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Biotech / Medical : Ligand (LGND) Breakout! -- Ignore unavailable to you. Want to Upgrade?

To: WTDEC who wrote (19720)	4/27/1998 11:39:00 PM
From: John O'Neill	Read Replies (9) \| Respond to of 32384

Do you think the complexity of LGND's approach causes it greater rikst for problems in human application. Tinkering with the inner working of the cell must be complex and have unforeseen implications.

To: WTDEC who wrote (19720)	4/28/1998 6:37:00 AM
From: Henry Niman	Respond to of 32384

Speaking of complexity: Monday April 27 6:45 PM EDT Obesity Tied To Adult-Onset Asthma CHICAGO (Reuters) -- Obesity appears to increase the risk of developing asthma in adulthood, Dr. Carlos A. Camargo of Harvard Medical School in Boston, Massachusetts, reported at the American Lung Association/American Thoracic Society 1998 International Conference here. After controlling for potentially confounding variables such as race, smoking and physical activity level, Camargo's team concluded that body mass index (a measure of obesity) "...has a strong, independent, positive association with risk of adult-onset asthma." Camargo and colleagues examined the relationship between obesity and asthma risk using data from the Nurses' Health Study II, a prospective cohort study of more than 100,000 female nurses. In 1991, the investigators collected information on body mass index (BMI) from 89,061 women, aged 27 to 41, who did not have asthma. Follow-up questionnaires sent over the next 4 years revealed that 1,652 women had developed physician-diagnosed asthma during this time period. "Obesity blows everything else away by a mile," Camargo told Reuters in an interview. "There's a perfectly linear relationship -- the higher the BMI, the higher the risk of developing asthma." The researchers report that the risk for adult-onset asthma was almost three times higher in women whose BMI was 30 or more compared with women whose BMI was less than 20. Asthma risk increased even in women whose weight was "high normal," notes Camargo, "...so it (risk) seems to be continuous all along." To ensure the accuracy of the diagnosis, Camargo's team sent a follow-up form to women who said that they had received an asthma diagnosis from their physician asking for additional confirmation. "What's also really interesting is that the epidemiology of asthma parallels that of obesity," Camargo observes. "Richer countries tend to have fatter people and more asthma. Paradoxically, within a rich country, it's the poorest people who are fattest and have the most asthma. It's odd that asthma and obesity track together in this weird sociodemographic way and it gives me more confidence that what we're describing is real." Camargo speculates that obesity results in "...compression of the lungs," which in turn increases bronchial reactivity. His group is now investigating three other groups of people -- men, older nurses, and the 10- to 14-year-old children of the nurses in the present study. "We'll look prospectively to see if the obesity (and asthma) relationship holds," he says.

To: WTDEC who wrote (19720)	4/28/1998 6:40:00 AM
From: Henry Niman	Respond to of 32384

Here's more good news for ERT: Monday April 27 6:46 PM EDT Estrogen Therapy Cuts Colorectal Cancer Risk WESTPORT (Reuters) -- Estrogen replacement therapy appears to cut the risk of colorectal cancer in postmenopausal women by more than a third, according to a report. Postmenopausal women who took estrogen replacement therapy, or who had taken it recently, were found to have a 35% lower risk of colorectal cancer compared with women who have never used estrogen, according to Dr. A. Paganini-Hill. She presented her findings during the Pacific Coast Fertility Society's annual meeting in Indian Wells, California. Paganini-Hill and her colleagues at the University of Southern California School of Medicine analyzed the medical histories, hospital records, and death certificates of women participating in the Leisure World Cohort, an ongoing study of residents in a California retirement community. The researchers focused on a subgroup of 7,701 women who were recent or current users of estrogen replacement therapy and who were initially cancer free, to determine their subsequent colorectal cancer risk during 15 years of follow-up. From the time the Leisure World Cohort was established in 1981 through December 1995, 336 cases of colorectal cancer occurred among the subgroup. Estrogen replacement therapy was "most protective in women who were recent or current users (of estrogen)" in terms of protection against colorectal cancer, Paganini-Hill told Reuters. Women on estrogen replacement therapy showed an age-adjusted colorectal cancer incidence rate of 2.64 per 1000 person years. Lifetime nonusers had an incidence rate of 3.27 per 1000 person years. The study shows that the effects of estrogen replacement therapy on reducing risk of colon cancer incidence and mortality were similar. The risk reduction was independent of the dose of conjugated estrogen, route of administration, or duration of estrogen replacement therapy. "The benefits of estrogen replacement therapy for most postmenopausal women outweigh the risks," Paganini-Hill asserted. "This is just one more reason to (consider) estrogen replacement therapy."

To: WTDEC who wrote (19720)	4/28/1998 6:42:00 AM
From: Henry Niman	Respond to of 32384

Here's yet another study on a positive relationship between ERT and brain function: More Evidence for Protective Role of Estrogen Therapy BY ANGELA LORIO c.1998 Medical Tribune News Service A New York study adds more support to the idea that estrogen replacement therapy may help maintain a woman's mental function as she ages. Investigators from the Columbia University College of Physicians & Surgeons evaluated the relationship between history of estrogen use and cognitive test performance in 727 postmenopausal women. The participants, all part of a large community-based study on aging and dementia, were followed for an average of 2.5 years. Women who had ever taken estrogen replacement therapy (ERT) scored higher on standard tests than women who had never taken the therapy, according to the study, published in the journal Neurology. And among previous estrogen users, those who had taken the hormone for more than one year performed better on the tests than those who had taken it for less than a year. The results suggest that estrogen may prevent age-associated cognitive decline, according to lead investigator Diane Jacobs. At menopause, a woman's production of estrogen declines dramatically, which can lead to hot flashes and other symptoms. As a result, many doctors recommend that their patients take ERT. Women also may be advised to continue with the therapy after menopause to protect against the brittle-bone disease osteoporosis and heart disease. The therapy, however, may also raise the risk of breast cancer in some women, such as those with a family history of the disease. The study's strengths are with its consistency of methods and its large sample size, commented Dr. Douglas Galasko, a neurologist at the University of California at San Diego. However, he said he does not believe the results provide definitive information. ''Although there are statistically significant differences between women who took estrogen and those who did not, the actual size of the differences, that is the differences in test scores, were small,'' Galasko said. The investigators also acknowledged some of the study's limitations. ''Our participants were ethnically diverse and varied in age and education level. Although we adjusted for these variables, it is impossible to determine how other confounding factors, for example lifestyle and socioeconomic variables, may have influenced our results,'' Jacobs noted. Carefully structured studies are needed, she said. ----- Neurology (1998;50:368-73)

To: WTDEC who wrote (19720)	4/28/1998 6:59:00 AM
From: Henry Niman	Read Replies (1) \| Respond to of 32384

Here's what Dow Jones had to say yesterday about the leptin/obesity deal with SBH: Dow Jones Newswires -- April 27, 1998 Ligand, SmithKline Get OK To Add Leptin-Obesity Research SAN DIEGO (Dow Jones)--Ligand Pharmaceuticals Inc. (LGND) received regulatory approval to add leptin-obesity research to its existing collaboration with SmithKline Beecham PLC. (SBH). In a press release Monday, Ligand said SmithKline purchased 274,423 Ligand common shares for $5 million, or $18.22 a share. The price reflects a 20% premium over a 15-day trading average of Ligand shares prior to the agreement. SmithKline also purchased a warrant for $1 million to purchase 150,000 Ligand common shares at $20 a share. The warrant expires in five years. Ligand may require SmithKline to exercise the warrant under certain circumstances after three years. SmithKline will acquire additional Ligand shares at a 20% premium if a research milestone is achieved. The agreement provides for cash payments for subsequent milestones. Milestone payments will be made as the compounds progress through preclinical and clinical development. SmithKline will obtain exclusive worldwide rights to products and make royalty payments on their sales. As reported March 18, the pharmaceutical companies plan to develop small molecule drugs that modulate the signaling pathway controlled by leptin as a means of discovering orally available drugs for obesity treatment. The companies are currently collaborating on hematopoietic growth factor.

To: WTDEC who wrote (19720)	5/1/1998 8:04:00 AM
From: Henry Niman	Read Replies (1) \| Respond to of 32384

Here's more on ERT and colon cancer prevention: Thursday April 30 7:08 PM EDT Hormone Replacement Cuts Colon Cancer Risk WESTPORT (Reuters) -- Hormone replacement therapy (HRT) can reduce the risk of colorectal cancer, but aspirin appears to have no protective effect, according to the results of two large studies published in the May 1st issue of Annals of Internal Medicine. Several observational studies have indicated that regular aspirin use may reduce the risk of colorectal cancer. However, 12-year follow-up data from over 22,000 participants in the Physicians' Health Study do not corroborate such reports, according to Dr. Til Sturmer of the University of Ulm in Germany and a multicenter German and American team. Twelve years after randomization to 325 milligrams of aspirin per day or placebo, the relative risk of colorectal cancer in patients assigned to aspirin was 1.03, indicating no protective effect of aspirin. And when the investigators looked specifically at men who continued to take aspirin regularly after the randomized aspirin trial was stopped in 1988, they found that the relative risk of colorectal cancer in continued aspirin users increased slightly to 1.07. Sturmer and colleagues believe that their "...findings indicate that a causal role of aspirin in the prevention of colorectal cancer is less likely..." than previously thought. Meanwhile, researchers in Boston, Massachusetts, and Tucson, Arizona, show that women taking postmenopausal HRT may have a substantially lower risk of colorectal cancer compared with those not taking HRT, according to findings from the Nurses' Health Study. Lead author Dr. Francine Grodstein of Channing Laboratory in Boston, and others found that women currently using HRT had a relative risk of developing colorectal cancer of 0.65, indicating a 35% reduction in risk relative to nonusers or never-users. The duration of hormone use did not significantly affect the risk of colorectal cancer, the researchers report, but the protective effect of HRT appeared to diminish after discontinuation of the therapy, disappearing completely after 5 years of nonuse. The Nurses' Health Study findings are "...consistent with substantial epidemiologic and biological data," Grodstein and colleagues write. Based on this study, they calculate that "...30 cases of colorectal cancer would be prevented per 100,000 person-years of hormone use among women 55 to 59 years of age." And the benefits of HRT would likely increase as women age and enter older age-groups at increased risk of colorectal cancer. The Boston and Tucson team stress that the potential for HRT to protect women against colorectal cancer must be weighed along with its other benefits, such as protection against osteoporosis and cardiovascular disease, and risks, including an increase in breast cancer risk. Dr. Robert N. Hoover of the National Cancer Institute (NCI) in Bethesda, Maryland, in a related editorial entitled, "Cancer Prevention: Better Late than Never?" comments that the Nurses' Health Study findings provide one more example of how "...'late' exposures may influence cancer risk and... (add) to the enthusiasm for interventions that may result in rapid risk reduction." According to the NCI researcher, more study is needed before adding colorectal cancer prevention to the list of indications for HRT. SOURCE: Annals of Internal Medicine (1998;128:705-712, 713-720, 771-772)