Fred Hutchinson Science and General News Releases

First report of using radiolabeled antibodies and stem cell transplantation to successfully treat advanced leukemia

November 05, 2009

SEATTLE Nov. 5, 2009 For the first time, researchers at Fred Hutchinson Cancer Research Center have reported the use of a radiolabeled antibody to deliver targeted doses of radiation, followed by a stem cell transplant, to successfully treat a group of leukemia and pre-leukemia patients for whom there previously had been no other curative treatment options.

All fifty-eight patients, with a median age of 63 and all with advanced acute myeloid leukemia or high-risk myelodysplastic syndrome - a pre-leukemic condition - saw their blood cancers go into remission using a novel combination of low-intensity chemotherapy, targeted radiation delivery by an antibody and a stem-cell transplant. Forty percent of the patients were alive a year after treatment and approximately 35 percent had survived three years, about the same rates as patients who received similar treatment but whose disease was already in remission and who had much more favorable risk for relapse when therapy began.

Results of the research appear online in the journal Blood. The principal investigator and corresponding author of the paper is John Pagel, M.D., Ph.D, a transplant oncologist and assistant member of the Hutchinson Center's Clinical Research Division.

The purpose of the study was to find the maximum dose of radiation that patients could tolerate with acceptable toxic side effects, not to assess how effective the novel treatment was, according to Pagel and colleagues. However, "the results appear to be very encouraging and warrant us to study it further for patients who really have no significant other curative options," Pagel said.

Older (over age 50) patients with active, advanced leukemia and myelodysplastic syndrome pose the most difficult treatment challenges because standard transplant therapy rarely works, according to Pagel. Both standard and low-dose therapies (a process sometimes known as a "mini transplant" and pioneered at the Hutchinson Center) used to kill leukemia cells in the bloodstream in preparation for a transplant usually require that patients be in remission.

The patients in this study, who came from all over the world to participate in the Phase 1 clinical trial, were in large part those with active relapsed disease that in many cases had failed to respond to standard therapies. Eighty-six percent of the 58 patients had active disease and only 10 percent were in remission when therapy was begun. Their cancers had failed previous treatment attempts. "These were people who had extremely advanced high-risk disease, they were typically older - most of them were in their 60s and some were in their 70s - and had few or no other options for a potential cure. In fact most, if not all, would not been offered a stem cell transplant here or elsewhere. It is fair to say that these patients would likely have died without a transplant being performed if they had not been given the opportunity to participate in this study."

To find the optimal dose of radiation, researchers began at 12 Gy (Gray, a unit of measurement of absorbed radiation dose) and escalated the dosages in increments of 2 Gy up to a Gy of 26. At that dose, some toxicity to the heart and lungs was found so they concluded 24 Gy to be the maximum effective dosage. The 21 patients who received the maximum radiation dose have survived the longest, researchers reported.

The key to success in this study was use of a radiolabeled antibody that has therapeutic iodine 131 attached and is designed to target leukemic bloods cells that carry a marker on the surface of the cell known as CD45. Its use in delivering targeted amounts of radiation was developed several years ago at the Hutchinson Center. Delivered intravenously, the radiation looks for the CD45 antigen receptor on the surface of blood cells. This approach results in a two- to four-fold increase in the amount of radiation that reaches cancerous cells as compared to standard external beam radiation, which also radiates normal surrounding organs and tissue. The more radiation that can be applied, the more cancer cells will be killed in preparation for donor stem cells to take over the diseased immune system and kill off the remaining cancer cells.

Pagel said further research is needed to test more patients at the highest radiation dose both at the Hutchinson Center and at other transplant centers around the country.

Joining Pagel in the study were colleagues from the Hutchinson Center, the Pacific Northwest Laboratory and the departments of Medicine, Pediatrics and Nuclear Medicine at the University of Washington School of Medicine.

Grants from the National Institutes of Health, the Leukemia and Lymphoma Society of America, the Damon Runyon Cancer Research Foundation, the Edson Foundation and the Frederick Kullman Memorial Fund supported this research.

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At Fred Hutchinson Cancer Research Center, our interdisciplinary teams of world-renowned scientists and humanitarians work together to prevent, diagnose and treat cancer, HIV/AIDS and other diseases. Our researchers, including three Nobel laureates, bring a relentless pursuit and passion for health, knowledge and hope to their work and to the world. For more information, please visit fhcrc.org.

CONTACT
Dean Forbes
206-667-2896
dforbes@fhcrc.org

Hutchinson Center researcher secures $7.9 million NCI grant for esophageal cancer research

October 30, 2009

SEATTLE Oct. 30, 2009 Thomas Vaughan, M.D., head of the Epidemiology Program in the Public Health Sciences Division of Fred Hutchinson Cancer Research Center, has received a three-year, $7.9 million grant from the National Cancer Institute to study genetic susceptibility for Barrett’s esophagus and esophageal adenocarcinoma, a rapidly fatal cancer whose incidence has increased more than 500 percent in the past 30 years, faster than any other cancer in the United States.

Vaughan and David Whiteman, Ph.D., a senior research fellow at Queensland Institute of Medical Research in Brisbane, Australia, will execute a large-scale genome-wide association study using pooled data and DNA from 18 epidemiological studies of more than 7,000 individuals making up the Barrett’s and Esophageal Adenocarcinoma Consortium to determine how genetic factors interplay with key environmental and personal risk factors for these conditions, including obesity, heartburn and smoking.

"The results will aid us in identifying the biological pathways that contribute to this cancer," Vaughan said. "The information also will help direct our screening, prevention and surveillance efforts to those at highest risk."

The Hutchinson Center's Genomics Resource will do the genotyping for the study, their largest project to date. Bruce Weir, Ph.D., professor and chairman of the Department of Biostatistics at the University of Washington School of Public Health will lead the statistical analysis team.

Genome-wide association studies involve a scan of hundreds of thousands of genetic markers across the genome in large numbers of individuals to find genetic variations associated with a particular disease. Early genome-wide scans have demonstrated considerable success in identifying genetic variants associated with common diseases.

MEDIA CONTACT:
Kristen Woodward
Fred Hutchinson Cancer Research Center
(206) 667-5095
kwoodwar@fhcrc.org

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Fred Hutchinson Cancer Research Center
At Fred Hutchinson Cancer Research Center, our interdisciplinary teams of world-renowned scientists and humanitarians work together to prevent, diagnose and treat cancer, HIV/AIDS and other diseases. Our researchers, including three Nobel laureates, bring a relentless pursuit and passion for health, knowledge and hope to their work and to the world. For more information, please visit www.fhcrc.org.

Cancer treatment guidelines for diverse Asian economies use model developed at Fred Hutchinson Cancer Research Center

October 30, 2009

SEATTLE Oct. 30, 2009 When the prestigious British medical journal The Lancet Oncology this week published six cancer treatment guideline papers aimed at the resource-diverse nations of Asia, it used as its model the economic template developed by the Breast Health Global Initiative (BHGI) based at Fred Hutchinson Cancer Research Center. It was an important affirmation that the BHGI’s unique resource-stratification approach to cancer treatment guidelines for low- and moderate-income countries is a viable model.

"Asia represents a tremendous clinical challenge: Cancer incidence is increasing rapidly; lifestyles are becoming more westernized causing changes in disease etiology; and resources for infrastructure and disease management vary widely from country to country," The Lancet Oncology editors said in their introduction to the papers. "For any clinical guidance to be universally applicable these differences need to be taken into account. The Breast Health Global Initiative provides an excellent economic template on how to achieve this goal."

Founded in 2002, the BHGI strives to develop evidence-based, economically feasible and culturally appropriate guidelines for underdeveloped nations to improve breast-health outcomes. BHGI is co-sponsored by the Hutchinson Center and the Susan G. Komen for the Cure. Benjamin O. Anderson, M.D., is founder, chair and director. He is a member of the Division of Public Health Sciences at Fred Hutchinson Cancer Research Center, director of the Breast Health Clinic at the Seattle Cancer Care Alliance and professor of surgery and global health medicine at the University of Washington.

"The BHGI guidelines are intended to assist ministers of health, policymakers, administrators and institutions in prioritizing resource allocation as breast cancer treatment programs are implemented and developed in their resource-constrained countries," Anderson said. "The guidelines are defined by levels of resources and offer evidence-based pathways for coordinated, step-by-step quality improvements. This systematic approach applies a tiered system of resource allotment: basic, limited, enhanced and maximal, and is based on the contribution of each resource toward improving clinical outcomes."

The papers published by The Lancet Oncology in its November 2009 issue cover management of a variety of malignancies: HER-2 positive breast cancer, neck cancer, T-cell and natural-killer-cell neoplasms, advanced non-small-cell lung cancer, liver cancer and endometrial cancer. The guidelines represent consensus statements from the 2009 Asian Oncology Summit held last April in Singapore. The journal co-hosted the event.

"I was tremendously impressed and pleased with how this worked and how the different key opinion leaders were brought together in the Asian Oncology Summit," Anderson said. "It was a great learning experience for me in addition to the fact that it was a demonstration that this stratified guideline approach is in fact useful and functional."

The first broad dissemination of the BHGI guidelines came in October 2008 when journal Cancer published a special supplement, "Guidelines for International Breast Health and Cancer Control," which detailed guidelines for low- and middle-income countries to implement programs to detect and treat breast cancer, the most common disease among women worldwide.

More information about The Lancet Oncology cancer papers can be found on its Web site here: http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(09)70324-9/fulltext

More information about the BHGI can be found on its Web site: www.bhgi.info

MEDIA CONTACT:
Dean Forbes
Fred Hutchinson Cancer Research Center
(206) 667-2896
dforbes@fhcrc.org

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$4.8 million federal stimulus grant launches feasibility study of massive endeavor to measure all human proteins

October 27, 2009

SEATTLE Oct. 27, 2009 An expert in cancer proteomics at Fred Hutchinson Cancer Research Center has received $4.8 million in federal stimulus funding from the National Cancer Institute to co-lead a pilot study to assess the feasibility and scalability of a project that aims to measure all of the proteins in the human body.

"If successful, this study could help to stimulate a larger international endeavor that would be comparable to the Human Genome Project," said Amanda Paulovich, M.D., Ph.D., a geneticist and oncologist in the Hutchinson Center's Clinical Research Division who is co-leading the effort with Steven Carr, Ph.D., a senior scientific leader in protein biochemistry and proteomics at the Broad Institute in Cambridge, Mass. A senior adviser on the project is N. Leigh Anderson, Ph.D., founder and chief executive officer of the Plasma Proteome Institute in Washington, D.C.

"In the same way that the Human Genome Project has had a tremendous impact on our ability to measure the expression levels of all 21,000 genes in human cells, we hope that the long-term output of this effort the human Proteome Detection and Quantitation (hPDQ) project will allow us to build a method to measure the products of those genes, which are the more than 100,000 proteins in the human body," Paulovich said.

Understanding the body's protein landscape is important because proteins are the workhorses of the cell that carry out genetic instructions. Changes in the structure or abundance of proteins are associated with genetic mutations that cause diseases such as cancer.

Currently there is no good way to simultaneously measure large numbers of human proteins, which presents a major obstacle to progress in both basic and applied translational research, in which fundamental scientific findings are translated into clinically useful results, from diagnostic and screening tests to drug development.

"You can't study what you can't measure," Paulovich said. "Currently the biomedical research enterprise is severely hindered by its inability to measure the vast majority of human proteins." Unlike gene signals, which can be amplified in the laboratory, protein volume cannot be dialed up.

Because many proteins are present in very low quantities like a needle in a haystack they are below the limits of detection with current techniques.
This study is designed to change that. "This pilot has the potential of developing the first step toward making the entire human proteome clinically accessible," said Henry Rodriguez, Ph.D., director of Clinical Proteomic Technologies for Cancer in the Office of the Director at the NCI.

"If we can create ways to measure a large fraction of human proteins, particularly those in very low abundance, this will facilitate the development of new drugs and personalized medicine," Paulovich said.

Ultimately, the "holy grail" of proteomics is the discovery of protein biomarkers that could be used to create reliable and inexpensive blood tests to identify the onset and risk of a wide range of cancers and other diseases so they could be prevented or treated at the earliest possible stage, when cure rates are highest.

For the project, Paulovich and colleagues will use a highly sensitive and targeted analytical technology multiple reaction monitoring mass spectrometry to develop 400 assays, or tests, to measure the levels of 200 proteins found in breast-cancer cells. While the purpose of the study is to test the feasibility of scaling this technology to a much broader scale, a side benefit may be to determine whether certain proteins are associated with specific subtypes of breast cancer.

This type of mass spectrometry is not new it has been used for years in clinical laboratories worldwide to measure drug metabolites and small molecules associated with inborn errors of metabolism. What is new is Paulovich and colleagues’ pioneering use of this technology, also known as triple quadropole mass spectrometry, to measure proteins.

Unlike traditional mass spectrometry, which attempts to detect all proteins in a biological sample in a scattershot fashion, this technology is highly targeted, allowing researchers to calibrate the equipment to specifically look for peptides, or protein fragments, of interest, filtering out the rest as white noise.

The approach used in the Hutchinson Center/Broad Institute collaboration is complementary to other ongoing protein-discovery initiatives such as the Human Proteome Project of the Human Proteome Organization (HUPO) and the Swedish Human Proteome Resource. "While these other groups are identifying proteins expressed in different human cell types, we will complement their work by quantifying the expression of proteins beginning with those of potential clinical interest," Paulovich said. "We'll measure these proteins to see if their abundance changes in relation to disease."

The project also includes collaborators at Massachusetts General Hospital in Boston and the University of North Carolina at Chapel Hill, as well as a commercial partnership with Applied Biosystems of Life Technologies, whose AB Sciex triple quadrupole mass-spectrometry equipment will be used for the project.

To maximize productivity, Paulovich and colleagues also will closely coordinate activities and share their results with Robert Moritz, Ph.D., a faculty member and director of proteomics at the Institute for Systems Biology in Seattle, who recently received federal stimulus funding to lead a related human proteome project.

MEDIA CONTACT:
Kristen Woodward
Fred Hutchinson Cancer Research Center
(206) 667-5095
kwoodwar@fhcrc.org

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A solution to Darwin's 'mystery of mysteries' emerges from the dark matter of the genome

October 26, 2009

SEATTLE Oct. 26, 2009 Biological species are often defined on the basis of reproductive isolation. Ever since Darwin pointed out his difficulty in explaining why crosses between two species often yield sterile or inviable progeny (for instance, mules emerging from a cross between a horse and a donkey), biologists have struggled with this question. New research into this field by basic scientists at Fred Hutchinson Cancer Research Center, published online Oct. 22 in Science Express, suggests that the solution to this problem lies within the "dark matter of the genome": heterochromatin, a tightly packed, gene-poor compartment of DNA found within the genomes of all nucleated cells.

"Speciation is one of the most fascinating, unsolved problems in biology," said Harmit Malik, Ph.D., an associate member of the Hutchinson Center's Basic Sciences Division and corresponding author of the paper.

Malik and first author Joshua Bayes, Ph.D., a former graduate student in the Malik lab, focused on understanding the cellular function of a particular fruit fly (Drosophila) gene dubbed Odysseus. The gene is so named because of its ability to cause havoc and male sterility when introduced into the genome of another species. Odysseus is a gene that is derived from a transcription factor, and it was long believed to be a protein that turned on expression of other genes in Drosophila testis.

Odysseus also had been previously shown to rapidly evolve in its DNA-binding domain. Based on this observation, Bayes and Malik reasoned that Odysseus must interact with some rapidly evolving DNA in the genome. They tested the hypothesis, first proposed by Malik and Hutchinson Center colleague Steven Henikoff, Ph.D., that such hybrid-sterility proteins may bind repetitive satellite DNA in heterochromatin. Such repeats are believed to evolve rapidly due to an "arms-race" for preferential transmission during the process of forming an egg, whereby only one of four chromosomes is non-randomly chosen to be included into the egg.

Consistent with this hypothesis, Bayes found that Odysseus proteins localize to heterochromatic DNA found next to centromeres and on gene-poor chromosomes, which leads to their decondensation. Dramatically, the hybrid-sterility-associated Odysseus from one species showed additional localization to the Y chromosome of the other species. Through experiments in cell lines and transgenic flies, Bayes further showed that Odysseus localization has rapidly evolved during recent evolution, evidence of the "arms-race" that drives rapid evolution of satellite DNA repeats. Altered expression and localization has profoundly deleterious consequences for the process of sperm formation, a process that remains a mystery and is under active study in the Malik lab.

The finding that rapidly evolving heterochromatin may underlie this phenomenon also ties in with other work in Malik's lab that explores how "mismatches" originating from rapid evolution of DNA and proteins could lead to chromosome segregation defects and aneuploidy events that are sometimes precursors in transitions to cancer.

Malik and Bayes have received recent honors for their work. Earlier this year Malik, a Howard Hughes Medical Institute Early Career Scientist, was awarded the Presidential Early Career Award for his unique combination of evolutionary and genetic approaches to tackle important problems like speciation and infectious disease. For his work describing the first-ever molecular explanation of a hybrid-sterility gene, Bayes earlier this year was awarded the prestigious Walter M. Fitch Prize. Bayes is now an HHMI postdoctoral research associate in the Department of Molecular and Cell Biology at the University of California, Berkeley.

Grants from the National Institutes of Health, the Mathers Foundation and the Howard Hughes Medical Institute funded this research.

MEDIA CONTACT
Kristen Woodward
Fred Hutchinson Cancer Research Center
(206) 667-5095
kwoodwar@fhcrc.org

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Hutchinson Center to build first U.S. cancer clinic and training facility in Africa thanks, in part, to a grant from USAID

October 23, 2009

Nurse Janet Nankoma Kwiri of the Uganda Cancer Institute tends to patient Ojambo Samwiri of Nyenga-Mukono, Uganda. (Photo by Rob Gipman, Uganda Program on Cancer and Infectious Diseases)

Check out the gallery of downloadable photos from the Uganda Cancer Institute »

SEATTLE Oct. 26, 2009 Building on the strengths of two institutions separated by nearly 9,000 miles over two continents both renowned in their work in the fight against cancer the United States Agency for International Development has awarded a $500,000 grant to Fred Hutchinson Cancer Research Center to aid in the construction of the first American cancer clinic and medical-training facility in Africa.

This is the first true collaboration between an African and a U.S. institution to attempt to reduce cancer-related suffering through collaborative medical care and training, said Hutchinson Center physician-scientist Corey Casper, M.D., M.P.H., scientific co-director of the Uganda Program on Cancer and Infectious Diseases, a research effort begun in 2004 between the Hutchinson Center and the Uganda Cancer Institute, the country’s sole cancer clinic. The institute is located at Makerere University Medical School on the campus of Mulago Hospital in Kampala, the nation’s capital.

The main goals of the collaboration, co-led by Jackson Orem, M.B.Ch.B., M.Med., director of the Uganda Cancer Institute, are to:

better understand the link between infectious disease and cancer;
improve access and delivery of clinical care to patients with infection-related cancers in the U.S. and Uganda; and
train the next generation of American and Ugandan physicians and scientists to combat infection-associated cancers at home and abroad.

"Up to one-quarter of the world’s cancers are attributable to chronic infections, Casper explained. Better understanding the link between infectious disease and cancer provides a unique opportunity to reduce cancer-related suffering and death in both resource-rich and resource-poor regions.

Casper and colleagues hope that this joint effort between the Hutchinson Center and the Uganda Cancer Institute will benefit the world by identifying new infectious causes of cancer, new ways to prevent infection-associated cancers such as through the development of new vaccines, and new ways to treat such cancers with nontoxic drugs, thus avoiding the need for chemotherapy.

Studying cancer in regions such as Uganda, where the burden of infection-related malignancies is extreme, is optimal for developing rapid and meaningful cancer treatments and diagnostics, said Casper, an assistant member of the Hutchinson Center’s Vaccine and Infectious Disease Institute, one of the nation’s largest infectious disease research groups.

The World Health Organization estimates that chronic infectious diseases cause more than 20 percent of all cancers in the world, including liver, cervical and gastric malignancies. Infection-related cancers are more frequent and often more severe in people infected with HIV. In resource-poor Uganda, the HIV epidemic is fueling a 20,000-fold upsurge in Kaposi’s sarcoma in adults and Burkitt’s lymphoma in children. Both are disfiguring cancers with abysmal survival rates due to lack of access to early diagnosis and treatment.

While the grant from USAID’s American Schools and Hospitals Abroad program will contribute significantly to the construction of a new outpatient cancer clinic and training facility, additional federal and private funding is being sought to complete the $1.4 million project and to construct an adjacent clinical and laboratory research building, said Banks Warden, executive director of the Hutchinson Center’s Vaccine and Infectious Disease Institute.

We will soon launch a campaign to see if other foundations and individuals are interested in supporting this effort. It is a wonderful opportunity for a foundation or individual to come forward with a major gift to support global health, Warden said.

Support for the project to date has come from several sources, from initial funding provided by the Hutchinson Center and the Doris Duke Charitable Foundation to satellite grants from the National Institutes of Health and, most recently, the USAID funding.

Securing this federal grant would not have been possible without broad support from the Washington congressional delegation, Warden said. We are deeply indebted to our senators and representatives who got behind our efforts 100 percent, he said.

A letter of support signed by the congressional members stated: Cancer is all too common in East Africa, with the number of new cases diagnosed annually approximating the number of deaths. With these infrastructure improvements, cancer treatment for Ugandans will dramatically improve. In addition, the collaboration will allow for important questions about the biology of infectious-disease related cancers to be answered. Solutions discovered will be applicable globally.

Research conducted to date through the Seattle/Uganda partnership already has determined that many of the infectious diseases that cause cancer in low-resource areas are treatable at minimal costs. For example, it is estimated that 85 percent of Burkitt’s lymphoma (associated with human herpesvirus 4, also known as Epstein-Barr virus), the most common cancer in children from East Africa who are on average 5 years old when afflicted, can be cured for less than $600 a case. Similarly, 75 percent of Kaposi’s sarcoma (associated with human herpesvirus 8, or HHV-8), the most common cancer in East African adults, can be treated for less than $720 a case.

The Uganda Cancer Institute, established in 1967 in collaboration with the U.S. National Cancer Institute, has been the site of many landmark accomplishments, such as discovering new cancers, including Burkitt’s lymphoma, and developing novel treatment regimens. Over the years, however, the institute has fallen victim to neglect attributable to periods of tumultuous national politics. Its five cinderblock buildings bear scars of the nation’s troubled past.

Upon completion of the new, state-of-the-art facility, the Ugandan Ministry of Health has pledged $1.8 million to renovate and repurpose the existing buildings of the cancer institute. The renovation will include the construction of an inpatient facility. The Hutchinson Center has also committed $400,000 to construct new laboratory space for molecular diagnostics. The master plan for these renovation and construction projects was provided by facilities planning and construction staff at the Hutchinson Center.

Ultimately, the provision of new facilities for inpatient and outpatient cancer care, education and research will allow the Seattle/Uganda collaboration to:

provide first-rate cancer care in Uganda a country of more than 30 million with one of the highest cancer rates in the world and improve survival from most common cancers from 10 percent to 90 percent, saving an estimated 6,000 lives each year;
study the intersection between infections and cancer by promoting cutting-edge research aimed at pathophysiology, prevention, diagnosis and treatment of infection-related cancers in Africa; and
improve the quality of medical education in oncology and increase the number of cancer specialists in Africa seven-fold (there are currently just two practicing full-time oncologists in Uganda).

One of the biggest benefits the Hutchinson Center is bringing to Uganda is a training program to address the country’s lack of cancer specialists. Two Ugandan physician-scientists have already spent year-long fellowships at the Hutchinson Center; five more will be trained in the next three years. There are also plans to expand the training program to include other medical professionals, such as nurses and pharmacologists, Casper said.

The Hutchinson Center also plans to send up to 20 of its faculty members to Uganda in the next five years as part of a faculty exchange program. Researchers in oncology, infectious disease and epidemiology will provide training in a wide variety of subjects to Ugandan clinicians and scientists. They also will have the opportunity to initiate research projects in collaboration with Ugandan researchers.

My hope, Casper said, is that over the next five years we establish a first-class facility in Uganda, train a significant number of Ugandan cancer-care providers and that people who are interested in international oncology will come to the Center for the chance to work in Uganda.

The collaborative effort is also an opportunity for the Hutchinson Center to help mobilize humanitarian aid in this East African nation, where proper nutrition and medical care is scarce and where the families of patients are responsible for all nonmedical care, including food.

Having a healthy population is essential for the fabric and stability of the nation, Casper said. It is the Hutchinson Center’s obligation to seek the resources needed to provide care to the patients and clinical-research volunteers in Uganda. It’s also the right thing to do. There can be no greater mandate in cancer research than to wage the fight by doing the right thing.

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Note for media only: Photos of the Uganda Program on Cancer and Infectious Diseases Clinic and Training Center are available upon request or from our online photo gallery. For more information about UPCID, please visit www.upcid.org.

At Fred Hutchinson Cancer Research Center, interdisciplinary teams of world-renowned scientists and humanitarians work together to prevent, diagnose and treat cancer, HIV/AIDS and other diseases. Hutchinson Center researchers, including three Nobel laureates, bring a relentless pursuit and passion for health, knowledge and hope to their work and to the world. For more information, please visit www.fhcrc.org.

This project is made possible in part by the support of the American people through the United States Agency for International Development (USAID). The contents are the sole responsibility of the Uganda Program on Cancer and Infectious Diseases (UPCID), a joint program of Fred Hutchinson Cancer Research Center and the Uganda Cancer Institute, and do not necessarily reflect the views of USAID or the United States Government.

MEDIA CONTACT:
Kristen Woodward
Fred Hutchinson Cancer Reserach Center
(206) 667-2896
kwoodwar@fhcrc.org

Statewide teen smoking-cessation trial is the first to achieve significant increase in prolonged quit rates

October 12, 2009

SEATTLE Oct. 12, 2009 For the first time, researchers at Fred Hutchinson Cancer Research Center have demonstrated that it is possible to successfully recruit and retain a large number of adolescent smokers from the general population into a smoking intervention study and, through personalized, proactive telephone counseling, significantly impact rates of six-month continuous quitting. These findings, by Arthur V. Peterson Jr., Ph.D., Kathleen A. Kealey and colleagues, are reported in a pair of papers in the Oct. 12 "Advance Access" online edition of the Journal of the National Cancer Institute.

"When this study started, despite decades of research and dozens of intervention trials, there was no proven way to reach teens from the general population and recruit them into smoking cessation programs, and there was no proven way to help these teens quit," said Peterson, a member of the Hutchinson Center's Public Health Sciences Division and lead author of the paper that reported the results of the Hutchinson Study of High School Smoking, the largest randomized trial of teen smoking cessation ever conducted.

The trial, funded by the National Institutes of Health, involved 2,151 teenage smokers from 50 high schools in Washington. Half of the schools were randomly assigned to the experimental intervention; teens in these schools were invited to take part in confidential, personalized telephone counseling designed to help motivate them to quit. The remaining 25 schools served as a comparison group; teen smokers from these schools did not participate in the telephone intervention. The study also included 745 nonsmokers to ensure that contacting students for participation in the trial would not reveal a participant’s smoking status.

Study recruitment was robust; in the experimental group 65.3 percent of the smokers were eligible and participated in the telephone intervention. Recruitment took place in their junior year and the counseling intervention took place during their senior year. "The literature says it is very difficult to recruit kids to teen smoking programs. People have tried. The field has encountered great obstacles in recruiting teens to smoking cessation programs. And so we took that as a challenge," Peterson said.

The study found that a proactive strategy of reaching out to teens and offering them the opportunity to receive up to nine personalized, confidential telephone counseling sessions effectively helped many of them to kick the habit. In addition, by proactively identifying and recruiting teen smokers (with parental consent for those under age 18), two-thirds of all identified smokers participated in the telephone counseling and nearly half completed all of their scheduled counseling calls.

At the completion of the study, 21.8 percent of all smokers (daily and less than daily) in the counseling group had achieved continuous quitting for six months, as compared to 17.7 percent of those in the comparison group, a difference of 4 percent.

The intervention also impacted three-month, one-month and seven-day smoking abstinence, with differences between the counseling group and the comparison group of 3.3 percent, 6.8 percent and 7.5 percent, respectively. Notably, the one-month and seven-day quit rates among the smokers who received telephone counseling were roughly three times higher than those reported in nearly 50 previous adolescent smoking-cessation trials of a variety of interventions conducted over the past two decades.

"These results are critically important for supporting and stimulating our nation’s search to find successful ways to help reduce smoking by teens and young adults," Peterson said.

An estimated 26.5 percent of high school seniors smoke monthly, and 13.6 percent smoke 10 or more cigarettes daily. Although nearly half of all current adolescent smokers report having tried to quit smoking in the past year, only about 4 percent per year succeed on their own. In addition, young adults ages 18 to 24 have the highest smoking rates in the U.S., ranging between 27 percent and 40 percent, depending on geographic region and socioeconomic status.

The telephone counseling intervention was based on the premise that smokers need to believe it is important to quit, have confidence they can quit and have the knowledge and skills needed to be successful with quitting. Therefore, the intervention integrated two types of counseling: motivational interviewing, which emphasizes building motivation and confidence for quitting, and cognitive behavioral skills training, which gives smokers the tools they need to learn how to quit.

Motivational interviewing, first described in the early '80s by William R. Miller, Ph.D., as a way to help treat problem drinkers, enhances a person’s motivation to change by exploring and resolving one's ambivalence about change. In this study, the technique was used to explore and resolve the participants' ambivalence about smoking and quitting, and to mobilize their inner resources to trigger a decision to quit.

"Motivational interviewing is very caring, nonjudgmental and respectful. It is non-confrontational. A counselor would never say, 'I want you to quit smoking.' Instead the counselor would ask what the behavior means to the participant. What do they like about it? What don’t they like about it?" explained Kealey, first author of the companion paper, which describes in detail the design and implementation of the telephone counseling intervention.

In motivational interviewing, the counselor would use reflective statements to repeat the participant’s own words back to him or her. For example: "So, it sounds to me like you smoke because it helps you to relax when you’re under stress. But on the other hand, you said that you really don’t like the way it smells, and that it’s really expensive. So what do you make of that?"

"In the end, it is the smoker's own reasons and desire to quit that motivate the quit attempt, said Kealey, project manager for the study.

Cognitive behavioral skills training seeks to help people build skills for quitting and preventing relapse through counseling strategies that emphasize practical tools, such as self-talk strategies, ways to cope with stress and smoking triggers, and collaborating on a plan for quitting. "While motivational interviewing increases a person’s motivation to quit, cognitive behavioral skills training gives them the resources and the confidence they need to be successful," Kealey said.

Adolescent smoking cessation studies conducted in the past 20 years have been largely unsuccessful in getting teens to quit. These studies have identified significant challenges. To date, only two other randomized controlled trials with smaller numbers of teen smokers than the Hutchinson Study and conducted in medical settings have shown promise in achieving significant teen quit rates.

So what makes the Hutchinson Study so effective? The researchers hypothesize that the reason is threefold:

The intervention was proactive, reaching out and engaging teens "Past research has shown that, for a multitude of reasons, many teen smokers do not seek out help with quitting. However, our study demonstrates that if we reach out to teens, without pressuring them to quit, many will talk to counselors about their smoking and some of those teens will decide to quit," Peterson said.

The counseling was offered by telephone "This allowed for private, confidential, one-to-one counseling and allowed the counselors to explore and focus on issues specific to the individual smoker," he said. Telephone counseling also gave teens control over the timing and length of the counseling sessions.

The counselors used motivational interviewing techniques in all communications with the teens "It seemed quite appropriate for us to test this deferential strategy in youth because teens, in particular, don't want to be told what to do," Peterson said. "Our goal was to put them in the driver’s seat."

So even though teens tend not to seek help for quitting smoking, this study indicates that they are more likely to succeed with quitting if they have help. "An important message from this study for teens and young adult smokers really for all smokers is that personalized telephone counseling can help one be successful with quitting smoking," Peterson said. Such help is available through the nation's network of quit lines, such as 1-800-QUIT-NOW offered through the Washington State Department of Health.

The National Cancer Institute funded the study, which also involved investigators at Group Health Research Institute in Seattle.

Note for media only: To obtain embargoed copies of the Journal of the National Cancer Institute papers, "Group-Randomized Trial of a Proactive, Personalized Telephone Counseling Intervention for Adolescent Smoking Cessation" by Peterson and "Design and Implementation of an Effective Telephone Counseling Intervention for Adolescent Smoking Cessation" by Kealey, or to arrange interviews with the authors, please contact Kristen Woodward in Hutchinson Center media relations, 206-667-5095 or kwoodwar@fhcrc.org.

MEDIA CONTACT:
Kristen Woodward
Fred Hutchinson Cancer Research Center
(206) 667-5095
kwoodwar@fhcrc.org

RELATED CONTENT:
Personalized Telephone Counseling For Teen Smokers Editorialist Dr. Scott Leischow discusses this research.
Journal of the National Cancer Institute podcast, Oct. 28, 2009

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Ten finalists chosen for Hutch Award®

October 08, 2009

SEATTLE Oct. 8, 2009 Ten Major League Baseball players have just learned they're in the running for the 2009 Hutch Award®. A national committee has released a list of 10 players, one of whom will go on to receive the prestigious Hutch Award and visit Fred Hutchinson Cancer Research Center in January. The finalists for the 45th annual Hutch Award are:

Jonny Gomes, Cincinnati Reds
Tim Hudson, Atlanta Braves
Torii Hunter, Los Angeles Angels of Anaheim
Mark Lowe, Seattle Mariners
Mike Lowell, Boston Red Sox
Nick Markakis, Baltimore Orioles
Kevin Millwood, Texas Rangers
Justin Morneau, Minnesota Twins
Albert Pujols, St. Louis Cardinals
Mark Teahen, Kansas City Royals

This year's Hutch Award recipient will be selected in November through a vote of all surviving former awardees. A total of 44 players have been honored since 1965, when Mickey Mantle accepted the inaugural award. Hall-of-Famers Sandy Koufax, Carl Yastrzemski, Al Kaline, Willie McCovey and Lou Brock all have received the Hutch Award, and in more recent years Jamie Moyer, Trevor Hoffman, Craig Biggio, Mark Loretta, Mike Sweeney and Jon Lester have joined their ranks.

The Hutch Award is given annually to the major league player who best exemplifies the honor, courage and dedication of renowned baseball player and manager Fred Hutchinson ("Hutch"). Fred Hutchinson Cancer Research Center -- which was named in Hutch's honor by his brother Dr. Bill Hutchinson, a surgeon, after Fred succumbed to cancer at age 45 -- is an independent, nonprofit research institution dedicated to the understanding, treatment and prevention of cancer and related diseases.

The award is presented each January in Seattle, Hutch's hometown and the site of the renowned cancer center that bears his name. The Hutch Award will be presented at a fundraising luncheon honoring the awardee on Wednesday, Jan. 27, 2010 at Safeco Field in Seattle.

For more information about the Hutch Award, including a full list of past recipients, or to learn more about the January luncheon, visit www.fhcrc.org/hutchaward.

MEDIA CONTACT
Christi Ball Loso
Fred Hutchinson Cancer Research Center
(206) 667-5215
closo@fhcrc.org

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Two Hutchinson Center scientists receive a total of $16.7 million for collaborative stem cell research

October 08, 2009

SEATTLE Oct. 7, 2009 The National Heart, Lung and Blood Institute has awarded a total of $16.7 million to Irwin Bernstein, M.D., and Beverly Torok-Storb, Ph.D., both members of the Clinical Research Division at Fred Hutchinson Cancer Research Center. The Hutchinson Center grants represent part of a $170 million effort involving 18 teams of research scientists dedicated to developing stem- and progenitor-cell tools and therapies.

The seven-year awards create the NHLBI Progenitor Cell Biology Consortium, which assembles nine research hubs with multidisciplinary teams of principal investigators and an administrative coordinating center.

While a stem cell can renew itself indefinitely or differentiate, a progenitor cell can only divide a limited number of times and is often more constrained than a stem cell in the kinds of cells it can become. Given the potential of these cells for clinical applications, the consortium aims to identify and characterize progenitor cell lines, direct the differentiation of stem and progenitor cells to desired cell fates, and develop new clinical strategies to address the unique challenges presented by the transplantation of these cells.

Torok-Storb, along with Fred Hutchinson/University of Washington Cancer Consortium colleagues, will collaborate with Mortimer Poncz, M.D., of Children's Hospital of Philadelphia to develop molecular- and cell-based therapies for a range of blood diseases, with an initial focus on the delayed recovery of blood-clotting platelets following stem-cell transplantation, a life-threatening complication called thrombocytopenia.

The partner institutions will focus on two complementary strategies to address delayed platelet production. With their $8.2 million grant, Torok-Storb's team will develop reagents that can be administered to patients to stimulate the differentiation and proliferation of precursor cells into platelets. The Philadelphia group will work to generate "ex vivo," or outside the body, platelets and their precursors from embryonic stem cells for use as cell therapy.

Bernstein, along with Hutchinson Center/UW Cancer Consortium researchers and the University of Pennsylvania's Edward Morrisey, Ph.D., is using his $8.5 million award to determine how certain signaling pathways-ordered sequences of biochemical reactions inside cells-affect cardiac and blood-forming cell development and cardiac regeneration and repair. The team will also study whether these pathways can be harnessed for therapeutic applications. Drawing on Bernstein's success in expanding cord-blood stem cells, the researchers hope to refine methods for deriving therapeutically useful numbers of cells for transplantation and other treatments.

# # #

CONTACT
Kristen Woodward
206-667-2896
kwoodwar@fhcrc.org

'Suspended animation' researcher Mark Roth to be featured next week on the Science Channel and CNN

October 08, 2009

SEATTLE Oct. 8, 2009 Next week the Science Channel and CNN will feature the work of Mark Roth, Ph.D., a cell biologist and "MacArthur genius" in the Basic Sciences Division of Fred Hutchinson Cancer Research Center who studies the therapeutic potential of suspended animation and reversible metabolic hibernation.

At 9 p.m. PT Monday, Oct. 12, the Science Channel will feature Roth's research in an episode of "Popular Science's Future of," an hour-long weekly program hosted by Baratunde Thurston. The show, a joint venture between the Science Channel and Popular Science magazine, will explore the future of immortality through suspended animation and organ regeneration research and longevity pills, among other topics. The show will be re-broadcast at midnight and 4 p.m. Oct. 13 and 4 a.m. Oct. 14. More information: http://press.discovery.com/us/sci/programs/future-of/

At 8 and 11 p.m. PT Saturday, Oct. 17 and Sunday, Oct. 18, Roth's work will be featured in an hour-long CNN documentary called "Another Day: Cheating Death" hosted by chief medical correspondent Sanjay Gupta, M.D. The program will recount extraordinary stories of people who have survived exceptional medical emergencies, such as prolonged clinical death caused by hypothermia. Roth’s work will also be featured in a companion book by Gupta, "Cheating Death," which will be available in book stores after Oct. 12. More information: http://news.turner.com/article_display.cfm?article_id=4681

Note for media only: A photo of Roth with CNN's Sanjay Gupta during a taping last fall in Roth's Hutchinson Center laboratory is available upon request.

MEDIA CONTACT
Kristen Woodward
Fred Hutchinson Cancer Research Center
(206) 667-5095
kwoodwar@fhcrc.org

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$16 million in federal stimulus funding establishes Seattle as a hub of comparative-effectiveness research in cancer

October 05, 2009

SEATTLE Oct. 5, 2009 Researchers at Fred Hutchinson Cancer Research Center, Group Health Research Institute and the University of Washington School of Public Health have been selected to lead four projects backed by approximately $16 million in federal stimulus funding for comparative-effectiveness research in cancer. The grants establish Seattle as a national hub for conducting such research, which aims to objectively analyze cancer diagnostic tools, screening tests and treatments to determine the optimal choices based on balancing benefits - including effectiveness - and harms, such as cost. Most of these projects involve extensive collaboration between these local institutions.

The American Recovery and Reinvestment Act has dedicated $1.1 billion to fund such research via the Grand Opportunities (GO) grants program of the National Institutes of Health, which supports high-impact ideas that lend themselves to short-term funding. The Seattle-led GO grants, each of which will fund two-year projects, account for approximately one-third of the National Cancer Institute's first investment in the burgeoning field of cancer-related comparative-effectiveness research.

"Cancer is one of the highest areas of health care spending," said Scott Ramsey, M.D., Ph.D., an internist and health care economist who is leading a Hutchinson Center-based project that will lay the foundation for research to evaluate how various cancer genetic tests influence cancer care, outcomes and costs. "We are spending multiple billions on cancer diagnostics and hundreds of millions on genetic tests, for example, but we're not certain what we're getting for all of that money. Are patients living longer? Are they living better quality lives? We just don't have that answer," he said.

The following Seattle-based comparative-effectiveness research projects aim to help provide some of those answers:

Cancer genomics A $4 million project based at the Hutchinson Center and led by Ramsey, a member of the Center's Public Health Sciences Division and a professor of medicine at UW School of Medicine, will fund the development of an infrastructure to support the "Center for Comparative Effectiveness Research in Cancer Genomics," or CANCERGEN. This public-private consortium will design and conduct prospective, controlled clinical trials of promising cancer genetic tests working in close collaboration with the University of Michigan-based Southwest Oncology Group (SWOG), one of the largest NCI-supported cancer clinical trials cooperative groups. Researchers in the SWOG Statistical Center, co-located at the Hutchinson Center and the Seattle nonprofit Cancer Research And Biostatistics (CRAB), will design the statistical structure of the study and lead data management and analysis. CANCERGEN will develop the tools that help SWOG researchers determine which proposed trials will have the greatest clinical benefit for patients. "Part of CANCERGEN's vision is to position SWOG as a national leader in cancer comparative-effectiveness research," Ramsey said. "Realizing that vision will go a long way to help achieve the health care reform goal of making cancer treatment more effective and less expensive," he said. Researchers at the UW School of Pharmacy and the Center for Medical Technology Policy in Baltimore will co-lead the effort.

Cancer diagnostics A $4 million project based at the UW School of Public Health and led by Larry Kessler, Sc.D., professor and chair of the UW Department of Health Services, will fund research to evaluate the effectiveness of cancer diagnostics - from mammography and MRI to ultrasound, PET-CT, and blood- or tissue-based biomarkers - to determine the extent of disease and plan treatment. "Over the past decade, the field of both medical imaging and laboratory-based diagnostics has taken a quantum leap forward. However, the evidence to determine how to best use these modern technologies in clinical practice hasn't kept pace with the technological developments," Kessler said. "Our research will help providers and patients make better decisions about the use of these technologies, which ultimately will lead to the best possible outcomes," he said. The project, called "Advancing Innovative Comparative Effectiveness Research in Cancer Diagnostics," or ADVICE, will be co-led by investigators from the UW schools of Pharmacy and Medicine, Group Health, Veterans Affairs and the Hutchinson Center, which will serve as the study's data center.

Breast imaging A $4 million project led by Group Health will support comparative-effectiveness research of conventional and cutting-edge breast cancer imaging techniques to help determine which modalities are most effective for women according to individual patient demographics and risk factors. It will use data from the NCI's Breast Cancer Surveillance Consortium, a nationwide collaborative network of mammography, tumor and pathology registries. With modeling experts from NCI's Cancer Intervention and Surveillance Modeling Network, the project will compare the effectiveness of various breast cancer screening strategies such as film-screen mammography, digital mammography and breast MRI. "A growing body of evidence is showing that screening tests can sometimes do more harm than good," said Diana Miglioretti, Ph.D., a senior investigator in biostatistics at Group Health and one of the project's leaders. "This study will let us evaluate different strategies for breast cancer screening so we can inform women about the best screening choices for them, based on their own age, risk factors and illnesses." The grant, "Comparative Effectiveness of Breast Imaging Strategies in Community Practice," will be co-led by investigators at Group Health, the University of North Carolina at Chapel Hill, the University of California at San Francisco, the University of Vermont and Georgetown University.

Cancer screening A $4 million project based at Group Health aims to lay the groundwork for studies to improve the effectiveness of colorectal and cervical cancer screening and increase participation in such screening. "How well cancer screening works in real-world settings depends not only on how well each screening test identifies cancer, but also on patients, health care providers and the context and systems in which health care is delivered," said Diana Buist, Ph.D., M.P.H., an associate investigator in epidemiology at Group Health and one of the project's leaders. "Our grant will study how to deliver colorectal and cervical cancer screening most effectively to populations. The goal is to detect cancer better, decrease the rates of screening's adverse effects and, ultimately, to reduce death from cancer," she said. The project, called "SEARCH: Screening Effectiveness and Research in Community Based Healthcare," will be co-led by Chyke Doubeni, M.D., M.P.H., an assistant professor in family medicine and community health at the University of Massachusetts Medical School. The project will be conducted in collaboration with seven other health-maintenance organizations in the NCI's Cancer Research Network, a consortium of 14 health plans across the U.S., to quickly and effectively translate and disseminate its findings directly into clinical practice.

In addition, Group Health is collaborating on a $4 million GO grant based at Dana Farber Harvard Cancer Center that will address two key issues: the costs and effectiveness of treating advanced cancer and the lack of population-based research on patterns and outcomes of cancer care in populations not covered by Medicare, such as those under 65 and the poor. The data from the study will be provided, in part, by the Cancer Research Network, a research-based consortium of health-maintenance organizations that is based at Group Health. "Most cancer research is done in patients in the early stages of their disease, so we know relatively little about patterns of treatment among patients whose cancer has recurred or progressed," said Paul Fishman, Ph.D., an associate investigator at Group Health and co-investigator on the project. "This study will provide evidence needed to support better care for more patients. Our research will be based on a wide range of patients who receive care in the full range of clinical settings where Americans receive their cancer care."

These GO grants represent just a fraction of federal stimulus funding for biomedical research awarded to these Seattle institutions. In total, as of Oct. 1, the UW schools of Medicine, Public Health and Pharmacy had received $79.6 million for 186 projects, the Hutchinson Center had received nearly $40.4 million for 60 projects, and Group Health had received more than $17 million for 15 projects.

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About Fred Hutchinson Cancer Research Center - At Fred Hutchinson Cancer Research Center, interdisciplinary teams of world-renowned scientists and humanitarians work together to prevent, diagnose and treat cancer, HIV/AIDS and other diseases. Center researchers, including three Nobel laureates, bring a relentless pursuit and passion for health, knowledge and hope to their work and to the world. For more information, please visit www.fhcrc.org.

About the University of Washington School of Public Health - The UW School of Public Health is one of 40 accredited schools of public health in the nation and the only one in the Northwest. The mission of the school is to promote better health, prevent illness and injury, and ensure more efficient and cost-effective health care services through education, research and service. The combination of discipline-oriented academic programs in the school's five departments and strong interdisciplinary research provides a setting for faculty and students to apply in-depth expertise to broad public health problems. For more information, please visit http://sph.washington.edu/

About Group Health Research Institute - Group Health Research Institute is a non-proprietary, public-domain research institution within Group Health, a health care system based in Seattle. To serve its mission, the Institute conducts and disseminates research and evaluation on: the organization, delivery, quality, and cost of health care; prevention, treatment and management of illness; and strategies at the individual, provider, system, community and policy levels that result in better health outcomes. The Institute has conducted comparative effectiveness research for more than 25 years; providing scientific evidence for effective, affordable care - and determining how well tests, treatments and preventive actions work in real clinical settings. For more information, please visit www.grouphealthresearch.org.

MEDIA CONTACTS:
Fred Hutchinson Cancer Research Center
Kristen Woodward
206-667-5095
kwoodwar@fhcrc.org

University of Washington School of Public Health
Clare Hagerty
206-685-1323
clareh@u.washington.edu

Group Health Research Institute
Rebecca Hughes
206-287-2055
hughes.r@ghc.org

Studies find few risks to newborn offspring of parents who are childhood cancer survivors

October 05, 2009

SEATTLE Oct. 5, 2009 Whether they can have children is one of the major concerns for adult survivors of childhood and adolescent cancer because fertility can be compromised by cancer treatment. For cancer survivors who can have children, two new studies led by researchers at Fred Hutchinson Cancer Research Center may help alleviate fears that their childhood disease will adversely impact their newborns.

The studies, presented as companion papers in the journal Archives of Pediatrics & Adolescent Medicine, observed few risks to babies born to parents who underwent cancer treatment in childhood or adolescence. The most significant finding was among women cancer survivors, who had a greater risk of giving birth to preterm and low birth weight infants compared to the general population. Among female cancer survivors, 15 percent of births were preterm versus 10 percent among women who never had cancer. However, babies born to female cancer survivors had no increased risk of birth defects or infant death, according to the paper that examined pregnancy outcomes.

In the companion paper, babies fathered by male childhood cancer survivors had a borderline risk of low birth weight but no increased risk of prematurity, being small for gestational age, or having birth defects when compared to controls.

"The take home message overall is positive. If you had cancer as a younger person and you are able to have children then most likely your children will be fine," said Eric Chow, M.D., Ph.D., corresponding author and research associate in the Hutchinson Center's Clinical Research and Public Health Sciences divisions. "Most of the other side effects that people have the most concern about - birth defects and more serious maternal complications during pregnancy - we didn't find those things."

Chow said pregnant women who had cancer in childhood should seek prenatal care early in their pregnancies and make sure their physicians and obstetricians know about their cancer history. Close monitoring may help prevent early births and underweight newborns.

A possible explanation for the increased rates of preterm delivery and underweight newborns found among female cancer survivors is that some cancer treatments may affect the growth of and blood flow to the uterus during pregnancy, said Chow, who is a pediatric oncologist. Previous studies have shown that radiation therapy to the uterus can increase the chances of subsequent preterm labor and low birth weight.

For the two papers, Chow and the principal investigator Beth Mueller, Ph.D., a cancer and reproductive health epidemiologist in the Hutchinson Center's Public Health Sciences Division, used data from cancer registries operated by the National Institutes of Health in four U.S. regions - Seattle, Detroit, Salt Lake City and Atlanta. They identified boys and girls who were diagnosed with cancer before the age of 20 between 1973 and 2000. Linked birth records from the four regions identified the first live births to these survivors after diagnosis. A total of 1,898 offspring of female cancer survivors were identified and their outcomes were compared to 14,278 controls selected from birth records. The study identified 470 offspring of male cancer survivors and compared them to 4,150 controls.

The National Cancer Institute funded the studies through its Surveillance, Epidemiology, and End Results (SEER) program. Co-authors of the papers included researchers from the University of Washington, Huntsman Cancer Institute in Salt Lake City, Wayne State University in Detroit, and Emory University in Atlanta.

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CONTACTS:
Dean Forbes
206 667-2896
dforbes@fhcrc.org

Kristen Woodward
206-667-5095
kwoodwar@fhcrc.org

Federal stimulus funding channels more than $40 million to Fred Hutchinson Cancer Research Center

October 05, 2009

SEATTLE Oct. 5, 2009 Scientists at Fred Hutchinson Cancer Research Center have been awarded 60 research grants totaling nearly $40.4 million under the American Recovery & Reinvestment Act of 2009. The totals reflect data available as of Oct. 1 and reported by the National Institutes of Health.

The individual projects range in amount from $4.8 million to $33,596 and benefit every level of researcher at the Hutchinson Center, from well-established principal investigators to predoctoral graduate students.

"It's a testament to the quality of the science we do and to the scientists who conduct our research that the Hutchinson Center was so successful in obtaining this level of stimulus funding," said Lee Hartwell, Ph.D., Center president and director.

One of the key goals of the Recovery Act is job retention and job creation.

"We estimate that for every $100,000 in grant funding that the Center receives, 2.3 jobs are retained or created internally and in the community by our suppliers. This means that the stimulus funds we received will retain and create about 920 jobs," Hartwell said.

The multiplier effect is backed by the National Institutes of Health and the Hutchinson Center's own economic impact studies.

A wide range of scientific subjects is covered by the grants, including developing assays to measure proteins expressed in cancer, cancer economics and cord blood transplantation.

Among Center faculty, Amanda Paulovich, M.D., Ph.D., an associate member of the Clinical Research Division, was awarded the single largest stimulus grant at $4.8 million. Paulovich is an expert in cancer proteomics, and her project is a pilot study to assess the feasibility and scalability of a human proteome detection and measurement project.

"The lack of sensitive, specific assays that can measure multiple proteins at the same time in a single sample is a major technical barrier that impedes progress in the biomedical sciences by prohibiting hypothesis testing in quantitative proteomics, where relationships between protein abundance and biology are sought," Paulovich said. "If a robust, economical, and widely diffused capability to measure all human proteins existed, the research community would have the collective means to assess the utility of all human proteins as biomarkers in hundreds of diseases and biological processes in the most efficient way. This would likely have a profound impact on health care costs and outcomes."

Ulrike Peters, Ph.D., an associate member of the Public Health Sciences Division, received a $4.6 million grant to identify genetic variants associated with colorectal cancer, the second leading cause of cancer death in the U.S.

"As this multi-site project will be conducted in well characterized cohorts, such as the Women's Health Initiative or the Health Professional Follow-up Study, we will also be able to examine whether environmental factors, including smoking, medications, alcohol, physical activity or diet change the risk of colorectal cancer related to these genetic variants," said Carolyn Hutter, Ph.D, a postdoctoral fellow working on this project.

"We expect our findings to enhance our understanding of the mechanisms underlying colorectal carcinogenesis. In turn, this will lead to improved prevention and treatment strategies," Peters said.

Scott Ramsey, M.D., Ph.D., an internist, health care economist and member of the Public Health Sciences Division, will lead a $4 million project to develop an infrastructure to support the "Center for Comparative Effectiveness Research in Cancer Genomics," or CANCERGEN.

"Dozens of genomic tests for cancer are coming to market without the high quality evidence that physicians and patients need to answer basic questions," said Ramsey, whose project will lay the foundation for designing research to study cancer genetic tests in collaboration with the Southwest Oncology Group, among others.

"Are patients living longer? Are they living better quality lives? Are there cost-effective alternatives to the way we currently treat patients? We just don't have those answers," he said.

Reducing the risk of infection and early death in patients who receive cord blood transplants to treat tumors of the blood, such as leukemia and lymphoma, is the goal of a $1.74 million grant to Colleen Delaney, M.D., an assistant member in the Clinical Research Division. Patients undergoing a cord blood transplant, who are often of minority or mixed ethnic background, are at increased risk of infection and early death following the transplant because of the significant delay in the recovery white blood cells, particularly cells called neutrophils. Neutrophils are the most common type of white blood cell and are the body's first line of defense against infections. However, using a novel culture methodology, Delaney demonstrated for the first time the ability to generate increased numbers of cells from a single unit of cord blood that are capable of rapid neutrophil recovery when infused in the clinical setting.

"Further development of this product to confirm our initial promising results requires additional clinical trials that, if successful, could change the way cord blood transplantation is performed," Delaney said.

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Note to editors/reporters: Dr. Scott Ramsey's grant and the subject of comparative effectiveness research is discussed in more detail in another news release distributed today, "$16 Million in Federal Stimulus Funding Establishes Seattle as a Hub of Comparative-Effectiveness Research in Cancer." Please contact Kristen Woodward if you would like to receive a copy.

CONTACT:
Kristen Woodward
Fred Hutchinson Cancer Research Center
(206) 667-5095
kwoodwar@fhcrc.org

Study find that vaccination of children and 70 percent of U.S. population could control swine flu pandemic

September 10, 2009

SEATTLE Sept. 10, 2009 An aggressive vaccination program that first targets children and ultimately reaches 70 percent of the U.S. population would mitigate pandemic influenza H1N1 that is expected this fall, according to computer modeling and analysis of observational studies conducted by researchers at the Vaccine and Infectious Disease Institute (VIDI) at Fred Hutchinson Cancer Research Center.

Published in the Sept. 11 issue of Science Express, the early online edition of the journal Science, the study which includes the first estimate of the transmissibility of pandemic H1N1 influenza in schools recommends that 70 percent of children ages 6 months to 18 years be vaccinated first, as well as members of high-risk groups as identified by the U.S. Centers for Disease Control and Prevention. These groups include health care and emergency services personnel and those at risk for medical complications from pandemic H1N1 illness such as persons with chronic health disorders and compromised immune systems. Two doses of vaccine, delivered three weeks apart, may be needed to confer adequate protection to the virus.

Corresponding author Ira Longini, Ph.D., and colleagues emphasized that a combination of factors the availability of an effective vaccine to protect people against pandemic H1N1, coupled with the timing of the outbreak will determine how quickly the epidemic can be slowed. The researchers estimate that to bring the epidemic under control aggressive vaccination of the population must begin at least a month before the epidemic peak, concentrating on children as much as possible.

"Our estimates of pandemic H1N1 in households, schools and in the community places this virus in the higher range of transmissibility," said Yang Yang, Ph.D., first author of the paper and a staff scientist at VIDI.

Although social distancing and the use of antiviral medicines can be partially effective at slowing pandemic flu spread, vaccination remains the most effective means of pandemic influenza control, the authors conclude. From a cost effectiveness measure, vaccination remains the most effective, while closing schools and other social gathering places is the least cost effective.

Vaccination increases population-level immunity and lowers the effective reproductive number of the virus, which results in two main effects: slowing the spread of infection and reducing the height of the epidemic peak; and reducing the overall illness attack rate, hospitalizations and mortality.

Other key findings in the study:

The current pattern of pandemic spread is most likely to be similar to the Asian influenza A (H2N2) pandemic of 1957-58. Substantial spread was expected to begin in early September with the epidemic peaking in mid to late October.

"In this case, child-first, phased vaccination would need to start as soon as possible, and no later than mid September to be effective for mitigation," said Longini, a biostatistician in the Center for Statistical and Quantitative Infectious Diseases at the Hutchinson Center. He is also a professor of biostatistics at the University of Washington School of Public Health. Longini said that the current U.S. plan called for the vaccination to probably start in mid October, which could still be effective if the epidemic peaked in November or December as it did during the Hong Kong influenza A(H3N2) of 1968-69.

Children will experience the highest illness attack rates based upon epidemiological observations from the U.S. and around the world. In addition, from an outbreak of pandemic H1N1 at a private school in New York last April, the authors estimate that the typical student will infect an average of 2.4 other children in his or her school.

Many findings in this study are based on epidemiological studies and vaccine trials in the past for seasonal influenza vaccines.

"We would hope to be able to estimate the effectiveness of pandemic vaccines and other mitigation measures so that we can understand the control of pandemic H1N1 influenza," said M. Elizabeth Halloran, D.Sc., M.D., a co-author of the study and member of VIDI and professor of biostatistics at the University of Washington School of Public Health.

The predicted rate of pandemic H1N1 transmissibility how many people an infected person will infect during influenza’s infectious period in the beginning of an outbreak is estimated to be 1.3 to 1.7. A value of 1.6 means that the epidemic could generate a total of 2.2 billion cases worldwide over a year. That translates to an overall illness attack rate of 32 percent of entire populations of a city or country. A person infected by someone else can expect to fall ill about two days after infection.

Longini and colleagues are considered among the world’s leading disease modeling experts. They are part of the federal government’s Models of Infectious Disease Agent Study (MIDAS) Network, an effort funded by the National Institute of General Medical Sciences at the National Institutes of Health.

Funding for the study came from the National Institute of General Medical Sciences and the National Institute of Allergy and Infectious Diseases.

Note to editors/reporters: To obtain a copy of the paper, "The Transmissibility and Control of Pandemic Influenza A (H1N1) Virus," please contact the Science press office at 202-326-6440 or scipak@aaas.org

MEDIA CONTACT:
Dean Forbes
Fred Hutchinson Cancer Research Center
(206) 667-2896
dforbes@fhcrc.org

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Study finds obesity, alcohol consumption and smoking increase the risk of developing a second breast cancer

September 08, 2009

SEATTLE Sept. 8, 2009 It is well known that survivors of breast cancer have a much higher risk of developing a second breast cancer than women in the general population have of developing a first breast cancer. However, little is known about what lifestyle factors may make survivors more vulnerable to a second cancer.

A new study by researchers at Fred Hutchinson Cancer Research Center, published online Sept. 8 in the Journal of Clinical Oncology has found that obesity, alcohol use and smoking all significantly increase the risk of second breast cancer among breast cancer survivors.

We found that obese women had a 50 percent increased risk, women who consumed at least one alcoholic drink per day had a 90 percent increased risk, and women who were current smokers had a 120 percent increased risk of developing a second breast cancer, said lead author Christopher I. Li, M.D., Ph.D., an associate member of the Public Health Sciences Division at the Hutchinson Center. Li, an epidemiologist, primarily studies what causes breast cancer and how it can be prevented.

His study adds to a small but growing body of evidence that obesity (a body mass index of 30 kg/m2 or more), alcohol consumption (consuming at least seven drinks a week) and current smoking may be important risk factors for second breast tumors, Li said. The research also suggests that current smokers who imbibe at least seven drinks a week may be at particularly high risk of second breast cancer.

Our study results afford breast cancer survivors three ways to potentially reduce their risk of second cancers: Stay at a normal weight, don’t smoke and drink in moderation, he said.

Both obesity and alcohol use are associated with increased levels of circulating estrogen, and this is thought to be the primary means through which they confer an increased risk of breast cancer, since estrogen can fuel breast cancer growth. The link between smoking and breast cancer may be attributed to carcinogens in tobacco smoke.

For the study, Li and colleagues assessed body mass index, alcohol use and smoking status in 365 women who were diagnosed with both a first and a second breast cancer, and compared them to 726 matched controls diagnosed with only a first breast cancer. Obesity, alcohol use and smoking data were collected from medical record reviews and participant interviews. The study participants, all from the Seattle/Puget Sound region, were first diagnosed with breast cancer between the ages of 40 and 79.

Breast cancer now has a greater than 90 percent five-year survival rate in the United States, resulting in a large and ever-growing number of survivors. Since these women are at two to six times greater risk of developing a second cancer compared to women in the general population, it is important to understand factors that may increase that risk, Li said. We know that lifestyle factors such as obesity, smoking and heavy alcohol consumption are linked with a number of life-threatening diseases in addition to cancer, and so reducing or eliminating these factors could have the added benefit of reducing a survivor’s risk of developing a second breast cancer.

The National Cancer Institute funded the research.

Note for media only: To obtain an embargoed copy of the Journal of Clinical Oncology paper, Relationship Between Potentially Modifiable Lifestyle Factors and Risk of Second Primary Contralateral Breast Cancer Among Women Diagnosed with Estrogen Receptor-Positive Invasive Breast Cancer, please contact Kelly Powell at the American Society of Clinical Oncology, 571-483-1365 or kelly.powell@asco.org. To arrange an interview with Li or obtain a post-embargo copy of the paper, please contact Kristen Woodward in Hutchinson Center media relations, 206-667-5095 or kwoodwar@fhcrc.org.

MEDIA CONTACT:
Kristen Woodward
Fred Hutchinson Cancer Research Center
(206) 667-5095
kwoodwar@fhcrc.org

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Turning back the clock: Fasting prolongs reproductive life span

August 27, 2009

SEATTLE Aug. 27, 2009 Scientific dogma has long asserted that females are born with their entire lifetime's supply of eggs, and once they're gone, they're gone. New findings by researchers at Fred Hutchinson Cancer Research Center, published online Aug. 27 in Science, suggest that in nematode worms, at least, this does not hold true.

Molecular physiologist Marc Van Gilst, Ph.D., and colleagues report that during starvation, sexually mature adult worms stop ovulating and the germline component of their reproductive system the sex cells, including mature and maturing eggs dies off and leaves behind nothing but a few stem cells. However, once normal food conditions resume, the conserved stem cells can produce a brand new crop of sex cells, complete with youthful and fertile eggs. This turning back of the reproductive clock all takes place in tiny C. elegans soil worms that are up to 15 times older than normally fed worms in their reproductive prime.

"For many, it has been assumed that cells and organs remain relatively stable during periods of starvation or caloric restriction," said Van Gilst, an assistant member of the Hutchinson Center’s Basic Sciences Division, who authored the study with postdoctoral research fellow Giana Angelo, Ph.D.

"The idea that an entire system would kill itself off during starvation and then regenerate upon food restoration was very surprising. The fact that extremely old worms could generate new eggs and produce healthy offspring long after their normally fed counterparts had reproduced and died was also unexpected," he said.

The mechanism behind the preservation and extension of fertility long past the worms' normal reproductive prime, Van Gilst suspects, is a signaling receptor protein in the cell nucleus called NHR-49, which promotes a major metabolic response to dietary restriction and fasting. While it has been hypothesized that this protein may interface with calorie restriction to extend life span, until now its role in protecting and extending reproductive longevity in the face of starvation had not been known. "In worms that contained an inactive NHR-49 gene, reproductive recovery and fertility after starvation were severely impaired," he said. "We found that reproductive arrest and recovery are highly dependent on a functioning NHR-49 gene."

NHR-49 in worms is analogous to various proteins in humans, all of which belong to a family of proteins called nuclear receptors. Nuclear receptors, such as estrogen receptors and androgen receptors, are particularly good targets for pharmaceutical intervention. "The identification of a nuclear receptor that turns on and off the beneficial response to nutrient deprivation would be of great interest because it would be a candidate for drugs aimed at tricking the body, or specifically the reproductive system, into thinking they are calorically restricted or starved, even when food intake is normal," Van Gilst said.

The biomedical implications of model organisms such as flies and worms cannot be overlooked, he said. "Many paradigm-shifting discoveries in C. elegans have since been replicated in humans. Therefore, the idea that our findings will be relevant to human reproduction is a possibility that certainly needs exploration," he said.

However, Van Gilst is quick to point out that even if this mechanism is conserved in humans, it is still unknown what degree of caloric restriction would be required to impact egg production in humans. "If such a process exists in humans, it likely evolved to help our ancestors preserve fertility during periods of famine or food shortage. We certainly don’t have a prescription for famine. Consequently, our study should not be used to promote potentially dangerous interventions such as severe caloric restriction and starvation as a means to restore a woman’s fertility," he said.

In the meantime, Van Gilst and colleagues will continue to study the tiny worm to better understand the basic mechanisms that control fertility. One question their research may help address is how in some cases women recovering from radiation and bone marrow transplantation which damages or destroys much of the germline, including mature and immature eggs can regain their fertility.

"There is controversy over how this occurs," Van Gilst said. "On the one hand, it has been argued that new eggs are generated from the woman's germline stem cells through a process that may mirror the germline regeneration we observed in C. elegans. In fact, there is controversy over whether or not germline stem cells exist in adult women. We believe that our work in C. elegans throws another hat in the ring, raising the possibility that germline stem cells may indeed be present in women and that their activity may surface under conditions of nutrient deprivation or stress," he said.

This work may also shed new light on cancer. "Cancer cells, when starved, are very susceptible to cell death. However, cancer stem cells, or progenitor cells, often thrive and flourish during starvation in cell-culture experiments. When nutrition is restored, these cells can trigger rapid regrowth. Consequently, understanding how germline stem cells in C. elegans survive starvation may help appreciate how cancers survive treatments aimed at starving tumors," he said.

For the study, the researchers withheld food from two types of nematodes: those that were genetically normal and those that lacked a functioning NHR-49 gene. The worms were monitored every few days by microscopy to observe changes in their reproductive system, including ovulation, cell death and germline stem cell survival. After different periods of starvation, food was restored and the worms were again monitored by microscopy to assess the recovery of their reproductive system. Fertility was determined by counting offspring after mating.

The research was supported by a National Institutes of Health Ruth L. Kirschstein National Research Service Award, the American Diabetes Association and the National Institute of Diabetes and Digestive and Kidney Diseases.

Note for media only: To obtain a copy of the paper, "Starvation Protects Germline Stem Cells and Extends Reproductive Longevity in C. elegans," or to arrange an interview with Van Gilst, please contact Kristen Woodard, 206-667-5095 or kwoodwar@fhcrc.org.

MEDIA CONTACT:
Kristen Woodward
Fred Hutchinson Cancer Research Center
(206) 667-5095
kwoodwar@fhcrc.org

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Long-term tamoxifen use increases the risk of an aggressive, difficult to treat type of second breast cancer

August 25, 2009

SEATTLEWhile long-term tamoxifen use among breast cancer survivors decreases their risk of developing the most common, less aggressive type of second breast cancer, such use is associated with a more than four-fold increased risk of a more aggressive, difficult-to-treat type of cancer in the breast opposite, or contralateral, to the initial tumor. These findings by Christopher Li, M.D., Ph.D., and colleagues at Fred Hutchinson Cancer Research Center were published online Aug. 25 in the journal Cancer Research.

Hormonal therapy with drugs like tamoxifen is one of the most common treatments for breast cancer because it has been shown to reduce the risk of dying from the disease but, as this study suggests, it does have risks.

Comparing breast-cancer patients who received the estrogen-blocking drug tamoxifen to those who did not, the researchers found that while the drug was associated with a 60 percent reduction in estrogen receptor-positive, or ER positive, second breast cancer the more common type, which is responsive to estrogen-blocking therapy it also appeared to increase the risk of ER negative second cancer by 440 percent. "This is of concern, given the poorer prognosis of ER-negative tumors, which are also more difficult to treat," said Li, an associate member of the Hutchinson Center's Public Health Sciences Division.

These findings confirm preliminary research by Li and colleagues, published in 2001, which was the first to suggest a link between long-term tamoxifen use and an increased risk of ER-negative second cancers. "The earlier study had a number of limitations. For example, we did not have information on the duration of tamoxifen therapy the women received," Li said. "The current study is larger, is based on much more detailed data, and is the first study specifically designed to determine whether tamoxifen use among breast cancer survivors influences their risk of different types of second breast cancers," Li said.

This new study assessed history of tamoxifen use among 1,103 breast cancer survivors from the Seattle-Puget Sound region who were initially diagnosed with ER positive breast cancer between the ages of 40 and 79. Of these, 369 of the women went on to develop a second breast cancer. Nearly all of the women in the study who took adjuvant hormonal therapy used tamoxifen specifically. Detailed information about tamoxifen use was ascertained from telephone interviews and medical record reviews.

While the study confirmed a strong association between long-term tamoxifen therapy and an increased risk of ER-negative second cancer, it does not suggest that breast cancer survivors should stop taking hormone therapy to prevent a second cancer, Li said.

"It is clear that estrogen-blocking drugs like tamoxifen have important clinical benefits and have led to major improvements in breast cancer survival rates. However, these therapies have risks, and an increased risk of ER negative second cancer may be one of them. Still, the benefits of this therapy are well established and doctors should continue to recommend hormonal therapy for breast cancer patients who can benefit from it," Li said.

The National Cancer Institute funded the research.

Note for media only: To obtain a copy of the paper, "Adjuvant Hormonal Therapy for Breast Cancer and Risk of Hormone Receptor-Specific Subtypes of Contralateral Breast Cancer," or to arrange an interview with Li, please contact Kristen Woodard, 206-667-5095 or kwoodwar@fhcrc.org.

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CONTACT
Kristen Woodward
Fred Hutchinson Cancer Research Center
(206) 667-5095
kwoodwar@fhcrc.org

W.M. Keck Foundation awards $1 million to Hutchinson Center scholar to study how cells go awry

August 03, 2009

SEATTLE Aug. 3, 2009 Anyone touched by the ravages of cancer knows the rapidly growing, opportunistic cells don't play fair. But in order to expose exactly how cancer cells cheat their host, scientists must first study the rules governing the orderly cooperation of normal cells.

For creating a system that studies the rules governing cellular order which enhances the potential for learning how cancer cells cheat Fred Hutchinson Cancer Research Center basic scientist Wenying Shou, Ph.D., has been named among the W.M. Keck Foundation’s 2009 class of Distinguished Young Scholars in Medical Research. Shou is among five U.S. scientists tapped to receive the five-year, $1 million award, established by Keck to provide resources to promising young scientists in pursuit of groundbreaking biomedical research.

Shou, an assistant member of the Center's Basic Sciences Division, studies social interactions between cells. Her lab set up an artificial system in which two sets of yeast cells are forced to cooperate when each lacks the ability to make an essential nutrient required for life. Each strain's essential nutrient is available in the other, so the two organisms can live together but not on their own. The system accommodates ongoing, quantitative measurements of population size and interaction and is compatible with mathematical modeling.

Shou and her colleagues are now investigating what happens when a third type of cell, a "cheater," which requires a nutrient but gives nothing back, is introduced into the system. The lab also looks into the role of spatial structure in stabilizing cooperation among cells.

Shou completed her postdoctoral work in quantitative biology at the Rockefeller University and in computational biology at Memorial Sloan-Ketting Cancer Center. She earned her doctorate from the California Institute of Technology.

Other Young Scholars awardees from the Hutchinson Center have included Adrian Ferre-D’Amare, Ph.D., of the Basic Sciences Division (2003) and Bruce Clurman, M.D., Ph.D., of the Clinical Research and Human Biology divisions (1999).

The W.M. Keck Foundation is a leading supporter of high-impact medical research, science and engineering. Established in 1998, the Keck Distinguished Young Scholars in Medical Research program was designed to support groundbreaking research addressing the fundamental mechanisms of human disease. 54 young investigators have received funding. More information about the Keck Foundation and its Young Scholars program is available at www.wmkeck.org/programs/scholars.html.

MEDIA CONTACT:
Christi Ball Loso
Fred Hutchinson Cancer Research Center
(206) 667-5215
closo@fhcrc.org

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Tuberculosis vaccines, drugs and diagnostics under development expected to have major impact on the disease

August 03, 2009

SEATTLE Aug. 3, 2009 The latest drug regimens, vaccines and diagnostic tools under development to combat tuberculosis could have a potentially large impact on the disease once they become available, according to research findings published in the Aug. 3 early edition online of the Proceedings of the National Academy of Sciences.

Using a mathematical model that examined TB in Southeast Asia, a region with a large proportion of TB cases worldwide, researchers in the Vaccine and Infectious Disease Institute at Fred Hutchinson Cancer Research Center found that the incidence of the disease could be reduced between 13 percent and 71 percent by 2050, depending upon the type of interventions used and whether they are implemented singly or in combination.

The study was led by M. Elizabeth "Betz" Halloran, M.D., D.Sc., a member of the Hutchinson Center’s Public Health Sciences Division and professor of biostatistics at the University of Washington, and directed by Laith Abu-Raddad, Ph.D., an assistant member of the Hutchinson Center’s Public Health Sciences Division and a visiting assistant professor of public health at Weill Cornell Medical College in Qatar.

Halloran and colleagues examined the expected benefits of implementing the new TB tools developed with support from the Bill & Melinda Gates Foundation. They chose to apply their modeling to the 11-country Southeast Asia region as defined by the World Health Organization (Bangladesh, Bhutan, Democratic People’s Republic of Korea, India, Indonesia, Maldives, Myanmar, Nepal, Sri Lanka, Thailand and Timor-Leste) because it already has successful TB-intervention programs.

"Our results demonstrate that each of the novel vaccines, drug regimens and diagnostics currently under development offers substantial reductions in TB incidence and TB-related mortality compared with current approaches," said Abu-Raddad, the study’s first author. "Were these technologies used in combination, there would be an additional powerful synergistic effect," he said.

Some of the study's key findings:

● Vaccination of newborns with the vaccine under development by the Aeras Global TB Vaccine Foundation could decrease TB incidence by 39 percent to 52 percent by 2050.
● The Global Alliance for TB Drug Development is working on new drug regimens that shorten treatment duration and are effective against drug-resistant TB strains which could reduce TB incidence 10 percent to 27 percent.
● The Foundation for Innovative New Diagnostics New leads the effort on new diagnostic tools that could reduce TB incidence by 13 percent to 42 percent. Diagnostics and treatment go hand-in-hand because new diagnostic tests have an epidemiological effect by moving people to treatment more rapidly. The three diagnostic methods examined in the study achieve their improvements in TB incidence and mortality fairly rapidly. The four-month, two-month, and 10-day novel active disease treatment regimens produce 10 percent, 23 percent, and 27 percent reductions in TB incidence by 2050 compared to 2015.
● In combination, the triple application of vaccination, new drugs and diagnostics the products could prevent 55.3 million cases and lower TB incidence by 71 percent (to 509.2 cases per million) by 2050, far more than any of the individual approaches.

"Combinations of the new technologies currently under development could have an enormous benefit," said Halloran. "However, there is a big difference between what is in the current portfolio and what could be achieved by going beyond it. To achieve further improvements, technologies and delivery strategies not currently under development should be considered."

The findings could alter the practice of tuberculosis control, particularly if mass vaccination catch-up campaigns were added to the current practice of vaccinating newborns, Halloran noted. The study results have already changed the way that Aeras is considering its vaccination strategies and goals to include mass vaccination options.

Halloran and colleagues are world renowned for creating disease models. For this study, they created a model of tuberculosis within a population, similar to previous TB models. Individuals have a defined disease state at all times, such as susceptible, latently infected, or recovered. The rates at which individuals transition from one state to another, and the factors that affect these transitions were determined from an extensive search of the existing TB literature. The team discussed the novel portfolio interventions with FIND, Aeras and TB Alliance to understand the expected efficacies and improvements over current approaches to TB intervention. The ways in which the new technologies are expected to work, and on whom, were plugged into the model. The group took the expected effects of the novel technologies and applied them to the large TB model to understand the results of these technologies on a population scale.

In 2006, Southeast Asia accounted for 35 percent of all new TB cases in the world and 32 percent of the world’s TB-related deaths. With no novel interventions, 101.7 million new TB cases and 17.9 million TB-related deaths are expected in the region between 2015 and 2050, according to researchers. Despite these grim numbers, the Southeast Asia region was chosen for the study because it already has generally successful TB intervention programs.

TB is considered to be the leading cause of death worldwide from a curable infection, and it is estimated that one-third of the world’s population is latently infected with the disease.

Co-authors on the paper included researchers from the Office of HIV/AIDS, Tuberculosis, Malaria and Neglected Tropical Diseases at the World Health Organization; the University of Washington; and the Vaccine and Infectious Disease Institute at the Hutchinson Center.

Note to reporters/editors: Please contact Dean Forbes to obtain a copy of the study or to arrange an interview with Dr. Halloran.

MEDIA CONTACT:
Dean Forbes
Fred Hutchinson Cancer Research Center
(206) 667-2896
dforbes@fhcrc.org

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Regular yoga practice is associated with mindful eating

August 03, 2009

SEATTLE Aug. 3, 2009 Regular yoga practice is associated with mindful eating, and people who eat mindfully are less likely to be obese, according to a study led by researchers at Fred Hutchinson Cancer Research Center.

The study was prompted by initial findings reported four years ago by Alan Kristal, Dr.P.H., and colleagues, who found that regular yoga practice may help prevent middle-age spread in normal-weight people and may promote weight loss in those who are overweight. At the time, the researchers suspected that the weight-loss effect had more to do with increased body awareness, specifically a sensitivity to hunger and satiety than the physical activity of yoga practice itself.

The follow-up study, published in the August issue of the Journal of the American Dietetic Association, confirms their initial hunch.

"In our earlier study, we found that middle-age people who practice yoga gained less weight over a 10-year period than those who did not. This was independent of physical activity and dietary patterns. We hypothesized that mindfulness a skill learned either directly or indirectly through yoga could affect eating behavior," said Kristal, associate head of the Cancer Prevention Program in the Public Health Sciences Division at the Hutchinson Center.

The researchers found that people who ate mindfully those were aware of why they ate and stopped eating when full weighed less than those who ate mindlessly, who ate when not hungry or in response to anxiety or depression. The researchers also found a strong association between yoga practice and mindful eating but found no association between other types of physical activity, such as walking or running, and mindful eating.

"These findings fit with our hypothesis that yoga increases mindfulness in eating and leads to less weight gain over time, independent of the physical activity aspect of yoga practice," said Kristal, who is also a professor of epidemiology at the University of Washington School of Public Health.

Kristal, a yoga enthusiast for the past 15 years, said that yoga cultivates mindfulness in a number of ways, such as being able to hold a challenging physical pose by observing the discomfort in a non-judgmental way, with an accepting, calm mind and focus on the breath. "This ability to be calm and observant during physical discomfort teaches how to maintain calm in other challenging situations, such as not eating more even when the food tastes good and not eating when you’re not hungry," he said.

To test whether yoga in fact increases mindfulness and mindful eating, Kristal and colleagues developed a Mindful Eating Questionnaire, a 28-item survey that measured a variety of factors:

disinhibition eating even when full;
awareness being aware of how food looks, tastes and smells;
external cues eating in response to environmental cues, such as advertising;
emotional response eating in response to sadness or stress; and
distraction focusing on other things while eating.

Each question was graded on a scale of 1 to 4, in which higher scores signified more mindful eating. The questionnaire was administered to more than 300 people at Seattle-area yoga studios, fitness facilities and weight-loss programs, among other venues. More than 80 percent of the study participants were women, well-educated and Caucasian, with an average age of 42. Participants provided self-reported information on a number of factors, including weight, height, yoga practice, walking for exercise or transportation and other forms of moderate and strenuous exercise.

More than 40 percent of the participants practiced yoga more than an hour per week, 46 percent walked for exercise or transportation for at least 90 minutes per week and more than 50 percent engaged in more than 90 minutes of moderate and/or strenuous physical activity per week.

The average weight of the study participants was within the normal range not surprising considering that the study sample intentionally consisted of people more physically active than the U.S. population in general. Body-mass index was lower among participants who practiced yoga as compared to those who did not (an average of 23.1 vs. 25.8, respectively).

Higher scores on the mindfulness questionnaire overall (and on each of the categories within the questionnaire) was associated with a lower BMI, which suggests that mindful eating may play an important role in long-term weight maintenance, Kristal said.

"Mindful eating is a skill that augments the usual approaches to weight loss, such as dieting, counting calories and limiting portion sizes. Adding yoga practice to a standard weight-loss program may make it more effective," said Kristal, who himself scored high on the mindful-eating survey and has a BMI within the normal range.

Moving forward, Kristal and colleagues suggest that their Mindful Eating Questionnaire, the first tool of its kind to characterize and measure mindful eating, may be useful both in clinical practice and research to understand and promote healthy dietary behavior.

"Beyond calories and diets, mindful eating takes a more holistic approach that can empower individuals to build positive relationships with food and eating, said first author Celia Framson, M.P.H., R.D., C.D., a former graduate student of Kristal's and former yoga teacher who now works with adolescents with eating disorders at Seattle Children's Hospital. "The Mindful Eating Questionnaire offers a new and relevant dimension for measuring the effectiveness of dietary behavior interventions. It also encourages nutrition and medical practitioners to consider the broad scope of behavior involved in healthy eating," she said.

Other authors on the paper included Denise Benitez, owner of Seattle Yoga Arts; Alyson Littman, Ph.D., an epidemiologist at the UW School of Public Health and Department of Veterans Affairs; Steve Zeliadt, Ph.D., of VA Puget Sound Healthcare; and Jeanette Schenk, R.D., a research dietitian in the Hutchinson Center's Cancer Prevention Program.

Fred Hutchinson Cancer Research Center funded the study.

Note for media only: To obtain a copy of the paper, Development and Validation of the Mindful Eating Questionnaire, or to arrange an interview with Kristal, please contact Kristen Woodard, 206-667-5095 or kwoodwar@fhcrc.org. Photos and broadcast quality B-roll of Kristal and co-author Denise Benitez practicing yoga are available upon request.

Photos: High-resolution, downloadable photos of Kristal and Benitez practicing yoga are available here.

MEDIA CONTACT:
Kristen Woodward
Fred Hutchinson Cancer Research Center
(206) 667-5095
kwoodwar@fhcrc.org

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