[Source: ScienceDaily ] - A secondary analysis of a large, multicenter clinical trial has shown that a diet loaded with fruits, vegetables and fiber and somewhat lower in fat compared to standard federal dietary recommendations cuts the risk of recurrence in a subgroup of early-stage breast cancer survivors – women who didn't have hot flashes – by approximately 31 percent. These patients typically have higher recurrence and lower survival rates than breast cancer patients who have hot flashes.
The study team, led by researchers at the Moores Cancer Center at the University of California, San Diego, along with six other sites, including the University of California, Davis, reported its results online December 15, 2008, in the Journal of Clinical Oncology.
The results come on the heels of a report last year on the findings of the original study, the Women's Healthy Eating and Living Trial (WHEL), which compared the effects of the two diets on cancer recurrence in more than 3,000 early-stage breast cancer survivors. That study showed no overall difference in recurrence among the two diet groups.
"Women with early stage breast cancer who have hot flashes have better survival and lower recurrence rates than women who don't have hot flashes," said Ellen B. Gold, Ph.D., professor and chair of the UC Davis Department of Public Health Sciences and first author of the study. "Our results suggest that a major change in diet may help overcome the difference in prognosis between women with and without hot flashes."
"Our interest in looking at this subgroup came because hot flashes are associated with lower circulating estrogen levels, while the absence of hot flashes is associated with higher estrogen levels. Reducing the effect of estrogen is a major treatment strategy in breast cancer," said the WHEL study principal investigator John P. Pierce, Ph.D., Sam M. Walton Professor for Cancer Prevention and director of Cancer Prevention and Control at the UC San Diego School of Medicine and the Moores UCSD Cancer Center. "It appears that a dietary pattern high in fruits, vegetables and fiber, which has been shown to reduce circulating estrogen levels, may only be important among women with circulating estrogen levels above a certain threshold."
About 30 percent of the original group of 3,088 breast cancer survivors did not report hot flashes at study entry. The women had been randomly assigned to one of the two diets between 1995 and 2000 and were followed until 2006. About one-half (447) of the "no hot flashes" group were randomized to the special, "intervention" high-vegetable fruit diet while the other half (453) was given the generally recommended diet of five servings of fruits and vegetables a day. The team found that those on the intervention diet had a significantly lower rate of a second breast cancer event (16.1 percent) compared to those eating the government-recommended five-a-day dietary pattern (23.6 percent).
The dietary effect was even larger (a 47 percent lower risk) in women who had been through menopause.
According to Pierce, another possible mechanism has been proposed recently for why this diet may have affected only 30 percent of the WHEL study population. Women with estrogen receptor-positive cancers usually receive hormone therapy (tamoxifen or aromatase inhibitors) aimed at combating the effect of circulating estrogen. However, more than 30 percent of these women appear to have a gene-drug interaction that prevents them from getting an effective dose of this therapy.
"This hypothesis says that if the endocrine therapy is working, no further reduction in estrogen levels would be needed," said Pierce. "If your genes are preventing you from getting a therapeutic dose, then following this rigorous dietary pattern may reduce estrogen levels enough to reduce risk." Because this is speculation, he said, the research team will be using biological samples collected throughout the study to further investigate the mechanisms behind the study diet's protective effects.
Other co-authors include: Cheryl Rock, Ph.D., Barbara Parker, M.D., Lisa Madlensky, Ph.D., Loki Natarajan, Ph.D., Linda Wasserman, M.D., Vicky Jones, M.D., Gail Laughlin, Ph.D., Nazmus Saquib M.D., Ph.D., Sheila Kealey MPH, Shirley Flatt, Jennifer Emond and Minya Pu, UCSD; Joanne Mortimer, M.D., City of Hope; Marcia Stefanek, Ph.D., Stanford University; Bette Caan, Dr.P.H, Kaiser Permanente, Oakland, Cynthia Thomson, Ph.D., University of Arizona, Njeri Karanja, Ph.D., Kaiser Permanente, Portland, OR; Richard Hajek, Ph.D., M.D. Anderson Cancer Center.
Showing posts with label University of Arizona. Show all posts
Showing posts with label University of Arizona. Show all posts
Monday, January 5, 2009
Monday, December 22, 2008
UA provost suggests pay cuts
[Source: AzCentral/AP] - When it comes to fixing budget shortfalls, some high earners at the University of Arizona should cut their pay.
That suggestion comes from one of the school's highest paid employees, University of Arizona Provost Meredith Hay, who earns more than $100,000 a year.
The number of employees making more than six figures at the UA has increased 45 percent since 2005 while costs of paying those workers jumped 53 percent, according to an Arizona Daily Star analysis.
Officials acknowledge there are more employees earning more than $100,000 in what they call the reality of the highly competitive academic market and a product of growth in programs such as the UA's medical school in Phoenix.
They add it's not as if those workers are getting raises at the expense of lower-paid staffers.
It costs the UA $76 million to pay 2,323 workers who earn less than $50,000 a year and account for nearly half of all state-paid employees.
It also costs about $71 million to pay the 568 employees making more than $100,000.
The idea to cut into UA employee earnings has gained steam as officials look at ways to offset what they expect to be a series of state cuts that could leave them $50 million in the red by next summer.
Cutting pay could pose potential long-term consequences that could affect the UA's ability to hire and retain employees.
"What does that do for our competitiveness? We're already below where we need to be," said Allison Vaillancourt, UA's vice president for human resources. "If we take another whack at employees, who will come to work for us? Will we be able to attract people in the future?"
Overall salary costs have increased by 18 percent since 2005, putting UA in line with other universities, she said.
Faculty members who get raises actually save the UA money in the long run because it's cheaper than advertising for an open position and training a new employee, university officials said.
"If they need lab equipment or special office space, we could be looking at several hundred thousand dollars," Vaillancourt said. "It doesn't make any sense for us to spend that money if we don't have to."
That suggestion comes from one of the school's highest paid employees, University of Arizona Provost Meredith Hay, who earns more than $100,000 a year.
The number of employees making more than six figures at the UA has increased 45 percent since 2005 while costs of paying those workers jumped 53 percent, according to an Arizona Daily Star analysis.
Officials acknowledge there are more employees earning more than $100,000 in what they call the reality of the highly competitive academic market and a product of growth in programs such as the UA's medical school in Phoenix.
They add it's not as if those workers are getting raises at the expense of lower-paid staffers.
It costs the UA $76 million to pay 2,323 workers who earn less than $50,000 a year and account for nearly half of all state-paid employees.
It also costs about $71 million to pay the 568 employees making more than $100,000.
The idea to cut into UA employee earnings has gained steam as officials look at ways to offset what they expect to be a series of state cuts that could leave them $50 million in the red by next summer.
Cutting pay could pose potential long-term consequences that could affect the UA's ability to hire and retain employees.
"What does that do for our competitiveness? We're already below where we need to be," said Allison Vaillancourt, UA's vice president for human resources. "If we take another whack at employees, who will come to work for us? Will we be able to attract people in the future?"
Overall salary costs have increased by 18 percent since 2005, putting UA in line with other universities, she said.
Faculty members who get raises actually save the UA money in the long run because it's cheaper than advertising for an open position and training a new employee, university officials said.
"If they need lab equipment or special office space, we could be looking at several hundred thousand dollars," Vaillancourt said. "It doesn't make any sense for us to spend that money if we don't have to."
Friday, December 19, 2008
Telemedicine protects Arizona, its many regional communities
[Source: Nogales International, Roger Conroy] - Centered in Phoenix and Tucson, a beneficial net covers Arizona communities from Ajo to Nogales to Yuma, the New Mexico communities of Bloomfield, Crownpoint, Gallup, Shiprock and Tohatchi and Utah’s Fort Duchesne and Salt Lake City.
The Arizona Telemedicine Network gives people in Santa Cruz County access to specialty care--that’s care beyond what is offered at Mariposa--applying the latest technology, said Mariposa Health Clinic CEO Jim Weldon. “Doctor (Ronald S.) Weinstein founded the program, and it’s very innovative--a national model.” Weinstein was the third guest speaker in the Mariposa Series on Thursday at Holiday Inn Express in Nogales.
The network gives local clinics access to information and specialties above the level normally available in Nogales, Mariposa chief of medicine Eladio Pereira said. Mariposa Clinic uses rheumatology, dermatology and gastroenterology services over the Telemedicine Network. “It’s incredible--speed, accuracy, consults right away. It’s very, very important.”
There are several cases each month that are aided by use of the network at Mariposa, Pereira said.
The network had it’s beginnings at Massachusetts General in 1968, Weinstein said. Telepathology, or remote diagnosis began in the 1980s. The concept is illustrated by the television shows “CSI,: and earlier, “Quincy, M.E.,” Weinstein said.
Arizona Sen. Robert Burns was instrumental in the establishment of the network, Weinstein said. “He’s now president of the Arizona state senate. He founded it. He came to us and asked us to do it.”
The network began at the Phoenix campus of the University of Arizona College of Medicine, where Weinstein is director of the program. It now includes 171 sites in 71 communities. “Doctor Pereira is the best director in those 71 communities,” Weinstein said. “He has been a supporter of Mariposa efforts in telemedicine since the beginning.”
24-hour access
The network gives 24/7 access to pathology (the study of disease) at the UA College of Medicine. “Telemedicine is a large program that provides services at a distance,” Weinstein said.
Nogales came on board through a grant from the Department of Agriculture. Originally, the program was designed for “end of the dirt road” clinics, Weinstein said. Mariposa was brought on to allow doctors in Phoenix and Tucson to travel to a remote site that was easily accessible to evaluate the network in the beginning.
The U of A created a unique network for Arizona. In 1996, there was a problem of broadband access in Arizona, and the U of A created the Telemedicine Network outside the Internet to meet its telecommunications needs, Weinstein said.
By 1998 there were 55 sites, including Nogales. Nogales was the first rural site, Weinstein said.
Communities served include remote Indian reservations and prisons in rural settings. The Department of Corrections facilities are placed in remote locations in Arizona. The Indian reservations saved $200,000 in costs over the last year. “The dollar savings in the Department of Corrections is enough to fund the entire program,” Weinstein said.
It is easier to use telemedicine for the prison system than to transport prisoners, and the prisoners like it better, Weinstein said.
Radiology is huge in the prison system, Weinstein said, but it is only one of the specialties that use the Telemedicine Network.
Real-time use
One example is doctors use real-time ultrasound to diagnose fetal problems. There are many applications, Weinstein said. They include tele-psychiatry, tele-dermatology, tele-cardiology, tele-ophthalmology, infectious disease diagnosis and family teleconferencing.
There are many times a patient is confined for long periods at a hospital and the family is in a remote community. The system allows families to continue interpersonal relations, which benefit the patient, Weinstein said.
Tele-pediatrics and tele-trauma, which began in Douglas, are also important, Weinstein said. “It provides a telepresence for trauma physicians. “It saves lives,” Weinstein said.
Broadband access promises more access for remote communities in the future, Weinstein said. “Many sites are now interoperable over the broadband network. Many of the communications issues are not minimized because of the availability of the Internet. That’s a real advance.”
Thus far, the network has handled more than 700,000 cases. More than 150 physicians from the college of medicine handle cases. “We have a long way to go,” Weinstein said. “The university still doesn’t have access to all the information to assist in all cases.”
That is due to the fragmented nature of the U.S. health-care system, Weinstein said. Some patient records may not be accessible through the network.
The latest advance is in digital mammography, Weinstein said. “The Navajo Nation wants to be first in telemedicine. They now have a 45-minute turn-around for digital mammography, where the follow up was only 50 percent, and entailed a long wait.”
Patients are often without communications on reservations, Weinstein explained. The network shortened a weeklong turnaround to allow patients to remain at the clinic to hear results.
Dramatic change
The change is dramatic. “It has altered the way physicians look at disease,” Weinstein said. It gives physicians the opportunity to communicate and to compare things.
Still, one of four to six visits should be in person, for most cases, Weinstein said. Some procedures can be completely remote, such as the digital mammography, with the on-site physician handling consultation.
The Mariposa Series of lectures is an opportunity to bring folks together for lunch and to hear about the latest developments in medical care from a well-respected speaker, Weldon said. The series began in 2007 and is held twice a year, said Norma Villasenor executive assistant to the CEO.
The Arizona Telemedicine Network gives people in Santa Cruz County access to specialty care--that’s care beyond what is offered at Mariposa--applying the latest technology, said Mariposa Health Clinic CEO Jim Weldon. “Doctor (Ronald S.) Weinstein founded the program, and it’s very innovative--a national model.” Weinstein was the third guest speaker in the Mariposa Series on Thursday at Holiday Inn Express in Nogales.
The network gives local clinics access to information and specialties above the level normally available in Nogales, Mariposa chief of medicine Eladio Pereira said. Mariposa Clinic uses rheumatology, dermatology and gastroenterology services over the Telemedicine Network. “It’s incredible--speed, accuracy, consults right away. It’s very, very important.”
There are several cases each month that are aided by use of the network at Mariposa, Pereira said.
The network had it’s beginnings at Massachusetts General in 1968, Weinstein said. Telepathology, or remote diagnosis began in the 1980s. The concept is illustrated by the television shows “CSI,: and earlier, “Quincy, M.E.,” Weinstein said.
Arizona Sen. Robert Burns was instrumental in the establishment of the network, Weinstein said. “He’s now president of the Arizona state senate. He founded it. He came to us and asked us to do it.”
The network began at the Phoenix campus of the University of Arizona College of Medicine, where Weinstein is director of the program. It now includes 171 sites in 71 communities. “Doctor Pereira is the best director in those 71 communities,” Weinstein said. “He has been a supporter of Mariposa efforts in telemedicine since the beginning.”
24-hour access
The network gives 24/7 access to pathology (the study of disease) at the UA College of Medicine. “Telemedicine is a large program that provides services at a distance,” Weinstein said.
Nogales came on board through a grant from the Department of Agriculture. Originally, the program was designed for “end of the dirt road” clinics, Weinstein said. Mariposa was brought on to allow doctors in Phoenix and Tucson to travel to a remote site that was easily accessible to evaluate the network in the beginning.
The U of A created a unique network for Arizona. In 1996, there was a problem of broadband access in Arizona, and the U of A created the Telemedicine Network outside the Internet to meet its telecommunications needs, Weinstein said.
By 1998 there were 55 sites, including Nogales. Nogales was the first rural site, Weinstein said.
Communities served include remote Indian reservations and prisons in rural settings. The Department of Corrections facilities are placed in remote locations in Arizona. The Indian reservations saved $200,000 in costs over the last year. “The dollar savings in the Department of Corrections is enough to fund the entire program,” Weinstein said.
It is easier to use telemedicine for the prison system than to transport prisoners, and the prisoners like it better, Weinstein said.
Radiology is huge in the prison system, Weinstein said, but it is only one of the specialties that use the Telemedicine Network.
Real-time use
One example is doctors use real-time ultrasound to diagnose fetal problems. There are many applications, Weinstein said. They include tele-psychiatry, tele-dermatology, tele-cardiology, tele-ophthalmology, infectious disease diagnosis and family teleconferencing.
There are many times a patient is confined for long periods at a hospital and the family is in a remote community. The system allows families to continue interpersonal relations, which benefit the patient, Weinstein said.
Tele-pediatrics and tele-trauma, which began in Douglas, are also important, Weinstein said. “It provides a telepresence for trauma physicians. “It saves lives,” Weinstein said.
Broadband access promises more access for remote communities in the future, Weinstein said. “Many sites are now interoperable over the broadband network. Many of the communications issues are not minimized because of the availability of the Internet. That’s a real advance.”
Thus far, the network has handled more than 700,000 cases. More than 150 physicians from the college of medicine handle cases. “We have a long way to go,” Weinstein said. “The university still doesn’t have access to all the information to assist in all cases.”
That is due to the fragmented nature of the U.S. health-care system, Weinstein said. Some patient records may not be accessible through the network.
The latest advance is in digital mammography, Weinstein said. “The Navajo Nation wants to be first in telemedicine. They now have a 45-minute turn-around for digital mammography, where the follow up was only 50 percent, and entailed a long wait.”
Patients are often without communications on reservations, Weinstein explained. The network shortened a weeklong turnaround to allow patients to remain at the clinic to hear results.
Dramatic change
The change is dramatic. “It has altered the way physicians look at disease,” Weinstein said. It gives physicians the opportunity to communicate and to compare things.
Still, one of four to six visits should be in person, for most cases, Weinstein said. Some procedures can be completely remote, such as the digital mammography, with the on-site physician handling consultation.
The Mariposa Series of lectures is an opportunity to bring folks together for lunch and to hear about the latest developments in medical care from a well-respected speaker, Weldon said. The series began in 2007 and is held twice a year, said Norma Villasenor executive assistant to the CEO.
When Medicine Meets Marketing
[Source: Newsweek, Mary Carmichael] - Dallas Hextell was just a baby when his parents bought him a walker—not because he was late reaching a milestone, but because they worried he might never toddle on his own. At 9 months he had been diagnosed with cerebral palsy, a form of brain injury caused by oxygen deprivation in utero or at birth. A neurologist had told Derak and Cynthia Hextell there was no cure, that it was best to wait and see if their son improved. But Cynthia, after months of research, enrolled Dallas in a highly experimental trial at Duke University, where a pediatric-transplant surgeon infused him with a sample of his own stem cells harvested from his umbilical-cord blood. A few days later, Derak and Cynthia went home with their son, who was 18 months old and still not crawling, much less walking or talking. They "stared at him" for a week, says Cynthia. "One day he just started saying, 'Mama, mama, mama.' And I started crying." The Hextells ended up donating the walker to another child. By 2, Dallas was not only walking unaided, he was chasing the family dogs.
If the Hextells' names sound familiar to some readers, it is because, in the wake of their son's remarkable recovery, they have become minor celebrities. Their story has appeared on the "Today" show and in advertisements in almost every pregnancy magazine in the country. The ads are not for the trial at Duke, which remains a small, academic endeavor. They are for a company called Cord Blood Registry, which charges parents $2,000-plus to freeze and store samples of their children's umbilical-cord blood, a fluid rich in stem cells. Cynthia Hextell paid the company to freeze Dallas's cord blood at his birth. That sample was the source of the stem cells used in the Duke trial—and as the ads remind parents, it was available only because the Hextells had paid for it to be.
The Hextells' story has become the centerpiece of CBR's marketing efforts. Recently the company invited about 30 obstetricians and midwives to the Westin La Paloma resort in Tucson, Ariz., for a weekend of sun, golf and medical briefings, including dinner in a ballroom with the Hextells as guest speakers. Since these doctors had collected cord blood for CBR clients in the past, the company hoped to turn them into evangelists. The next day, the group went for a tour of CBR's glittering 60,000-square-foot lab. The agenda also included more time at the La Paloma, home to a Jack Nicklaus golf course, a spa, five restaurants and a swim-up bar. CBR can easily afford to put on this kind of show. Ten years ago it was a fledgling business with 10,000 clients. Today it is the country's largest private cord-blood bank, with 250,000 samples in storage, 300 employees and $100 million in annual revenue.
In medicine, money often comes with controversy—and right now, CBR has plenty of both. The company says it is providing precious biological insurance, that to freeze a child's cord-blood stem cells is to provide him a medical option for the future, perhaps a lifesaving treatment for childhood cancer or brain injuries. But critics, including the American Academy of Pediatrics, accuse private cord-blood banks like CBR of making exaggerated medical promises and exploiting vulnerable new parents. Cord blood's uses are limited at best, they say. The blood does not provide enough cells to cure an adult of a disease or injury; it is not appropriate for treating genetic conditions; and thus far there have been few trials to determine how effectively the cells can repair damaged tissue. Even Joanne Kurtzberg, the Duke transplant specialist who treated Dallas Hextell, is skeptical. She says it's difficult to know if his improvement is related to the cells or would have occurred without them—he probably would have gotten better on his own; some cerebral-palsy patients do—and she points out that her trial is small and yet to be analyzed and published. But CBR has a response for this. It says more uses for cord-blood stem cells will surely be discovered in the future. It also knows the power of a good story. David Zitlow, the company's senior vice president of public affairs, says doctors "haven't made a big enough deal about anecdotes" like the Hextells'.
So what are other parents, faced with the choice of banking their children's cord blood or brushing off the idea as a luxury—the medical equivalent of an $800 stroller—supposed to make of Dallas Hextell's case? Is it a breakthrough, a harbinger? Or is it ultimately just an anecdote, a moving tale with a happy outcome that may or may not have anything to do with cord blood and stem cells?
Doctors have been wondering if cord blood is something of a miracle cure for the past 15 years. The blood—which is usually thrown away in delivery rooms—contains a distinct type of stem cell that may act as a biochemical foreman, helping to build healthy tissues and repair damaged ones. In the early 1990s— before embryonic stem cells took over the spotlight—researchers began to explore whether cord-blood cells might be of practical medical use. At Duke, Kurtzberg performed a few cord-blood transplants on patients with leukemia and rare types of bone-marrow failure, sending them into remission. Meanwhile, the National Institutes of Health started funding public banks of frozen, donated cord-blood samples, modeled on adult blood banks. A cord-blood stem-cell transplant at that point was a long shot, an experiment to see if stem cells could either become new tissue or trick the body into fixing itself. But the idea behind the public banks was to make the option available to all families who might want to try it as a last resort.
It was around this time, in 1992, that Tom Moore, a technology and pharmaceutical executive with passion for startups, hatched a plan to found a cord-blood bank of his own. Unlike the NIH banks, this one would operate for profit. Its clients would retain exclusive access to their own genetically identical samples, for a fee of $1,500 up front plus $125 for each year of storage. One problem: Moore "didn't really know anything about stem cells except the name," he admits. So he sought out David Harris, a University of Arizona immunologist and cord-blood researcher, to serve as CBR's scientific director; meanwhile, as the CEO, he took care of the business side. Now it takes care of him. CBR is the largest of 30-some private cord-blood banks in the United States, with a 45 percent share of the $250 million market. It's probably not done growing yet. Moore's "big, hairy, audacious goal" is a million clients, quadruple the company's current size.
A number of trends have likely contributed to CBR's growth, including the enormous boom in the baby-products market and the hype around stem cells in general. But one thing that has not been a factor is a rapid rise in medical uses for cord blood—because there hasn't been one yet. Just as it was in the '90s, a cord-blood stem-cell transplant is still an experimental procedure. This hasn't deterred CBR from publicizing the results of a few positive studies, including a small, preliminary trial in kids with type 1 diabetes from last year.
In Dallas Hextell, CBR has another case to promote. In ads, the Hextells call the cord-blood treatment "a miracle." But nobody really knows what has happened in Dallas's brain. The story sounds less clear-cut coming from Kurtzberg, the doctor who performed the transfusion and who examined Dallas again in November. "He has made progress, there's no question," she says. "But he still has a global developmental delay of about a year. He looks like where we would have expected him to be without cells." When she saw him at his follow-up visit, she adds, "I thought, wow, he doesn't look as good as I was expecting based on what's been in the press." (The Hextells find Kurtzberg's assessment frustrating and note that Dallas's therapists at home—who knew him before the transfusion—are impressed and surprised at his improvement.) Kurtzberg also has not completed the follow-up and analysis of the study or published the results from 50 other kids with cerebral palsy who have enrolled in her trial thus far.
Kurtzberg, it turns out, is not a big booster for private cord-blood banks; although she uses samples from CBR, she does not receive funding from the company, and also uses cells from public banks and other companies. In fact, she's one of the authors of a statement the American Academy of Pediatrics put out last year discouraging parents from using private banks on the grounds that the science isn't solid enough yet to justify a multi-thousand-dollar gamble. (The AAP does support public, nonprofit banks, which patients can use for free.) The American College of Obstetricians and Gynecologists released its own statement in February, noting that "there is no reliable estimate of a child's likelihood of actually using his or her own saved cord blood later." Then it made a guess anyway: 1 in 2,700, which Kurtzberg calls "generous."
Why is this number so small? There are reasons to think cord-blood treatment will never be a widespread medical procedure. The blood contains only enough stem cells to treat a small child; unlike embryonic stem cells, cord-blood cells cannot be multiplied into self-rejuvenating "lines" in a petri dish. The cells are limited in other ways, too. There's little point in treating a genetic condition with a patient's own cord-blood cells, which have the same DNA and thus the same deleterious mutations. Scientists could someday overcome these hurdles; they could develop new ways of cultivating and genetically tweaking cord-blood cells in the lab. But by then, the same scientists will probably know much more about all stem cells, especially once restrictions on embryonic research are lifted—and there may be better ways of getting safe, usable cells from other sources, ways that won't require a lot of technological wizardry.
These difficulties don't deter everyone, of course. The pediatrician Robert Sears, a talk-show regular and the coauthor of popular parenting books, supports private cord-blood banking; he froze his own kids' samples with CBR. It's also possible that 1 in 2,700 is too conservative. CBR's executives toss around much more dramatic odds. Harris, the scientific director, puts them at a breathtaking 1 in 3. His calculations, unlike the professional groups', include injuries to the brain. There is, he notes, "no genetic predisposition to falling out of a crib"—so as he sees it, every child, technically, is at risk.
Until widespread trials of cord-blood treatment take place, both sides will be able to use arbitrary calculations. Those trials, alas, are probably far off: rare conditions are difficult to study on a large scale, since by definition there aren't many patients to enroll. Three years ago, Congress tried to put cord-blood trials on a faster track by expanding funds for the NIH's public banks—more donations to the banks could mean more studies—but the law hasn't made much of an impact. Public banks have collected cord blood from just 105,000 babies, and fewer than 200 hospitals in the U.S. are able to draw and ship the blood to public centers. The private banks, of course, have larger stores. But they are not huge contributors to research either: only 100 of CBR's 250,000 clients have enrolled in trials thus far.
For now, parents are left to make the same speculative wager at the heart of CBR's business model: how much should you invest in science that's promising but not proven? Back in the ballroom in Tucson, the OBs and midwives on the CBR junket were considering that question too. They pressed Cynthia Hextell for more details. How were the other kids in the Kurtzberg trial doing? Cynthia said the few other families she had talked to had seen improvements like Dallas's. And what risks were they warned about? "The only risk was that it wouldn't work and we would be out the money," she said. "But we just knew in our hearts that it was going to work." Other parents will have to decide whether they have that kind of faith.
If the Hextells' names sound familiar to some readers, it is because, in the wake of their son's remarkable recovery, they have become minor celebrities. Their story has appeared on the "Today" show and in advertisements in almost every pregnancy magazine in the country. The ads are not for the trial at Duke, which remains a small, academic endeavor. They are for a company called Cord Blood Registry, which charges parents $2,000-plus to freeze and store samples of their children's umbilical-cord blood, a fluid rich in stem cells. Cynthia Hextell paid the company to freeze Dallas's cord blood at his birth. That sample was the source of the stem cells used in the Duke trial—and as the ads remind parents, it was available only because the Hextells had paid for it to be.
The Hextells' story has become the centerpiece of CBR's marketing efforts. Recently the company invited about 30 obstetricians and midwives to the Westin La Paloma resort in Tucson, Ariz., for a weekend of sun, golf and medical briefings, including dinner in a ballroom with the Hextells as guest speakers. Since these doctors had collected cord blood for CBR clients in the past, the company hoped to turn them into evangelists. The next day, the group went for a tour of CBR's glittering 60,000-square-foot lab. The agenda also included more time at the La Paloma, home to a Jack Nicklaus golf course, a spa, five restaurants and a swim-up bar. CBR can easily afford to put on this kind of show. Ten years ago it was a fledgling business with 10,000 clients. Today it is the country's largest private cord-blood bank, with 250,000 samples in storage, 300 employees and $100 million in annual revenue.
In medicine, money often comes with controversy—and right now, CBR has plenty of both. The company says it is providing precious biological insurance, that to freeze a child's cord-blood stem cells is to provide him a medical option for the future, perhaps a lifesaving treatment for childhood cancer or brain injuries. But critics, including the American Academy of Pediatrics, accuse private cord-blood banks like CBR of making exaggerated medical promises and exploiting vulnerable new parents. Cord blood's uses are limited at best, they say. The blood does not provide enough cells to cure an adult of a disease or injury; it is not appropriate for treating genetic conditions; and thus far there have been few trials to determine how effectively the cells can repair damaged tissue. Even Joanne Kurtzberg, the Duke transplant specialist who treated Dallas Hextell, is skeptical. She says it's difficult to know if his improvement is related to the cells or would have occurred without them—he probably would have gotten better on his own; some cerebral-palsy patients do—and she points out that her trial is small and yet to be analyzed and published. But CBR has a response for this. It says more uses for cord-blood stem cells will surely be discovered in the future. It also knows the power of a good story. David Zitlow, the company's senior vice president of public affairs, says doctors "haven't made a big enough deal about anecdotes" like the Hextells'.
So what are other parents, faced with the choice of banking their children's cord blood or brushing off the idea as a luxury—the medical equivalent of an $800 stroller—supposed to make of Dallas Hextell's case? Is it a breakthrough, a harbinger? Or is it ultimately just an anecdote, a moving tale with a happy outcome that may or may not have anything to do with cord blood and stem cells?
Doctors have been wondering if cord blood is something of a miracle cure for the past 15 years. The blood—which is usually thrown away in delivery rooms—contains a distinct type of stem cell that may act as a biochemical foreman, helping to build healthy tissues and repair damaged ones. In the early 1990s— before embryonic stem cells took over the spotlight—researchers began to explore whether cord-blood cells might be of practical medical use. At Duke, Kurtzberg performed a few cord-blood transplants on patients with leukemia and rare types of bone-marrow failure, sending them into remission. Meanwhile, the National Institutes of Health started funding public banks of frozen, donated cord-blood samples, modeled on adult blood banks. A cord-blood stem-cell transplant at that point was a long shot, an experiment to see if stem cells could either become new tissue or trick the body into fixing itself. But the idea behind the public banks was to make the option available to all families who might want to try it as a last resort.
It was around this time, in 1992, that Tom Moore, a technology and pharmaceutical executive with passion for startups, hatched a plan to found a cord-blood bank of his own. Unlike the NIH banks, this one would operate for profit. Its clients would retain exclusive access to their own genetically identical samples, for a fee of $1,500 up front plus $125 for each year of storage. One problem: Moore "didn't really know anything about stem cells except the name," he admits. So he sought out David Harris, a University of Arizona immunologist and cord-blood researcher, to serve as CBR's scientific director; meanwhile, as the CEO, he took care of the business side. Now it takes care of him. CBR is the largest of 30-some private cord-blood banks in the United States, with a 45 percent share of the $250 million market. It's probably not done growing yet. Moore's "big, hairy, audacious goal" is a million clients, quadruple the company's current size.
A number of trends have likely contributed to CBR's growth, including the enormous boom in the baby-products market and the hype around stem cells in general. But one thing that has not been a factor is a rapid rise in medical uses for cord blood—because there hasn't been one yet. Just as it was in the '90s, a cord-blood stem-cell transplant is still an experimental procedure. This hasn't deterred CBR from publicizing the results of a few positive studies, including a small, preliminary trial in kids with type 1 diabetes from last year.
In Dallas Hextell, CBR has another case to promote. In ads, the Hextells call the cord-blood treatment "a miracle." But nobody really knows what has happened in Dallas's brain. The story sounds less clear-cut coming from Kurtzberg, the doctor who performed the transfusion and who examined Dallas again in November. "He has made progress, there's no question," she says. "But he still has a global developmental delay of about a year. He looks like where we would have expected him to be without cells." When she saw him at his follow-up visit, she adds, "I thought, wow, he doesn't look as good as I was expecting based on what's been in the press." (The Hextells find Kurtzberg's assessment frustrating and note that Dallas's therapists at home—who knew him before the transfusion—are impressed and surprised at his improvement.) Kurtzberg also has not completed the follow-up and analysis of the study or published the results from 50 other kids with cerebral palsy who have enrolled in her trial thus far.
Kurtzberg, it turns out, is not a big booster for private cord-blood banks; although she uses samples from CBR, she does not receive funding from the company, and also uses cells from public banks and other companies. In fact, she's one of the authors of a statement the American Academy of Pediatrics put out last year discouraging parents from using private banks on the grounds that the science isn't solid enough yet to justify a multi-thousand-dollar gamble. (The AAP does support public, nonprofit banks, which patients can use for free.) The American College of Obstetricians and Gynecologists released its own statement in February, noting that "there is no reliable estimate of a child's likelihood of actually using his or her own saved cord blood later." Then it made a guess anyway: 1 in 2,700, which Kurtzberg calls "generous."
Why is this number so small? There are reasons to think cord-blood treatment will never be a widespread medical procedure. The blood contains only enough stem cells to treat a small child; unlike embryonic stem cells, cord-blood cells cannot be multiplied into self-rejuvenating "lines" in a petri dish. The cells are limited in other ways, too. There's little point in treating a genetic condition with a patient's own cord-blood cells, which have the same DNA and thus the same deleterious mutations. Scientists could someday overcome these hurdles; they could develop new ways of cultivating and genetically tweaking cord-blood cells in the lab. But by then, the same scientists will probably know much more about all stem cells, especially once restrictions on embryonic research are lifted—and there may be better ways of getting safe, usable cells from other sources, ways that won't require a lot of technological wizardry.
These difficulties don't deter everyone, of course. The pediatrician Robert Sears, a talk-show regular and the coauthor of popular parenting books, supports private cord-blood banking; he froze his own kids' samples with CBR. It's also possible that 1 in 2,700 is too conservative. CBR's executives toss around much more dramatic odds. Harris, the scientific director, puts them at a breathtaking 1 in 3. His calculations, unlike the professional groups', include injuries to the brain. There is, he notes, "no genetic predisposition to falling out of a crib"—so as he sees it, every child, technically, is at risk.
Until widespread trials of cord-blood treatment take place, both sides will be able to use arbitrary calculations. Those trials, alas, are probably far off: rare conditions are difficult to study on a large scale, since by definition there aren't many patients to enroll. Three years ago, Congress tried to put cord-blood trials on a faster track by expanding funds for the NIH's public banks—more donations to the banks could mean more studies—but the law hasn't made much of an impact. Public banks have collected cord blood from just 105,000 babies, and fewer than 200 hospitals in the U.S. are able to draw and ship the blood to public centers. The private banks, of course, have larger stores. But they are not huge contributors to research either: only 100 of CBR's 250,000 clients have enrolled in trials thus far.
For now, parents are left to make the same speculative wager at the heart of CBR's business model: how much should you invest in science that's promising but not proven? Back in the ballroom in Tucson, the OBs and midwives on the CBR junket were considering that question too. They pressed Cynthia Hextell for more details. How were the other kids in the Kurtzberg trial doing? Cynthia said the few other families she had talked to had seen improvements like Dallas's. And what risks were they warned about? "The only risk was that it wouldn't work and we would be out the money," she said. "But we just knew in our hearts that it was going to work." Other parents will have to decide whether they have that kind of faith.
Thursday, December 18, 2008
Vit. E, selenium don't cut risk of prostate cancer, big study finds
[Source: Arizona Daily Star, Evan Pellegrino] - Two natural supplements that have been promoted as possibly helping prevent prostate cancer actually have no effect, according to a national study that included University of Arizona researchers at the Arizona Cancer Center.
According to the study, vitamin E and selenium supplements do not aid in preventing prostate cancer, the most common cancer in American men other than skin cancers.
The study examined the effects of both supplements in more than 35,000 men nationally, including several hundred in Tucson. It was the largest trial ever on prostate-cancer prevention, according to officials at the Arizona Cancer Center. The study included the Southern Arizona VA Health Care System.
Called SELECT (the Selenium and Vitamin E Cancer Prevention Trial), the study was funded by the National Cancer Institute and coordinated through the Southwest Oncology Group.
"A large trial like SELECT is the only way to determine for certain the real value of supplements," said Frederick Ahmann, professor of medicine and director of the Hematology/Oncology Fellowship Program at the Arizona Cancer Center, in a news release.
"Using science to study and determine whether there is value to taking a specific substance for health or disease prevention is vital, telling us what is helpful, what is harmful and what is not useful to take."
Millions of Americans take dietary supplements such as vitamins, minerals and herbs with the thought that they can help prevent or cure illnesses and ailments.
The Food and Drug Administration considers supplements foods, not drugs, so they don't need to be approved by the FDA before going on the market.
The SELECT study on vitamin E and the trace mineral selenium was based on previous research on other cancers that suggested the supplements might reduce the risk of prostate cancer.
In 1998, a study of 29,133 male smokers in Finland who took vitamin E to prevent lung cancer showed 32 percent fewer prostate cancers. In 1996, a study of 1,312 men and women with skin cancer who took selenium showed that men who took the supplement had 52 percent fewer prostate cancers than those who did not take it, according a National Cancer Institute news release.
Based on these and other earlier findings, men age 50 and older were recruited to participate in SELECT earlier this decade. The men were randomly chosen and grouped to take one of four combinations of supplements or placebos. One group took selenium and vitamin E; one took selenium and a vitamin E placebo; one took vitamin E and a selenium placebo; and the final group received placebos of both supplements.
It was a blinded study — neither the men nor their physicians knew who was taking supplements.
Now, five years after the trial phase of SELECT began, an initial, independent analysis of the study data determined that taking vitamin E and selenium together or alone didn't prevent prostate cancer.
The study actually showed very small increases in the number of cases of prostate cancer in men taking only vitamin E as well as diabetes in men taking only selenium, but researchers dismissed the increase as statistically insignificant.
Participants in the study are being told to stop taking their supplements; however, they will continue to have their health monitored.
Researchers intend to follow the participants for about three years to determine the long-term effects of having taken the supplements.
"As we continue to monitor the health of these 35,000 men, this information may help us understand why two nutrients that showed strong initial evidence to be able to prevent prostate cancer did not do so," said Eric Klein, a study co-chair for SELECT and a physician at the Cleveland Clinic, in the national news release.
The $114 million study was funded by the National Cancer Institute, with additional support from the National Center for Complementary and Alternative Medicine.
According to the study, vitamin E and selenium supplements do not aid in preventing prostate cancer, the most common cancer in American men other than skin cancers.
The study examined the effects of both supplements in more than 35,000 men nationally, including several hundred in Tucson. It was the largest trial ever on prostate-cancer prevention, according to officials at the Arizona Cancer Center. The study included the Southern Arizona VA Health Care System.
Called SELECT (the Selenium and Vitamin E Cancer Prevention Trial), the study was funded by the National Cancer Institute and coordinated through the Southwest Oncology Group.
"A large trial like SELECT is the only way to determine for certain the real value of supplements," said Frederick Ahmann, professor of medicine and director of the Hematology/Oncology Fellowship Program at the Arizona Cancer Center, in a news release.
"Using science to study and determine whether there is value to taking a specific substance for health or disease prevention is vital, telling us what is helpful, what is harmful and what is not useful to take."
Millions of Americans take dietary supplements such as vitamins, minerals and herbs with the thought that they can help prevent or cure illnesses and ailments.
The Food and Drug Administration considers supplements foods, not drugs, so they don't need to be approved by the FDA before going on the market.
The SELECT study on vitamin E and the trace mineral selenium was based on previous research on other cancers that suggested the supplements might reduce the risk of prostate cancer.
In 1998, a study of 29,133 male smokers in Finland who took vitamin E to prevent lung cancer showed 32 percent fewer prostate cancers. In 1996, a study of 1,312 men and women with skin cancer who took selenium showed that men who took the supplement had 52 percent fewer prostate cancers than those who did not take it, according a National Cancer Institute news release.
Based on these and other earlier findings, men age 50 and older were recruited to participate in SELECT earlier this decade. The men were randomly chosen and grouped to take one of four combinations of supplements or placebos. One group took selenium and vitamin E; one took selenium and a vitamin E placebo; one took vitamin E and a selenium placebo; and the final group received placebos of both supplements.
It was a blinded study — neither the men nor their physicians knew who was taking supplements.
Now, five years after the trial phase of SELECT began, an initial, independent analysis of the study data determined that taking vitamin E and selenium together or alone didn't prevent prostate cancer.
The study actually showed very small increases in the number of cases of prostate cancer in men taking only vitamin E as well as diabetes in men taking only selenium, but researchers dismissed the increase as statistically insignificant.
Participants in the study are being told to stop taking their supplements; however, they will continue to have their health monitored.
Researchers intend to follow the participants for about three years to determine the long-term effects of having taken the supplements.
"As we continue to monitor the health of these 35,000 men, this information may help us understand why two nutrients that showed strong initial evidence to be able to prevent prostate cancer did not do so," said Eric Klein, a study co-chair for SELECT and a physician at the Cleveland Clinic, in the national news release.
The $114 million study was funded by the National Cancer Institute, with additional support from the National Center for Complementary and Alternative Medicine.
UA Vice President Dr. William Crist to Lecture on Childhood Cancer
[Source: East Valley Living] - Conquering Childhood Cancer: A Paradigm for Translational Research; Lecture to be Held Wednesday January 14, 2009 at Virginia G. Piper Auditorium
PHOENIX - The advances in treatment of childhood cancer in the last generation have been nothing less than life-changing, says William M. Crist, MD, the new vice president for health affairs for The University of Arizona.
The University of Arizona College of Medicine-Phoenix in partnership with Arizona State University and the Flinn Foundation will host Dr. Crist, who will talk about his experience in a presentation titled, “Conquering Childhood Cancer: A Paradigm for Translational Research,” on Wednesday, Jan. 14, 2009, 5:30 p.m., in the Virginia G. Piper Auditorium, 550 E. Van Buren, in downtown Phoenix. The lecture is free and open to the public. Parking in the College of Medicine lot, with entrance on Seventh Street, also is free. (Dr. Crist also will speak in Tucson on Thursday, Jan. 15, 5 p.m., at DuVal Auditorium at University Medical Center, 1501 N. Campbell Ave.)
Dr. Crist is among the scientists credited with dramatically improving our understanding of childhood leukemias and their treatments. He spent much of his career from the 1970s through the 1990s in the field of pediatric hematology and oncology first at the University of Alabama, Birmingham, the University of Tennessee College of Medicine at Memphis, and St. Jude Children’s Hospital in Memphis before becoming chairman of pediatric and adolescent medicine at Mayo Medical Center in Rochester, Minn. Dr. Crist had been serving as dean of the School of Medicine at the University of Missouri before being named UA vice president for health affairs last summer. He began his new duties Oct. 31.
The Donald K. Buffmire Visiting Lectureship in Medicine, begun in 1997, continues the Flinn Foundation’s commitment to bringing to Arizona leading practitioners and thinkers in the medical field. The lectureship aims to offer to physicians, students and community members opportunities to hear from distinguished leaders in the field of medicine and medical education. In 2008, the annual lecture was expanded to a biannual basis and includes presentations in both Phoenix and Tucson.
The lectureship is named for late Donald K. Buffmire, MD, in recognition of his distinguished career as a medical practitioner in Arizona and his leadership role with the Flinn Foundation in supporting the College of Medicine. Dr. Buffmire, who died this year, served as a board director from 1965-99, including 15 years as president and chairman.
The Phoenix-based Flinn Foundation is a privately endowed organization that awards grants to nonprofit organizations in Arizona, primarily to improve the competitiveness of the state’s biomedical-research enterprise.
The UA College of Medicine is the only MD degree-granting college in Arizona. Beginning in 1967 with a class of 32 students on its Tucson campus, the college today encompasses full, four-year medical-education programs in Tucson and since 2007, in Phoenix.
PHOENIX - The advances in treatment of childhood cancer in the last generation have been nothing less than life-changing, says William M. Crist, MD, the new vice president for health affairs for The University of Arizona.
The University of Arizona College of Medicine-Phoenix in partnership with Arizona State University and the Flinn Foundation will host Dr. Crist, who will talk about his experience in a presentation titled, “Conquering Childhood Cancer: A Paradigm for Translational Research,” on Wednesday, Jan. 14, 2009, 5:30 p.m., in the Virginia G. Piper Auditorium, 550 E. Van Buren, in downtown Phoenix. The lecture is free and open to the public. Parking in the College of Medicine lot, with entrance on Seventh Street, also is free. (Dr. Crist also will speak in Tucson on Thursday, Jan. 15, 5 p.m., at DuVal Auditorium at University Medical Center, 1501 N. Campbell Ave.)
Dr. Crist is among the scientists credited with dramatically improving our understanding of childhood leukemias and their treatments. He spent much of his career from the 1970s through the 1990s in the field of pediatric hematology and oncology first at the University of Alabama, Birmingham, the University of Tennessee College of Medicine at Memphis, and St. Jude Children’s Hospital in Memphis before becoming chairman of pediatric and adolescent medicine at Mayo Medical Center in Rochester, Minn. Dr. Crist had been serving as dean of the School of Medicine at the University of Missouri before being named UA vice president for health affairs last summer. He began his new duties Oct. 31.
The Donald K. Buffmire Visiting Lectureship in Medicine, begun in 1997, continues the Flinn Foundation’s commitment to bringing to Arizona leading practitioners and thinkers in the medical field. The lectureship aims to offer to physicians, students and community members opportunities to hear from distinguished leaders in the field of medicine and medical education. In 2008, the annual lecture was expanded to a biannual basis and includes presentations in both Phoenix and Tucson.
The lectureship is named for late Donald K. Buffmire, MD, in recognition of his distinguished career as a medical practitioner in Arizona and his leadership role with the Flinn Foundation in supporting the College of Medicine. Dr. Buffmire, who died this year, served as a board director from 1965-99, including 15 years as president and chairman.
The Phoenix-based Flinn Foundation is a privately endowed organization that awards grants to nonprofit organizations in Arizona, primarily to improve the competitiveness of the state’s biomedical-research enterprise.
The UA College of Medicine is the only MD degree-granting college in Arizona. Beginning in 1967 with a class of 32 students on its Tucson campus, the college today encompasses full, four-year medical-education programs in Tucson and since 2007, in Phoenix.
Breast Cancer: Diet High In Vegetables, Fruit And Fiber May Cut Risk Of Cancer Recurrence In Women Without Hot Flashes
[Source: ScienceDaily ] - A secondary analysis of a large, multicenter clinical trial has shown that a diet loaded with fruits, vegetables and fiber and somewhat lower in fat compared to standard federal dietary recommendations cuts the risk of recurrence in a subgroup of early-stage breast cancer survivors – women who didn't have hot flashes – by approximately 31 percent. These patients typically have higher recurrence and lower survival rates than breast cancer patients who have hot flashes.
The study team, led by researchers at the Moores Cancer Center at the University of California, San Diego, along with six other sites, including the University of California, Davis, reported its results online December 15, 2008, in the Journal of Clinical Oncology.
The results come on the heels of a report last year on the findings of the original study, the Women's Healthy Eating and Living Trial (WHEL), which compared the effects of the two diets on cancer recurrence in more than 3,000 early-stage breast cancer survivors. That study showed no overall difference in recurrence among the two diet groups.
"Women with early stage breast cancer who have hot flashes have better survival and lower recurrence rates than women who don't have hot flashes," said Ellen B. Gold, Ph.D., professor and chair of the UC Davis Department of Public Health Sciences and first author of the study. "Our results suggest that a major change in diet may help overcome the difference in prognosis between women with and without hot flashes."
"Our interest in looking at this subgroup came because hot flashes are associated with lower circulating estrogen levels, while the absence of hot flashes is associated with higher estrogen levels. Reducing the effect of estrogen is a major treatment strategy in breast cancer," said the WHEL study principal investigator John P. Pierce, Ph.D., Sam M. Walton Professor for Cancer Prevention and director of Cancer Prevention and Control at the UC San Diego School of Medicine and the Moores UCSD Cancer Center. "It appears that a dietary pattern high in fruits, vegetables and fiber, which has been shown to reduce circulating estrogen levels, may only be important among women with circulating estrogen levels above a certain threshold."
About 30 percent of the original group of 3,088 breast cancer survivors did not report hot flashes at study entry. The women had been randomly assigned to one of the two diets between 1995 and 2000 and were followed until 2006. About one-half (447) of the "no hot flashes" group were randomized to the special, "intervention" high-vegetable fruit diet while the other half (453) was given the generally recommended diet of five servings of fruits and vegetables a day. The team found that those on the intervention diet had a significantly lower rate of a second breast cancer event (16.1 percent) compared to those eating the government-recommended five-a-day dietary pattern (23.6 percent).
The dietary effect was even larger (a 47 percent lower risk) in women who had been through menopause.
According to Pierce, another possible mechanism has been proposed recently for why this diet may have affected only 30 percent of the WHEL study population. Women with estrogen receptor-positive cancers usually receive hormone therapy (tamoxifen or aromatase inhibitors) aimed at combating the effect of circulating estrogen. However, more than 30 percent of these women appear to have a gene-drug interaction that prevents them from getting an effective dose of this therapy.
"This hypothesis says that if the endocrine therapy is working, no further reduction in estrogen levels would be needed," said Pierce. "If your genes are preventing you from getting a therapeutic dose, then following this rigorous dietary pattern may reduce estrogen levels enough to reduce risk." Because this is speculation, he said, the research team will be using biological samples collected throughout the study to further investigate the mechanisms behind the study diet's protective effects.
Other co-authors include: Cheryl Rock, Ph.D., Barbara Parker, M.D., Lisa Madlensky, Ph.D., Loki Natarajan, Ph.D., Linda Wasserman, M.D., Vicky Jones, M.D., Gail Laughlin, Ph.D., Nazmus Saquib M.D., Ph.D., Sheila Kealey MPH, Shirley Flatt, Jennifer Emond and Minya Pu, UCSD; Joanne Mortimer, M.D., City of Hope; Marcia Stefanek, Ph.D., Stanford University; Bette Caan, Dr.P.H, Kaiser Permanente, Oakland, Cynthia Thomson, Ph.D., University of Arizona, Njeri Karanja, Ph.D., Kaiser Permanente, Portland, OR; Richard Hajek, Ph.D., M.D. Anderson Cancer Center.
The study team, led by researchers at the Moores Cancer Center at the University of California, San Diego, along with six other sites, including the University of California, Davis, reported its results online December 15, 2008, in the Journal of Clinical Oncology.
The results come on the heels of a report last year on the findings of the original study, the Women's Healthy Eating and Living Trial (WHEL), which compared the effects of the two diets on cancer recurrence in more than 3,000 early-stage breast cancer survivors. That study showed no overall difference in recurrence among the two diet groups.
"Women with early stage breast cancer who have hot flashes have better survival and lower recurrence rates than women who don't have hot flashes," said Ellen B. Gold, Ph.D., professor and chair of the UC Davis Department of Public Health Sciences and first author of the study. "Our results suggest that a major change in diet may help overcome the difference in prognosis between women with and without hot flashes."
"Our interest in looking at this subgroup came because hot flashes are associated with lower circulating estrogen levels, while the absence of hot flashes is associated with higher estrogen levels. Reducing the effect of estrogen is a major treatment strategy in breast cancer," said the WHEL study principal investigator John P. Pierce, Ph.D., Sam M. Walton Professor for Cancer Prevention and director of Cancer Prevention and Control at the UC San Diego School of Medicine and the Moores UCSD Cancer Center. "It appears that a dietary pattern high in fruits, vegetables and fiber, which has been shown to reduce circulating estrogen levels, may only be important among women with circulating estrogen levels above a certain threshold."
About 30 percent of the original group of 3,088 breast cancer survivors did not report hot flashes at study entry. The women had been randomly assigned to one of the two diets between 1995 and 2000 and were followed until 2006. About one-half (447) of the "no hot flashes" group were randomized to the special, "intervention" high-vegetable fruit diet while the other half (453) was given the generally recommended diet of five servings of fruits and vegetables a day. The team found that those on the intervention diet had a significantly lower rate of a second breast cancer event (16.1 percent) compared to those eating the government-recommended five-a-day dietary pattern (23.6 percent).
The dietary effect was even larger (a 47 percent lower risk) in women who had been through menopause.
According to Pierce, another possible mechanism has been proposed recently for why this diet may have affected only 30 percent of the WHEL study population. Women with estrogen receptor-positive cancers usually receive hormone therapy (tamoxifen or aromatase inhibitors) aimed at combating the effect of circulating estrogen. However, more than 30 percent of these women appear to have a gene-drug interaction that prevents them from getting an effective dose of this therapy.
"This hypothesis says that if the endocrine therapy is working, no further reduction in estrogen levels would be needed," said Pierce. "If your genes are preventing you from getting a therapeutic dose, then following this rigorous dietary pattern may reduce estrogen levels enough to reduce risk." Because this is speculation, he said, the research team will be using biological samples collected throughout the study to further investigate the mechanisms behind the study diet's protective effects.
Other co-authors include: Cheryl Rock, Ph.D., Barbara Parker, M.D., Lisa Madlensky, Ph.D., Loki Natarajan, Ph.D., Linda Wasserman, M.D., Vicky Jones, M.D., Gail Laughlin, Ph.D., Nazmus Saquib M.D., Ph.D., Sheila Kealey MPH, Shirley Flatt, Jennifer Emond and Minya Pu, UCSD; Joanne Mortimer, M.D., City of Hope; Marcia Stefanek, Ph.D., Stanford University; Bette Caan, Dr.P.H, Kaiser Permanente, Oakland, Cynthia Thomson, Ph.D., University of Arizona, Njeri Karanja, Ph.D., Kaiser Permanente, Portland, OR; Richard Hajek, Ph.D., M.D. Anderson Cancer Center.
Just A Little Squeeze Lets Proteins Assess DNA
[Source: ScienceDaily] - To find its target, all a protein needs to do is give quick squeezes as it moves along the DNA strand, suggests new research from The University of Arizona in Tucson.
Scientists had thought DNA-binding proteins primarily used full-body hugs for accurate readings of the information coded in the DNA's sequence.
Even a protein known to use the hug method, called direct readout, can effectively pinpoint sites on DNA using indirect readout, found researcher Nancy C. Horton and her colleagues.
"It was a total surprise," said Horton, a UA associate professor of biochemistry and molecular biophysics. "No one had ever seen it before."
Doing the quick squeezes that scientists call indirect readout probably works faster than requiring full-body contact with all the DNA, the researchers suggest. Quick and accurate identification of key sites on DNA is important for the health of all kinds of cells, from bacteria to humans.
To detect the protein-DNA connection in such detail, Horton and her co-authors Elizabeth J. Little and Andrea C. Babic studied a DNA-binding protein that bacteria use to protect themselves from viral infections.
The finding has implications for the development of designer drugs.
"People have and are developing DNA-binding proteins to turn genes on and off," Horton said. Such designer proteins can be used to cut out the bad copy of a gene and help replace it with good copy.
"We found that indirect readout is important for finding the right sequence, and we now think indirect readout is also important for finding it quickly," she said.
The team published their paper, "Early Interrogation and Recognition of DNA Sequence by Indirect Readout," in the December issue of the journal Structure. First author Little and co-author Babic were postdoctoral research associates in Horton's laboratory when they did the research. The two are now senior scientists at Ventana Medical Systems, Inc. in Tucson, Ariz.
The National Institutes of Health funded the research.
Horton studies proteins that bind to DNA.
Seven years ago, she figured out the structure of a protein called HincII that snips up DNA. The protein is a type of enzyme called a restriction endonuclease and comes from Haemophilus influenzae bacteria.
Since that time, Horton has been trying to learn how HincII interrogates the DNA to find the right place to cut.
The protein protects bacteria by cutting up DNA from invading viruses. Without the protective protein, viral DNA would commandeer the bacterium's cellular machinery to produce viruses and ultimately kill the bacterial cell.
The HincII protein distinguishes between bacterial DNA and viral DNA by recognizing certain sequences on DNA. Such a defense requires speed to prevent the marauding virus from killing the cell and also accuracy so the protein doesn't accidentally hack up the bacterium's own DNA.
Horton knew from her previous work that the HincII protein used the direct readout method to find the particular sequence of DNA that corresponded to enemy DNA. The protein seemed to distort the DNA to read it.
Removing the direct readout contact between the protein and the DNA might show whether the DNA distortion or the contact itself was important, Horton said.
Therefore Little and Babic created a mutant protein that couldn't hug DNA closely and therefore couldn't use the direct readout method. Little described the mutant protein as missing the fingers the normal protein used to probe the DNA.
"If the finger was doing all the recognition, then the mutant should cut any DNA sequence," Horton said.
To see how the mutant interacted with DNA, the researchers crystallized the mutant protein-DNA complex in action.
Initially, Horton thought the assay had gone wrong and almost threw the results in the trash, she wrote in an e-mail.
The mutant protein had chosen the proper site on the DNA with 100 percent specificity, which was opposite from what she expected. In addition, the DNA was distorted, even though the mutant couldn't make the strong contact a normal protein would.
"I did a double-take. I was just taking a picture to have a record that it was non-specific," she said.
Understanding how endonucleases and other DNA binding-proteins recognize a particular DNA sequence provides insight into key cellular processes including the replication, transcription and repair of DNA.
Little said, "In every single one of your cells are proteins looking for the proper sequences in DNA in order to make the proteins you need to stay alive."
Horton added, "Understanding how these processes work helps in the understanding of diseases so that we could potentially cure the disease."
Scientists had thought DNA-binding proteins primarily used full-body hugs for accurate readings of the information coded in the DNA's sequence.
Even a protein known to use the hug method, called direct readout, can effectively pinpoint sites on DNA using indirect readout, found researcher Nancy C. Horton and her colleagues.
"It was a total surprise," said Horton, a UA associate professor of biochemistry and molecular biophysics. "No one had ever seen it before."
Doing the quick squeezes that scientists call indirect readout probably works faster than requiring full-body contact with all the DNA, the researchers suggest. Quick and accurate identification of key sites on DNA is important for the health of all kinds of cells, from bacteria to humans.
To detect the protein-DNA connection in such detail, Horton and her co-authors Elizabeth J. Little and Andrea C. Babic studied a DNA-binding protein that bacteria use to protect themselves from viral infections.
The finding has implications for the development of designer drugs.
"People have and are developing DNA-binding proteins to turn genes on and off," Horton said. Such designer proteins can be used to cut out the bad copy of a gene and help replace it with good copy.
"We found that indirect readout is important for finding the right sequence, and we now think indirect readout is also important for finding it quickly," she said.
The team published their paper, "Early Interrogation and Recognition of DNA Sequence by Indirect Readout," in the December issue of the journal Structure. First author Little and co-author Babic were postdoctoral research associates in Horton's laboratory when they did the research. The two are now senior scientists at Ventana Medical Systems, Inc. in Tucson, Ariz.
The National Institutes of Health funded the research.
Horton studies proteins that bind to DNA.
Seven years ago, she figured out the structure of a protein called HincII that snips up DNA. The protein is a type of enzyme called a restriction endonuclease and comes from Haemophilus influenzae bacteria.
Since that time, Horton has been trying to learn how HincII interrogates the DNA to find the right place to cut.
The protein protects bacteria by cutting up DNA from invading viruses. Without the protective protein, viral DNA would commandeer the bacterium's cellular machinery to produce viruses and ultimately kill the bacterial cell.
The HincII protein distinguishes between bacterial DNA and viral DNA by recognizing certain sequences on DNA. Such a defense requires speed to prevent the marauding virus from killing the cell and also accuracy so the protein doesn't accidentally hack up the bacterium's own DNA.
Horton knew from her previous work that the HincII protein used the direct readout method to find the particular sequence of DNA that corresponded to enemy DNA. The protein seemed to distort the DNA to read it.
Removing the direct readout contact between the protein and the DNA might show whether the DNA distortion or the contact itself was important, Horton said.
Therefore Little and Babic created a mutant protein that couldn't hug DNA closely and therefore couldn't use the direct readout method. Little described the mutant protein as missing the fingers the normal protein used to probe the DNA.
"If the finger was doing all the recognition, then the mutant should cut any DNA sequence," Horton said.
To see how the mutant interacted with DNA, the researchers crystallized the mutant protein-DNA complex in action.
Initially, Horton thought the assay had gone wrong and almost threw the results in the trash, she wrote in an e-mail.
The mutant protein had chosen the proper site on the DNA with 100 percent specificity, which was opposite from what she expected. In addition, the DNA was distorted, even though the mutant couldn't make the strong contact a normal protein would.
"I did a double-take. I was just taking a picture to have a record that it was non-specific," she said.
Understanding how endonucleases and other DNA binding-proteins recognize a particular DNA sequence provides insight into key cellular processes including the replication, transcription and repair of DNA.
Little said, "In every single one of your cells are proteins looking for the proper sequences in DNA in order to make the proteins you need to stay alive."
Horton added, "Understanding how these processes work helps in the understanding of diseases so that we could potentially cure the disease."
Male Circumcision May Decrease Risk Of HPV Infection And Cervical Cancer
[Source: ScienceDaily] - Two new studies suggest that male circumcision may assist in the prevention of human papillomavirus (HPV) infection, particularly infection with the high-risk subtypes associated with cervical, penile, and other cancers.
Both studies are published in the January 1 issue of The Journal of Infectious Diseases, now available online.
High-risk subtypes of HPV have been estimated to be present in 99.7 percent of cervical cancers worldwide. Evidence has shown that women with circumcised partners have a reduced risk for genital cancer. Two new studies sought to discover if HPV infection is more likely to occur in uncircumcised compared with circumcised men.
Bertran Auvert MD, PhD, and his team of researchers in France and colleagues from South Africa studied data from a trial conducted in Orange Farm, South Africa. Uncircumcised men aged 18-24 years were randomized into either an intervention group, to be circumcised, or a control group, to remain uncircumcised. During this study, urethral swab samples were collected and analyzed for presence of HPV among men followed up for 21 months. Information about sexual behavior was also collected.
Dr. Auvert and colleagues found that the percentage of high-risk HPV genotypes was lower in the circumcised group than in the control group. The most important implication, according to researchers, was that “reducing the frequency of HPV infection among men will reduce the risk of exposure in their female sexual partners.”
A second study by Carrie Nielson PhD, at the Oregon Health & Science University and colleagues at the University of Arizona, H. Lee Moffitt Cancer Center and Research Institute, and the Centers for Disease Control and Prevention tested more than four hundred men aged 18-40 years in two U.S. cities during 2002-2005. Sixteen percent of participants were uncircumcised. Researchers tested for HPV in skin swabs of the anogenital area and semen samples in participants with no HPV symptoms (such as warts or lesions).
Investigators found that circumcised men were about half as likely to have HPV as uncircumcised men, after adjustment for other differences in the two groups. These results demonstrated that lack of circumcision is associated with cervical cancer because of the increased risk of HPV infection. Nielson suggested that it may be useful to consider circumcising newborn boys in order to decrease the risk of HPV infection for them and their future partners. “Parents are not currently advised of this risk,” she said. “These studies contribute to the evidence that might help to inform that decision.”
In an accompanying editorial, Ronald H. Gray, MD, of Johns Hopkins University, said that the evidence was persuasive but not entirely consistent and that it may be premature to promote circumcision as a way to prevent HPV infection in men and to protect female sex partners from infection. He advised that policy decisions should await results from two ongoing trials of male circumcision. Alternatively, Gray noted that consistent evidence has suggested that male circumcision reduces the frequency of HIV infection in men.He also pointed out that because of the lack of conclusive data relating circumcision and prevention of HPV, Medicaid does not cover circumcision costs, which may account for a decline in neonatal circumcisions in the United States.
According to Dr. Nielson, the findings they reported present compelling arguments to promote male circumcision in developing countries where circumcision is not widely used and the HIV epidemic is severe. Additionally, she said, it is “the first clear demonstration of the indirect but substantial beneficial effect of male circumcision for women.” The authors of both studies and the editorialist agreed that more studies will be needed to confirm the efficacy of male circumcision in HPV prevention.
Both studies are published in the January 1 issue of The Journal of Infectious Diseases, now available online.
High-risk subtypes of HPV have been estimated to be present in 99.7 percent of cervical cancers worldwide. Evidence has shown that women with circumcised partners have a reduced risk for genital cancer. Two new studies sought to discover if HPV infection is more likely to occur in uncircumcised compared with circumcised men.
Bertran Auvert MD, PhD, and his team of researchers in France and colleagues from South Africa studied data from a trial conducted in Orange Farm, South Africa. Uncircumcised men aged 18-24 years were randomized into either an intervention group, to be circumcised, or a control group, to remain uncircumcised. During this study, urethral swab samples were collected and analyzed for presence of HPV among men followed up for 21 months. Information about sexual behavior was also collected.
Dr. Auvert and colleagues found that the percentage of high-risk HPV genotypes was lower in the circumcised group than in the control group. The most important implication, according to researchers, was that “reducing the frequency of HPV infection among men will reduce the risk of exposure in their female sexual partners.”
A second study by Carrie Nielson PhD, at the Oregon Health & Science University and colleagues at the University of Arizona, H. Lee Moffitt Cancer Center and Research Institute, and the Centers for Disease Control and Prevention tested more than four hundred men aged 18-40 years in two U.S. cities during 2002-2005. Sixteen percent of participants were uncircumcised. Researchers tested for HPV in skin swabs of the anogenital area and semen samples in participants with no HPV symptoms (such as warts or lesions).
Investigators found that circumcised men were about half as likely to have HPV as uncircumcised men, after adjustment for other differences in the two groups. These results demonstrated that lack of circumcision is associated with cervical cancer because of the increased risk of HPV infection. Nielson suggested that it may be useful to consider circumcising newborn boys in order to decrease the risk of HPV infection for them and their future partners. “Parents are not currently advised of this risk,” she said. “These studies contribute to the evidence that might help to inform that decision.”
In an accompanying editorial, Ronald H. Gray, MD, of Johns Hopkins University, said that the evidence was persuasive but not entirely consistent and that it may be premature to promote circumcision as a way to prevent HPV infection in men and to protect female sex partners from infection. He advised that policy decisions should await results from two ongoing trials of male circumcision. Alternatively, Gray noted that consistent evidence has suggested that male circumcision reduces the frequency of HIV infection in men.He also pointed out that because of the lack of conclusive data relating circumcision and prevention of HPV, Medicaid does not cover circumcision costs, which may account for a decline in neonatal circumcisions in the United States.
According to Dr. Nielson, the findings they reported present compelling arguments to promote male circumcision in developing countries where circumcision is not widely used and the HIV epidemic is severe. Additionally, she said, it is “the first clear demonstration of the indirect but substantial beneficial effect of male circumcision for women.” The authors of both studies and the editorialist agreed that more studies will be needed to confirm the efficacy of male circumcision in HPV prevention.
Monday, December 15, 2008
NHLBI Opens Resource for Genetic and Clinical Asthma Data
[Source: GenomeWeb News, a GenomeWeb staff reporter] — The National Heart, Lung, and Blood Institute has expanded its genetic and clinical data collection to include information collected from three asthma research networks, the National Institutes of Health said today.
The new project is part of the NHLBI’s SNP Health Association Resource (SHARe), a web-based dataset that provides researchers with free access to data from multiple, large population-based studies such as the Framingham Heart Study.
The new asthma component, called the SHARe-Asthma Resource Project (SHARP), includes data on 2,332 people with asthma and 805 families whose DNA was tested for 1 million genetic variations. SHARP also includes clinical data about lung function, allergy status, and respiratory symptoms.
The clinical data used in SHARP is being provided by the Childhood Asthma Management Program, the Childhood Asthma Research and Education Network, and the Asthma Clinical Research Network, all of which are funded by NHLBI.
The project will enable scientists to link participants’ genetic variations to their lab test results, making it possible to find out more about genetic influence on asthma and other airway diseases.
“Expanding the SHARe program to include asthma through the SHARP initiative will greatly expand our understanding of lung disease biology using genetic and genomic technologies,” NHLBI Director Elizabeth Nabel said in a statement.
SHARP data is available through the database of Genotypes and Phenotypes, or dbGaP, hosted by the National Center for Biotechnology Information.
Affymetrix developed SNP genotyping data for the asthma program under a contract with NHLBI.
More information about the new asthma program is available at the NIH’s website.
The new project is part of the NHLBI’s SNP Health Association Resource (SHARe), a web-based dataset that provides researchers with free access to data from multiple, large population-based studies such as the Framingham Heart Study.
The new asthma component, called the SHARe-Asthma Resource Project (SHARP), includes data on 2,332 people with asthma and 805 families whose DNA was tested for 1 million genetic variations. SHARP also includes clinical data about lung function, allergy status, and respiratory symptoms.
The clinical data used in SHARP is being provided by the Childhood Asthma Management Program, the Childhood Asthma Research and Education Network, and the Asthma Clinical Research Network, all of which are funded by NHLBI.
The project will enable scientists to link participants’ genetic variations to their lab test results, making it possible to find out more about genetic influence on asthma and other airway diseases.
“Expanding the SHARe program to include asthma through the SHARP initiative will greatly expand our understanding of lung disease biology using genetic and genomic technologies,” NHLBI Director Elizabeth Nabel said in a statement.
SHARP data is available through the database of Genotypes and Phenotypes, or dbGaP, hosted by the National Center for Biotechnology Information.
Affymetrix developed SNP genotyping data for the asthma program under a contract with NHLBI.
More information about the new asthma program is available at the NIH’s website.
DFMO May Affect Barrett's Esophagus
[Source: ScienceDaily] - "While there was a suggestion that DFMO may influence the extent of Barrett's dysplasia, this finding is very preliminary and further study of this agent in a larger number of patients is needed," said Frank A. Sinicrope, M.D., professor of medicine and oncology at the Mayo Clinic, Rochester, MN.
Sinicrope presented his findings at the American Association for Cancer Research's Seventh Annual International Conference on Frontiers in Cancer Prevention Research.
The single-arm study included 10 patients with Barrett's esophagus and low-grade dysplasia. The patients received 0.5 g/m2/d of DFMO for six months. Using an endoscope, the researchers examined esophageal biopsies at enrollment and at three, six and 12 months (where available). A gastrointestinal pathologist who was blinded to the clinical/biomarker data graded the dysplasia.
Sinicrope conducted this study while at The University of Texas M. D. Anderson Cancer Center. He collaborated with colleagues at the National Cancer Institute, and the Arizona Cancer Center, Tucson.
After six months of DFMO treatment, one patient's dysplasia regressed, one patient's progressed, and eight patients had stable disease. At six months, two patients in the stable group who started with extensive low-grade abnormal cells had only limited or focal dysplasia based on four or more biopsies. These improvements remained at 12 months.
DFMO lowered the level of the polyamine putrescine, a target of the drug and a possible cancer risk marker. The agent works by inhibiting an enzyme in polyamine synthesis called ornithine decarboxylase (ODC). "ODC activity in Barrett's mucosa has been shown to be significantly higher in Barrett's than in normal adjacent mucosa from the same patients," Sinicrope said.
"Since DFMO inhibits polyamine synthesis, the fact that putrescine levels were decreased at six months and later returned to baseline after being off the drug for six months suggests that the drug is affecting its target."
Interestingly, DFMO also reduced expression of Kruppel-like factor 5 (KLF5) gene, an important marker of abnormal cell proliferation in the esophagus that may represent a novel drug target.
"The results are encouraging because they identify KLF5 as a potential target of DFMO, which suggests a potential mechanism contributing to the chemopreventive effects of DFMO," Sinicrope said. "KLF5 has been shown to regulate proliferation, apoptosis and invasion in esophageal cancer cells."
Generally, DFMO was well tolerated. One patient had hearing loss and balance-related problems related to treatment.
"DFMO warrants further evaluation as a chemopreventive agent in patients with Barrett's esophagus and mucosal dysplasia," Sinicrope said. Currently, the Mayo Clinic researcher and his colleagues are planning a placebo-controlled chemoprevention trial in this patient population.
Sinicrope presented his findings at the American Association for Cancer Research's Seventh Annual International Conference on Frontiers in Cancer Prevention Research.
The single-arm study included 10 patients with Barrett's esophagus and low-grade dysplasia. The patients received 0.5 g/m2/d of DFMO for six months. Using an endoscope, the researchers examined esophageal biopsies at enrollment and at three, six and 12 months (where available). A gastrointestinal pathologist who was blinded to the clinical/biomarker data graded the dysplasia.
Sinicrope conducted this study while at The University of Texas M. D. Anderson Cancer Center. He collaborated with colleagues at the National Cancer Institute, and the Arizona Cancer Center, Tucson.
After six months of DFMO treatment, one patient's dysplasia regressed, one patient's progressed, and eight patients had stable disease. At six months, two patients in the stable group who started with extensive low-grade abnormal cells had only limited or focal dysplasia based on four or more biopsies. These improvements remained at 12 months.
DFMO lowered the level of the polyamine putrescine, a target of the drug and a possible cancer risk marker. The agent works by inhibiting an enzyme in polyamine synthesis called ornithine decarboxylase (ODC). "ODC activity in Barrett's mucosa has been shown to be significantly higher in Barrett's than in normal adjacent mucosa from the same patients," Sinicrope said.
"Since DFMO inhibits polyamine synthesis, the fact that putrescine levels were decreased at six months and later returned to baseline after being off the drug for six months suggests that the drug is affecting its target."
Interestingly, DFMO also reduced expression of Kruppel-like factor 5 (KLF5) gene, an important marker of abnormal cell proliferation in the esophagus that may represent a novel drug target.
"The results are encouraging because they identify KLF5 as a potential target of DFMO, which suggests a potential mechanism contributing to the chemopreventive effects of DFMO," Sinicrope said. "KLF5 has been shown to regulate proliferation, apoptosis and invasion in esophageal cancer cells."
Generally, DFMO was well tolerated. One patient had hearing loss and balance-related problems related to treatment.
"DFMO warrants further evaluation as a chemopreventive agent in patients with Barrett's esophagus and mucosal dysplasia," Sinicrope said. Currently, the Mayo Clinic researcher and his colleagues are planning a placebo-controlled chemoprevention trial in this patient population.
Monday, December 8, 2008
Pharmacy dean elected to national position
[Source: Daily Wildcat, Adam Curtis] - The UA College of Pharmacy has just added another notch on its post of faculty with distinguished honors, with the election of its associate dean of academic and professional affairs, Dr. John Murphy, as president of the American College of Clinical Pharmacy.
As president of the ACCP, Murphy will lead an organization of approximately 10,000 clinical pharmacists while also continuing his work with the UA.
Murphy said although the position will require him to work more, "The opportunity to work with dedicated individuals in an attempt to improve the lives and conditions of others truly provides great returns."
"The extra work yields so much that it is hardly noticed," Murphy said.
"(Murphy) is helping to promote the profession at a time when we desperately need more pharmacists," said Karin Lorentzen, communications coordinator for the College of Pharmacy.
Lyle Bootman, the college's dean, said that because of Arizona's aging population, the demand for pharmacists is high.
"There is … an extreme shortage of pharmacists, especially in a fast-growing state like Arizona," Bootman said.
Murphy said there is a high burden on writing prescriptions, both due to the fact that "baby boomers are reaching the point of high medication use" and that there are a lot of new drugs being discovered and promoted.
Writing prescriptions is not the only concern, however. "There are many opportunities to serve patients better, but we don't have time," Murphy said.
Murphy said he is working to "pursue payment for direct patient care services" not only for dispensing medication but also rendering services like counseling, medication monitoring and preventative care, Murphy said.
He is also working to promote pharmacogenomics, a branch of pharmacology that focuses on prescribing personalized medication, Murphy said. This enables pharmacists to find "who (the medication) works best for" with the fewest adverse effects, he said.
Murphy's election to the ACCP is an "indicator that the college is among the highest ranked in the world," Bootman said. "For the past 20 years, someone (from the College of Pharmacy) has been an officer of a national or international professional health-related association."
Health care is one of the top three priorities of President-elect Barack Obama's administration, and "they will be looking to the John Murphys for guidance," Bootman said.
"(Murphy) is a highly developed problem-solver and innovator," but students are always the first thing on his mind, Bootman said. "He serves as a role model for students" who want to serve their profession by becoming leaders in their profession, he said.
"I think it is invaluable for students to realize that their faculty serves the public, so students learn to serve as well," Murphy said.
As president of the ACCP, Murphy will lead an organization of approximately 10,000 clinical pharmacists while also continuing his work with the UA.
Murphy said although the position will require him to work more, "The opportunity to work with dedicated individuals in an attempt to improve the lives and conditions of others truly provides great returns."
"The extra work yields so much that it is hardly noticed," Murphy said.
"(Murphy) is helping to promote the profession at a time when we desperately need more pharmacists," said Karin Lorentzen, communications coordinator for the College of Pharmacy.
Lyle Bootman, the college's dean, said that because of Arizona's aging population, the demand for pharmacists is high.
"There is … an extreme shortage of pharmacists, especially in a fast-growing state like Arizona," Bootman said.
Murphy said there is a high burden on writing prescriptions, both due to the fact that "baby boomers are reaching the point of high medication use" and that there are a lot of new drugs being discovered and promoted.
Writing prescriptions is not the only concern, however. "There are many opportunities to serve patients better, but we don't have time," Murphy said.
Murphy said he is working to "pursue payment for direct patient care services" not only for dispensing medication but also rendering services like counseling, medication monitoring and preventative care, Murphy said.
He is also working to promote pharmacogenomics, a branch of pharmacology that focuses on prescribing personalized medication, Murphy said. This enables pharmacists to find "who (the medication) works best for" with the fewest adverse effects, he said.
Murphy's election to the ACCP is an "indicator that the college is among the highest ranked in the world," Bootman said. "For the past 20 years, someone (from the College of Pharmacy) has been an officer of a national or international professional health-related association."
Health care is one of the top three priorities of President-elect Barack Obama's administration, and "they will be looking to the John Murphys for guidance," Bootman said.
"(Murphy) is a highly developed problem-solver and innovator," but students are always the first thing on his mind, Bootman said. "He serves as a role model for students" who want to serve their profession by becoming leaders in their profession, he said.
"I think it is invaluable for students to realize that their faculty serves the public, so students learn to serve as well," Murphy said.
Friday, December 5, 2008
Breast Cancer Treatment Offers Better Outcome To Women With Implants
[Source: ScienceDaily] - Women with early-stage breast cancer who have undergone breast augmentation may be treated successfully with a partial-breast radiation treatment called brachytherapy, according to a study presented today at the annual meeting of the Radiological Society of North America (RSNA). Patients treated with brachytherapy have better cosmetic outcomes and avoid the risk of the implant hardening, compared to patients who undergo whole-breast radiation therapy.
"We are seeing an increasing number of breast cancer patients with augmentation," said Robert R. Kuske Jr., M.D., clinical professor at the University of Arizona Health Sciences Center and radiation oncologist at Arizona Oncology Services in Scottsdale, Ariz. "By nature, these women are concerned about their appearance and we need to have options for them."
According to the American Society of Plastic Surgeons, breast augmentation is the most popular cosmetic surgery in the U.S. with 347,500 procedures performed in 2007. This represents an increase of 64 percent since 2000.
Approximately one in eight women who undergo breast augmentation will develop breast cancer at some point in their lives.
The most common breast cancer treatment for patients with breast implants is skin-sparing mastectomy and implant exchange. Whole-breast radiation therapy after lumpectomy is an option, but carries a substantial risk during the healing process of scar tissue wrapping around the implant, causing it to become rock-hard and extremely painful. This condition, known as capsular contracture, also distorts the appearance of the breast.
Dr. Kuske set out to determine if partial-breast radiation with brachytherapy might offer a better outcome for women with implants wishing to avoid mastectomy.
Breast brachytherapy is a radiation treatment that can be given in higher doses to a small, targeted area of the breast after lumpectomy. Radioactive "seeds" are guided into place through small plastic tubes, or catheters, with the aid of imaging and a computer. The seeds emit high doses of radiation in short bursts.
Scar tissue is minimal, the implant remains unaffected and treatment time is shortened from 6 ½ weeks with whole-breast radiation therapy to five days with brachytherapy.
For the study, 65 women who were diagnosed with small, early stage malignant tumors were treated with brachytherapy after a lumpectomy. The women received two doses per day, separated by six hours, over a five-day period. Follow-up was six months to five years. None of the patients experienced tumor recurrence during the follow-up period. Cosmetic outcome was determined to be good to excellent in 100 percent of patients with 95 percent judged excellent. Implant hardening was not observed in any of the patients.
"Compared to traditional treatments, brachytherapy offers an excellent alternative for these women," Dr. Kuske said. "It offers very high rates of tumor control with fewer side effects and is easier on their lifestyle."
"We are seeing an increasing number of breast cancer patients with augmentation," said Robert R. Kuske Jr., M.D., clinical professor at the University of Arizona Health Sciences Center and radiation oncologist at Arizona Oncology Services in Scottsdale, Ariz. "By nature, these women are concerned about their appearance and we need to have options for them."
According to the American Society of Plastic Surgeons, breast augmentation is the most popular cosmetic surgery in the U.S. with 347,500 procedures performed in 2007. This represents an increase of 64 percent since 2000.
Approximately one in eight women who undergo breast augmentation will develop breast cancer at some point in their lives.
The most common breast cancer treatment for patients with breast implants is skin-sparing mastectomy and implant exchange. Whole-breast radiation therapy after lumpectomy is an option, but carries a substantial risk during the healing process of scar tissue wrapping around the implant, causing it to become rock-hard and extremely painful. This condition, known as capsular contracture, also distorts the appearance of the breast.
Dr. Kuske set out to determine if partial-breast radiation with brachytherapy might offer a better outcome for women with implants wishing to avoid mastectomy.
Breast brachytherapy is a radiation treatment that can be given in higher doses to a small, targeted area of the breast after lumpectomy. Radioactive "seeds" are guided into place through small plastic tubes, or catheters, with the aid of imaging and a computer. The seeds emit high doses of radiation in short bursts.
Scar tissue is minimal, the implant remains unaffected and treatment time is shortened from 6 ½ weeks with whole-breast radiation therapy to five days with brachytherapy.
For the study, 65 women who were diagnosed with small, early stage malignant tumors were treated with brachytherapy after a lumpectomy. The women received two doses per day, separated by six hours, over a five-day period. Follow-up was six months to five years. None of the patients experienced tumor recurrence during the follow-up period. Cosmetic outcome was determined to be good to excellent in 100 percent of patients with 95 percent judged excellent. Implant hardening was not observed in any of the patients.
"Compared to traditional treatments, brachytherapy offers an excellent alternative for these women," Dr. Kuske said. "It offers very high rates of tumor control with fewer side effects and is easier on their lifestyle."
Thursday, December 4, 2008
ART OF HEALTHY LIVING: UA staff updates its cancer prevention book; it's on sale
[Source: The Explorer News] - Faculty of the nationally renowned Cancer Prevention and Control Program at the Arizona Cancer Center have updated their collaborative work, “Fundamentals of Cancer Prevention.” The second edition of the work was published in October.
The book delivers “leading-edge information for primary physicians and health care providers in an effort to continually stress the importance of cancer prevention and the latest early-detection strategies,” a release said.
The book was edited by Arizona Cancer Center Director David S. Alberts, M.D., and Lisa M. Hess, PhD., a former scientific investigator for the Arizona Cancer Center.
“A famous 17th century physician, Dr. Thomas Adams, once said, ‘Prevention is better than treatment, because it saves the labor of being sick,’” said Dr. Alberts. “We continue to be convinced that the war on cancer can be won. That effort starts with educating primary care physicians and caregivers.”
Contributing Arizona Cancer Center authors include Frederick Ahmann, David Alberts, Setsuko Chambers, Zhao Chen, Kathryn Coe, Stephen Joel Coons, Francisco Garcia, Linda Garland, Eugene Gerner, Iman Hakim, Karen Taraszka Hastings, Ayaaz Ismail, Myron Jacobson, Lindsay Kreykes, Robert Krouse, Peter Lance, Linda Larkey, Maria Lluria-Prevatt, Ana María López, Naja McKenzie, Jessica Ray, Alison Stopeck, Cynthia Thomson, Patricia Thompson, G.T. Wondrak.
Fundamentals of Cancer Prevention is available for purchase online at www.springer.com.
The Arizona Cancer Center is a National Cancer Institute-designated comprehensive cancer center. With primary locations at the University of Arizona in Tucson and in Scottsdale, the center has more than a dozen research and education offices throughout the state and 300 physician and scientist members working to prevent and cure cancer. For more information, go to www.azcc.arizona.edu.
The book delivers “leading-edge information for primary physicians and health care providers in an effort to continually stress the importance of cancer prevention and the latest early-detection strategies,” a release said.
The book was edited by Arizona Cancer Center Director David S. Alberts, M.D., and Lisa M. Hess, PhD., a former scientific investigator for the Arizona Cancer Center.
“A famous 17th century physician, Dr. Thomas Adams, once said, ‘Prevention is better than treatment, because it saves the labor of being sick,’” said Dr. Alberts. “We continue to be convinced that the war on cancer can be won. That effort starts with educating primary care physicians and caregivers.”
Contributing Arizona Cancer Center authors include Frederick Ahmann, David Alberts, Setsuko Chambers, Zhao Chen, Kathryn Coe, Stephen Joel Coons, Francisco Garcia, Linda Garland, Eugene Gerner, Iman Hakim, Karen Taraszka Hastings, Ayaaz Ismail, Myron Jacobson, Lindsay Kreykes, Robert Krouse, Peter Lance, Linda Larkey, Maria Lluria-Prevatt, Ana María López, Naja McKenzie, Jessica Ray, Alison Stopeck, Cynthia Thomson, Patricia Thompson, G.T. Wondrak.
Fundamentals of Cancer Prevention is available for purchase online at www.springer.com.
The Arizona Cancer Center is a National Cancer Institute-designated comprehensive cancer center. With primary locations at the University of Arizona in Tucson and in Scottsdale, the center has more than a dozen research and education offices throughout the state and 300 physician and scientist members working to prevent and cure cancer. For more information, go to www.azcc.arizona.edu.
Desert plant's properties eyed for Canadian oilseed
[Source: Manitoba Cooperation] - Properties of a "cactus-like" plant from Arizona might have a future in Canada in an oilseed crop for the industrial lubricant market.
Randall Weselake, a professor at the University of Alberta's department of agricultural, food and nutritional science, has lined up $360,000 for a research team to experiment with seeds from the plant, called lesquerella.
Lesquerella naturally produces high levels of certain fatty acids that are "particularly suited" to production of lubricants and other industrial oils, the university said in a release Friday.
Weselake's team aims to transfer that particular trait into a "canola-like" oilseed plant grown in Canada, the end goal being to produce a "fine liquid wax with superior industrial properties."
If such research pans out, it could "substantially increase the industrial uses of plant oils and serve as a high-performance lubricant," Weselake said in the release Friday.
The canola-like plant in this case would be Brassica carinata, which would be genetically modified using an enzyme from lesquerella, to help convert the plant oils into a liquid wax that's more resistant to high temperatures and pressures than unmodified plant oils, the university said.
Potential applications include automobile transmission fluid, hydraulic fluids, adhesives and numerous industrial lubricants, the university added.
"The overall goal is to decrease reliance on fossil oils currently used in the global chemicals industry," Chris Kazala, manager of the university's BioActive Oils program and a research team member, said in the same release.
"Using plants to produce these products provides a secure, environmentally sustainable supply of these materials for industry and is, in many cases, easier to manufacture."
The funding for the U of A project comes from Avac Ltd., the Calgary-based venture capital fund launched in 1997 by the province with added start-up money from the federal government, to expand value-added industry in Alberta with a focus on the "agrivalue" sector.
The U of A noted this research is part of the ICON Project, a four-year worldwide collaboration involving 23 partners from 11 countries and sponsored by the European Union.
Several U.S. research projects have recently focused on bringing lesquerella itself directly into crop production, for its seed oil's use in industrial oils and biodiesel additives.
Randall Weselake, a professor at the University of Alberta's department of agricultural, food and nutritional science, has lined up $360,000 for a research team to experiment with seeds from the plant, called lesquerella.
Lesquerella naturally produces high levels of certain fatty acids that are "particularly suited" to production of lubricants and other industrial oils, the university said in a release Friday.
Weselake's team aims to transfer that particular trait into a "canola-like" oilseed plant grown in Canada, the end goal being to produce a "fine liquid wax with superior industrial properties."
If such research pans out, it could "substantially increase the industrial uses of plant oils and serve as a high-performance lubricant," Weselake said in the release Friday.
The canola-like plant in this case would be Brassica carinata, which would be genetically modified using an enzyme from lesquerella, to help convert the plant oils into a liquid wax that's more resistant to high temperatures and pressures than unmodified plant oils, the university said.
Potential applications include automobile transmission fluid, hydraulic fluids, adhesives and numerous industrial lubricants, the university added.
"The overall goal is to decrease reliance on fossil oils currently used in the global chemicals industry," Chris Kazala, manager of the university's BioActive Oils program and a research team member, said in the same release.
"Using plants to produce these products provides a secure, environmentally sustainable supply of these materials for industry and is, in many cases, easier to manufacture."
The funding for the U of A project comes from Avac Ltd., the Calgary-based venture capital fund launched in 1997 by the province with added start-up money from the federal government, to expand value-added industry in Alberta with a focus on the "agrivalue" sector.
The U of A noted this research is part of the ICON Project, a four-year worldwide collaboration involving 23 partners from 11 countries and sponsored by the European Union.
Several U.S. research projects have recently focused on bringing lesquerella itself directly into crop production, for its seed oil's use in industrial oils and biodiesel additives.
Arizona Biotechs Won’t Escape Pain in Economic Upheaval, Communications Consultant Says
[Source: Bioregion News] - The economic upheaval will hurt the prospects of Arizona life sciences companies seeking capital for growth, a marketing and communications consultant to life-sci and other tech companies has told the Arizona Daily Star.
“I wish I could say otherwise, but the current economic situation is going to hurt biotechnology and all emerging tech sectors — and now even green/clean tech will probably take a hit, too. Everybody is holding onto their cash,” Sandra Kay Helsel, founder and managing director of SK Helsel & Associates, told the newspaper.
“The emerging technology sectors such as biotechnology are the very businesses that will eventually bring us out of this collapse. Innovation and emerging tech are the drivers of the future,” added Helsel, whose firm has offices in Tucson, Ariz., and San Diego. “The downward spiral of the economy may slow things down a bit, but the strengths of Tucson and the greater Arizona biotech cluster are evident.”
Tucson’s strengths, Helsel said, include research activity at the University of Arizona, cohesion among life-sci and civic leaders, and the region’s quality of life. But the region lacks a regional focus on how to compete against aggressive biotech clusters elsewhere, she added.
“I wish I could say otherwise, but the current economic situation is going to hurt biotechnology and all emerging tech sectors — and now even green/clean tech will probably take a hit, too. Everybody is holding onto their cash,” Sandra Kay Helsel, founder and managing director of SK Helsel & Associates, told the newspaper.
“The emerging technology sectors such as biotechnology are the very businesses that will eventually bring us out of this collapse. Innovation and emerging tech are the drivers of the future,” added Helsel, whose firm has offices in Tucson, Ariz., and San Diego. “The downward spiral of the economy may slow things down a bit, but the strengths of Tucson and the greater Arizona biotech cluster are evident.”
Tucson’s strengths, Helsel said, include research activity at the University of Arizona, cohesion among life-sci and civic leaders, and the region’s quality of life. But the region lacks a regional focus on how to compete against aggressive biotech clusters elsewhere, she added.
UA president: Job cuts likely permanent
[Source: The Associated Press] - Until now, University of Arizona officials have tried to downplay the possibility of long-term layoffs.
But this week, University President Robert N. Shelton and Provost Meredith Hay sent out a strongly worded e-mail warning of permanent cuts to the school's budget that will lead to job losses on campus.
Shelton wrote that to address the long-term budget challenge at the university, there will need to be permanent reductions through the elimination and merger of programs.
That process will necessitate job losses on campus.
Shelton says "there is no way to meet our long-term, permanent budget needs without them."
But this week, University President Robert N. Shelton and Provost Meredith Hay sent out a strongly worded e-mail warning of permanent cuts to the school's budget that will lead to job losses on campus.
Shelton wrote that to address the long-term budget challenge at the university, there will need to be permanent reductions through the elimination and merger of programs.
That process will necessitate job losses on campus.
Shelton says "there is no way to meet our long-term, permanent budget needs without them."
Napolitano exit worries biotech, climate-change, education boosters
[Source: The Arizona Republic] - Gov. Janet Napolitano's selection for a job in Washington, D.C., may be secure, but her vision of a research-based economy in Arizona is no sure thing.
Napolitano has been a key figure in the state's push to foster the biosciences since she became governor in 2003. She played a critical role in securing funding for the Translational Genomics Research Institute (TGen) and establishing Science Foundation Arizona.
But if she takes over the reins of the Homeland Security Department in Barack Obama's administration, she will leave Arizona as the state faces a $1.2 billion budget shortfall this year and the Legislature is poised to make sharp cuts.
Fiscal conservatives may see biotechnology programs as a ripe target, which is making many bioscience and research boosters nervous. They insist that cutting research programs now would be a mistake.
"If this economic downturn does anything, it shows we must diversify our economy," said John Murphy, president and chief executive officer of the Flinn Foundation in Phoenix. "The investments that have been made should be sustained."
The state's push to grow a bioscience economy has been ambitious.
Arizona and Phoenix combined have committed more than $1 billion to bioscience and research initiatives this decade.
A large chunk has paid for new research labs such as the TGen building in downtown Phoenix, the Biodesign Institute at Arizona State University in Tempe and Bio5 Institute at the University of Arizona. The Legislature this year also approved a stimulus package that would provide $470 million to expand the campus of the UA College of Medicine, in partnership with ASU, in downtown Phoenix.
Science Foundation Arizona secured a $25 million annual commitment over five years from the state Legislature provided that it raises an equal amount from private donors.
The funding commitment is subject to review each year, and groups such as the Arizona Federation of Taxpayers have targeted the foundation for cuts in past years.
The nonprofit foundation uses the state money to fund grants for everything from science education in high school to new research projects that cement ties between university researchers and large corporations in Arizona.
William Harris, the foundation's chief executive officer, said the group already has secured its matching private funds for 2009 from a large base of donors. Harris realizes that Napolitano has been the foundation's prime backer, but he also has high hopes that successor Jan Brewer, a fiscal conservative, will support the foundation's goals of strengthening the state's economy through targeted investments in science and research.
"We have to control our own destiny and get out of this ditch we're in," said Harris, who modeled the foundation after a similar group he led in Ireland. "We do that by diversifying our economy and strengthening our education in Arizona."
Climate change
Napolitano's departure could also portend a major shift in policy for one of her biggest local priorities: climate change.
Environmental groups, elected officials and other political watchers say that a new Republican administration would likely significantly reduce Arizona's involvement in the Western Climate Initiative.
Napolitano was a founding member of the regional effort, which brings several Western states and a handful of Canadian provinces together to limit and reduce man-made greenhouse gases, among other things.
"As far as what I know about Jan Brewer, I would say she is probably not going to go along with (the WCI)," said Republican Rep. Ray Barnes, who serves as chairman of the House Environment Committee, adding that other priorities, such as dealing with the state's billion-dollar budget deficit, would likely be higher on the new governor's to-do list.
Education
Educators agree that Napolitano's most substantial contributions were providing free full-day kindergarten, allocating new money to rebuild dilapidated buildings on state university campuses and preventing cuts to existing education budgets.
With Napolitano's expected departure, some education leaders worry about keeping the gains made under her leadership, but many expect Brewer to be a similar, practical politician. Brewer has not been willing to talk about her role as governor or her education agenda.
"I'm sure Miss Brewer will have the best interests of the state at heart and a good agenda at all levels," said Fred Boice, president of the Arizona State Board of Regents, which oversees the state's three universities.
Napolitano has been a key figure in the state's push to foster the biosciences since she became governor in 2003. She played a critical role in securing funding for the Translational Genomics Research Institute (TGen) and establishing Science Foundation Arizona.
But if she takes over the reins of the Homeland Security Department in Barack Obama's administration, she will leave Arizona as the state faces a $1.2 billion budget shortfall this year and the Legislature is poised to make sharp cuts.
Fiscal conservatives may see biotechnology programs as a ripe target, which is making many bioscience and research boosters nervous. They insist that cutting research programs now would be a mistake.
"If this economic downturn does anything, it shows we must diversify our economy," said John Murphy, president and chief executive officer of the Flinn Foundation in Phoenix. "The investments that have been made should be sustained."
The state's push to grow a bioscience economy has been ambitious.
Arizona and Phoenix combined have committed more than $1 billion to bioscience and research initiatives this decade.
A large chunk has paid for new research labs such as the TGen building in downtown Phoenix, the Biodesign Institute at Arizona State University in Tempe and Bio5 Institute at the University of Arizona. The Legislature this year also approved a stimulus package that would provide $470 million to expand the campus of the UA College of Medicine, in partnership with ASU, in downtown Phoenix.
Science Foundation Arizona secured a $25 million annual commitment over five years from the state Legislature provided that it raises an equal amount from private donors.
The funding commitment is subject to review each year, and groups such as the Arizona Federation of Taxpayers have targeted the foundation for cuts in past years.
The nonprofit foundation uses the state money to fund grants for everything from science education in high school to new research projects that cement ties between university researchers and large corporations in Arizona.
William Harris, the foundation's chief executive officer, said the group already has secured its matching private funds for 2009 from a large base of donors. Harris realizes that Napolitano has been the foundation's prime backer, but he also has high hopes that successor Jan Brewer, a fiscal conservative, will support the foundation's goals of strengthening the state's economy through targeted investments in science and research.
"We have to control our own destiny and get out of this ditch we're in," said Harris, who modeled the foundation after a similar group he led in Ireland. "We do that by diversifying our economy and strengthening our education in Arizona."
Climate change
Napolitano's departure could also portend a major shift in policy for one of her biggest local priorities: climate change.
Environmental groups, elected officials and other political watchers say that a new Republican administration would likely significantly reduce Arizona's involvement in the Western Climate Initiative.
Napolitano was a founding member of the regional effort, which brings several Western states and a handful of Canadian provinces together to limit and reduce man-made greenhouse gases, among other things.
"As far as what I know about Jan Brewer, I would say she is probably not going to go along with (the WCI)," said Republican Rep. Ray Barnes, who serves as chairman of the House Environment Committee, adding that other priorities, such as dealing with the state's billion-dollar budget deficit, would likely be higher on the new governor's to-do list.
Education
Educators agree that Napolitano's most substantial contributions were providing free full-day kindergarten, allocating new money to rebuild dilapidated buildings on state university campuses and preventing cuts to existing education budgets.
With Napolitano's expected departure, some education leaders worry about keeping the gains made under her leadership, but many expect Brewer to be a similar, practical politician. Brewer has not been willing to talk about her role as governor or her education agenda.
"I'm sure Miss Brewer will have the best interests of the state at heart and a good agenda at all levels," said Fred Boice, president of the Arizona State Board of Regents, which oversees the state's three universities.
Keeping Chromosomes From Cuddling Up
[Source: Mari N. Jensen, UA College of Science] - If chromosomes snuggle up too closely at the wrong times, the results can be genetic disaster.
Now University of Arizona researchers have found the molecular machines in fruit flies that yank chromosomes, the DNA-carrying structures, apart when necessary.
The machines, proteins called condensin II, separate chromosomes by twisting them into supercoils that kink up and therefore can no longer touch.
Scientists had known of condensin II but did not know how it functioned inside cells.
Keeping specific parts of chromosomes from touching can change how the instructions carried in the DNA are read, said BIO5 member Giovanni Bosco, a UA assistant professor of molecular and cellular biology.
"It's like picking up your favorite book and, depending on what chair you chose to sit in, it turned into a different story -- even though the printed words in the book never changed," research team leader Bosco wrote in an e-mail.
"This now changes the way we think about genetic information. Taking a literal reading of it is not what actually happens," he wrote. "Instead, context matters."
The team also found that condensin II plays a key role in making sure that fruit fly sperm cells each receive the proper number of chromosomes -- not too many, not too few.
Bosco suspects that condensin II plays the same role in the formation of human sperm and eggs.
Having too many or too few chromosomes in egg or sperm cells is the source of several important genetic disorders, including Down syndrome.
Abnormalities in chromosome number is also the cause of some miscarriages of early-term fetuses in humans.
The research is published in two separate papers. "Chromosome Alignment and Transvection are Antagonized by Condensin II," by Tom A. Hartl and Helen F. Smith, UA doctoral students, and Bosco is in the Nov. 28 issue of the journal Science.
Hartl, Sarah J. Sweeney, Peter J. Knepler and Bosco published their paper, "Condensin II Resolves Chromosomal Associations to Enable Anaphase I Segregation in Drosophila Male Meiosis," in the October 2008 issue of PLoS Genetics. Sweeney and Knepler, now doing research at UA, were UA undergraduates when they conducted the research.
The National Institutes of Health and the National Science Foundation funded the research.
Learning how cells control chromosomes and how DNA is transcribed will lead to better understanding of how an organism's DNA affects the organism's final form.
Scientists have known for about 50 years that when chromosomes are in direct contact, the transcription machinery can choose to transcribe either the gene from the mother or the gene from the father.
Many researchers investigated how the specific genes were brought close together so that process, known as transvection, could happen.
Bosco wondered, what if the chromosomes stayed stuck together?
To find something that separated chromosomes, he looked for female fruit flies that were sterile because chromosomes in their eggs had stuck together.
Once he had those fruit flies, Hartl isolated the gene that kept the chromosomes from coming apart. He found that the gene coded for condensin II, indicating that the sterile flies couldn't make condensin II.
To be able to watch how condensin II affects chromosomes, the researchers used the salivary glands from normal Drosophila melanogaster fruit flies. Fruit fly salivary glands are unusual, because they have many copies of the same chromosome coiled together like a rope.
Hartl said, "You can actually see chromosomes, because the cells are so huge and the chromosomes are so huge."
The team inserted an additional gene into the chromosomes that would turn the condensin II-producing gene off at 77 F (21 C) and on at 95 F (35 C). The researchers also marked one gene on the chromosomes with green fluorescent protein, or GFP, to be able to see changes in the chromosomes' positions.
The scientists then looked at the salivary glands at the two temperatures to see what happened when condensin II was present and when it was absent.
Bosco said, "Simply turning the condensin gene on or off, we could watch the chromosomes move right before our eyes, demonstrating that condensin was mostly likely the tiny machine that was ripping the chromosomes apart."
He said these findings are significant because more and more genetic tests to sequence people's DNA are becoming available, but the DNA sequence alone does not completely determine what diseases the person will have.
Even if it's in the genes, it might not show, he said. "It's what your cells are doing with your genes that's important."
To pull the chromosomes apart, condensin II changes its shape. Smith said the team's next step is figuring out how condensin II proteins are recruited to the chromosomes and how the condensin II proteins use the cellular energy packets known as ATP to change shape.
Now University of Arizona researchers have found the molecular machines in fruit flies that yank chromosomes, the DNA-carrying structures, apart when necessary.
The machines, proteins called condensin II, separate chromosomes by twisting them into supercoils that kink up and therefore can no longer touch.
Scientists had known of condensin II but did not know how it functioned inside cells.
Keeping specific parts of chromosomes from touching can change how the instructions carried in the DNA are read, said BIO5 member Giovanni Bosco, a UA assistant professor of molecular and cellular biology.
"It's like picking up your favorite book and, depending on what chair you chose to sit in, it turned into a different story -- even though the printed words in the book never changed," research team leader Bosco wrote in an e-mail.
"This now changes the way we think about genetic information. Taking a literal reading of it is not what actually happens," he wrote. "Instead, context matters."
The team also found that condensin II plays a key role in making sure that fruit fly sperm cells each receive the proper number of chromosomes -- not too many, not too few.
Bosco suspects that condensin II plays the same role in the formation of human sperm and eggs.
Having too many or too few chromosomes in egg or sperm cells is the source of several important genetic disorders, including Down syndrome.
Abnormalities in chromosome number is also the cause of some miscarriages of early-term fetuses in humans.
The research is published in two separate papers. "Chromosome Alignment and Transvection are Antagonized by Condensin II," by Tom A. Hartl and Helen F. Smith, UA doctoral students, and Bosco is in the Nov. 28 issue of the journal Science.
Hartl, Sarah J. Sweeney, Peter J. Knepler and Bosco published their paper, "Condensin II Resolves Chromosomal Associations to Enable Anaphase I Segregation in Drosophila Male Meiosis," in the October 2008 issue of PLoS Genetics. Sweeney and Knepler, now doing research at UA, were UA undergraduates when they conducted the research.
The National Institutes of Health and the National Science Foundation funded the research.
Learning how cells control chromosomes and how DNA is transcribed will lead to better understanding of how an organism's DNA affects the organism's final form.
Scientists have known for about 50 years that when chromosomes are in direct contact, the transcription machinery can choose to transcribe either the gene from the mother or the gene from the father.
Many researchers investigated how the specific genes were brought close together so that process, known as transvection, could happen.
Bosco wondered, what if the chromosomes stayed stuck together?
To find something that separated chromosomes, he looked for female fruit flies that were sterile because chromosomes in their eggs had stuck together.
Once he had those fruit flies, Hartl isolated the gene that kept the chromosomes from coming apart. He found that the gene coded for condensin II, indicating that the sterile flies couldn't make condensin II.
To be able to watch how condensin II affects chromosomes, the researchers used the salivary glands from normal Drosophila melanogaster fruit flies. Fruit fly salivary glands are unusual, because they have many copies of the same chromosome coiled together like a rope.
Hartl said, "You can actually see chromosomes, because the cells are so huge and the chromosomes are so huge."
The team inserted an additional gene into the chromosomes that would turn the condensin II-producing gene off at 77 F (21 C) and on at 95 F (35 C). The researchers also marked one gene on the chromosomes with green fluorescent protein, or GFP, to be able to see changes in the chromosomes' positions.
The scientists then looked at the salivary glands at the two temperatures to see what happened when condensin II was present and when it was absent.
Bosco said, "Simply turning the condensin gene on or off, we could watch the chromosomes move right before our eyes, demonstrating that condensin was mostly likely the tiny machine that was ripping the chromosomes apart."
He said these findings are significant because more and more genetic tests to sequence people's DNA are becoming available, but the DNA sequence alone does not completely determine what diseases the person will have.
Even if it's in the genes, it might not show, he said. "It's what your cells are doing with your genes that's important."
To pull the chromosomes apart, condensin II changes its shape. Smith said the team's next step is figuring out how condensin II proteins are recruited to the chromosomes and how the condensin II proteins use the cellular energy packets known as ATP to change shape.
Tuesday, November 25, 2008
Gasping Helps Cardiac Arrest Victims Survive, New Research Shows
[Source: ScienceDaily ] - People who witness an individual collapse suddenly and unexpectedly should perform uninterrupted chest compressions even if the patient gasps or breathes in a funny way, research from the Resuscitation Research Group at The University of Arizona Sarver Heart Center shows.
When an individual breathes abnormally or gasps after collapsing from sudden cardiac arrest there is a greater chance of surviving, the researchers report. Gasping can be thought of as a survival reflex triggered by the brain.
Each day, about 500 Americans collapse because their hearts suddenly stop beating. Data collected by Sarver Heart Center researchers show that in more than half of witnessed cardiac arrest cases, the patient gasped.
"Gasping is an indication that the brain is still alive, and it tells you that if you start and continue uninterrupted chest compressions, the person has a high chance of surviving," said Gordon A. Ewy, MD, corresponding author of the study, professor and chief of cardiology at the UA and director of its Sarver Heart Center. "We need people to promptly recognize sudden cardiac arrest, to call 9-1-1 and to start chest compressions right away."
Gasping has been described as snoring, gurgling, moaning, snorting or agonal or labored breathing. However, bystanders often misinterpret gasping and other unusual vocal sounds as normal breathing and don't call 9-1-1 or begin lifesaving chest compressions quickly enough, Dr. Ewy said.
The authors hope their findings lead to greater willingness of untrained bystanders to jump in and perform continuous chest compressions. Bystander-initiated CPR has been shown to be a cardiac arrest victim's only chance of survival until an automated external defibrillator or the paramedics get to the scene.
Many bystanders are hesitant to perform mouth-to-mouth ventilation, and in a case of a witnessed (seen or heard) collapse, so-called rescue breathing is not necessary and may be harmful, Dr. Ewy said. "When the patient gasps, there is a negative pressure in the chest, which not only sucks air into the lungs but also draws blood back to the heart. In contrast, mouth-to-mouth breathing creates overpressure in the chest and actually inhibits blood flow back to the heart. Gasping during cardiac arrest is much better than mouth-to-mouth breathing."
But what about choking? "That's very different," Dr. Ewy said. "Someone who is choking will be seen to grasp their throat and struggle to breathe, which means they're responsive. These individuals need the Heimlich maneuver." A primary cardiac arrest is the witnessed unexpected collapse of an individual who is not responsive, Dr. Ewy said. "Cardiac arrest will cause the stricken individual to pass out and collapse to the ground within seconds."
The Arizona researchers examined data from two sources. Transcripts from the Phoenix Fire Department Regional Dispatch Center included information on gasping in patients found by bystanders, whether their collapse was witnessed or not. The department's first-care reports on 1,218 witnessed patients provided the incidence of gasping upon or after the arrival of emergency medical service (EMS) personnel. Among the 481 patients who received bystander CPR, 39 percent of gaspers survived, but only 9.4 percent of those who didn't gasp survived.
Performing uninterrupted chest compressions (a technique developed at the UA Sarver Heart Center and endorsed by the American Heart Association as "Hands-Only CPR" for lay individuals) may cause a person who has stopped gasping to resume gasping. "This scares many people and they stop pressing on the chest," Dr. Ewy said, "This is bad because gasping is an indication that you're doing a good job."
The study is set to publish in the Nov. 24 online issue of Circulation, the official journal of the American Heart Association.
The authors of the study are: Bentley J. Bobrow, MD; Mathias Zuercher, MD; Gordon A. Ewy, MD; Lani Clark, BS; Vatsal Chikani, MPH,; Dan Donahue BS, NREMT-P, Arthur B. Sanders, MD; Ronald W. Hilwig, DVM; Robert A. Berg, MD; and Karl B. Kern, MD.
Experts continue to promote a combination of rescue breathing and chest compressions for victims of cardiac arrest due to non-cardiac causes, like near drowning or electrocution, and all victims of pediatric cardiac arrest.
The study was funded in part by a grant from the Arizona Department of Health Services Bureau of Emergency Medical Services.
When an individual breathes abnormally or gasps after collapsing from sudden cardiac arrest there is a greater chance of surviving, the researchers report. Gasping can be thought of as a survival reflex triggered by the brain.
Each day, about 500 Americans collapse because their hearts suddenly stop beating. Data collected by Sarver Heart Center researchers show that in more than half of witnessed cardiac arrest cases, the patient gasped.
"Gasping is an indication that the brain is still alive, and it tells you that if you start and continue uninterrupted chest compressions, the person has a high chance of surviving," said Gordon A. Ewy, MD, corresponding author of the study, professor and chief of cardiology at the UA and director of its Sarver Heart Center. "We need people to promptly recognize sudden cardiac arrest, to call 9-1-1 and to start chest compressions right away."
Gasping has been described as snoring, gurgling, moaning, snorting or agonal or labored breathing. However, bystanders often misinterpret gasping and other unusual vocal sounds as normal breathing and don't call 9-1-1 or begin lifesaving chest compressions quickly enough, Dr. Ewy said.
The authors hope their findings lead to greater willingness of untrained bystanders to jump in and perform continuous chest compressions. Bystander-initiated CPR has been shown to be a cardiac arrest victim's only chance of survival until an automated external defibrillator or the paramedics get to the scene.
Many bystanders are hesitant to perform mouth-to-mouth ventilation, and in a case of a witnessed (seen or heard) collapse, so-called rescue breathing is not necessary and may be harmful, Dr. Ewy said. "When the patient gasps, there is a negative pressure in the chest, which not only sucks air into the lungs but also draws blood back to the heart. In contrast, mouth-to-mouth breathing creates overpressure in the chest and actually inhibits blood flow back to the heart. Gasping during cardiac arrest is much better than mouth-to-mouth breathing."
But what about choking? "That's very different," Dr. Ewy said. "Someone who is choking will be seen to grasp their throat and struggle to breathe, which means they're responsive. These individuals need the Heimlich maneuver." A primary cardiac arrest is the witnessed unexpected collapse of an individual who is not responsive, Dr. Ewy said. "Cardiac arrest will cause the stricken individual to pass out and collapse to the ground within seconds."
The Arizona researchers examined data from two sources. Transcripts from the Phoenix Fire Department Regional Dispatch Center included information on gasping in patients found by bystanders, whether their collapse was witnessed or not. The department's first-care reports on 1,218 witnessed patients provided the incidence of gasping upon or after the arrival of emergency medical service (EMS) personnel. Among the 481 patients who received bystander CPR, 39 percent of gaspers survived, but only 9.4 percent of those who didn't gasp survived.
Performing uninterrupted chest compressions (a technique developed at the UA Sarver Heart Center and endorsed by the American Heart Association as "Hands-Only CPR" for lay individuals) may cause a person who has stopped gasping to resume gasping. "This scares many people and they stop pressing on the chest," Dr. Ewy said, "This is bad because gasping is an indication that you're doing a good job."
The study is set to publish in the Nov. 24 online issue of Circulation, the official journal of the American Heart Association.
The authors of the study are: Bentley J. Bobrow, MD; Mathias Zuercher, MD; Gordon A. Ewy, MD; Lani Clark, BS; Vatsal Chikani, MPH,; Dan Donahue BS, NREMT-P, Arthur B. Sanders, MD; Ronald W. Hilwig, DVM; Robert A. Berg, MD; and Karl B. Kern, MD.
Experts continue to promote a combination of rescue breathing and chest compressions for victims of cardiac arrest due to non-cardiac causes, like near drowning or electrocution, and all victims of pediatric cardiac arrest.
The study was funded in part by a grant from the Arizona Department of Health Services Bureau of Emergency Medical Services.
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