clinical study
Rice-Sized Device Tests Brain Tumor’s Drug Responses During Surgery
Posted on by Lawrence Tabak, D.D.S., Ph.D.
Scientists have made remarkable progress in understanding the underlying changes that make cancer grow and have applied this knowledge to develop and guide targeted treatment approaches to vastly improve outcomes for people with many cancer types. And yet treatment progress for people with brain tumors known as gliomas—including the most aggressive glioblastomas—has remained slow. One reason is that doctors lack tests that reliably predict which among many therapeutic options will work best for a given tumor.
Now an NIH-funded team has developed a miniature device with the potential to change this for the approximately 25,000 people diagnosed with brain cancers in the U.S. each year [1]. When implanted into cancerous brain tissue during surgery, the rice-sized drug-releasing device can simultaneously conduct experiments to measure a tumor’s response to more than a dozen drugs or drug combinations. What’s more, a small clinical trial reported in Science Translational Medicine offers the first evidence in people with gliomas that these devices can safely offer unprecedented insight into tumor-specific drug responses [2].
These latest findings come from a Brigham and Women’s Hospital, Boston, team led by Pierpaolo Peruzzi and Oliver Jonas. They recognized that drug-screening studies conducted in cells or tissue samples in the lab too often failed to match what happens in people with gliomas undergoing cancer treatment. Wide variation within individual brain tumors also makes it hard to predict a tumor’s likely response to various treatment options.
It led them to an intriguing idea: Why not test various therapeutic options in each patient’s tumor? To do it, they developed a device, about six millimeters long, that can be inserted into a brain tumor during surgery to deliver tiny doses of up to 20 drugs. Doctors can then remove and examine the drug-exposed cancerous tissue in the laboratory to determine each treatment’s effects. The data can then be used to guide subsequent treatment decisions, according to the researchers.
In the current study, the researchers tested their device on six study volunteers undergoing brain surgery to remove a glioma tumor. For each volunteer, the device was implanted into the tumor and remained in place for about two to three hours while surgeons worked to remove most of the tumor. Next, the device was taken out along with the last piece of a tumor at the end of the surgery for further study of drug responses.
Importantly, none of the study participants experienced any adverse effects from the device. Using the devices, the researchers collected valuable data, including how a tumor’s response changed with varying drug concentrations or how each treatment led to molecular changes in the cancerous cells.
More research is needed to better understand how use of such a device might change treatment and patient outcomes in the longer term. The researchers note that it would take more than a couple of hours to determine how treatments produce less immediate changes, such as immune responses. As such, they’re now conducting a follow-up trial to test a possible two-stage procedure, in which their device is inserted first using minimally invasive surgery 72 hours prior to a planned surgery, allowing longer exposure of tumor tissue to drugs prior to a tumor’s surgical removal.
Many questions remain as they continue to optimize this approach. However, it’s clear that such a device gives new meaning to personalized cancer treatment, with great potential to improve outcomes for people living with hard-to-treat gliomas.
References:
[1] National Cancer Institute Surveillance, Epidemiology, and End Results Program. Cancer Stat Facts: Brain and Other Nervous System Cancer.
[2] Peruzzi P et al. Intratumoral drug-releasing microdevices allow in situ high-throughput pharmaco phenotyping in patients with gliomas. Science Translational Medicine DOI: 10.1126/scitranslmed.adi0069 (2023).
Links:
Brain Tumors – Patient Version (National Cancer Institute/NIH)
Pierpaolo Peruzzi (Brigham and Women’s Hospital, Boston, MA)
Jonas Lab (Brigham and Women’s Hospital, Boston, MA)
NIH Support: National Cancer Institute, National Institute of Biomedical Imaging and Bioengineering, National Institute of Neurological Disorders and Stroke
Ultra-Processed Diet Leads to Extra Calories, Weight Gain
Posted on by Dr. Francis Collins
If you’ve ever tried to lose a few pounds or just stay at a healthy weight, you’ve likely encountered a dizzying array of diets, each with passionate proponents: low carb, low fat, keto, paleo, vegan, Mediterranean, and so on. Yet most nutrition experts agree on one thing: it’s best to steer clear of ultra-processed foods. Now, there’s some solid scientific evidence to back up that advice.
In the first randomized, controlled study to compare the effects of ultra-processed with unprocessed foods, NIH researchers found healthy adults gained about a pound per week when they were given a daily diet high in ultra-processed foods, which often contain ingredients such as hydrogenated fats, high fructose corn syrup, flavoring agents, emulsifiers, and preservatives. In contrast, when those same people ate unprocessed whole foods, they lost weight.
Intriguingly, the weight differences on the two diets occurred even though both kinds of foods had been carefully matched from a nutritional standpoint, including calorie density, fiber, fat, sugar, and salt. For example, breakfast for the ultra-processed group might consist of a bagel with cream cheese and turkey bacon, while the unprocessed group might be offered oatmeal with bananas, walnuts, and skim milk.
The explanation for the differences appears to lie in the fact that study participants were free to eat as little or as much food as they wished at mealtimes and to snack between meals. It turns out that when folks were on the ultra-processed diet they ate significantly more—about 500 extra calories per day on average—than when they were on the unprocessed diet. And, as you probably know, more calories without more exercise usually leads to more weight!
This might not seem new to you. After all, it has been tempting for some time to suggest a connection between the rise of packaged, ultra-processed foods and America’s growing waistlines. But as plausible as it might seem that such foods may encourage overeating, perhaps because of their high salt, sugar, and fat content, correlation is not causation and controlled studies of what people actually eat are tough to do. As a result, definitive evidence directly tying ultra-processed foods to weight gain has been lacking.
To explore the possible connection in the study now reported in Cell Metabolism, researchers at NIH’s National Institute of Diabetes and Digestive and Kidney Diseases took advantage of the Metabolic Clinical Research Unit at the NIH Clinical Center, Bethesda, MD. The unit is specially equipped to study issues involving diet and metabolism.
The researchers asked 20 healthy men and women of stable weight to stay at the center for 28 days. Each volunteer was randomly assigned to eat either an ultra-processed or unprocessed diet for two consecutive weeks. At that point, they switched to the other diet for another two weeks.
Both diets consisted of three daily meals, and volunteers were given permission to eat as much food as they liked. Importantly, a team of dieticians had carefully designed the ultra-processed and unprocessed meals such that they were well matched for total calories, calorie density, macronutrients, fiber, sugars, and salt.
At lunch, for example, one of the study’s processed meals consisted of quesadillas, refried beans, and diet lemonade. An unprocessed lunch consisted of a spinach salad with chicken breast, apple slices, bulgur, and sunflower seeds with a side of grapes.
The main difference between each diet was the proportion of calories derived from ultra-processed versus unprocessed foods as defined by the NOVA diet classification system. This system categorizes food based on the nature, extent, and purpose of food processing, rather than its nutrient content.
Each week, researchers measured the energy expenditure, weight, and changes in body composition of all volunteers. After two weeks on the ultra-processed diet, volunteers gained about two pounds on average. That’s compared to a loss of about two pounds for those on the unprocessed diet.
Metabolic testing showed that people expended more energy on the ultra-processed diet. However, that wasn’t enough to offset the increased consumption of calories. As a result, participants gained pounds and body fat. The study does have some limitations, such as slight differences in the protein content of the two diets. and the researchers plan to address such issues in their future work.
During this relatively brief study, the researchers did not observe other telltale changes associated with poor metabolic health, such as a rise in blood glucose levels or fat in the liver. While a couple of pounds might not sound like much, the extra calories and weight associated with an ultra-processed diet would, over time, add up.
So, it appears that a good place to start in reaching or maintaining a healthy weight is to follow the advice shared by all those otherwise conflicting diet plans: work to eliminate or at least reduce ultra-processed foods in your diet in favor of a balanced variety of unprocessed, nutrient-packed foods.
Reference:
[1] Ultra-processed diets cause excess calorie intake and weight gain: An inpatient randomized controlled trial of ad libitum food intake. Hall KD et al. Cell Metab. 2019 May 16.
Links:
Obesity (National Institute of Diabetes and Digestive and Kidney Diseases/NIH)
Healthy Eating Plan (National Heart, Lung, and Blood Institute/NIH)
Body Weight Planner (NIDDK/NIH)
Kevin D. Hall (NIDDK/NIH)
Metabolic Clinical Research Unit (NIDDK/NIH)
NIH Support: National Institute of Diabetes and Digestive and Kidney Diseases
Celebrating Our Nation’s Birth and What It Means for All of Us
Posted on by Dr. Francis Collins
Happy Fourth of July! It’s the perfect time to fire up the grill, go watch some fireworks, and pay tribute to the vision of all who founded the United States of America. The Fourth of July also stands as a reminder of the many new opportunities that our nation and its people continue to pursue. One of the most exciting is NIH’s All of Us Research Program, which is on the way to enrolling 1 million or more Americans from all walks of life to create a resource that will accelerate biomedical breakthroughs and transform medicine.
What exactly do I mean by “transform?” Today, most medical care is “one-size-fits-all,” not tailored to the unique needs of each individual. In order to change that situation and realize the full promise of precision medicine, researchers need a lot more information about individual differences in lifestyle, environment, and biology. To help move precision medicine research forward, our nation needs people like you to come together through the All of Us program to share information about your health, habits, and what it’s like where you live. All of your information will be protected by clear privacy and security principles.
All of Us welcomes people from across our diverse land. Enrollment in the research program is open to all, and anyone over the age of 18 who is living in the United States can join. Since full enrollment began in May, three of every four volunteers have come from groups traditionally underrepresented in biomedical research. These include people from a multitude of races and ethnicities, as well as folks with disabilities and those who live in remote or rural communities.
So, as you celebrate the birth of the United States this Independence Day, I ask you also to look ahead to our nation’s future and what you can do to make it brighter. One way you can do that is to consider joining me and thousands of other Americans who’ve already signed up for All of Us. Together, we can build a resource that will revolutionize medicine for generations to come. Thanks, and have a safe and glorious Fourth of July!
Links:
All of Us (NIH)
Video: What is All of Us?
Video: All of Us: Importance of Diversity
Video: All of Us Launch
I Handed Over My Genetic Data to the NIH. Here’s Why You Should, Too (STAT)
NIH Support: NIH Office of the Director
New ‘Liquid Biopsy’ Shows Early Promise in Detecting Cancer
Posted on by Dr. Francis Collins
Caption: Liquid biopsy. Tumor cells shed protein and DNA into bloodstream for laboratory analysis and early cancer detection.
Early detection usually offers the best chance to beat cancer. Unfortunately, many tumors aren’t caught until they’ve grown relatively large and spread to other parts of the body. That’s why researchers have worked so tirelessly to develop new and more effective ways of screening for cancer as early as possible. One innovative approach, called “liquid biopsy,” screens for specific molecules that tumors release into the bloodstream.
Recently, an NIH-funded research team reported some encouraging results using a “universal” liquid biopsy called CancerSEEK [1]. By analyzing samples of a person’s blood for eight proteins and segments of 16 genes, CancerSEEK was able to detect most cases of eight different kinds of cancer, including some highly lethal forms—such as pancreatic, ovarian, and liver—that currently lack screening tests.
In a study of 1,005 people known to have one of eight early-stage tumor types, CancerSEEK detected the cancer in blood about 70 percent of the time, which is among the best performances to date for a blood test. Importantly, when CancerSEEK was performed on 812 healthy people without cancer, the test rarely delivered a false-positive result. The test can also be run relatively cheaply, at an estimated cost of less than $500.
Malaria Vaccine Shows Promise
Posted on by Dr. Francis Collins
Courtesy of the National Institute of Allergy and Infectious Diseases, NIH
Malaria has confounded biomedical researchers for decades because it’s been impossible so far to develop a vaccine that offers a high level of protection. But, thanks to a different approach to vaccine design and delivery, there’s hope that we may have finally turned the corner in the fight against this mosquito-borne health threat.
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