What's Hot Archive
February 28, 2001
New gene therapy technique may be future cancer preventive
The latest issue of Proceedings of the National Academy of Sciences published an article that discussed the findings of scientists from Jefferson Medical College in Philadelphia who investigated tumor suppressor gene FHIT in mice. FHIT induces apoptosis and slows proliferation of tumor cells. The gene exists at a fragile site on the chromosome and is easily damaged by environmental carcinogens. It has been found to be deleted in many types of cancer, including breast, lung, esophageal, pancreatic, gastric and head and neck cancers. Alterations in the gene's expression have been found to in 86% of individuals with Barrett's metaplasia, which is a premalignant condition of the esophagus, and in 93% of esophageal adenocarcinomas. Also, most precancerous conditions of the lung and over 85% of squamous cell lung cancers were found by the researchers in this study to lack FHIT expression, and loss of FHIT expression is more frequently found in the tumors of smokers than nonsmokers.
In a strain of mice susceptible to tumors induced by environmental carcinogens, researchers knocked out the gene for FHIT to breed the strain that was used for this study. The researchers used an adenovirus, an adenoassociated virus, or both vectors to deliver the FHIT gene through an oral route to three groups of mice. A group of control mice did not receive the gene therapy. The mice were then given the carcinogen NMBA, a substance whose presence has been epidemiologically linked to the high rate of esophageal cancer in Northern China and Iran.
Upon examination, the mice treated with gene therapy were found to express FHIT in their esopagus and forestomachs and to have half the tumor incidence of the control group, in whom no mice remained tumor-free. The treated mice also experienced a reduction in tumor size.
The study's authors suggest that delivery of the FHIT gene could be used not only as a treatment for early stage cancer, but as a cancer preventive.
February 26, 2001
Aspirin and ACE inhibitors lower mortality after heart attack
The February 26, 2001 issue of Archives of Internal Medicine published the results of a study that examined 14,129 patients aged sixty-five and older who were hospitalized for an acute myocardial infarction. Twenty-six percent of the participants received a regimen consisting of aspirin alone, 20% received angiotensin-converting enzyme inhibitor (ACE inhibitor) drugs, 38% received both drugs and the remaining 16% of the participants received neither of the drugs. Aspirin and ACE inhibitors have both been shown to help prevent a second heart attack in acute myocardial infarction survivors. Because several studies had indicated a possible negative effect when both aspirin and ACE inhibitor drugs were combined, the study sought to further investigate this possibility.
After one year, the study participants who had taken the drugs experienced a significantly lower mortality than those who received neither drug. The participants who received both drugs experienced a slightly lower mortality than those who were on either aspirin or ACE inhibitors alone, however the researchers considered this to be an insignificant difference.
The study reconfirmed the survival enhancing benefit of aspirin or ACE inhibitor drugs in patients at risk for a second heart attack, and demonstrated that the combination of the two drugs not only failed to negatively impact this benefit but slightly enhanced it.
February 23, 2001
Helicobacteria pylori found in atherosclerotic lesions
The February 2001 issue of Stroke: Journal of the American Heart Association published the results of a study in which atherosclerotic lesions were examined and the majority found to contain the bacteria H pylori, a known cause of stomach ulcers. Recent evidence has implicated inflammation and possible infection as playing causative roles in atherosclerotic vascular disease, with Chlamydia pneumoniae, herpes simplex 1 and 2, hepatitis A, cytomegalovirus and H pylori diagnosed more often in people with atherosclerosis. Acute infections frequently precedes stroke and heart attack, possibly acting as a trigger. While several of the above noted infectious agents have been isolated from atherosclerotic lesions, H pylori's presence had not previously been confirmed.
Thirty-eight specimens were obtained from patients undergoing carotid endarectomy and seven were obtained from autopsied subjects who did not have atherosclerosis of the carotid artery. Twenty of the thirty-eight atherosclerotic plaques tested positive for H pylori while none of the nonatherosclerotic normal carotid arteries contained the bacteria. The presence of the bacteria was not associated with previous neurologic symptoms, vascular risk profile or age, but was more prevalent in samples taken from men than women. The authors believe that the failure of previous studies to detect H pylori in vascular lesions was due to less sensitive methods of detection. They conclude that infectious processes are implicated in the occurrence of cerebrovascular disease and offer three possible mechanisms of action: first, that acute infections may precipitate ischemic events due to their effect on coagulation; second, that chronic infection in remote sites can cause an increase in atherosclerotic load; and third, that the microorganisms themselves contribute to atherosclerosis by their presence in the artery wall, either by initiating the plaque or furthering its progression.
February 21, 2001
Rare disease research leads to breast cancer discovery
Research seeking the genetic pathway of Fanconi's anemia, a rare disease that effects only 500 American families, has found that the genes form a path to BRCA1, the gene that helps repair DNA damage in cells, preventing them from becoming cancerous, and which, when defective, causes hereditary breast cancer. Faconi's anemia is a recessive hereditary cancer susceptibility disorder caused by a mutation in one of seven genes, and is characterized by a cellular sensitivity to ionizing radiation. Its victims develop bone marrow failure by age five and frequently develop cancer as young adults. The February 2000 issue of the journal Molecular Cell published a study showing that if the gene BRCA1 or any of the genes involved in Fanconi's anemia are abnormal, cancer risk greatly increases. Previous research showed that proteins produced from five of the genes involved in Fanconi's anemia form an enzyme that activates a sixth, and the current study shows how that gene expresses a protein that works with BRCA1. A mutation in the Fanconi genes can block BRCA1 from being activated, preventing it from repairing DNA. Testing for mutations in these genes could be a new method to identify women who are found to have normal BRCA1 genes, but remain at risk for breast cancer.
Research team leader Alan D'Andrea MD of Dana-Farber Cancer Institute and Harvard Medical School stated, "There's strong evidence that under normal conditions, BRCA1 helps repair DNA damage in cells, preventing the cells from becoming cancerous. But until now, little was known of how BRCA1 is switched on. This new study presents a pathway leading to BRCA1 and it was discovered by studying a condition that's known to affect only 500 families in the United States . . . It might be possible to design a drug that amplifies this pathway, accelerating the repair work of BRCA1 and reducing the chances that breast cancer will occur in people with a genetic risk for it. Much work, however, remains to be done before such therapies become a reality."
February 19, 2001
Inflammation and genetics both causative in Alzheimer's
Various causes have been proposed for Alzheimer's disease, including a gene or genes, and inflammation. Neurochem Corporation announced the results of a study which indicated that the inflammatory response of brain cells to amyloid protein is genetically predetermined. Amyloid protein is a protein found in the plaques that form in the brains of Alzheimer's patients, which according to recent research is responsible for the disruption of signals in the brain that contributes to the memory loss that is the hallmark of the disease.
In a study presented at the IBC conference this month, researchers sought to determine whether the level of microglial response to amyloid is genetically controlled. Microglia are the brain's phagocytes, which when activated cause an inflammatory response that releases neurotoxic substances. In the study, different strains of mice known to have a high or low response to inflammation were stimulated with amyloid and their key markers analzyed. The microglia and inflammatory mediators were analyzed and found to differ between the strains of mice, demonstrating a genetic predisposition toward an inflammatory response to amyloid. The researchers believe this demonstrates that differences in the levels of amyloid-induced inflammation by the microglia are genetically controlled and could effect the events leading to the neurodegeneration typical of Alzheimer's disease.
President and Chief Executive Officer of Neurochem, Louis R Lamontagne, commented, "Alzheimer's Disease continues to challenge the medical community because the exact pathway leading to neurodegeneration in this disease is not well understood. This finding is important not only because it adds significant information about the AD mechanism, but it shows that early treatment for those patients who are genetically predisposed to suffer earlier from the inflammatory damages caused by amyloid can have a dramatic effect in halting the disease's progression."
February 7, 2001
Hyperthyroidism associated with Alzheimer's risk
A study published in the December 2000 issue of the journal Clinical Endocrinology, found that low levels of thyroid stimulating hormone (TSH) indicating hyperthyroidism are correlated with a higher risk of Alzheimer's disease and dementia. The hormone is released when the body perceives that levels of essential thyroid hormone are low. It tells the thyroid gland to produce more of its hormone, consequently, levels of TSH are high when the body's levels of thyroid hormone are low (hypothyroidism), and low when thyroid hormone is high, indicating the condition of hyperthyroidism.
A random sample of 1,843 participants age fifty-five and older from the Rotterdam Study in the Netherlands were evaluated for serum TSH and antibodies to thyroid peroxidase at the beginning of the study, and were screened for dementia at baseline and at a two year follow-up. Subjects who had abnormal TSH levels were also screened for serum thyroxin (T4). Those with low TSH levels developed Alzheimer's disease and dementia at three and a half times the rate of those with normal levels, after adjustment for age and gender. For those whose TSH was low who also had antibodies to thyroid peroxidase the risk of dementia was particularly elevated. Although serum thyroxin levels were not elevated above normal (greater than 140 nmol/Liter) in participants who had low TSH, these levels were also found to be related to the risk of dementia. The authors conclude, "This is the first prospective study to suggest that subclinical hyperthyroidism in the elderly increases the risk of dementia and Alzheimer's disease."
February 14, 2001
Deadly pancreatic cancer responds to vaccine
Cancer of the pancreas is the fifth leading cause of cancer, and one of the most lethal because the majority of cases are found only in advanced stages. Once diagnosed, modern medical science has offered little hope. One year survival rates are currently 18% and 4% at five years. A vaccine for this form of cancer has shown success in mice, but it has been unknown whether it would help humans.
A study conducted at Johns Hopkins University published in the January 2001 issue of the Journal of Clinical Oncology revealed the results of a tumor vaccine tried on fourteen patients in stages 1, 2 or 3 pancreatic cancer whose tumors had been surgically removed. The vaccine, which had cured tumors in mice, consisted of tumor cell lines that were genetically engineered to produce the immune system-stimulating cytokine known as granulocyte-macrophage colony-stimulating factor.
The patients received varying amounts of vaccine eight weeks after their surgeries, followed by six months of chemotherapy and radiation therapy in twelve of the patients. One month following the chemotherapy and radiation, six patients who were in remission received additional vaccinations. Three patients receiving one of the higher vaccine dosages showed immunity to their tumor cells and experienced a disease free survival time of at least twenty-five months following their diagnosis. The researchers concluded that the vaccine is safe and without side effects, and the response dose-dependent.
February 12, 2001
Spirulina boosts body's cancer defenses
Spirulina, a blue-green algae that grows on lakes and ponds, has been the subject of studies at North Carolina State University, the University of California, Davis and other research facilities, which demonstrated an immune-boosting effect. In a clinical study reported at the Japanese Society for Immunology's 30th Annual Meeting, spirulina extract was found to boost the tumor fighting ability of interferon gamma and natural killer cells.
Researchers at the Osaka Institute of Public Health in Japan gave volunteers over forty years of age 50 mL of a spirulina extract and measured the activity in the blood of interferon gamma and natural killer cells. For one to two weeks following the participants' ingestion of spirulina, the activity of these substances was found to increase, and this increased activity continued for twelve to twenty-four weeks.
At the 59th Annual Meeting of the Japanese Cancer Association held in October of 2000, researchers from the Osaka Institute reported that adding spirulina to a bacterial cell wall product known as BCG-CWS known to cause tumor shrinkage, caused more tumor regression in implanted tumors in mice than that caused by the BCG-CWS alone. BCG-CWS has been used to activate cytotoxic T-cells in lung cancer patients. The coadministration of spirulina with BCG-CWS caused an 80% regression of tumors, attributable to the combined enhancement of the activity of interferon gamma, natural killer cells and cytotoxic T-cells.
February 9, 2001
New test diagnoses congestive heart failure in minutes
Congestive heart failure (CHF) is the fourth leading cause of hospitalization in the United States, and the leading cause of hospitalization in people over sixty-five. The condition has been defined as that occurring when the heart is incapable of maintaining a cardiac output adequate to accomodate metabolic requirements and the venous return. Diagnosis of CHF is sometimes difficult, with symptoms and signs such as shortness of breath and edema being diagnostic of several conditions and physical examination prone to error. Although markers such as cytokines and catecholamines are elevated in CHF, they are hard to measure and often not elevated until the disease becomes severe. Echocardiogram is effectively employed in CHF diagnosis, but is time-consuming and expensive. A new blood test has been developed which can diagnose CHF in fifteen minutes. The test measures blood levels of a peptide called B-type natriuretic peptide (BNP) which is released in response to increased pressure load of the heart's ventricles, the lower chambers of the heart.
In a study published in the February 2, 2001 issue of the Journal of the American College of Cardiology, 250 patients with shortness of breath who were seen in urgent care and emergency departments had blood samples drawn and BNP levels measured without their attending physicians being informed of the results. Two cardiologists evaluated the patient's clinical data and symptoms to provide a diagnosis. Using the cardiologists' diagnoses as the standard, concentrations of 80 pg/mL BNP were 95% accurate in diagnosing congestive heart failure, and values lower than this were 98% accurate in ruling out the condition. Thirty cases of congestive heart failure diagnosed by the cardiologists were missed by the urgent care physicians, but a BNP test could have brought this figure down to one. Study coauthor Alan S Maisel MD remarked that the test has greater diagnostic accuracy than does the PSA for prostate cancer, mammogram for breast cancer or a PAP smear for cervical cancer. In view of the fact that one study estimated up to 20% of all congestive heart failure cases as being misdiagnosed, the new test will enable urgent care physicians to provide a more rapid, accurate diagnosis for this group of patients.
February 5, 2001
Drug breaks up crosslinks
A new drug that breaks crosslinks was found to cause a partial reversal of hardening of the blood vessels in primates studied by National Institute of Aging scientists and other researchers. The drug, ALT-711 manufactured by Alteon, Inc, snips the crosslinks created in the body by glycosylation, which is the process by which glucose bonds to collagen, more frequently seen with elevated glucose levels in diabetes. Crosslinks increase with aging, toughening the tissue and contributing to arteriosclerosis, hypertension, heart failure, skin aging, kidney impairment and some diabetic complications.
The research, published in the January 30, 2001 issue of Proceedings of the National Academy of Sciences, was conducted on older nondiabetic rhesus monkeys who received ALT-711 for three weeks. Six weeks following the final dose, all of the vessel walls that were tested showed increased flexibility which continued for more than four months. Improved blood flow through the heart was observed for nearly ten months following the conclusion of treatment. Blood chemistry, heart rate and weight remained normal.
Study coauthor and National Institute of Aging Laboratory of Cardiovascular Sciences chief, Edward Lakatta MD, commented, "Arterial stiffening is a major factor in many of the vascular diseases associated with advancing age. The significance of this drug is it alters the properties of the arterial wall and makes it easier for the heart to eject blood into the blood vessels. These results, coupled with prior studies in smaller animals, certainly suggest that ALT-711 may be a safe and efficacious approach to decreasing the impact of arterial stiffness on cardiovascular health. However, further research, including on-going studies in people, will be needed in order to confirm and extend these findings."
February 2, 2001
Lack of COX-2 helps protect mice from stroke damage
Cyclooxygenase-2, or COX-2, is enzyme that is overexpressed in pathological inflammatory states. Inhibition of the enzyme has been found to be helpful in arthritis and some cancers, although not without possible side effects. The January 30 2001 issue of Proceedings of the National Academy of Sciences journal featured an article in which researchers attempted to determine COX-2's role in stroke damage. COX-2 is present in some brain cells and its expression is increased in stroke, seizures, and Alzheimer's dementia, but its effects in the ischemic brain are have not been defined. The researchers created a mouse model in which the gene for COX-2 was nullified and occluded the middle cerebral artery to induce ischemic stroke. The mice lacking the COX-2 gene were found to have a lack of COX-2 expression in their brains upon postmortem examination, as well as a reduction in the inflammatory hormone-like substance prostaglandin E2. Significantly, these mice were found to have a reduction in brain injury as compared to matched control mice who expressed COX-2.
The mice lacking COX-2 expression were found to have smaller infarct volumes than normal mice twenty-four hours after the ischemic event, a point in time at which inflammation related damage does not yet contribute to tissue damage. At ninety-six hours, when the damage from post-ischemic inflammation is believed to be fully expressed, infarct volume was significantly smaller in the COX-2 null mice than controls.
Glutamate neurotoxicity is a known factor in the initiation of ischemic brain injury. The researchers injected NMDA, a glutamate receptor agonist, into the cerebral cortex of normal mice and mice lacking the COX-2 gene. Both a lack of the COX-2 gene and the administration of a COX-2 inhibitor to normal mice were found to result in smaller brain lesion volume than in normal mice who did not receive the inhibitor. However, the authors conclude that lowering glutamate excitotoxicity is not the only neuroprotective benefit of COX-2 inhibition, and that COX-2 also appears to be involved in the inflammatory damage of ischemia. COX-2 inhibition could be effective in both early and late treatment of stroke, offering biomodal neuroprotection and conferring greater success than unimodal therapies.
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