Posts tagged chemo brain
Articles and news from the latest research reports.
Neuroscientists use snail research to help explain “chemo brain”
It is estimated that as many as half of patients taking cancer drugs experience a decrease in mental sharpness. While there have been many theories, what causes “chemo brain” has eluded scientists.
In an effort to solve this mystery, neuroscientists at The University of Texas Health Science Center at Houston (UTHealth) conducted an experiment in an animal memory model and their results point to a possible explanation. Findings appeared in The Journal of Neuroscience.
In the study involving a sea snail that shares many of the same memory mechanisms as humans and a drug used to treat a variety of cancers, the scientists identified memory mechanisms blocked by the drug. Then, they were able to counteract or unblock the mechanisms by administering another agent.
“Our research has implications in the care of people given to cognitive deficits following drug treatment for cancer,” said John H. “Jack” Byrne, Ph.D., senior author, holder of the June and Virgil Waggoner Chair and chairman of the Department of Neurobiology and Anatomy at the UTHealth Medical School. “There is no satisfactory treatment at this time.”
While much work remains, Byrne, who runs the university’s Neuroscience Research Center, said understanding how these drugs impact the brain is an important first step in alleviating this condition characterized by forgetfulness, trouble concentrating and difficulty multitasking.
Byrne’s laboratory is known for its use of a large snail called Aplysia californica to further the understanding of the biochemical signaling among nerve cells (neurons). The snails have large neurons that relay information much like those in humans.
When Byrne’s team compared cell cultures taken from normal snails to those administered a dose of a cancer drug called doxorubicin, the investigators pinpointed a neuronal pathway that was no longer passing along information properly.
With the aid of an experimental drug, the scientists were able to reopen the pathway. Unfortunately, this drug would not be appropriate for humans, Byrne said. “We want to identify other drugs that can rescue these memory mechanisms,” he added.
The scientists confirmed their findings in tests on the nerve cells of rats.
“The big picture is to determine if this cancer drug acts in the same way in humans,” Byrne said.
Memory Problems After Chemo Linked to Brain Changes
Breast cancer survivors who had chemotherapy show changes in brain activity during multitasking chores, according to a new Belgian study.
These findings may partly explain the phenomenon dubbed “chemo brain.” For years, people who’ve had chemotherapy have reported changes in thinking and memory, especially when doing more than one thing at once.
"Before you can fix a problem, you need to know what the problem is. And this study demonstrates what the problem may be. It’s a really good first step to understanding the what. Now we need to understand the why and how to fix it," said Dr. Courtney Vito, a breast surgeon and assistant clinical professor of surgical oncology at the City of Hope Comprehensive Cancer Center in Duarte, Calif. Vito was not involved in the current study, but reviewed the study’s findings.
In her experience, Vito said, women tend to be affected more by chemo brain than are men after chemotherapy. However, she said, ”women tend to multitask more, so this might explain part of it.”
The new study was published online May 27 in the Journal of Clinical Oncology.
Mental Fog with Tamoxifen is Real; Scientists Find Possible Antidote
A team from the University of Rochester Medical Center has shown scientifically what many women report anecdotally: that the breast cancer drug tamoxifen is toxic to cells of the brain and central nervous system, producing mental fogginess similar to “chemo brain.”
However, in the Journal of Neuroscience, researchers also report they’ve discovered an existing drug compound that appears to counteract or rescue brain cells from the adverse effects of the breast cancer drug.
Corresponding author Mark Noble, Ph.D., professor of Biomedical Genetics and director of the UR Stem Cell and Regenerative Medicine Institute, said it’s exciting to potentially be able to prevent a toxic reaction to one of the oldest and most widely used breast cancer medications on the market. Although tamoxifen is more easily tolerated compared to most cancer treatments, it nonetheless produces troubling side effects in a subset of the large number of people who take it.
By studying tamoxifen’s impact on central nervous system cell populations and then screening a library of 1,040 compounds already in clinical use or clinical trials, his team identified a substance known as AZD6244, and showed that it essentially eliminated tamoxifen-induced killing of brain cells in mice.
“As far as I know, no one else has discovered an agent that singles out and protects brain and central nervous system cells while also not protecting cancer cells,” said Noble, who also collaborates with researchers at the UR’s James P. Wilmot Cancer Center. “This creates a whole new paradigm; it’s where we need to go.”
The research is the result of two separate but related projects from Noble’s lab. One investigates the science underlying a condition known as “chemo brain,” and another is looking at how to exploit tamoxifen’s attributes for use in other types of cancer besides early-stage, less-aggressive breast cancer. (The drug is a type of hormonal therapy, which works by stopping the growth of estrogen-sensitive tumors.)
In the Journal of Neuroscience paper, Noble’s team first identified central nervous system (CNS) cells that are most vulnerable to tamoxifen toxicity. Chief among these were oligodendrocyte-type 2 astrocyte progenitor cells (O-2A/OPCs), cells that are essential for making the insulating sheaths (called myelin) required for nerve cells to work properly. Exposure to clinically relevant levels of tamoxifen for 48 hours killed more than 75 percent of these cells.
In earlier work, while studying the biology of the cognitive difficulties that linger in some people being treated for cancer, Noble and colleagues discovered that 5-fluorouracil, (cisplatin, cytarabine, carmustine), and multiple other types of chemotherapy, damages populations of stem cells in the CNS. Published in the Journal of Biology (1, 2) in 2006 and 2008, these studies pioneered analysis of the biological foundations of chemo brain.
“It’s critical to find safe treatments that can rescue the brain from impairment,” Noble said, “because despite increasing awareness and research in this area, some people continue to endure short-term memory loss, mental cloudiness, and trouble concentrating. For some patients the effects wear off over time, but others experience symptoms that can lead to job loss, depression, and other debilitating events.”
Noble’s lab, led by post-doctoral fellow Hsing-Yu Chen, Ph.D., identified 27 drugs that protected O-2A/OPCs from the effects of tamoxifen. Further testing resulted in singling out AZD6244, by other laboratories as a potential cancer therapy.
In mice co-treated with tamoxifen plus AZD6244, cell death in the corpus callosum, the largest white matter (myelinated) structure in the brain, was prevented, the paper reported. Meanwhile, several national clinical trials are testing the safety and effectiveness of AZD6244 in treating multiple cancers, from breast and colon to melanoma and lung.
Researchers were also optimistic about finding that while AZD6244 protected brain cells, it did not also protect cancer cells. New drug compounds have greater value if they do not compromise the effects of existing treatments, and in this case, Noble said, the experiments in his laboratory agreed with studies by other research groups, who found that the combined use of AZD6244 and chemotherapy enhances targeting of cancer cells.
In future work, Noble’s group plans to identify the dosage of AZD6244 that provides maximum protection and minimum disruption to differentiating brain cells. Their research was supported by the U.S. Department of Defense, National Institutes of Health, Susan Komen Race for the Cure, and the Carlson Stem Cell Fund.
This is the second tamoxifen-related study to come from Noble’s lab in 2013. In April they showed in pre-clinical research they could leverage the drug’s various cellular activities so that it might work on more aggressive triple-negative breast cancer. In the journal EMBO Molecular Medicine, Noble and Chen also reported finding an experimental compound that enhances tamoxifen’s ability to work in this new way.
(Source: urmc.rochester.edu)
Researchers Identify Physiological Evidence of ‘Chemo Brain’
Chemotherapy can induce changes in the brain that may affect concentration and memory, according to a study presented at the annual meeting of the Radiological Society of North America (RSNA). Using positron emission tomography combined with computed tomography (PET/CT), researchers were able to detect physiological evidence of chemo brain, a common side effect in patients undergoing chemotherapy for cancer treatment.
"The chemo brain phenomenon is described as ‘mental fog’ and ‘loss of coping skills’ by patients who receive chemotherapy," said Rachel A. Lagos, D.O., diagnostic radiology resident at the West Virginia University School of Medicine and West Virginia University Hospitals in Morgantown, W.V. "Because this is such a common patient complaint, healthcare providers have generically referred to its occurrence as ‘chemo brain’ for more than two decades."
While the complaint may be common, the cause of chemo brain phenomenon has been difficult to pinpoint. Some prior studies using magnetic resonance imaging (MRI) have found small changes in brain volume after chemotherapy, but no definitive link has been found.
Instead of studying chemotherapy’s effect on the brain’s appearance, Dr. Lagos and colleagues set out to identify its effect on brain function. By using PET/CT, they were able to assess changes to the brain’s metabolism after chemotherapy.
"When we looked at the results, we were surprised at how obvious the changes were," Dr. Lagos said. "Chemo brain phenomenon is more than a feeling. It is not depression. It is a change in brain function observable on PET/CT brain imaging."
PET/CT results demonstrated statistically significant decreases in regional brain metabolism that were closely associated with symptoms of chemo brain phenomenon.
"The study shows that there are specific areas of the brain that use less energy following chemotherapy," Dr. Lagos said. "These brain areas are the ones known to be responsible for planning and prioritizing."
Dr. Lagos believes that PET/CT could be used to help facilitate clinical diagnosis and allow for earlier intervention.