Story contributed by the Lymphoma Research Foundation
| New ways to attack an aggressive and incurable type of lymphoma will be studied at UNMC with the help of a $300,000 grant from the Lymphoma Research Foundation (LRF).
Kai Fu, M.D., Ph.D., associate professor of pathology and microbiology, has received the grant — called the 2009 Millennium Pharmaceuticals, Inc./Lymphoma Research Foundation Clinical Investigator Career Development Award — to support his mantle cell lymphoma research. This substantial investment by the Lymphoma Research Foundation is indicative of the group’s high esteem for Dr. Fu’s work, said Tom Rosenquist, Ph.D., vice chancellor for research at UNMC.
“I know that, with his innovative research approach and high level of energy, the investment will pay dividends in new, improved therapy for patients with mantle cell lymphoma,” he said.
Lymphoma — the most common type of blood cancer — is broadly categorized into Hodgkin’s lymphoma (HL) and non-Hodgkin’s lymphoma (NHL). According to the World Health Organization, there are six types of HL and more than 61 types of NHL.
Mantle cell lymphoma is a rare B-cell NHL that is very aggressive. It accounts for 6 percent of all new diagnoses of NHL — or about 3,000 new cases per year in the United States.
It is characterized by over expression of the gene called cyclin D1 due to a chromosomal translocation.
A subset of mantle cell lymphoma also shows higher levels of a group of small RNA molecules, called miR-17~92.
Dr. Fu and his colleagues have found that this higher expression correlates directly with poorer patient survival. These findings indicate that higher miR-17~92 expression induces abnormal activation of a pathway in tumor cells that leads to increased resistance to standard chemotherapy.
This recent award will help Dr. Fu conduct a pre-clinical study to determine whether suppression of miR-17~92 will improve the effect of chemotherapy. His study may lead to a novel approach to treat MCL patients.
“Dr. Fu’s elegant proposal explores a new avenue for understanding MCL and identifying potential therapeutic targets,” said Michael Williams, M.D., director of the University of Virginia’s Hematologic Malignancy Program and chairman of the LRF’s Mantle Cell Consortium, of which Dr. Fu also is a member. “We are delighted that Dr. Fu has chosen MCL as the focus of his Clinical Career Development Project.”
In 2008, The Nebraska Medical Center was recognized with the Gold Achievement Award of the American Heart Association’s Get With The Guidelines-Stroke program, which recognizes 24 consecutive months of providing care that meets or exceeds stroke treatment guidelines set by the association.
Stewart Becker of Omaha suffered a stroke while on a skiing vacation in Colorado. After a week in a Denver hospital, he came home to Omaha and met with Dr. Fayad.
“The perception was that in the middle of the country I wouldn’t have the resources I needed (as a stroke survivor),” Becker said. “In Dr. Fayad, I’ve got an individual with a great reputation with a great institution, and I can get as good of care right in my home city as I could get anywhere.”
Dr. Fayad currently chairs the Advisory Committee of the American Stroke Association, a division of the American Heart Association. He is also a member of the association’s International Stroke Conference Program Committee and National Science Advisory & Coordinating Committee.
UNMC’s hospital partner, The Nebraska Medical Center, has been named one of the 2009 ‘Top 100 Hospitals’ for nurses to work for by Nursing Professionals magazine. The Spring 2009 Top 100 Hospitals issue is now available.
“The Nebraska Medical Center appreciates and promotes a strong nursing care delivery model,” said Rosanna Morris, senior vice president and chief nursing officer at The Nebraska Medical Center. “The hospital ensures that nursing has a seat at every table where decisions are made not only organizationally, but particularly those that impact nursing practice and patient care.
“Support, recognition and promotion of the value of the nursing profession at The Nebraska Medical Center is what sets us apart from other organizations.”
Hospitals are selected based on a survey that is sent out to 25,000 randomly selected hospital nurses throughout the country that measures their job satisfaction. The survey featured questions such as, “How well does your hospital manage personal training and development?” and “Is your hospital a family-friendly employer?”
News of The Nebraska Medical Center’s award did not come as a surprise to many nursing staff.
“The thing that impresses me the most about working at the medical center is how much management involves nurses in decisions that affect us,” said Missy Schreiber, a staff nurse in the cancer care area at The Nebraska Medical Center for the past 21 years. “The hospital realizes nurses are the front line to patients and they want us to our job well and to do that, we have to have the right tools and resources.”
Mike Diggins, an emergency department nurse at The Nebraska Medical Center for 23 years, agreed.
“Nurses have a large voice in the hospital and that is supported by management’s open door policy,” Diggins said. “I can talk to my manager or director anytime. They welcome my input and they often will act upon it if they feel it’s valid.”
Diggins, who works three 12-hour weekly shifts, said the opportunity to have a flexible work schedule that fits his needs and allows him to have a balanced family and work life, is another attractive aspect of working at The Nebraska Medical Center.
“The hospital staff support me 100 percent when I’m here, but when my shift is over, I can leave my phone behind and focus on my family,” he said. “We truly have a state-of-the-art facility, so when I’m here, I know I have the equipment, tools and personnel to do my job well and provide exceptional nursing care.”
The support of education and of professional growth has been attractive factors for Schreiber.
“Support, recognition and promotion of the value of the nursing profession at The Nebraska Medical Center is what sets us apart from other organizations.” Rosanna Morris
“I’ve always been encouraged to participate in conferences, certifications and other educational opportunities,” Schreiber said. “The medical center wants nurses to be knowledgeable and current because that directly relates to how we care for our patients and allows us to provide the most current and up-to-date care.”
The working relationship between nurses and doctors is also important, Diggins said.
“The physicians respect our skills and judgment and rely on our input,” he said. “It is very much a team environment.”
A recent testament to nursing satisfaction at The Nebraska Medical Center was the hospitals “60 Nurses in 60 Days” recruitment campaign this past summer, which ended with 90 nurses joining the organization.
“A great majority of these nurses were from the local area and came with previous experience,” Morris said. “One of the greatest outcomes of this campaign, in addition to surpassing the initial goal, was that every one of the new nurses had been internally referred by a medical center employee.
“We are very pleased that our staff has such confidence in this organization to refer individuals that they knew to become a part of our team.”
Twenty-five years — 4,000 transplants.
UNMC and its hospital partner, The Nebraska Medical Center, are celebrating a significant milestone this year.
“Jim and his team always wanted the transplant program to be the best in the world and it has become the best,” UNMC Chancellor Harold M. Maurer, M.D., said Wednesday at a ceremony commemorating the program’s 25th anniversary. “(The program is made up of a) marvelous team of people that cannot be duplicated very easily anywhere else.”
Drawing patients from around the world, the program is ranked as one of the busiest adult lymphoma and pediatric programs in the country. The program averages 150 transplants a year and has performed more than 4,000 transplants since its founding.
There are many reasons why people come from around the world to receive care from the medical center’s transplant program.
Since its founding 25 years ago, physicians and researchers in the program have been pioneers in the field and have been recognized internationally for a number of ground-breaking advancements.
These advancements have helped improve success rates and have made bone marrow and stem cell transplants a more viable and promising option for a growing number of patients. This includes those with malignancies that include primarily lymphomas, leukemias, multiple myeloma as well as some blood disorders.
The first of these revolutionary achievements was the study and introduction of autogolous transplantation by Dr. Armitage and his colleagues, which served as the starting point and foundation for the program’s success.
“At the time, bone marrow transplants were still a very new thing,” Dr. Armitage said. “Allogeneic transplants, in which stem cells are harvested from a donor, were increasingly being done, but they were quite dangerous and risky. We wanted to find a way to help people who had otherwise incurable lymphoma. So we developed a hypothesis and began testing autogolous transplants as another option for these people.”
Autogolous transplants involve using the patient’s own stem cells, which reduces the complexity of the procedure and eliminates rejection issues such as graft versus host disease. This condition, which Dr. Armitage said occurs in more than half of all allogeneic transplants, happens when the new immune cells recognize that they are not in the right body and attack the other cells of the body.
Today, autogolous transplants are the preferred form of transplantation for more than 75 percent of lymphoma patients, he said.
Another milestone in the field of bone marrow and stem cell transplantation was the development of stem cell transplantation, which was introduced in 1984 by Anne Kessinger, M.D., professor of oncology/hematology at UNMC and a hematologist/oncologist at The Nebraska Medical Center.
The use of peripheral blood-derived stem cells, as opposed to bone marrow-derived stem cells, has become the standard of care for transplantation. This has helped improve outcomes for autogolous transplant patients, contributed to much quicker recovery times and decreased infection rates.
Peripheral blood-derived stem cell transplant is similar to bone marrow transplant except the cells are collected from those circulating in the blood rather than bone marrow. Bone marrow is the spongy tissue found inside the bones. It produces the body’s blood cells and cells of the immune system. The blood cells of the bone marrow, white blood cells, red blood cells, platelets and others, all come from one type of cell called the stem cell.
The process for removing stem cells is much easier, quicker and more comfortable for the patient, said Julie Vose, M.D., chief of hematology/oncology at UNMC. For instance, bone marrow removal required general anesthesia and was performed by using numerous needles to inject the patient until enough marrow had been withdrawn.
In comparison, stem cells are removed during a two- to three-hour procedure in which a catheter is placed into the chest and inserted into a large blood vessel. The blood is circulated through a special machine that separates out the stem cells from the rest of the blood. The stem cells are then frozen and stored until they are ready to be re-infused back into the patient.
“Research is critical. As leaders in research, we are able to offer our patients new and promising therapies before anyone else. You can either watch others do it or you can be the ones doing it, and we are definitely leaders in this area.”
Physicians and researchers at UNMC and The Nebraska Medical Center also have been extensively involved in the study and use of colony stimulating factors, also called growth factors. Growth factors are drugs that are used to stimulate the growth of cells before the collection of stem cells and are used during and after transplant.
“By being able to stimulate and increase the growth of stem cells after transplant, today we are seeing decreased infections, lower death rates, fewer transfusions and reduced recovery time in the hospital,” Dr. Vose said.
Other important treatment advancements that have had a significant impact in improving the outcomes for patients, Dr. Vose said, include improvements in supportive care techniques, anti-rejection medications and the ability to prevent and treat complications, especially infections.
“Twenty years ago, 30 to 40 percent of adult patients died from complications of an autogolous transplant,” she said. “Today, that number is down to 1 to 2 percent.”
In addition, adult transplant candidates used to be limited to those younger than 60 years of age. Today, transplants are performed on individuals as old as 75 years old. Survival rates average 50 to 60 percent, depending on the type of malignancy, compared to approximately 20 to 40 percent 10 years ago.
“Research is critical,” Dr. Armitage said. “As leaders in research, we are able to offer our patients new and promising therapies before anyone else. You can either watch others do it or you can be the ones doing it, and we are definitely leaders in this area.”
Pediatric transplants are another component of the bone marrow and stem cell transplant program. Started in 1987 by Peter Coccia, M.D., vice chairman of the department of pediatrics at UNMC and chief of pediatric hematology/oncology at The Nebraska Medical Center, the program has performed more than 335 transplants. Transplants in the pediatric population are normally reserved for patients with more aggressive disease and are far less common than adult transplants.
The majority of pediatric transplants are performed on patients with acute lymphoblastic leukemia. More than 80 percent of these patients will be cured with conventional chemotherapy, said Al Grovas, M.D., hematologist/oncologist at UNMC and The Nebraska Medical Center and clinical director for the pediatric bone marrow and stem cell transplant program, leaving about 20 percent of patients who will need a stem cell transplant.
“The knowledge curve has risen steadily since the first pediatric transplant in 1987,” Dr. Grovas said. “And with that, improved success rates have followed suit.
“The Nebraska Medical Center program is unique in that it shares the same transplant unit as the adult program. This provides us the advantage of sharing all of the same resources and the expertise of our experienced nursing staff and other health care professionals.”
–Dr. Armitage with Nancy Wurtele of Nebraska City, who was the second person to receive a transplant through the bone marrow and stem cell transplant program.
The program also is part of the National Institutes of Health/National Cancer Institute Bone Marrow Transplant Clinical Trials Network. This is a consortium of 16 transplant centers across the country that collaborate on clinical trials in order to derive data from a larger population of patients and to allow for greater sharing of information between centers.
Through this network, doctors can study and refine their techniques to diagnose, treat and follow patients to provide them with optimal care.
The medical center’s program is the only one of its kind in the region, said Theresa Franco, executive director of the cancer program.
“We have experienced physicians focused around specific diseases, an investigational mentality and pioneering treatments,” she said. “We have built this program on total commitment, total expertise and total engagement of our patients and families.”
Dr. Armitage said his ultimate hope is that the bone marrow and stem cell transplant program will some day go out of business.
“Because that would mean that we had learned enough about treating these cancers that patients would no longer need transplants,” he said.
And you can be sure that Dr. Armitage and researchers at UNMC and The Nebraska Medical Center will have played a major role in that scenario should it some day come to fruition.
Complex and rare cancers comprise approximately 15 percent of new cancer cases each year, making it difficult for patients to locate or research facilities with oncologists or surgical teams that are experienced in treating these specific malignancies.
Blue Cross and Blue Shield of Nebraska has named UNMC’s hospital partner, The Nebraska Medical Center, as a Blue Distinction Center for Complex and Rare Cancers.
Only 88 other medical centers in the United States have earned the same distinction.
Blue Distinction Centers for Complex and Rare Cancers were developed in strategic collaboration with the National Comprehensive Cancer Network (NCCN) with input from a panel of leading clinicians and professional organizations.
The NCCN is an elite group of 21 cancer centers across the United States, of which The Nebraska Medical Center is the only one in the region.
Peter Coccia, M.D., a pediatric oncologist at UNMC and The Nebraska Medical Center and member of the board of directors of NCCN, said, “We are very pleased to receive the Blue Distinction designation. As a founding member of the NCCN and as a National Cancer Institute Designated Cancer Center, it re-enforces our reputation as a nationally recognized referral site for rare and complex cancers. This designation and our recent award of being named one of the top 50 cancer care hospitals in the U.S. truly set this medical center apart.”
“Blue Distinction reflects the commitment of the entire organization to provide extraordinary care,” said Glenn Fosdick, president and CEO of The Nebraska Medical Center. “We care for some of the most seriously ill patients in the region. Our clinicians have worked diligently to make this one of the elite centers in the United States for these rare and complex cancers.”
“We want to recognize and reward those network providers who are setting new standards of excellence in the quality of health care,” said Dr. Bill Minier, chief medical officer at Blue Cross and Blue Shield of Nebraska. “Cancer touches the lives of so many Nebraskans. We are thrilled at the level of outstanding specialty care available to our members right here in our state.”
The Blue Distinction Centers for Complex and Rare Cancers designation is focused primarily on multidisciplinary treatment planning and complex, major surgical treatments.
Among other selection criteria, The Nebraska Medical Center met the following thresholds necessary to be named as a Blue Distinction Center for Complex and Rare Cancers:
Has multidisciplinary team input, including sub-specialty trained teams for complex and rare cancers and demonstrated depth of expertise across cancer disciplines in medicine, surgery, radiation oncology, pathology and radiology;
Demonstrates ongoing quality management and improvement programs for cancer care;
Demonstrates an ongoing commitment to using clinical data registries and providing access to appropriate clinical research for complex and rare cancers.
Demonstrates sufficient volume of experience in treating rare and complex cancers.
Blue Distinction is a designation awarded by Blue Cross and Blue Shield of Nebraska to medical facilities that have demonstrated expertise in delivering quality health care. The designation is based on rigorous, evidence-based selection criteria established in collaboration with leading clinicians, medical societies and professional organizations.
The Nebraska Medical Center recognizes that the majority of patients’ multidisciplinary treatment may be best accomplished by integrating the expertise available in a Blue Distinction Center with locally available treatment resources, especially for outpatient chemotherapy and radiotherapy, based on individual circumstances and patient preference. Optimal support of a patient’s comprehensive cancer care needs may be achieved by coordination of care between the patient and their family, local physicians, The Nebraska Medical Center and Blue Cross and Blue Shield of Nebraska.
UNMC researchers are part of a team that studied simple urine samples and found that certain estrogen derivatives can react with DNA to cause damage that may initiate breast, prostate and other cancers.
These findings — which are published in the Dec. 20 issue of the International Journal of Cancer — could result in better assessment of cancer risk and prevention, the researchers said. The team published similar findings in the journal The Prostate in 2006.
“We have a novel approach to cancer. We know the initiating step,” said Ercole Cavalieri, D.Sc., a professor at the UNMC Eppley Cancer Center. “We think prevention of cancer can be solved by eliminating this initiating step.”
The team’s findings were confirmed in a second, larger study and presented at a recent gathering of international scientists and physicians in San Antonio.
The study involves researchers at UNMC, Mayo Clinic and the Italian National Cancer Institute. The majority of the study was funded by a U.S. Army Breast Cancer Research Program Center of Excellence Award.
Estrogens can initiate cancer when natural mechanisms of protection do not work properly in the body, allowing estrogen metabolites to react with DNA.
“If these protections are insufficient, due to genetic, lifestyle or environmental influences, we think cancer can result,” Dr. Cavalieri said. “Now that we have the basic knowledge about this unifying mechanism of cancer initiation, we have a greater sense of urgency to assess people at risk and, at the same time, begin studies of prevention by using specific natural compounds.”
The screening test developed by the researchers analyzes estrogen metabolite profiles in humans and can simultaneously associate the profile with one’s risk of getting breast cancer. It involves testing a one-ounce sample of urine using a sophisticated method called tandem mass spectrometry, which analyzes about 40 estrogen-related compounds, including estrogen-DNA adducts formed by a chemical reaction of estrogen metabolites and DNA.
“We know the initiating step. We think prevention of cancer can be solved by eliminating this initiating step.”
Ercole Cavalieri, D.Sc.
Researchers analyzed estrogen-DNA adducts from 46 women with normal risk for breast cancer, 12 women at high risk of developing breast cancer, and 17 women diagnosed with breast cancer.
They found women at high risk of breast cancer and the women with breast cancer had significantly higher levels of the estrogen-DNA adducts in their urine samples, while the women with normal risk for breast cancer had low levels of the DNA adducts in their urine.
Nilesh Gaikwad, Ph.D., a UNMC researcher who developed the methodology for the screening tool, said the simple, non-invasive test could easily be applied in the clinical setting.
“We have found the first step that starts a cell down the road to becoming a cancer cell,” said UNMC research collaborator Eleanor Rogan, Ph.D. “By preventing this first step from happening, we think we can stop the development of breast or prostate cancer. The combination of an early detection test for cancer risk with administration of preventing agents should enable us to significantly reduce the number of women and men that develop breast or prostate cancer.”
The results are exciting because they show women at high risk of breast cancer can be identified by the level of adducts in a urine sample, researchers said.
“Similarly, initial studies in men have shown that healthy men have relatively low levels of estrogen-DNA adducts in their urine samples, but men with prostate cancer have much higher levels of the estrogen-DNA adducts in their samples,” Dr. Cavalieri said.
Researchers can use these estrogen-DNA adducts as a measure of cancer risk, he said.
Dr. Cavalieri also said accumulating evidence suggests that specific metabolites of estrogens, if abundantly formed, can become cancer-initiating agents by reacting with DNA and generating mutations leading to cancer.
DNA is composed of four bases called adenine, guanine, cytosine and thymine.
He said estrogen metabolites react predominantly with the first two DNA bases, adenine and guanine, to form estrogen-DNA adducts.
The resulting damage generated by the reaction can give rise to mutations that eventually initiate cancer. The important estrogen-DNA adducts spontaneously fall out of the DNA, leaving behind gaps that generate the cancer-initiating mutations.
The estrogen-DNA adducts eventually make their way out of cells and are excreted in urine.
“This finding identifies a new biomarker in the urine, which appears to correlate with a women’s risk of developing breast cancer,” said Kenneth Cowan, M.D., Ph.D., director of the UNMC Eppley Cancer Center. “While these studies need to be confirmed in a prospective study in a larger group of patients, this could become an important screening assay for women and could lead to new therapies to prevent breast cancer.”
Dr. Cavalieri said one of the major obstacles in cancer research is related to the concept that cancer is a problem of 200 diseases — a viewpoint that has impeded researchers from looking at the origin of cancers because the search would be prohibitively complex.
While the expression of various cancers coincides with the concept of 200 diseases, some scientists consider there to be a common origin for many prevalent types of cancer. There is widespread agreement in the scientific community that cancer is triggered by genetic mutations in critical genes, he said.
“The article is the best example of translational research. They have generated a unified concept of carcinogenesis and obtained a practical marker detectable in the urine of breast cancer patients,” said Jose Russo, M.D., senior member, at the Fox Chase Cancer Center in Philadelphia. “This article provides the adequate setting to explore this concept further by laying the basis to prepare a set of prospective clinical trials testing the preventive effects of the agents or mixtures of agents that can intercept the initiation event in breast or other cancers.”
The work represents a paradigm shift in detection of cancer risk in humans and provides the earliest possible rational marker for prevention strategies and regimens, said David Longfellow, Ph.D., president and chief executive officer of the Toxicology Forum — an international, nonprofit organization devoted to conducting open dialogues about problems in toxicology.
“This work conveys a very exciting message — that breast and prostate cancer risk can be identified years before the development of a tumor and suggests that natural preventive agents may be effectively used to prevent the initiation step in cancer,” Dr. Longfellow said. “Although this is a single manuscript, it is based on an extensive body of work in animal models and humans that consistently supports these findings and is complemented by collaboration with many international cancer scientists.”
Windle, John – Cardiovascular Disease
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Mysore, Mohan – Pediatric Specialist
Reynolds, George – Pediatric Specialist
Vanderhoof, Jon – Pediatric Specialist
Wilson, Mark – Pediatric Specialist/Allergy & Immunology
Bleicher, Stacie – Pediatrics (general)
Brabec, Bradford – Pediatrics (general)
Brown, Larry – Pediatrics (general)
Domet , Mark – Pediatrics (general)
Ebers, Douglas – Pediatrics (general)
Gasseling, Philip – Pediatrics (general)
Germer, Michael – Pediatrics (general)
Harrison, Francis – Pediatrics (general)
Higgins, Karen – Pediatrics (general)
Kaufman, David – Pediatrics (general)
Kinberg, Jo Ann – Pediatrics (general)
Koch, Robert – Pediatrics (general)
Krenzer, Kari – Pediatrics (general)
Kronberg, Kent – Pediatrics (general)
Lerner , Gary – Pediatrics (general)
Mikuls, Mary Jane – Pediatrics (general)
Moore, John – Pediatrics (general)
Nelson, Paul – Pediatrics (general)
Nielsen, Laura – Pediatrics (general)
Severson, Gregory – Pediatrics (general)
Shaffer, Kenton – Pediatrics (general)
Stephenson, Betsy – Pediatrics (general)
Straley, Joseph – Pediatrics (general)
Swisher, William – Pediatrics (general)
Willman, Brent – Pediatrics (general)
Woodford, Robert – Pediatrics (general)
Edney, John – Plastic Surgery
Heieck, John – Plastic Surgery
Stice, R. Coleen – Plastic Surgery
Bhatia, Shashi – Psychiatry
Chu, Chung-Chou – Psychiatry
Malin, Paula Jo – Psychiatry
Marcil, William – Psychiatry
Wilson, Daniel – Psychiatry
Floreani, Anthony – Pulmonary & Critical Care Medicine
Nelson, Nick – Radiology
Palmer, William – Rheumatology
Cole, Timothy – Surgery
Kingston, Timothy – Surgery
Raynor, Stephen – Surgery
Voigt, David – Surgery
Waltke, Eugene – Surgery
Thorson, Alan – Surgical Oncology/Colon & Rectal Surgery
Thanks in large part to the work of a UNMC scientist, an international group of researchers has demonstrated that embryonic stem cells can be converted into liver cells and used to restore liver function in mice with liver failure. The findings are reported in the Nov. 5 issue of Nature Biotechnology, the leading international science journal in the field.
Ira Fox, M.D., McLaughlin Professor of Surgery and senior associate dean for research in the UNMC College of Medicine, served as the senior author on the article and headed the study along with Naoya Kobayashi, M.D., Ph.D., of Okayama University Graduate School of Medicine and Dentistry in Japan.
In the study, the researchers generated liver stem cells from mouse embryos to help power a liver assist device in mice with acute liver failure. Typically, mice with acute liver failure die within a matter of days. However, using the liver assist device containing mouse liver cells derived from embryonic stem cells, 90 percent of the mice in the study experienced long-term survival.
After implanting the liver assist device seeded with the embryo-derived cells, the new cells developed characteristics nearly identical to those of primary hepatocytes (liver cells). The new cells filtered the blood much as the liver does, and kept the mice alive, while mice not fitted with the liver device died within two days.
The study was one of two articles in Nature Biotechnology this week that describe making liver cells from mouse embryonic stem cells. A research team at Mount Sinai School of Medicine in New York City headed the second study.
A third article in Nature Biotechnology, written by a San Diego research team, described an efficient method for converting human embryonic stem cells into cells that produce hormones made by the pancreas, a technique that could lead to a cure for diabetes.
“Both (liver) articles lay out a road map for how to regenerate a failed liver using embryonic stem cells,” Dr. Fox said. “The next step is to apply this approach to producing human liver cells.
“Our study is an important first step, but there’s still plenty of work to be done. Our work, and the other studies published this week, show we’re getting closer and closer (to making this applicable to humans).”
Embryonic stem cells are the body’s master cells and have the ability to transform into any kind of cell or tissue in the body.
Drs. Fox and Kobayashi have worked together for years on liver cell regeneration. Dr. Kobayashi worked at UNMC for two years completing his post-doctoral training under Dr. Fox during the late 1990s. In 2005, two UNMC research teams – one headed by Dr. Fox, the other by Stephen Rennard, M.D., Larson Professor of Pulmonary Medicine – received training on how to use human embryonic stem cells in research. Both groups brought human embryonic stem cell lines back to Nebraska for their research. The embryonic stem cell lines are among the stem cell lines approved by President Bush.
A liver transplant surgeon, Dr. Fox is trying to determine if embryonic stem cells can be safely turned into liver cells that would ultimately be infused into failing livers. This form of therapy, cell transplantation, could be used as an alternative to organ transplantation for some patients with liver failure.
Due to the shortage of organ donors to meet the increased demand for organ transplants, Dr. Fox has, over the past decade, examined a variety of alternative ways – other than organ transplantation – to regenerate damaged livers. During this period, Dr. Fox has also studied the properties of adult stem cells and pig liver cells for this purpose.
Infusing human liver cells into a diseased liver in 1997, Dr. Fox was the first to get transplanted individual liver cells to partially correct a rare metabolic liver disease in a 10-year old child. In doing so, the patient was able to avoid undergoing a liver transplant for many years. The research was reported in the New England Journal of Medicine in May 1998.
Currently, more than 17,000 Americans are on the waiting list for a new liver. Liver failure can be caused by viruses such as hepatitis, by drug or alcohol damage and by a range of other diseases. Often the only cure is a transplant, and more than 5,000 liver transplants are done in the United States each year.
Physician to Physician Collegial Consultation Services
International Healthcare Services at UNMC is very pleased to introduce its latest Collegial Consultation services.
We provide the best solution for electronic consultation, pathology review and second opinion.
In today’s world there are many times we would like to consult with another colleague or expert when treating our patients. It may be something as simple as an opinion to back up your decisions about a particular treatment, or a complex pathological diagnosis, or gene rearrangement studies, or treatment protocol recommendations.
UNMC is internationally renowned for the diagnosis, treatment and research of lymphoma, cancer care, transplantation and other serious diseases. UNMC has treated patients from all over the world. Our patients come from across the globe for initial diagnosis, second opinions, treatment, and participation in clinical research trials, bone marrow / stem cell and solid organ transplants. UNMC is among the top three transplant centers in the USA.
UNMC employs over 1,500 staff physicians/faculty/researchers in all healthcare disciplines to assist in collegial consultations.
Our service provides you with an opportunity to share opinions, discuss cases and collaborate with world-renowned physician experts at a very reasonable cost. The system employs the latest state-of-the-art, easy to use, Web-based software (provided at no cost to partner institutions) to facilitate worldwide transmission of electronic medical information, images, interactive diagnoses and “real-time” consultations in all areas of medicine. This sophisticated, yet easy-to-use, secure communication technology, enables UNMC specialists to receive patient reports for evaluation and consultation, in a matter of seconds, from any location across the globe.
2007 Pan Pacific Lymphoma Conference – June 11-15 Maui, Hawaii
We would so enjoy seeing members of our Global Strategic Partnership Program attend the Pan Pacific Lymphoma Conference. This year it is being held June 11-15 at the Grand Wailea Hotel in Maui, Hawaii. Please review and download our brochure and contact us with any questions you may have.
Bone Marrow Transplantation; A Success Story
Editorial in Middle East Health Magazine, Dec. 2006 by James O. Armitage, MD/University of Nebraska Medical Center, Omaha, NE, USA
It is very popular today to speak of stem cell research and the use of stem cells to treat disease. However, many involved in the debate regarding research and clinical applications of stem cells might not appreciate that hematopoietic stem cells have been used therapeutically for half a decade. Attempts to use hematopoietic stem cells to replace marrow aplastic anemia or to support intensive therapy of cancer began even more than 50 years ago. However, it was not until more was understood about bone marrow functions and the nature of the hematopoietic stem cell before the procedure that we know today as hematopoietic stem cell transplantation became practical. In the 1960’s successful allogeneic (i.e. from one individual to another) hematopoietic stem cell transplantation was reported for the treatment of leukemia and for the treatment of inherited immune defects. Working at the University of Washington in Seattle Dr. Don Thomas (i.e. who won the Nobel Prize) and his colleagues worked out the techniques of hematopoietic stem cell transplantation to treat leukemia and aplastic anemia. By the mid 1970s they reported 100 patients with acute leukemia treated with this approach with some patients surviving free of disease and apparently cured.
In the late 1970’s and early 1980’s, it became apparent that the new hematopoietic stem cells and the new immune system that they produced in the patient might also have an anticancer effect. The main complication of allogeneic hematopoietic stem cell transplantation is the development of a condition known as graft versus host disease. In this illness, the new immune system produced by the infused, allogeneic hematopoietic stem cells can recognize the patient as “foreign” and carry out an immune attack on the patient’s organs. Injury in this condition is especially frequently seen in the skin, liver, and gastrointestinal tract, and can some times be fatal. In the late 1970s and early 1980s remission of relapsed leukemia was noted in patients who developed severe graft versus host disease. It was speculated that there might be a graft versus leukemia effect and that it could be therapeutically important. Careful studies of large numbers of patients demonstrated that patients who developed graft versus host, were less likely to have recurrent leukemia. In fact, it appeared that much of the curative effect of allogeneic hematopoietic stem cell transplantation might be from the anticancer effect of the new immune system.
This observation led to attempts at reducing the intensity of the pretransplant therapy to reduce some of the risks of the procedure. It is possible to use predominantly drugs that impair lymphocyte function with relatively minor toxic effects in the patient and avoid very high doses of other chemotherapeutic agents or total body radiotherapy. It became apparent that sufficient impairment of the patient’s lymphocytes could allow the new hematopoietic stem cell graft to grow and eventually destroy the residual host lymphocytes giving a complete graft. In some cancers that seem to be particularly sensitive to immunological attack, e.g. chronic myeloid leukemia and chronic lymphoid leukemia, the graft versus leukemia effect seems to be potentially curative and the reduced intensity treatment before the transplant appears to reduce transplant related mortality. In those patients in whom the cancer does recur, reinfusing more of the donor’s lymphocytes often will reestablish remission. This approach is sometimes termed reduced intensity allogeneic hematopoietic stem cell transplantation, or mini transplant is now undergoing intensive study in transplant centers throughout the world.
The idea that very high doses of anticancer therapy might be curative for some patients with cancer, and that the use of reinfusion of the patients own hematopoietic stem cells could avoid the dangers of graft versus host disease, led to clinical trials in what is called autologous hematopoietic stem cell transplantation. In this treatment, hematopoietic stem cells have to be removed from the patient and stored until after the intensive cancer therapy is administered. Since the patient’s own hematopoietic stem cells would be used to reestablish bone marrow function after the treatment, there would be no risk of graft versus host disease. However, early problems with this treatment approach included occasional difficulties in collecting hematopoietic stem cells that were free of contamination by cancer cells and finding a way to store the hematopoietic stem cells for extended periods of time and keep them alive. In allogeneic transplantation, the hematopoietic stem cells are taken from one individual and reinfused quickly into another. However, since it takes time to administer the very intensive therapy, hematopoietic stem cells in autologous transplantation have to be cryopreserved for days to weeks before they are used. Initial attempts at autologous hematopoietic stem cell transplantation involved repetitive bone marrow aspirations from the pelvis and sternum to collect sufficient cells. It was not unusual for 200 aspirates to be required. However, in the mid to late 1980s it became apparent that circulating hematopoietic stem cells could be collected using the process called aphersis where the blood is taken from the body, separated by centrifugation, and the desired cells collected with the rest of the blood reinfused into the patient.
Autologous hematopoietic stem cell transplantation tested the hypothesis that very intensive anticancer therapy could cure some patients when standard therapy failed. Early studies in lymphoma showed that this can, in fact, be the case. In patients whose recurrent or resistant lymphoma still can partially respond to standard doses or chemotherapy and achieve a minimal disease state, hematopoietic stem cell transplantation can often be curative. As is the situation with allogeneic hematopoietic stem cell transplantation, treatment doesn’t benefit patients with all cancers, but is especially effective in patients with lymphoma, certain leukemias, multiple myeloma, and occasional other cancers.
Today both allogeneic and autologous hematopoietic stem cell transplantation are widely utilized to treat patients with cancer. Many patients who would otherwise have died of their malignancy are now cured because of these procedures. Allogeneic hematopoietic stem cell transplantation is also utilized for patients with aplastic anemia, inherited immune deficiency states, and certain other inherited disorders of blood production. Both allogeneic and autologous hematopoietic stem cell transplantation are being studied in the treatment of patients with other life threatening immune diseases. It is likely that both treatments will continue to be an important part of our therapeutic armentarium for years to come.
Lied Transplant Center
987835 Nebraska Medical Center
Omaha, NE 68198-7835
The Nebraska Medical Center
Management and classification of lymphoma and leukemia
Bone marrow transplantation
University of Nebraska Medical Center, Omaha, NE, Intern, (1974)
University of Nebraska Medical Center, Omaha, NE, Resident, (1975)
University of Nebraska, Lincoln, NE, B.S., (1969)
University of Nebraska Medical Center, Omaha, NE, M.D., (1973)
University of Iowa Hospitals and Clinics, Iowa City, IA, Fellow, (1977)’
Academic Rank:Shapiro Professor of Medicine
Department: Internal Medicine
College: College of Medicine
Membership in Societies: ASCO; ASH, AFCR, ASCR, ASCR, ASBMT, Royal College of Physicians
Dr. James O. Armitage graduated from the University of Nebraska Medical Center in 1973 where he completed his internship and residency in internal medicine in 1975. In 1977 he completed a fellowship in hematology-oncology at the University of Iowa Hospitals and Clinics, Iowa City, Iowa. Dr. Armitage was in private practice from 1977-79, and in 1979 he returned to the University of Iowa as an Assistant Professor of Medicine, where he developed and was director of the Bone Marrow Transplantation Program. In 1982 he returned to Nebraska as Associate Professor of Medicine and was promoted in 1987 to Professor of Medicine. He has served as Vice Chairman of the Department of Medicine (1982-90), Chief of the Section of Oncology/Hematology (1986-89), Chairman of the Department of Internal Medicine (1990-99), Dean, College of Medicine (2000-03), and presently holds the position of the Joe Shapiro Professor of Medicine. He is a member of several professional organizations as well as serving on the editorial boards of several peer-reviewed journals. He serves on several national and international committees and served as President of ASCO (1996-97) and President of ASBMT (2000-01). He has authored or co-authored 400 articles, 86 book chapters, more than 450 abstracts, and is the editor/co-editor of 21 books. He is married to Nancy Armitage and the father of four children and grandfather of two grandchildren.
Armitage JO, Weisenburger DD, Hutchins M, Moravec DF, Dowling M, Sorensen S, Mailliard J, Okerbloom J, Johnson PS, Howe D, Bascom GK, Casey J, Linder J, Purtilo DJ: Chemotherapy for Diffuse Large Cell Lymphomas–Rapidly Responding Patients Have More Durable Remissions. Journal of Clinical Oncology 4:160-164, 1986.
Kessinger A, Armitage JO, Landmark JD, Weisenburger DD: Reconstitution of Human Hematopoietic Function with Autologous Cryopreserved Circulating Stem Cells. Experimental Hematology 14:192-196, 1986
Philip T, Armitage JO, Spitzer G, Chauvin F, Jagannath S, Cahn JY, Colombat P, Goldstone AH, Groin NC, Flesh M. Laporte JP, Maraninchi D, Pico JL, Bosly A, Anderson C, Schots R, Biron P, Cabanillas F, Dicke K: High Dose Therapy and Autologous Bone Marrow Transplantation in 100 Adults with Intermediate or High Grade Non-Hodgkin’s Lymphoma. N Engl J Med 316:1493-1498, 1987
Kessinger A, Smith DM, Strandjord SE, Landmark JD, Dooley DC, Law P. Coccia PF, Warkentin PI, Weisenburger DD, Armitage JO: Allogeneic Transplantation of Blood-Derived, T-cell Depleted Hematopoietic Stem Cells after Myeloablative Treatment in Patients with Acute Lymphblastic Leukemia. Bone Marrow Transplantation 4:643-646, 1989.
Hasenclever D, Diehl V, Armitage JO, Assouline D, Bjorkholm M, Brusamolino E, Canellos Gp, Carde P, Crowther D, Cunningham D, Eghbali H, Ferme C, Fisher RI, Glick JH, Glimelius B, Gobbi PG, holte H, Horning SJ, Lister TA, Longo DL, Mandelli F, Polliack A, Proctor SJ, Specht L, Sweetenham JW, Vaughan Hudson G for the International Prognostic Factors Project on Advanced Hodgkin’s Disease: A Prognostic score for advanced Hodgkin’s disease. NEJM 339:1506-14, 1998
Allzadeh AA, Elson MB, David RE, MaC, Lossos IS, Rosenwald A, Boldrick JC, Sabet H, Tran T, Yu X, Powel JI, Yang L, Martl GE, Moore T, Hudson J, Lu L, Lewis DB, Tibshirani R, Sherlock G, Chan WC, Greiner TC, Weisenburger DD, Armitage JO, Warnke R, Levy R, Wilson W, Grover MR, Byrd JC, Boststein D, Brown PO, Staudt LM: Distinct Types of Diffuse Large B-cell Lymphoma Identified by Gene Expression Profiling. Nature 403:503-511, 2000.
Weisenburger DD, Anderson JR, Diebold J, Gascoyne RD, MacLennan KA, Muller-Hermelink HK, Nathwani BN, Ullrich F, Armitage JO for the Non-Hodgkin’s Lymphoma Classification Project. Systemic Anaplastic Large Cell Lymphoma. Results from the Non-Hodgkin’s Lymphoma Classification Project. American J Hemat 67:172-178, 2001.
Weekes CD, Vose JM, Lynch JC, Weisenburger DD, Bierman PJ, Greiner T, Bociek G, Enke C, Bast M, Chan WC, Armitage JO for the Nebraska Lymphoma Study Group. Hodgkin’s Disease in the Elderly: Improved Treatment Outcome With a Doxorubicin-Containing Regimen. J Clin Oncol 20:1087-1093, 2002.
Vose JM, Sharp G, Chan WC, Nichols C, Loh K, Inwards D, Rifkin R, Bierman PJ, Lynch JC, Weisenburger DD, Kessinger A, Armitage JO: Autologous Transplantation for Aggressive Non-Hodgkin’s Lymphoma: Results of Randomized Trial Evaluating Graft Source and Minimal Residual Disease. J Clin Oncol 20:2344-2352, 2002
Armitage JO. Staging Aggressive Non-Hodgkin’s Lymphoma: A Work in Progress. New England J Medicine 2005.
Dr. McCashland was sworn in recently at the 2006 International Congress in Milan, Italy.
Throughout his one-year term, he will be responsible for representing the society, monitoring the strategic direction of the organization, serving as a voice for the membership and acting on the members’ behalf. As president, one of his key responsibilities will be to help shape the future agenda and direction of the society.
“Volunteer leadership is a critical component to the success of any association, and ILTS is fortunate to have such a dedicated individual leading the society,” said Diann Stern, ILTS executive director. “We are confident Tim’s leadership and expertise will be an asset to ILTS and help ensure continued growth and success for the association moving forward.”
Dr. McCashland said it is an honor and privilege to serve the society.
“Its unique ability to bring to together leaders in the field of transplantation … is exciting,” Dr. McCashland said. “We look to expand our role in providing educational opportunities for physicians in training and to be an informational resource for patients and families concerning liver transplantation.”
Dr. McCashland earned his medical degree from UNMC in 1987 and completed his internal medicine residency at UNMC in 1990. He served a fellowship in gastroenterology at UNMC before completing a fellowship in therapeutic endoscopy at Western General Hospital in Edinburgh, Scotland, in 1993. Dr. McCashland is board-certified in internal medicine and gastroenterology.
ILTS is an international organization dedicated to the advancement of the science and practice of liver transplantation. Since its inception in 1990, the goal of the society has been to raise the standard of care for patients requiring liver transplantation and to promote education and research by disseminating and exchanging information related to liver transplantation within the medical community, as well the public.