TAG: "Cancer"

Vegetable oil ingredient is key to destroying gastric disease bacteria


Therapeutic nanoparticle that contains linolenic acid shows promise.

Liangfang Zhang, UC San Diego

By Heather Buschman, UC San Diego

The bacterium Helicobacter pylori is strongly associated with gastric ulcers and cancer. To combat the infection, researchers at the UC San Diego School of Medicine and Jacobs School of Engineering developed LipoLLA, a therapeutic nanoparticle that contains linolenic acid, a component in vegetable oils. In mice, LipoLLA was safe and more effective against H. pylori infection than standard antibiotic treatments.

The results are published online Nov. 24 in the Proceedings of the National Academy of Sciences.

“Current H. pylori treatments are facing a major challenge — antibiotic resistance,” said Liangfang Zhang, Ph.D., professor in the UC San Diego Moores Cancer Center and Department of Nanoengineering. “Our goal was to develop a nanotherapeutic that can tolerate the harsh gastric environment, kill H. pylori and avoid resistance.” Zhang and Marygorret Obonyo, Ph.D., assistant professor in the Moores Cancer Center and Department of Medicine, are co-senior authors of the study.

LipoLLA is a lipid (fat) particle that contains linolenic acid. When LipoLLA encounters H. pylori, it fuses with the bacterial membrane. Then the particle’s linolenic acid payload spills out, disrupting the membrane and killing the bacteria.

Zhang, Obonyo and their team labeled LipoLLA particles with fluorescent markers, fed them to mice and watched as the particles distributed themselves in the stomach lining — and stayed there. After treatment, they measured bacterial load in the stomach and markers of inflammation. Compared to standard antibiotic therapies, LipoLLA was more effective at getting rid of H. pylori. What’s more, LipoLLA was not toxic to the mice and the bacteria did not develop resistance to the therapy.

“This is the first step to verify that we can make this therapeutic nanoparticle and demonstrate that it works to reduce H. pylori colonization. We’re now working to further enhance the particle, making it more stable and more effective,” Zhang said.

Co-authors include Soracha Thamphiwatana and Weiwei Gao, UC San Diego.

This research was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (grant R01DK095168), part of the National Institutes of Health.

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Building the future of health care


More than 1,000 donors give $131M in support of UC San Diego Jacobs Medical Center.

By Judy Piercey and Jade Griffin, UC San Diego

Committed to fostering the future of health care in San Diego, more than 1,000 donors have contributed $131 million to UC San Diego’s Jacobs Medical Center. Included in the total are gifts that matched a donation of $25 million, meeting the Challenge goal of the initiative.

Today (Nov. 20), the campus announced that the Challenge donation, originally anonymous, was made by Joan and Irwin Jacobs. They provided a $75 million lead gift for the new facility in 2010; with the Challenge gift, that brings their contributions to the Jacobs Medical Center to a total of $100 million. Continued private support will help fund the completion of the new medical center, which is the largest hospital project currently underway in Southern California.

Under construction and projected to open in 2016, Jacobs Medical Center is a $839 million, 10-story facility on the university’s La Jolla campus, which will include three new clinical care units in one location: The A. Vassiliadis Family Hospital for Advanced Surgery, The Pauline and Stanley Foster Hospital for Cancer Care and the Hospital for Women and Infants.

“We are deeply grateful to Joan and Irwin Jacobs for their generosity, including the recent $25 million match challenge,” said UC San Diego Chancellor Pradeep K. Khosla. “We also thank Carol Vassiliadis and Pauline Foster, who made leadership gifts, as well as all of the other donors who participated in meeting this challenge. These visionaries support UC San Diego’s commitment and vision to create a healthier world through new science, new medicine and new cures.”

“Jacobs Medical Center is part of a multibillion dollar university investment in the future of health care for the region,” said Dr. David A. Brenner, vice chancellor for Health Sciences and dean of the UC San Diego School of Medicine. “I want to thank all of the donors who have helped make this extraordinary medical center a reality.”

Irwin and Joan Jacobs

“When we came here in 1966, the medical school was just starting,” said Irwin Jacobs, co-founder, former chairman and CEO of Qualcomm Inc. and UC San Diego founding faculty member, who served as a professor in electrical and computer engineering from 1966 to 1972. “There was no hospital, just a school. So it’s very exciting to make Jacobs Medical Center possible. More and more, we’re learning how to bring results from basic research in biology and engineering to medicine, and to the clinic. I think this medical center is going to show how effective that can be. The innovations will spread out from San Diego, and go all around the world.”

The 509,500-square-foot facility will house 245 patient beds and be connected on multiple floors with the existing John M. and Sally B. Thornton Hospital on UC San Diego’s La Jolla campus, in the heart of the area’s nexus of biomedical research centers. Jacobs Medical Center has been designed with the patient in mind. From spacious private rooms to soothing color schemes and artwork, to next-generation medical equipment, the vision and needs of patients, doctors and nurses, all aspects of the Jacobs Medical Center have been fully integrated. Each floor will combine all the necessary healing elements while achieving optimal safety and efficient delivery of care.

“Soon we will have the largest, most technologically advanced hospital in the region, dedicated to offering specialized care for every kind of patient, in every phase of life,” said Paul Viviano, CEO of UC San Diego Health System.

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UCSF Mission Bay hospital complex to open Feb. 1


Three new hospitals for women, children and cancer patients.

UCSF Medical Center at Mission Bay will open Feb. 1, 2015. (Photo by Mark Citret)

After more than 10 years of planning and construction, UCSF Medical Center at Mission Bay will open Feb. 1, 2015 on UC San Francisco’s world-renowned biomedical research campus. UCSF Medical Center at Mission Bay comprises UCSF Benioff Children’s Hospital San Francisco, UCSF Betty Irene Moore Women’s Hospital and UCSF Bakar Cancer Hospital. The new facilities include a 289-bed hospital complex, with children’s emergency and outpatient services that will integrate research and medical advancements with patient-focused, compassionate care.​

UCSF Medical Center at Mission Bay will welcome its first patients the morning of Feb. 1, when teams of health care professionals and ambulances begin moving some inpatients from the UCSF Parnassus campus and Mount Zion campus into the new facilities.

The new medical center, strategically located on UCSF’s 60.2-acre Mission Bay research campus, will enhance UCSF’s ecosystem of innovation by putting physicians in close proximity to researchers and near biotechnology and pharmaceutical companies in Mission Bay and beyond. The new cancer hospital, for example, will sit near the UCSF Helen Diller Family Cancer Research Building, where every day leading scientists are seeking causes and cures for cancer.

UCSF Medical Center at Mission Bay also will feature the only operating hospital helipad in San Francisco to transport critically ill babies, children and pregnant women to the medical center from outlying hospitals.

“UCSF Medical Center at Mission Bay profoundly advances our ability to fulfill our mission as a public hospital, providing high-quality health care that meets the future needs of the entire Bay Area,” said Mark R. Laret, CEO, UCSF Medical Center and UCSF Benioff Children’s Hospitals. “By embedding clinical care within our research enterprise at Mission Bay, UCSF physicians and scientists in the forefront of cancer medicine, and women’s and children’s health will be able to more readily translate discoveries into next-generation therapies and cures.”

Each of the new hospitals’ designs reflects significant input from patients and families, as well as clinicians.

“UCSF Medical Center at Mission Bay sets a national benchmark for patient- and family-centered health care by offering an unparalleled healing environment that supports and connects patients and their families during hospital stays,” said Cindy Lima, executive director, UCSF Mission Bay Hospitals Project. “These new hospitals expand our capacity to provide the most advanced treatments in buildings that reflect input from the people who will use them.”

The hospitals feature state-of-the art technology, including the world’s largest hospital fleet of autonomous robotic couriers which will deliver linens, meals and medications. Interactive media walls in each private room will enable patients to communicate with their families and clinicians, and an imaging suite specially designed to eliminate anxiety during an MRI offers children the chance to virtually experience a San Francisco trolley ride, or to play with a cast of animated critters as they boat around the San Francisco Bay.

Distinctive features of UCSF Medical Center at Mission Bay include 4.3 acres of green space and 1.2 acres of rooftop gardens, soothing art- and light-filled interiors and a public plaza created in partnership with the City of San Francisco. In addition, UCSF Medical Center at Mission Bay is on target to be one of the first LEED Gold-certified hospital in California.

The Integrated Center for Design and Construction brought together more than 200 architects, engineers and contractors working side by side in a command center on the construction site. Construction of the hospitals began in December 2010.

“The healing power of UCSF Medical Center at Mission Bay extends beyond the hospitals’ walls, as clinicians and researchers work side by side to accelerate medical breakthroughs and transform the delivery of health care in this country,” said Sam Hawgood, M.B.B.S., chancellor of UC San Francisco. “It’s important to note that the hospital complex was built only through the generous philanthropic support of the Bay Area community, who share our vision of advancing health care across the world. We are greatly appreciative of their unwavering commitment to our mission over the past decade. ”

UCSF Benioff Children’s Hospital San Francisco

UCSF Benioff Children’s Hospital San Francisco, one of the nation’s leading children’s hospitals, provides treatment for virtually all pediatric conditions, as well as for critically ill newborns. The Neonatal Intensive Care Nursery at UCSF Benioff Children’s Hospital San Francisco was one of the first of its kind in the world. The hospital is the only California state-designated children’s medical center in San Francisco and is affiliated with UCSF Benioff Children’s Hospital Oakland.

The new 183-bed facility at Mission Bay creates an environment where children and their families find quality care at the forefront of scientific discovery. Private rooms in the intensive care nursery support the youngest patients, while the fully accredited classroom and teachers enable school-age patients to continue their education while focusing on their health. The hospital offers accommodations for families of pediatric patients and nearby lodging for those requiring longer stays.

UCSF Bakar Cancer Hospital

UCSF ranks consistently among the top cancer care centers in the nation, according to the “America’s Best Hospitals” survey from U.S. News & World Report. UCSF Bakar Cancer Hospital sets the standard in personalized care, delivering advanced cancer therapies tailored to individual patient needs. The hospital increases UCSF’s inpatient and outpatient capacity to meet growing demand, in a state-of-the-art facility. The new hospital will absorb many of the cancer surgery beds currently located at UCSF Medical Center at Mount Zion, offering cancer surgeries in specialties ranging from urology and orthopedics, to head and neck and gynecologic oncology. Specialists also serve the individual needs of cancer patients from the children’s and women’s hospitals. In the future, Mission Bay could house as many as 250 or more surgery beds, with a full complement of outpatient cancer care services.

UCSF Betty Irene Moore Women’s Hospital

As the region’s first dedicated women’s hospital, UCSF Betty Irene Moore Women’s Hospital will embody the philosophy of the UCSF National Center of Excellence in Women’s Health. The new hospital will deliver care that addresses health needs across a woman’s lifetime, including cancer treatment, specialty surgery, a 36-bed birth center, nine deluxe labor and delivery rooms, and select outpatient services. Customizing care to each patient, the hospital will provide the best available diagnostic tests and treatments in a caring, women- and family-focused environment that incorporates the latest technology. Spacious rooms allow loved ones to spend the day or night comfortably.

Each labor and delivery room is designed to be respectful to patients and families during the life-altering event of childbirth. Combining sophisticated technical capabilities with carefully considered design choices, each room emits a sense of calm for the birthing experience. At the same time, it is a highly functional space for clinicians to provide quality care.

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The basics behind healthy growth — and disease


UC Irvine professor builds mathematical models to help identify underlying cancer causes.

How does understanding the basics of what goes on in our tissues during normal development help us explain the causes and progression of diseases such as cancer? While attending a Society for Industrial & Applied Mathematics conference this summer on the life sciences, Arthur Lander – the Donald Bren Professor of Developmental & Cell Biology at UC Irvine – talked about the biological systems that control cell proliferation to achieve or maintain desired outcomes.

In this video, he explains that regulated growth not only is essential for biological development, but also establishes the context in which the out-of-control state we call cancer occurs. Lander’s research group builds mathematical models that mimic real tissues in order to understand normal growth control. Using such models, his lab is learning how morphogenesis – the process by which tissues take on complex three-dimensional forms – can be achieved by turning growth on and off in certain locations, through regulated feedback between mature cells and the cells that produce them.

Lander is a recognized leader in the emerging field of systems biology, and his research is helping to identify the underlying causes for some cancers and birth defects. He’s the founding director of the campus’s Center for Complex Biological Systems. Founded in 2002, the center was the first of its kind in California dedicated to systems biology and employs the latest technology and computational methods to explore how networks of molecules, cells, tissues and organs interact in complex, dynamic ways to enable reliable biological functions.

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Soap’s dirty side


Triclosan, common antimicrobial in hygiene products, causes liver fibrosis, cancer in mice.

Triclosan is an antimicrobial commonly found in soaps, shampoos, toothpastes and many other household items. Despite its widespread use, researchers at the UC San Diego School of Medicine report potentially serious consequences of long-term exposure to the chemical. The study, published today (Nov. 17) by Proceedings of the National Academy of Sciences, shows that triclosan causes liver fibrosis and cancer in laboratory mice through molecular mechanisms that are also relevant in humans.

“Triclosan’s increasing detection in environmental samples and its increasingly broad use in consumer products may overcome its moderate benefit and present a very real risk of liver toxicity for people, as it does in mice, particularly when combined with other compounds with similar action,” said Robert H. Tukey, Ph.D., professor in the departments of chemistry and biochemistry and pharmacology. Tukey led the study, together with Bruce D. Hammock, Ph.D., professor at UC Davis. Both Tukey and Hammock are directors of National Institute of Environmental Health Sciences (NIEHS) Superfund Programs at their respective campuses.

Tukey, Hammock and their teams, including Mei-Fei Yueh, Ph.D., found that triclosan disrupted liver integrity and compromised liver function in mouse models. Mice exposed to triclosan for six months (roughly equivalent to 18 human years) were more susceptible to chemical-induced liver tumors. Their tumors were also larger and more frequent than in mice not exposed to triclosan.

The study suggests triclosan may do its damage by interfering with the constitutive androstane receptor, a protein responsible for detoxifying (clearing away) foreign chemicals in the body. To compensate for this stress, liver cells proliferate and turn fibrotic over time. Repeated triclosan exposure and continued liver fibrosis eventually promote tumor formation.

Triclosan is perhaps the most ubiquitous consumer antibacterial. Studies have found traces in 97 percent of breast milk samples from lactating women and in the urine of nearly 75 percent of people tested. Triclosan is also common in the environment: It is one of the seven most frequently detected compounds in streams across the United States.

“We could reduce most human and environmental exposures by eliminating uses of triclosan that are high volume, but of low benefit, such as inclusion in liquid hand soaps,” Hammock said. “Yet we could also for now retain uses shown to have health value — as in toothpaste, where the amount used is small.”

Triclosan is already under scrutiny by the FDA, thanks to its widespread use and recent reports that it can disrupt hormones and impair muscle contraction.

Co-authors include Koji Taniguchi, Shujuan Chen and Michael Karin, UC San Diego; and Ronald M. Evans, Salk Institute for Biological Studies.

This research was funded, in part, by U.S. Public Health Service grants ES010337, GM086713, GM100481, A1043477, ES002710 and ES004699.

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Anti-leukemia drug also may work against ovarian cancer


Findings extend anti-cancer potential of monoclonal antibody developed at UC San Diego.

An antibody therapy already in clinical trials to treat chronic lymphocytic leukemia (CLL) also may prove effective against ovarian cancer – and likely other cancers as well, report researchers at the UC San Diego School of Medicine in a study published in today’s (Nov. 17) online early edition of the Proceedings of the National Academy of Sciences (PNAS).

The findings extend the anti-cancer potential of an experimental monoclonal antibody called cirmtuzumab, developed at UC San Diego Moores Cancer Center by Thomas Kipps, M.D., Ph.D., and colleagues. Cirmtuzumab is currently in a first-in-human phase one clinical trial to assess its safety and efficacy in treating CLL.

Cirmtuzumab targets ROR1, a protein used by embryonic cells during early development and exploited by cancer cells to promote tumor growth and metastasis, the latter being responsible for 90 percent of all cancer-related deaths.

Because normal adult cells do not express ROR1, scientists suspect ROR1 is a specific biomarker of cancer cells in general and cancer stem cells in particular. Because it appears to drive tumor growth and disease spread, they believe it also presents an excellent target for anti-cancer therapies. Earlier research by Kipps and colleagues has shown a link between ROR1 and both breast cancer and CLL.

In their latest PNAS paper, Kipps and colleagues investigated whether cirmtuzumab also might be effective against ovarian cancer, which has rebuffed efforts to find a cure or long-term remedy. Most ovarian cancer patients initially respond well to standard chemotherapy, sometimes appearing to become disease-free, but 85 percent relapse within two years after systemic treatment, often with a more aggressive and disseminated form of the disease.

More than 21,000 women are diagnosed with ovarian cancer annually; more than 14,000 die from the disease each year. The 5-year survival rate after diagnosis is 44.6 percent.

The Moores Cancer Center team found that ovarian cancer stem cells, which are thought to be responsible for cancer recurrence and metastasis and are largely resistant to standard chemotherapies, singularly express ROR1. Patients whose tumors had high levels of ROR1 experienced more aggressive forms of ovarian cancer. They had higher rates of relapse and shorter median survival times than patients with lower levels of ROR1.

“ROR1 is used by embryo cells to migrate and to develop new organs,” said Kipps. “Cancer stem cells subsequently use ROR1 for their own growth and dissemination throughout the body. They are essentially the seeds of the cancer. The more seeds a tumor has, the greater its ability to recur after therapy or metastasize.”

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Nonsmokers in cars can be exposed to significant secondhand smoke


UCSF researchers find elevated carcinogen markers for first time in car passengers.

Nonsmokers sitting in an automobile with a smoker for one hour had markers of significantly increased levels of carcinogens and other toxins in their urine, indicating that secondhand smoke in motor vehicles poses a potentially major health risk according to a groundbreaking study led by UC San Francisco researchers.

The nonsmoking passengers showed elevated levels of butadiene, acrylonitrile, benzene, methylating agents and ethylene oxide. This group of toxic chemicals is “thought to be the most important among the thousands in tobacco smoke that cause smoking-related disease,” said senior investigator Neal L. Benowitz, M.D., a UCSF professor of medicine and bioengineering and therapeutic sciences and chief of the division of clinical pharmacology at San Francisco General Hospital and Trauma Center.

“Ours is the first study to measure exposure to these particular chemicals in people exposed to secondhand smoke,” said Benowitz. “This indicates that when simply sitting in cars with smokers, nonsmokers breathe in a host of potentially dangerous compounds from tobacco smoke that are associated with cancer, heart disease and lung disease.”

The scientists published their results today (Nov. 14) in the journal Cancer, Epidemiology, Biomarkers & Prevention, published by the American Association for Cancer Research.

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Eating walnuts slows prostate cancer growth, study finds


UC Davis research finds health benefits in walnuts.

Paul Davis, UC Davis

Researchers at UC Davis and other institutions have found that diets rich in whole walnuts or walnut oil slowed prostate cancer growth in mice. In addition, both walnuts and walnut oil reduced cholesterol and increased insulin sensitivity. The walnut diet also reduced levels of the hormone IGF-1, which had been previously implicated in both prostate and breast cancer. The study was published online in the Journal of Medicinal Food.

“For years, the United States government has been on a crusade against fat, and I think it’s been to our detriment,” said lead scientist and research nutritionist Paul Davis. “Walnuts are a perfect example. While they are high in fat, their fat does not drive prostate cancer growth. In fact, walnuts do just the opposite when fed to mice.”

Davis and colleagues have been investigating the impact of walnuts on health for some time. A previous study found that walnuts reduced prostate tumor size in mice; however, there were questions about which parts of the nuts generated these benefits. Was it the meat, the oil or the omega-3 fatty acids? If it was the omega-3 fats, the benefit might not be unique to walnuts. Since the fatty acid profile for the soybean oil used as a control was similar, but not identical, to walnuts, more work had to be done.

In the current study, researchers used a mixture of fats with virtually the same fatty acid content as walnuts as their control diet. The mice were fed whole walnuts, walnut oil or the walnut-like fat for 18 weeks. The results replicated those from the previous study. While the walnuts and walnut oil reduced cholesterol and slowed prostate cancer growth, in contrast, the walnut-like fat did not have these effects, confirming that other nut components caused the improvements – not the omega-3s.

“We showed that it’s not the omega-3s by themselves, though, it could be a combination of the omega-3s with whatever else is in the walnut oil,” Davis said. “It’s becoming increasingly clear in nutrition that it’s never going to be just one thing; it’s always a combination.”

While the study does not pinpoint which combination of compounds in walnuts slows cancer growth, it did rule out fiber, zinc, magnesium and selenium. In addition, the research demonstrated that walnuts modulate several mechanisms associated with cancer growth.

“The energy effects from decreasing IGF-1 seem to muck up the works so the cancer can’t grow as fast as it normally would,” Davis said. “Also, reducing cholesterol means cancer cells may not get enough of it to allow these cells to grow quickly.”

In addition, the research showed increases in both adiponectin and the tumor suppressor PSP94, as well as reduced levels of COX-2, all markers for reduced prostate cancer risk.

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Two UC physicians win cancer research award


Lung cancer research award encourages ‘out-of-the-box thinking.’

Jonathan Riess, UC Davis

Medical oncologists Jonathan Riess of UC Davis, Trever Bivona of UC San Francisco and Ryan Corcoran of Massachusetts General Hospital Cancer Center and Harvard Medical School are recipients of a 2014 Young Innovators Team Award for Lung Cancer Research. They will share $500,000 in funding for translational lung cancer research.

They were honored Nov. 8 by the Bonnie J. Addario Lung Cancer Foundation and Van Auken Private Foundation at the Simply the Best Gala in San Francisco.

The awardees were selected based on a rigorous, multilevel peer review, as well as in-person presentation, to the foundation’s scientific review committee.

“The idea is to encourage out-of-the-box thinking and foster leadership skills among young innovators, instilling confidence in them to drive breakthrough research under a collaborative paradigm,” said Guneet Walia, director of research and medical affairs at the Addario Foundation. “We are proud to announce recipients who truly embody the multidisciplinary, translational and cross-institutional spirit of the award, and will collaboratively work on a unique biomarker and drug target in lung cancer patients.”

Trever Bivona, UC San Francisco

The three will work to evaluate a unique drug target in non-small cell lung cancer, identified in preliminary studies to be active in 20 to 30 percent of all patients with the disease, and a potential cause for resistance to therapy.

The Addario Foundation, devoted exclusively to eradicating lung cancer, has raised more than $20 million for lung cancer research and related programs. The Van Auken Private Foundation provides contributions and assistance to other charitable organizations in arts, science, medicine, education and other worthy social causes.

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Leukemia expert to lead UC Irvine’s cancer research efforts


Susan O’Brien comes from MD Anderson Cancer Center.

Susan O'Brien

Susan M. O’Brien, M.D., one of the nation’s foremost leukemia experts, will join UC Irvine Health as associate director for clinical science for the Chao Family Comprehensive Cancer Center and Medical Director of the Sue and Ralph Stern Center for Cancer Clinical Trials and Research. Her appointment is effective Jan. 1, 2015.

A renowned researcher and clinician, O’Brien’s leadership will help UC Irvine Health and the Chao Family Comprehensive Cancer Center increase both the number and complexity of innovative, outcomes-focused clinical trials.

“This is an exciting time for cancer research. UC Irvine Health has an opportunity to build on its decades-long commitment to serving our region with leading-edge treatments and access to clinical trials,” said Richard A. Van Etten, M.D., Ph.D., director, Chao Family Comprehensive Cancer Center, UC Irvine.

“As a comprehensive cancer center, we have an obligation to lead the way in our region and nationally,” he said. “Dr. O’Brien’s appointment is a critical step toward achieving those goals.”

O’Brien comes to UC Irvine from the University of Texas MD Anderson Cancer Center where she was the Ashbel Smith Professor in the Department of Leukemia, Division of Cancer Medicine.  She has been principal investigator for more than 40 funded clinical research protocols and has authored more than 600 articles in peer-reviewed journals, 30 invited articles, and numerous book chapters and abstracts.

She is the chair of the National Comprehensive Cancer Network (NCCN) Chronic Myelogenous Leukemia Guidelines Committee, a member of the NCCN Acute Lymphoblastic Leukemia Guidelines Committee and is the hematology member of the Southwest Oncology Group Executive Committee.

As associate director for clinical science, O’Brien will be responsible for overseeing and coordinating clinical cancer research across the entire UC Irvine Health enterprise, including medical oncology, radiation oncology, surgical oncology and gynecologic oncology.

O’Brien will take the lead with UC Irvine Health clinical investigators to expand the portfolio of early phase clinical trials and launch a formal Experimental Therapeutics Program in her role as medical director of the Sue and Ralph Stern Center for Cancer Clinical Trials and Research.

One of 41 National Cancer Institute-designated comprehensive cancer centers in the U.S. and the only one in Orange County, the UC Irvine Health Chao Family Comprehensive Cancer Center is dedicated to excellence in cancer treatment, prevention, research and education. Its specialists provide compassionate, comprehensive care during 91,000 annual patient visits and conduct more than 150 ongoing clinical trials that offer access to the latest, cutting-edge cancer treatments.

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Bridging the gap in precision medicine


UCSF takes steps to solve the ‘last mile’ problem.

By Pete Farley, UC San Francisco

For entertainment giants such as Netflix and HBO, there’s an oft-cited concept known as “the last mile.”

It refers to the performance bottleneck that can arise in the short, final stretch of cable that links their vast, sophisticated server farms to the humble jack on a subscriber’s wall.

More than a decade after the immense promise unleashed by the completion of Human Genome Project, precision medicine has struggled with its own “last mile.” Despite major leaps in the field as a whole, the technical work needed to integrate a patient’s genomic information into the day-to-day practice of medicine has lagged far behind.

This month, UCSF is unveiling its bridge across that persistent gap.

Through its Genomic Medicine Initiative (GMI), UCSF has integrated data from a comprehensive cancer genetic testing program into the electronic medical records of patients at the Helen Diller Family Comprehensive Cancer Center. Not only does it allow for continuity of care with all testing and treatment results tied to the same electronic record, but it also allows physicians and researchers to identify larger patterns in the data that can lead to the development of better treatments.

“Many major medical institutions, including UCSF, have long had the science and the technology to generate genomic test results,” said Kristen McCaleb, Ph.D., program manager for the GMI. “The problem we’ve had is a lack of IT infrastructure to return those results to the clinicians who order the tests in a clearly actionable, doctor-friendly format.

This new project is a powerful new cloud-based software platform built in partnership with Palo Alto-based Syapse that seamlessly unites genomic testing and analysis, personalized treatment regimens, clinical data, and outcomes data, and –  crucially – integrates all of these features directly into APeX, UCSF Medical Center’s Epic-based electronic medical record (EMR) system.

“Genomics has the potential to dramatically improve patient care in oncology, but the full promise of precision medicine cannot be realized without a software platform to bring genomics to the point of care,” said Jonathan Hirsch, who founded Syapse six years ago as a 23-year-old Stanford University graduate student. “It is critical that genomic data be integrated with the patient’s medical history and presented to the clinician within the workflow of their EMR.”

One of the most comprehensive genetic tests for cancer

A major feature of the UCSF-Syapse partnership is that, beginning in the spring of 2015, UCSF oncologists will be able to order the “UCSF 500,” a panel of more than 500 gene mutations that have been implicated in a range of cancers. The test results will automatically feed into their adult and pediatric patients’ EMRs.

The assembly of the UCSF 500 wouldn’t have been possible without UCSF’s medical oncologists collaborating with Syapse to define which genomic alterations in which cancer types can be best treated with targeted therapies,” he said.

“The collaboration between the UCSF Helen Diller Family Comprehensive Cancer Center and Syapse is just one example of what the UCSF Genomic Medicine Initiative, launched two years ago, is doing to bring genomics to bear on clinical medicine,” said Robert Nussbaum, M.D., director of the GMI. “We are excited with the results and look forward to using it to improve the care of our patients here in the Cancer Center.”

When completed, test results from the UCSF 500 will automatically appear in a Syapse-powered window in the EMR, and from there, physicians can trigger consultation by a newly formed Molecular Tumor Board, a group of expert physicians and researchers that can recommend customized treatment plans for each patient.

These recommendations are recorded in Syapse alongside the physician’s decisions, and the patient’s clinical course will be continuously tracked. The resulting information is displayed to the physician in an easy-to-understand graphical format, and clinical notes and summaries are automatically populated in the EMR.

Learning from the data

Because the Syapse system is cloud-based, on Amazon Web Services (AWS), physicians and members of the Molecular Tumor Board can query a patient’s test results in real time against the latest entries in UCSF’s knowledge-base, which is also drawn from public genetics, oncology and clinical trial databases, as well as the current scientific literature. AWS was selected for its robust security, support for compliance with medical information privacy laws, scalability and redundancy, Hirsch said.

A de-identified version of each patient’s clinical history from APeX and information on how patients respond to treatments is simultaneously added to a dedicated clinical research knowledge-base within Syapse, so future recommendations of the Molecular Tumor Board for any patient’s case will always be informed by the latest clinical experience.

Because APeX is based on Epic, a widely used EMR system, the new platform is easily scalable, and could easily capture clinical data from many medical centers in a consistent, easily accessible form, said Hirsch.

“Our top priority is benefitting our patients today, but if we can begin to collect and leverage the knowledge we gain from each positive patient outcome, and combine our experience with that of others doing similar work worldwide, future patients may be able to sidestep conventional therapies and go directly to the best targeted therapy as a first-line treatment,” McCaleb said.

“And that would be truly powerful.”

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Discovery could lead to better head and neck cancer therapies


UCLA researchers find link between protein gigaxonin and head and neck cancer.

UCLA scientists have discovered that a protein usually linked to rare neurological disorders is also associated with head and neck cancer in people who are infected with the human papilloma virus. And when that protein is combined with another cancer-suppressing protein, it helps improve the effectiveness of chemotherapy treatments, according to a new study by UCLA researchers.

Head and neck cancer is the sixth-most common form of cancer worldwide, and represents 5 percent of cancers diagnosed annually in the United States. Of the more than 42,000 people diagnosed with head and neck cancer each year, 12,000 will die from the disease.

Human papilloma virus is the most common sexually transmitted infection, and HPV diagnoses are at epidemic proportions. The Centers for Disease Control and Prevention estimate that nearly all sexually active men and women will get it at some point in their lives.

Led by Dr. Eri Srivatsan and Dr. Marilene Wang, UCLA Jonsson Comprehensive Cancer Center members and co-authors of the study, researchers found the link between the protein gigaxonin and head and neck cancer while investigating the chemotherapy drug cisplatin. The drug is successfully able to kill cancer cells by interacting with the protein p16 which is commonly produced in HPV-positive cancers.

“We studied the interaction of p16 in the nucleus of the cancer cell after treatment with cisplatin, and observed how the protein interacted with gigaxonin,” said Wang, professor-in-residence of head and neck surgery. “We found the combination of the proteins stops the cell cycle, allowing chemotherapy treatment to prevent the cell from growing and killing the cancer cell.”

For the study, Wang, Srivatsan and eight colleagues at UCLA also analyzed 103 archival clinical samples from head and neck cancer patients to identify the relationship between p16 nuclear expression and cancer-free survival. They found that patients with cancers with p16 expression had better survival rates than without p16 expression.

Though HPV has mostly been seen in cervical cancer, during the past several years there has been an increase in HPV-positive head and neck cancers, which often affect non-smoking younger adults, who previously were not considered to be at high risk for head and neck cancer.

The researchers said they hope that the new findings will lead to an enhanced form of personalized targeted therapy for head and neck cancer patients, ultimately reducing the harsh side effects of chemotherapy and radiation.

“This discovery opens new possibilities in the diagnosis and treatment of HPV-positive head and neck cancers,” said Srivatsan, who is a professor of general surgery.

The study was recently published online in the Journal of Biological Chemistry.

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