What's Hot Archive
July 31, 2000
Fewer mastectomies needed
The July 19 issue of The Journal of the National Cancer Institute published the longterm results of a randomized multicenter trial in which 868 women with breast cancer were given either breast conserving therapy (BCT) or a modified radical mastectomy. Breast conserving therapy consisted of a lumpectomy with removal of a margin of one centimeter around the tumor and radiation. The trial was conducted between 1980 and 1986 and the patients were followed up for a median of 13.4 years. Eighty percent of the women in the study had tumors measuring between 2.1 and 5 centimeters. At the present, only women with tumors 2 centimeters or smaller are routinely given breast conserving therapy, while women with larger tumors are advised to undergo mastectomy. Prior research has demonstrated BCT to be as effective as mastectomy in women with these smaller tumors.
After ten years, survival was 65% in those who received BCT and 66% in those receiving the mastectomy, considered to be statistically the same. Women who retained their breasts had a somewhat higher rate of recurrence, but this still had no effect on their survival rate. The two groups also experienced approximately the same rate of metastasis, with 66% of those undergoing a mastectomy remaining free of metastasis in distant locations as compared to 61% of those who received breast conserving therapy.
According to BBC news, the majority of women in developing countries are diagnosed with breast cancer before the tumor reaches 5 centimeters in size. "Breast conserving therapy instead of mastectomy can therefore now be offered to the large majority of breast cancer population, said research team leader Dr Harry Bartelink of the Netherlands Cancer Institute.
July 28, 2000
Human virus causes obesity in lab animals
The August issue of the International Journal of Obesity published a study in which mice and three groups of chickens injected with a human adenovirus experienced increased gains in body fat. The University of Wisconsin scientists also innoculated another group of chickens with a different, avian adenovirus to ascertain if the fat gain could be in response to viral infection in general, but found that this group did not experience the increase in adipose tissue of those injected with the human virus. The human virus did not damage the hypothalamus, the gland which controls energy expenditure, nor did the animals eat more. Interestingly, the infected animals experienced lower levels of triglycerides and cholesterol.
Experiments such as this have previously been conducted on animals, using animal viruses. This is the first study utilizing a human virus to cause obesity in animals, which leads researchers to believe that some human obesity may have a viral cause. In a prior study that included fifty-two obese people, lead study author Dr Nikhil V Dhurandhar found that only the ten most obese subjects showed antibodies to a chicken adenovirus, SMAM-1.
A viral infection having the potential to cause obesity might necessitate cofactors such as having an obesity gene, overeating or eating a high fat diet, or not exercising. This study coincides with the current train of thought that proposes infectious causes for various diseases such as ulcer, multiple sclerosis, and heart disease. Dr Dhurandhar told the Life Extension Foundation, "Several chronic diseases are increasingly being linked with various bacteria and viruses. Obesity in some cases may be one more such disease in which infection may play a role."
July 26, 2000
Two studies find gene defect in primary pulmonary hypertension
What's Hot readers may recall news of an effective treatment for pulmonary hypertension posted on May 31. Now two separate research teams, both funded by the National Heart, Lung, and Blood Institute (NHLBI) have discovered that defects in the BMPR2 gene are responsible for primary pulmonary hypertension (PPH), a rare disease of the lung in which uncontrolled growth of cells in the lungs' blood vessels leads to blockages which force the heart to pump harder and increases pulmonary artery blood pressure. The PMPR2 gene controls growth and development of the lung.
Although primary pulmonary hypertension can occur at any age, including infancy, it mainly effects women in their reproductive years, with twice as many women as men diagnosed with the disease. Patients with the disease have a limited life expectancy; treatment options for advanced PPH being lung transplantation and continuous intravenous prostacyclin to relax blood vessels, both fraught with difficulty. The studies will be published in the September issues of the journals Nature Genetics and American Journal of Human Genetics.
"This research is the culmination of nearly 20 years of work to identify possible immunologic and genetic factors in the cause and progression of PPH. Now that we have pinpointed a gene, we can focus on learning how it works. That information should enable us to devise better treatments and perhaps eventually a preventive therapy or cure," stated NHLBI Director Dr. Claude Lenfant. Both groups of researchers agree that BMPR2 defects are not the only cause of the disease. There are many individuals who contract the disease who do not have a family history of PPH, which leads researchers to believe that other factors are involved. The researchers next wish to find out if the same genetic defect exists in these individuals.
July 24, 2000
Spherons linked to Alzheimer's
The latest issue of Alzheimer's Reports featured an article in which Spherons, tiny balls of tightly packed protein found in some brain cells throughout human brains, have been linked with Alzheimer's disease. Using forensic techniques to date amyloid beta proteins found in the Spherons, researchers from Nymox Corporation found them be quite old, some as old as eighty years. Other than proteins in teeth and bones, most proteins in the body last no longer than a few weeks. Previous research by other scientists found that senile plaques, the brain lesions found in Alzheimer's disease, also contained similarly aged amyloid beta proteins. Senile plaques and Spherons have been the only sites in the brain in which this aged protein is found. The scientists concluded that as humans age, the Spherons grow until they become too large for the cell that contains them, which causes them to be released. The Spherons then burst, causing senile plaques.
Lead study author Dr Paul Averback stated, "In our view, these unusually old proteins are like fingerprints left behind in the center of the senile plaques by the bursting Spherons, serving to identify Spherons as a leading suspect in the cause of Alzheimer's disease. This evidence also confirms that Spherons are very old entities in our brains, dating back to infancy, and that they accumulate proteins as we age. We believe that, on the basis of this evidence and our earlier findings, that Spherons are a uniquely important target for the development of drugs for the treatment of Alzheimer's disease."
Alzheimer's disease is the leading cause of dementia in the elderly and is the fourth leading cause of death in developed nations. It currently effects four million Americans, and it is estimated that the total will increase to 14 million by 2050. It is devastating to both the sufferer and the family of the afflicted individual. Lifetime costs of caring for an Alzheimer's patient are estimated at $174,000.
July 21, 2000
Most cancer not inherited
A study of 44,788 pairs of Scandinavian twins just published in the New England Journal of Medicine revealed that while more cancers are hereditary than previously thought, they still comprise a minority of cancers. The study examined twins because they share the same genetics. Researchers were able to observe whether cancer appeared in one or both twins. In identical twins, the average of cancer appearing in both twins was generally less than 15%, clearly a low rate. Cancers with the strongest hereditary component were prostate, colorectal and breast cancer, however genetics still accounted for the minority of these cases. Prostate cancer appeared to be the type of cancer that was associated with the greatest (42%) inherited risk.
While the bad news is that the rapid decipherment of the genetic code will not impact most cancers, the good news is that most cancers are caused by factors we can do something about. Smoking, alcohol, viruses, radiation, drugs, diet and occupational toxins are all environmental factors that cause most cancers, and can be avoided. These findings confirm previous observations of populations whose incidence of cancer changes after migrating to another country. For example, Asian women have an 80% lower incidence of breast cancer before immigrating to the United States compared to third generation Asian-American women living in this country, whose breast cancer risk is the same or higher than that of Caucasian-American women. This demonstrates the impact of lifestyle and environmental factors on the development of breast cancer and refutes the possibility of a strong genetic protective factor in Asian women. Similar observations have been made of other types of cancers. This study should offer hope that most cancers can be avoided if people are willing to adopt the lifestyle factors known to prevent it.
July 19, 2000
Water breaks up blood clots
Six locations in the US will be the sites of a multicenter research study that utilizes pressurized saline (salt water) at a speed of 300 miles per hour to break up blood clots in the brain. The technique involves the use of a device called the Angiojet Rheolytic Thrombectomy System made by Possis Medical, Incorporated, which is threaded from a leg artery to the site of the bloodclot in the brain. The Angiojet is then used to deliver the saline which breaks up the clot and removes the residue. Patients are initially given a CT scan to determine that their stroke is not of the hemmorhagic variety, resulting from bleeding within the brain, and are followed up with an angiogram to ascertain that the clot has been dissolved. In some cases patients are additionally given TPA, a clot-dissolving drug.
Principal study investigator Lawrence Wechsler, MD, of the University of Pittsburgh School of Medicine stated, "The goal of the use of this experimental device is to open the blood vessel and quickly restore blood flow to the region of the stroke and restore function. It may be possible to remove the blood clot within minutes instead of the 30 to 90 minutes needed for infusion of the clot-busting drug TPA. The faster we can restore blood supply to the affected area of the brain, the less damage the stroke will cause . . . We can use this experimental treatment up to six hours after the patient has a stroke compared to intravenous TPA treatment, which only has a three-hour window of opportunity"
Although the Angiojet is currently has not yet been approved by the FDA for strokes, it is currently approved for use in removing clots in coronary and leg arteries, and dialysis access grafts.
July 17, 2000
Drug shows promise in Alzheimer's disease
The World Alzheimer's Congress 2000 held in Washington DC this week was the site of the announcement by NeoTherapeutics Corporation and scientists from Indiana University that the drug Neotrofin tm improved memory in Alzheimer's patients and reduced the level of beta amyloid in cell cultures. Beta amyloid is a protein found in increasing amounts in the brains of Alzheimer's patients which results in the formation of plaques that lead to the death of brain cells. Neotrofin tm effects the processing of the amyloid precursor protein, for which there is altered processing in the disease. It also stimulates the production of neurotrophic (nerve growth) factors necessary for nerve regeneration.
Alzheimer's therapies have focused on administering drugs that mimic neurotransmitters, or otherwise increasing them. Neurotransmitters are chemicals made by the body that enable nerve cells to communicate with one another. However, the loss of brain cells makes neurotransmission difficult, even with increased neurotransmission ability. Neotrofin tm stimulates existing nerve cells to form new connections, which can help to compensate for their loss.
The announcement was the result of preliminary analysis of a clinical trial involving 400 patients. Full analysis of all the data obtained in the trial will be released at a later date. Scott Wieland, PhD, NeoTherapeutics' vice President of Product Development and Regulatory Affairs stated, "The limited data analyzed thus far showed that the beneficial effects increased over the course of the 90 days of treatment and was most pronounced in patients with more marked memory deficits. The results available to date are consistent with our expectations and provide further evidence that Neotrofin improves cognitive function in many patients with Alzheimer's disease and confirms our decision to move rapidly into our Phase 2b/3 clinical trial involving over 1500 patients in 16 countries being treated with Neotrofin tm for six months."
July 14, 2000
Antibodies aid remyelination
In what has been called a major scientific discovery, researchers at the Mayo Clinic have stimulated the regrowth of damaged myelin in mice through the use of two human antibodies. Mice given a virus that causes multiple sclerosis symptoms were injected with two human monoclonal antibodies, and were pathologically examined five weeks later. Remyelination occurred in an amount equal to or great than the current treatment of human intravenous immunoglobulin. Mice given one antibody showed remyelination of one quarter of their damaged tissue.
The researchers acted on the theory that demyelinated central nervous nervous system tissue contains cells that are capable of remyelination as well as containing growth and differentiation factors. The antibodies join with antigens on the oligodendrocites, which are the cells that produce the myelin sheaths for central nervous system. Although their mechanism of action in remyelination is not certain, they may have a direct effect on the recognized cells or may enhance the removal of cellular debris from damaged areas which allows the central nervous system to spontaneously repair itself. Lead study author Moses Rodriguez MD, commented, "Clearly, our study shows that the two natural human antibodies, when introduced into mice that had nervous system damage, safely caused substantial repair to the myelin and the nervous system. This is a significant step forward in our understanding of the nervous system and the immune system. Whereas we know that the immune system can have a protective effect on the body, we now are beginning to discover that the immune system may be harnessed to effect repair to the nervous system in the mouse model . . . This type of basic scientific research is needed to advance medicine and our potential to develop new treatments and therapies for humans."
This research has implications for patients with multiple sclerosis or spinal cord injury. The study was published in the June 5 issue of Proceedings of the National Academy of Sciences.
July 12, 2000
Tumor reversion studied
The start up company, Molecular Engines Laboratories is seeking to develop new cancer therapies by studying a phenomenon called tumor reversion. Tumor reversion rests on an observation made by Adam Telerman and Robert Amson ten years ago that a tumor cell can be reprogrammed into a noncancerous state. Telerman and Amson joined genomics researcher Daniel Cohen and Nobel laureate Jean Dausset of the Human Polymorphism Study Center, who collaberated with another Nobel laureate, physicist Georges Charpak, and Claude Hennion, formerly the president of Biospace Instruments. Certain members of the group founded the new company based on encouraging results in their research.
One quarter of the genes involved in tumor reversion have so far been identified. These genes are potential targets for anticancer therapies and are also involved in the cell death program which implicates them in Alzheimer's and other neurodegenerative diseases. Molecular Engines Laboratories seeks to identify the majority of the tumor reversion genes so that strategies can be developed that cause the death of tumor cells. Reprogramming cancer cells to be noncancerous is a unique therapy that holds tremendous promise.
July 10, 2000
Cardiac bypass given under local anesthetic
For the first time in the US, an a coronary bypass operation was given to a patient who received a local anesthetic. On June 15, a team of surgeons at the VA Pittsburgh Healthcare System working with surgeons from the University of Pittsburgh Medical Center operated on a fifty-one year old patient who received an epidural anesthetic which numbed his chest area. The patient was fully awake and was able to speak to the staff during the procedure.
The surgical technique used was a minimally invasive direct coronary bypass, also called beating-heart bypass, which means that the heart is not stopped, as in the standard bypass procedure which utilizes a heart-lung machine to perform the heart's functions during the operation. This procedure lessens the amount of hospitalization necessary and lowers the risk of neurological complications. With a local anesthetic, the procedure may make time currently spent in the intensive care unit unnecessary, requiring only an overnight hospital stay.
Attending anesthesiologist, Juhan Paiste, MD, of the University of Pittsburgh commented, "Combining two well-established techniques--minimally invasive cardiac surgery and epidural anesthesia--may become a new innovative approach to heart bypass surgery for select patients."
Over 600,000 bypasses were performed in the United States in 1997, according to the American Heart Association. The originator of the procedure is Haldun Y Karagoz, MD in Ankara, Turkey, who has since 1998 performed thirty bypasses on patients given local anesthetics, most of them standard bypasses in which a heart-lung machine was used.
Bartley P Griffith, MD chief of the division of cardiothoracic surgery at the University of Pittsburgh stated, "This represents an extremely important step for cardiothoracic surgery as we continue to try and make procedures more safe and cost-effective for patients."
July 7, 2000
Resveratrol fights cancer, heart disease
Researchers at the University of North Carolina, Chapel Hill have discovered the reason why trans-resveratrol, a substance found in grapes, is effective against cancer and heart disease. The findings help to explain the protective benefit exerted by regular wine consumption observed in some studies. Resveratrol (or Res) was found to turn off a mechanism involving a protein that attaches to DNA inside the cell, NF-kappa B, which prevents cancer cells from being killed. The study was published in this month's issue of Cancer Research.
Study author Minnie Holmes-McNary, PhD summarized, "A couple of years ago, a group at the University of Illinois found that Res has both anti-inflammatory and anticancer properties. The question then became how does it exert its effects, and that's what we show in our paper . . . Using Res, we were able to promote apoptosis, a process that the body uses to kill cancer cells and other cells it needs to get rid of. When Res was absent from the cell culture system, cancer cells continued to survive, but when Res was there under experimental conditions, we could successfully promote death of cancer cells . . . This is very exciting work because we believe it explains how diet modulates changes at the molecular level."
The study was carried out on cultured rat and human cells, and plans are underway to study resveratrol in rats, followed by humans. Resveratrol was also able to inhibit a NF-kappa B dependent gene involved in the development of atherosclerosis.
NF-kappa B seems to be a protector of both healthy cells and cancer cells from chemical attack. This offers an explanation as to why many cancers become chemotherapy and radiation unresponsive. In another study, University of North Carolina researchers were able to treat mice more successfully with chemotherapy by inhibiting NF-kappa B.
July 5, 2000
Cancer cells killed by virus
A team of Canadian scientists have discovered that vesicular stomatitis virus, or VSV, is able to kill cancer in some tumor cells. The theory that infection by a virus may have an adverse effect on cancer has piqued the curiosity of researchers for some time. In this study, published in the July 2000 issue of the journal Nature Medicine, researchers acted on the knowledge that interferon has had limited results in inhibiting the growth of cancerous tumors because of mutations specific to cancer in the genes involved in the interferon pathway. Interferon is a substance produced by cells infected with a virus, that inhibits viral growth. It is effective against many different viruses, and has the ability to induce growth inhibiting signals in normal and tumor cells. Cancer cells that do not respond to interferon have developed a survival advantage, and the hypothesis in this study is that this may have also compromised their own antiviral response, rendering them vulnerable to viral infection. The researchers infected with VSV several normal cell lines and tumor cell lines grafted into mice. VSV is known to be sensitive to treatment by interferon. The tumor cell lines used in the experiment included ovary, lung, prostate and colon cancer, and melanoma. The cell lines were each subdivided into two groups, one which was pretreated with interferon and the other left untreated. The tumor cells produced much higher viral counts the following day than did the normal cells, and experienced more rapid cell death. The virus killed all of the melanoma cells within twenty-four hours, pretreatment with interferon not having a protective effect. Some tumor lines showed a limited response to interferon after pretreatment, demonstrating that their interferon response was functional, but impaired. Normal prostate and ovarian tissue infected with VSV began to display signs of cell death after thirty-six hours, but those pretreated with interferon were indistinguishable from uninfected cells seventy-two hours after infection.
This study demonstrates the ability of a virus to kill several types of cancer cells well as interferon's ability to protect healthy tissue while leaving cancerous tissue open to attack.
July 3, 2000
Vitamin C status correlates with male mortality
The July 2000 issue of the American Journal of Clinical Nutrition reported the results of a study in which 7071 adults, aged thirty to seventy-five, were tested for serum vitamin C as part of the National Health and Nutrition Examination survey conducted between 1976 and 1980. The status of the participants was examined in 1992. Men who had the lowest serum vitamin C experienced a 57% greater risk of dying from any cause and a 62% greater risk of dying from cancer than did men who had the highest serum ascorbate levels. This correlation was not observed in women. These statistics were the same when when analyses were limited to nonsmokers or further to adults who never smoked.
Vitamin C is believed to protect against cancer by detoxifying carcinogens and enhancing immune function. It protects against the number one cause of death, heart disease, though its role in collagen and prostacyclin production as well as by its antioxidant ability.
According to the study, women tend to have higher serum ascorbate levels. Since the increased risk of mortality was observed in men whose serum ascorbate levels fell within the lowest grouping, this may explain why the lowest grouping of women did not experience the same risk. Vitamin C also appears to be more protective against nonhormone-dependent cancers which occur more frequently in men, and may explain why men with higher levels of vitamin C experienced fewer deaths from cancer.
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