Sirtuin gene blocks prostate cancer growth
A report published in the November 1, 2006 issue of the journal Molecular and Cellular Biology revealed that expression of SIRT1, a gene involved in the regulation of aging which is activated by calorie restriction, blocks the growth of prostate cancer cells.
Oncology researchers at the Kimmel Cancer Center at Thomas Jefferson University in Philadelphia led by Richard Pestell, MD, PhD, showed that SIRT1 blocks the activity of mutated androgen receptor cells found in prostate cancer patients who are resistant to androgen blockade therapy. Androgens are hormones such as dihydrotestosterone which can fuel prostate cancer growth. Blocking the production of these hormones normally inactivates the androgen receptor, causing a regression in prostate tumor growth.
“We’ve shown that by making a prostate cancer with cells overexpressing a mutation for the androgen receptor, which is resistant to current forms of therapy, we can almost completely block the growth of these cells with SIRT1,” explained Dr. Pestell, who is the Kimmel Cancer Center director. "We systematically tested each androgen receptor mutation. These mutant receptors are resistant to current therapies and are all blocked by expression of SIRT1.”
Dr Pestell's team confirmed the effect by measuring levels of prostate specific antigen levels, a prostate tumor marker that is used to evaluate the effectiveness of cancer treatments. Additionally, they confirmed that a single amino acid in the androgen receptor reacts with SIRT1’s enzymatic activity to block cancer growth.
“We know that sirtuins play a role in aging, and that the risk for prostate cancer increases with aging, but no one has ever linked the two until now,” Dr. Pestell stated. “This study shows that there is potentially new opportunity for these cancer patients with drugs that regulate SIRT1."
Unhealthy dietary patterns linked with increased colorectal tumor risk
A study published in the December 1, 2006 issue of the American Journal of Epidemiology found that of four common dietary patterns, labeled "healthy," "Western," "drinker," and "meat-eater," only the healthy diet pattern was associated with a reduction in the risk colorectal tumors in women.
Dr M. C. Boutron-Ruault and colleagues at Inserm in France utilized data obtained from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, which included 100,000 women, and took place between 1993 and 2000. The participants' diets were scored according to their adherence to four dietary patterns using data provided by dietary questionnaires completed at the beginning of the study. The healthy diet included frequent consumption of vegetables, legumes, fruit, yogurt, fresh cheese, cereals, sea products, eggs, and vegetables, with a low intake of sweets. The Western pattern was characterized by potatoes, pizza, pie, sandwiches, legumes, sweets, cakes, cheese, bread, rice, pasta, processed meat, eggs, and butter. The drinker pattern of eating included sandwiches, snacks, coffee, processed meat, sea products, wine and other alcoholic beverages, and a low intake of soup and fruit. The meat-eater group featured a high intake of potatoes, legumes, coffee, meat, poultry, vegetable oils with the exception of olive oil, margarine, and reduced consumption of tea, olive oil and cereals.
Separate analyses of the risks of developing colorectal adenomas (a precursor to colorectal cancer) and colorectal cancer found that greater adherence to the Western and drinker diets was associated with an increase in the risk of colorectal adenomas, and the meat-eater diet was associated with a greater risk of colorectal cancer. The healthy diet pattern was associated with a small reduction in developing adenomas.
"Our findings are consistent with a deleterious effect of patterns associated with a Western way of life... on colorectal carcinogenesis," the authors conclude.
Childhood soy consumption helps women avoid breast cancer
At the American Association for Cancer Research's Frontiers in Cancer Prevention Research meeting, held November 12-15, 2006 in Boston, it was reported that Asian-American women who frequently consumed soy during childhood, adolescence, and adulthood had a reduced risk of developing breast cancer. The strongest anticancer effect was associated with soy consumption between the ages of 5 and 11.
Larissa Korde, MD, MPH, who is a staff clinician at the National Cancer Institute's Clinical Genetics Branch in the Division of Cancer Epidemiology and Prevention, along with epidemiologists at the University of Hawaii, the Northern California Cancer Center, and the University of Southern California, conducted a case-control study of 597 American women of Chinese, Japanese and Filipino descent with breast cancer and 966 women who were free of the disease. Subjects were recruited from the San Francisco bay area, Los Angeles, and Oahu, Hawaii. Participants were queried on adolescent and adult diet lifestyle and diet. Additionally, the mothers of 255 subjects were asked about their daughters' early childhood diet.
The researchers found that while women whose intake of soy during adolescence and adulthood was in the top one-third of participants had a 25 percent lower risk of developing breast cancer than those whose intake was in the lowest third, participants who consumed the most soy during childhood experienced a 58 percent lower risk. "Childhood soy intake was significantly associated with reduced breast cancer risk in our study, suggesting that the timing of soy intake may be especially critical," Dr Korde stated.
"Hormonal exposures in adulthood, such as use of estrogen and progesterone replacement therapy, are established breast cancer risk factors," she noted. "However, a growing body of evidence suggests that hormonally related exposures early in life may also modify susceptibility to breast cancer."
Men who frequently consume fish have lower colorectal cancer risk
In a study presented at the American Association for Cancer Research's Frontiers in Cancer Prevention Research meeting in Boston on November 13, 2006, researchers at Harvard Medical School found that men who were regular consumers of fish had a lower risk of developing colorectal cancer than men who consumed fish infrequently.
The study analyzed data from 22,071 participants in the Physicians' Health Study, a randomized, double blind, placebo-controlled trial that investigated the effect of aspirin and beta-carotene supplementation on the development of cardiovascular disease and cancer. Food frequency questionnaires completed by participants one year after the beginning of the study were analyzed for type and frequency of fish intake. The men were followed for an average of 19.4 years.
In addition to the 40 percent reduction in risk found among men who consumed fish five or more times per week, the risk of developing colorectal cancer was 20 percent lower among those who consumed fish 2 to 4 times per week, and 13 percent lower for those who reported eating fish less than twice per week compared to those who ate fish less than once per week. Risks were similar between men who received aspirin during the trial and those who did not.
The researchers attribute the cancer-preventive benefit of fish consumption to the food's omega-3 fatty acid content. Omega-3 fatty acids can inhibit the enzyme cyclooxygenase-2, which is involved in inflammatory responses that may be associated with the development of cancer.
Lead author Megan Phillips, who is a doctoral student at the Harvard School of Public Health, commented, "We already know that eating fish can reduce the risk of sudden cardiac death, and this might provide another reason to add fish to your diet.
B vitamins may improve athletic performance
The October, 2006 issue of the International Journal of Sport Nutrition and Exercise Metabolism published a report which concluded that athletes who are deficient in B vitamins may experience diminished performance during high-intensity exercise and reduced ability to repair and grow muscle compared with those whose diets are nutrient replete. The B vitamins thiamin, riboflavin, and vitamin B-6 are used by the body's energy producing pathways, and vitamin B12 and folate are needed for the synthesis of new cells and to repair those that are damaged.
Melinda M. Manore of Oregon State University's Colleges of Agricultural and Health and Human Sciences along with Kathleen Woolf analyzed the nutritional status and dietary intake as well as performance of athletes and active individuals. Manore expressed the concern that the increased stress on the body's energy producing pathways and tissues, combined with the loss of nutrients after strenuous activity and the need for extra nutrients to repair tissue could result in an increased requirement for the B complex. "Many athletes, especially young athletes involved in highly competitive sports, do not realize the impact their diets have on their performance," she stated. "By the time they reach adulthood they can have seriously jeopardized their abilities and their long-term health."
"The most vulnerable people are often the individuals society expects to be the healthiest," Manore observed. "There's a lot of pressure on women in particular to look like an 'athlete.' Unfortunately for some people that means skinny and petite, rather than healthy and strong."
Manore noted that that current U.S. recommended daily allowances may be inadequate for active individuals. The report concludes that "Athletes who have poor diets, especially those restricting energy intakes or eliminating food groups from the diet, should consider supplementing with a multivitamin/mineral supplement."
Low dose aspirin reduces risk of heart attack and stroke in stable cardiovascular disease
The results of a meta-analysis presented at the annual scientific sessions of the American Heart Association in Chicago on November 15, 2006 found that low dose daily aspirin lowered the risk of heart attack or stroke as well as the risk of death over a given period of time among patients with stabilized cardiovascular disease.
Jeffrey Berger, MD and colleagues at Duke University analyzed data from six trials involving low dose aspirin that included 9,853 patients with stable cardiovascular disease, stable angina, or chest pain. They found that participants who received aspirin experienced a 21 percent reduction in the risk of experiencing a major cardiovascular event, a 26 percent reduction in nonfatal heart attack risk, a 25 percent reduction in stroke risk, and a 13 percent reduction in the risk of dying over the course of the studies.
The results of the analysis suggest that treating 83 patients with stable cardiovascular disease with low dose aspirin would prevent one heart attack, treating 40 would prevent one stroke, and treating 71 would prevent one death. This makes aspirin a less expensive and more effective option than ACE inhibitors commonly use to treat cardiovascular disease.
"Among patients with stable cardiovascular disease, we found that low-dose aspirin reduced incidence of heart attack, stroke and death," Dr Berger concluded. "We also saw an increased risk of bleeding among patients taking aspirin, but as in the decision-making process involving any therapy, there is always the weighing of benefits and risks. Since a great majority of patients can tolerate aspirin, the benefits appear to outweigh the risks. Aspirin is a drug that has been used for many years. It is well-understood, effective, inexpensive and widely available. In aspirin we have a proven life-saver."
Reduced magnesium and fiber intake linked with inflammation
An article published in the November, 2006 issue of the American Journal of Clinical Nutrition reported the finding of researchers at the University of Turin in Italy of an association between a higher intake of magnesium and fiber and a lower incidence of C-reactive protein (CRP), a marker of inflammation.
The researchers determined the fiber and magnesium intake of 1,653 participants by evaluating the results of food frequency questionnaires. Height, weight, blood pressure, and waist circumference were measured, and blood samples were analyzed for glucose, insulin, total cholesterol, HDL cholesterol, triglycerides, CRP and other factors. A second glucose test was performed when a participant's fasting glucose concentration was greater than or equal to 110 milligrams per deciliter. Diabetes was diagnosed when two glucose measurements were at least 126 milligrams per deciliter, or if the disease was recorded by the participant's physician.
The risk of having diabetes, metabolic syndrome, or elevated C-reactive protein defined as as a value of greater than or equal to 3 milligrams per liter was three to four times greater among subjects in the lowest third of magnesium and fiber intake than among those whose intake was in the top one-third of participants. Controlling the analysis for fiber intake confirmed the association of magnesium with elevated CRP, but weakened the association with a reduction in diabetes and metabolic syndrome, suggesting that magnesium's effect could be confounded by the presence of fiber in foods that provide magnesium. Having an intake of fiber in the lowest third remained associated with a greater risk of diabetes, metabolic syndrome and elevated CRP after adjustment for magnesium.
Low magnesium and fiber intake were concluded to be independently associated with a higher level of C-reactive protein, adding evidence to a protective role for the nutrients against systemic inflammation.
Study findings suggest antioxidants do not interfere with radiation treatment
The Society of Integrative Oncology's Third International Conference held in Boston is the site of a presentation that will be given during the weekend of November 11-12 concerning the finding of researchers at Cancer Treatment Centers of America that consuming antioxidants during radiation therapy may not interfere with treatment.
It has been a longtime concern that antioxidant supplements, due to their ability to protect tissues from free radicals, could also protect cancerous tumors from the intended destructive effects of ionizing radiation when taken before or during treatment.
The study compared prostate cancer patients given radiation therapy who did not take antioxidant supplements with those who used green tea extract, melatonin, high potency multivitamins, and vitamins C and E. The researchers found that prostate specific antigen (PSA) levels, a prostate cancer marker, did not differ between the two groups, showing that the supplements did not impede the effects of radiation.
Lead author Timothy Birdsall, ND, who is vice president of integrative medicine for Cancer Treatment Centers of America commented, "In cancer treatment today, we have to look beyond the traditional focus of treating only the tumor. Cancer patients will be the first to tell you that's not enough. The integrated, whole person approach to cancer is highly valued, so much so that cancer patients and their caregivers are seeking out complementary or alternative therapies on their own."
"This study provides evidence that antioxidants as a complementary therapy in cancer treatment do not interfere with external beam radiation therapy," he concluded. "Antioxidants are one of many complementary and alternative medicine (CAM) therapies that are crucial in today's fight against cancer."
Antioxidants tested for pain relief
In a report published in the October, 2006 issue of the journal Behavioral Brain Research, professor Robert Stephens of Ohio State University and colleagues tested the ability of three antioxidants to relieve pain in mice and found that the compounds eliminated symptoms in almost 75 percent of the animals. Antioxidants neutralize cell-damaging fee radicals which could contribute to chronic pain, in addition to a number of other health conditions and diseases.
Dr Stephens' team injected mice with the synthetic antioxidant PBN, another synthetic antioxidant TEMPOL, NAC (N-acetyl-L-cysteine), or saline as a placebo prior to injecting the left hind paw with an irritant that causes inflammation and discomfort. The subsequent observation period was divided into a 5 minute acute phase during when the body first senses and reacts to pain, a 5 to 15 minute period of relative stillness in which the body utilizes its own mechanisms to inhibit pain, and a 15 to 30 minute tonic phase, during which the animals again show pain-like behavior by licking the irritated paw. They found that the three antioxidants were associated with a 70 to 90 percent reduction in pain-related behavior during the acute phase and a 78 to 98 percent decrease during the tonic phase compared to the control animals.
“When it comes to pain killers, there aren't many choices between over-the-counter pain relievers like ibuprofen and aspirin and prescription opiates like morphine,” Dr Stephens observed. “We need drugs that fall somewhere between these two extremes. Someone suffering from chronic pain can become dependent on, or even addicted to, heavy-duty pain killers like morphine.”
“Studying the pain-killing effects of antioxidants is an emerging area of research,” Dr Stephens stated. “The FDA hasn't approved antioxidants for the treatment of chronic pain. But down the road we may see some drugs that contain antioxidants.”
Cool mice live longer
In the first study of its kind in a warm-blooded animal, scientists at Scripps Research Institute in LaJolla, California reduced the core body temperature of mice and showed that, despite eating as much as they wanted, the animals lived up to 20 percent longer than their normal littermates. The finding, published in the November 3, 2006 issue of Science, helps answer long-standing questions concerning whether the life-extending effect of calorie restriction is due to a reduction in body temperature.
Previous research exploring the effect of body temperature reduction utilized cold-blooded animals that lack an internal temperature-regulating thermostat. For the current study, Scripps Research associate professor Bruno Conti and colleagues created a mouse model that produced large amounts of uncoupling protein 2 in neurons near the brain's thermostat in the hypothalamus. The action produced heat in the surrounding areas, causing the hypothalamus to lower the animals' body temperature by 0.3 to 0.5 degrees. This resulted in an extension of median lifespan of 12 percent in males and 20 percent in females, despite the animals eating as much food as they wanted. The mice retained the ability to generate a fever and maintained the same activity level as normal mice.
Although the two groups of female mice were similar in weight, male mice in the experimental group weighed approximately 10 percent more than the control males, an effect that may be due to the reduction in energy required to maintain a lower temperature.
Scripps Research Molecular and Integrative Neurosciences Department chair and report coauthor Tamas Bartfai commented, "Our model addresses something more basic than the amount of food. It works at the level of the thermoregulatory set point that is governed by intra-brain temperature and neurotransmitters. This mechanism, we believe, will be a good target for pharmacological manipulation or heating."
Folate protective against colorectal cancer
An article published in the November 1, 2006 issue of the journal Cancer Research reported that diets that fail to provide enough folate increase the risk of colorectal cancer in a laboratory model of the disease. Folate is a B vitamin that is particularly high in leafy green vegetables, whose presence in adequate amounts in the diet has been shown to have a protective benefit against a number of diseases.
Dr. Rima Rozen and colleagues at the McGill University Health Centre in Montreal created a spontaneous tumor model in which mice develop intestinal masses when consuming reduced folate diets. Animals provided with control diets remained tumor free. The team found that folate deficiency increased DNA damage and decreased the expression of two genes involved in DNA damage response compared to mice on the control diet.
"This research, which is consistent with previous epidemiological studies in humans, demonstrates a clear link between low dietary folate and the initiation of colorectal cancer in animal models," stated Dr Rozen, who is the Scientific Director of the Montreal Children's Hospital and Deputy Scientific Director of McGill University Health Centre. "None of the mice fed a control diet developed tumors whereas 1 in 4 mice on the folate-deficient diet developed at least one tumor."
Dr Philip Branton, who is Scientific Director of the Canadian Institutes of Health Research Institute of Cancer Research commented, "It is estimated that 20,000 men and women will be diagnosed with colorectal cancer this year, and an estimated 8,500 will die from the disease. The result of this study highlights how simply adding a supplement to your daily diet could have tremendous long-term benefits to the individual and the health care system."
Cancer-free mice protected by immune system
In an article published on October 31, 2006 in Cancer Immunity, Zheng Cui, MD, PhD, and Mark C. Willingham, MD, of Wake Forest University School of Medicine and colleagues reported that a strain of mice previously discovered to be protected from developing cancer owes its protection to the innate immune system, which defends the body against bacteria and had once been believed to be unable to combat malignancies.
In an earlier report, published on May 16, 2006 in the Proceedings of the National Academy of Sciences, the team revealed that white blood cells derived from these mice treated advanced cancers in normal mice and protected them from the development of new cancers when different types of cancer cells were injected.
In the current research, Dr Cui and colleagues found that white blood cells known as neutrophils, macrophages and natural killer cells find and kill cancer cells in these spontaneous regression/complete resistance (SR/CR) mice. While in ordinary mice these leukocytes are suppressed by signals coming from the cancer cells, the white blood cells of the SR/CR mice interpret the signals as cause to attack.
The researchers identified three steps used by the white blood cells in the SR/CR mice to kill cancer: the migration of white blood cells to the cancer site after sensing the presence of cancer cells, the recognition of properties on the cancer cell surface and the surrounding of the cancer cells, and the deliverance of a cancer-destroying compound to the cells. In normal mice, only the third step takes place.
"Apparently, the mutation in the SR/CR mice renders the white blood cells capable of sensing unique diffusible and surface signals from cancer cells and responding to those signals by migration and physical contact," the authors write. "Identifying the mutated gene (or genes) will likely explain this unique resistance to cancer through immunity," they conclude.