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CityNews

A QUARTERLY PUBLICATION OF CITY OF HOPE

VOLUME 19 NUMBER 2

SUMMER 2008

BeatIng Breast cancer:


$5 million gift

from scientist funds new academic center

Diabetes answers may lie in stem cells

Cancers self-destruct button

Can the right lifestyle choices improve your odds?

Leadership Messages

A future rife with opportunity


Following an extensive review and application process, the National Cancer Institute (NCI) recently renewed City of Hopes core grant and Comprehensive Cancer Center status for five years, carrying the institution through 2013, its centennial year. Today, only 41 Comprehensive Cancer Centers across the nation have earned NCI designation. These centers are characterized by strong organizational capabilities, institutional commitment and transdisciplinary, cancer-focused science. According to the NCI, they also must possess experienced scientific and administrative leadership, and state-of-the-art cancer research and patient care facilities, so I am proud City of Hope again met the institutes stringent criteria. The NCI renewal is a meaningful indicator that we are well on our way to achieving the goals of our strategic plan. Rapid progress on the construction of the Arnold and Mabel Beckman Center for Cancer Immunotherapeutics and Tumor Immunology and the Michael Amini Transfusion Medicine Center also dramatically demonstrates that we are aggressively moving forward in realizing our aspiration to become the leading cancer center in Southern California and a top cancer center nationally. Creating greater visibility of our recent achievements in both California and nationwide is vitally important for us to continue this momentum. Furthering City of Hopes reputation enables us to keep attracting top talent to secure more important grants and other vital funding, and to continue enhancing our clinical and research excellence. You can help us in building awareness. I encourage you to join me in sharing the news of our remarkable accomplishments with others. As City of Hope supporters, one of the most important contributions we can make is to inspire others to find out more about the institution. When they learn about City of Hopes impact on biomedical research, I am confident they will come to share our own excitement about the institutions future. Terry R. Peets
Chair, City of Hope Board of Directors

A mission of prevention
Cancer remains complicated and unpredictable. Once thought of as a disease that just randomly strikes out of nowhere, cancer risk can clearly be reduced when people make healthy lifestyle choices. Avoiding tobacco, exercising, being careful of sun exposure and regularly eating a low-fat diet with a variety of fruits and vegetables are all well-known paths to risk reduction. When researchers talk about prevention through these lifestyle choices, they are actually describing ways to diminish cancer risks. It is an important distinction, because not every person who adopts healthy habits can necessarily avoid cancer. Genetics and other factors play a part in the complex evolution of cancer within the human body. But as a group, those who reduce these known risk factors are less likely to develop certain cancers than others. As members of a National Cancer Institute-designated Comprehensive Cancer Center, City of Hope researchers see prevention as a crucial mission. It is not enough to find the most effective therapies for cancer scientists must also seek to keep cancer from happening in the first place. But just how much influence do scientists and individuals have on risk? City of Hope researchers continue to ask that complicated question. In this issue of City News, City of Hope investigators from physicians to scientists examine the roots of risk in just one of the many malignancies they are studying: breast cancer. By understanding the role of environmental factors such as diet and sharing that knowledge, researchers help women take a greater part in deterring disease. At the same time, by discerning how important genetics are in the development of cancer, researchers can then hone strategies for early detection and find targets for therapy. Science is closing in on cancer from all directions, and City of Hope will continue the pursuit with vigor. Thank you for supporting this important quest. Michael A. Friedman, M.D.
President and Chief Executive Officer

City of Hope, an innovative biomedical research, treatment and educational institution, is dedicated to the prevention and cure of cancer and other lifethreatening diseases, guided by a compassionate patient-centered philosophy, and supported by a national foundation of humanitarian philanthropy.
City of Hope

City News is published quarterly for donors, volunteers and friends of City of Hope.

Brenda maceo Senior Vice President, Communications KeVIn Koga Vice President, Communications Fran rIzzI Senior Director, Communications

steVe KIrK Managing Editor alIcIa di rado Story Editor KIm hosozawa Associate Director, Creative Services rIcK amaya Designer

roya alt alIcIa di rado carmen r. gonzalez JennIFer healy elIse lamar shawn le roBerta nIchols h. chUng so sUsan doUglass yates Writers

City News SuMMER 2008

CityNews
A QUARTERLY PUBLICATION OF CITY OF HOPE

VOLUME 19 NUMBER 2

SUMMER 2008

Reducing your risk of breast cancer


One out of eight American women will be diagnosed with breast cancer during her lifetime. Are there any steps they can take to improve their chances? Some researchers believe so.

Another beginning for type 1 diabetes patients

Adult stem cells might hold the key to a new life for many living with the disease.

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A quick demise for cancer cells

New treatment strategies might make tumor cells even more vulnerable to chemotherapy.

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Gentle treatment for a harsh disease
Innovative applications expand the use of hematopoietic cell transplants.

Renowned investigator supports aspiring researchers

The new Cabilly-Riggs Academic Center will centralize City of Hopes Graduate School of Biological Sciences.

New leadership at Beckman Research Institute

Nationally recognized cancer researcher Richard Jove, Ph.D., assumes the role of director.

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Business leaders bring new perspectives

Eddy W. Hartenstein, Michael E. Keane and Kathleen McNamara are welcomed to City of Hopes board of directors.

W.M. Keck Foundation accelerates pace of research


Generous support furthers investigations into the molecular mechanisms underlying lymphoma.

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Spotlighting cancers below the waist


A unique fundraiser raises awareness and funds for several cancers not often discussed.
City News SuMMER 2008 I 1

ODDS
Breast cancer: Your role in prevention

BEATING THE

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By Roberta Nichols

Whether he is looking into the eyes of a 36-year-old mother or a 73-year-old retired teacher, delivering a breast cancer diagnosis is always difficult for George Somlo, M.D., co-director of City of Hopes Breast Cancer Program. As patients struggle to grasp the news, they ask hard questions that have no easy answers.

ILLuSTRATIONS: RAFAEL LOPEZ

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But Ive been taking my vitamins and going to the gym Im a healthy person. Why do I have breast cancer? Why me? Did I get this from my mother? Will I pass this on to my daughter? The truth is that no one knows, at least most of the time. Researchers do know this: In cancer, the bodys regular process of renewal breaks down, and cells multiply out of control then hidden genetic errors appear to kick off and encourage the process. These genetic errors do not seem to act alone. Research shows that environmental factors, diet and lifestyle also seem to influence risk. What matters more: the inherited patterns that mark womens genetic blueprints, or womens lifestyles? As science debates the question, City of Hope researchers pursue answers. They analyze the genes that might drive tumors, screen high-risk women to determine their inherited genetic risk of breast cancer, and work on ways to prevent breast cancers onset and recurrence. By tackling risk both from the genes within the body as well as the lifestyle factors that influence it, they aim to help women to survive breast cancer and reduce the chance of developing cancer altogether.

What matters more: a womans genes, or her lifestyle?

Somlo. So, the short answer to the environmentversus-genetics question is both. He cites the example of second-generation Japanese-American women. Research shows that breast cancer risk rises significantly in these women, compared to women living in Japan, and some believe that dietary changes may be to blame. Environmental factors matter.

genetIc VarIaBles
Beginning in 1990, the Human Genome Project sought to determine the sequence of chemical base pairs that make up DNA and to identify the more than 35,000 genes of the human genome. News stories about the studies may have led people to believe that genes determine health fate, said Jeffrey N. Weitzel, M.D., director of the Department of Clinical Cancer Genetics and the Cancer Screening & Prevention ProgramSM. This is partially true. Some genes strongly influence breast cancer risk; others only moderately affect it, Weitzel said, and moderate-risk genes are more common. unless they are in a specific sort of alignment, however, these moderate-risk genes dont necessarily cause a problem for most people, he said. Thats where were facing the greatest challenges right now: differentiating those moderate-risk genes from the high-risk ones. Researchers want to understand how moderate-risk genes affect the average womans breast cancer risk. Can you prevent a mutation? Of course not, said Weitzel. Can you lower the risk of cancer or enhance the chance of finding it at an earlier, more curable stage? Yes. Modifying environmental or behavioral influences such as weight, diet and exercise affects outcomes.

how mUch Is In the cards?


When it comes to cancer, especially breast cancer, said Thehang Luu, M.D., assistant professor in the Division of Medical Oncology & Therapeutics Research, we always wonder, are we born with it, is it in our genes, or is it something environmentally induced? Certainly, some women face risk factors like heredity and ancestry. Inheritance of mutations in certain genes called tumor suppressor genes causes about 5 to 10 percent of breast cancer cases, according to researchers. These genes are supposed to keep breast cells growing normally and prevent cancer, but when they are abnormal, or mutated, they are linked to greater breast cancer risk. The most common genes associated with hereditary breast cancer are the BRCA genes. Women with BRCA1 or BRCA2 mutations may have a family history of early onset breast cancer, ovarian cancer or both. Men with these genetic mutations face risks, too: BRCA2 is associated with male breast and prostate cancers. Less than Researchers at City of Hope are studying various 10 percent kinds of mutations in these genes and how much each of breast variation raises the risk of breast cancer, as well as investigating the prevalence of risk-raising mutations cancer cases in different ethnic groups. are currently We dont know in about 90 to 95 percent of the attributable patients what caused their breast cancer, so you cannot to inherited pinpoint it down to one particular genetic mutation, said

genes.

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Researchers continue to learn about the genetic underpinnings of breast cancer, seeking to understand how genetic mutations that accumulate over time might drive cancer development. Breast cancer researcher Susan Kane, Ph.D., professor in the Department of Surgical Research, though, has noted a common frustration shared by breast cancer researchers and patients: Knowledge does not necessarily yield immediate answers. We can detect breast cancer much earlier, diagnose it much more accurately and subcategorize it into different types based on gene expression patterns, she said. But that doesnt necessarily help us yet in making decisions about therapy and in having any more certainty in the likelihood of success or failure with particular types of therapy. So thats really the Holy Grail to me: trying to match what we are learning about genetic changes, environmental influences and gene expression patterns with specific therapies that we think are going to be the most effective.

For Kane, the most interesting work being done in this field is trying to understand the molecular activity surrounding different kinds of cancer. Identifying the specific genes that are turned on or off in breast cancer may yield valuable clues.

the role oF estrogen One of the factors that influences risk is a hormone essential to women: estrogen. Reproductive factors linked to estrogen and other female hormones clearly influence disease risk. Starting menstruation later and entering

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menopause earlier, for example, reduce a womans lifetime exposure to large amounts of estrogen coursing through her body and reduce the risk of developing breast cancer. Having children before age 30 and breastfeeding also reduces incidence. Yet, some of these factors are more history than habits, Weitzel said. For years, postmenopausal women were routinely advised to use hormone replacement therapy (HRT) to prevent cardiovascular disease and osteoporosis and lessen symptoms such as hot flashes. In 2002, much-publicized results from the Womens Health Initiative Trial for Hormone Replacement Therapy prompted many to stop HRT. The trial suggested that HRT particularly estrogen combined with progesterone increased breast cancer risk, so many women stopped taking the drugs. Afterward, breast cancer incidence began to decline. Clearly, hormones are a major part of the development of breast cancer, said Joanne Mortimer, M.D., vice chair and professor in the Division of Medical Oncology & Therapeutics Research and associate director for affiliate programs. Research shows that about 70 percent of breast cancers depend on estrogen to grow. Two clinical trials involving Shiuan Chen, Ph.D., director of the Department of Surgical Research and a co-director of the Breast Cancer Program, and Melanie Palomares, M.D., assistant professor in the divisions of Population Sciences and Medical Oncology & Therapeutics Research and a staff physician in the Department of Clinical Cancer Genetics, are investigating ways to lower hormone exposure in a unique way: by blocking a protein called aromatase. Aromatase is the enzyme that converts male hormones, androgens, into estrogens. After menopause, blocking aromatase can halt the most significant source of estrogen in the body, so new aromatase-inhibiting drugs have become a big part of physicians strategies in recent years to remove breast cancers fuel and keep the disease from recurring after treatment. Since aromatase comes from peripheral tissues such as fat cells, its presence is probably the mechanism linking the risk factor obesity to breast cancer, explained Palomares. Reproductive Chen and Palomares are examining whether factors substances from natural sources grape seed extract linked to and mushrooms can block aromatase and lower estrogen and breast cancer risk. Chens laboratory was one of three labs that originally characterized the human aromatase gene. Chen is widely known for his work in understanding drugs that inhibit aromatase. His lab is conducting extensive studies to evaluate why people become resistant to these drugs, and is developing strategies to reduce the drugs side effects.

a personal preVentIon menU


There is a lot women can do to affect their risk of developing breast cancer, Luu said. Diet plays an important role. We have more food choices available to us than previous generations, but not necessarily healthier, she said. She advocates a diet rich in fruits and vegetables. Luu also believes such foods that are purchased within 20 miles of where they are grown provide the most benefit, since they are more likely to be picked at the peak of freshness and retain 80 to 90 percent of their nutrients. Limiting alcohol consumption and avoiding smoking also lowers risk. Exercise also has been shown to reduce the risk of developing breast cancer (not to mention warding off diabetes, osteoporosis and cardiovascular disease). Studies show women with breast cancer who exercise have more stamina during their treatments, and that such activity may help prevent recurrence, as well. In addition to lifestyle choices, measures such as breast self-exams and regular mammograms can detect the disease early, greatly improving the odds for successful treatment. And genetic testing is beneficial for some individuals. Anyone with a personal or family history of breast or colon cancer before age 50, a woman who has had ovarian cancer at any age or those with a personal or family history of cancer in several close relatives on the same side of the family is a prime candidate for this testing, which scans DNA for inherited genetic mutations linked to cancer.

other female hormones clearly affect disease risk.

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worKoUts worK

There is perhaps no more renowned expert in the link between regular exercise and breast cancer risk reduction than Leslie Bernstein, Ph.D., director of the Department of Cancer Etiology in the Division of Population Sciences and professor and dean for faculty development. Her first study demonstrating that link was published in the Journal of the National Cancer Institute in 1994. Just weeks before, scientists had identified BRCA1 and BRCA2 genes. The news at that time was somewhat frightening and also good, Bernstein said. Women could be tested and theyd know if their chances were higher for getting breast cancer. And my study provided some hope, because it showed that physically active women experienced lower breast cancer risk. Physical activity was the good news story. It hit everywhere, and it hasnt stopped, she added. Bernstein began her research by searching for something that could modulate womens hormones, which were already known to influence breast cancer risk. Recalling her own teenage years as an athlete with altered menstrual cycle patterns, she turned to exercise as a target. Her first study focused on moderately active teenage girls. We measured hormone levels during their menstrual cycles, and saw that they didnt have the usual periodic increases of estrogen and spikes of progesterone, she said. From those data, we predicted that physical activity would reduce breast cancer risk. In 1995, Bernstein and her colleagues started the California Teachers Study. Funded by the National Cancer Institute until 2009, the study follows 133,500 current and former educators, comparing those who developed cancer to those who did not. The study has confirmed activitys link to reduced risk. Women who were the most active when they were younger are less likely to die of breast cancer, she said. Bernstein, who is the principal investigator for the study, and her colleagues continue to follow the women. She has conducted six other studies confirming that exercise helps prevent breast cancer, mitigate its effects and decrease the chance of recurrence. More than 30 other studies have validated her findings. In recognition of her work, Bernstein received the 2007 Komen Brinker Award for Scientific Distinction in breast cancer clinical research from Susan G. Komen for the Cure and the Cancer Prevention Award for Excellence in Cancer Prevention Research from the American Association for Cancer Research. Bernstein practices what she preaches, too. She has maintained her weight

Exercise reduces the risk of new and recurrent breast cancer.

by eating a balanced diet and exercising regularly. She suggests that all women exercise at least three to four hours per week. When Bernstein published the results from the first study, she encountered skeptical media who asked, So what if youre wrong? And I said, So what? Even if it doesnt prevent breast cancer, it might prevent you from dying from it if you do happen to get it, she said. Your overall health will improve, as well. This potential impact on prognosis following breast cancer is now an area of great interest in the field. Preliminary studies, including the California Teachers Study, indicate that women who exercise after diagnosis benefit in terms of lower chances of recurrence and better survival, she added. While researchers strive to define the role of genetics and environment in breast cancer risk, women can help themselves by fully exploring their family medical history, sharing it with their physicians and making smart lifestyle choices. Controlling what you can control your lifestyle really may have a meaningful impact, said Bernstein. n n n

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Stem cells may help type 1 diabetes patients

START OvER
By Elise Lamar

A diagnosis of type 1 diabetes comes with a lifelong burden of new responsibilities: regular monitoring of blood sugar levels, careful adherence to strict diet and exercise regimens, and daily insulin injections.
Researchers hope to ease the burden by developing new treatments for type 1 diabetes treatments that might one day even cure the disease. One promising area is stem cells. City of Hope researchers believe they may be able to engineer them into new cells that produce insulin. These new cells would replace islet cells, the insulinproducing cells in the pancreas that are destroyed in type 1 diabetes. Adult stem cells from human bone marrow can mature into cells resembling islet cells when placed within pancreas tissue, according to research by Chu-Chih Shih, Ph.D., assistant professor in the Division of Hematology & Hematopoietic Cell Transplantation. Shih published the findings in the journal Stem Cells and Development in October 2007. Scientists are looking for a variety of ways that would allow the body to keep producing insulin despite type 1 diabetes. City of Hope researchers, for example, perform islet cell transplants, investigative procedures in which surgeons transfer islet cells from a deceased donor into patients with diabetes. But supplies of donated islet cells are limited. Shih believes the stem cell strategy could relieve pressure to collect muchneeded islet cells from relatively few cadaveric donors. There have been only 2,000 pancreatic donors, but there are millions of patients with diabetes, Shih said. Stem cell therapies could supply alternative sources of cells that can differentiate into pancreatic islet cells, which would benefit most patients with diabetes. Shih and his colleagues began by asking whether a type of human stem cell could form islet-like cells. The researchers labeled these stem cells with a green tracer dye and then injected them into human pancreas tissue that had been transplanted onto laboratory mice. Four months later, we harvested tissue and saw green cells, meaning that the stem cells survived, Shih said. But the important question was, did they produce insulin? Not only did they produce insulin, but they pumped it out in proportion to the amount of the blood sugar glucose they were exposed to, just like islet cells would. Insulin is the hormone that signals the bodys cells to absorb glucose. Cells need glucose for energy. But without insulin around, glucose simply stays in the bloodstream and cells cannot absorb it. The group also reported another remarkable finding: When they transplanted these cells into laboratory mice engineered to have type 1 diabetes, the transplant relieved diabetes symptoms. Basically this experiment proves that the green islets derived from the stem cell graft are physiologically functional that they are as good as the islets you would purify from the pancreas, Shih said. He cautions that researchers are several years away from trying these therapies in humans. Of the more than 20.8 million people with diabetes in the united States, 5 to 10 percent have type 1. Although it can develop at any age, type 1 diabetes most commonly appears in children and young adults. One in every 400 to 600 children has been found to have the disease. The National Institutes of Health, the Ella Fitzgerald Charitable Foundation, the California Community Foundation and The Rosalinde and Arthur Gilbert Foundation funded the research. n n n

ILLuSTRATION: NEIL BRENNAN

Chu-Chih Shih

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CANCERS SELF-DESTRUCT
BuTTON
By Elise Lamar

PuSHING

The drive to survive runs strong in humanity and, despite illness, the body clings tightly and almost defiantly to life until the final breath. Within the body, though, different rules apply. While young, healthy and vibrant cells thrive, damaged and old cells seem to know when their time is up and commit a sort of cellular suicide.

Many cancer drugs work by damaging tumor DNA so severely that cancer cells do indeed commit suicide. Now, David K. Ann, Ph.D., professor in the Department of Clinical and Molecular Pharmacology, has learned how that self-destruct program gets switched on, suggesting strategies that might make cells more vulnerable to chemotherapy. He showed that when a cellular protein called ATM senses that DNA strands are badly broken, it instructs cells to selfdestruct by inactivating a protein that normally holds cell-death signals in check. Ann published the results in the Oct. 17 issue of the Journal of Biological Chemistry.

Several agents can activate ATM and stimulate cancer cell death. These include radiation and drugs like doxorubicin, which fights breast cancer by breaking strands of DNA in cancer cells. Ann and his collaborators showed that ATM goes into overdrive after a cells DNA is damaged and inactivates a protective protein called KAP1, whose job is to block cell death. The team found that KAP1 is often aided by a stabilizer a small molecule called SuMO. Being tethered to SuMO makes KAP1 resistant to ATM, protecting cells from self-destruct signals that might occur in response to mild DNA damage.

Reasoning that clipping off the stabilizer would deactivate KAP1 and leave cells more vulnerable to chemotherapy, Ann and colleagues tested the idea by doing the experiment in reverse. First, they created an artificial protein with SuMO irreversibly stuck to KAP1. Then they forced this protein into human breast cancer cells in a lab dish and tried to kill them with doxorubicin. Their findings bore out their idea: The tumor cells simply could not be eradicated by the cell-killing doxorubicin, most likely because they were protected by the super-stable KAP1. The study suggests that prior to treatment with therapies like radiation

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or cell-killing chemotherapy, a patients tumor cells could be analyzed for the presence of KAP1 protein as a predictor of how responsive the tumor might be to treatment that damages DNA. The less KAP1 they have, the better tumor cells should respond to radiation or chemotherapy, Ann said. Ann is collaborating with Yun Yen, M.D., Ph.D., director of the Department of Clinical and Molecular Pharmacology, to identify small molecules that could block KAP1 activation or stabilization. Yen, a co-author of the study, describes his and Anns partnership this way: I look for drugs, and he looks at

mechanisms. We must understand the mechanism of drug resistance in cancer; when we do, we will be able to screen patients to help them make a decision about whether a particular type of treatment would be useful. Ann thinks that anti-KAP1 drugs could be used as neoadjuvant therapy. Neoadjuvants are treatments given before radiation or chemotherapy to make cells more receptive to chemotherapy. In this case, giving patients a drug that eliminates or inactivates KAP1 in tumor cells before doxorubicin treatment could make cancer cells easier to eradicate. The National Institutes of Health

and the Taiwan National Health Research Institute funded the study. n n n

David K. Ann

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ILLuSTRATION: JEFFREY PELO

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ENErGy To BurN: PoTENTiAL SoLuTioNS To A

weighty problem
By Elise Lamar

Special mice in the lab of Shiuan Chen, Ph.D., can consume calories with the best of them and somehow still stay skinny. Chen, director and professor in City of Hopes Department of Surgical Research, and colleagues reported in the Journal of Biological Chemistry that mice engineered to lack a specific gene stay thin compared to regular mice, even when fed fatty foods. This effect is much more obvious when mice are fed a high-fat diet, Chen said. Regular mice tend to get chubby on this diet, but the mutants stay skinny. The findings impact research on obesity, which is linked to heart disease, stroke, diabetes and cancer. united States Surgeon General Richard Carmona calls obesity the greatest threat to public health today. Chens group is best known for identifying compounds that inhibit the enzyme aromatase, which helps the body make estrogen. Blocking aromatase activity is an effective therapy for estrogen-dependent breast cancer in postmenopausal women. The discovery of the lean mouse was a direct offshoot of these studies. The researchers are studying a gene that encodes a protein called PNRC2. The mice lack this gene. This project started because we were interested in whether PNRC2 regulated aromatase in breast cancer, said Chen. Instead, the researchers found that mice without the gene had fewer fat cells. That effect was most pronounced in male mice. And the mice are not skinny simply because they do not eat. Associate research scientist Dujin Zhou, M.D., Ph.D., lead author of the study, actually thinks they may eat a little more than normal mice. They just do not gain weight. Tests showed that the mice consume more oxygen and generate more heat than normal mice. Both can indicate a revvedup metabolism, which means that the mutant mice expend a lot
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more energy and burn off more calories from food than their normal, chunkier cousins. The PNRC2 protein, identified four years ago by Zhou, is a cofactor for proteins known as nuclear receptors, a large family that includes receptors responsive to sex hormones. That means these nuclear receptors need PNRC2 to help do their work. Zhou believes that PNRC2 may be especially critical for nuclear receptors involved in metabolizing fats and using energy but sex hormones might play an unknown role in the leanness of the mice, since the effect is stronger in males. The lab is currently investigating that connection. Metabolic disease is a new direction for Chens lab. We now need to understand why these mice are thin at the molecular level, said Chen, noting that they are looking for drugs that block PNRC2 activity. We are interested in whether we can manipulate PNRC2 activity and apply it to obesity in humans. Research has linked calorie restriction to longer life spans in organisms ranging from worms to mice, so the investigators will watch how long these mice which appear calorierestricted even though they are not will live. Laboratory mice normally live about two years. The National Institutes of Health funded Shiuan Chen the research. n n n

MArkiE rAMirEz

ILLuSTRATION: MARLENA ZuBER

Eating super-sized, fast-food meals every day sounds like a recipe for immediate obesity, but not for everyone.

lifting tHE AgE bArriEr on A PotEntiAlly

lifesaving treatment
By Roberta Nichols

Hearing a diagnosis of cancer is tough enough without also finding out that you are too old for a treatment that might save your life.
Non-Hodgkins lymphoma patients ages 60 and older have traditionally been excluded from hematopoietic stem cell transplants commonly known as bone marrow transplants because of the side effects. Yet these patients often have aggressive lymphomas that respond to such treatment. Now Amrita Krishnan, M.D., and her City of Hope colleagues have devised a new transplant procedure that appears to work well among older patients. The issue was that older patients with lymphoma do badly. So, can we transplant them with something that will increase the efficacy of the treatment? said Krishnan, associate professor in the Division of Hematology & Hematopoietic Cell Transplantation. PHYSICIANS LOOK BEYOND AGE There has been a lot of literature about older patients, examining why they do less well in cancer therapies, Krishnan explained. Is it because were afraid to give it to them? Cant they tolerate it? Is their disease more aggressive? The groups study, published in the Jan. 1 issue of the Journal of Clinical Oncology, showed that older patients can successfully undergo transplants if they have good functional status: in other words, they can perform normal daily activities to meet their basic needs and maintain health. That means their physiologic age is more important than the number of candles on their birthday cakes. Physicians today use hematopoietic cell transplantation, or HCT, to treat

four powerful anticancer drugs, it includes a radioimmunotherapy drug called Zevalin, which consists of tiny, engineered antibodies that carry radioactive isotopes directly to cancerous cells. In the groups clinical trial of more than 40 patients, the typical patient was 60 years old while the oldest was 78 (and is now 81). Researchers found that patients tolerated the addition of Zevalin to the treatment and had side effects comparable to those among patients taking the chemotherapy combination alone. Patients outcomes were promising enough to warrant more A GENTLER APPROACH study, Krishnan said. City of Hope researchers new Results are especially encouraging strategy includes a more for patients with diffuse intense, high-dose large-cell lymphomas, she conditioning regimen added. Researchers will but without increased next look at the regimens toxicity, which can effectiveness against certain often come from types of lymphoma to see if total body irradiation it is more successful than the (administering beams of traditional approach. radiation across nearly This has become a regimen the whole body). people are very interested in Besides a group of worldwide, Krishnan said. n n n Amrita Krishnan
PAulA MyErS

a patients malignancy or to repair diseased or defective bone marrow. These transplanted hemopoietic (blood) stem cells can come from patients themselves or matching donors. HCT starts with a conditioning regimen, in which chemotherapy is used with or without radiation therapy to kill many of the cancerous cells riddling the body. After the conditioning regimen, patients receive infusions of replacement stem cells. These new cells give rise to the patients new immune system.

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tHEy kill CEllS WitH

KINDNESS
By Roberta Nichols

Hematopoietic cell transplants can offer patients a second chance at life after a cancer diagnosis, but the seeming miracle may come at a price. A patients new, transplanted immune system often begins to attack the patients own body a condition called graft-versus-host disease.
Now, a new twist on treatment developed by City of Hope researchers may prevent this potentially deadly complication. Proceedings of the National Academy of Sciences published the findings from Defu Zeng, Ph.D., and his City of Hope colleagues in March. The procedure could expand the use of hematopoietic cell transplantation, or HCT, to treat autoimmune diseases such as lupus and type 1 diabetes as well as among more patients with blood-based cancers. Known as GvHD for short, graftversus-host disease is among the most common side effects for patients who undergo allogeneic HCT with radiation and chemotherapy. Allogeneic HCT means that cells used in the transplant come from a donor rather than the patient. We have developed a radiation-free, GvHD-preventive regimen that potentially can promote the application of allogeneic HCT for the cure of hematologic cancers and autoimmune diseases, said Zeng, principal investigator and assistant professor in City of Hopes Department of Diabetes, Endocrinology & Metabolism and Division of Hematology & Hematopoietic Cell Transplantation. As physicians explain, patients receive HCT to replace their own immune system and cancerous cells with healthy cells from a donor. Physicians must first destroy or inactivate patients own immune cells to make room for the new donor cells. They do this through what is called a conditioning regimen. Conditioning regimens traditionally include a combination of chemotherapy and full-body irradiation. Zengs team created a different conditioning regimen. The regimen first uses a special antibody to target and kill the patients T cells, cells of the immune system, which would otherwise attack donated bone marrow. The antibody does this without damaging the patients other tissue. Secondly, it uses the epigenetic drug vorinostat to kill cancer cells, as well as residual T cells, and reduce the side effects of the antibody infusion. unlike traditional chemotherapies, which cause the bodys tissues to release inflammatory chemicals that spur GvHD, vorinostat actually can keep tissues from releasing these chemicals. That helps the combination of the antibodies and vorinostat prevent GvHD. Physicians believe that HCT has the

From left, Dongchang Zhao, Defu Zeng and Nainong Li

potential to help autoimmune disorders such as lupus that fail to respond to other treatments, but the toxicity of radiation and chemotherapy and the possibility of GvHD have prevented the use of HCT in these patients. This proposed regimen may change that. The research was backed by the Marcus Foundation, a gift from Lynn Davis an enthusiastic supporter of research into treating autoimmune diseases with HCT and a pilot grant from the Lymphoma Specialized Program of Research Excellence, led by Stephen J. Forman, M.D., Francis and Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation. Forman and Mark Kirschbaum, M.D., Tim Nesvig Lymphoma Fellow and director of new drug development in the Division of Medical Oncology & Therapeutics Research, are developing a clinical trial of the method. n n n

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tAngSHEng yi

A LOOK AT THE LONG TERM


By Shawn Le

Cancer does not stop when patients leave the hospital and return home after treatment. Even if the disease itself never returns, its effects can last a lifetime.
Ask the breast cancer survivor whose arm swells with fluid long after surgery, or the colon cancer survivor who lost the feeling in his fingertips after therapy. The legacy of cancer often remains through the health effects its treatment leaves behind. People who undergo hematopoietic cell transplants (HCT) are at particularly significant risk of developing chronic health problems, so they need careful medical attention even decades after treatment, City of Hope researchers said. (HCT is often referred to as bone marrow transplantation.) Advances in cancer research and treatment have allowed more people to overcome and survive their diagnosis, but all cancer survivors, especially those who have undergone HCT, need regular medical follow-up care for the rest of their lives so we can help maintain their quality of life, said Can-Lan Sun, M.D., Ph.D., assistant research scientist in the Division of Population Sciences. Sun recently studied HCT survivors to better understand the challenges they face long after therapy. We wanted to learn what health issues most affected HCT patients, because no study has yet assessed the long-term morbidity of these survivors or attempted to identify which patients may be at highest risk, she said. The study, conducted with the university of Minnesota, examined 1,013 survivors who underwent HCT between 1974 and 1998. Researchers looked at how many

survivors experienced severe or lifethreatening conditions such as coronary artery disease, congestive heart failure, second cancers and kidney failure, and then compared that to the survivors 309 siblings. The most frequently reported conditions were cardiovascular and gastrointestinal problems and significant hearing or vision impairments. Among the HCT survivors, 69 percent had at least one chronic condition, which meant the HCT survivors had two-and-a-half times the risk of developing at least one chronic health condition compared to their siblings. About 29 percent of the HCT survivors reported a severe or life-threatening Can-Lan Sun condition, about five

times the risk of their siblings. HCT survivorship can be counted in decades now, and the chronic health burden carried by this group is significant, said Sun. Weve made great inroads into successfully treating cancer patients, and we should put as much effort into care for cancer survivors. Additional studies that monitor and evaluate the health and quality of life of cancer survivors will help to ensure that patients thrive after treatment. n n n

City News SuMMER 2008 I 15

MArkiE rAMirEz

ReseaRCh aNd tReatmeNt

gRaduate sChool suppoRt

$5 MILLION
By Jennifer Healy

GIFT

from renowned former City of Hope scientist funds new academic center

A $5 million gift from orly and shmuel cabilly, Ph.D., will support the new Cabilly-riggs Academic Center, centralizing City of Hopes Graduate School of Biological Sciences. The center will include teaching laboratories, classrooms and administrative offices, as well as a 150-seat auditorium for scientific seminars for students, faculty and outside scientists.
The new center will be housed within City of Hopes Arnold and Mabel Beckman Center for Cancer Immunotherapeutics and Tumor Immunology. Now under construction, the academic center is named for Shmuel Cabilly and Arthur D. Riggs, Ph.D., director emeritus of City of Hopes Beckman Research Institute. It is slated to open in 2009. In the early 80s, Riggs and Cabilly then a postdoctoral fellow in Riggs laboratory at City of Hope set in motion discoveries that would eventually result in a completely new way to treat cancer. The pair collaborated with scientists at Genentech on a novel method of making antibodies through recombinant DNA technology, the process in which scientists edit DNA to form DNA sequences that do not appear in nature. That work led to the development of significant cancer-fighting treatments including the drugs Herceptin, Rituxan and Avastin. Cabilly is the first-named inventor of the Cabilly patent, the basis for numerous widely used drugs. Several pharmaceuticals are licensed under the Cabilly patent, including therapies for rheumatoid arthritis and an antibody to prevent organ rejection in kidney transplant patients. This gift continues the longstanding and collaborative relationship between Dr. Cabilly and City of Hope, which has enabled scientific advances that have significantly improved the lives of patients with life-threatening diseases, said
16 I City News SuMMER 2008
PAulA MyErS

John J. Rossi, left, discusses ideas with budding scientists including graduate student Daniel Kim and postdoctoral fellow Pritsana Ehomchan. Such teaching moments will be commonplace in the Cabilly-Riggs Academic Center.

Michael A. Friedman, M.D., president and chief executive officer of City of Hope. It is fitting that this generous gift from the Cabillys will support a vibrant academic center for students in the biological sciences to pursue and uncover their own scientific discoveries. Cabilly and his wife, Orly, both have strong ties to City of Hope. While Cabilly served as a postdoctoral researcher in Riggs laboratory, Orly worked as a research technician in the laboratory of John J. Rossi, Ph.D., now Lidow Family Research Chair and dean of the graduate school. This gift represents our belief in the impact of City of Hopes research and education programs, Cabilly said. We believe strongly in giving researchers the freedom and resources to explore new scientific avenues and to pursue innovative ideas to fight life-threatening diseases. The center is a fitting acknowledgment of the impact and influence of Cabilly and Riggs in science and the training of subsequent scientists. Dr. Cabilly was trained in immunology. I have a longstanding interest in immunology, so it is most appropriate that the Cabilly-Riggs Academic Center is the ground floor of the

new Arnold and Mabel Beckman Center, which is largely devoted to research in immunology, said Riggs, a researcher at City of Hope for more than three decades. This gift from the Cabilly family will support an array of new initiatives to improve human welfare through scientific advances while offering a robust learning environment for future generations of scientists. Added Rossi: This generous gift will have a long-lasting impact on our graduate school and the educational experience of our students by enhancing our ability to integrate clinical and academic programs. Cabilly is the founder of Ethrog Biotechnologies Ltd., which is now a subsidiary of Invitrogen Corporation Inc. Ethrog Biotechnologies Ltd., located in Israel, is dedicated to the development, production and commercialization of advanced tools for biological research. The City of Hope Graduate School of Biological Sciences is a fully accredited education program that offers students both academic coursework and practical laboratory training to prepare them for careers in academic, medical or pharmaceutical and biotech industry organizations. n n n

GENEROSITY
By Jennifer Healy

of health-care industry leader benefits City of Hope graduate school students

A $1 million gift from the private foundation of norman and melinda payson will support City of Hopes Graduate School of Biological Sciences.
Half of the gift will establish the Dr. Norman and Melinda Payson Graduate Studies Center, which will serve as a resource for future scientists in training within City of Hopes graduate school. The remaining $500,000 will endow a graduate fellowship at the school that will support student stipends. The Graduate School of Biological Sciences provides an outstanding atmosphere for learning and discovery, and its faculty members are widely recognized as leaders in their fields, said Norman Payson, M.D. We are thrilled to have the opportunity to support such a visionary academic facility and help enrich the experience of tomorrows brightest researchers. The Dr. Norman and Melinda Payson Graduate Studies Center will be a unique space where students will learn advanced research concepts, best practices and newly refined techniques within a formal teaching environment. The space will consist of two classrooms, a study hall, student lounge and other facilities, and will be housed in the Cabilly-Riggs Academic Center, future home to City of Hopes Graduate School of Biological Sciences. The first floor of the Arnold and Mabel Beckman Center for Cancer Immunotherapeutics and Tumor Immunology will house the academic center and all operations and facilities of the graduate school. The Dr. Norman and Melinda Payson Graduate Student Fellowship will be awarded annually to students who show the highest promise as scientific researchers. Payson, who is a member of City of Hopes national board of directors, was chair and chief executive officer (CEO) of Oxford Health Plans Inc., a leading provider of health benefit plans. From 1998, when he joined Oxford as CEO, until his retirement in 2002, Payson led the company through a financial revitalization and transformation into one of the most successful health plans in the nation. Prior to joining Oxford, Payson was co-founder and CEO of Healthsource Inc., from its inception in 1985 until its sale to CIGNA Corporation in 1997. During his tenure, Healthsource became one of the nations largest health plan companies, operating in 15 states with more than 3 million members. Payson was CEO of a 120-member physician group, with more than 100,000 health plan members, before helping to establish Healthsource. Payson is a graduate of the Massachusetts Institute of Technology and received his medical degree at Dartmouth Medical School. He practiced medicine as a board-certified family physician until 1982 and previously served in the united

Graduate students such as Sumanth Putta, left, Louisa villeneuve and Yan Li will benefit from new facilities.

States Public Health Service Commissioned Corps on an American Indian reservation in Arizona. City of Hopes Graduate School of Biological Sciences is a vital component of our institution and offers a unique and challenging research and learning environment for graduate education, said John J. Rossi, Ph.D., dean of the Graduate School of Biological Sciences and the Lidow Family Research Chair. In our new facility on campus, and with support from people like the Paysons, we can build our program and continue to attract talented aspiring scientists from throughout the world. n n n Norman Payson

City News SuMMER 2008 I 17

CourtESy of norMAn PAySon

PAulA MyErS

City of Hope board of directors welcomes


New leadeRs

tHrEE nEW MEMbErS


By Jennifer Healy

Communications industry veteran eddy w. hartenstein, financial executive michael e. Keane and health-care executive Kathleen mcnamara, r.N., B.S.N., P.H.N., have been appointed to City of Hopes board of directors.
The diverse professional experience Michael E. Keane, until most recently and insight these three individuals bring vice president and chief financial officer to our board is invaluable, said Terry R. (CFO) of Computer Sciences Corporation Peets, board chair. City of Hope is focused in El Segundo, Calif., is a financial on rapidly accelerating the translation of executive with experience in finance, scientific discovery into better treatments. strategic analysis, operations, accounting, The additional leadership contributed by management and administration. Before these individuals will help foster that effort. moving into the role of CFO in 2006, he served as the companys vice president of Eddy W. Hartenstein is the retired finance. From 1997 to 2005, Keane was vice chair of The DIRECTv Group Inc., a senior vice president and CFO of unova world-leading provider of digital television Inc., a $1.3 billion industrial technologies entertainment services previously known company comprising global businesses as Hughes Electronics Corporation. Prior to in automated data collection, mobile serving as vice chair, Hartenstein was chair computing and industrial automation and chief executive officer of the company. systems. Prior to that, he served as He assembled DIRECTvs management senior vice president and CFO for team and guided its strategic efforts to Western Atlas Inc., and held a series launch the countrys premier direct-toof financial management positions at home entertainment distribution service. Litton Industries Inc., including assistant Before joining DIRECTv, Hartenstein treasurer and director of pensions and served as president of Equatorial insurance. Both companies were located Communications Services Company in in Beverly Hills, Calif. Mountain view, Calif., from 1984 to 1987. Keane began his career as a He previously worked at Hughes Aircraft certified public accountant with Price Company, which he joined in 1972; from Waterhouse in Chicago. He holds a 1981 to 1984, he was vice president bachelors degree in accounting from of Hughes Communication, where he Illinois State university and a Master in directed the marketing and development Business Administration degree from the of the original Galaxy satellite fleet, which served the broadcast television and cable programming industries. Hartenstein holds a bachelors degree in aerospace engineering and mathematics from California State Polytechnic university in Pomona, and a Master of Science degree in applied mechanics from the California Institute of Technology in Pasadena. Michael E. Keane Eddy W. Hartenstein
CourtESy of DirECtV

university of California, Los Angeles. Kathleen McNamara is a health-care executive with more than 19 years of experience building entrepreneurial and profitable health-care operations through new start-up companies, mergers and acquisitions, and strategic planning. She most recently served as a consultant to Priority Healthcare/Express Scripts Inc. Before that, she was president and chief executive officer of Integrity Healthcare Services Inc. Previously, as a partner at McNamara and Associates, she consulted for venture capital companies on product development, as well as with infusion therapy companies on the development of clinical and reimbursement programs. In 2006, along with her husband, she endowed the Francis and Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation held by Stephen J. Forman, M.D. McNamara is a licensed registered nurse in Kentucky and California and holds a bachelors degree in nursing from Mount St. Marys College in Los Angeles. n n n

Kathleen McNamara

18 I City News SuMMER 2008

yono PHotogrAPHy

CourtESy of CSC

uNDER NEW LEADERSHIP


By Roya Alt

richard Jove, Ph.D., a nationally recognized cancer researcher, has been named director of City of Hopes Beckman research institute.
An accomplished scientist, Jove funded by the National Institutes of Health leads the institutes research efforts and for two decades since establishing his facilitates collaborations between basic independent research laboratory. He has scientists and physicians to accelerate authored more than 150 scientific papers development of new therapies for cancer, in leading research journals and serves as diabetes and other life-threatening an expert reviewer of cancer centers for the diseases. Jove, who is also deputy director National Cancer Institute. of City of Hopes Comprehensive Cancer This year, City of Hope will Center, succeeds Arthur D. Riggs, Ph.D., commemorate Beckman Research now Beckman Research Institute director Institutes 25th anniversary and celebrate emeritus and professor of biology. its numerous contributions to the field of Founded in 1983, City of Hopes biomedical research. We are pleased that Beckman Research Institute was the first we will have the outstanding leadership of only five such institutes endowed by the of Dr. Jove to begin this new era, said Arnold and Mabel Beckman Foundation. Michael A. Friedman, M.D., City of Hope Beckman scientists pursue studies in president and chief executive officer. In molecular and cellular biology, exploring his career, Dr. Jove has been instrumental normal and abnormal biological processes in facilitating collaborations between basic related to human disease. scientists and clinical investigators to apply These scientists also have achieved new laboratory insights to the treatment major advances in genetics, cancer biology, of patients with cancer. His scientific gene therapy, immunology, neurosciences achievements and leadership experience and recombinant DNA technology, are ideally suited to lead the institutes including development of a patented mission of excellence in innovative process to make recombinant, or synthetic, human insulin and monoclonal antibodies. Recombinant insulin is widely used today to treat diabetes, and monoclonal antibodies are increasingly used to treat cancer. In his own research, Jove investigates the mechanisms that help cancer develop and thrive. He and his colleagues pioneered investigations into the STAT3 protein as a molecular target for cancer therapy, and he has increased understanding of the role of STAT3 in abnormal growth and survival of tumor cells. Jove has been continuously Richard Jove biomedical research. Noted Riggs: Dr. Jove brings outstanding leadership qualities and a record of superior achievement in research to this position. His combination of skills will ensure City of Hope remains at the forefront of scientific excellence. Jove joined City of Hope in 2005 from the H. Lee Moffitt Cancer Center and Research Institute in Florida, where he served as director of the Molecular Oncology Program and associate director of basic research. Previously, he was a tenured faculty member at the university of Michigan Medical School, where he also served as director of molecular oncology. He began his research career as a doctoral fellow at Columbia university and subsequently received postdoctoral research training at Rockefeller university, both in New York City. I am honored to serve as director of Beckman Research Institute and follow in the steps of Dr. Riggs, whose work was critical to modern genetics and the birth of biotechnology, and who fostered the collaborative environment that has come to define City of Hope, Jove said. My role will be to focus, promote and shape collaborations across different disciplines, with the ultimate goal of translating new laboratory findings into better treatments for patients with life-threatening diseases. n n n
MArkiE rAMirEz

City News SuMMER 2008 I 19

fouNdatioN suppoRt

Foundations provide key support for blending science with caring


By Carmen R. Gonzalez

Long-term City of Hope supporters Mark and Pearle Rae Levey were moved to fund the Biller Patient and Family Resource Center as part of their foundations missions. Our primary goals are to promote medical and health causes that significantly improve our community, Pearle Rae Levey said. Having lost loved ones to cancer also motivated the Leveys to help. City of Hope has been my charity of choice for more than 35 years, added Mark Levey. He has aided City of Hope in a number of key volunteer leadership roles: He served for 18 years on City of Hopes board of

directors and is an honorary life board member; he also is a founding member of the Southern California Food Industries Circle, and served as its president in 1983. His sense of philanthropic dedication is matched by that of his wife, Pearle Rae, who supports the Rose Community Foundation, Shalom Park Senior Community Center and 9Health Fair in Denver, and is actively involved with Cedars-Sinai Medical Center, the JvS Scholarship Fund and Helps International in Los Angeles. Mark Levey introduced his friends Sheri and Les Biller to City of Hope and has

Pearle Rae and Mark Levey

encouraged their involvement. When the Biller Patient and Family Resource Center was conceived, the Levey family knew they wanted to support it. We are so impressed by this particular effort to enhance patient care at City of Hope we knew we wanted to be a part of it, said Pearle Rae Levey. The facility is slated to open this summer. n n n

20 I City News SuMMER 2008

CourtESy of lEVEy fAMily

A $250,000 gift from the levey cherry Foundation and the Jess & rose Kortz and pearle rae Foundation will advance the construction of the sheri & les Biller Patient and Family resource Center, a facility designed to blend science with caring through services such as patient navigation, health education, psychological counseling and healing arts programs.

W.M. keck foundation furthers collaborative lymphoma study


By Roberta Nichols

City of Hope researchers and colleagues from the California institute of Technology (Caltech) received a three-year, $1.5 million grant from the w.m. Keck Foundation to continue a collaborative study investigating the molecular mechanisms underlying lymphoma.
The study focuses on developing targeted, less-toxic treatments for the disease based on short interfering RNA (siRNA) technology that can inhibit the protein products of specific genes. The W.M. Keck Foundation previously funded the first phase of the lymphoma study in 2006 with a one-year, $450,000 pilot grant. Lymphoma is a cancer that develops in the immune system and is the fifth most common type of cancer in the united States. Even though the current standard treatment of radiation and chemotherapy can control the disease, relapse is common and more effective therapies are needed. Researchers began testing a novel compound composed of a polymer created by Caltech researcher Mark Davis, Ph.D., and an engineered antibody developed at City of Hope to see if it could attack lymphoma cells without disturbing healthy cells. Such targeted, less invasive therapies also may help lessen the side effects many patients experience with standard treatment. Collaborative studies with institutions like Caltech allow great scientific minds to share information and open doors to innovative discoveries in the battle against cancer and other

life-threatening diseases, said Michael A. Friedman, M.D., president and chief executive officer of City of Hope. The generosity of the W.M. Keck Foundation will enable more advanced research to develop better treatments for lymphoma that also may prove potent against other types of cancer. The multidisciplinary team is targeting the polymers molecules that do not stimulate the immune system and have very low toxicity directly into the cancer cells. Once inside, they deliver their payload of siRNA, which disrupts the genetic coding in cancer cells to either kill them or render them incapable of multiplying. We have been able to gain a better understanding of lymphoma through our research with Caltech, and have identified targets for potential new lymphoma therapies, said Stephen

Mark Davis

Stephen J. Forman

J. Forman, M.D., the Francis and Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation at City of Hope and principal investigator of the study. There is a real need for improved treatments, because not all lymphoma patients are able to tolerate chemotherapy and radiation. Our older patients, in particular, would greatly benefit from new targeted therapies. City of Hopes Division of Hematology & Hematopoietic Cell Transplantation has been a leader in the development of stem cell transplantation for the treatment of lymphoma, as well as the creation of new immune-based therapies and drugs to treat the disease. Based in Los Angeles, the W.M. Keck Foundation was established in 1954 by the late W.M. Keck, founder of the Superior Oil Company. The foundation is focused primarily on pioneering efforts in the areas of medical research, science and engineering. n n n
City News SuMMER 2008 I 21

MArCElo CoEHlo

CourtESy of CAltECH

advaNCiNg ReseaRCh

StoP CAnCEr grants propel liver and hematologic cancer research


By Elise Lamar

Promising young cancer researchers who have not yet had time to secure the major grants needed to run a laboratory face challenges in advancing their work. For 20 years, however, a vital organization has pushed these researchers important studies ahead.
The STOP CANCER organization grants career development awards to talented cancer researchers in Southern California, and two talented scientists from City of Hope recently joined their ranks. Wendong Huang, Ph.D., assistant professor in the Department of Gene Regulation and Drug Discovery, and Takahiro (Taka) Maeda, M.D., Ph.D., assistant professor in the Department of Hematopoietic Stem Cell and Leukemia Research, each will receive $150,000 over three years to conduct research leading to new cancer therapies. City of Hope will match the grants, bringing each to a total of $300,000. Huang will target liver cancer by analyzing a family of proteins that help the body regulate metabolism. He has shown that those proteins which belong to a family known as nuclear receptors not only protect liver cells against potential damage from obesity, diabetes and alcohol, but they also defend against liver cancer. In Huangs studies, mice engineered to lack a specific nuclear receptor known as the farnesoid X receptor or FXR developed spontaneous liver cancers. What that means is that FXR is not only necessary for normal liver metabolism, but that without it, mice have a predisposition to liver cancer, Huang said. The STOP CANCER funding will help Huang determine how FXR protects mouse and human cells from liver cancer. We have been working primarily with animal models, but now we can look at FXR expression levels and mutations in human tumor samples, he said. Huang aims to develop ways to treat liver cancer and sensitive
PAulA MyErS MArkiE rAMirEz

Wendong Huang

Taka Maeda
22 I City News SuMMER 2008

methods to detect potential cancer-causing mutations in the human FXR gene. Maeda will focus on how a protein known as leukemia/lymphoma related factor (LRF) promotes blood cancer. He has found that LRF is required for normal development of immune cells called B cells. The results were published in the journal Science. Maeda also has shown that LRF is highly expressed in non-Hodgkins lymphoma, and when he genetically engineered mice to make too much LRF in immune system cells, the mice developed leukemia or lymphoma. He is currently studying LRFs normal activities, as well as those that cause cancer. We know this gene is important for normal B cell development and is a critical oncogene in lymphoma, but no one knows how it works, said Maeda. He will use his award to determine how precisely LRF protein regulates normal B cell development in mice and to develop drugs to turn off overactive LRF in human lymphomas. STOP CANCER is a nonprofit, philanthropic organization founded in 1988 by the late entrepreneur and philanthropist Armand Hammer in partnership with Sherry Lansing, then chief executive officer and chair of Paramount Pictures. Based in Southern California, it is dedicated to helping find a cure for cancer by funding research at National Cancer Institutedesignated Comprehensive Cancer Centers such as City of Hope. It provides grants to scientists engaged in innovative cancer research, particularly research with clinical applications. For more information about STOP CANCER, please visit www.stopcancer.net. n n n

City of Hope is a nationally recognized leader in biomedical research. The institution ranked in the top 5 percent among independent research institutes in total grants awarded by the National Institutes of Health in 2007. Following is a roundup of some notable grants recently awarded.

The National Institute of Neurological Disorders and Stroke, a branch of the National Institutes of Health, has awarded a four-year grant totaling $1,478,752 to Yanhong Shi, Ph.D., assistant professor of neurosciences, for brain tumor research. Shi

Immunotherapeutics and Tumor Immunology and director of pediatric neuro-oncology, directs the project. Jensens lab will study a novel cellular immunotherapy approach to treating children with relapsed embryonal brain tumors. The PCRF has supported his research since 2006. The Rosalinde and Arthur Gilbert Foundation has awarded a one-year, $150,000 grant to support the TumorTargeting and Insulin-Producing Stem Cell Project led by Karen S. Aboody, M.D., and ChuChih Shih, Ph.D., assistant professors in the Division of Hematology & Hematopoietic Cell Transplantation. The project investigates the tendency of neural stem cells to migrate toward tumor cells and seeks to harness this migration for treatment. The project also explores methods for developing neural stem cells and insulinproducing cells from bone marrow cells. The Rosalinde and Arthur Gilbert Foundation has supported the program for the past three years. The Susan E. Riley Family Foundation has awarded a two-year, $165,000 grant to support the pancreatic cancer research of Joseph Kim, M.D., assistant professor of surgery.

Kims lab will investigate some of the first steps in the transformation of normal pancreas tissue to invasive pancreatic cancer. Pancreatic cancer is the fourth leading cause of cancer-related death in the united States. The William Randolph Hearst Foundations have awarded a $100,000 grant to support City of Hopes Childhood Cancer Survivorship Program. The grant will provide childhood cancer survivors with access to follow-up care to help them thrive after treatment. More than 300,000 childhood cancer survivors are alive in the united States today. The Mark J. Gordon Foundation has contributed $10,000 to the Sheri & Les Biller Patient and Family Resource Center. The foundations mission is to increase childhood survival rates, end extreme poverty and bring opportunities to the disadvantaged, while strengthening families. n n n
City News SuMMER 2008 I 23

and her team will study the maintenance, proliferation and self renewal of adult neural stem cells so they may better combat brain cancer. The Pediatric Cancer Research Foundation (PCRF) has awarded a two-year grant of $245,316 to support development of T cell-based cancer therapeutics for children. Michael C. Jensen, M.D., associate chair of the Division of Cancer

g R a N t s

a t

g l a N C e

uNCovEriNG THE CurE: Bringing awareness to lesser-known cancers


By Carmen R. Gonzalez

Sometimes, dealing with a sensitive issue requires revealing vulnerability.


City of Hope soon will encourage supporters in the Los Angeles area to wear that vulnerability a little more openly in public. Event participants will don their undergarments as outerwear for City of Hopes underwear Affair Presented by Jockey a unique fundraiser featuring an afternoon 10K run and a 5K walk focusing on cancers below the waist. The Aug. 2 event will begin and end at the La Brea Tar Pits Great Lawn in the citys Miracle Mile district and raise awareness and funds for prostate, cervical, colorectal, ovarian, testicular and bladder cancers, some of the most devastating malignancies for men and women worldwide. City of Hope is organizing the event in partnership with CauseForce, a company that has helped many nonprofit organizations raise tens of millions of dollars for cancer causes. Numbers back up the importance of the event. Among men, prostate cancer is the most common cancer and secondleading cause of cancer death in the united States today, and colorectal cancer is the third-largest cancer killer among

both men and women. Despite the prevalence of these cancers, and others in the lower body, their links to the midsection and the reproductive system may make them a taboo topic for discussion. The result: cancers that go undetected for too long because people are too embarrassed or uncomfortable about testing. in addition to raising funds for research, prevention and treatment, the fun and lighthearted event aims to raise awareness and erase the stigma often associated with these cancers. race participants are encouraged to wear anything from traditional jogging togs to their most comfortable pair of boxers. runners, walkers and their supporters then will celebrate their accomplishments with an after-party including entertainment and refreshments. Twenty-five years ago, breast cancer was something most people didnt talk about. Today, because of efforts like Susan G. Komen and our own Walk for Hope, we are making great strides in conquering the disease, said Michael A. Friedman, M.D., City of Hope president and chief executive officer. City of Hopes underwear Affair can begin to do the same for another group of cancers: highlighting their significance, encouraging more public dialogue about them and

raising funds for much-needed research. To register or learn more about City of Hopes underwear Affair Presented by Jockey, please visit www.uncoverthecure.org. n n n

A uNiTED TEAM supports patients and their families through the cancer journey
By Alicia Di Rado

City of Hope has become one of the first institutions in the nation to unite all of its psychosocial support and palliative care programs under one multidisciplinary umbrella.
The new Division of Supportive Care Medicine embodies a growing national movement to treat and support all aspects of patients cancer experiences, from physical and mental health to emotional and spiritual issues. It encompasses a wide variety of professionals including pain physicians, clinical social workers, psychiatrists, psychologists and chaplains. The Division of Supportive Care Medicine reflects City of Hopes longstanding commitment to compassionate care for the whole patient, said Alexandra Levine, M.D., chief medical officer. With the establishment of this division, City of Hope becomes a national leader in the movement to integrate our outstanding clinical care with a full spectrum of psychosocial and supportive care services. The division grew out of an evolving team at the Sheri & Les Biller Patient and Family Resource Center, the hub of supportive care for City of Hope patients and their loved ones.

The center brings together and coordinates much-needed services and aims to ensure that all patients and their families get the tools they need to fight cancer and get healthy right from the beginning. We are truly breaking new ground here, said Matthew J. Loscalzo, M.S.W., co-chair of the Division of Supportive Care Medicine and administrative director of the Biller Patient and Family Resource Center. We are bringing the best of all our specialties together to help people who truly need support: people with cancer and those who love them. This will be a national model for how to provide care. The new division includes specialists in pain management, palliation, psychiatry, psychology, The new Division of Supportive Care Medicine brings together professionals from throughout City of Hope. clinical social work,

spiritual care, patient navigation and health education. Creation of the new division dovetails with national calls for more comprehensive care for cancer patients. In the most public call for such services, the prestigious Institute of Medicine of the National Academies issued a report in late 2007 pushing medical centers to better address patients social, emotional and spiritual needs and overall sense of well-being. Noted Loscalzo: Were looking forward to setting the pace for this movement. The patients and their families will stand to benefit from what we learn. n n n

24 I City News SuMMER 2008

tHoMAS broWn

CALiForNiA SuPrEME CourT ruLES iN GENENTECH CASE


The California Supreme Court on April 24 upheld a 2002 jury verdict of $300.1 million in compensatory damages in favor of City of Hope for Genentech Inc.s breach of a 1976 agreement in which City of Hope entrusted a groundbreaking invention to Genentech that launched the biotechnology industry. The decision also reversed the jurys verdict that Genentech breached a fiduciary duty to City of Hope and the jurys award of $200 million in punitive damages. City of Hope is extremely pleased that the California Supreme Court followed sound legal precedent in ruling the jurys verdict on compensatory damages was correct, said Robert W. Stone, City of Hope general counsel. While we are disappointed that the court did not agree with our position on fiduciary duty, we are delighted by the overall outcome. At the 2002 trial, the Los Angeles County Superior Court jury decided that Genentech breached a 1976 contract with, as well as its fiduciary duty to, City of Hope. under the contract, City of Hope entrusted a still-confidential invention to Genentech, which agreed to develop, patent and exploit it for their mutual benefit in exchange for the payment of royalties. The invention, created by Arthur D. Riggs, Ph.D., and Keiichi Itakura, Ph.D., is a broadly applicable method for producing human proteins through recombinant DNA technology. This method was used by Genentech and many other biotechnology companies in developing a number of important drug therapies, including synthetic human insulin. At the conclusion of the trial, the jury awarded City of Hope $300.1 million in compensatory damages. In a second phase of the trial, the jury awarded City of Hope $200 million in punitive damages. In 2004, the California Court of Appeal upheld the jurys 2002 decision in its entirety. The April 24 decision from the state Supreme Court follows Genentechs appeal of that ruling. The verdict payment will be used to further City of Hopes mission of conducting research to quickly and safely bring new lifesaving treatments to patients. n n n

ExtEnDing An oliVE brAnCH to help cure cancer


By Carmen R. Gonzalez

Bill Wallace is no ordinary businessman.


Soon after retiring from a successful 30-year career with the office furniture company Steelcase in 2002, he and his wife, Jill, bought a five-acre estate in Sonoma, Calif. While completing a universitys Master Gardener program, the budding entrepreneur launched a second career by planting a few specimen olive trees evocative of Tuscany. Soon after, in 2004, Wallace was diagnosed with papillary renal carcinoma, a rare form of kidney cancer. Following two surgeries, the Wallaces planted 400 more trees and produced Hawks Feather Oliveto their own olive oil varietal. Their involvement in the project provided a welcome respite in coping with Wallaces health concerns. The couples commitment to the orchard involved loved ones nationwide. Each year since, more than two dozen family members and friends have convened at the Wallace compound to pick olives and the personalized efforts paid off. At the 2007 Los Angeles International Extra virgin Olive Oil competition, Hawks Feather Oliveto captured the gold as a domestic North Coast blend. unfortunately, the outlook for Wallaces health was not as bright. His treatments failed to vanquish his spreading cancer. Through referrals from friends, including former White House Chief of Staff Hamilton Jordan Sr., Wallace was steered to the university of California Los Angeles (uCLA) Robert A. Figlin, M.D., now the Arthur and Rosalie Kaplan Professor of Medical Oncology at City of Hope and acting director of City of Hopes Comprehensive Cancer Center. While at uCLA, Figlin began to treat Wallace, enrolling him in a clinical trial that provided temporary improvement. Now in his second clinical trial at City of Hope, Wallace is responding well to the new treatment. He has brought the same passion he has for olive oil to the fight against kidney cancer, and he encourages friends and business associates to help fund City of Hopes research into the disease. Ive learned that current research advances into kidney cancer are helpful to other cancers, too, so supporting kidney cancer research essentially helps all kinds of cancer patients, Wallace said. As a tasty incentive, Wallace is

Bill Wallace

offering a bottle of Hawks Feather Oliveto for every donation exceeding $500 made to the Friends of William Wallace kidney cancer research fund at City of Hope, while supplies last. Research is critical to fighting cancer, and donating to City of Hope supports such efforts, Wallace said. For more information, contact City of Hope Gift Planning Officer Randy Lapin at 800-232-3314. n n n

City News SuMMER 2008 I 25

DAViD nEMEr

Cause foR hope

Companies align with City of Hope to save lives


City of Hopes corporate supporters have helped raise tens of millions of dollars since 1999 through causerelated marketing programs. These programs generate considerable national awareness and strengthen community support for the institutions mission to eradicate disease. We thank all of the companies and their customers that support our research, treatment and education efforts through these programs.

The National Office Products Industry this year honors United Stationers, North Americas largest wholesale distributor of business products, for its support of City of Hope. The company backs the institution in many ways. Starting in 2008 through its Innovera office product line, for example, united Stationers will donate $5 from the sale of each computer laser mouse to City of Hopes breast cancer research, treatment and education efforts. In addition, united Stationers will spearhead an ink cartridge recycling program and other consumer promotions to benefit City of Hope. Through a separate $100,000 donation, the company also will participate as a national sponsor of Walk for Hope to Cure Breast Cancer.

The Newell Rubbermaid Office Products Company has supported breast cancer research at City of Hope through sales of several of its products, including Paper Mate Write for Hope pen-and-eraser packs and Parker Jotter Special Edition pink pens, and specially marked office organizer products from Rolodex, through a flat donation. This year, the company has added other products, including specially marked Sharpie and Sharpie Accent markers, EXPO dry erase markers, Liquid Paper DryLine correction film and the uniball 207 gel pen. The company aims to raise more than $300,000 through the effort this year.

Customers of ACCO Brands Corporation, one of the worlds largest suppliers of branded office products, can support cancer research and treatment through their purchases. Five percent of sales of specially labeled products appearing in the companys office supply flyer will be donated to City of Hope.

MWV, makers of AT-A-GLANCE and Cambridge office products, is supporting breast cancer research, treatment and education at City of Hope through sales of an array of pinkcolored and pink-ribbondisplaying products, which hit store shelves in May. Mead will include tips about breast cancer awareness and selfexaminations on some products. MWv will donate $50,000 to City of Hope during the two-year promotion.

Through Kelloggs Spring Challenge, consumers were encouraged to lose one inch from their waists using selected Special K products. Nearly 160 Albertsons stores in Southern California participated in the promotion, which featured Special K products including cereal, snack bars, protein bars, protein water, protein powder mix and frozen waffles. Products were displayed on in-store beach cabanas from April 16 to 29, and Albertsons made a 25 cent donation for each item purchased, up to $25,000, to City of Hope.

26 I City News SuMMER 2008

INSPIRE HOPE
By Roberta Nichols

remembering an extraordinary young man who continues to

tim nesvig appeared to be an unlikely candidate for serious illness. At 28, the handsome, 64 account executive for ESPN/ABC Sports Customer Marketing in New york seemed the proverbial picture of health. yet, in September 2003, he received an astonishing diagnosis: He had non-Hodgkins B cell lymphoma.

Less than a year later, Nesvig, a lifelong athlete who captained his water polo teams in high school and at Bucknell university, underwent a stem cell transplant at City of Hope. He soon resumed his busy work and social schedule. By early 2005, though, his aggressive form of lymphoma had stopped responding to therapy. His death on Feb. 8, 2005, at age 30 came as a shock to all of those who knew him. In the midst of their grief, the Nesvig family including Tims mother, father and two sisters and their friends took steps to keep his memory alive. To further the understanding of lymphoma and develop better treatment options, they created the Tim Nesvig Fellowship for Lymphoma Research Fund, under the direction of Stephen J. Forman, M.D., Francis and Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation and chair of the Division of Hematology & Hematopoietic Cell Transplantation at City of Hope. Each year, a donor-supported fund and an endowed fellowship advance crucial lymphoma research conducted at City of Hope. Such private support plays a crucial role in supporting the work of innovative specialists like Mark Kirschbaum, M.D., the 2007-08 Tim Nesvig Lymphoma Fellowship recipient. Both a physician and researcher, Kirschbaum is director of new drug development for the Division of Hematology & Hematopoietic Cell Transplantation. He also serves as hematologic malignancies coordinator for the California Cancer Consortium, a major component of City of Hopes federally funded grant for phase I and II clinical trials through the National Institutes of Health Cancer Therapy Evaluation Program. An accomplished and dedicated scientist, Kirschbaum is pursuing potential new targeted and epigenetics-based drugs for blood cancers in labs and clinical settings. Often, he is among the first to offer From left, Stephen J. Forman, Mieke (Nesvig) Duxbury, Jon Nesvig, Hanneke Nesvig, Mark Kirschbaum and Carrie Nesvig certain drugs to patients through clinical trials.

Among his targets are lymphomas, cancers that arise in the lymph nodes, which filter the blood and rid the body of bacteria and viruses. The implications of this work seem boundless. Were going to unravel a set of diseases that really has a much broader impact than lymphoma, he said. Past fellowship recipients have included Leslie Popplewell, Tim Nesvig M.D., assistant professor in the Division of Hematology & Hematopoietic Cell Transplantation, and Aung Naing, M.D. Three years after Nesvigs death, the Tim Nesvig Fellowship for Lymphoma Research Fund continues to thrive and is supported by hundreds of generous and committed donors through various fundraisers. In July 2007, the Nesvig family and friends reunited for the third annual City of Hope Golf Classic for the Tim Nesvig Fellowship for Lymphoma Research Fund at the Bel-Air Bay Club and the Sherwood Country Club in Los Angeles. Nearly 300 dinner guests and 150 golfers attending the event helped raise more than $713,000. In the past three years, the event has raised more than $2.3 million. Along with continued fundraising efforts throughout the year, the tournament and fellowship fund have generated a combined $3.3 million for lymphoma research. For more information on the 2008 tournament, which is scheduled for July 27 and 28, please call events coordinator Linda Bruce at 213-241-7111. n n n
bill riCH

City News SuMMER 2008 I 27

AMyCAntrEll.CoM

exemplaRy youth

regional prize for breast cancer research efforts


By Elise Lamar

TEENAGE CiTy oF HoPE iNTErN WiNS


Sarah Waliany is eminently self-possessed for a mere 16 years of age. No ums or you knows clutter her speech. it is no wonder the Arcadia, Calif., teenager already has her eye on becoming a physician and scientist.
She recently used her focus in partnership with friend Shelina Kurwa, 17, to win the 2007-2008 Siemens Team Competition in Math, Science & Technology regional finals at the California Institute of Technology. The pairs experiments, which focused on how breast cancer cells resist chemotherapy, were done when Waliany interned at City of Hope. Waliany, a Rose Hills Foundation scholar, participated in City of Hopes Eugene and Ruth Roberts Summer Student Academy and has worked two summers in the laboratory of scientist Susan Kane, Ph.D., professor in the

Shelina Kurwa (left) and Sarah Waliany display their work at the Siemens regional science competition at the California Institute of Technology.

Department of Surgical Research. From day one, Sarah was thinking about her project, reading the literature and coming up with her own ideas. said Kane. Thats remarkable for someone so young, a real mark of drive and maturity. Mentored by assistant research scientist Long Gu, Ph.D., Waliany showed that when too much of a certain protein is produced in some breast cancer cells, they became resistant to the common breast cancer drug Herceptin. The protein is called t-Darpp. If scientists find that t-Darpp helps breast cancers resist Herceptin, the discovery could suggest strategies to maintain the drugs effectiveness. Kurwa conducted much of the projects background research. Walianys first experiments were on lettuce plants in her backyard when she was only 12. Her mother Shenaz, a cytologist, said that when her daughter asked to study

math in fourth grade, her parents took her to a Japanese after-school program, where she learned high school algebra. Although her father is an oncologist, Walianys first interest in cancer research grew from seeing how friends lives were impacted when their parents developed cancer. In high school, Waliany started a club to support the Desi Geestman Foundation, which aids children with cancer. Last year we raised $700 from bake sales for this little boy, Robert, treated for cancer at City of Hope, she said. It helped his family take him on a longneeded vacation. The teammates will divide $16,000 in scholarship money from both the regional and national competitions. Waliany hopes to earn both a medical degree and a doctor of philosophy degree and become either an oncologist or a dermatologist. n n n

28 I City News SuMMER 2008

SiEMEnS founDAtion

concetta nocera

A mothers

steadfast determination

Once I gave birth to Dominic in March 2003, I didnt feel any better. Thats when my doctors began worrying. Three months later, they called about a bone marrow test I had taken and told me the worst news of my life: I had leukemia. When you hear you have cancer, your life just stops. I began researching my disease on the Internet. Thats how I came across City of Hope and Stephen J. Forman, M.D. I knew that he was the man who was going to save my life. My doctors recommended that I complete my initial chemotherapy at another hospital in Los Angeles, then go to City of Hope for my bone marrow transplant. But I told them I was going to do my entire treatment at City of Hope. Two months after beginning my treatment, I was in remission and was ready for my stem cell transplant. Thankfully, my brother, Lawrence Perpoli, was a match for me, so he served as my stem cell donor. Thank God for Dr. Forman. He arranged it so that my infant son could visit me while I was in isolation. We all got

Concetta and Giovanna Nocera

scrubbed up and dressed in the special clothes. All my son could see was my eyes, but he knew it was me. It was so important for me to have that time with my son. When my daughter, Giovanna, visited me, she decided to make a beaded bracelet to thank Dr. Forman. We spelled the letters H-O-P-E in beads to represent City of Hope. That hope kept me alive. The staff at City of Hope does not just care for your body. They care for your spirit, just like it says on the Golter Gate: There is no profit in curing the body if, in the process, we destroy the soul. City of Hope is the perfect name. Thats really what it is. After making the bracelet for Dr. Forman, my daughter was inspired to make more, which she sold to help raise money for City of Hope. It was her way of thanking everyone who helped save my life. Giovanna told her friends at school

about City of Hope, and they all wanted to help out and buy bracelets. We ended up handing Dr. Forman a check for about $135. More than four years have passed since my ordeal. Though I still face challenges from my battle with cancer such as a side effect from the transplant called graft-versus-host disease I am grateful to be alive. I have plenty to celebrate: most of all, my wonderful family. Dr. Forman invited us to sell HOPE bracelets at the 2007 Celebration of Life Hematopoietic Cell Transplantation Reunion. Through that effort, we were able to give him a check for $320. At this years reunion, we ended up raising $550.
Concetta Nocera is a homemaker who lives with her husband, Dominic, and their children, Giovanna and Dominic, in Thousand Oaks, Calif. To purchase HOPE bracelets, which range in price from $6 to $10, please send an e-mail to Hopebeads@nocera.cc. n n n

City News SuMMER 2008 I 29

DoMiniC noCErA

i cant tell you how many times i heard friends and family tell me that being tired was a normal part of pregnancy. When i was pregnant with my son, Dominic, i knew my fatigue was not typical. id had a child before, and my experience wasnt anything like this. i had infections, and i was worn down. i finally told my husband that i thought i was dying.

fiRst peRsoN: patieNt pRofile

g i v i N g

bEttEring tHE liVES of otHErS


By Carmen R. Gonzalez

p l a N N e d

Creative thinker sets her sights on improving health


A retired sportswear designer who now embraces a vision of improving health care worldwide recently included a bequest for City of Hope in her estate plan. Harriet Karols interest in the institution began 12 years ago when she joined the Medical Center Aides Chapter in Los Angeles. An active chapter member, she dedicated herself to developing new ideas to help raise funds. I have always lived Harriet Karol my life in a charitable way, and strived to raise money for those in less-fortunate circumstances, she said. She remembers the qualities that initially drew her to City of Hope and to the Medical Center Aides chapter in particular. They were a group that showed a quiet determination and honesty in their approach to developing new ideas to help people around the world, she said. Her affinity for her chapter, as well as her interest in City of Hopes research, moved her to regularly contribute throughout the years. Originally from the East Coast, Karol launched her successful design career with such firms as Junior Miss and Sporteens more than six decades ago. Her early experience in the fashion industry nurtured her budding creativity and fueled her inspiration for pursuing later interests, including home renovation and other design projects. In spite of her struggles with macular degeneration, Karol reads avidly and remains dedicated to keeping abreast of developments in the world of politics. A committed activist, she also has taken an interest in military affairs in Afghanistan and Iraq. Karol also enjoys attending art shows, where she often mentors young designers. Now, Karol encourages others to follow her lead in charitable giving, adding that supporting a cause to which she is deeply committed has brought her profound personal satisfaction. She believes her contribution will ultimately touch many lives. Karol has two children, Steven and Joan, as well as four grandchildren: Kendra, Katie, Lexie and Julia. She was widowed in 1999 with the death of her second husband, Harold Karol, who shared her compassion for helping others by supporting City of Hope. n n n

Happiness is not so much in having, as sharing. We make a living by what we get, but we make a life by what we give, according to the philosopher Norman MacEwan. in addition to cultivating a deep sense of personal fulfillment, City of Hope supporters touch countless lives through their unwavering generosity.

30 I City News SuMMER 2008

Engineering creative solutions through philanthropy


A mechanical engineer for 45 years, Morris Kaufman approaches philanthropy with the same problemsolving acumen that he used in his vocation. Through a unique and inventive arrangement, Kaufman recently made two major commitments to City of Hope: a $1 million testamentary charitable remainder trust and a gift Bertha Kass and Morris Kaufman of $100,000 in appreciated stock. Created in honor of Chicagos Howard S. Golden Chapter, the gifts reap significant tax advantages for Kaufman while enabling him to support his favorite charity. When we needed help, City of Hope was there, said Kaufman, referring to the treatment his late first wife, Annette, received at the medical center nearly 30 years ago. I will never forget the extraordinary care she experienced. Kaufman places a premium on efficiency in charity giving. If youre going to donate, dont waste it on an organization that uses it for bloated administrative costs, he said. Give your money to those who put it where it can do the greatest good in research. Thats City of Hope. The gift of stock provides Kaufman with a deduction at its full, appreciated value and shelter from capital gains taxes. Both the stock gift and the charitable remainder trust represent a mutually beneficial arrangement for Kaufman and City of Hope. Kaufman encourages others in his situation to create financial strategies with City of Hope gift planners and their financial advisors. I enjoy tax advantages while City of Hope advances its lifesaving research. Its a win-win, he explained. Previously a Chicago resident, Kaufman lives in Northbrook, Ill., a suburb of the city. Now retired, Kaufman worked his entire career at Echo Products. He has one daughter, Gale, along with two grandchildren, Robert and Annie. Twice widowed, Kaufman now enjoys the company of his friends, including his longtime companion, Bertha Kass a City of Hope supporter of more than 30 years and still-active member of the Howard S. Golden Chapter. n n n
CourtESy of kAufMAn fAMily

A legacy advocating for healthy women and children


The late philanthropist Maureen Holthe championed two causes dear to her heart: breast cancer research and children. From an estate totaling more than $600,000, including a real estate gift, three charities will benefit from her altruism: City of Hope, the Boys & Girls Club of Maureen Holthe Tustin and the Susan G. Komen Foundation. As a breast cancer survivor, Holthe was moved to support innovative research into the disease. Although she was not treated at City of Hope, she believed strongly in the institutions efforts to advance breast cancer research. The Boys & Girls Club of Tustin an organization founded by her mother, Helen, and her brother, Merwin was another priority for her. Maureen believed that every child deserved a chance at a better life, said Esther Laspada, her college friend and the trustee of her will. She was strongly committed to serving the youth in her community. Raised in Oregon, Holthe established herself in her familys business. Graduating from Santa Ana College with a business degree in the 1950s, she helped transform Holthe Disposal, a waste management company, from a single truck to a massive fleet, which once served all of Orange County, Calif. various civic and business organizations in Tustin benefited from her business savvy. Holthe served on the boards of several local banks, as well as the Boys & Girls Club. Her contributions earned her the Tustin Woman of the Year award in 1974 as well as the Athena Award in 2003, which honored her professional excellence, community service and her support of fellow businesswomen. Holthe even earned a pilots license, which served as a metaphor for her wanderlust. She traveled to Africa for safaris and to the Antarctic to walk among penguins, Laspada said. She even learned to parasail in her 60s. n n n
CourtESy of EStHEr lASPADA

City News SuMMER 2008 I 31

goveRNmeNt spotlight

iMProviNG THE LivES of young cancer survivors


By Congresswoman Hilda L. Solis
32nd Congressional District of California

As a result of research at City of Hope and other institutions, as well as the efforts of childhood health-care advocates across the country, a child diagnosed with cancer today has an 80 percent chance of survival, according to the National Cancer institute. A few decades ago, the survival rate was just about 20 percent.
Although the odds have improved, survivors of childhood cancer still face numerous challenges. The Pediatric, Adolescent and Young Adult Cancer Survivorship and Quality of Life Act, also known as the Childhood Cancer Survivorship Act, or H.R. 4450, will help. This bill, which I authored, seeks to improve the quality of life for young cancer survivors so they may receive the care and support they need to lead long and healthy lives. The initial diagnosis is only the beginning of a lifelong battle for a child with cancer. Even after successful treatment, more than two-thirds of childhood cancer survivors face formidable trials, including neurocognitive and psychological difficulties and cardiopulmonary, endocrine and musculoskeletal effects, as well as other complications or disabilities. Children from underserved communities confront even more obstacles. Because of disparities in health-care delivery throughout the cancer-care continuum, minority, poor and other medically underserved communities are more likely to experience less-thanoptimal treatment and have decreased survival rates and quality of life. The Institute of Medicine noted these challenges and provided recommendations to enhance the delivery of follow-up care, increase education and training for health-care providers and expand research to improve the lives of childhood cancer survivors.

The Childhood Cancer Survivorship Act seeks to implement these recommendations. It would expand cancer control programs to improve the health status of childhood cancer survivors and establish grants at the National Institutes of Health to conduct research on disparities in survivorship. This legislation also would create grants to establish and operate childhood survivorship clinics providing comprehensive long-term follow up services, as well as grants for childhood cancer organizations to improve physical and psychosocial care. The bill also would establish grants to develop model systems of monitoring and caring for such survivors. We must not forget about children once they are declared cancer free. I hope that public support and that of City of Hope, as well as the Lance Armstrong Foundation, PADRES Contra El Cncer, Childrens Cause for Cancer Advocacy, the Leukemia & Lymphoma Society, the American Society of Clinical Oncology and the American Psychological Association will encourage my colleagues in Congress to pass this important legislation. Supporters may contact their representative in Congress to support H.R. 4450, the Childhood Cancer Survivorship Act, to help improve the quality of life for all childhood cancer survivors. n n n

Hilda L. Solis

32 I City News SuMMER 2008

SCulPtor lEAVES lEgACy through Spirit of Life


By Susan Douglass Yates

fountain

robert I. russin, the world-renowned sculptor who created the Spirit of Life sculpture and fountain gracing the entrance to City of Hope, died on Dec. 13, 2007, at age 93.
The artist was originally commissioned to create a bas-relief on the medical centers exterior in 1963 as a tribute to the memory of President John F. Kennedy. But after spending time at City of Hope, seeing patients and their families and interacting with the staff, Russin asked himself, What do you put in front of a hospital to make it joyful? Russin decided on a sculpture, and used his family members as the basis for the figures depicting a man, woman and child. He believed the setting was integral to the sculpture, so he also participated in redesigning the medical centers entrance. Russin spent three years on the sculpture and fountain, at one point taking a leave of absence from his academic position at the university of Wyoming to move with his family to Monrovia, Calif. The resulting nine-foot bronze statue was mounted on top of three tiers of Italian marble and centered in a 30-foot circular reflecting pool. The redesigned main entrance with the statue and fountain, along with the integrated landscaping and seating, achieved a distinctive and uplifting architectural introduction to City of Hope. Seven hundred guests gathered to celebrate the fountains July 1967 dedication. Speakers included author Irving Stone and actor/ producer Carl Reiner. More than 40 years later, the Spirit of Life

Robert I. Russin oversees installation of the Spirit of Life fountain on May 3, 1967.

sculpture continues to symbolize hope and joy. Russin also created a bronze statue and fountain located in Heritage Park. Dedicated in 1969, it honors Evelyn Fineman, wife of former City of Hope board chair Mannie Fineman. n n n

Cancer patients thrive through writing and sharing experiences


By H. Chung So

When writer, professor and two-time cancer survivor Julie davey first began her writing workshops at City of Hope, she wanted to help patients, survivors, caretakers and loved ones express their emotions about cancer through prose and poetry.
Now, she and her students have found a way to do just that. A collection of her students writings appear in the book Writing for Wellness: A Prescription for Healing, published by Seattle-based Idyll Arbor Inc. The tome contains inspiring poems and stories from more than 60 participants in Daveys class, also known as Writing for Wellness. The books foreword is cowritten by City of Hopes Michael A. Friedman, M.D., president and chief executive officer, and Lucille A. Leong, M.D., associate director of clinical affairs in the Division of Medical Oncology & Therapeutics Research. Davey noted that the seed of publishing a book was always there when she started the biweekly classes in collaboration with the Department of Patient, Family & Community Education. The idea gradually grew as Davey noticed the improvement in her students pieces and when local media published some of the writing. Their stories were so compelling, and they communicated a shared experience we all have, Davey said. We want to let others going through a difficult time know that they are not alone, and reading these inspirational stories and writing their own can help get them through. In addition to students stories, Davey also wrote in the book. She included details about her own cancer journey, along with tips and advice for effective writing. She also left blank space in the book for readers to

write their own tales of courage and healing. Since the books publication, Daveys concept of guided group writing is being adopted at other cancer care facilities around the country. Its wonderful that Julie got this together, said patient and class participant Anna Escobosa. People can read this and know how we feel, and it will do a lot of good for them. n n n

City of HoPE ArCHiVES

Julie Davey talks to participants in a writing workshop.

City News SuMMER 2008 I 33

MArkiE rAMirEz

An ounce of prevention
By H. Chung So

How can the latest medical research help reduce the risk of cancer and other lifethreatening diseases? Here is what experts suggest*:
are seniors at a greater risk for colorectal cancer? A German study published in the journal Gut in November 2007 found that advanced polyps are more likely to turn into colon cancer as people age. The researchers reviewed more than 800,000 colonoscopies and cancer registries. They learned that advanced polyps found in people ages 80 and older are about twice as likely to become colorectal cancer compared to those in people between the ages of 55 to 59. Although other factors such as family history of colorectal cancer also play a role, this finding underscores an important American Cancer Society recommendation: Healthy adults need regular screenings for colorectal cancer beginning at age 50. does restful sleep inhibit diabetes? A study in the December 2007 Proceedings of the National Academy of Sciences

showed that a lack of deep sleep may impair the bodys ability to use insulin to process glucose, potentially increasing the risk for type 2 diabetes. Study researchers saw that three consecutive nights of interrupted deep or slow-wave sleep resulted in the production of significantly higher levels of blood glucose and a lowered sensitivity to insulin. While further study is needed, researchers recommended adopting good sleep habits to possibly reduce the risk of diabetes and enhance overall quality of life. will a steady diet of red meat raise the risk of lung cancer? Numerous studies have linked regular consumption of red and processed meats to several kinds of cancer. However, new research by the National Cancer Institute (NCI) and the American Association of Retired People suggests that meat consumption may also be linked to higher rates of a cancer not commonly associated with diet: lung cancer. The study, published in the December issue of PLoS Medicine, followed 500,000 participants and found that those who regularly ate red and processed meats were

16 percent more likely to get lung cancer even after smoking habits were taken into account. The NCI suggests moderation in red and processed meat intake, noting that consuming less could reduce the incidence of cancer at multiple sites. can green tea prevent prostate cancer? Findings recently published in the American Journal of Epidemiology showed that men who drank five or more cups of green tea daily cut their risk of developing advanced prostate cancer in half when compared to those who drank less than a cup each day. Researchers tracked 50,000 study participants over 14 years. However, study investigators cautioned that further research is needed to validate the preventive effects of green tea. Other large-scale studies have shown no relationship between green tea consumption and prostate cancer risk.
*Before making significant lifestyle changes, consult with your physician. n n n

Check out the new online version of City News.


City News can now be accessed online in an interactive, HTML format. This new format allows you to quickly access news about City of Hopes research, treatment and education programs, and enables you to easily share articles about the institution with others.
n Comment n Print

on articles and create dialog with other readers and e-mail articles easily to your family, friends and colleagues

To see the online version of City News, go to www.cityofhope.org/citynews.

34 I City News SuMMER 2008

city of hope

By H. Chung So

These are just a few of the City of Hope developments that have been making news across the country:
On Feb. 27, actress and singer Miley Cyrus discussed her participation in City of Hopes pediatric cancer patients picnic on NBCs The Tonight Show.
PAulA MyErS

Joanne Mortimer, M.D., was quoted in a May 16 Los Angeles Times article about a Canadian study linking vitamin D deficiency to breast cancer. Her commentary was also included in a May 15 KABC-TV segment. Leslie Bernstein, Ph.D., director of the Department of Cancer Etiology, was featured in an April 25 New York Times blog post and podcast about how exercise can lower cancer risk. On March 6, Reuters Health highlighted a lung cancer biomarker study conducted by Karen Reckamp, M.D., M.S., assistant professor of the Lung Cancer and Thoracic Oncology Program, and her colleagues at City of Hope in collaboration with researchers from university of California, Los Angeles. Mark H. Kawachi, M.D., associate professor in the Department of urology and urologic Oncology, was featured on KABC-TV on March 14 in a segment about the prevalence and screening for penile cancer. City of Hopes 32nd annual Celebration of Life Hematopoietic Cell Transplantation Reunion was covered by KABC-TV, KTLATV and KCOP-TV on April 25 and the Los Angeles Daily News, Dodgers.com, Pasadena Star-News, San Gabriel Valley Tribune and Whittier Daily News on April 26. The 10th annual Hike for Hope fundraiser in Palm Springs, Calif., received substantial local media coverage, including the Desert Sun on Feb. 24, Palm Springs Sun on Feb. 29, the March issue of Inland

Empire and KPSP-TV (CBS), KMIR-TV (NBC) and KESQ-TV (ABC) on March 2. An April 25 HealthDay article that was picked up in numerous outlets, including WashingtonPost.com and MSN. com, included commentary from vijay Trisal about recent findings suggesting former President Franklin Delano Roosevelt may have had melanoma. On March 18, LATimes.com reported on a bone marrow drive City of Hope held in collaboration with the Los Angeles Police Departments Central Traffic Division for an officer diagnosed with leukemia. The January/February 2008 issue of Nurses World magazine featured Betty Ferrell, Ph.D., professor in the Department of Nursing Research and Education, and her colleagues in their cover article, discussing their ongoing study of cancer pain management. nnn

Articles on the California Supreme Courts decision on the dispute between City of Hope and Genentech trial ran in numerous outlets on April 24 and 25, including the Wall Street Journal, Associated Press, FOX Business, Thomson Reuters, Bloomberg News Service, Dow Jones News Wire, San Francisco Chronicle, Pasadena StarNews, San Gabriel Valley Tribune, KCBS-AM and KFWB-AM. Vijay Trisal, M.D., was quoted in an April 21 TIME.com story about recent research showing patients with scalp or neck melanoma having lower survival rates compared to other sites. He was also interviewed on this topic for segments on KCAL-TV on April 21 and KCBS-TV on April 21 and 22. Commentary from Behnam Badie, M.D., about Senator Edward Kennedys brain cancer diagnosis was included in May 21 articles in the Los Angeles Times, Seattle Times, Newsday.com, AM New York and Arizonas East Valley Tribune.

The Feb. 28 edition of the Los Angeles Times reported on the Dodgers historic exhibition game on March 29 against the Boston Red Sox, noting that the event benefited ThinkCure, the Dodgers official charity supporting cancer research at City of Hope and Childrens Hospital Los Angeles. The event raised $2 million for ThinkCure, including $1 million in net proceeds from the game, and a $1 million matching personal donation from the McCourt family. The game as well as a related fundraising telethon aired on KCAL-TV in Los Angeles.

Jon SooHoo PHotogrAPy/loS AngElES DoDgErS

AMy CAntrEll.CoM

City News SuMMER 2008 I 35

i N

t h e

MAKING News Across the couNtry

N e w s

NuMBErS
t o K n o w
cIty oF hope medIcal center
800-423-7119

inDuStry SuPPort
Alan Barry (left), retired president and chief operating officer of Masco Corporation, is presented with The Spirit of Life Award by Paul Hylbert, chief executive officer of Pro Build Holdings and a 2005 Spirit of Life honoree, at the Hardware/Homebuilding Industrys annual fundraising kickoff, held in Orlando, Fla., on Feb. 12. Hundreds of the industrys supporters gathered to honor Barry and toast the launch of the groups 2008 effort, which is expected to raise more than $3 million. Barry and his wife, Karen, commenced the effort with their own gift of $300,000. In addition, organizers announced a $100,000 pledge from the Richard and Jane Manoogian Foundation at the event. Since its inception more than two decades ago, the industry group has raised more than $146 million for City of Hope. n n n

patIent reFerral lIne


800-826-4673

DriVES DonAtionS

gIFt plannIng
800-232-3314

cIty oF hope regIonal deVelopment oFFIces:


los angeles deVelopment headqUarters 800-544-3541 mIdwest regIon
Chicago regional Headquarters

800-779-5893 northeast regIon


Philadelphia regional Headquarters

800-344-8169 northwest regIon


San francisco regional Headquarters

800-732-7140
Seattle office

800-934-9196 soUtheast regIon


florida office (fort lauderdale)

800-584-6709 soUthwest regIon


los Angeles Development Headquarters

800-544-3541
Desert Communities office (Cathedral City, Calif.)

800-732-7121
Phoenix office

800-732-7309
San Diego office

888-805-8911

S TAy iN T o u C H
you may have received this fundraising communication because you previously received services at City of Hope. if you do not wish to receive such communications in the future, send a written request to the following address: city of hope 1055 wilshire Blvd. los angeles, ca 90017 attn.: publications manager, communications

Save Mart Supermarkets executives Cecil Russell (left), vice president of merchandising, and Steve Junqueiro, executive vice president, helped generate $204,000 to support breast cancer education, research and treatment initiatives at City of Hope through a companywide promotion in 248 stores in Northern California during October 2007. Save Mart Supermarkets has long supported City of Hope through the Northern California Food Industries Circle (NCFIC), which includes leading retailers, manufacturers, brokers and associated vendors in the region. To date, the NCFIC has raised more than $25 million. n n n

Lee Golub, executive vice president of Golub and Company, performed for a capacity crowd of more than 1,200 supporters at the Chicago House of Blues on April 24 for the 12th annual REACH (Real Estate Action Committee for City of Hope) Social. Raising more than $340,000, the event featured five live bands, comprising local professionals from the real estate and construction industries, and provided attendees with a combination of networking, socializing and concert-going. Since its inception in 1997, the REACH Social has garnered nearly $2 million. n n n

CALENDAr

To find out about events taking place across the country that support City of Hope, visit our Web site at www.cityofhope.org/calendar. For details about activities happening in your area, please contact your nearest City of Hope Regional Development Office.

36 I City News SuMMER 2008

gErbEr & SCArPElli

StACy lAnDry

MAnuEl PErEz, CHriStiES PHotogrAPHiC StuDioS

Retirement is off in the distance but the time to cure cancer is now.
A charitable retirement annuity through City of Hope gives you a way to prepare for your future and support lifesaving research at the same time. Youll receive a nice tax break now, and a guaranteed income for life when you retire. To learn more about how a charitable retirement annuity can help you achieve your personal and charitable goals, call City of Hopes Gift Planning Department today.

1055 Wilshire Blvd., Los Angeles, CA 90017 800-232-3314 giftplanning@coh.org www.cityofhope.org/giftplanning

1055 Wilshire boulevard los Angeles CA 90017 800-260-HoPE (4673) citynews@coh.org

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www.cityofhope.org

DELivEr To:

TO CONTACT US
If your address is incorrect, or you are receiving duplicate copies of this publication, please update the label and mail to City News, 1055 Wilshire Blvd., Los Angeles, CA 90017. You can also call 866-906-4673 (HOPE), or e-mail citynews@coh.org. By giving the code number that appears above your name, your request can be processed quickly. Thank you for helping us to be more efficient in communicating how your support is touching millions of lives.
J02-14215.ap.Su08.125M E Printed on recycled paper