A new study provides the best evidence to date that a psychological intervention program designed for breast cancer patients not only improves their health - it actually increases their chance of survival.

Researchers at Ohio State University’s Comprehensive Cancer Center found that patients participating in an intervention program reduced their risk of dying of breast cancer by 56 percent after an average of 11 years.

Participants in the program, which taught strategies to reduce stress, improve mood and alter health behaviors, also reduced the risk of breast cancer recurrence by 45 percent.

“The results suggest that we can help breast cancer patients make positive steps that may help them live longer and make recurrence less likely,” said Barbara Andersen, lead author of the study and a member of Ohio State’s Comprehensive Cancer Center and professor of psychology.

“We already knew a psychological intervention program could help breast cancer patients to handle their stress, function more effectively, and improve their health. Now we know it does even more.”

The study will be published in the Dec. 15 issue of the journal Cancer, and is currently available to subscribers online.

The study is part of the long-running Stress and Immunity Breast Cancer Project at Ohio State. Participants included 227 patients who were surgically treated for Stage II or Stage III breast cancer.

Half of the patients were enrolled in the intervention program, while the other half were simply assessed on a regular basis. All received their regular medical treatments as well.

Those in the intervention group met weekly in groups of 8 to 12 with a clinical psychologist. During these weekly sessions, which continued for four months, participants learned progressive muscle relaxation for stress reduction, problem solving for common difficulties (such as fatigue), how to find support from family and friends, exercise and diet tips, and how to deal with treatment side effects and keep up with medical treatment and follow-up.

After four months of weekly sessions, participants met monthly for eight months.

Researchers have followed up regularly with all those who took part in the study. By October 2007, patients had been followed from 7 to 13 years.

In addition to improving survival and reducing recurrence, the intervention program had other positive effects, said Andersen.

Among patients who died of breast cancer, those who participated in the intervention program lived longer - an average of 6.1 years for program participants versus 4.8 years for those who were simply assessed.

Intervention participants were also less likely to die from causes other than breast cancer, such as heart disease or other cancers. For those who died of any cause, participants in the intervention lived an average of 6 years compared to 5 years for those who didn’t.

“Many of the strategies patients learned in the intervention program, such as stress reduction, may have protected them from heart disease and other causes of death,” Andersen said.

Researchers did a follow-up analysis in which they excluded people who were put in the intervention group, but who attended fewer that 20 percent of the sessions (16 of the 114 participants fit this requirement). When the infrequent attendees were excluded, the remainder had a 68-percent reduced risk of breast cancer death, compared to the 56-percent risk reduction for the whole participant group.

Andersen said this study was unique in several ways. In the 1980s and 90s, two separate studies found higher survival rates for cancer patients who participated in intervention programs; one study involved breast cancer patients whose disease had already recurred, and the other study included newly diagnosed melanoma patients. But these studies were not designed to look at how the interventions affected survival rates. When other researchers tried to replicate these results, they found no effect for intervention programs.

This new study, though, was designed to look specifically at recurrence and survival rates, Andersen said. In addition, the intervention program is different and so are the participants in the study.

Participants in the Ohio State study had Stage II and III breast cancer, which means their chance of survival were better than those with Stage IV cancer (which means the cancer has spread to other parts of the body), but not as good as those diagnosed with Stage I.

“We wanted those patients in the middle, where we felt we had the most chance of influencing their future course with the disease,” she said.

How did the intervention program help cancer patients?

“We believe the significant psychological improvements and behavior changes may have been critical,” according to Andersen.

For example, the researchers found that patients in the intervention group who had the greatest reductions in distress and physical symptoms were those who practiced progressive muscle relaxation most frequently. They also understood and remembered that continued stress could hurt their health and now knew several ways to reduce stress.

“We found a strong relationship between patients’ use of the intervention strategies we taught them and better health,” she said.

Previous research with the same women in this study showed that women in the intervention showed signs of improved immune function compared to those who did not participate. That is most likely related to the lower levels of distress they felt, Andersen said.

Overall, the results show a promising new way to help treat cancer patients, she said.

“If psychological interventions to reduce stress are delivered early, they can improve mental health, health, and possibly even their odds of survival.”

Barbara Andersen
Ohio State University

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Scientists at the University of Texas at Austin have identified pathways by which a reduced-calorie diet and exercise can modify a postmenopausal woman’s risk of breast cancer.

The results, presented at the American Association for Cancer Research’s Seventh Annual International Conference on Frontiers in Cancer Prevention Research, suggest that both caloric restriction and exercise affect pathways leading to mTOR, a molecule involved in integrating energy balance with cell growth. Dysregulation of the mTOR pathway is a contributing factor to various human diseases, including cancers. Diet and exercise reach mTOR through different means, with calorie restriction affecting more upstream pathways, which could explain why caloric restriction is more efficient in delaying tumor growth than exercise in animal models.

“One of the few breast cancer modifiable risk factors is obesity,” said lead author Leticia M. Nogueira, Ph.D., a research graduate assistant at the University of Texas. “Our study may provide a good scientific basis for medical recommendations. If you’re obese, and at high risk for breast cancer, diet and exercise could help prevent tumor growth.”

Epidemiological data has suggested that inducing a so-called “negative energy balance” (where less energy is taken in than expended) through eating a low-calorie diet or increasing exercise levels, decreases the postmenopausal breast cancer risk associated with obesity. Although the mechanism responsible for these anti-obesity strategies was unknown, scientists have suspected hormone alteration plays a critical role. Increased fat tissue is known to be associated with alterations in adipokines, proteins secreted by fat tissue that help modify appetite and insulin resistance. For example, increased levels of leptin and decreased levels of adiponectin have been associated with breast cancer risk.

For the study, Nogueira and colleagues sought to compare the changes in adipokines, and their downstream signaling pathways proven to be altered in human breast cancers, following either caloric restriction or exercise in a mouse model of post-menopausal obesity.

For eight weeks, they administered a high-fat diet to 45 mice that had their ovaries surgically removed to model the post-menopausal state. During week nine of the study, the diet-induced obese mice were randomly assigned to one of three groups: a control group, permitted to eat at will; a group fed a diet reduced in calories by 30 percent; and a group that was permitted to eat at will but exercised on a treadmill for 45 minutes a day, five days a week. At week 16, researchers collected tissue from the mice for analysis.

At the study’s end, the mice fed a calorie-restricted diet weighed an average of 19.9 grams - significantly less than the control mice (average weight 28.8 grams) and the exercised mice (average weight 26 grams). The calorie-restricted mice and the exercised mice showed no significant difference in percentage of body fat, but both groups had significantly less body fat than the sedentary mice that were fed at will.

In addition, blood levels of leptin, a hormone that plays a role in fat metabolism, were significantly reduced in the calorie-restricted and exercised mice compared to the controls. The calorie-restricted mice also displayed increased blood levels of adiponectin, a hormone produced in fat tissue that regulates some metabolic processes, compared to the exercised mice.

Some of the cell signaling pathways regulated by these hormones converge at mTOR, Nogueira explains. She and her colleagues found that the key proteins found downstream of mTOR activation were less active in both the calorie-restricted and exercised mice compared to the controls.

“These data suggest that although exercise can act on similar pathways as caloric restriction, caloric restriction possesses a more global effect on cell signaling and, therefore, may produce a more potent anti-cancer effect,” Nogueira said.

Jeremy Moore
American Association for Cancer Research

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All of us have experienced being in a new place and feeling certain that we have been there before. This mysterious feeling, commonly known as déjà vu, occurs when we feel that a new situation is familiar, even if there is evidence that the situation could not have occurred previously. For a long time, this eerie sensation has been attributed to everything from paranormal disturbances to neurological disorders. However, in recent years, as more scientists began studying this phenomenon, a number of theories about déjà vu have emerged, suggesting that it is not merely a glitch in our brain’s memory system. A new report by Colorado State University psychologist Anne M. Cleary, published in Current Directions in Psychological Science, a journal of the Association for Psychological Science, describes recent findings about déjà vu, including the many similarities that exist between déjà vu and our understanding of human recognition memory.

Recognition memory is the type of memory that allows us to realize that what we are currently experiencing has already been experienced before, such as when we recognize a friend on the street or hear a familiar song on the radio. The brain fluctuates between two different types of recognition memory: recollection and familiarity. Recollection-based recognition occurs when we can pinpoint an instance when a current situation has previously occurred. For example, seeing a familiar man at a store and realizing that we’ve seen him before on the bus. On the other hand, familiarity-based recognition occurs when our current situation feels familiar, but we don’t remember when it has happened before. For example, we see that familiar man in the store, but we just can’t remember where we know him from. Déjà vu is believed to be an example of familiarity-based recognition - during déjà vu, we are convinced that we recognize the situation, but we are not sure why.

Cleary conducted experiments testing familiarity-based recognition in which participants were given a list of celebrity names. Later on, they were shown a collection of celebrity photographs; some photographs corresponded to the names on the list, other photographs did not. The volunteers were told to identify the celebrities in the photographs and indicate how likely it was the celebrity’s names were on the list they had seen previously. The findings were surprising. Even when the volunteers were unable to identify a celebrity by photo, they had a sense of which names they had studied earlier and which they had not. That is, they couldn’t identify the source of their familiarity with the celebrity, but they knew the celebrity was familiar to them. Cleary repeated the experiment substituting famous places (such as Stonehenge and the Taj Majal) for celebrities and got similar results. These findings indicate that the participants stored a little bit of the memory, but it was hazy, so they were not able to connect it to the new experience.

Cleary also ran experiments to figure out what features or elements of situations could trigger feelings of familiarity. She had participants study a random list of words. During a word recognition test, some of the words on the test resembled the earlier words, although only in sound (e.g. lady sounds similar to eighty), but the volunteers reported a sense of familiarity for the new words, even when they could not recall the earlier-presented, similar-sounding words that were the source of this familiarity. Previous research has also shown that people feel familiarity when shown a visual fragment containing isolated geometric shapes from an earlier experience. This suggests that familiar geometric shapes may create the sense that an entire new scene has been viewed before.

These results support the idea that events and episodes which we experience are stored in our memory as individual elements or fragments of that event. Déjà vu may occur when specific aspects of a current situation resemble certain aspects of previously occurring situations; if there is a lot of overlap between the elements of the new and old situations, we get a strong feeling of familiarity. “Many parallels between explanations of déjà vu and theories of human recognition memory exist”, Cleary concludes, “Theories of familiarity-based recognition and the laboratory methods used to study it may be especially useful for elucidating the processes underlying déjà vu experiences.”

Catherine West
Association for Psychological Science

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The cancer preventive properties of broccoli and other cruciferous vegetables appear to work specifically in smokers, according to data presented at the American Association for Cancer Research’s Seventh Annual International Conference on Frontiers in Cancer Prevention Research.

Cruciferous vegetables have been shown to be protective in numerous studies, but this is the first comprehensive study that showed a protective benefit in smokers, specifically in former smokers, according to lead author Li Tang, Ph.D., a post-doctoral fellow at Roswell Park Cancer Institute.

“Broccoli is not a therapeutic drug, but for smokers who believe they cannot quit nor do anything about their risk, this is something positive,” Tang said. “People who quit smoking will definitely benefit more from intake of cruciferous vegetables.”

Li and colleagues conducted a hospital-based, case-controlled study with lung cancer cases and controls matched on smoking status. The study included all commonly consumed cruciferous vegetables, and also considered raw versus cooked form. Researchers performed statistical calculations to take into account smoking status, duration and intensity.

Among smokers, the protective effect of cruciferous vegetable intake ranged from a 20 percent reduction in risk to a 55 percent reduction in risk depending on the type of vegetable consumed and the duration and intensity of smoking.

For example, among current smokers, only the consumption of raw cruciferous vegetables was associated with risk reduction of lung cancer. No significant results were found for consumption of vegetables in general and fruits.

Researchers further divided their findings by four subtypes of lung cancer and found the strongest risk reduction among patients with squamous or small-cell carcinoma. These two subtypes are more strongly associated with heavy smoking.

“These findings are not strong enough to make a public health recommendation yet,” said Li. “However, strong biological evidence supports this observation. These findings, along with others, indicate cruciferous vegetables may play a more important role in cancer prevention among people exposed to cigarette-smoking. ”

Jeremy Moore
American Association for Cancer Research

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New research has traced elevated levels of a specific compound in the brain to problem-solving deficits in patients with schizophrenia.

The finding suggests that drugs used to suppress the compound, called kynurenic acid, might be an important supplement to antipsychotic medicines, as these adjuncts could be used to treat the disorder’s most resistant symptoms - cognitive impairments.

Though schizophrenia is commonly characterized by hallucinations and delusions, patients also have problems with what is known as cognitive flexibility or executive decision-making. Many patients can set a goal and plan one way to achieve it, but cannot adjust their thinking if circumstances force them to consider alternative strategies.

“We’ve got this core cluster of symptoms that is the Achilles heel for these individuals, and we’re not really doing a good job of treating them,” said John P. Bruno, professor of psychology, psychiatry and neuroscience at Ohio State University and principal investigator of the research.

Bruno and colleagues have combined advanced animal modeling of schizophrenia-related chemical changes in the brain with the observation that the production of too much kynurenic acid is linked to troubled thinking that affects the research animals’ behavior.

The compound is present in all human brains and has some useful functions. But in excessive amounts, the researchers found, kynurenic acid interferes with other chemical processes that govern the ability to pay attention and think strategically under changing conditions.

“If we try to make predictions about how disabled patients with schizophrenia will be and how likely are they to be integrated into the social fabric, it’s the severity of the cognitive deficits that are most predictive,” Bruno said. “Antipsychotics are particularly good at what we call positive symptoms, but these same drugs are very poor at treating the cognitive deficits.

“There are a lot of therapeutic strategies for dealing with schizophrenia, but one which has not been explored, and which we think has a great deal of promise, has to do with regulating production of kynurenic acid,” Bruno said.

He described the research Tuesday (11/18) at the Society for Neuroscience meeting in Washington, D.C.

Bruno and colleagues tested kynurenic acid’s effects on cognitive abilities in rats. Seven rats were given a compound that stimulated excess production of the molecule in their brains, while a control group of rats received no such stimulation. All of the rats were subjected to a test gauging their ability to make what is called an extra-dimensional set shift, requiring them to change response strategies based on changing contingencies - in this case, in a quest to find food.

Only 28 percent of the rats with elevated kynurenic acid were able to solve problems to receive a food reward, compared to 100 percent of the control animals. Before the intervention, all of the animals were equally able to find the food under changing circumstances.

The kynurenic acid essentially exacerbates a phenomenon already observed in patients with schizophrenia - the fact that two neurotransmitters in their brains are not as active as they need to be to allow for normal problem-solving capabilities.

These two neurotransmitters critical to normal cognition are acetylcholine and glutamate. Their activity is partially regulated by what are called alpha-7 receptors, a class of proteins involved in the brain’s chemical communication system. In the case of schizophrenia, these neurotransmitters are already at abnormally low levels, most likely because of genetic mutations.

Excess levels of kynurenic acid inhibit the work of the alpha-7 receptors, meaning they suppress the release of these neurotransmitters even more.

“So we’ve already got problems with these neurotransmitters, and then to make matters worse, we’ve got all this extra kynurenic acid antagonizing the alpha-7 receptors, which just throws gasoline onto the fire,” Bruno said. “If we can design drugs that are able to inhibit the enzymes that are responsible for overproducing kynurenic acid, we may improve cognitive performance in these patients.”

Antipsychotic agents used to control hallucinations and delusions act on different neurotransmitters. Agents targeting kynurenic acid production could be part of a medication cocktail that could restore additional neurochemistry responsible for cognition, Bruno said.

Bruno’s research group is able to precisely gauge the effects of the compound on neurotransmitters in the brain because of the animal model used for the research. Schizophrenia was once considered too complex a disorder to model in an animal brain, but Bruno and colleagues have developed a rat model to focus on specific cognitive deficits traced to the part of the brain known as the prefrontal cortex.

An element of the modeling is the painless use of microelectrodes in the animals’ brains to measure neurotransmitter levels before and after introduction of the agent that elevates kyurenic acid. The real-time measurements allow the scientists to prove the causal relationship between the elevated compound and the reduced presence of the neurotransmitters.

“No one is claiming that we’re producing rats with schizophrenia. What we can do is model the neural side pathologies and see if those pathologies lead to behavioral impairments that look like what see on the clinical side. When we get both of those to line up as we have in this model, we have a valid model to ask questions about developing novel therapeutics,” Bruno said. “This has allowed us to move from molecules to neurotransmitters to cognitive behavior all in one fell swoop. These findings set the foundation for several years of research that we hope will have some very big implications.”

John Bruno
Ohio State University

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A new study confirms that exercise can reverse the age-related decline in the production of neural stem cells in the hippocampus of the mouse brain, and suggests that this happens because exercise restores a brain chemical which promotes the production and maturation of new stem cells.

Neural stem cells and progenitor cells differentiate into a variety of mature nerve cells which have different functions, a process called neurogenesis. There is evidence that when fewer new stem or progenitor cells are produced in the hippocampus, it can result in impairment of the learning and memory functions. The hippocampus plays an important role in memory and learning.

The study, “Exercise enhances the proliferation of neural stem cells and neurite growth and survival of neuronal progenitor cells in dentate gyrus of middle-aged mice,” was carried out by Chih-Wei Wu, Ya-Ting Chang, Lung Yu, Hsiun-ing Chen, Chauying J. Jen, Shih-Ying Wu, Chen-Peng Lo, Yu-Min Kuo, all of the National Cheng Kung University Medical College in Taiwan. The study appears in the November issue of the Journal of Applied Physiology, published by The American Physiological Society.

American Physiological Society

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Researchers at the University of California, San Francisco have reported that two common cancer drugs have been used to block and reverse type 1 diabetes in mice. The JDRF-funded study, published in The Proceedings of the National Academy of Sciences, was led by Jeffrey Bluestone, Ph.D., director of the Diabetes Center at UCSF and an expert in the field of autoimmunity.

“The findings suggest that kinase inhibitors - successfully used in cancer - may provide an important new therapeutic approach for treatment of new onset type 1 diabetes and potentially other autoimmune disorders,” said JDRF Director of Immunology Teodora Staeva, Ph.D.

The drugs - Imatinib and Sunitnib, sold as Gleevec and Sutent, respectively - are used to treat cancer by blocking tyrosine kinases, an enzyme that modify cells’ signaling proteins through a simple biochemical change. Kinases trigger cell growth, and it is widely believed that tyrosine kinases are a contributing factor to autoimmune diseases and cancer. The researchers hypothesized that tyrosine kinases may also serve as a trigger to the body’s attack on the immune system.

The researchers at the University of California, San Francisco treated non-diabetic mice prone to developing diabetes with imatinib or sunitinib, and found that the drugs prevented the onset of diabetes past the seven-week treatment. Mice that already developed diabetes were treated with the drugs and results concluded that after two months of treatment, 80 percent no longer had diabetes.

Jillian Lubarsky
Juvenile Diabetes Research Foundation International

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