Health Meaning

artificial antibodies can shrink tumors in women with advanced breast cancer, researchers announced yesterday at the American Society of Clinical Oncology meeting (ASCO) in Los Angeles. Experts said it is not yet known if treatment can extend patients' lives, but the news suggests renewed promise for these compounds, which have suffered disappointing clinical results in the late 1980s

antibodies are a first line of the body natural defenses against infection. Each antibody captures a specific target and holds on, alert meanwhile the rest of the immune system to the intruder. Genentech researchers have designed an artificial antibody to a particular molecule, a receptor for a growth factor called HER-2 / neu, which is found in abundance on the surface of recalcitrant breast tumors. Numerous studies have shown that the unlucky 25% to 30% of breast cancer patients whose tumors occur more HER-2 / neu have worse prognoses.

When the antibody was combined with the chemotherapy drug Taxol, 42% of 96 women with metastatic breast cancer have reacted with tumors decreased nearly half. This was much better than the 16% of 92 patients who improved with taxol alone. The addition of the antibody also appears to have extended the four months of time to relapse for up to 11 months. Side effects were minor. "For the marginal additional toxicity [to the patient], you get a huge amount of profit," says project leader Genentech Robert Cohen.

breast cancer patients who have exhausted other treatment options are already calling for the antibody, and the FDA has promised consideration within 6 months. "We estimate that 30,000 to 50,000 women would be eligible" to receive orders for Herceptin if approved, said Cohen.

Although Herceptin slows the progression of the disease, it is too early to say it extends women's lives, simulations radiation oncologist guard Alan Lichter of the University of Michigan Medical School in Ann Arbor and president of ASCO. Lichter calls "modest" response, but significant in that it shows that antibody therapies, considered the best for cancers of the blood, can work against solid tumors as well.

The cracks are widening in the first line of defense against the virus that causes AIDS - drugs that inhibit the essential viral enzymes called proteases and reverse transcriptase. At the World Conference against AIDS 12 in Geneva, Switzerland, separate teams of US and Swiss researchers reported today the first cases in which HIV strains resistant to both classes of drugs were sent to new confirmed victims. While multidrug resistance does not come as a surprise, researchers had hoped that HIV, by mutating to survive exposure to the two classes of compounds will be rendered incapable of infecting new hosts.

The ability of HIV to mutate rapidly -and, of course, hiding in the immune system of its host - was one of the worst AIDS epidemics of infectious diseases worldwide. But the tide began to turn in late 1995 and early 1996, when the US Food and Drug Administration approved the first inhibitors 3 protease that prevent HIV machines clipping viral proteins newly formed just the right size needed to assemble new virus. Used in combination with reverse transcriptase inhibitors, which prevent the HIV genome to be incorporated in infected cells, the drugs have caused new cases of AIDS in the United States to decrease by 15% compared to early 1996 in mid-1997 - the first decline since the beginning of the epidemic in 1981.

The drugs seemed as promising as agents for blocking HIV transmission. Although AIDS patients regularly develop strains of HIV resistant to one or more protease inhibitors, only a handful of unconfirmed reports have suggested that resistant strains - probably less virulent because of mutations that help them survive treatment drug - could be passed on to new victims. "The thought was that the inhibitor resistant virus protease was unlikely to be transmitted to new hosts," says Frederick Hecht epidemiologist at the University of California, San Francisco. At the conference, however, Hecht described a patient who was infected with HIV already resistant strain in six of the 11 approved antiretroviral medicines, including four protease inhibitors. A second study presented by researchers from Geneva University Hospital had three cases of similar-resistant HIV transmission drugs.

These reports represent "the best documentation to date of the multiple drug resistance against HIV," said infectious disease specialist Joel Gallant, director of the Moore HIV Clinic at the Medical School of the Johns Hopkins University. "We do not yet know the implications of resistance to multiple drugs public health, but it will likely be increasingly important," says Gallant, adding that it is a threat that highlights the need to . prevent HIV transmission Hecht agrees: ". While we must continue to develop new drugs against HIV, they are all likely to be prey to resistance "

Scientists have identified a chemical in the blood that can indicate ovarian cancer at an early stage. If confirmed by larger studies, the finding may provide a way to detect ovarian cancer when the disease is most treatable.

Because ovarian cancer usually escapes detection until it has spread beyond the ovaries, it is the deadliest of all gynecological cancers. The survival rate at 5 years with advanced disease is not more than 15%. But if so the cancer can be detected it is still localized, almost 0% of patients live longer than 5 years. A possible early warning sign was on Yan Xu cancer biologist at the Cleveland Clinic Foundation while studying lysophosphatidic acid (LPA), a chemical blood which stimulates the growth of cancer cells of ovary in the laboratory. Because some patients with advanced ovarian cancer have elevated levels of the APL, Xu asked whether women in the early stage of the disease may also have elevated LPA levels.

Xu and colleagues at the Cleveland Clinic Foundation has recruited 84 women with various gynecological cancers and tested their LPA levels. They report in tomorrow's issue of Journal of the American Medical Association that all women with advanced ovarian cancer and 95% of women with other gynecological cancers had blood levels LPA higher than their healthy counterparts. Particularly noteworthy was the finding that nine out of 10 women with early stage ovarian cancer have also documented the high scorer. "If we have a chance to pick up early stages of the disease by 0%, then you can say that would be a good test," said team member Maurie Markman, a medical oncologist. First, however, many more women with cancer of early stage ovarian must be tested to determine whether it would be useful to screen healthy women and people at high risk of developing ovarian cancer .

other experts consider these results with cautious optimism. James Roberts, a gynecologic oncologist at the medical School at Stanford University, would like to see a simple test has tried with more patients. by linking high levels of the APL to gynecological cancers, especially on stage ovarian cancer, "you have a much more treatable disease."

Three US researchers learned yesterday that they will share the Nobel Prize in Physiology or Medicine for his discovery that nitric oxide gas ( NO) acts as a messenger molecule in the body. The discovery led to the development of the drug to the popular impotence Viagra and offered hope of new treatments for blood pressure and tumor.

price $ 975,000 will be divided equally between Robert Furchgott pharmacologists at the University of New York in New York City, Louis Ignarro at the University of California, Los Angeles, and Ferid Murad to University of Texas Medical School, Houston, for their discovery of how the nitric oxide can pass a signal from one cell to another. Because NO is a simple molecule - it is a common pollutant in car exhaust gases -. Scientists were surprised by its sophisticated operation

In 1986, Furchgott and Ignarro presented their work independently showing that NO has worked as a signaling factor in the blood vessels, triggering research worldwide. It was later discovered that NO indicates blood vessels throughout the body to relax, which lowers blood pressure and increases blood flow. Murad, meanwhile, discovered that nitroglycerin, a longtime treatment for heart disease, works by releasing NO from cells. White blood cells also use gas to defend against tumors.

The price has already started. Strict rules prevent the Nobel committee to award the prize to more than three people, but critics say that the committee overlooked key researchers. In particular, the decision not to include pharmacologist Salvador Moncada at University College London drew fire from top scientists. Rudi Busse, a researcher of nitric oxide at the University of Frankfurt, said he was "extremely surprised" that Moncada, who led key experiences when he worked for the Wellcome Foundation in the 1980s, n has not been included.

P ARIS - The controversy erupted on the southern government decision -africain retain the antiviral drug AZT to pregnant women infected with HIV - despite the compound to demonstrate efficacy in preventing HIV transmission to offspring

AIDS officials, doctors and activists say that they are puzzled by the decision, in which the south African government. last month said it would not provide AZT to pregnant women in any health program funded. "We believe that the drug prices unaffordable," said Ian Roberts, Special Adviser to the Minister of Health of South Africa Nkosazana Zuma. But Peter Piot, executive director of UNAIDS, argues that South Africa " clearly [hasn't] done enough "to contain the mother's infection rate to alarming child: in some areas, more than a fifth of pregnant women are HIV-positive, and a hospital based in Soweto delivered nearly 1,000 children infected HIV this year. Overall, nearly 15% of South African adults are home HIV, said Bernhard Schwartländer, senior epidemiologist of UNAIDS.

While Africa is currently the main victim of the epidemic, the latest figures published by the United Nations last week reveal disturbing trends on the other. In India, sampling in rural areas found adult HIV prevalence of infection up to 2%. Even in Western Europe and North America, where AIDS deaths are down thanks to antiviral therapies, the proportion of the population infected with HIV continues to rise; Epidemiologists registered 74,000 new infections on both continents in 1998. Some 5.8 million people worldwide were infected with HIV in 1998, bringing the total number of people infected with HIV to 33.4 million.

Malignant tumors in transplant patients are generally attributed to a weakened immune system by medication. But a study in tomorrow's issue of Nature shows that drugs can play a more direct role: A common immunosuppressive can stimulate tumor cells to divide and spread. The conclusion suggests that it might be possible to design new drugs without the lethal side

For nearly 20 years, doctors have used cyclosporin to reduce the immune response, which would otherwise reject a transplant. - A strategy that carries with it an increase of 100 times the risk of tumors in these patients compared to healthy individuals. Recent experiments have shown, however, that cyclosporine may increase the body's production of TGF b , a growth factor known to promote tumor spread.

To further explore the role of cyclosporine in cancer, Minoru Hojo and colleagues from Tokyo University Medical School tested whether cyclosporine may help cancer cells become more mobile. They bathed a relatively mild strain of lung cancer cells in cyclosporine. Within 72 hours, the drugged cells began to extend pseudopods - appendages that help cell migration. Another experiment showed that the treated cells were in fact move more easily.

When the researchers injected these tumor cells into the tail veins of mice 35, almost twice sprouted new tumors in the lungs of cyclosporine treated mice compared to control animals. Exposed to cyclosporine, "tumor cells become smarter and more invasive" said Hojo. In experiments in both petri dish and the mouse, the effects of cyclosporine can be reversed by adding antibody against TGF b . for Hojo, this suggests that cyclosporine stimulates TGF b production in transplant patients, which in turn spurs cancer cells.

the discovery "sheds monkey wrench in our view of cyclosporine mechanism "for promoting tumor, says Gary Nabel, a molecular biologist at the University of Michigan, Ann Arbor. It can also force people to rethink the role of the immune system in cancer transplant patients, he said. the group of Hojo is now looking for ways to block TGF b 's tumor promoting capacity without reducing its effectiveness in reining in the immune system during transplant operations.

The virus that causes herpes could one day provide relief, rather than misery. In today Proceedings of the National Academy of Sciences , biologists show that the herpes virus can shuttle human genes in nerve cells in mouse pain, increasing their tolerance to pain. If the technique works in people, it could be used to relieve chronic pain.

pharmacologist Steven Wilson at the University of South Carolina, Columbia, and molecular geneticist Joseph Glorioso of the University of Pittsburgh sought to exploit the herpes virus tends to take residence in sensory neurons. First, the duo removed pieces of several genes of the virus to prevent it from causing disease. They also attached to a human gene that produces the pro-enkephalin, a peptide of natural pain blocking, and a second gene that produces a blue dye, to trace the path of the virus under the microscope. They were then infected mice with the modified virus.

To determine how the treatment affected mice, David Yeomans, University of Illinois, Chicago, watched how they reacted to a pain test standard. Mice get their away leg of a heat lamp in about 12 to 15 seconds, but they feel pain and yank back much more quickly after being sensitized by capsaicin, the active ingredient in hot peppers. Capsaicin stimulates the nerve cells that also cause chronic burning pain in humans. The sensitizing effect "was completely abolished by the virus," says Wilson. Infected mice withdrew their paws again - proving that they could feel the normal sensations of pain -., But the hypersensitivity of chronic pain was past

"This is the first evidence that genes neuropeptides delivered in this way can actually have an effect on pain, "says Gudarz Davar, an anesthesiologist at Brigham and Women's hospital in Boston, Massachusetts. Davar is "cautiously optimistic" that gene therapy will eventually be used to control pain in people. Before that happens, he said, researchers need to show it works in animal models that more closely mimic human disease. They must also ensure that the herpes virus mails can not go back to the enemy by friends "recombine" with active herpes virus hides in the body.

Johannes Fibiger, a Danish pathologist and bacteriologist who improved public health and research on cancer revitalized, was born that day

in 1867. early in his career, Fibiger discovered that there are two distinct forms of diphtheria, a disease that caused frequent epidemics in children and remains a problem in parts of the world. Based on the finding, Fibiger developed an antitoxin that was successfully tested in 1897.

At the turn of the century, cancer research has been stagnant because scientists did not know how to provoke cancer in laboratory animals. In 107 Fibiger noticed that some TB rats showed gastric tumors infested with tiny worms called nematodes. Intrigued, he investigated the source of the rats, a sugar refinery. Having collected cockroaches from the refinery, Fibiger fed them to rats that had been trapped elsewhere. When the first dead rat, he found stomach cancer. To create the first reproducible animal model of cancer, Fibiger received the Nobel Prize for medicine in 1926. He died two years later

[Source:EmilyMcMurrayEd Notable Twentieth Century Scientists (Gale Research Inc., ITP, 1995); Tyler Wasson, Ed., Nobel laureates (H. P. Wilson, 1987)]

A new drug taken for a few months prevented monkeys rejecting transplanted kidneys. The drug described in the June Nature Medicine also lack the side effects of immunosuppressive drugs, such as increased susceptibility to infection. Human trials are just beginning in progress, but the results of primates are "really, really incredible," said transplant immunologist Norma Kenyon of the University of Miami in Florida.

The drug is an antibody that binds to a protein called CD154, a signal that the immune system needs to launch an attack against a microbial invader or transplanted tissue. The antibody counteracts attack by binding to CD154 and preventing it from binding to its receptor.

The strategy has far exceeded. Immunologist Allan Kirk and endocrinologist David Harlan of the Naval Medical Research Center in Bethesda, Maryland, and colleagues gave nine monkeys weekly doses of the antibody for the first month after transplant, and monthly doses for 5 months. All treatment was then arrested. More than a year later, eight of the nine are alive and well. The only death was due to complications during a routine blood test; an autopsy revealed that the monkey had normal kidney function when he died. monkeys witnesses who received conventional immunotherapy died in 9 weeks.

No one knows why the immune system in apes accept foreign tissue long after stopping the drug. Some scientists suspect that immune cells activated by the foreign organ, but lacking the CD154 signal die soon after a transplant, although it is not known why the new generation of immune cells would not recognize and attack the tissue. Others suspect that the cells "blocked" can be immune sort of protection

Scientists warn it is too early to know if the acceptance is permanent -. Activated immune cells that scientists have found in the kidneys could still lead to possible rejection. Although Christian Larsen said transplant immunologist from Emory University, "It is spectacular to have a monkey out of immunosuppression with good graft function, for more than a year."

Science now wants a happy 21st birthday of the first test tube baby, Louise Joy Brown, born in England 25 July 1978. Brown debuted through in vitro fertilization technique developed by the gynecologist Patrick Steptoe and physiologist Robert G. Edwards. The success has attracted praise and ethical debates

Steptoe pioneered the use of laparoscopic surgery -. In which a long, thin telescope is inserted through a small incision in the abdominal cavity inflated - and he has developed a method for obtaining eggs from the ovaries. Edwards understood how to fertilize eggs outside the body and got his first success in 1968. In 1972, the pair attempted the first settlement, but had no luck until 1977. Critics have expressed concerns ethical and moral about the falsification of the creation of human life, and Steptoe and Edwards were reluctant to discuss the new procedure. They finally presented their work to the scientific community in 1979.

Brown was the first, but it is hardly the only test tube baby life today. . According to a global survey by the pharmaceutical company Oragnon, by 1994 more than 150,000 babies worldwide were born after in vitro fertilization

[Sources:EmilyMcMurrayEd Notable The Twentieth Century scientists (Gale Research Inc., ITP, 1995).]