February 20, 2013
By Robin Lally
Study finds fog-like condition related to Chemotherapy's effect on new brain cells and rhythms
It's not unusual for Cancer patients being treated with chemotherapy to complain about not being able to think clearly, connect thoughts or concentrate on daily tasks. The complaint – often referred to as chemo-brain – is common. The scientific cause, however, has been difficult to pinpoint.
New research by Rutgers University behavioral neuroscientist Tracey Shors offers clues for this fog-like condition, medically known as chemotherapy-induced Cognitive impairment. In a featured article published in the European Journal of Neuroscience, Shors and her colleagues argue that prolonged chemotherapy decreases the development of new brain cells, a process known as neurogenesis, and disrupts ongoing brain rhythms in the part of the brain responsible for making new memories. Both, she says, are affected by learning and in some cases are necessary for learning to occur.
"One of the things that these brain rhythms do is to connect information across brain regions," says Shors, Professor II in the Department of Psychology and Center for Collaborative Neuroscience at Rutgers. "We are starting to have a better understanding of how these natural rhythms are used in the process of communication and how they change with experience."
Working in the Shors laboratory, postdoctoral fellow Miriam S. Nokia from the Department of Psychology at the University of Jyvaskyla in Finland and Rutgers neuroscience graduate student Megan Anderson treated rats with a chemotherapy drug – Temozolomide (TMZ) – used on individuals with either Malignant brain tumors or skin cancer to stop rapidly dividing cells that have gone out of control and resulted in cancer.
In this study, scientists found that the production of new healthy brain cells treated with the TMZ was reduced in the hippocampus by 34 percent after being caught in the crossfire of the drug's potency. The cell loss, coupled with the interference in brain rhythms, resulted in the animal being unable to learn difficult tasks.
Shors says the rats had great difficulty learning to associate stimulus events if there was a time gap between the activities but could learn simple task if the stimuli were not separated in time. Interestingly, she says, the drug did not disrupt the memories that were already present when the treatment began.
For cancer patients undergoing long-term chemotherapy this could mean that although they are able to do simple everyday tasks, they find it difficult to do more complicated activities like processing long strings of numbers, remembering recent conversations, following instructions and setting priorities. Studies indicate that while most cancer patients experience short-term memory loss and disordered thinking, about 15 percent of cancer patients suffer more long-lasting cognitive problems as a result of the chemotherapy treatment.
"Chemotherapy is an especially difficult time as patients are learning how to manage their treatment options while still engaging in and appreciating life. The disruptions in brain rhythms and neurogenesis during treatment may explain some of the cognitive problems that can occur during this time. The good news is that these effects are probably not long-lasting," says Shors.
Median survival in a Phase I clinical trial at Cedars-Sinai’s Johnnie L. Cochran, Jr. Brain Tumor Center was 38.4 months, significantly longer than the typical 14.6-month survival of patients with newly diagnosed glioblastoma receiving standard therapy alone, which includes radiation and chemotherapy.
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Wake Forest Baptist Only Center in Southeast to Participate in Clinical Trial
WINSTON-SALEM, N.C., Jan. 5, 2012 /PRNewswire-USNewswire
A national clinical trial testing the efficacy of a novel brain tumor vaccine has begun at Wake Forest Baptist Medical Center, the only facility in the Southeast to participate.
The vaccine will be tested in patients with newly diagnosed glioblastoma multiforme (GBM), the most aggressive and highest grade malignant glioma. Wake Forest Baptist will treat a minimum of 25 patients in this randomized, placebo-controlled phase II clinical trial of ICT-107. A total of 20 sites across the country are participating in the trial to test the safety and efficacy of this novel cancer vaccine.
All patients enrolled in the study will receive the current standard treatment for GBM, which includes surgery followed by radiation and chemotherapy. Two thirds of the participants will then also get the experimental vaccine treatment, which will be administered in the post radiation phase of treatment, while the others will get a "dummy," or placebo vaccine in addition to standard therapy.
"This vaccine is for newly-diagnosed patients," said Glenn Lesser, M.D., a professor of internal medicine, hematology-oncology, at Wake Forest Baptist and principal investigator for the study. "Scientifically, it's a very well designed study and we are excited to participate in this clinical trial. We've been asked to participate based on our reputation as an outstanding brain tumor center and the expertise our center has with bringing novel therapies and novel therapeutics to patients."
The approach with this particular vaccine is unique, Lesser added, because it is targeting the antigens or proteins that are present on glioma stem cells, whereas other treatment approaches mostly target differentiated tumor cells.
"The antigens used in this vaccine target the tumor stem cells – the handful of cells that keep the tumor alive and dividing. Most of the cells we kill with standard treatment are likely not the ones driving the tumor growth. If the stem cells aren't targeted, they keep generating more tumors."
According to the biotechnology company that is conducting the trial, the Phase I clinical study of ICT-107 in GBM involved 16 newly-diagnosed patients who received the vaccine in addition to standard therapy – surgery, radiation and chemotherapy. Those patients demonstrated a one-year overall survival of 100 percent and a two-year survival of 80 percent. Although only a small number of patients were treated, these results compare favorably with historical 61 percent one-year and 26 percent two-year survival with standard care alone.
Vaccines for brain tumors are new and experimental, said Lesser, but are gaining more attention in the glioma world.
"Vaccines are a way to harness the body's own defenses – which are usually used to ward off or control infections like the flu – to fight cancer cells instead," Lesser explained. "It is a way of presenting antigens or proteins normally found on the surface of the cancer cells to the immune system so that immune cells can seek out and kill those cancer cells anywhere in the body. This is not unlike giving a piece of clothing to a bloodhound and then letting it loose to find a missing person."
Wake Forest Baptist is also involved in another brain tumor vaccine trial for patients with low-grade or slower growing gliomas. Among the targets of both of these vaccines is a new protein found on the surface of glioma cells discovered by Waldemar Debinski, M.D., Ph.D., director of the Wake Forest Baptist Brain Tumor Center of Excellence.
"Early studies of vaccines for patients with brain tumors are showing promising results," Lesser said. "We want to help definitively determine how good these novel therapies really are for patients."
A noninvasive device that creates an alternating electrical current in brain tumors may be as effective against recurrent glioblastoma multiforme as chemotherapy, according to updated survival data from a phase III trial.
To read more about this article, click on the CURE.
Submitted by Keri Boer
NEW YORK (Reuters Health)
July 13, 2011
PHILADELPHIA — Stem cell therapy may restore cognition in patients with brain cancer who experience functional learning and memory loss often associated with radiation treatment, according to a laboratory study published in Cancer Research, a journal of the American Association for Cancer Research.
Charles Limoli, Ph.D., a professor in the department of radiation oncology at the University of California, Irvine, said radiation therapy is the standard of care for most brain cancers, but the side effects can be devastating.
“In almost every instance, people experience severe cognitive impairment that is progressive, debilitating and adversely impacts quality of life,” he said. “Pediatric cancer patients can experience a drop of up to three IQ points per year.”
In the current study, Limoli and colleagues subjected rats to cranial irradiation and followed up two days later with human neural stem cell transplants. A significant proportion of these cells survived and turned into brain cells found at one- and four-month evaluations. Cognitive function significantly improved compared with control rats.
Limoli said the findings of this study were significant, and may help pave the way for a human safety trial to be conducted within a few years if appropriate funding can be secured. Neural stem cells like those used in this study do not present the same ethical questions as embryonic stem cells.
Submitted by Keri Boer