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Researchers Find A Chink In Deadly Glioblastoma's Armour

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Glioblastoma is an aggressive type of cancer in adults that primarily develops in the cerebral hemispheres of the brain. There is no cure yet for glioblastoma. Surgery is the mainstay of treatment, and glioblastoma cells are extremely resistant to existing drug therapies. The complexity of this cancer makes it difficult to treat, and the average survival of glioblastoma patients is only about 12 to 18 months.

A discovery by researchers from the University of Helsinki led by Professor Pirjo Laakkonen raises hopes of a potential treatment for this lethal brain cancer.

According to the researchers, glioblastoma cells depend on the expression of a gene which produces MDGI (mammary-derived growth inhibitor) protein to invade tissues. The structure of the cells' lysosomal membrane is regulated and maintained by the MDGI protein.

Therefore, by silencing the MDGI gene, the stability of lysosomal membrane, and membranes of cleaning organelles found inside tumor cells can be affected, which in turn can lead to leakage of acidic and proteolytic enzymes contained in the lysosomes into the cytoplasm, increase the permeability of the membrane, eventually, initiating cell death, say the researchers.

In the study, which involved cell cultures and mouse models, the researchers used an antihistamine known as Clemastine to activate the lysosome-mediated cell death in glioblastoma cells.

Clemastine was able to reduce the spread of brain tumors and improve the survival rate of the mouse models of glioblastoma, even leading to the disappearance of the entire tumor in the case of the most invasive brain tumor model.

Commenting on the findings, Laakkonen said, "Our research demonstrates that MDGI is a key factor regulating and maintaining the structure of the lysosomal membrane. This is the first gene found to regulate the stability of the membrane".

The study was published in EMBO Molecular Medicine journal.

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