Therapeutic for pancreatic cancer

In most pancreatic cancer patients, the diagnosis occurs when the disease is already advanced, and currently, there is no effective treatment. A group of researchers from the Spanish National Cancer Research Centre (CNIO) may have found a new therapeutic approach.

One of the characteristics of pancreatic cancer is that the tumour cells are embedded in the stroma, which represents 90 percent of the tumour mass and which seems to form a barrier (physical and chemical) hindering treatment with inhibitors, chemotherapy and immunotherapy.

Researchers focused their work on identifying a stromal cell population that fosters tumour growth, to later discover why they have this capacity and reverse it. The strategy to achieve the latter is innovative, because instead of eliminating these stromal cells which help the tumour, the objective has been their selective reprogramming. The researchers focused on a subpopulation of fibroblasts known to play a role in inflammation, because inflammation fosters tumour growth.

Their analysis revealed that the Saa3 gene is responsible for CAFs helping tumour cells to progress. When the researchers eliminated the expression of this gene in the CAFs, these cells behaved like normal fibroblasts, losing the ability to accelerate tumour cell progression. Researchers had managed to "reprogramme" these cells, which had been stripped of their pro-tumour properties.

In human samples of pancreatic cancer, the researchers have identified the same population of pro- tumour fibroblasts, and have observed that when the SAA1 gene (the human version of Saa3) is overexpressed, the prognosis for the patients is far worse.
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Gata4 repairs a broken heart

Blood flow to the heart ceased during heart attack, this leads to death of the heart muscles, heart muscle does not regenerate; it replaces dead tissue with scars made of fibroblasts that do not pump blood to the heart.

People who had severe heart attack will develop heart failure, restoring cardiac function by reprogramming scar tissue into cardiomyocyte-like can reduce risk of heart failure.

Researchers has shown that applying a cocktail made of transcription factors Gata4, Mef2c and Tbx5 GMT results in less scar tissue, or fibrosis, and up to a fifty percent increase in cardiac function in small animal models of the disease.

This result was presumed to be mostly a consequence of the reprograming of heart fibroblasts into cardiomyocyte-like cells. They noticed that reduced fibrosis and improved cardiac function far exceeded the extent of induced new cardiomyocyte-like cells.

The research team investigated how the GMT cocktail activated mechanisms that reduced fibrosis. They discovered that of the three components in the GMT cocktail, only Gata4 was able to reduce post-heart attack fibrosis and improve cardiac function in a rat model of heart attack.

Adding Gata4 to rat fibroblasts showed an reduced expression of Snail, the master gene of fibrosis. Gata4 plays a complex role in heart regeneration: as part of the GMT cocktail, it contributes to the reprograming of fibroblasts into cardiomyocyte-like cells. It can also contributes to the development of an enlarged heart and decrease cardiac fibrosis.
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Molecules in zebrafish may heal spinal cord injury

Researchers have discovered mechanism in the damaged spines of zebrafish that helps nerve connections to regrow. Zebrafish have the remarkable ability to regain full movement within four weeks of injury to their spinal cord.

Damage to human spinal cord leads to paralysis. After injury to the spinal cord in zebrafish, wound-healing cells called 'fibroblasts' move into the site of damage.

The fibroblasts produce a molecule called collagen 12, which changes the structure of the support matrix that surrounds nerve fibres.

This enables the damaged fibres to grow back across the wound site and restore the lost connections.
Scientists found that fibroblasts are instructed to make collagen 12 by a chemical signal called 'wnt'.

Understanding these signals could hold clues for therapies to heal the spinal cord after injury. This connections between the brain and muscles of the body lost after spinal cord injury in humans can be used to provide better treatment
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