ROCHESTER, Minn. — Mayo Clinic researchers have identified a protein that acts like a traffic controller for DNA, preventing damage during cell division — a discovery that could lead to new cancer therapies, according to a study published in Nature.

"DNA is the code of life. It's critical for how a cell functions, but it's also critical for our own being and defines what we are," says Zhenkun Lou, Ph.D., the Swanson/Schmucker Endowed Professor to Support Health and Cancer Research at Mayo Clinic and the senior author of the new study.

When cells divide, DNA must be copied from one cell to the next — a process called replication. Dr. Lou's research team discovered that a protein called KCTD10 plays a surprising role in protecting DNA during this critical stage. Acting like a built-in sensor, KCTD10 helps shield the DNA replication machinery from damage. 

Cells also depend on another key process called transcription, where the cell decodes the DNA to create RNA. That RNA then can be translated into proteins, which are essential for healthy tissues and the body's everyday functions.

The problem is that the different machines that run these two processes — replication and transcription — travel on the same strand of DNA, like a narrow highway. The replication machinery moves faster than the transcription machinery. Therefore, collisions resulting in DNA damage inevitably occur. Researchers did not know how cells communicate to prevent or recover from these collisions until now.

Dr. Lou's research team saw that KCTD10 can sense when a collision is about to occur and act like a traffic controller, triggering a series of responses to prevent it. The protein activates an enzyme called CUL3 that steps in to tell the slower transcription machinery to move aside and allow the replication machinery to pass, avoiding harmful breaks to the DNA. CUL3 and KCTD10 achieve this through a process called ubiquitination that removes the proteins in front of the replication machinery.

It has long been observed that DNA replication and transcription run in the same direction. The findings in this study suggest that KCTD10 may play a significant part in this, shaping the overall organization of the human genome.

Killing cancer cells

"I became interested in the idea that if we can better understand how these processes normally occur, then we can more effectively target cancer cells where these processes malfunction, tipping them over the edge towards cell death," says Jake Kloeber, an M.D.-Ph.D. student and co-lead author of the study. He conducted the study in the Ph.D. component of his dual degree at Mayo Clinic Graduate School of Biomedical Sciences and Mayo Clinic Alix School of Medicine. Kloeber plans to pursue a career as a physician-scientist in radiation oncology.

When KCTD10 is missing, it leads to genomic instability and mutations that can result in tumor formation. Previous research has also shown that developmental delays are linked to the loss of KCTD10.

On the other hand, in cancer cells that lack the protection of KCTD10 because the replication and transcription machinery do not work properly, the missing protein can serve as a biomarker for the vulnerability of these cancer cells.

"We can take advantage of that and attack those cancer cells when they are most vulnerable, which opens a new therapeutic window for us to treat certain types of cancer," says Dr. Lou.

Next steps in this research are identifying which types of cancer are missing this protein and pinpointing ways to target those cancer cells with new or existing cancer drugs. 

The research is part of a larger effort at Mayo Clinic called the Precure initiative focused on developing tools that empower clinicians to predict and intercept biological processes before they evolve into disease or progress into complex, hard-to-treat conditions.

Review the study for a complete list of authors, disclosures and funding. 

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

• Julie Ferris-Tillman, Mayo Clinic Communications, newsbureau@mayo.edu

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The needs of patients are at the forefront of healthcare transformation through artificial intelligence (AI). This was the overarching theme at Mayo Clinic's AI Summit, held recently in Rochester, Minnesota.  

Dr. Cui Tao, chair of Mayo Clinic's Department of Artificial Intelligence and Informatics and the Nancy Peretsman and Robert Scully Chair of AI and Informatics, opened the summit by sharing that the goal of the event was to explore how AI can be used to potentially revolutionize healthcare and biomedicine.  

The summit, which brought together clinicians, scientists, engineers and innovators, was chaired by Dr. Hamid Tizhoosh and Dr. Fred Fan, both from the Department of Artificial Intelligence and Informatics. 

These were some key takeaways from the event:  

Patient needs drive AI innovation 

Dr. Clark Otley, chief medical officer of Mayo Clinic Platform, emphasized that Mayo Clinic's leadership in AI is rooted in its responsibility to best serve the needs of patients. He said patients want to see improved, accessible, personalized and affordable care, along with trusted information and privacy protection.  

Dr. Matthew Callstrom, medical director of Mayo Clinic's Generative Artificial Intelligence Program, added, "When you start talking to patients about how important AI will be for their healthcare, they start to raise their hand and say, 'Please include me. I want to have the best possible outcomes.'" 

Transforming medicine from reactive to proactive care 

Summit speakers highlighted the need for a shift from reactive, symptom-based healthcare to proactive, preemptive care.  

Dr. Callstrom shared the story of a patient with rheumatoid arthritis whose disease had progressed to joint destruction and chronic symptoms, due to the need to trial different treatments with the current standard of care. He said AI may have the potential to improve outcomes for such patients.  

"If we use the data in a different way — if we start to be able to predict outcomes for patients for methotrexate, for targeted therapies — maybe we can get onto the right therapy sooner," he said.  

Mayo Clinic Platform: A foundation for innovation 

Mayo Clinic Platform, a key initiative in Mayo's Bold. Forward. strategy, is building a rich dataset of de-identified patient data to drive innovation that will help realize this vision. 

Dr. Otley outlined Mayo Clinic Platform's strategy for responsible AI implementation, including ethical development and deployment, human-centered design, and scientific evidence. He highlighted the importance of supporting healthcare teams in using AI to augment patient care.  

AI applications across specialties offer practical solutions 

Dr. Otley shared AI's promise in specialties such as radiology, mammography, personalized medicine and mental health, emphasizing its potential to help healthcare professionals improve diagnostic accuracy, efficiency and access to care.  

Dr. Callstrom highlighted AI-powered tools for reducing administrative burden by streamlining medical records review and clinical decision-making, improving diagnostic accuracy through voice analysis and digital pathology, and ongoing research in genomics and cancer care.  

He emphasized the need for practical solutions that help healthcare professionals, such as an application that can remotely monitor patients and alert their care team to assist and prevent patient falls if necessary. 

Other featured speakers were Dr. Jeroen van der Laak, Radboud University Medical Center; Dr. Yifan Peng, Weill Cornell Medicine; and Dr. Greg Corrado, Google Research.   

Watch the AI Summit keynotes and panel discussions. 

Related post:

• Advancing AI in healthcare: Highlights from Mayo Clinic's 2024 AI Summit 

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During the Undiagnosed Hackathon, which was hosted by the Wilhelm Foundation in collaboration with Mayo Clinic, each ring of the bell became a symbol of discovery and global unity. 

Inside Mayo Clinic, a bell rang six times, each chime signaling that a diagnosis was discovered for another person with a rare and undiagnosed condition. For at least eight more families, scientists believe answers are within reach. 

These breakthroughs unfolded during the first U.S.-based Undiagnosed Hackathon, held Sept. 21–23 — an intensive, three-day effort to solve 29 rare disease cases that had resisted explanation. The event drew nearly 130 researchers, clinicians and data scientists from 28 countries, reflecting a global spirit united in the pursuit of answers. 

The hackathon was founded by the Wilhelm Foundation, established by Helene and Mikk Cederroth of Sweden after losing three children to an undiagnosed condition. Their commitment to international collaboration created the model for events like this, tackling the rarest and most complex diseases. 

Laptops, whiteboards and hope 

In hackathon rooms, scientists leaned over laptops, combing through millions of data points from DNA, RNA and the chemical signals that control genes. Whiteboards were filled with gene names and arrows mapping possible pathways. At one table, a group debated whether a rare mutation explained symptoms. Across the room, others scoured medical literature. Every clue was weighed against the rest. 

Confirming a diagnosis meant more than spotting a mutation. In many ways, DNA tells a story: a typo, a missing page, a chapter read out of order, an extra paragraph. The challenge was proving whether the story matched the patient's symptoms. Piece by piece, teams layered evidence until they could call it a diagnosis — and ring the bell. 

When one diagnosis reaches further 

Each solved case carried weight beyond the room. A single diagnosis can redefine a condition worldwide, guiding care for others with similar symptoms. To build on that progress, hackathon data and tools will remain open through the year's end, with biweekly meetings planned to pursue the unsolved cases. 

"The sun has set on working one genetic test at a time for complex patient cases," says Dr. Eric Klee, the Everett J. and Jane M. Hauck Midwest Associate Director of Research and Innovation and co-leader of the hackathon. "We can now see the bigger picture, and I look forward to the day when every diagnosis leads to action." 

His co-leader, Dr. Cherisse Marcou, assistant professor and co-director of the Clinical Genomics laboratory echoed the sentiment: "When people and ideas come together, barriers fall. This week we witnessed that truth, fueled by the tireless commitment of everyone devoted to this cause." 

Rare diseases affect an estimated 350 million people worldwide, yet only about 40 percent of cases yield to existing diagnostics, and even fewer have treatment options. 

Searching for treatments 

Finding a diagnosis is often the first breakthrough. The next challenge is turning knowledge into care. Sometimes Mayo scientists test existing drugs to see if one approved for another condition might help. In others, they study patient-derived cells to understand how a mutation alters function and whether a drug might counter it. Artificial intelligence also helps clinicians sift through vast libraries of potential drugs. The goal: ensure that a genetic answer is not the end of the story, but the beginning of care. 

A global lens on rare disease

The momentum of the hackathon carried into Mayo's Rare Disease Symposium, where the conversation widened to global challenges in diagnosis and treatment. 

Keynote speaker Dr. Salman Kirmani of Aga Khan University in Pakistan, and a former Mayo Clinic physician, reminded the audience that for much of the world, even inconclusive testing remains out of reach.

"Most families are not just undiagnosed. They are untested," he said. He noted another barrier: genomic reference databases remain overwhelmingly Eurocentric, skewing interpretations and limiting accuracy. "Data diversity is not a matter of fairness alone," he argued. "It is a diagnostic tool. Without it, families remain invisible." 

Hope rings out 

From hackathon rooms to the symposium stage, the message was the same: progress against rare disease depends on collaboration across borders and disciplines. 

Each time the bell rang, scientists cheered and exchanged hugs, then quickly returned to their work. Beyond the celebration, the bell stood as a symbol of what science can achieve when pursued together. 

The post Sounds of discovery ring at the Undiagnosed Hackathon appeared first on Mayo Clinic News Network.

Researchers are leading the nation in developing powerful and precise radiopharmaceutical theranostics intended to treat people with deadly cancers.  

ROCHESTER, Minn. — Mayo Clinic recently became the first institution to administer an investigational radioactive medicine to a patient with hepatocellular carcinoma (HCC), the most common type of liver cancer. The investigational medicine is a targeted radiopharmaceutical theranostic (RPT) that is designed to target a novel protein called glypican-3 (GPC3). The RPT was administered to the patient as part of a first-in-human clinical trial for the targeted therapy. This investigational RPT includes both a diagnostic imaging agent, intended to identify the cancer cells, and a therapeutic agent, intended to target and kill cancer cells.

GPC3 was identified as a potentially viable and promising target because it is produced at higher levels in HCC tissue than in a normal, healthy adult liver. It is also considered an oncofetal cell surface protein because GPC3 is normally only active during fetal development. In adults, the protein is turned off, but when cancer forms, it "reawakens" the protein to support rapid growth and evade the immune system. This means that GPC3 is found only on cancer cells, which makes it a strong potential target for treatment.  

With this knowledge, Mayo Clinic researchers are participating in a first-in-human clinical trial investigating alpha-emitting RPTs, which use alpha particle radiation to precisely and powerfully diagnose, target, and potentially kill cancer cells. In this trial, the RPT includes an agent that binds to GPC3.

The phase 1/1b study is being conducted at all three academic Mayo Clinic sites in Rochester; Phoenix; and Jacksonville, Florida. The first person to receive the clinical trial procedure was at Mayo Clinic in Florida.

"Whole-body GPC3 targeted molecular imaging shows high localization to the tumor and minimal accumulation in normal tissues, indicating that the therapeutic radiation effects will be limited to sites of disease," says Ephraim Parent, M.D., Ph.D., a radiologist and division chair of Nuclear Medicine at Mayo Clinic in Florida. Dr. Parent is co-principal investigator on the trial.

Mayo Clinic in Florida researchers recently were the first in the U.S. to apply an investigational alpha-emitting radiopharmaceutical therapy in a treatment setting to a patient living with metastatic breast cancer. Mayo Clinic has now marked another remarkable first by delivering a different novel alpha-emitting investigational therapy to a patient with liver cancer, the second-leading cause of cancer-related deaths worldwide.

"At Mayo Clinic, we are committed to advancing innovative therapies that expand possibilities for those facing this devastating disease," says Lionel Kankeu Fonkoua, M.D., a medical oncologist at Mayo Clinic in Rochester and principal investigator of the trial. "Being able to offer access to this novel radiopharmaceutical approach reflects our dedication to pushing the boundaries of liver cancer care."

The drug for the study is being developed by RayzeBio Inc., a Bristol Myers Squibb Company, the sponsor of the active phase 1/1b clinical trial.

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Study Title: Study of the Theranostic Pair RYZ811 (Diagnostic) and RYZ801 (Therapeutic) to Identify and Treat Subjects with GPC3+ Unresectable HCC (GPC3)

• Descriptor: Study of the Theranostic Pair RYZ811 (diagnostic) and RYZ801 (therapeutic) to Identify and Treat Subjects with GPC3+ Unresectable HCC
• Principal Investigators: Principal investigators at Mayo Clinic are Lionel Kankeu Fonkoua, M.D.; Umair Majeed, M.B.B.S., M.D.; and Mitesh Borad, M.D. Co-principal investigators are Ephraim Parent, M.D., Ph.D.; Geoffrey Johnson, M.D., Ph.D.; and Felipe Martinez, M.D.
• Sponsor: RayzeBio Inc.
• Link: www.mayo.edu/research/clinical-trials/cls-20583570  

About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

• Brittany Cordeiro, Mayo Clinic Communications, newsbureau@mayo.edu

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Mayo Clinic will lead the Hospital Air QUality (HAIQU): Breathing Life into Patient Care project, focusing on improving indoor air quality in hospitals to enhance health. "Maintaining high indoor air quality is essential to supporting respiratory health and preventing the spread of airborne illnesses — just one of the many ways we prioritize staff, patient and visitor well-being," says Connie Chang, Ph.D., associate professor of biomedical engineering at Mayo Clinic and the project's principal investigator. "This initiative will push innovation in public health as we study and design systems that can continuously monitor air quality in real time and establish cost-effective interventions."

Through the HAIQU project, Mayo Clinic will introduce cutting-edge biosensors, artificial intelligence and smart air filtration systems in emergency departments across Mayo Clinic's campuses in Florida, Arizona and Minnesota. These innovative technologies work together to enhance air quality by proactively monitoring the environment, assessing potential risks and automatically improving air safety when needed — creating healthier spaces for patients and care teams alike.

The work is directly aligned with the design priorities of Bold. Forward. Unbound., which emphasizes clean, flexible and intelligent environments to support optimal healing.

"This award reinforces Mayo Clinic's commitment to harnessing the power of technology and data to prevent illness before it starts," says Vijay Shah, M.D., Kinney Executive Dean of Research at Mayo Clinic. "Our research will help create resilient clinical systems capable of sensing, interpreting and responding to data in real time, making the hospital of the future even more sophisticated for our patients."

The project will unfold in three phases over five years, beginning with the development of a biosensor to monitor emergency room air for aerosols such as viruses, bacteria, mold and allergens. Once validated, the system will undergo real-world testing and could lay the foundation for future indoor air quality standards and public health policies.

The Mayo Clinic-led effort includes a multidisciplinary team of collaborators from Siemens Corporation, Metalmark Innovations, Princeton University, University of Minnesota Twin Cities, and The University of Chicago. The coalition brings together expertise from the healthcare, biotechnology and academic sectors. Mayo team members also include Jim Wilking, Ph.D. (biomedical engineering), who will lead the engineering effort to design the biosensor; Chung Wi, M.D. (Precision Population Science Laboratory), who will lead a clinical study to validate the research; Alexander Revzin, Ph.D. (biomedical engineering); Clifton Haider, Ph.D. (biomedical engineering); Priya Sampathkumar, M.D. (infectious diseases); Casey Clements, M.D., Ph.D. (emergency medicine, Minnesota); Andrej Urumov, M.D. (emergency medicine, Arizona); and Jesse St Clair IV, M.D. (emergency medicine, Florida). 

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

• Julie Ferris-Tillman, Mayo Clinic Communications, newsbureau@mayo.edu

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Dr. Richard Sharpe Jr., a Mayo Clinic radiologist, says it's crucial to talk with your healthcare team to find the screening method that is right for you. An MRI is one option. Reporter Jason Howland has more.

Watch: The Mayo Clinic Minute

Journalists: Broadcast-quality video (1:00) is in the downloads at the end of this post. Please courtesy: "Mayo Clinic News Network." Read the script.

"The first thing to know if you get notified is that dense breast tissue is completely normal. 

Half of all women will have dense tissue," says Dr. Sharpe.

He says dense breasts are identified through a mammogram. Additional testing is the next step.

"The most widely available supplemental screening test for women with dense tissues is probably an ultrasound of the breast or an MRI," says Dr. Sharpe. "There have been lots of studies showing that MRI is the most sensitive test for finding breast cancer."

An MRI is meant to be used along with a mammogram, not instead.

"MRI is the most sensitive test we have for finding breast cancer. It can see through density. It can find hard-to-see, small cancers," says Dr. Sharpe.

But it's not for everyone. You'll lie face down on a table and then guided into the MRI machine."Some patients that have challenges with claustrophobia might struggle to be comfortable in the smaller space of the MRI scanner," explains Dr. Sharpe.

The benefit is clear, he says.

"Women with dense tissue or high risk for breast cancer that undergo breast MRI, we are able to see cancers that would be hiding from the mammogram."

Supplemental screening options

Other supplemental screening options include molecular breast imaging (MBI), ultrasound and contrast-enhanced mammography. 

Dr. Sharpe says choosing what screening method works for you is an individual decision that should be made with your healthcare team, but he says it's important to start with your annual screening.

"The most important thing for women to know is that you should get your annual mammogram, starting at age 40. Also, if you have dense tissue, consider a supplemental screening, another imaging test looking at the breast tissues in a different way — and you should get that exam regularly as well," he says.

"The most important thing for women to know is that you should get your annual mammogram, starting at age 40. Also, if you have dense tissue, consider a supplemental screening, another imaging test looking at the breast tissues in a different way — and you should get that exam regularly as well," he says.

Related posts:

• Mayo Clinic leads 4 decades of advances in breast cancer care
• Mayo Clinic research improves dense breast cancer screening and early detection
• Top 10 questions about breast cancer answered
• Mayo Clinic treats first person in the US with a novel radiopharmaceutical therapy for breast cancer

The post Mayo Clinic Minute: MRI for dense breasts — what to know appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — Early detection is key to breast cancer survival. But nearly half of all women in the U.S. have dense breast tissue, which can make detecting breast cancer difficult with a mammogram. Mayo Clinic researchers found that adding another test, called molecular breast imaging, or MBI, to a 3D mammogram improved the ability to find cancer in dense tissue by more than double.
 
"A mammogram is an important screening test that has been proven beneficial. But we've learned that in areas of dense breast tissue, breast cancers can hide from detection on a mammogram until they reach an advanced size. Our research focuses on detecting the most lethal cancers, which can include invasive tumors that grow quickly. If these are detected earlier, we likely can save more lives," says Carrie Hruska, Ph.D., a professor of medical physics and the lead author of a study published in Radiology. 

She and her research team studied 2,978 women with dense breasts between 40-75 years old at five separate centers. The study participants received two annual breast cancer screenings that included the combination of a supplemental MBI test and a 3D mammogram, also called digital breast tomosynthesis. 

Breast radiologists detected more cancerous tissue from the combined MBI and mammography screenings compared to either technique alone.

"MBI is a fairly simple, low cost and safe option for women who have dense breasts and are seeking a supplemental screening test," says Dr. Hruska.

MBI combined with a mammogram is available at about 30 sites in the U.S., including Mayo Clinic Health System in La Crosse, Wisconsin; Mayo Clinic Health System in Eau Claire, Wisconsin; and Mayo Clinic campuses in Rochester, Phoenix, and Jacksonville, Florida.

With more screening, there is a risk of being called back for additional testing to evaluate the findings. The researchers were pleased to find that although the addition of MBI to mammography led to 279 more women being called back in the first year of screening, this rate of callbacks decreased by half in the second round of screening.

Next steps to improve breast cancer screening

Dr. Hruska's team is working on developing an algorithm that would cut the time it takes from 40 minutes to about 20 minutes or less to capture an image using this technique. This would make it more comfortable for women and enable more women to schedule this screening.

Review the study for a complete list of authors, disclosures and funding.

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news. 

Media contact:

• Julie Ferris-Tillman, Mayo Clinic Communications, newsbureau@mayo.edu
    
   
  

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ROCHESTER, Minn. — A new international study led by Mayo Clinic researchers has identified a genetic factor that may explain why some patients with colorectal cancer that has spread to the liver experience more severe liver damage after chemotherapy.

For patients with colorectal liver metastases, surgery offers the best chance of long-term survival. To improve outcomes, many patients receive chemotherapy before surgery. While this approach can shrink tumors to make them more operable, one potential side effect is injury to the liver. Until now, it hasn't been clear why certain patients' livers are more prone to chemotherapy-associated liver injury.

"This is the first study to clearly show that a genetic predisposition plays a significant role in how the liver tolerates chemotherapy," says Patrick Starlinger, M.D., Ph.D., a Mayo Clinic Comprehensive Cancer Center hepatobiliary and pancreas surgeon and senior author of the study published in The Lancet eBioMedicine.

In this study, the researchers reviewed 551 patients who had chemotherapy followed by surgery to remove the tumor. They looked at liver health tests to see how chemotherapy affected liver function and genetic markers that are already linked to liver disease in other settings. 

They found that a specific gene variant in the PNPLA3 gene, which is known to affect fat metabolism in the liver, was strongly linked to liver injury after chemotherapy. Patients with two copies of this variant were especially vulnerable, and all of them developed signs of significant liver injury after chemotherapy.

Genetic differences help explain global variation

According to Dr. Starlinger, the PNPLA3 variant is common worldwide, but its prevalence differs by population. For example, in Japan, the mutation is present in more than 41% of the population. It's found in more than 71% among people of Peruvian descent, but fewer than 10% of people in some European populations have it.

Because the genetic variation is more common in certain groups, such as people of Asian or Latin American descent, this may help explain why previous studies in different countries have reported conflicting results about the benefits of giving chemotherapy before and/or after surgery when treating colorectal liver metastases.

Personalizing care to maximize benefit, minimize risk

The findings suggest that a blood test to check for the PNPLA3 variant, along with monitoring liver health, could help doctors identify patients at higher risk for liver damage from chemotherapy.

"These findings offer us insight into how we can adjust treatment strategies to best manage the care for patients diagnosed with colorectal liver metastases, while potentially avoiding a negative side effect of chemotherapy," says Dr. Starlinger. "Chemotherapy may still be an appropriate treatment option, and with this information, we can personalize treatment for each patient — for example, tailoring chemotherapy or allowing more time for the liver to recover before surgery."

For a complete list of authors, disclosures and funding, review the study.

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About Mayo Clinic 
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news. 

Media contact: 

• Chloe Corey, Mayo Clinic Communications, newsbureau@mayo.edu

The post New study links genetic variation to chemotherapy-related liver damage in patients with colorectal cancer liver metastases appeared first on Mayo Clinic News Network.

Mayo Clinic researchers found that transplanting patients' own stem cells from fat cells into the vein often helped prevent inflammation and vein narrowing. This could help millions of people with end-stage kidney disease tolerate dialysis longer, extending the time before they require a kidney transplant.

That is because these adult stem cells called mesenchymal stem cells secrete healing growth factors that appear to be effective for certain patients with an AVF, according to Sanjay Misra, M.D., a Mayo Clinic interventional radiologist and senior author of the study published in Science Translational Medicine.

"Mesenchymal stem cells have anti-inflammatory properties," he says. "Inflammation is a significant problem, especially in Western society, because it's a hallmark of a lot of medical problems: heart disease, vascular disease, hypertension, high cholesterol and cancer. They are all driven by inflammation."

Dr. Misra collaborates with other physicians and researchers to explore stem cell therapies for a variety of diseases, from inflammatory bowel disease to osteoarthritis. However, his lab's primary focus is on the mechanisms that lead to the failure of hemodialysis graft, a surgical procedure that creates a permanent access point in the bloodstream for hemodialysis.

Improving kidney disease treatment options

In this study, 21 participants received AVFs as part of a phase I clinical trial. Eleven participants were injected with their own fat-derived mesenchymal stem cells before AVF surgery; 10 were part of the control group. The AVFs healed faster and were more durable in most of those who received the stem cells. However, not everyone responded to them.

"We were surprised by these differences in response to the mesenchymal stem cells. This spurred us to delve further into our research and include preclinical models and RNA sequencing technology," says lead author Sreenivasulu Kilari, Ph.D.

The researchers identified specific anti-inflammatory gene factors in those who responded well to the stem cells. They say these genetic biomarkers could help predict which patients are most likely to benefit from this stem cell application and help inform personalized treatment options. The researchers hope to garner more information through larger clinical trials.

This research was supported by Michael S. and Mary Sue Shannon through the Mayo Clinic Center for Regenerative Biotherapeutics. It sets the stage for Genesis, Mayo Clinic's initiative to advance new cures for end-organ failure beyond traditional transplantation.

Review the study for a complete list of authors, disclosures and funding. 

Additional resources:
Stem cell research to improve hemodialysis

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

• Kelley Luckstein, Mayo Clinic Communications, newsbureau@mayo.edu
  
  

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ROCHESTER, Minn. — Mayo Clinic researchers have developed artificial intelligence (AI) tools that help identify which children with asthma face the highest risk of serious asthma exacerbation and acute respiratory infections. The study, published in the Journal of Allergy and Clinical Immunology, found the tools can detect those risks as early as age 3. 

The work is part of Mayo Clinic's Precure strategic priority, which aims to predict and prevent serious diseases before they advance. Through innovative technologies and population-based studies, precure is designed to bring prevention-focused care directly to patients sooner. 

Toll of childhood asthma

Asthma affects nearly 6 million U.S. children and is a leading cause of missed school, emergency visits and hospital stays, according to the Centers for Disease Control and Prevention. Respiratory infections are the most common trigger of asthma attacks, but symptoms vary widely and change over time. That makes it hard for clinicians to know which children are most vulnerable, a gap these AI tools are designed to help address. 

"This study takes us a step closer to precision medicine in childhood asthma, where care shifts from reactive care for advanced severe asthma to prevention and early detection of high-risk patients," says Young Juhn, M.D., M.P.H., professor of pediatrics at Mayo Clinic and senior author of the study. Dr. Juhn directs several Mayo Clinic research programs, including the AI Program of Mayo Clinic Children's, the Precision Population Science Lab and the HOUSES socioeconomic health program. 

New AI tools for early detection

For the study, researchers examined electronic health records from more than 22,000 children born between 1997 and 2016 in southeastern Minnesota. To interpret the data at scale, they developed multiple artificial intelligence tools that use machine learning and natural language processing to extract details from doctors' notes. 

The tools captured information such as symptoms and family history, allowing the team to apply two widely used diagnostic checklists for asthma in young children: the Predetermined Asthma Criteria and the Asthma Predictive Index. These checklists are how clinicians assess signs such as recurring wheezing, coughs or allergic conditions. Children who met the criteria on both lists formed a distinct subgroup at higher risk for serious complications. 

Asthma risk revealed by age 3

When researchers compared this subgroup with other children in the study, the differences were clear. By age 3, the subgroup members were experiencing pneumonia more than twice as often and influenza nearly three times as often. They also had the highest rates of asthma attacks requiring steroids, emergency visits or hospitalization. Respiratory syncytial virus (RSV) infection was also more common in this group during their first three years of life.  

Children in this subgroup were more likely to have a family history of asthma, eczema, allergic rhinitis or food allergies. Further, their laboratory tests from a previous study showed signs of allergic inflammation — including higher eosinophil counts, allergen-specific IgE and periostin, which reflect type 2 inflammation — as well as impaired lung function. Together, the findings point to a high-risk asthma subtype that makes some children more vulnerable to acute respiratory infections and asthma exacerbation. 

Next steps

The research team plans to test the tools in broader clinical settings as well as more diverse populations and health systems. They aim to combine the tools with biological data to refine how asthma subtypes are defined and treated early. 

The team is also planning a study to explore a compound that could calm overactive immune responses linked to asthma. By using lab-grown cell models, known as organoids, they hope to find ways to detect and prevent childhood asthma earlier and on a larger scale.      

This research was supported by a National Institutes of Health–funded R01 grant. For a complete list of authors, disclosures and funding, review the study.   

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About Mayo Clinic 
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news. 

Media contact:  

• Terri Malloy, Mayo Clinic Communications, newsbureau@mayo.edu 

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