Exercise Could Fortify Immune System Against Future Cancers

Researchers may soon be able to add yet another item to the list of exercise's well-documented health benefits: A preliminary study suggests that when cancer survivors exercise for several weeks after they finish chemotherapy, their immune systems remodel themselves to become more effective, potentially fending off future incidents of cancer. The finding may help explain why exercise can significantly reduce the chances of secondary cancers in survivors or reduce the chances of cancer altogether in people who have never had the disease.

Laura Bilek, Graham Sharp, and Geoffrey Thiele, all of the University of Nebraska Medical Center, and Daniel Shackelford, Colin Quinn, and Carole Schneider, all of Rocky Mountain Cancer Rehabilitation Institute, analyzed T cells in the blood of cancer survivors before and after a 12-week exercise program. They found that a significant portion of these immune cells converted from a senescent form, which isn't as effective at combating disease, to a naïve form, ready to fight cancer and infections.

Their poster presentation entitled, "Effect of Exercise on T Cells in Cancer Survivors," will be discussed at The Integrative Biology of Exercise VI meeting being held October 10-13 at the Westin Westminster Hotel in Westminster, CO. This popular meeting is a collaborative effort between the American Physiological Society, the American College of Sports Medicine and the Canadian Society for Exercise Physiology. The conference is supported in part by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, an institute of the National Institutes of Health, GlaxoSmithKline, Inc., Stealth Peptides, Inc., and Seahorse Biosciences.

Exercise and Immunity

Study leader Laura Bilek explains that previous research had turned up a variety of positive associations between exercise and cancer -- notably, that exercise can reduce the risk of getting initial incidence of several different types of cancers, can often improve prognosis in cancer patients, and can reduce the risk of recurrence and secondary cancers survivors of some types of cancers. However, the mechanism behind these phenomena has been unknown.

Since other research has suggested that exercise can remodel the immune system, making it more effective at fighting disease in general, Bilek and her colleagues decided to investigate how exercise affects the immune system of cancer patients. Working with a group of 16 cancer survivors, all but one of who recently finished chemotherapy cancer treatment, the researchers focused on T cells, a type of immune cell that attacks a variety of infectious agents as well as cancer cells. After chemotherapy, previous research had shown that the majority of T cells become senescent, with a decreased ability to fight infections and cancers. However, Bilek says, rebuilding the population of responsive (naïve) T cells is critical for regaining normal immune function and cancer-fighting ability.

The researchers first took blood samples from each of the volunteers to examine how many senescent and naïve T cells each had. Then, these study subjects were all enrolled into 12-week exercise programs at the Rocky Mountain Cancer Rehabilitation Institute. All programs were individualized for the study participants, incorporating elements of cardiovascular exercise, strength and endurance training, and exercises for flexibility, posture, and balance, with extra emphasis in areas where participants were weak.

After the 12-week program, the researchers drew a second blood sample from each volunteer and ran the same T cell analysis.

Another Reason to Work Out Results showed that the ratio of senescent to naïve T cells changed favorably in the majority of participants, with most of the study subjects regaining greater numbers of the naïve variety.

"What we're suggesting is that with exercise, you might be getting rid of T cells that aren't helpful and making room for T cells that might be helpful," Bilek says.

She adds that this finding highlights the importance of exercise for all, including those with cancer and cancer survivors. These two populations might benefit especially from the heightened "cancer surveillance" -- the ability of the immune system to seek out and destroy budding cancers -- that this study suggests exercise brings, Bilek explains.

"There's a litany of positive benefits from exercise," Bilek says. "If exercise indeed strengthens the immune system and potentially improves cancer surveillance, it's one more thing we should educate patients about as a reason they should schedule regular activity throughout their day and make it a priority in their lives."

Fast walking and jogging halve development of heart disease and stroke risk factors

But an hour's walk every day makes no difference: Intensity rather than duration is what counts

The findings indicate that it is the intensity, rather than the duration, of exercise that counts in combating the impact of metabolic syndrome - a combination of factors, including midriff bulge, high blood pressure, insulin resistance, higher than normal levels of blood glucose and abnormal blood fat levels - say the authors.

Genes, diet, and lack of exercise are thought to be implicated in the development of the syndrome, which is conducive to inflammation and blood thickening.

The authors base their findings on more than 10,000 Danish adults, between the ages of 21 and 98, who were initially assessed in 1991-94 and then monitored for up to 10 years. All the participants were quizzed on the amount of physical activity they did, which was categorised according to intensity and duration.

At the initial assessment, around one in five (20.7%) women and just over one in four (27.3%) men had metabolic syndrome. Prevalence was closely linked to physical activity level.

Among the women, almost one in three of those who had a sedentary lifestyle had the syndrome whereas only one in 10 of those who were very physically active had it. Among men, the equivalent proportions were just under 37% and just under 14%

Of the remaining 6,088 participants without metabolic syndrome, just under two thirds (3,992) completed the fourth and final survey and assessment, by which point one in seven (15.4%; 585) had developed it.

Again, the prevalence was higher among those leading a sedentary lifestyle, with almost one in five (19.4%) affected compared with around one in nine (11.8%) of those who were very physically active.

It was not only the amount of exercise, but also the intensity which helped curb the likelihood of developing the syndrome.

After taking account of factors likely to influence the results, fast walking speed halved the risk, while jogging cut the risk by 40 per cent. But going for an hour's walk every day made no difference.

"Our results confirm the role of physical activity in reducing [metabolic syndrome] risk and suggest that intensity rather than volume of physical activity is important," conclude the authors.

Caffeine may block inflammation linked to mild cognitive impairment

Recent studies have linked caffeine consumption to a reduced risk of Alzheimer's disease, and a new University of Illinois study may be able to explain how this happens.

"We have discovered a novel signal that activates the brain-based inflammation associated with neurodegenerative diseases, and caffeine appears to block its activity. This discovery may eventually lead to drugs that could reverse or inhibit mild cognitive impairment," said Gregory Freund, a professor in the U of I's College of Medicine and a member of the U of I's Division of Nutritional Sciences.

Freund's team examined the effects of caffeine on memory formation in two groups of mice—one group given caffeine, the other receiving none. The two groups were then exposed to hypoxia, simulating what happens in the brain during an interruption of breathing or blood flow, and then allowed to recover.

The caffeine-treated mice recovered their ability to form a new memory 33 percent faster than the non-caffeine-treated mice. In fact, caffeine had the same anti-inflammatory effect as blocking IL-1 signaling. IL-1 is a critical player in the inflammation associated with many neurodegenerative diseases, he said.

"It's not surprising that the insult to the brain that the mice experienced would cause learning memory to be impaired. But how does that occur?" he wondered.

The scientists noted that the hypoxic episode triggered the release of adenosine by brain cells.

"Your cells are little powerhouses, and they run on a fuel called ATP that's made up of molecules of adenosine. When there's damage to a cell, adenosine is released," he said.

Just as gasoline leaking out of a tank poses a danger to everything around it, adenosine leaking out of a cell poses a danger to its environment, he noted.

The extracellular adenosine activates the enzyme caspase-1, which triggers production of the cytokine IL-1β, a critical player in inflammation, he said.

"But caffeine blocks all the activity of adenosine and inhibits caspase-1 and the inflammation that comes with it, limiting damage to the brain and protecting it from further injury," he added.

Caffeine's ability to block adenosine receptors has been linked to cognitive improvement in certain neurodegenerative diseases and as a protectant against Alzheimer's disease, he said.

"We feel that our foot is in the door now, and this research may lead to a way to reverse early cognitive impairment in the brain. We already have drugs that target certain adenosine receptors. Our work now is to determine which receptor is the most important and use a specific antagonist to that receptor," he said.

New link between high-fat 'Western' diet and atherosclerosis identified

A diet high in omega-3 polyunsaturated fat lowers levels of problem enzyme

Columbia University Medical Center (CUMC) researchers have found that a diet high in saturated fat raises levels of endothelial lipase (EL), an enzyme associated with the development of atherosclerosis, and, conversely, that a diet high in omega-3 polyunsaturated fat lowers levels of this enzyme. The findings establish a "new" link between diet and atherosclerosis and suggest a novel way to prevent cardiovascular heart disease. In addition, the research may help to explain why the type 2 diabetes drug rosiglitazone (Avandia) has been linked to heart problems.

The study, conducted in mice, was published in the October 4 online edition of Atherosclerosis, Thrombosis, and Vascular Biology.

Like other lipases, EL plays a role in the metabolism of blood lipoproteins, which are complexes of lipids (fats) and proteins. EL, which is secreted by macrophages (a type of white blood cell) and other cells in arteries, was discovered in 1999. Studies have shown that elevated EL is associated with atherosclerosis and inflammation. Until now, however, little was known about how dietary fats might affect this enzyme, said study leader Richard Deckelbaum, MD, the Robert R. Williams Professor of Nutrition professor of pediatrics and of epidemiology and director of the Institute of Human Nutrition at CUMC.

In the current study, a strain of mice susceptible to atherosclerosis was fed a normal diet enriched with either palmitic acid (a common saturated fat) or eicosapentaenoic acid (an omega-3 fatty acid, or polyunsaturated fat, found in fish oil, among other foods). After 12 weeks, the mice's aortas were examined for changes in the expression of EL and inflammatory factors. Aortas of mice fed the saturated fat diet showed a significant increase in EL and detrimental changes in inflammatory factors, while those of mice fed the polyunsaturated fat diet showed a significant decrease in EL and beneficial changes in inflammatory factors. Studies in cultured macrophages showed similar results.

"Our study identifies a new way in which the high-saturated-fat Western diet could lead to the development of atherosclerosis, though, of course, these results need to be confirmed in human studies," said Dr. Deckelbaum. "The findings might also explain some of the cardiovascular benefits that have been attributed to omega-3 fatty acids."

The researchers also found, in cell culture studies, that macrophages fed saturated fat showed increased expression of PPAR-gamma, a cell signaling molecule that plays a role in regulating lipid metabolism and inflammatory responses. This increase was blocked when the cells were fed an omega-3 fatty acid.

"These findings are intriguing, because we know that the diabetes drug rosiglitazone (sold under the brand name Avandia) is a strong PPAR-gamma activator and that it has been associated with an increased risk of heart disease," said Dr. Deckelbaum. "So we hypothesized that if rosiglitazone activates ppar-gamma, it might also activate EL, which would explain its effects on the heart."

In fact, when the macrophages were given rosiglitazone, the expression of EL increased markedly. The addition of omega-3 fatty acids to the cells blocked this increase. "This would suggest that besides raising LDL cholesterol levels, rosiglitazone can raise the risk of cardiovascular disease by increasing EL," said Dr. Deckelbaum. "In addition to its potential role in increasing arterial inflammatory responses, EL increases the anchoring of LDL to cell surfaces, which could be associated with increased LDL accumulation in coronary arteries."

Use of Avandia was severely restricted in 2010, when the drug was linked to the development of heart disease.

Eat seven portions of fruit and vegetables for happiness and mental health

Happiness and mental health are highest among people who eat seven portions of fruit and vegetables a day, according to a new report.

Economists and public health researchers from the University of Warwick studied the eating habits of 80,000 people in Britain. They found mental wellbeing appeared to rise with the number of daily portions of fruit and vegetables people consumed. Wellbeing peaked at seven portions a day.

The research was carried out in conjunction with Dartmouth College in the USA and is due to be published in the journal Social Indicators Research.

Most western governments currently recommend ‘5 a day’ for cardiovascular health and as protection against cancer risk.

In Britain today, a quarter of the population eat just one portion or no portions of fruit and vegetables per day. Only a tenth of the British population currently consume the magic number of seven or more daily portions. The study does not distinguish among different kinds of fruits and vegetables and it defines a portion as approximately 80 grams.

Study co-author Professor Sarah Stewart-Brown, Professor of Public Health at Warwick Medical School, said “The statistical power of fruit and vegetables was a surprise. Diet has traditionally been ignored by well-being researchers.”

She emphasized that much remained to be learned about cause-and-effect and about the possible mechanisms at work, and that randomized trials should now be considered.

Fellow co-author, economist Professor Andrew Oswald from the Centre for Competitive Advantage in the Global Economy (CAGE) in the Department of Economics at the University of Warwick, said: “This study has shown surprising results and I have decided it is prudent to eat more fruit and vegetables. I am keen to stay cheery.”

Aspirin may decrease risk of aggressive form of ovarian cancer

New research shows that women who regularly use pain relief medications, particularly aspirin, have a decreased risk of serous ovarian cancer—an aggressive carcinoma affecting the surface of the ovary. The study published in Acta Obstetricia et Gynecologica Scandinavica, a journal of the Nordic Federation of Societies of Obstetrics and Gynecology, reports that non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs), paracetamol (acetaminophen), or other analgesics did not decrease ovarian cancer risk.

Ovarian cancer is the deadliest gynecological malignancy and the fifth-leading cause of death by cancer for women in developed countries. Previous studies report that Denmark has one of the highest incidence and mortality rates at 11 and 7 per 100,000 women, respectively. According to the Centers for Disease Control and Prevention (CDC), each year 20,000 women in the U.S. are diagnosed with ovarian cancer, with 90% of cases occurring in women older than 40 years of age and the greatest number in those 60 years or older.

"Ovarian cancer has a high mortality. Understanding what factors are involved in the development of this disease and investigating preventative interventions for women are vitally important," said lead author Dr. Susanne Kjær with the Danish Cancer Society Research Center. "Our study examined the role of analgesics in development of ovarian cancer."

For the present study, researchers used data from the malignant ovarian cancer (MALOVA) study, a population-based, case-control study investigating this cancer in Danish women between 1995 and 1999. The team analyzed data from 756 women with epithelial ovarian cancer, classified by type of glandular tumors (adenocarcinomas); 447 were serous, 138 were mucinous, and 171 were other types. A random sample of 1564 women between the ages of 35 and 79 were drawn from the general population as controls. Personal interviews were conducted to determine analgesic drug use.

Findings indicate that women taking aspirin on a regular basis decreased their risk of serous ovarian cancer (odds ratio, OR=.60). Researchers did not find a decrease in ovarian cancer risk in women who regularly used non-aspirin NSAIDs, acetaminophen, or other types of pain relievers.

Dr. Kjær concludes, "Our findings suggest a potential protective effect of analgesic use on ovarian cancer risk, but that benefit should be balanced against adverse effects of pain medication use, such as risk of bleeding and peptic ulcers." The authors recommend that larger studies, which accurately assess dosage, frequency and duration of pain medications, are necessary to understand the impact of analgesic use on ovarian cancer.

In his editorial, also published in this month's issue, Dr. Magnus Westgren from Karolinska University Hospital in Stockholm, Sweden concurs with the study authors that strategies for preventing ovarian cancer are imperative. Dr. Westgren discusses preventive procedures such as bilateral salingectomy (BSE)—a removal of the fallopian tubes—in women at risk for ovarian cancer.

"If we informed women about the possibility of performing BSE at repeat cesarean section for ovarian cancer prevention, it is likely that many women would opt for this procedure," writes Dr. Westgren. He suggests that gynecology professionals discuss changing policies and setting up randomized trials to further understand how BSE could reduce ovarian cancer risk.

Eating Tomatoes Lowers the Risk of Stroke

Eating tomatoes and tomato-based foods is associated with a lower risk of stroke, according to new research published in the October 9, 2012, print issue of Neurology®, the medical journal of the American Academy of Neurology. Tomatoes are high in the antioxidant lycopene.

The study found that people with the highest amounts of lycopene in their blood were 55 percent less likely to have a stroke than people with the lowest amounts of lycopene in their blood.

The study involved 1,031 men in Finland between the ages of 46 and 65. The level of lycopene in their blood was tested at the start of the study and they were followed for an average of 12 years. During that time, 67 men had a stroke.

Among the men with the lowest levels of lycopene, 25 of 258 men had a stroke. Among those with the highest levels of lycopene, 11 of 259 men had a stroke. When researchers looked at just strokes due to blood clots, the results were even stronger. Those with the highest levels of lycopene were 59 percent less likely to have a stroke than those with the lowest levels.

"This study adds to the evidence that a diet high in fruits and vegetables is associated with a lower risk of stroke," said study author Jouni Karppi, PhD, of the University of Eastern Finland in Kuopio. "The results support the recommendation that people get more than five servings of fruits and vegetables a day, which would likely lead to a major reduction in the number of strokes worldwide, according to previous research."

The study also looked at blood levels of the antioxidants alpha-carotene, beta-carotene, alpha-tocopherol and retinol, but found no association between the blood levels and risk of stroke.