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Human Cells with ‘Built-in Genetic Circuit’ can impair ability of Cancer Cells to Survive and Grow, say Researchers

As tumours develop and grow, they rapidly outstrip the supply of oxygen delivered by existing blood vessels

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FILE - A biotechnician demonstrates the loading of a genome sequencing machine at the J. Craig Venter Institute in Rockville, Maryland. Relative to their ability to pay, cancer patients in China and India face much higher prices than wealthier U.S. patients. VOA

London, Nov 26, 2016: Researchers have engineered cells with a “built-in genetic circuit” that produces a molecule that impairs the ability of cancer cells to survive and grow in their low oxygen environment.

The genetic circuit produces the machinery necessary for the production of a compound that inhibits a protein which has a significant and critical role in the growth and survival of tumours.

This results in the cancer cells being unable to survive in the low oxygen, low nutrient tumour micro-environment.

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“In a wider sense, we have given these engineered cells the ability to fight back — to stop a key protein from functioning in cancer cells,” said lead researcher Ali Tavassoli, Professor at the University of Southampton in Britain.

“This opens up the possibility for the production and use of sentinel circuits, which produce other bioactive compounds in response to environmental or cellular changes, to target a range of diseases including cancer,” Tavassoli said.

As tumours develop and grow, they rapidly outstrip the supply of oxygen delivered by existing blood vessels. This results in cancer cells needing to adapt to a low oxygen environment.

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To enable them to survive, adapt and grow in the low oxygen or ‘hypoxic’ environment, tumours contain increased levels of a protein called Hypoxia-inducible factor 1 (HIF-1).

This protein senses reduced oxygen levels and triggers many changes in cellular function, including a changed metabolism and sending signals for the formation of new blood vessels.

It is thought that tumours primarily hijack the function of this protein (HIF-1) to survive and grow.

“In an effort to better understand the role of HIF-1 in cancer, and to demonstrate the potential for inhibiting this protein in cancer therapy, we engineered a human cell line with an additional genetic circuit that produces the HIF-1 inhibiting molecule when placed in a hypoxic environment,” Tavassoli explained.

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“We’ve been able to show that the engineered cells produce the HIF-1 inhibitor, and this molecule goes on to inhibit HIF-1 function in cells, limiting the ability of these cells to survive and grow in a nutrient-limited environment as expected,” Tavassoli noted.

The genetic circuit was incorporated onto the chromosome of a human cell line, which encodes the protein machinery required for the production of their cyclic peptide HIF-1 inhibitor.

The research, published in the journal ACS Synthetic Biology, demonstrates the possibility of adding new machinery to human cells to enable them to make therapeutic agents in response to disease signals. (IANS)

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Fat Around Arteries May Help Keep Blood Vessels Healthy: Study

Fat around arteries proven to be good for health as said by health researchers.

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Arteries
Fat around our arteries may play an important role in keeping those blood vessels healthy. (Representational Image). Pixabay

Researchers have found that fat around our arteries may play an important role in keeping those blood vessels healthy. This is a new health news.

The fat, known as perivascular adipose tissue, or PVAT, helps arteries do what scientists call “stress relax,” or let go of muscular tension while under constant strain.

This is similar to the bladder, which expands to accommodate more liquid while at the same time keeping it from spilling out.

“In our study, PVAT reduced the tension that blood vessels experience when stretched, and that’s a good thing, because the vessel then expends less energy. It’s not under as much stress,” said study researchers Stephanie Watts from Michigan State University in the US.

The findings, published in the journal Scientific Reports, could affect how researchers test for treatments related to plaque buildup in our arteries, or atherosclerosis, an issue that can often lead to a heart attack, which is currently a leading cause of death in the US.

What made the finding so exciting, Watts said, is that PVAT has largely been ignored by researchers who have thought its main job was to store lipids and do little more.

Arteries
The fat, known as perivascular adipose tissue, or PVAT, helps arteries do what scientists call “stress relax,” or let go of muscular tension while under constant strain. (Representational Image). Pixabay

Right now, scientists only divide blood vessels into three parts, the innermost layer called the tunica intima, the middle layer called the tunica media and the outermost layer called the tunica adventitia.

Watts would like scientists to recognise PVAT as the fourth layer, which others have called tunica adiposa – tunica means a membranous sheath enveloping or lining an organ and adiposa is a synonym for fat.

Other investigators have shown that PVAT plays a role in the functioning of blood vessels, finding that it secretes substances that can cause blood vessels to relax as well as substances that can cause it to contract.

But Watts and her colleagues wanted to test whether PVAT itself, rather than the substances it secretes, might play a role in how blood vessels perform. So, they decided to test whether PVAT provides a structural benefit to arteries by assisting the function of stress relaxation.

To do that, they tested the thoracic aorta in rats and found those with intact PVAT had more stress relaxation than those without. “My mind was blown,” Watts said when she saw that the pieces with surrounding fat had measurably relaxed more than those without.

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The research team also tested other arteries and were able to duplicate the same response.

“So, this tells us, it’s not just a one off, it’s not something you see only in this particular vessel or this particular species or this particular strain. But that maybe it’s a general phenomenon,” Watts added. (IANS)