KU Medical Center researchers receive a grant to combat radiation-related injury

Not many scientists can claim that they are working full time to improve cancer treatment and combat the effects of bioterrorism, but Suprajit Saha can.

Saha, PhD, associate professor and director of basic science research in the Department of Radiation Oncology at the University of Kansas Medical Center. He has spent the past decade trying to figure out how to reduce the injury caused by radiotherapy to normal tissues that fall into the path of x-rays targeting malignancies. What he and his colleagues learned by solving these biological puzzles could also be applied to help injured people from exposure to radiation in the event of a nuclear accident, missile or bioterrorism.

“Science has this advantage, that if you let your knowledge go out of the box, it can find new problems to solve,” said Saha, who is also part of the Cancer Biology Program at the University of Kansas Cancer Center.

essential question

In the summer of 2022, Saha’s lab at Kuwait University Medical Center, along with collaborators at Children’s Mercy and St. Louis University, received a nearly five-year, $3.6 million grant from the National Institute’s Radiological and Nuclear Countermeasures Program (RNCP). Allergies and infectious diseases. NIAID is the lead institute within the National Institutes of Health to develop medical countermeasures to mitigate and treat radiation injuries. This is the second consecutive grant for his lab from the RNCP, the only research group in Kansas to run a federally funded research program to develop an anti-radiation procedure.

Radiation therapy, which causes DNA breakage and cell death, is more effective than chemotherapy in treating certain types of cancer. However, some parts of the body, such as the gastrointestinal (GI) tract, are particularly susceptible to radiation poisoning and injury. Cells in the digestive system regenerate themselves more often, which means that cells divide more often, making the intestines sensitive to radiation and more susceptible to infection.

Organs such as the intestine are difficult to avoid when treating someone with pancreatic cancer or liver cancer. The result for patients is nausea, diarrhea, vomiting and abdominal pain. The effect of radiation-induced gastrointestinal injury on nuclear blast victims is even greater; It can cause sepsis and death within a few days.

There are no FDA approved medications to prevent or relieve these infections.

“It is also painful for the doctors, because we want the treatment [cancer patients] With our high dose [of radiation]Saha noticed. “So that’s a fundamental question — how can we protect these organs without compromising the treatment itself?”

Evil Pac-Man

The researchers hope this new grant will help them find a strategy to mitigate radiation injury, specifically by blocking a specific type of macrophage from entering tissues targeted by cancer radiotherapy. Macrophages, sometimes called the Pac-Men of the immune system, are white blood cells that gobble up cellular debris while also releasing a variety of beneficial proteins.

In 2016, Saha’s lab found that macrophages can also help repair and regenerate radiation-damaged organs by delivering proteins that stimulate cell proliferation and growth.

But not all macrophages are identical. They are all from the same type of cell, but they can acquire different functions. “It’s kind of like, you’re the same person when it’s 45 degrees and you’re wearing a jacket as you are in the summer when you’re wearing a T-shirt,” Saha said. “But your actions change as the clothes change. The same thing happens with these macrophages.”

The type of macrophage that Saha’s lab will try to block is an inflammatory type, derived primarily from inflammatory white blood cells known as monocytes. These inflammatory cells do the opposite of what is required for radiation injury: they exacerbate the injury. Saha and colleagues want to prevent the recruitment of circulating inflammatory monocytes into injured tissues by inhibiting their interaction with chemokines, which are biochemicals released by the tissue itself.

comprehensive goal

They plan to block it in two different ways, both using a mouse model. First, they’ll use gene editing to knock out chemical receptors on the surface of inflammatory cells. In response to radiation, these receptors promote the recruitment of inflammatory cells to affected tissues. Second, they will try to use a drug compound, a compound already in clinical trials for another type of cancer treatment, to block the interaction of chemokines with these receptors.

If we don’t allow them to be recruited [inflammatory monocytes] To target tissues, like the intestines, we can prevent inflammation and mitigate radiation injury,” Saha said. “So, we can help with the repair process.”

Unlike acute radiation injuries such as those of the intestine, which are known within only a few days, injuries to the lungs of patients being treated for breast or lung cancer can take up to six months to appear. The researchers plan to look at how their experiments affect the repair process in these chronic radiation injuries as well.

And what they learned in the lab to improve cancer care in the clinic could be used in a mass disaster or terrorist situation, a concern that has been growing especially since 9/11, although Saha said he hopes his work can remain confined to the clinic.

“We don’t want any possible treatment for this scenario because nobody wants a nuclear accident,” he said. “Radiation was discovered for the good of mankind, not to destroy it. What we really hope is that we can contribute this knowledge to improve radiotherapy for multiple types of cancer. That is the overarching goal.”

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