Further evidence lycopene inhibits prostate cancer
More evidence is emerging that lycopene, one the substances found in tomatoes and other fruits and vegetables that gives them their red color, can prevent and slow prostate cancer. The two hundred twenty-second national meeting of the American Chemical Society was the site of a presentation on August 29 by researchers from the University of Illinois in Chicago who gave tomato sauce daily for three weeks to a population consisting mainly of prostate cancer patients of African-American descent, a group who has the highest incidence of prostate cancer worldwide. The volunteers were found to have a significant reduction in DNA damage to prostate cells and white blood cells and well as lower prostate specific antigen levels. Prostate specific antigen, or PSA is a protein used as a blood marker for prostate cancer risk.
African-Americans have 34% more prostate cancer diagnoses than Caucasians and they are twice as likely not to survive the disease. Current thinking has pointed to genetics and diet as culprits. Mediterranean men, such as those living in Italy and Greece, who consume more tomato sauce than other parts of the world have shown a lower incidence of prostate cancer. The cooking process used when making tomato sauce breaks down tomato cell walls to release more lycopene.
Lead investigator Phyllis E Bowen, PhD commented, "This study does not say that tomato sauce reduces cancer. It says that it reduces DNA damage that we think is associated with cancer." This study is the first to associate a decrease in human DNA damage with consuming tomato sauce. DNA damage is a marker for increased cancer risk. Bowen stated that the current study suggests that eating more tomato sauce may be worth considering to help protect DNA, particularly for those at risk for prostate cancer.
Resveratrol from grapes inhibits angiogenesis and tumor growth
The polyphenol resveratrol, found in grapes, pine bark and peanuts, inhibits tumor growth and angiogenesis in several in vivo models according to an article published in the June 8, 2001 issue of Federation of American Societies for Experimental Biology (FASEB) journal. Angiogenesis is the process by which new blood vessels are formed, essential to cancer tumor growth. Researchers at the Karolinska Institute in in Sweden stimulated bovine endothelial cells with fibroblast growth factor 2 and found that resveratrol was able to dose-dependently inhibit capillary endothelial growth. In pig aortic endothelial cell lines that express receptors for fibroblast growth factor 2 and vascular endothelial growth factor (VEGF), resveratrol inhibited the proliferation and migration of cell growth mediated by these receptors.
The researchers subsequently sought to confirm resveratrol's antiangiogenic activity in a live model, and found that resveratrol was able to induce areas lacking vascularization in the chorioallantoic membrane of developing chick embryos. Further confirmation was obtained by administering a solution to mice containing the equivalent amount of resveratrol in three glasses of red wine per day in humans. The mice had significantly less new vascularization induced by VEGF in their corneas compared to a control group that received water only. Additionally, mice with fibrosacrcomas experienced an inhibition of tumor growth after receiving oral resveratrol.
The researchers conclude that resveratrol inhibits angiogenesis when given orally, which is an improvement over the injectable route of administration currently in use with angiogenesis inhibitors. The researchers emphasized that resveratrol could be harmful in situations involving wound healing, and that wine drinking should not be encouraged to obtain resveratrol. Other food products or nonalcoholic beverages should be considered as sources.
Oxidative damage to DNA associated with aging confirmed, slowed by calorie restriction
Preventing oxidative damage caused by free radicals and restricting the amount of calories consumed are two methods of attempting to extend lifespan. The increased survival of animals given diets limited in calories compared to those fed ad libitum has been associated with less oxidative damage to the cells. Oxidative damage to cellular macromolecules rises with age and has been linked with the loss of many physiological functions. In the past decade, researchers have uncovered an association between oxidative damage to cellular DNA and aging, as measured by 8-oxo-2-deoxyguanosine (oxo8dG) levels, while others have not verified this finding. The current study, published online before print in the Proceedings of the National Academy of Sciences August 21 2001, examined DNA oxo8dG levels of two strains of mice and one strain of rats at varying ages and in some who were administered calorie restricted diets. Because of the contradictory results of the prior research, the scientists utilized a method of isolating DNA involving sodium iodide that eliminated the possibility of further oxidation which could generate oxo8dG, which could have created a false elevation in previous studies.
After isolating nuclear DNA from liver, heart, brain, kidney, muscle and spleen, and mitochondrial DNA from liver, the scientists found oxo8dG levels increased with age in all strains and tissues. The mice and rats that were fed 60% of the diet consumed by a companion group or rodents showed significantly lower levels of oxo8dG in DNA in the heart, skeletal muscle and brain at twenty-four months than those of rats and mice the same age fed ad libitum.
This study confirms the increase of DNA oxidation with age, and shows that calorie restriction can slow the process. The researchers concluded that an age-related sensitivity of the tissue to oxidative stress rather than a decline in the ability to remove oxidative damage is responsible for the increase.
Decreased lung function increases all cause mortality
A longterm study published in the September 2001 issue of the journal Thorax that a reduction in lung function caused by smoking increased the risk of mortality from all causes. The study, initiated in 1959 and lasting thirty years, involved over 1000 Finnish men who were part of the international Seven Countries Study. Participants were between the ages of forty and fifty-nine at the study's onset. Follow up was conducted five times over the course of the study, and deaths were tracked until the year 2000.
Loss of lung function occurred more slowly, to a lesser degree, and at an older age in nonsmokers compared to smokers. During the first fifteen years of the study, the decline in forced expiratory volume in 0.75 seconds (a measure of lung function) was 46.4 milliliters per year in those who had never smoked compared to 66 milliliters per year in continuous smokers. Risk of mortality from all causes was 20% higher in smokers than in those who did not smoke. For those who quit smoking, even temporarily, the decline in lung function was slowed. Individuals who survived the longest had less loss of lung function measured by forced expiratory volume in 0.75 seconds than those who died, whether they smoked or not.
The study's authors posit that the constant stimulation of the lungs' inflammatory responses caused by smoking causes changes in the anatomy and function of the lungs leading a greater loss of function. They conclude that preserving as much lung function as possible predicts a longer lifespan, and that the beneficial effect of smoking cessation on the risk of death may partly be caused by a reduced decline in pulmonary function.
JAMA study predicts folic acid, vitamin B12 supplements will save money, lives
A study published in the August 22, 2001 issue of the Journal of the American Medical Association examined the future benefits of flour fortification on the incidence of cardiovascular events, and sought to predict cost-effectiveness of vitamin B12 and folic acid supplementation. The study utilized the Coronary Heart Disease Policy Model of coronary heart disease events and costs for residents of the United States ages 35 to 85, updated to include homocysteine-level distribution. Elevated homocysteine levels have emerged as an important risk factor in heart disease, and have can be lowered by folic acid and B12. The model was validated in its ability predict death from coronary heart disease to within 2% of the 1990 US Vital Statistics.
Using this model, the researchers predicted that grain fortification with folic acid currently mandated by the FDA could result in an 11% decline in homocysteine levels, resulting in an approximate 13% decrease in heart attack and cardiovascular mortality in men and an 8% decrease in women over a ten year period. If all patients with known heart disease received 500 micrograms supplementary vitamin B12 and one milligram supplementary folic acid, the model predicted 310,000 fewer deaths in the same period than would occur with a fortified diet alone, with the greatest number of lives saved being older individuals. For men aged forty-five and older without coronary heart disease, savings to the U.S. over a ten year period if supplementation were initiated is projected at two billion dollars. Cost effectiveness for women emerged in the fifty-five and older group. The authors of the study recommend, "since combined therapy with folic acid and cyanocobalamin is well tolerated, it is reasonable to consider routine therapy in men older than 45 years and women older than 55 years."
Citrus pectin may aid in prostate cancer prevention
The June 2001 issue of Journal of Agriculture and Food Chemistry published the results research collaboration among scientists at Texas A & M University and the University of Texas-Pan American at Edinburgh, demonstrating that citrus pectin may help to prevent prostate cancer. Pectin has several benefits, including an ability to reduce blood sugar and cholesterol. Modified citrus pectin has also shown an ability to help prevent cancer metastasis. The researchers in this study showed that a component of pectin effects the miscommunication that occurs between cells of the prostate that leads to cancer.
Study coauthor Wallace McKeehan, of the Institute of Biosciences and Technology at Texas A & M University System Health Science Center in Houston explained, "There's cross-talk among cells of the prostate that keeps the prostate healthy. During malignancy, the signals get garbled and the cells don't understand each other. You end up with rogue cells that are not behaving properly because they are not getting the right signals. They begin signaling and stimulating themselves and grow too much. We've plugged the elements of citrus pectin into the signal mechanisms that have gone haywire and shown that pectin can potentially effect that system and set it back to normal. Once we identify exactly what it is in pectin that has this effect, the long term goal would then be to resolve the issue of how best to deliver it to the consumer."
This study is the first to identify the target by which citrus pectin may modify cancer development. The researchers hope to break down the pectin molecule into smaller molecules and then separate them to determine if one part of the pectin molecule is responsible for the cancer preventing benefit.
Fish oil, not corn oil prevents colon cancer
Researchers at Texas A&M University have found that fish oil, a popular supplement used in the prevention of heart disease and arthritis, has a protective effect against cancer of the colon, while corn oil acts as a promoter. The research, ongoing for the past four years, discovered that the oils effect the fatty acid composition of the cell membrane, which affects whether or not a cell will become cancerous. Lead researcher Professor Joanne R Lupton, explained, "Once the fatty acid composition of the membranes of colon cells is changed that sets up a different fate for the cell. A signal can go from the cellular membrane to the nucleus of the cell and tell it either to divide and become a tumor or give up the ghost and undergo programmed cell death."
The researchers have also investigated how cancer spreads among the colon's cells. Rats were fed either corn oil or fish oil and were injected with azoxymethane, a substance that induces colon cancer. The cells in the indentations in the walls of the colon called crypts in which colon cells grow and replicate were subsequently examined. Cells at the bottom of the crypts are the youngest, while the oldest are on the surface. Rats fed a fish oil diet were found to have cells equally damaged at the bottom of the crypts at both ends of their colons, while the corn oil fed rats experienced more damage to one side of the colon and little to the other. Lupton noted, " Within the colon, there are different degrees of cancer at different sites. Indeed, most humans have left-sided tumors rather than right-sided tumors."
Research collaborator Jeffrey Morris, assistant professor of biostatistics at M.D. Anderson Cancer Center noted that greater damage to the crypts one side of the colon signifies greater localization and concentration which could worsen the effects, as compared to the diffuse damage observed when both sides of the colon are equally damaged. He suggested that fish oil and corn oil may create different environments in the colon. The researchers are planning studies utilizing more rats.
Free fatty acids in blood linked to sudden death in men
A study reported in the August 14 2001 issue of Circulation: Journal of the American Heart Association reported that high serum levels of nonesterified (free) fatty acids are associated with sudden death in middle-aged men. Stored in fatty tissue after digestion, free fatty acids become free when released during fasting or smoking, or in diabetes, hyperthyroidism or heart attack. An elevation in free fatty acids has been known to cause potentially fatal cardiac arrhythmias in individuals with heart disease.
This study is the first to show that it does so in healthy men as well. 5,250 men enrolled in the Paris Prospective Study between 1967 and 1972 were followed for an average of 22 years. Blood samples were taken one year following enrollment and analyzed for nonesterified fatty acid levels. After adjustment for age, heart rate, smoking and other factors, levels of nonesterified fatty acids were found to have a positive association with sudden cardiac arrest but not with fatal heart attack. Sudden cardiac arrest can occur independently of heart attack, and is often caused by ventricular fibrillation, a type of arrhythmia. Study author Xavier Jouven, MD, PhD noted that in one study, patients who were administered a substance that lowered serum free fatty acid levels had a decreased incidence of ventricular arrhythmia.
In an editorial in the same issue of Circulation, author Alexander Leaf, MD stated that omega-6 fatty acids, such as those found in corn, sunflower or safflower oils are more likely to cause arrhythmias while omega-3 fatty acids found in fish or canola oil can exert a protective effect. He observed, ""Only relatively small amounts of omega-3 fatty acids seem needed for protection, but the intake must be accompanied by a reduction of omega-6 fatty acids to reach closer to a 1-1 ratio of omega-6 to omega-3 polyunsaturated fatty acids. The findings of Jouven and co-authors suggest that the subjects included in the Paris Prospective Study were probably consuming diets low in omega-3 fatty acids, as has been the case during the past century in Western industrialized countries."
Atherosclerosis associated with accelerated cellular aging
In a article appearing in the August 11 2001 issue of The Lancet, researchers discovered by examining telomeres that patients with coronary artery disease had cellular aging comparable to that of individuals and average 8.6 older. The researchers investigated the hypothesis that if atherosclerosis were an inflammatory disease, characterized among other things by increased cell turnover in response to injury, patients with the disease might have evidence of early cellular aging.
Blood was drawn from ten patients aged 42 to 72 with angiographically determined severe triple-vessel coronary artery disease, and twenty control patients of a comparable age range who did not have the disease, also verified by angiography. The measurement of terminal restriction fragments in white blood cell DNA allowed the determination of average telomere size. Telomeres are caps at the ends of chromosomes which shorten with cellular each cell division, hence longer telomeres indicate younger cellular aging. There was a strong association observed between telomere shortening and age. After adjustment for age and sex, individuals with coronary artery disease had terminal restriction fragments that averaged 303 base pairs shorter than controls, equivalent to someone approximately 8.6 years older.
This difference could be caused by genetic or early life factors. The study's authors observed that there is increasing evidence that atherosclerosis involves more than the vascular system, and that systemic inflammation and other generalized abnormalities may be present. They hypothesized that the cellular dysfunction that accompanies the aging of blood vessel cells could contribute to atherosclerosis. Increased cell turnover and increased biological age as measured by telomere length in noninvolved cells could prove to be a valid disease marker.
Research reveals how feverfew acts as an antiinflammatory
A research team at Yale University has discovered the antiinflammatory mechanism of action of a known substance in the herb feverfew. Feverfew has long been a natural therapy to help prevent and treat migraine headache. The researchers found, through a combination of chemical and biochemical approaches, that the active compound found in feverfew, parthenolide, binds to a protein that plays a role in inflammation called IkappaB kinase. Other herbs have been found to contain parthenolide as well. The research was published in the August 2001 issue of the journal Chemistry and Biology.
Research team leader Craig Crews, associate professor of molecular, cell and developmental biology, chemistry and pharmacology at Yale University had this to say: "The results pave the way for the development of novel anti-inflammatory drugs for a variety of illnesses and symptoms, such as headache, swelling, redness and inflammation. We showed that the binding disrupted the protein's ability to function, and we also were able to identify the part of the protein to which the compound binds. Now that we have identified one inhibitor of this protein, that information can be used to develop additional inhibitors.
This is important because a single inhibitor may not always make a successful drug due to side effects, so it's always useful to have a series of inhibitors." The antiinflammatory property of feverfew may be why it has been found to be effective against migraine by so many individuals, since migraine involves inflammation and dilation of the blood vessels. The discovery encourages other possible uses of the herb or its component in treating inflammatory conditions.
Aneurysm patients may benefit from cooling
Boston's Massachusetts General Hospital will be the site of a study which will investigate the benefit of a new cooling technology in hemorrhagic stroke patients who develop a fever. The Celsius Control™ System, manufactured by Innercool therapies Incorporated, involves the utilization of a catheter that can be inserted into a vein or artery in order that blood can be cooled as it flows past an element. The system can also be used to rewarm patients.
Hemorrhagic stroke, which results from the rupture of a blood vessel in the brain, often causes an increase in body temperature for two to three days following the event. Elevated temperatures result in a cascade of damaging conditions that can impair recovery. The induction of lowered body temperature, or hypothermia, has been shown to help prevent this tissue damage from occurring. Current methods involving the use of acetaminophen and cooling blankets have shown limited success.
To cool the whole patient, a catheter is inserted into the inferior vena cava via the femoral vein, while the cooling of target organs such as the brain necessitates placement of the catheter in an artery. The system does not require the perfusion of fluids into the body, nor is any outside blood circulation necessary. It is also being tried during the surgical repair of unruptured aneurysms.
Innercool president and CEO John Dobak MD, enthused, "We are very excited about the progress of our clinical studies. Our System allows physicians to quickly induce, maintain and reverse hypothermia. Our TCAS (Temperature Control During Aneurysm Surgery) study in unruptured brain aneurysms is progressing rapidly and, with the initiation of our fever control study, we are exploring another important clinical indication for our technology. We also plan to investigate additional clinical applications, such as acute stroke and heart attack."
Antiinflammatory drug to be tried as lung cancer preventive
Lung cancer causes more cancer fatalities than any other form of cancer, and will take the lives of over 157,000 people in the United States this year, more than those with breast, prostate and colon cancer combined. The American Cancer Society estimates that 169,500 new diagnoses will be made in 2001. Celebrex is currently approved by the FDA as a colon cancer preventive for those who are in the highest risk group for the disease. Previous UCLA research found the drug can prevent the development and growth of lung cancer in mice.
The current research will test the drug's preventive ability in nonsmall cell lung cancer survivors and in heavy smokers with mild chronic obstructive pulmonary disease. Lead investigator and UCLA School of Medicine assistant professor Dr Jenny Mao announced, "This is the first time that Celebrex is being studied in humans for the purpose of preventing lung cancer. We have detected changes in lung cancer cells at the molecular level that suggest a favorable response in terms of prevention. Celebrex is considered to be safer than aspirin, so Celebrex's safety profile further enhances its promise as a preventive agent for lung cancer." Anyone wishing to participate in either of the studies can call the Jonsson Cancer Center clinical trials hotline at 888-798-0719.
Soy protects postoperative heart
Soy isoflavones may protect the heart from damage that occurs during reperfusion following open heart surgery. The knowledge arose from the observation that the administration of estrogen to rodents bred to lack the hormone protects the heart of rodents during periods of ischemia, or lack of blood flow, to the heart. Otherwise, damage to heart cells and a buildup of calcium occurs. Estrogen offers protection to both male and female animals.
Vitamin A derivatives to be tried with emphysema patients
The benefit of vitamin A derivatives all-trans-retinoic acid and 13 cis-retinoic acid against emphysema is the subject of an upcoming study funded by the National Institutes of Health known as the FORTE, or Feasibility of Retinoid Therapy for Emphysema study. Research will be conducted at five universities throughout the United States. Adult patients with mild to moderate emphysema will randomly receive one two strengths of all-trans-retinoic acid, 13 cis-retinoic acid, or a placebo for six months. The placebo group will then receive the retinoids and the retinoid group will receive the placebo for the remaining three months of the study. The study seeks to confirm the benefits of retinoids against the disease observed in previous human and animal studies.