New treatment for blocked vessels
The latest of the journal Nature Medicine reported a new treatment to reverse blood vessel obstruction. Obstruction of lung blood vessels is the cause of pulmonary hypertension, which occurs in heart and lung diseases or independently, and can lead to heart failure. Researchers at Toronto's Hospital for Sick Children used an elastase inhibitor to successfully treat the condition in laboratory animals. Elastase is an enzyme that causes rapid division of blood vessel cells leading to obstruction. "We were able to completely reverse fatal pulmonary hypertension in an animal model using an elastase inhibitor. Not only did it stop the progression of the disease, but the blood vessel reverted to a normal condition," stated Researcher Dr Kyle Cowan.
The elastase brought about death of blood vessel cells and caused the excess tissue to be reabsorbed, thereby widening the vessel.
"This research may lead to new avenues in the treatment of many cardiovascular conditions. While this study deals with obstructed pulmonary arteries, a similar mechanism may be applicable in reversing coronary disease as well," said research team leader Professor Marlene Rabinovitch. "Let's hope that this novel approach does bear fruit in future to help some of the people with this debilitating condition."
Colon cancer treated with antiangiogenesis antibody
At the annual meeting of the American Society of Clinical Oncology, Emily Bergsland, MD presented information concerning anti-VEGF, a recombinant humanized monoclonal antibody to vascular endothelial cell growth factor, which has demonstrated the ability to shrink cancerous colon tumors in humans. Anti-VEGF blocks the protein VEGF from initiating the growth of endothelial cells, which form new blood vessels. Without this process of angiogenesis, tumors cannot grow. Dr Bergsland stated, "This is the first time that an agent specifically developed to block blood vessel growth has shown activity in a randomized clinical trial. These results are preliminary and need to be validated in larger clinical trials, but they do lend support to the idea that angiogenesis plays a critical role during tumor progression and represents a fundamentally new target for cancer treatment."
The clinical trial included 104 patients previously untreated for metastatic colon cancer, a disease that has a median survival rate of one year. Patients received either chemotherapy, chemotherapy with a low dose of anti-VEGFor chemotherapy with a high dose of anti-VEGF. The group receiving the low dose of anti-VEGF had the best response with 40% experiencing a reduction of 50% or more in the size of their tumors, compared to 17% in the group that received only chemotherapy. The group receiving the higher dose experienced a 24% response rate. Patients receiving anti-VEGF also experienced longer times to disease progression and survived more months.
Dr. Bergsland commented, "This study gives us a sense that we are heading in right direction and is an important step toward improving therapies available for cancer patients. While it is not clear why low-dose rhuMAb VEGF appears to be more active than the high dose, both arms of the study seemed to show increased benefit compared to the control."
Stem cells treat injured spines
In a report published this week in the journal Proceedings of the National Academy of Sciences, researchers demonstrated in rats that embryonic stem cells can be used to regrow the myelin that insulates nerve fibers. Damaged myelin is the cause of paralysis in most spinal injuries because nerve fibers do not send signals to the brain without myelin. In the study, spinal cords of adult rats were chemically demyelinated. Three days later, embryonic stem cells from mice were transplanted to the area. Large numbers of stem cells survived and differentiated into cells called oligodendrocites that were capable of myelinating neurons.
Embryonic stem cells are cells formed early in development that have the ability to differentiate into any type of cell. In December of 1998, scientists announced the breakthrough of being able to culture these cells outside of the body. Embryonic stem cells offer the ability to regenerate many areas of damaged tissue. In this study, researchers used compounds which transformed mouse embryonic stem cells into the precursors of neurons, which upon injection migrated to the site of injury and covered the demyelinated areas with new myelin. Lead study author Dr John McDonald of Washington University School of Medicine in St. Louis, Missouri stated, ``This is the first demonstration that oligodendrocytes from embryonic stem cells can remyelinate the injured adult nervous system.''
Dr. McDonald announced that the next step is to see if the technique will enable lab animals with spinal injuries to regain functions such as movement.
It may be some time before humans benefit from these procedures as regulations prohibit federal funding from being granted to labs using human embryonic stem cells. ``Essentially we are blocked from working with human embryonic stem cells. This has been a big hold up,'' commented Dr McDonald.
New cancer drug
A drug code-named IMC-C225 discovered by Dr. John Mendelsohn of Memorial Sloan-Kettering Cancer Center in New York is showing potential in patients for whom other treatments have been ineffective. IMC-C225 is an antibody that blocks epidermal growth factor receptors which are areas on the cell that receive chemicals that signal them to divide. Because of a genetic error, a number of cancer cells have extra copies of epidermal growth factor receptors, which contributes to their ability to multiply. Rather than attack all rapidly dividing cells as chemotherapy does, this drug and others in the pipeline are a new attempt to focus directly on a tumor, by targeting the mutations that make them different. By stopping the growth of the tumor, it is then more receptive to the action of chemotherapy.
IMC-C225 was first tested against colon cancer by Dr Mark S Rubin with one of his patients who failed to respond to chemotherapy and whose cancer was spreading. When IMC-C225 was given with chemotherapy drug, the patient's tumor shrank by 80 percent and the rest was removed surgically. She is now cancer free. Dr Rubin stated, "It's a two-hit hypothesis. The one-two punch takes the cancer down.''
Imclone, the developer of the drug, is sponsoring studies that although in their early stages, are showing the ability of IMC-C225 to shrink tumors in 20% of patients studied with colon cancer and 30% of those with head and neck cancer. Studies are planned to test the drug against cancer of the esophagus, lung, pancreas and ovaries.
"The hope is to characterize each tumor with DNA analysis to target the therapy directly,'' said Dr. Lori Goldstein of the Fox Chase Cancer Center in Philadelphia, stating that the majority of future studies could involve similar therapies.
Less dyskinesia with new Parkinson's drug
A study published in the May 18 issue of The New England Journal of Medicine demonstrated the effectiveness of a new drug, Requip® (ropinirole hydrochloride) in managing the symptoms of Parkinson's disease while producing fewer side effects than the standard treatment, dopamine. Requip was approved by the FDA as second-generation dopamine agonist for the treatment of Parkinson's disease. Parkinson's disease occurs when nerve cells in the substantia nigra in the brain die. Because these cells produce the chemical messenger dopamine, which transmits signals between different areas of the brain and is needed for movement, treatment of the disease consists of levodopa which acts as a precursor of dopamine. Levodopa produces a high incidence of dyskinesias, which are jerky, uncontrollable body movements.
The study monitored two groups of Parkinson's patients, one taking Requip and one taking levodopa, for up to five years. Some patients in both groups whose symptoms warranted additional levodopa were given the drug. Twenty percent of patients in the Requip group developed dyskinesias, while 45 percent of patients in the levodopa group had the side effect. Those taking Requip alone were seven times more likely than those taking levodopa alone to remain free of dyskinesia.
Lead study author Olivier Rascol MD, PhD stated, "I think these results will impact physicians' treatment strategy to help improve the daily lives of patients coping with Parkinson's disease."
Clinical Director of the National Parkinson Foundation, Abraham Lieberman MD commented, "Parkinson's disease affects nearly one million Americans, including Michael J. Fox, Janet Reno and Muhammad Ali. If we can better treat the condition in the early stages, patients may be able to live more active lives. While searching for a cure to this disease, our hope is to better manage patients who are living with it now."
Colorectal cancer screening neglected
Colorectal cancer is the third most common form of cancer in both men and women, with the exception of Hispanic, native American, Asian and Pacific Islander women for whom it ranks second. Lung, breast and prostate cancers remain the most frequently diagnosed cancers and a great amount of attention has been given to their prevention. Antismoking campaigns target all age groups, yearly mammograms are urged for women over forty and prostate screening tests such as an annual PSA are finally being given the attention they deserve.
A new report released this week by the National Cancer Institute (NCI), the American Cancer Society (ACS), the North American Association of Central Cancer Registries (NAACCR), and the Centers for Disease Control and Prevention (CDC), including the National Center for Health Statistics (NCHS) showed an encouraging decline in the rates of cancer incidence and death over the past decade. Some of this decline is attributed to improved cancer screening.
Colorectal cancer is screened by either a fecal occult blood test, proctoscopy or sigmoidoscopy. Fecal occult blood testing looks for the presence of blood in the stool, which can be indicative of cancer. Based on the Behavioral Risk Factor Surveillance System (BRFSS) results, 21 percent of women age 50 and older and 18.4 percent of men in this age group had had a fecal occult blood test. In women, 26.8 had undergone proctoscopy or sigmoidoscopy while 35.2 percent of men had either procedure. Although the use of these screening procedures is increasing, these statistics are considered low. "The findings of this Report underscore the need to improve rates of colorectal cancer screening. This is one cancer where screening clearly has benefits by saving lives," stated James S. Marks, M.D., director, National Center for Chronic Disease Prevention and Health Promotion, CDC.
When colorectal cancer is detected in its earliest stage the rate of survival is 96 percent, but when the disease progresses to Stage IV, survival is only 5 percent.
Snake venom treats stroke
The Journal of the American Medical Association this week published an article on the outcome of a trial of a new drug made from the venom of the Malaysian pit viper. Ancrod, made by Knoll Pharmaceuticals, acts by producing defibrinogenation in stroke patients. Depletion of fibrinogen creates and anticoagulative effect, and decreases the viscosity of blood leading to an improvement in circulation.
Ancrod has been used in Canada and Europe over the past two decades as a therapy for peripheral vascular disease, central retinal venous thrombosis and deep vein thrombosis. Several studies have indicated that it could be effective against stroke. The current trial included 500 people, with roughly half receiving the drug within three hours of a stroke, the other half receiving a placebo. Neurologic functional status, determined by the Scandinavian Stroke Scale, was assessed in both groups. The group receiving Ancrod achieved better functional status, although the mortality of this group at ninety days was the same as the placebo group. Intracranial hemorrhage was experienced by a small number of patients who received the drug, and although occurring with greater frequency than in the placebo group, the incidence was lower than that observed in patients treated with other drugs such as TPA or streptokinase in separate trials. Although Ancrod is not completely safe, it may offer an improved therapeutic option for stroke patients.
High levels of the blood-clotting agent fibrinogen predispose a person to coronary and cerebral artery disease, even when other known risk factors such as cholesterol are low. The role of fibrinogen in the development of cardiovascular disease has been documented in several studies. The Life Extension Foundation was the first research group to recognize the importance of fibrinogen as an independent risk indicator for cardiovascular disease. A fibrinogen test can be ordered to determine if one has a high level. The following supplements may help to reduce fibrinogen levels: aspirin, vitamins B6, C and E; folic acid, niacin, ginkgo biloba, green tea, fish oil and aspirin.
Ginkgo protects brain from stroke damage
The annual meeting of the American Academy of Neurology was the site of a presentation of a study demonstrating the benefit of ginkgo biloba in the prevention of stroke damage in mice. The damage that follows a stroke is caused by free radicals, unstable molecules that are responsible for much of what we call aging and the diseases associated with aging. Ginkgo biloba is a popular herb used for several purposes among health consumers, including enhancing memory and learning, improving circulation and preventing blood clots. Ginkgo's antioxidant ability led to the investigation of its ability to mitigate some of the damaged caused by stroke.
Most strokes are caused by blockage of an artery leading to the brain by a blood clot, although the hemorrhagic variety are caused by a blood vessel in the brain rupturing. (Ginkgo would not be indicated with this type of stroke.) The blockage starves a portion of the brain of oxygen and nutrients, leading to damage of that area which can result in paralysis, speech difficulties or memory loss.
The researchers gave mice ginkgo for one week and then induced strokes. A low dose of ginkgo reduced by 30% the area of the brain affected by the stroke, while a larger dose had no effect. The report's author, Wayne Clark MD of the Oregon Stroke Center at Oregon Health Sciences University stated, "More work is needed to determine the proper dose. In addition, because ginkgo is also a mild blood thinner, it may be risky to use it in patients already on blood thinning medications commonly prescribed in people at risk for stroke." He added, "In addition to reducing stroke injury, ginkgo may also be useful in improving memory following a stroke."
New antioxidant astaxanthin
Astaxanthin is classified as a carotenoid, the family of over 700 pigments that includes beta-carotene, canthaxanthin and lutein. Although widely found in nature, it is only recently that its health promoting characteristics have been researched. Studies have demonstrated the ability of astaxanthin to enhance energy metabolism and immune function, increase HDL levels, protect against chemically induced cancers, reduce macular degenertion and protect against sunburn. Even more astounding is astaxanthin's antioxidant capability, ten times that of beta-carotene, xeaxanthin, lutein and canthaxanthin, and up to 550 times that of vitamin E! It is able to quench singlet oxygen as well as scavenge free radicals. Its effectiveness is better expressed in the lower oxygen concentrations found in tissues than higher levels associated with in vitro conditions.
One of the challenges associated with eye nutrition is the body's limited ability to deliver nutrients to the proper areas in the eye. Unlike beta-carotene, astaxanthin can cross the blood-brain barrier to offer protection to the retina of the eye against oxidation caused by sunlight. Injury caused by light is the primary cause of macular degeneration, a disease that results in a loss of photoreceptor cells. Astaxanthin does not have the drawback of the possibility of crystallization in the retina associated with another carotenoid, canthaxanthin. It also protects the retina against free radical damage.
Astaxanthin aided in protecting mice from the development of cancer resulting from carcinogens such as benzopyrene, azoxymethane and aflatoxin. Scientists speculate that its anticancer effect is due its antioxidant ability and its antiproliferative effect on areas exposed to the carcinogen. It may also work by its enhancement of immune function. Astaxanthin has a significant effect on antibody production when the body is presented with antigens.
Cyanotech corporation produces astaxanthin from Haematoccus microalgae.
Region of telomerase possible target for cancer, HIV therapy
Telomerase is an enzyme that replenishes telomeres, which are caps found at the ends of chromosomes that shorten with age, signaling cells to stop dividing. Telomerase copies the RNA within the telomeres into DNA and assembles it on the ends of the chromosomes, thereby lengthening the life of the cells. The May 5 issue of Science reported a study conducted at the University of California, San Francisco in which researchers found the area in telomerase that could be a target for regenerating damaged cells, for killing cancer cells and for attacking HIV. The researchers determined that a structure within the RNA of yeast telomerase controls how it performs its function. When this area was disrupted, the telomerase manufactured telomeres uncontrollably, until abruptly halting, resulting in cell death.
Study coauthor and codiscoverer of telomerase, Elizabeth Blackburn, PhD stated, "This discovery represents the first time anybody has shown a mechanistic role for a structure of RNA in the action of telomerase, and we think this is probably a universal kind of feature of telomerase."
Blackburn explained how human telomerase appears to have a region similar to that found in yeast and that the area could be a target for killing cancer cells and for regenerating cells that have been damaged.
Reverse transcriptases such as telomerase and HIV both contain RNA enfolded in protein, whereas most enzymes contain only protein. Research on telomerase and HIV had previously been conducted on the protein components. The findings of this research lend credence to the possibility that the RNA of HIV may play an critical role in the virus' ability to reproduce.
"This discovery should turn researchers' spotlights back to the RNA components of both telomerase and HIV," said Blackburn. "Our finding in telomerase gives strength to the importance of looking at the RNA component of HIV because by making just a simple change in telomerase RNA we can make it act more like HIV, and this suggests that HIV is actually like telomerase -- when it acts in cells to make new viruses, it really is acting together with its RNAs. I think this is something one should be thinking about for drug targets."
Black holes reduced by drug
Those of you who hear the term "black holes" and immediately think of the far reaches of outer space will be interested to learn that the term is also used to describe hypointense T1 lesions found in the brains of people suffering from multiple sclerosis. At the annual meeting of the American Academy of Neurology, Ludwig Kappos MD of University Hospital, Basel, Swizerland reported that black holes were prevented from developing in the brains of secondary progressive multiple sclerosis patients by administration of the drug Betaseron(R) (Interferon beta-1b). The study was performed in five centers, with 95 secondary progressive MS patients taking part. Patients receiving the drug were injected every other day and received six MRIs per month for three years. Black holes showing up on the MRI images indicate brain cell loss, especially axonal loss. This destruction of axons interrupts nerve impulses in the brain which interferes with the ability of these patients to perform activities of daily living. After thirty-six months, the median black hole volume increase was 23 percent in the Betaseron(R) treated group compared to 42 percent in the placebo group. Dr Kappos commented, "A 45 percent reduction in the development of 'black holes' clearly illustrates the efficacy of Betaseron therapy in delaying axonal damage in secondary progressive MS patients. By reducing damage to axons, Betaseron is able to slow the disabling effects of secondary progressive MS. This study reinforces previous clinical findings from a European trial that indicated Betaseron slowed disease progression in people with secondary progressive MS." Secondary progressive multiple sclerosis is defined as MS that initially is relapsing-remitting that becomes progressive at a variable rate, with a possible occasional relapse and minor remission. Approximately half the people with relapsing-remitting MS advance into this manifestation of the disease.
Betaseron(R) was developed by Chiron Corporation and Berlex Laboratories.
Regimen protects mice against cancer
The May 2000 issue of Carcinogenesis featured an article in which researchers from the University of California, Davis reported that for the first time a preventive regimen has proven to protect against the development of lung cancer in mice exposed to tobacco smoke. Mice given inositol and the drug dexamethasone were exposed to tobacco smoke for five months, followed by four months of exposure to clean air. The periods of smoke and clean air exposure were intended to simulate that of humans who had just given up smoking, as lung cancer diagnoses are highest in those who have recently quit. (The reason for this phenomenon could be that symptoms of lung cancer, such as a chronic cough, prompt the smoker to stop .)
The mice were protected against cancer during their exposure to tobacco smoke as well as during the smoke-free period. Mice who were exposed to smoke without receiving the inositol and dexamethasone had a tumor incidence of 89%, while those who received the preventive regimen experienced a 62% rate, which is similar to what mice who had not been exposed to smoke exhibit. The researchers hope these findings will be useful in the prevention of lung cancers in humans.
Research team member Dr. Hanspeter Witschi stated that this study is the first animal model for testing substances that may have a protective effect on the lungs against cancer caused by smoking. Several other regimens of substances known to prevent cancer in animals were tested without success.
High iron levels linked to greater stroke damage
The Life Extension Foundation has long warned of the dangers of high levels of iron. Elevated iron levels have been linked to higher risk of cancer, heart disease and Parkinson's disease. Now researchers from the Hospital Universitari in Girona, Spain, have found that elevated iron increases damage from stroke.
In a study published in Neurology, a research team led by Dr Antoni Davalos measured ferritin levels in one hundred stroke patients. Ferritin is a measure of the amount of iron stored in the body. The median plasma ferritin concentration was much higher (391 ng/mL) in the forty-five stroke patients who had progressing neurological decline, defined by increased weakness, decreased levels of consciousness, and speech problems, compared to the stroke patients whose condition was improved or stable, whose median ferritin measured 148 ng/mL. Dr Davalos commented, "High body iron stores might contribute to stroke progression by increasing the production of free radicals in brain cells and in the walls of brain microvessels. Free radicals destroy the cell components and promote other mechanisms of injury that might enlarge the damaged area of the brain, referred to as the cerebral infarct volume."
"Stored iron increases with age in normal people, but iron accumulation is accelerated among a small percentage of the population. For these people a diet low in iron should be recommended. Blood ferritin levels should be tested as we test cholesterol or glucose levels in patients with cardiovascular diseases or cardiovascular risk factors," stated Dr Davalos. "Our findings support future therapeutic studies of agents which inhibit iron's toxic effects on brain cells immediately after stroke. The effect of reducing iron levels among people at risk for stroke with ferritin levels higher than 275 ng/mL should also be evaluated."