Medical Updates

Colon cancer is the number-two leading cause of cancer deaths in the U.S., surpassed only by lung cancer. The findings here suggest that genes may have an important role in cancer formation. High levels of two oncogene DNA (oncogenes are genes that can be linked to the development of cancer) were found in 54% of the colorectal cancers tested, compared with normal tissue. What's more, when the researchers artificially increased levels of one of the genes in cultured rat cells, the cells underwent cancer-like changes. These two oncogenes control the allocation of chromosomes into new cells during cell division. The two genes were traced to a region on chromosome 20 that has been linked to a variety of cancers, including a large proportion of colorectal cancers as well as breast, ovarian and pancreatic cancers. By targeting these oncogene-signaling processes, work is being done to develop a new class of target-specific growth inhibitors that may help turn cancer into a manageable disease.

Recent studies have shown that the accumulation of free radicals (toxic by-products of cellular metabolism) plays an important role in the aging process. Now, research in fruit flies indicates that an enzyme involved in the detoxification of free radicals, superoxide dismutase, may help protect against aging and actually increase life span. The aging effects of free radicals are specifically examined here in motorneurons (neurons involved in controlling muscles in the brain and spinal cord) that tend to deteriorate with age. Researchers have linked the gradual loss of these neurons with the build-up of free radicals. The result is either increased production of free radicals with age or decreased detoxification of them.

Researchers generated fruit flies that expressed the gene for the human form of superoxide dismutase specifically in adult motorneurons. Expression of this gene extended the life span of fruit flies by 40%, leading researchers to call it a "longevity-assurance" gene. Expression of the human gene also partially rescued the short life span of a mutant fruit fly (in whom the life span is normally reduced by 85%-95%) from 5% of its normal length to 60%.

The findings define a new and critical role for free radicals and their detoxification in determining life span. Superoxide dismutase may be a target for intervention designed to reduce the gradual loss of function associated with "normal" aging.

Note: Prior research has shown that naturally long-lived strains of fruit flies are different from short-lived strains because they possess a gene that allows the manufacture of greater amounts of the antioxidant superoxide dismutase. Greater amounts of this antioxidant prevent more free-radical damage; less damage results in a significantly longer life span. This study shows that this is indeed the case. Free radicals are now implicated in many chronic disease processes, including many forms of cancer, atherosclerosis, cataracts, Alzheimer's disease, skin wrinkling, and the aging process itself.

Parkinson's disease is characterized by progressive degeneration of the dopamine-producing cells in the brain, resulting in tremor, difficulty walking, and eventual paralysis. Nine people with early to moderate Parkinson's disease showed improvement in both learning and memory (including reaction time and central processing speed) after being given nicotine by intravenous injection and then wearing a nicotine patch for 2 weeks. The improvements appeared to be sustained for up to 1 month after the drug had been discontinued. After chronic use of nicotine, the researchers also saw improvements in the ability to move. Some studies have shown that smokers are significantly less likely to develop Parkinson's disease than nonsmokers. It's also been shown that cells in laboratory culture dishes release dopamine in the presence of nicotine. These results are intriguing, and nicotinic stimulation may hold promise for improving both cognitive and motor aspects of Parkinson's disease.

Disk degeneration is a common condition in which the spongy cushions separating the vertebral bones in the back become dehydrated and damaged. Heavy lifting may trigger a range of physiological changes, eventually leading to back pain and disability. Researchers examined the way compression affects the disks in the tails of mice. A mouse's tail is an extension of its spine, and includes disks similar to those in the human back. The greater the pressure, the greater the number of cells killed in the disks. Widespread cell death eventually limited the surviving cells' ability to maintain and repair the disks. Over time, this caused water loss inside the disks, leaving them dehydrated. Once dehydrated, the disks are less able to withstand pressure, and bulge outward. Dehydration of the disks trigger other changes, including the release of chemicals that appear to irritate surrounding nerves. The release of these chemicals, and the pressure that bulging disks might exert on nearby nerves, may cause the pain associated with disk degeneration. The researchers are now testing a procedure to treat degeneration by injecting damaged disks with growth factors that stimulate cell repair. If successful, it could be an alternative to back surgery, the current treatment for disk degeneration.

A new form of gene therapy dramatically reduced the inflammation and joint regeneration associated with arthritis in rats. According to the National Institutes of Health and the Food and Drug Administration, it can effectively suppress the development and progression of chronic arthritis, even after the onset of disease. The study focuses on a new line of gene therapy research involving an immune system protein called transforming growth factor beta (TGF-B). Experts have long believed that TGF-B might help influence the inflammation processes that help trigger arthritis pain. The results of the treatments were dramatic. "Delivery of the TGF-B1...virtually eliminated subsequent inflammation and arthritis." Tissue examination conducted at the cellular level revealed "essentially no cartilage and bone destruction" following each injection. These benefits occurred through all stages of arthritis, and were sustained "in some cases for several months after treatment." It was noted that gene therapy administered before the onset of arthritis did not seem to prevent the outbreak of later disease. However, these findings provide the first evidence that gene transfer of plasmid DNA encoding TGF-B1 effectively suppresses ongoing inflammation in arthritis.

Androgens such as testosterone are generally considered to be "masculinizing" hormones, potentially harmful to the female reproductive system. But a report suggests that testosterone may be required for the normal development of ovarian follicles, which yield ova (eggs). In fact, according to the NIH, a shot of testosterone could be the answer to infertility in some women. Researchers treated a series of female monkeys with either testosterone, a testosterone metabolite, or an inactive control drug (placebo). Developing ovarian follicles in monkeys treated with testosterone increased significantly in size and number, compared with follicles in placebo-treated animals. Also, testosterone appeared to reduce the number of follicles undergoing natural cell death (apoptosis). These findings show that, over the short term at least, androgens actually stimulate the growth and survival of small follicles. The results aid in the understanding of polycystic ovarian syndrome (PCOS), a disorder estimated to affect 10% of women. In PCOS, the ovaries are enlarged, with large numbers of developing follicles. The NIH said that PCOS is caused by ovarian over-activity, but that this situation could be disrupted, perhaps reversed, using a drug such as flutamide that blocks the activity of androgens at the cellular level.

Long-term use of the fat substitute olestra, marketed by Procter & Gamble under the name Olean, may be linked to an increased risk of cancer, stroke and heart disease. Nutrition experts are worried about what they call the "dramatic" drop in blood levels of some protective vitamins and carotenoids associated with the consumption of even a small serving of olestra. Daily consumption of a 1-ounce serving of olestra has been shown to lower blood carotenoid concentrations by as much as 50% to 70%. Low levels of carotenoids have been associated in various studies with increased rates of coronary heart disease, stroke and myocardial infarction, cancers of the lung, prostate and uterus, and cataracts as well as degenerative changes of the eye that can lead to blindness. A Harvard researcher estimated that consumption of olestra in the average quantities predicted by Proctor & Gamble would result each year in an additional 2,000 to 9,800 cases of prostate cancer; 32,000 cases of coronary heart disease; 1,400 to 7,400 cases of lung cancer; and 80 to 390 cases of macular degeneration in the U.S. population. An FDA panel is reviewing the evidence regarding the safety of olestra.

Researchers have found a way to inhibit the growth of aggressive brain tumor cells (known as malignant gliomas) in rats by using a genetically engineered snippet of RNA. They often fail to respond to radiation or chemotherapy. A Norwegian team developed a genetically engineered RNA molecule, known as a ribozyme, to attack the production of an enzyme that spurs the growth of the glioma cells. They injected glioma cells into rats, a process that causes tumors to form in about 3 weeks. The tumors were then injected with either an inactive substance, or the modified ribozyme. Twenty days after treatment, rats that received the inactive substance had tumors that weighed an average of 14 grams. In contrast, rats that received the modified ribozyme had tumors that shrunk to an average of 0.25 grams. Similar ribozymes have been used in past studies to treat rat tumors. However, the ribozymes could be degraded by enzymes found in the body, and thus were limited as a potential treatment. But the ribozyme developed here was resistant to degradation, lasting up to 14,000 times longer than similar molecules.

Women who smoke are often unaware that they run an increased risk of developing cervical cancer. Only 49% of the 613 women patients in a health maintenance organization contacted in a survey knew that smoking increased their risk of cervical cancer. Less than one-third were aware of proven risk factors for cervical cancer, such as a high number of lifetime sexual partners and intercourse without a condom. When asked about prevention, women ranked follow-up of abnormal Pap smear results and regular Pap testing as the two most important measures. They rated "not smoking" fourth, after the third-ranked behavior, "eating five fruits and vegetables per day." A diet high in fruit and vegetables has been reported to prevent cancer in general but has not been specifically linked to cervical cancer. When asked what would help them quit, the strongest motivator was the fact that smoking might cause them to get cervical cancer.

Plasma viscosity (the fluid portion of blood's resistance to flow ) may be a marker of risk for coronary heart disease. According to the researchers, plasma viscosity is determined by levels of fibrinogen, immunoglobulins and lipoproteins. Because fibrinogen has been implicated as a major independent cardiovascular risk factor, the researchers attempted to determine whether plasma viscosity itself could forecast heart disease. The result was a positive and statistically significant unadjusted relationship between plasma viscosity and the incidence of coronary heart disease. It is suggested that plasma viscosity could serve as a new parameter identifying those individuals at risk for clinically important cardiovascular complications, and thus deserves further study.