered this to be a clue that BCAT1 might be linked to therapy resistance. Cancer researchers have suspected for some time that the BCAT1 enzyme, which is responsible for the breakdown of specific proteins in food, plays a role in the development of malignant tumors.

 They discovered that an overproduction of BCAT1 increases the aggressiveness of malignant brain tumors and breast cancer. BCAT1 reduces the levels of this key molecule and this leads to increased levels of chemical labels in the DNA. The tiny methyl groups that are attached to DNA determine whether particular genes are active or silent and, thus, have an immense impact on all cellular functions.

They increase cancer-promoting methylation of DNA. AML is known for an extremely heterogeneous pattern of genetic alterations. However, misregulated methylation with its drastic consequences for the whole cell appears to be a common characteristic of this malignant disease.

The finding that BCAT1 drives cancer-promoting methylation in AML stem cells and other cancer stem cells opens up new options for therapy. A blockade of the enzyme using a targeted agent might normalize DNA methylation and thereby reduce cancer spread and therapy resistance.
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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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Zika kills brain cancer stem cells

Zika virus is a mosquito-borne infection known for causing birth defects in unborn fetuses. Latest research discovered that it is possible to use the virus to target tumor cells in adult brains. Combining Zika virus with chemotherapy and radiation can be use to remove brain tumors.

Glioblastoma is the most common and deadly forms of brain cancer with patients dying within two years of diagnosis. The growth and development of glioblastomas is driven by stem cells that proliferate and give rise to other tumor cells.

Stem cells of the cancer are hard to kill because they avoid body's immune system and are resistant to chemotherapy and radiation. Killing these cells is very important to prevent new tumors from recurring after the original tumor has been surgically removed.

 Glioblastoma can occur in any part of the brain, when glioblastoma is diagnosed, microfibers can spread to the rest of the brain which magnetic resonance imaging MRI would not detect. It is common in men between the age of 50 and 60, and there is no link between developing glioblastoma and having a previous cancer history.

Intense exposure to radiation increases the risk of brain cancer. Zika virus disrupts fetal brain development targeting neural stem and progenitor cells, however the virus' effects on adult brains are less severe.

 The preference of Zika virus for neural precursor cells could be leveraged against glioblastoma stem cells, researchers found the virus infected and killed patient-derived glioblastoma stem cells compared with other glioblastoma cell types or normal neural cells.

When mice with aggressive glioblastoma were injected with a mouse-adapted strain of Zika virus, the virus slowed tumor growth and significantly extended the animals' lifespan.

Researchers also tested a mutated strain of Zika on body's immune response, which was more effective when combined with a chemotherapy drug, temozolomide, that usually has little effect on these cells. Zika virus can kill the kind of glioblastoma cells that tend to be resistant to current treatments.
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How cancer spreads

A research study led by University of Minnesota engineers gives new method of how cancer cells move based on their ability to sense their environment.

The researchers discovered that cells have the ability to sense the stiffness of their environment and their ability to move is depend on their environment ranging from bone tissue to fatty tissue and muscle tissue.

Researchers compared cells from human brain cancer to mobile but normal cells from embryonic chick brains. They did five different experiments that included environments with six different stiffnesses.

The researchers slowed the cancer cells down in a petri dish in the lab by following the predictions of their computer models, which were based on an understanding the mechanics of the cancer cell movement.

Cells are like cars, they have motors that generate force, and a clutch to transfer that force to structures that grip the tissue along which they move. When the environment is good like a paved road, they can move into higher gear, with the engine spinning faster and the clutch transferring more force to the parts that, like wheels, get more grip.

They discovered that the combination of the two drugs they tested inhibit the motor and clutch functions of cancer cells and therefore hindered their movement.

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