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UM researchers identify protein linked to heart failure in chemo patients: Finding could save millions of lives

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November 4, 2022 — 

A team led by Dr. Lorrie Kirshenbaum from the Rady Faculty of Health Sciences and St. Boniface Hospital Research has identified a protein called TRAF2 that stops functioning in cancer patients taking the chemotherapy drug doxorubicin, which can result in heart failure.

“The finding could lead to new drugs that save cancer patients,” said Kirshenbaum, lead investigator and UM Canada Research Chair in molecular cardiology and director of the Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre.

Dr. Lorrie Kirshenbaum

While doxorubicin is used to treat many types of cancer, particularly breast and ovarian cancer, some patients who receive the drug develop heart problems that lead to heart failure.

Using a variety of state-of-the-art approaches, the researchers discovered that doxorubicin impairs the activity of TRAF2 in the heart which leads to heart failure. The team also showed that interventions that restored the TRAF2 activity suppressed the unwanted side effects and heart failure induced by doxorubicin treatment.

“This is a significant finding that we are very excited about,” said Kirshenbaum, professor of physiology & pathophysiology and pharmacology & therapeutics, Max Rady College of Medicine, University of Manitoba. “We discovered that TRAF2 was consistently down-regulated in cancer patients with heart failure who had received doxorubicin treatment. Our pre-clinical study showed that by restoring TRAF2, we could prevent injury to the heart muscle and heart failure induced by doxorubicin.”

The results of the study, titled Proteasomal Degradation of TRAF2 Mediates Mitochondrial Dysfunction in Doxorubicin-Cardiomyopathy, were published in the American Heart Association’s cardiac journal Circulation, the top journal for cardiovascular medicine.

Kirshenbaum said the research has revealed a novel cellular pathway that connects the loss of TRAF2 to the undesirable cardiotoxic effects of doxorubicin that could lead to new ways to completely eliminate this unwanted side-effect in millions of cancer patients.

“Essentially, we’re talking about the difference of the heart tissue surviving unscathed versus experiencing premature and irreversible cell damage as a result of these powerful cancer-treating drugs,” said Dr. Richard Kitsis, professor of medicine and cell biology, director, Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine in New York. “Enhancement of TRAF2 function in the heart may provide a novel therapeutic approach.”

Kirshenbaum and his team are currently working on new therapies and drugs that could be used to prevent cardiac injury in cancer patients undergoing doxorubicin treatment.

Dr. Peter Nickerson, UM vice-provost (health sciences), and dean of the Rady Faculty of Health Sciences, said he’s excited about the study and prospects of new therapies that could improve patient care.

“This study builds upon Dr. Kirshenbaum’s leadership in cardiovascular sciences globally, and importantly, it reflects the high calibre of CIHR funded research at the Rady Faculty of Health Sciences and St. Boniface Hospital Albrechtsen Research Centre,” Nickerson said.

The research was supported by a foundation grant to Kirshenbaum from the Canadian Institutes of Health Research and St. Boniface Hospital Foundation.

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Whooping cough is at a decade-high level in US

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MILWAUKEE (AP) — Whooping cough is at its highest level in a decade for this time of year, U.S. health officials reported Thursday.

There have been 18,506 cases of whooping cough reported so far, the Centers for Disease Control and Prevention said. That’s the most at this point in the year since 2014, when cases topped 21,800.

The increase is not unexpected — whooping cough peaks every three to five years, health experts said. And the numbers indicate a return to levels before the coronavirus pandemic, when whooping cough and other contagious illnesses plummeted.

Still, the tally has some state health officials concerned, including those in Wisconsin, where there have been about 1,000 cases so far this year, compared to a total of 51 last year.

Nationwide, CDC has reported that kindergarten vaccination rates dipped last year and vaccine exemptions are at an all-time high. Thursday, it released state figures, showing that about 86% of kindergartners in Wisconsin got the whooping cough vaccine, compared to more than 92% nationally.

Whooping cough, also called pertussis, usually starts out like a cold, with a runny nose and other common symptoms, before turning into a prolonged cough. It is treated with antibiotics. Whooping cough used to be very common until a vaccine was introduced in the 1950s, which is now part of routine childhood vaccinations. It is in a shot along with tetanus and diphtheria vaccines. The combo shot is recommended for adults every 10 years.

“They used to call it the 100-day cough because it literally lasts for 100 days,” said Joyce Knestrick, a family nurse practitioner in Wheeling, West Virginia.

Whooping cough is usually seen mostly in infants and young children, who can develop serious complications. That’s why the vaccine is recommended during pregnancy, to pass along protection to the newborn, and for those who spend a lot of time with infants.

But public health workers say outbreaks this year are hitting older kids and teens. In Pennsylvania, most outbreaks have been in middle school, high school and college settings, an official said. Nearly all the cases in Douglas County, Nebraska, are schoolkids and teens, said Justin Frederick, deputy director of the health department.

That includes his own teenage daughter.

“It’s a horrible disease. She still wakes up — after being treated with her antibiotics — in a panic because she’s coughing so much she can’t breathe,” he said.

It’s important to get tested and treated with antibiotics early, said Dr. Kris Bryant, who specializes in pediatric infectious diseases at Norton Children’s in Louisville, Kentucky. People exposed to the bacteria can also take antibiotics to stop the spread.

“Pertussis is worth preventing,” Bryant said. “The good news is that we have safe and effective vaccines.”

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AP data journalist Kasturi Pananjady contributed to this report.

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The Associated Press Health and Science Department receives support from the Robert Wood Johnson Foundation. The AP is solely responsible for all content.

The Canadian Press. All rights reserved.

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Scientists show how sperm and egg come together like a key in a lock

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How a sperm and egg fuse together has long been a mystery.

New research by scientists in Austria provides tantalizing clues, showing fertilization works like a lock and key across the animal kingdom, from fish to people.

“We discovered this mechanism that’s really fundamental across all vertebrates as far as we can tell,” said co-author Andrea Pauli at the Research Institute of Molecular Pathology in Vienna.

The team found that three proteins on the sperm join to form a sort of key that unlocks the egg, allowing the sperm to attach. Their findings, drawn from studies in zebrafish, mice, and human cells, show how this process has persisted over millions of years of evolution. Results were published Thursday in the journal Cell.

Scientists had previously known about two proteins, one on the surface of the sperm and another on the egg’s membrane. Working with international collaborators, Pauli’s lab used Google DeepMind’s artificial intelligence tool AlphaFold — whose developers were awarded a Nobel Prize earlier this month — to help them identify a new protein that allows the first molecular connection between sperm and egg. They also demonstrated how it functions in living things.

It wasn’t previously known how the proteins “worked together as a team in order to allow sperm and egg to recognize each other,” Pauli said.

Scientists still don’t know how the sperm actually gets inside the egg after it attaches and hope to delve into that next.

Eventually, Pauli said, such work could help other scientists understand infertility better or develop new birth control methods.

The work provides targets for the development of male contraceptives in particular, said David Greenstein, a genetics and cell biology expert at the University of Minnesota who was not involved in the study.

The latest study “also underscores the importance of this year’s Nobel Prize in chemistry,” he said in an email.

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The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Science and Educational Media Group. The AP is solely responsible for all content.

The Canadian Press. All rights reserved.

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