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Hormone therapy is often used to treat prostate cancer that has spread to other parts of the body, but many patients develop resistance to hormone therapy, causing their disease to become more aggressive and potentially more deadly.
“One of the big challenges we have in the field is that the majority of prostate cancer therapies target hormones — the androgen axis,” says University of Colorado Cancer Center mentored member Cecilia Caino, PhD. “But nearly all patients develop resistance to those drugs and then get a more aggressive disease that starts moving to other parts of the body. It’s been confined to the prostate, but now it might move over to the bones or the liver, or the lungs. That’s really a big problem, because when you start to compromise the vital organs, the patient eventually will die.”
In spring 2021, Caino received an Idea Award from the U.S. Department of Defense’s Peer Reviewed Cancer Research Program to investigate the role of mitochondria — the small energy factories in cells that help to break down food into fuel — in metastatic prostate cancer.
In initial research recently published in the journal Molecular Cancer Research, Caino and her co-investigators discovered that tumor cells use mitochondria to control their growth and detect stress that can destroy a tumor cell if it is not controlled. In addition to the Department of Defense, the research is funded by the American Cancer Society, the Boettcher Foundation, and the National Institute of General Medical Sciences.
“We know that tumor cells are very resistant to stress in general; that’s what makes them so hard to target with therapies,” Caino says. “But when the tumors grow too fast, they start running out of nutrients to keep building. They utilize this mitochondrial pathway that we describe to slow down for a moment, adapt, and expand their capacity to synthesize more blocks to build the cells.”
A compound to target
Caino and her team also found that a mitochondrial protein called MIRO2 is overexpressed in metastatic prostate cancer tumors. Having previously found that MIRO2 works together with two other proteins called GCN1 and GCN2 to help metastatic prostate cancer cells tolerate conditions where growth of normal cells would be prevented, Caino now hypothesizes that targeting this protein compound can inhibit the mitochondrial process that prevents tumor cells from destroying themselves by expanding too quickly.

A recently published study by Houston Methodist scientists suggests telltale signs of concussions might be found in the gut. By taking blood, stool and saliva samples from 33 Rice University football players, the researchers were able to examine the diagnostic potential of the gut’s microbiome. They say their findings demonstrate that a simple, objective diagnostic test could be developed to track the impact of concussions and signal when it’s safe to return to action.
The findings of this study are described in a paper titled “Alterations to the gut microbiome after sport-related concussion in a collegiate football players cohort: A pilot study” appearing in the May issue of Brain, Behavior, & Immunity — Health, a peer-reviewed journal of the Psychoneuroimmunology Research Society with an emphasis on research that has translational impact and clinical implications. Sonia Villapol, Ph.D., an assistant professor of neurosurgery at the Center for Neuroregeneration in the Houston Methodist Research Institute, is the corresponding author on the study.
While brain movement within the skull may cause injury to nerve cells, such microscopic cellular injuries are not visible on imaging tests like X-rays, CT scans and MRIs, which are more capable of finding injuries on the scale of skull fractures, brain bleeding or swelling. So, the most commonly used test for diagnoses of concussions relies exclusively on self-reported symptoms like blurry vision, dizziness, nausea and headaches, which can be very vague, subjective and often underreported by athletes who want to continue playing. This can make them notoriously difficult to diagnose.
The study, conducted over the course of one season, found a post-concussion drop-off of two bacterial species normally found in abundance in stool samples of healthy individuals. It also found a correlation between traumatic brain injury linked proteins in the blood and one brain injury linked bacterial species in the stool.
While there have been dozens of brain injury biomarkers identified, there has been limited success in developing commercial blood tests sensitive enough to detect tiny increases in biomarker concentrations. However, the central nervous system is also intimately linked to the enteric nervous system, occurring in the intestines, and head trauma invariably leads to changes in the gut microbiota, Villapol said.
After a concussion, the injuries cause inflammation, sending small proteins and molecules circulating through the blood that breach the intestinal barrier and cause changes in the gut, affecting metabolism.
She said these changes in the microbiota could offer an opportunity to acquire a readout of the ongoing injury to the central nervous system.
“Until your gut microbiome has returned to normal, you haven’t recovered,” Villapol said. “This is why studying the gut is so useful. It doesn’t lie. And that is why there is so much interest in using it for diagnostic purposes.”
While only four of the players in the study were diagnosed with major concussions, the researchers say the results will need to be confirmed in a larger sample size. They also plan to conduct a similar study soon using women’s soccer athletes, who similarly have frequent head trauma.
“Women and men don’t have the same immunities or gut microbiomes, and as a woman and a mother of daughters, I would hate to be that researcher who only looks at men’s issues while overlooking women,” Villapol said. “Women soccer players have very high rates of concussions, as well, and all the same problems when it comes to existing diagnostic methods.”
Villapol’s collaborators on this study were Rice University investigators Kristen Curry, Qi Wang, Michael Nute, Elizabeth Reeves, Sarah Schodrof and Todd Treangen from the computer science and?athletics departments; and Houston Methodist colleagues Sirena Soriano, Saeed S. Sadrameli, Rasadul Kabir, Jonathan Wiese, Amber Criswell, Gavin W. Britz, Rajan Gadhia and Kenneth Podell.
This work was supported by the National Institute for Neurological Disorders and Stroke (grant number R21NS106640), Institute of Biosciences and Bioengineering Hamill Innovation Award, National Institute of Allergy and Infectious Diseases (grant number P01AI152999-01) and funds from the Houston Methodist Research Institute.

Research that examines how the body adapts to new movements is shedding new light on how the nervous system learns, and could help to inform a wide range of applications, from customized rehabilitation and athletic training to wearable systems for healthcare. The research is published this week in the journal Current Biology.
“How does our brain figure out how to best move our body? It turns out that this can be a challenging problem for the nervous system, considering we have hundreds of muscles that can be coordinated hundreds of times per second — with more possible coordination patterns to choose from than moves on a chessboard,” says study senior author and SFU professor Max Donelan, director of SFU’s Locomotion Lab.
“We often experience changes to our body and our environment. Perhaps you enjoy a long run on a Saturday morning — your muscles may fatigue as the length of the run increases. Perhaps you choose to run on the beach on vacation — the sand may be uneven and loose in comparison to the pavement on the sidewalk. While we might register that these changes have occurred, we might not appreciate how our body adapts to these changes.”
Donelan’s team of neuroscientists that study motor learning collaborated with a Stanford University team of mechanical engineers that design human-robot systems. Together, they tracked the walking characteristics of study participants wearing exoskeletons.
Findings
Researchers found that the nervous system solves the problem of learning a new movement coordination pattern by first exploring and evaluating many different coordination patterns. This exploration was measured as a general increase in variability spanning the levels of the whole movement, joint, and muscle.

Gun deaths reached the highest level ever recorded in the United States in 2020, the first year of the pandemic, the Centers for Disease Control reported on Tuesday. Gun-related homicides in particular rose by 35 percent, a surge that exacted an unprecedented toll on Black men, agency researchers said.“This is a historic increase, with the rate having reached the highest level in over 25 years,” Dr. Debra E. Houry, acting principal deputy director of the C.D.C. and the director of the National Center for Injury Prevention and Control, said at a news briefing on Tuesday.“We need to be vigilant in addressing the conditions that contribute to homicides and suicides and the disparities observed,” she added.More than 45,000 Americans died in gun-related incidents as the pandemic spread in the United States, the highest number on record, federal data show. But more than half of gun deaths were suicides, and that number did not substantially increase from 2019 to 2020.The overall rise in gun deaths was 15 percent in 2020, lower than the percentage increase in gun homicides, the C.D.C. said.The rise in gun murders was the largest one-year increase seen in modern history, according to Ari Davis, a policy adviser at the Johns Hopkins Center for Gun Violence Solutions, which recently released its own analysis of C.D.C. data.He said preliminary figures suggest that gun deaths remained persistently high in 2021.Federal officials and outside experts are not certain what caused the surge in gun deaths. The rise corresponded to accelerated sales of firearms as the pandemic spread and lockdowns became the norm, the C.D.C. noted.But federal researchers also cited increased social, economic and psychological stressors; disruptions in routine health care; tension between police and community members following George Floyd’s murder; a rise in domestic violence; inequitable access to health care; and longstanding systemic racism that contributes to poor housing conditions, limited educational opportunities and high poverty rates.Murders involving firearms were generally highest, and showed the largest increases, in impoverished communities.“One possible explanation is stressors associated with the Covid pandemic that could have played a role, including changes and disruption to services and education, social isolation, housing instability and difficulty covering daily expenses,” said Thomas R. Simon, associate director for science at the agency’s division of violence prevention.Black Americans remained disproportionately affected by gun violence in 2020. Firearm homicide rates increased by 39.5 percent among Black people from 2019 to 2020, to 11,904. The victims were overwhelmingly young men.The Johns Hopkins analysis found that Black men ages 15 to 34 accounted for 38 percent of all gun murder victims in 2020, though they represented just 2 percent of the U.S. population.Black men aged 15 to 34 were more than 20 times more likely to be murdered with a gun than white men of the same age. The number of Black women killed by guns also increased by almost 50 percent in 2020, compared to 2019, Mr. Davis said.Rising rates of gun-related homicides were seen in all racial and ethnic groups, the C.D.C. said — except among Americans of Asian and Pacific Islander descent, who saw a small decrease.Gun-related suicides have long been more common among older white men. But in 2020, rates rose mostly sharply among Native Americans and Alaska Native groups.“Suicides impact a different population, typically middle-aged to older white men in rural communities,” Mr. Davis said. “We’re going to need to develop different types of solutions to deal with different types of gun violence.”

MIT researchers have discovered that before cells start to divide, they do a little cleanup, tossing out molecules that they appear not to need anymore.
Using a new method they developed for measuring the dry mass of cells, the researchers found that cells lose about 4 percent of their mass as they enter cell division. The researchers believe that this emptying of trash helps cells to give their offspring a “fresh start,” without the accumulated junk of the parent cell.
“Our hypothesis is that cells might be throwing out things that are building up, toxic components or just things that don’t function properly that you don’t want to have there. It could allow the newborn cells to be born with more functional contents,” says Teemu Miettinen, an MIT research scientist and the lead author of the new study.
Scott Manalis, the David H. Koch Professor of Engineering in the departments of Biological Engineering and Mechanical Engineering, and a member of the Koch Institute for Integrative Cancer Research, is the senior author of the paper, which appears today in eLife. MIT biological engineering undergraduates Kevin Ly and Alice Lam are also authors of the paper.
Measuring mass
Measuring the dry mass of a cell — the weight of its contents not including the water — is commonly done using a microscopy technique called quantitative phase microscopy. This technique can measure cell growth, but it does not reveal information about the molecular content of the dry mass and it is difficult to use with cells that grow in suspension.

Medical interventions, such as improving diet, lowering blood lipids, or controlling blood pressure and blood sugar, can only do so much when it comes to treating atherosclerotic disease. Is it possible to make earlier predictions for risk factors for plaque formation within the carotid arteries via characteristics of vascular structure and the dynamics of blood flow before the disease progresses?
In Physics of Fluids, from AIP Publishing, researchers in China present clinicians with information about the risk factors for atherosclerotic plaque formation from a mechanical point of view. The scientists are exploring whether it is possible to screen and intervene early for people at risk for atherosclerotic disease from the perspective of hemodynamics, using color Doppler ultrasound, coronary computed tomography angiography, and other screenings.
“Carotid endarterectomy and carotid artery stenting are the main methods for treatment of carotid artery stenosis,” said Zhiyong Song, from the University of Science and Technology Beijing. “Changes of postoperative vascular structure and fluid mechanics are important for restenosis, so determining how to minimize risk factors of postoperative flow is important for improving the therapeutic effect.”
A multipoint, noncontact laser flow measurement method called microparticle image velocimetry (Micro-PIV) was used by the researchers, something they said has been continuously improved during the past few decades and exceeds the limitations of single-point measurement technologies.
“It could record speed distribution information on a large number of spatial points within the same transient state to provide rich spatial structure of flow field and flow characteristics,” said Song.
The researchers discovered a significant gap between their study and the clinical method in terms of wall shear strength calculation, which could lead to confusion about the physiological mechanism.
“Based on the plateau-like distribution of the velocity field at the central carotid stenosis location shown by Micro-PIV and simulations, the current clinical estimation method of wall shear stress at the stenosis location could result in a difference of up to 60%,” Song said.
The group’s hemodynamic study of carotid atherosclerotic plaque has important clinical significance for understanding the formation and development mechanism of atherosclerotic disease, improving surgical treatment technology, and researching and developing future medical devices.
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Materials provided by American Institute of Physics. Note: Content may be edited for style and length.

Healthy adults who eat a diverse diet with at least 8-10 grams of soluble fiber a day have fewer antibiotic-resistant microbes in their guts, according to a study published by Agricultural Research Service scientists and their colleagues in mBio.
Microbes that have resistance to various commonly used antibiotics such as tetracycline and aminoglycoside are a significant source of risk for people worldwide, with the widely held expectation that the problem of antimicrobial resistance (AMR) — the term that refers to bacteria, viruses, and fungi that are resistant to antibiotics — is likely to worsen throughout the coming decades.
Antimicrobial resistance in people is largely based in their gut microbiome, where the microbes are known to carry genetically encoded strategies to survive contact with antibiotics.
“And the results lead directly to the idea that modifying the diet has the potential to be a new weapon in the fight against antimicrobial resistance. And we’re not talking about eating some exotic diet either, but a diverse diet, adequate in fiber, that some Americans already eat,” explained research molecular biologist Danielle Lemay with the ARS Western Human Nutrition Research Center in Davis, California, and leader of the study.
In this study, the researchers were looking for specific associations of the levels of antibiotic resistance genes in the microbes of the human gut with both fiber and animal protein in adult diets.
The researchers found regularly eating a diet with higher levels of fiber and lower levels of protein, especially from beef and pork, was significantly correlated with lower levels of antimicrobial resistance genes (ARG) among their gut microbes. Those with the lowest levels of ARG in their gut microbiomes also had a greater abundance of strict anaerobic microbes, which are bacteria that do not thrive when oxygen is present and are a hallmark of a healthy gut with low inflammation. Bacterial species in the family Clostridiaceae were the most numerous anaerobes found.

Less than half of Americans who received treatment for opioid use disorder over a five-year period were offered a potentially lifesaving medication, researchers at Washington University School of Medicine in St. Louis and Saint Louis University have found. And treatment with the medication was even more rare for those with what’s known as polysubstance use disorder — when opioid users also misuse other substances, such as alcohol, methamphetamine, benzodiazepines or cocaine.
The findings build on the knowledge that medications to treat those who use opioids are generally underutilized.
“This is equivalent to giving those with advanced cancer a less aggressive treatment,” said senior investigator Laura J. Bierut, MD, the Alumni Endowed Professor of Psychiatry at Washington University. “It seems obvious to many of us that we should be giving the most aggressive and effective treatments to those who are most seriously ill.”
The potentially lifesaving drug, buprenorphine, has been shown to reduce overdose risk — yet an analysis of health insurance data involving about 180,000 people treated for opioid use disorder showed that nearly 53% of the patients with the disorder alone were not prescribed the medication. Among those with polysubstance use disorder, the number prescribed buprenorphine dropped to about 30%.
The study is published May 10 in the journal JAMA Network Open.
“It’s concerning that the majority of people misusing multiple substances don’t appear to be getting the lifesaving medication they really need,” said first author Kevin Xu, MD, a resident physician in the Department of Psychiatry at Washington University. “Even among those who used opioids exclusively, buprenorphine was prescribed only about half the time. While the data we analyzed predates COVID-19, the pandemic saw an escalation in overdoses, yet we’re still not seeing many eligible patients get buprenorphine prescriptions.”
Xu and his colleagues — including Bierut and Richard A. Grucza, PhD, a professor in the Department of Family and Community Medicine at Saint Louis University — analyzed data compiled from 2011-2016 by insurance companies for the U.S. IBM MarketScan databases. The databases include detailed information about patients treated for opioid use disorder, as well as those treated for using opioids together with other drugs.

Alterations in metabolic processes are a hallmark of cancer and can lead to a tumor environment that is acidic. As a result, cancer cells must adapt to survive in this inhospitable environment. In a new study published in the journal Cell Reports, Moffitt Cancer Center researchers show that cancer cells in an acidic environment undergo lipid synthesis and accumulation. The team identified the key signaling molecules responsible for these changes and discovered that these alterations are associated with poor outcomes and disease progression among breast cancer patients.
Cancer cells undergo numerous changes that promote cell survival and continued growth. One of the hallmark changes of cancer cells is the increased breakdown of the sugar glucose, which when combined with poor blood flow, leads to the development of a highly acidic surrounding tumor environment. To survive in this environment, cancer cells undergo adaptations, such as activation of the self-degradation and recycling process called autophagy, and the accumulation of lipid fat droplets. Lipid droplets play an important role in the regulation of energy, metabolism and signal transduction; however, scientists are unsure how lipid droplets accumulate in tumor cells or what their impact is on cancer survival and progression.
Moffitt researchers performed a series of laboratory experiments with cell lines and mouse models to improve their understanding of lipid droplets in cancer. They discovered that breast cancer cell lines grown in acidic conditions accumulate intracellular lipid droplets that express the lipid droplets biomarker protein PLIN2. Lipid droplets formed when a protein in the cellular membrane called OGR1 sensed the presence of the acidic environment. OGR1 subsequently activated downstream signal transduction through the proteins phospholipase C and PI3K/AKT, which led to the formation of lipid droplets from the products of amino acids that had undergone a metabolic breakdown into smaller components.
Next, the team wanted to assess the biological effects of lipid droplets and OGR1 on cancer. Interestingly, the acid sensing receptor OGR1 is highly expressed in breast tumors and strongly associated with disease progression. They demonstrated that by targeting OGR1, they could reduce levels of lipid droplets, inhibit stress responses and cell growth in acidic conditions, and decrease tumor growth in mice. Additionally, the researchers discovered that high expression of the lipid droplets biomarker PLIN2 was associated with shorter survival and disease progression in breast cancer patients.
These combined observations suggest that lipid droplets formation mediated by OGR1 is an important contributor to tumor development and may be a potential target for anti-cancer drugs.
“Recent studies have established reprogramming of lipid metabolism as an emerging hallmark of many cancers, providing opportunities for therapeutic targeting. Many lipid inhibitors are being investigated as anticancer drugs in clinical trials. Our studies provide a strong foundation for future investigations that will lead to a more detailed characterization of the role of OGR1 in ER stress response, autophagy and lipogenesis in animal models and human breast tumors,” explained Smitha Pillai, Ph.D., lead study author and a research scientist in the Cancer Physiology Department at Moffitt.
This study was supported by the National Institutes of Health (R010-17536-99-02, R01-DK105346, P41-GM122698, 5U2C-DK119889, P30-CA076292), the Florida Department of Health Bankhead-Coley Cancer Research Program, the Florida Breast Cancer Foundation, the McKnight Brain Institute at the National High Magnetic Field Laboratory’s Advanced Magnetic Resonance Imaging and Spectroscopy Facility (National Science Foundation Cooperative Agreement DMR-1644779) and the European Research Council Consolidator Grant “Survive” (723997).
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Materials provided by H. Lee Moffitt Cancer Center & Research Institute. Note: Content may be edited for style and length.

Tumors can force neighboring cells into supporting cancer growth by releasing lactate into their local environment, according to researchers at Weill Cornell Medicine. The findings pave the way for future drug treatments that thwart that defense mechanism to help cancer patients.
In the study, published May 10 in Cell Reports, the researchers determined how tumors, as they develop, recruit nearby cells called fibroblasts to work as their enablers. Fibroblasts are part of the “stroma,” or connective tissue of organs, and normally have important repair and maintenance functions. But cancer-associated fibroblasts (CAFs) acquire properties that allow them to assist tumors in ways that make the tumors more malignant and harder to kill.
The researchers also discovered that widely used cancer drugs called PARP-1 inhibitors mimic one of the key steps in CAF recruitment, and thus may often hobble their own effectiveness by switching local fibroblasts to this cancer-enabling mode.
“Future therapeutics that block this cancer-associated state of fibroblasts might be useful on their own or as a way to improve the effectiveness of PARP-1 inhibitors,” said study co-senior author Dr. Maria Diaz-Meco, the Homer T. Hirst III Professor of Oncology in Pathology and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine.
Dr. Diaz-Meco collaborated in the study with the laboratory of co-senior author Dr. Jorge Moscat, also the Homer T. Hirst III Professor of Oncology in Pathology and a member Meyer Cancer Center at Weill Cornell Medicine. The co-first authors are Dr. Juan Linares, instructor in pathology and laboratory medicine, and Dr. Tania Cid-Diaz, postdoctoral associate in pathology and laboratory medicine.
Scientists have known for decades that developing tumors often modify their local environments in ways that promote their own survival and growth. Cancer-associated fibroblasts are a central component of the tumor microenvironment in prostate, lung, colon and many other cancer types. Targeting these cells is therefore seen as a promising complementary approach to standard cancer treatment — and one that could work very broadly against cancers of different cellular and genetic origins.