Broccoli compound offers protection from bladder cancer
On July 18 2005 at the annual Institute of Food Technologists meeting held in New Orleans, Ohio State University food science and technology professor Steven Schwartz presented the findings that a compound found in broccoli inhibits the growth of bladder cancer cells. The scientists' work confirms earlier findings from Ohio State and Harvard Universities that men who consumed more than two servings of broccoli per week had a 44 percent lower incidence of bladder cancer than men whose intake was one serving or less.
The researchers tested compounds known as glucosinolates and isothiocyanates on cultured human and mouse bladder cancer cells. Isothiocyanates are formed from glucosinolates in broccoli sprouts when they are chopped, chewed or digested.
Dr Schwartz and his colleagues found that while glucosinolates failed to inhibit the growth of the cancerous cells, isothiocyanates decreased cell growth in all of the lines tested, particularly in the most aggressive bladder cancer cell line, that of human invasive transitional cell carcinoma.
While the mechanism of action of isothiocyanates remains unknown, the researchers believe that there are other compounds in broccoli that could have anticancer benefits, and note that other members of the cruciferous family of vegetables such as cabbage and cauliflower may contain similar phytochemicals.
Dr Schwartz stated, “We're starting to look at which compounds in broccoli could inhibit or decrease the growth of cancerous cells. Knowing that could help us create functional foods that benefit health beyond providing just basic nutrition.” He added, "Cruciferous veggies have an effect on other types of cancer, too. We already know that they contain compounds that help detoxify carcinogens. We're thinking more along the lines of progression and proliferation, such as once cancer starts, is there a way to slow it down?”
Beneficial bacteria induce colitis remission
Consuming so-called "good" bacteria has been found in a clinical trial to relieve the pain of ulcerative colitis, causing the disease to go into remission. The bacteria, known as probiotics, are believed to colonize the intestinal tract and prevent the overgrowth of harmful microorganisms. The finding was published in the July 2005 issue of American Journal of Gastroenterology (www.amjgastro.com).
Researchers at the University of Alberta, in conjunction with scientists from the University of Bologna and the University of North Carolina, gave 30 men and women with mild to moderate ulcerative colitis a mixture of 8 probiotic bacteria, consisting of Lactobacillus casei, Lactobacillus plantarum, Lactobacillus acidophilus, Lactobacillus delbrueckii bulgaricus, Bifidobacterium longum, Bifidobacteria breve, Bifidobacterium infantis and Streptococcus salivarius thermophilus. The patients were between the ages of 18 and 65 and had a two week or greater history of active ulcerative colitis that did not respond to a standard drug.
After six weeks of daily consumption of the probiotic mixture, 86 percent experienced relief, with 23 percent reporting improvement of symptoms and healing of the lining of the colon as determined by signmoidoscopy, and 63 percent experiencing remission of the disease. No adverse effects from the probiotic were reported.
The researchers believe that the probiotics may exert their benefits by reducing the amount of harmful bacteria in the colon, lowering inflammation, increasing the gut mucosal layer, and elevating intestinal anti-inflammatory molecules. A randomized placebo-controlled trial to confirm the therapy's effectiveness is currently underway.
Research team member Richard N Fedorak, M.D. of the University of Alberta commented that the probiotic combination could be considered a potential treatment for ulcerative colitis patients who do not respond to standard therapy.
Greater stress response means longer life
Research conducted at the University of Colorado at Boulder has found that the ability to respond to stress predicts length of life--at least if you're a worm. Shane Rea and colleagues genetically engineered roundworms with a fluorescent reporter protein coupled to a stress protein called heat shock protein-16 (HSP-16), that is present in most organisms as a monitor of cellular health. Worms who fluoresced the brightest after having been exposed to stress in the form of high temperatures while they were young adults lived longer than worms whose fluorescence was not as bright. The report is an advance online publication in the journal Nature Genetics (www.nature.com/ng/index.html).
Coauthor Thomas Johnson of the University of Colorado's Institute for Behavioral Genetics announced, "We have shown it's possible to predict the life span in an organism on the first day of adult life based on how it responds to stress. This is something that has not been done before, and has implications for human longevity and health."
Using genetically identical roundworms, the team found that those who fluoresced the brightest typically lived 16 days compared to 3 days among those who fluoresced the least. Rea and colleagues believe that the individual variation shown in these identical worms may be due to chance alterations in the maintenance of stress-response mechanisms.
The authors conclude, "HSP-16 alone is probably not responsible for observed differences in survival, but instead is likely reflective of a hidden, heterogeneous, but now quantifiable state that dictates the ability of an organism to deal with the rigors of living."
Future research may uncover other biomarkers similar to HSP-16 to help predict life span. Rea adds, "They might even be able to tweak each stress-response system and set them for maximum longevity, which is believed to be about 120 years."
Diet and exercise program lowers breast cancer risk factors in less than two weeks
The International Research Conference on Food, Nutrition, and Cancer was the site of a presentation this week by researchers from UCLA concerning their findings that women who followed the Pritikin Diet and engaged in regular exercise experienced reduced levels of serum estradiol, insulin and insulin-like growth factor, all of which are positively associated with an elevated risk of breast cancer. The Pritkin diet, which is low in fat, sugar and sodium, consists mainly of vegetables, fruits and grains.
Lead researcher and UCLA professor of physiological science James Barnard, PhD, and colleagues collected blood samples from 26 postmenopausal women who enrolled in a thirteen day diet and exercise program at the Pritikin Longevity Center in Florida. Blood samples drawn on the first and last days of the program were analyzed for serum estradiol, insulin and insulin-like growth factor. The serum samples were transferred to UCLA and administered to three different breast cancer cell line cultures.
By the end of the 13 day period, the participants' estradiol levels dropped by 37 percent, insulin by 29 percent and IGF-1 by 19 percent. Serum from blood drawn at the conclusion of the program increased programmed cell death in the cancer cell cultures by 20 to 30 percent and reduced their growth by as much as 19 percent compared to cultures treated with serum collected at the beginning of the program. Dr Barnard concluded, “This is the first study to my knowledge to show that lifestyle changes can induce apoptosis, or cell death, in breast cancer cells.”
William McCarthy, PhD of UCLA’s School of Public Health added, “This is exciting research because it shows that women can make changes in a very short period of time that can have a dramatic impact on their health – in this case, on the growth and death of breast cancer cells.”
Higher selenium levels linked with lower risk of fatal liver cancer
Chinese researchers in collaboration with American scientists at the National Cancer Institute and Fox Chase Cancer Center in Philadelphia have found an inverse relationship between the risk of dying from hepatocellular carcinoma and levels of selenium. Hepatocellular carcinoma accounts for 80 to 90 percent of all liver cancers, and is the third leading cause of cancer deaths worldwide. The findings were published in the July 1 2005 issue of the International Journal of Cancer (www3.interscience.wiley.com/cgi-bin/jhome/29331).
Data from 166 men and women with hepatocellular cancer who were part of a large prospective cohort study in Haimen City, China was age and gender matched with 394 healthy participants. Hepatocellular carcinoma is a leading cause of death in Haimen City, and median survival time from diagnosis is less than six months. Selenium levels were measured in toenail clippings, which provide a more accurate picture of long term average selenium intake than blood levels or levels determined by dietary questionnaires.
The researchers found that average toenail selenium was lower in participants who did not have hepatocellular carcinoma than in those who did. Subjects in the top 25 percent of selenium intake had half the risk of the disease than those in the lowest fourth. The difference was particularly striking in women, who composed a minority of the subjects in this study. Women whose selenium was in the top three-quarters of participants had an 82 percent lower risk of hepatocellular carcinoma than those in the lowest quarter. Nondrinkers also experienced a more pronounced reduction in risk compared to drinkers.
The authors acknowledge the need to further explore the interrelationship between hepatocellular carcinoma and hepatitis B and C, in order to understand the chemopreventive potential of selenium in liver diseases.
Memory loss may be not only preventable, but reversible
For the first time in history, researchers were able to reverse memory loss in mice bred to experience significant brain degeneration. The finding is important for the millions of people with Alzheimer's disease, for whom current treatments are minimally effective.
In a study published in the July 15 2005 issue of Science (www.sciencemag.org) researchers at the University of Minnesota bred mice to express human tau, which is a protein found in neurofibrillary tangles. Neurofibrillary tangles, which are tangled bundles of fibers within the neurons, and amyloid-beta plaque are two findings characteristically observed in the brains of Alzheimer's patients. Mice expressing tau exhibited neurofibrillary tangles and brain atrophy. They also demonstrated a loss of memory, as evaluated by a water maze test.
When the animals' tau gene was turned off by administering doxycycline, loss of memory was not just halted, but memory was restored. Interestingly, while the mice in the study regained their memory, neurofibrillary tangles remained and even increased, suggesting that they may not play the causative role in dementia that had been attributed to them. The authors write that "recovery of memory in this mouse model implies either that reversible neuronal dysfunction rather than irreversible structural degeneration is responsible for initial memory deficits or that neuronal remodeling of some form occurs after doxycycline treatment and allows recovery."
Lead author and professor of neurology at the University of Minnesota Medical School, Karen Ashe, predicted "Most Alzheimer's disease treatments focus on slowing the symptoms or preventing the disease from progressing, but our research suggests that in the future we may be able to reverse the effects of memory loss, even in patients who have lost brain or neural tissue."
Study indicates that programmed cell death may be major cause of aging
A report published in the July 15, 2005 issue of Science (www.sciencemag.org) contributed evidence to the theory that damage to mitochondrial DNA resulting in programmed cell suicide known as apoptosis could be a major cause of aging. Mitochondria are intracellular organs which have their own DNA, which provide energy to the cell.
Geneticist Thomas Prolla, PhD of the University of Wisconsin-Madison and colleagues investigated a strain of mice engineered to be deficient in a protein that "proofreads" mitochondrial DNA for errors, allowing their DNA to accumulate a greater number of mutations than normal mice. The team found an accleration of apoptosis accompanied by graying hair, hair loss, and muscle and bone atrophy at a more rapid rate than that experienced by unaltered control mice. Addtionally, there was a loss of adult stem cells needed for replacing cells that die. Dr Prolla explained, "If these stem cells are lost, tissue structure and the ability of tissue to regenerate are impaired. We have observed that in tissues like bone marrow, intestine and hair follicles."
Dr Prolla suggests future research in which mice engineered to have fewer mitochondrial DNA defects would be useful to help find ways to control the aging process. "The idea would be to reduce the level of cell death and improve function. If that pans out, then we can begin to think about pharmaceutical interventions to retard aging by preserving mitochondrial function," he stated.
The hypothesis is supported by the fact that calorie restriction, which slows aging, delays the accumulation of mitochondrial DNA mutations. "We think that the key to what is happening in aging is that as (genetic) mutations or DNA damage accumulates, critical cells die," Dr Prolla concluded. "These experiments favor a major role for programmed cell death in aging."
Homocysteine levels predict atherosclerosis progression
In the July 2005 issue of the journal Atherosclerosis (www.sciencedirect.com/science/journal/00219150), researchers from Harbor-UCLA Medical Center Research Institute and Johns Hopkins Ciccarone Preventive Cardiology Center reported a relationship between elevated homocysteine levels and the progression of atherosclerotic plaques. They found that having elevated homocysteine doubled the progression of coronary artery calcium, an indicator of atherosclerotic plaque burden, within a mean 20 month period compared to those that of individuals with lower homocysteine values.
Among newly emerged cardiovascular risk factors are homocysteine and C-reactive protein levels. Electron-beam computed tomography (EBT) has also emerged as a useful tool to measure coronary artery calcium to identify atherosclerosis and help predict the risk of future coronary events.
The current investigation enrolled 100 men and 33 women without symptoms of coronary artery disease or kidney disease who had undergone previous EBT scans within the previous 8 to 80 months at Harbor-UCLA Medical Center. The participants received repeat EBT scans and blood samples were tested for CRP, homocysteine, and other cardiovascular risk factors upon enrollment .
Participants whose homocysteine levels were greater than 12 micromoles per liter were found to have a 35 percent mean increase in coronary artery calcium progression compared to a 17 percent increase in those whose homocysteine was less than 12. The difference in plaque progression between those with high and low CRP levels was not significant. No other factors determined in the current study, such as cholesterol or body mass index, predicted coronary calcium progression.
The authors conclude that elevated homocysteine "strongly and independently predicts progression of coronary plaque burden."
Curcumin combats melanoma
The August 15, 2005 issue of the American Cancer Society journal Cancer (www.interscience.wiley.com/cancer), published a report showing that the yellow pigment found in the spice turmeric known as curcumin inhibits melanoma cell growth and stimulates tumor cell death in cell cultures. Curcumin has been demonstrated to have antioxidant and anti-inflammatory abilities, and research is revealing anticancer properties against a variety of tumor cell lines.
Melanoma is a cancer characterized by the abnormal proliferation of melanocytes. The disease exhibits a resistance to a number of chemotherapeutic drug once it has spread, resulting in a poor prognosis for individuals diagnosed with metastatic melanoma. Therefore, an agent that could help treat the disease would be of great benefit to a number of people.
Razelle Kurzrock, MD of the University of Texas M. D. Anderson Cancer Center in Houston and colleagues tested varying doses of curcumin on three melanoma cell lines. They found that curcumin irreversibly decreased cell viability dose-dependently, and induced apoptosis (programmed cell suicide) at high concentrations over short periods and at low concentrations over long periods of exposure.
An investigation of curcumin's mechanism of action found that it suppressed two proteins that are part of a pathway that prevents apoptosis: nuclear factor kappa beta (NF-kB), and its upstream regulator IkB kinase (IKK), which additionally independently inhibits apoptosis. Curcumin did not, however, suppress several other signaling pathways investigated in the current research.
Report coauthor and professor of cancer medicine at M.D. Anderson's Department of Experimental Therapeutics, Bharat B. Aggarwal, PhD, commented "The antioxidant, anti-inflammatory and anticarcinogenic properties of curcumin derived from turmeric are undergoing intense research here and at other places worldwide." He noted, "Curcumin affects virtually every tumor biomarker that we have tried."
Early screening for prostate cancer may reduce risk of dying from the disease
In a study published in the August 2005 issue of The Journal of Urology (www.jurology.com) researchers from the University of Toronto found that screening asymptomatic men for prostate cancer results in a reduction in the risk of developing the metastatic form of the disease, which can be fatal.
Professor of public health sciences and health policy management and evaluation Vivek Goel and colleagues matched 236 men with advanced metastatic prostate cancer with 462 men who did not have the disease. Participants' medical records were reviewed for prostate specific antigen (PSA) testing, which is used to screen for prostate cancer, but is not diagnostic of the disease. They found that asymptomatic men who had been tested for the disease reduced their risk of metastatic prostate cancer by 35 percent.
Dr Goel commented, "Early screening with the prostate specific antigen is quite controversial. There are many arguments both for and against the efficacy of this form of early screening. Our study shows a fairly significant benefit, and this benefit is demonstrated even among men who were not screened regularly as part of a screening program. There may be greater benefit from an organized screening program."
Because the PSA test often generates false positives, its value as a screening test has of late been questioned, however the current study suggests that PSA screening is valuable. Study coauthor Jacek Kopec, who is a professor at the University of British Columbia, added, "The clinical members of our study team feel that these findings are confirming what they had believed all along; we were a bit more surprised. A 35 per cent difference is quite a large amount so from our perspective it is quite a significant link in the chain supporting that early prostate screening has a positive impact."
Soy helps lower blood pressure
A study reported in the July 5 2005 issue of Annals of Internal Medicine (www.annals.org) found that supplementing with soy protein helped lower the blood pressure of individuals with high-normal blood pressure, which is considered to be indicative of prehypertension, or mildly elevated (stage 1) hypertension.
Three hundred two men and women aged 35 to 64 residing in three Chinese communities participated in the current double-blind controlled trial. Systolic blood pressure averaged 135 mm Hg and diastolic averaged 84.7 mm Hg at the beginning of the study. None of the subjects were using antihypertensive drugs. Participants were randomly assigned to receive cookies containing 40 grams isolated soy protein or a complex wheat carbohydrate daily for 12 weeks. Blood pressure was reassessed at 6 weeks and at the trial's conclusion.
After twelve weeks, the group who received soy experienced a decline in systolic blood pressure that was 4.31 mm Hg lower and a reduction in diastolic blood pressure that was 2.76 mm Hg lower than that experienced by the control group. Subjects diagnosed with stage 1 hypertension experienced the greatest benefit, with a mean reduction of 7.88 mm Hg systolic and 5.27 mm Hg diastolic pressure. It is unknown whether the benefits observed in the trial were due to the protein or the isoflavones that occur in soy.
The amount of soy consumed in this study is equivalent to the amount found in one soy burger plus one to two cups soy milk, which is more soy than most people regularly consume. The authors conclude that the findings suggest that increasing soy protein intake could help to prevent and treat hypertension in some individuals.
Higher chromium levels associated with lower risk of nonfatal heart attack
A study published in the July 15 2005 issue of the American Journal of Epidemiology (aje.oxfordjournals.org) found that toenail levels concentrations of the mineral chromium were inversely correlated with the risk of nonfatal heart attack in men.
European, Israeli and American researchers studied 684 men with a first heart attack who were participants in the EURopean Multicenter Case-Control Study on Antioxidants, Myocardial Infarction, and Cancer of the Breast (the EURAMIC Study). Participants in the study were men aged 70 or younger who resided in eight European countries or Israel. Seven hundred twenty-four men from population registers or other sources with no history of heart attack were age-matched as a control group. Toenail clippings were analyzed for chromium levels, serum cholesterol levels were measured, and questionnaires obtained information from the participants on smoking habits and the history of hypertension, angina and diabetes, all of which are associated with cardiovascular disease.
It was found that chromium levels declined an average of 9 percent with each decade of age. Men with hypertension had lower chromium levels than those without the condition. An inverse association was observed between chromium levels and the risk of a first heart attack. Among men who had experienced a heart attack, chromium levels averaged 1.1 micrograms per gram compared to 1.3 micrograms per gram in the control group.
The authors acknowledged the popularity of chromium supplements in the United States, which are used for improving glucose control, weight loss, exercise capacity and longevity, and note that their use is low among the population in whom the study was conducted. They conclude that their study "supports the increasing body of evidence pointing to the importance of chromium for cardiovascular health."