Health
Nutrient found in beef and dairy improves immune response to cancer
Newswise — Trans-vaccenic acid (TVA), a long-chain fatty acid found in meat and dairy products from grazing animals such as cows and sheep, improves the ability of CD8+ T cells to infiltrate tumors and kill cancer cells, according to a new study by researchers from the University of Chicago.
The research, published this week in Nature, also shows that patients with higher levels of TVA circulating in the blood responded better to immunotherapy, suggesting that it could have potential as a nutritional supplement to complement clinical treatments for cancer.
“There are many studies trying to decipher the link between diet and human health, and it’s very difficult to understand the underlying mechanisms because of the wide variety of foods people eat. But if we focus on just the nutrients and metabolites derived from food, we begin to see how they influence physiology and pathology,” said Jing Chen, PhD, the Janet Davison Rowley Distinguished Service Professor of Medicine at UChicago and one of the senior authors of the new study. “By focusing on nutrients that can activate T cell responses, we found one that actually enhances anti-tumor immunity by activating an important immune pathway.”
Finding nutrients that activate immune cells
Chen’s lab focuses on understanding how metabolites, nutrients and other molecules circulating in the blood influence the development of cancer and response to cancer treatments. For the new study, two postdoctoral fellows, Hao Fan, PhD and Siyuan Xia, PhD, both co-first authors, started with a database of around 700 known metabolites that come from food and assembled a “blood nutrient” compound library consisting of 235 bioactive molecules derived from nutrients. They screened the compounds in this new library for their ability to influence anti-tumor immunity by activating CD8+ T cells, a group of immune cells critical for killing cancerous or virally infected cells.
After the scientists evaluated the top six candidates in both human and mouse cells, they saw that TVA performed the best. TVA is the most abundant trans fatty acid present in human milk, but the body cannot produce it on its own. Only about 20% of TVA is broken down into other byproducts, leaving 80% circulating in the blood. “That means there must be something else it does, so we started working on it more,” Chen said.
The researchers then conducted a series of experiments with cells and mouse models of diverse tumor types. Feeding mice a diet enriched with TVA significantly reduced the tumor growth potential of melanoma and colon cancer cells compared to mice fed a control diet. The TVA diet also enhanced the ability of CD8+ T cells to infiltrate tumors.
The team also performed a series of molecular and genetic analyses to understand how TVA was affecting the T cells. These included a new technique for monitoring transcription of single-stranded DNA called kethoxal-assisted single-stranded DNA sequencing, or KAS-seq, developed by Chuan He, PhD, the John T. Wilson Distinguished Service Professor of Chemistry at UChicago and another senior author of the study. These additional assays, done by both the Chen and He labs, showed that TVA inactivates a receptor on the cell surface called GPR43 which is usually activated by short-chain fatty acids often produced by gut microbiota. TVA overpowers these short-chain fatty acids and activates a cellular signaling process known as the CREB pathway, which is involved in a variety of functions including cellular growth, survival, and differentiation. The team also showed that mouse models where the GPR43 receptor was exclusively removed from CD8+ T cells also lacked their improved tumor fighting ability.
Finally, the team also worked with Justin Kline, MD, Professor of Medicine at UChicago, to analyze blood samples taken from patients undergoing CAR-T cell immunotherapy treatment for lymphoma. They saw that patients with higher levels of TVA tended to respond to treatment better than those with lower levels. They also tested cell lines from leukemia by working with Wendy Stock, MD, the Anjuli Seth Nayak Professor of Medicine, and saw that TVA enhanced the ability of an immunotherapy drug to kill leukemia cells.
Focus on the nutrients, not the food
The study suggests that TVA could be used as a dietary supplement to help various T cell-based cancer treatments, although Chen points out that it is important to determine the optimized amount of the nutrient itself, not the food source. There is a growing body of evidence about the detrimental health effects of consuming too much red meat and dairy, so this study shouldn’t be taken as an excuse to eat more cheeseburgers and pizza; rather, it indicates that nutrient supplements such as TVA could be used to promote T cell activity. Chen thinks there may be other nutrients that can do the same.
“There is early data showing that other fatty acids from plants signal through a similar receptor, so we believe there is a high possibility that nutrients from plants can do the same thing by activating the CREB pathway as well,” he said.
The new research also highlights the promise of this “metabolomic” approach to understanding how the building blocks of diet affect our health. Chen said his team hopes to build a comprehensive library of nutrients circulating in the blood to understand their impact on immunity and other biological processes like aging.
“After millions of years of evolution, there are only a couple hundred metabolites derived from food that end up circulating in the blood, so that means they could have some importance in our biology,” Chen said. “To see that a single nutrient like TVA has a very targeted mechanism on a targeted immune cell type, with a very profound physiological response at the whole organism level—I find that really amazing and intriguing.”
The study, “Trans-vaccenic acid reprograms CD8+ T cells and anti-tumor immunity,” was supported by the National Institutes of Health (grants CA140515, CA174786, CA276568, 1375 HG006827, K99ES034084), a UChicago Biological Sciences Division Pilot Project Award, the Ludwig Center at UChicago, the Sigal Fellowship in Immuno-oncology, the Margaret E. Early Medical Research Trust, the AASLD Foundation a Harborview Foundation Gift Fund, and the Howard Hughes Medical Institute.
Source: University of Chicago Medical Center
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Lifestyle
Clinical Trials Expand Patients’ Treatment Options
Clinical trials play a crucial role in developing effective treatments for chronic health conditions. They evaluate safety and efficacy, but low enrollment delays drug approvals, limiting patient options.
(Family Features) For health conditions with no cure, effective treatments are the next best option. However, in order to make medical interventions including new drugs, devices, vaccines and lifestyle modifications available, they must undergo a thorough evaluation process to demonstrate their benefits.
Clinical trials are an important part of this process because they provide data for researchers on the effectiveness of various treatments and interventions. However, many myths about clinical trials deter people from enrolling. In fact, more than 70% of clinical trials are delayed at least one month due to unfulfilled enrollment, according to the “Journal of Medical Internet Research.”
Delays create barriers to the drug approval process and result in fewer available treatments for chronic conditions like Crohn’s disease and ulcerative colitis. The experts at the Crohn’s & Colitis Foundation offer these facts about the importance of clinical trials:
- More patients can benefit from clinical trials While hundreds of participants may take part in a trial, the results can lead to new care and treatment options for an entire patient community.
- Clinical trials lead to better and improved medications. For a new treatment to be approved, it needs to demonstrate a meaningful benefit to patients, such as improved outcomes, treating a wider range of symptoms, fewer side effects or more convenience for patients.
- They provide information. Clinical trials provide evidence of a treatment’s effectiveness and safety that can be used to guide patient care.
- Trials test safety and efficacy. Clinical trials are conducted in four phases. During the first phase, the main objective is to assess the safety of a new treatment. Experimental treatments only advance to the next stages if they pass certain safety and efficacy standards
. - They help prevent bias. In a randomized controlled trial, the effects of treatment with a new drug are compared with that of a control group – either a placebo (a treatment that looks identical to the new drug but contains no active medicine) or the current standard of care. Treatment assignments are “randomized,” which means neither the trial doctors nor the participants choose which treatment each participant will receive.
How Clinical Trials Work
Before a clinical trial begins, a research team develops a clinical trial protocol. This is the research plan that describes who can join the trial, which treatments the participants will receive, what questions the researchers will try to answer, how long the trial will last and how participant privacy and safety will be protected.
Conducting clinical research relies on volunteer trial participants. Those interested in joining a clinical trial meet with clinical research professionals to discuss the trial, treatments, eligibility requirements and expectations.
Joining a Trial
If you are interested in participating in a clinical trial, do some research. Your doctor may not be aware of or proactively tell you about trials you may be eligible to join. If you find a clinical trial you may be interested in joining, discuss the trial with your doctor and other health care professionals on your research team.
Foundations supporting chronic conditions can be a good source of information. For example, you can learn more about trials affecting individuals with inflammatory bowel disease by exploring the Clinical Trials Community at crohnscolitisfoundation.org.
Photo courtesy of Shutterstock
SOURCE:
Crohn’s & Colitis Foundation
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Lucas A. Berenbrok, University of Pittsburgh; Michael Murphy, The Ohio State University, and Sophia Herbert, University of Pittsburgh
Neighborhood pharmacies are rapidly shuttering.
Not long ago, Walgreens, one of the nation’s biggest pharmacy chains, announced plans to close 1,200 stores over the next three years. That’s part of a larger trend that has seen nearly 7,000 pharmacy locations close since 2019, with more expected in the coming years.
Many community pharmacies are struggling to stay open due to an overburdened workforce, shrinking reimbursement rates for prescription drugs and limited opportunities to bill insurers for services beyond dispensing medications.
As trained pharmacists who advocate for and take care of patients in community settings, we’ve witnessed this decline firsthand. The loss of local pharmacies threatens individual and community access to medications, pharmacist expertise and essential public health resources.
The changing role of pharmacies
Community pharmacies – which include independently owned, corporate-chain and other retail pharmacies in neighborhood settings – have changed a lot over the past decades. What once were simple medication pickup points have evolved into hubs for health and wellness. Beyond dispensing prescriptions, pharmacists today provide vaccinations, testing and treatment for infectious diseases, access to hormonal birth control and other clinical services they’re empowered to provide by federal and state laws.
Given their importance, then, why have so many community pharmacies been closing?
There are many reasons, but the most important is reduced reimbursement for prescription drugs. Most community pharmacies operate under a business model centered on dispensing medications that relies on insurer reimbursements and cash payments from patients. Minor revenue comes from front-end sales of over-the-counter products and other items.
However, pharmacy benefit managers – companies that manage prescription drug benefits for insurers and employers – have aggressively cut reimbursement rates in an effort to lower drug costs in recent years. As a result, pharmacists often have to dispense prescription drugs at very low margins or even at a loss. In some cases, pharmacists are forced to transfer prescriptions to other pharmacies willing to absorb the financial hit. Other times, pharmacists choose not to stock these drugs at all.
And it’s not just mom-and-pop operations feeling the pinch. Over the past four years, the three largest pharmacy chains have announced plans to close hundreds of stores nationwide. CVS kicked off the trend in 2021 by announcing plans to close 900 pharmacy locations. In late 2023, Rite Aid said that thousands of its stores would be at risk for closure due to bankruptcy. And late in 2024, Walgreens announced its plans to close 1,200 stores over the next three years.
To make matters worse, pharmacists, like many other health care providers, have been facing burnout due to high stress and the lasting effects of the COVID-19 pandemic. At the same time, pharmacy school enrollment has declined, worsening the workforce shortage just as an impending shortfall of primary care physicians looms.
Why pharmacy accessibility matters
The increasing closure of community pharmacies has far-reaching consequences for millions of Americans. That’s because neighborhood pharmacies are one of the most accessible health care locations in the country, with an estimated 90% of Americans living within 5 miles of one.
However, research shows that “pharmacy deserts” are more common in marginalized communities, where people need accessible health care the most. For example, people who live in pharmacy deserts are also more likely to have a disability that makes it hard or impossible to walk. Many of these areas are also classified as medically underserved areas or health professional shortage areas. As pharmacy closures accelerate, America’s health disparities could get even worse.
So if your neighborhood pharmacy closes, what should you do?
While convenience and location matter, you might want to consider other factors that can help you meet your health care needs. For example, some pharmacies have staff who speak your native language, independent pharmacy business owners may be active in your community, and many locations offer over-the-counter products like hormonal contraception, the overdose-reversal drug naloxone and hearing aids.
You may also consider locations – especially corporate-owned pharmacies – that also offer urgent care or primary care services. In addition, most pharmacies offer vaccinations, and some offer test-and-treat services for infectious diseases, diabetes education and help with quitting smoking.
What to ask if your pharmacy closes
If your preferred pharmacy closes and you need to find another one, keep the following questions in mind:
• What will happen to your old prescriptions? When a pharmacy closes, another pharmacy may buy its prescriptions. Ask your pharmacist if your prescriptions will be automatically transferred to a nearby pharmacy, and when this will occur.
• What’s the staffing situation like at other pharmacies? This is an important factor in choosing a new pharmacy. What are the wait times? Can the team accommodate special situations like emergency refills or early refills before vacations? Does the pharmacist have a relationship with your primary care physician and your other prescribers?
• Which pharmacies accept your insurance? A simple call to your insurer can help you understand where your prescriptions are covered at the lowest cost. And if you take a medication that’s not covered by insurance, or if you’re uninsured, you should ask if the pharmacy can help you by offering member pricing or manufacturer coupons and discounts.
• What are your accessibility needs? Pharmacies often offer services to make your care more accessible and convenient. These may include medication packaging services, drive-thru windows and home delivery. And if you’re considering switching to a mail-order pharmacy, you should ask if it has a pharmacist to answer questions by phone or during telehealth visits.
Remember that it’s best to have all your prescriptions filled at the same pharmacy chain or location so that your pharmacist can perform a safety check with your complete medication list. Drug interactions can be dangerous.
Community pharmacies have been staples of neighborhoods for more than a century. Unfortunately, current trends in pharmacy closures pose real threats to public health. We hope lawmakers address the underlying systemic issues so more Americans don’t lose access to their medications, health services and pharmacists.
Lucas A. Berenbrok, Associate Professor of Pharmacy and Therapeutics, University of Pittsburgh; Michael Murphy, Assistant Professor of Pharmacy Practice and Science, The Ohio State University, and Sophia Herbert, Assistant Professor of Pharmacy, University of Pittsburgh
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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(Family Features) Clinical trials help researchers studying chronic conditions answer important questions about the diseases and their treatment options. However, uncertainty about what to expect and a lack of knowledge about how to get started can prevent patients from joining a clinical trial.
Choosing to take part in a clinical trial means helping a study team figure out if a new method of diagnosis, treatment or prevention is effective. If you live with a chronic condition, such as Crohn’s disease or ulcerative colitis, and want to help find answers for others who share your experience, a clinical trial is an option to consider.
Once you identify a study that interests you, you’ll want to talk with the professionals involved in your ongoing treatment, a clinical research coordinator and your family to gather information necessary to determine whether the clinical trial is a good fit.
To find additional information about clinical trials and begin exploring trials in your area, visit crohnscolitisfoundation.org, and consider these steps for participating in a trial.
1. Talking with Your Doctor
Your gastroenterologist and other care providers can help determine whether a clinical trial is right for you and may be able to help point you toward recommended trials. It’s important to ask if or how your doctor will continue to be involved in your care if you participate in a trial.
2. Finding a Study
If you need help beyond your care team in identifying clinical trial opportunities in your area, organizations dedicated to your condition can be a good resource. For example, the Crohn’s & Colitis Foundation offers an online Clinical Trial Finder for individuals with inflammatory bowel disease.
3. Talking with the Research Coordinator
A clinical trial research coordinator can provide details specific to your circumstances and needs. You can discuss potential benefits and risks, why the trial is being conducted and who is involved in the health care team. You can talk about past treatments and how this study may differ from your previous experiences. Other questions you might ask include what your options are if the trial doesn’t work, any costs you might expect and what your personal commitment will be.
4. Evaluating the Fit for You
Once you have the necessary information, you’ll be able to consider whether you’re ready to move forward with registering for the trial. You’ll want to weigh factors like your time commitment, travel distance and whether the trial will affect your personal or professional obligations.
Photos courtesy of Shutterstock
SOURCE:
Crohn’s & Colitis Foundation
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