Cancer drug may treat sepsis

New York, April 29 (IANS) Tiny doses of a cancer drug may stop the raging, uncontrollable immune response to infection that leads to sepsis, say researchers.

A small dose of topoisomerase I (Top 1) inhibitor can dampen an acute inflammatory reaction to infection while still allowing the body’s protective defense to take place, showed the findings published in the journal Science.

The treatment may help control not only sepsis but also new and brutal assaults on human immunity such as novel influenza strains and pandemics of Ebola and other singular infections, said the study’s senior investigator, Ivan Marazzi, assistant professor at Icahn School of medicine at Mount Sinai in New York.

Sepsis — deadly infections often acquired in hospital by patients with a weak immune system — is caused by an excessive host response to infection, which in turn leads to multiple organ failure and death.

The team found that use of one to three doses of a Top 1 inhibitor that is one fiftieth the strength of normal chemotherapy was enough to rescue 70-90 percent of mice from an inflammatory storm death due to either acute bacterial infection, liver failure, or virus-bacteria co-infection.

The treatment did not produce overt side effects.

They also tested the inhibitor in cells infected with influenza, Ebola, and other viral and bacterial microbes that over-stimulate the immune system, and found the drug blunted a dangerous immune reaction.

“Our results suggest that a therapy based on Top 1 inhibition could save millions of people affected by sepsis, pandemics, and many congenital deficiencies associated with acute inflammatory episodes — what is known as a cytokine, or inflammatory, storm,” Marazzi said.

“These storms occur because the body does not know how to adjust the appropriate level of inflammation that is good enough to suppress an infection but doesn’t harm the body itself,” he said.

“This drug appears to offer that life-saving correction,” Marazzi explained.

When treated, cancer cells can switch to a different mode

London, April 29 (IANS) When medication is used to shut off the oxygen supply to tumours, the cells adapt their metabolism in the medium term — by switching over to producing energy without oxygen, new research has found.

Medicines can initially slow or even stop tumour growth. However, as the treatment goes on, the tumours begin to develop resistance to these therapies — and they start to grow again.

The new findings, reported in the journal Cell Reports, could be used for treatments that can inhibit tumour growth in the long term.

Today, it is common knowledge that the disease develops in a series of stages. One of these stages, tumor angiogenesis, involves the formation of new blood vessels to supply oxygen and nutrients to the growing tumour.

Now, the research team has shown that, although the latest medications are effective at preventing blood vessel formation, the tumours can continue growing even without a supply of new blood vessels.

Analysis of this finding from a biochemical and molecular genetic perspective revealed that the tumour cells convert to a different type of metabolism. They no longer produce energy using oxygen delivered via the blood vessels — but instead switch over to glycolysis, a form of anaerobic energy production.

The lactic acid formed as a result is delivered to cells that are still receiving sufficient oxygen and that can use the lactic acid, together with the oxygen, to produce energy.

The research group also showed that this specific mode of metabolism — and therefore the tumour’s growth — can be interrupted, namely by inhibiting anaerobic energy production or transport of the lactic acid.

“Our findings open up new approaches for the optimisation of anti-angiogenic therapies and for inhibiting tumor growth effectively in the long term,” said lead researcher Gerhard Christofori, professor at University of Basel in Switzerland.

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