Medical Bulletin 05/February/2024

Here are the top medical news of the day:

A new protein linked to metastasis in pancreatic cancer says study

Pancreatic cancer is the No. 3 cause of cancer-related deaths in the United States, and only 12% of patients survive five years after being diagnosed. Severe pancreatic cancer is associated with metastasis, and it is this spread of secondary tumors that usually causes death, but little is known about the molecular mechanisms that drive metastasis.

In a study published in Advanced Science, researchers from the University of California, Davis showed that abnormal expression of the protein Engrailed-1 (EN1) promotes pancreatic cancer progression and metastasis in vitro and in mouse models. The team also found that elevated EN1 was associated with severe, metastatic pancreatic cancer in human patients, which suggests that EN1 might make a good target for pancreatic cancer therapies.

“We identified a novel epigenetic factor that can contribute to metastasis in pancreatic cancer, which is one of the most challenging cancers to treat,” said Chang-Il Hwang, an assistant professor in the UC Davis Department of Microbiology and Molecular Genetics and a senior author on the paper. “A better understanding of these mechanisms would allow us to identify potential targets and improve patient survival.”

One of these proteins, EN1, is essential for the survival of neurons during development and is not usually produced in adult pancreatic cells. EN1 has been shown to promote aggressive forms of breast cancer, and it is also associated with poor prognosis in other cancers, including glioblastoma and salivary gland adenoid cystic carcinoma, but its role in pancreatic cancer had not previously been described.

The researchers tested whether inhibiting EN1 or ramping up its expression impacted the growth and survival of pancreatic cancer “organoids” — three-dimensional clumps of lab-grown tissue. They found that, without EN1, pancreatic cancer cells were less likely to survive and divide, but adding extra EN1 increased the tumors’ survival. Furthermore, when the researchers genetically modified mouse pancreatic cancer cell lines so that they produced more EN1 than usual, the cells showed increased rates of cell invasion and migration, key features of metastasis.

Reference: Researchers identify protein linked to metastasis in pancreatic cancer; Advanced Science; DOI: 10.1002/advs.202308537

Comprehensive care for people with severe epilepsy, guidelines to elevate care

The National Association of Epilepsy Centers (NAEC) has developed updated guidelines that outline the comprehensive services and resources epilepsy centers should provide to improve quality of care for people whose epilepsy is not well-controlled.

An Executive Summary of the 2023 Guidelines for Specialized Epilepsy Centers: Report of the National Association of Epilepsy Centers Guideline Panel was published online on February 2, 2024, in Neurology®, the medical journal of the American Academy of Neurology. The complete NAEC guidelines are published as an eAppendix on the journal’s website.

Epilepsy is one of the most common chronic neurologic conditions worldwide, with an estimated prevalence of 3.4 million in the United States. The condition, which causes recurring seizures, can be debilitating and life-threatening. It is associated with decreased quality of life and far-reaching socioeconomic implications.

About 30 percent of people with epilepsy have seizures that do not respond to medication. Uncontrolled seizures affect all aspects of life, such as the ability to learn or live independently. For these individuals, and those experiencing unacceptable side effects from antiseizure medications, epilepsy centers can provide a more personalized level of care that improves a patient’s total well-being.

The 2023 guidelines include 52 recommendations that span the range of services that should be part of high-quality epilepsy centers, including inpatient evaluation, therapeutic options, and outpatient chronic disease management. The guidelines recognize the importance of multi-disciplinary care teams in coordinating the effort of different specialists working together to diagnose and treat patients.

For the first time, the guidelines recommend centers should

offer genetic testing and counseling.

provide more education and communication for patients.

give greater attention to special needs populations.

employ a care coordinator who organizes and facilitates multidisciplinary care.

provide mental health screening (anxiety, depression, and learning difficulties are much more common in people with epilepsy than the general population).

address health disparities and inequities among the epilepsy patient population.

The recommendations were informed by an evidence review and reflect the consensus of a multidisciplinary panel of 41 stakeholders with diverse expertise, including patient and caregiver representatives, EEG technologists, nurse practitioners, social workers, neurosurgeons, neuroradiologists, and others who support epilepsy center care.

Reference: New guidelines aim to elevate comprehensive care for people with severe epilepsy; Neurology; DOI: 10.1212/WNL.0000000000208087

Common food preservative has unexpected effects on the gut microbiome

Food manufacturers often add preservatives to food products to keep them fresh. A primary purpose of these preservatives is to kill microbes that could break down and otherwise spoil the food. Common additives like sugar, salt, vinegar and alcohol have been used as preservatives for centuries, but modern-day food labels now reveal more unfamiliar ingredients such as sodium benzoate, calcium propionate, and potassium sorbate.

Bacteria produce chemicals called bacteriocins to kill microbial competitors. These chemicals can serve as natural preservatives by killing potentially dangerous pathogens in food. Lanthipeptides, a class of bacteriocins with especially potent antimicrobial properties, are widely used by the food industry and have become known as “lantibiotics” (a scientific portmanteau of lanthipeptide and antibiotics).

Despite their widespread use, however, little is known about how these lantibiotics affect the gut microbiomes of people who consume them in food. Microbes in the gut live in a delicate balance, and commensal bacteria provide important benefits to the body by breaking down nutrients, producing metabolites, and—importantly—protecting against pathogens. If too many commensals are indiscriminately killed off by antimicrobial food preservatives, opportunistic pathogenic bacteria might take their place and wreak havoc—a result no better than eating contaminated food in the first place.

A new study published in ACS Chemical Biology by scientists from the University of Chicago found that one of the most common classes of lantibiotics has potent effects both against pathogens and against the commensal gut bacteria that keep us healthy.

Nisin is a popular lantibiotic used in everything from beer and sausage to cheese and dipping sauces. It is produced by bacteria that live in the mammary glands of cows, but microbes in the human gut produce similar lantibiotics too. Zhenrun “Jerry” Zhang, PhD, a postdoctoral scholar in the lab of Eric Pamer, MD, the Donald F. Steiner Professor of Medicine and Director of the Duchossois Family Institute at UChicago, wanted to study the impact of such naturally-produced lantibiotics on commensal gut bacteria.

“Nisin is, in essence, an antibiotic that has been added to our food for a long time, but how it might impact our gut microbes is not well studied,” Zhang said. “Even though it might be very effective in preventing food contamination, it might also have a greater impact on our human gut microbes.”

Reference: Common food preservative has unexpected effects on the gut microbiome; ACS Chemical Biology, DOI: 10.1021/acschembio.3c00577