TAG: "Cancer"

Robotic surgery technique developed to treat head and neck cancer


Pioneering method, developed at UCLA, gives patients new hope to live cancer-free lives.

By Peter Bracke, UCLA

In a groundbreaking new study, UCLA researchers have advanced a robotic surgical technique to successfully access a previously unreachable area of the head and neck.

This pioneering method can now be used safely and efficiently in patients to remove tumors that many times were previously considered inoperable, or that necessitated the use of highly invasive surgical techniques in combination with chemotherapy or radiation therapy.

Abie Mendelsohn, UCLA

Developed by Dr. Abie Mendelsohn, UCLA Jonsson Comprehensive Cancer Center member and director of head and neck robotic surgery at UCLA, this new approach provides the surgical community with a leading-edge technology roadmap to treat patients who had little or no hope of living cancer-free lives.

“This is a revolutionary new approach that uses highly advanced technology to reach the deepest areas of the head and neck,” said Mendelsohn, lead author of the study. “Patients can now be treated in a manner equivalent to that of a straightforward dental procedure and go back to leading normal, healthy lives in a matter of days with few or even no side effects.”

The parapharyngeal space is pyramid-shaped area that lies near the base of the human skull and connects several deep compartments of the head and neck. It is lined with many large blood vessels, nerves and complex facial muscles, making access to the space via traditional surgical options often impossible or highly invasive.

Current surgical techniques can necessitate external incisions be made to the patient’s neck, or the splitting of their jaw bone or areas close to the voice box. Chemotherapy and radiation therapy are also often required, further complicating recovery and potentially putting patients at risk for serious (or even lethal) side effects.

Approved by the U.S. Food and Drug Administration in 2009, Trans Oral Robotic Surgery (or TORS) utilizes the Da Vinci robotic surgical system, the state-of-the-art technology that was developed at UCLA by the specialized surgical program for the head and neck. TORS uses a minimally invasive procedure in which a surgical robot, under the full control of a specially trained physician, operates with a three-dimensional, high-definition video camera and robotic arms.

These miniature “arms” can navigate through the small, tight and delicate areas of a person’s mouth without the need for external incisions. A retraction system allows the surgeon to see the entire surgical area at once. While working at an operating console just steps away from the patient’s bed, every movement of the surgeon’s wrists and fingers are transformed into movements of the surgical instruments.

Over the course of the robotic program’s development, Mendelsohn refined, adapted and advanced the TORS techniques to allow surgical instruments and the 3-D imaging tools to at last reach and operate safely within the parapharyngeal space and other recessed areas of the head and neck.

Currently, Mendelsohn’s new procedure largely benefits patients with tumors located in the throat near the tonsils and tongue, but it continues to be adapted and expanded in scope and impact.

“We are tremendously excited about the possibilities for the surgical community with this new advancement of TORS,” said Mendelsohn. “Now patients have options they never had before, and we can even develop potential applications for the procedure beyond the surface of the head and neck.”

The study was published online ahead of print in the journal Head and Neck.

David Alpern: one patient’s story

UCLA patient David Alpern and son. Alpern is now cancer-free after his throat tumor was removed using Dr. Abie Mendelsohn’s breakthrough robotic surgery technique.

In 2012, David Alpern received devastating news. He was diagnosed with throat cancer, and the treatment options given to him by his doctors sounded worse than the disease.

“They described a procedure where your face is split in half and it’s basically reconstructive surgery. I was completely freaked out,” said Alpern, a husband and father of two.

After careful examination and imaging at UCLA, Mendelsohn determined that Alpern was a perfect candidate for TORS. Alpern was up and about just days after the procedure. Like the more than 100 similar TORS surgeries performed with Mendelsohn at the controls, Aplern’s tumor was removed and he’s now cancer free.

“I try not to get too cocky or excited that I beat cancer, but I think I did,” Alpern said. “There are no side effects at this point. My hopes are just to watch my kids grow up and enjoy my family and my life.”

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A sense for biosensors


UC Irvine’s Weian Zhao has created a device that improves detection of bacterial, viral invaders in blood samples.

The Integrated Comprehensive Droplet Digital Detection system invented by Weian Zhao of UC Irvine converts blood samples directly into billions of very small droplets. (Photo by Steve Zylius, UC Irvine)

By Tom Vasich, UC Irvine

As a doctoral student at McMaster University in Hamilton, Ontario, Weian Zhao took part in a Canada-wide research effort to develop bioactive paper that would detect, capture and deactivate waterborne and airborne pathogens.

As part of this project, he helped invent gold nanoparticle-coated paper that could detect common pathogens, such as E. coli, but ultimately, the product didn’t meet his exacting standards of diagnostic speed and sensitivity. With a freshly minted Ph.D. in chemistry, Zhao moved on to a joint postdoctoral fellowship at both the Massachusetts Institute of Technology and Harvard, where he dove into stem cell research, his biosensor work seemingly left north of the border.

But the challenge of creating a technology that could rapidly and selectively identify bacterial and viral invaders in blood samples nagged at the young scientist, even as he joined UC Irvine in 2011 as an assistant professor of pharmaceutical sciences with state-of-the-art lab space in the Sue & Bill Gross Stem Cell Research Center.

And then he met Enrico Gratton. In his Laboratory for Fluorescence Dynamics, the UCI biomedical engineer and colleagues have been developing imaging tools for biomedical applications. Among them is a three-dimensional particle counter that tags low-concentration fluorescent particles in large volumes of solution within several minutes, which drew Zhao’s attention. He knew he was back in the biosensor game.

Employing this particle counter, Zhao created a bloodstream infection test that speeds up diagnosis times with unprecedented accuracy – allowing physicians to treat patients with potentially deadly ailments more promptly and effectively.

Zhao says that the Integrated Comprehensive Droplet Digital Detection system can, in as little as 90 minutes, detect bacteria in milliliters of blood with single-cell sensitivity; no cell culture is needed. He published his latest results in the November issue of Nature Communications.

“We are extremely excited about this technology because it addresses a long-standing unmet medical need in the field,” says Zhao, who also holds a faculty appointment in biomedical engineering. “As a platform technology, it may have many applications in detecting extremely low-abundance biomarkers in other areas, such as cancers, HIV and, most notably, Ebola.”

Bloodstream infections are a major cause of illness and death. In particular, infections associated with antimicrobial-resistant pathogens are a growing health problem in the U.S. and worldwide. According to the Centers for Disease Control & Prevention, more than 2 million people a year globally get antibiotic-resistant blood infections, with about 23,000 deaths. The high mortality rate for blood infections is due, in part, to the inability to rapidly diagnose and treat patients in the early stages.

Recent molecular diagnosis methods, including polymerase chain reaction, can reduce the assay time to hours but are often not sensitive enough to detect bacteria that occur at low concentrations in blood, as is common in patients with incipient blood infections.

The Integrated Comprehensive Droplet Digital Detection technology differs from other diagnostic techniques in that it converts blood samples directly into billions of very small droplets. Fluorescent DNA sensor solution infused into the droplets detects those with bacterial markers, lighting them up with an intense fluorescent signal. Zhao says that separating the samples into so many small drops minimizes the interference of other components in blood, making it possible to directly identify target bacteria without the purification typically required in conventional assays.

“The IC 3D instrument is designed to read a large volume in each measurement, to speed up diagnosis,” Gratton says. “Importantly, using this technique, we can detect a positive hit from hundreds of millions of measurement samples with very high confidence.”

But invention was only the first step. Zhao wants to commercialize IC 3D. At UCI, faculty researchers with an entrepreneurial bent can work with the Institute for Innovation, an interdisciplinary and campuswide center focused on integrating research, entrepreneurship and technology to create real-world applications that benefit the public and drive the economy. The Office of Technology Alliances, part of the institute, helped Zhao patent-protect the IC 3D technology and establish a spin-off company, Velox Biosystems, to test and manufacture a commercial IC 3D device.

Currently, Zhao is focusing on applying IC 3D to cancer treatments – an extension of the research he’s been advancing since joining UCI.

Zhao has been developing stem cell messengers that selectively migrate to cancer sites to deliver tumor-fighting drugs or probes for contrast-enhanced medical imaging. This could, potentially, enable the identification of cancer micro-metastases at their early stages and increase the effectiveness of chemotherapeutic treatments for metastatic cancer while mitigating the symptoms associated with systemic chemotherapy.

For this work, Zhao was included in the MIT Technology Review’s 2012 list of the world’s top innovators under the age of 35, and this year he earned a prestigious National Institutes of Health Director’s New Innovator Award to further his efforts to create stem cell-based detection methods and treatments for cancer.

He’s also collaborating with Dr. Jason Zell, an assistant professor of medicine and co-leader of the Colon Cancer Disease-Oriented Team at UCI’s Chao Family Comprehensive Cancer Center, to use IC 3D to identify biomarkers in colon cancers. This could enable oncologists to gauge the effectiveness of treatment during the cancer’s early stages more accurately than with current methods, which Zell says are not reliable.

Zhao is now seeking business partners to accelerate Velox Biosystems’ growth and hopes to conduct clinical studies of IC 3D’s utility in patient diagnosis and treatment.

“That’s what’s so important about this project,” he says. “We’ve created a multi-platform tool that has the potential to work with a variety of infections and diseases. I’m very excited about its future.”

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FDA approves drug that extends survival in most common type of lung cancer


Drug offers new hope for people with lung cancer who often have few treatment options.

Edward Garon, UCLA

By Peter Bracke, UCLA

The Food and Drug Administration today (Dec. 12) approved a new drug to treat non-small-cell lung cancer (NSCLC), offering people new hope in fighting the disease. Lung cancer is expected to lead to more than 150,000 deaths in the United States this year alone, and NSCLC accounts for about 85 percent of all lung cancers. The drug, Cyramza (ramucirumab), was tested on more than 1,200 people with NSCLC whose cancer worsened during or after first-line chemotherapy. The research was conducted as part of a multiyear, phase three clinical trial at UCLA and other centers in 26 countries on six continents. This is the first study in a decade to demonstrate a survival benefit in people with that type of lung cancer who had already received treatments.

Cyramza is an antibody that targets the extracellular domain of VEGFR-2, an important protein in the formation of vessels that supply blood to cancer cells. Patients were given the experimental drug in combination with docetaxel, a clinically approved therapy that is considered the cornerstone of second-line treatment in advanced NSCLC, said Dr. Edward Garon, the study’s principal investigator and a researcher at the UCLA Jonsson Comprehensive Cancer Center. Results of the study were recently published by Garon and colleagues in The Lancet.

The standard treatment regimen for people whose cancer worsens during or after initial therapy is chemotherapy with a single drug. This is a patient population for whom survival is typically several months, with approximately only 10 percent of patients responding to therapy.

The percentage of people who responded to treatment and the period of time before the disease worsened were both greater when Cyramza was added to docetaxel compared to what was seen with docetaxel alone, Garon said. In the study, 23 percent of patients responded to the combination of Cyramza and docetaxel, meaning that their tumors shrank more than a specific threshold used in clinical trials. Overall, the median survival was more than 10 months.

”It is exciting to see that by adding ramucirumab (Cyramza) to docetaxel, patients were able to live longer than those who were treated with the standard approach,” Garon said. “We are pleased to have access to a drug that lengthens survival time in a population of lung cancer patients who often have few treatment options.”

Although adverse effects were experienced by patients, most commonly neutropenia (low levels of white blood cell that fight infection), fatigue and high blood pressure, these were largely manageable with appropriate dose reductions and supportive care, and without substantial reduction in planned dose intensity.

Garon said that in the future Cyramza will be evaluated in combination with other drugs to treat lung cancer. In addition, he noted that efforts are underway to understand which patients are most likely to benefit when Cyramza is added to docetaxel.

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Boy battling cancer honored as UCLA’s No. 1 sports fan


He’s chosen as first Kid Captain by the basketball team and Mattel Children’s Hospital UCLA.

Logan Nobriga, with ball, and friends cheering at Bruins basketball game.

By Amy Albin, UCLA

Logan Nobriga, a 10-year-old-boy who is battling cancer, never expected he’d see his story played out on the giant monitor at Pauley Pavilion. But on Wednesday, he stood on the basketball court before the tip-off of a game watching a video about the fight of his young life.

Logan, who comes from Oak Park, was honored at the Bruins’ game against UC Riverside as the first “Kid Captain” selected by Mattel Children’s Hospital UCLA and the UCLA Men’s Basketball team. The new program will recognize UCLA pediatric patients who face life-threatening illnesses with courage, strength and determination.

Logan, who has spent half of his young life in the battle against acute lymphoblastic leukemia (ALL), is an inspiration to everyone, a hospital staff member said.

“Logan, who transforms his hospital room into a ‘sports zone,’ has been known to play a couple of wild games of basketball in the hospital, even when he was in the intensive care unit,” said Hilary Gan, a child-life specialist with the Chase Child Life program at Mattel. “Recently, he donated his birthday presents to the other children in the hospital.”

On Wednesday night, Logan high-fived Bruin players as they entered the court at the start of the game and then took a complimentary courtside seat with a friend he invited before having dinner at Pauley Pavilion.

“My college basketball team is definitely UCLA,” said Logan, a huge sports fan, in the video.

IIn 2009, he was diagnosed with ALL, a type of cancer of the blood and bone marrow. In 2013, he relapsed and is currently receiving chemotherapy as an outpatient.

“Having ALL … you don’t get to do a lot of other things that kids do,” he said on the video. So being treated as UCLA’s No. 1 Bruin fan with all the perks, including getting the game ball, was a special moment for him.

“We are excited to partner with our colleagues at Mattel Children’s Hospital UCLA to recognize these special young patients who inspire us all with their stories of hope and courage,” added Paul Engl, general manager of IMG College Los Angeles, the official sports marketing agency for UCLA Athletics.

See Logan’s story:

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The art of healing


The concept is drawing increasing interest from the medical and science communities.

By Kathleen Masterson and Suzanne Leigh, UC San Francisco

Seated at a table dotted with paintbrushes, pencils and curios, Hideka Suzuki is creating an abstract on a small canvas. It’s not an idle craft project; for her, it’s a form of therapy.

“Sometimes I don’t even know what I’m thinking until I sit down and start drawing. Then my feelings come out on paper,” said Suzuki, a teacher in remission from uterine cancer.

She’s a participant at Art for Recovery, a pioneering program at the UCSF Helen Diller Family Comprehensive Cancer Center that has brought patients together since 1988 under the philosophy that creating art – no skills required – has a central role in healing.

It’s hard to empirically measure that impact because so many of art’s benefits are indirect, said Theresa Allison, M.D., Ph.D., an assistant professor in the UCSF Division of Geriatrics who has a background in musical anthropology. But, she said, therapies that benefit a patient’s emotional wellbeing can have real impact on overall health.

“We are finally at a tipping point, where the health sciences recognize the impact of loneliness and depression on health care outcomes, and we recognize the positive impact of visual and performing arts on symptoms management,” Allison said.

“Now we’re starting to ask why, and to bring in the science to study art’s impact. National funding agencies are starting to support this, and we’re going to see a lot of research emerge in upcoming years.”

Over the last few decades, a growing body of studies and anecdotal evidence suggesting that art is healing have driven the incorporation of art into medical settings. Nearly half of the health care institutions in the United States reported including arts in health care programming, ranging from art and music therapy to featuring visual art in hospitals.

“It’s a huge opportunity to think about using different modes of healing,” said Julene Johnson, Ph.D., a cognitive neuroscientist and professor at the UCSF Institute for Health & Aging. She’s running a study measuring the health impacts of singing in a choir. “The nice thing about the arts is our long, long history of using music and arts for healing across thousands of years, and the fact that it’s relatively low cost to implement.”

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Researchers awarded funding for work on childhood cancers


Alex’s Lemonade Stand Foundation funds work of two UCSF researchers.

Adam de Smith, UC San Francisco

Two UC San Francisco faculty members are among three promising young researchers nationally recognized for their work in pediatric oncology. UCSF’s Adam de Smith, Ph.D., and Kyle Walsh, Ph.D., will share a $1.35 million award with Duke University’s Lisa Crose, Ph.D.

The funding comes from Alex’s Lemonade Stand Foundation (ALSF), a nonprofit organization dedicated to finding cures for childhood cancers. Its three ‘A’ Awards will provide each recipient $450,000 over three years to further their work. De Smith plans to examine acute lymphoblastic leukemia (ALL), Walsh will study osteosarcoma, and Crose’s research interest is rhabdomyosarcoma.

“I truly feel honored to have been selected for this award from such a prominent childhood cancer charity,” said de Smith, an assistant professional researcher in the UCSF School of Medicine’s Department of Epidemiology & Biostatistics. “It is also the first research grant that I have received in my academic career to date, and it will enable me to carry out a comprehensive and unique investigation into the causes of acute lymphoblastic leukemia in children with Down syndrome.”

Acute lymphoblastic leukemia is the most common childhood cancer, and children with Down syndrome have an approximately 20-fold increased risk of developing ALL, as well as higher rates of relapse and treatment-related mortality than children without Down syndrome. De Smith hopes that by understanding the causes of ALL in children with Down syndrome, this might lead to earlier detection and better treatment of this disease, as well as shedding light on the etiology of ALL in the general population.

Kyle Walsh, UC San Francisco

“This ALSF ‘A’ Award will provide an invaluable source of funding that will hopefully help me to establish my own research lab here at UCSF, with a particular focus on identifying risk factors for childhood leukemia,” de Smith said.

Walsh, the co-award recipient from UCSF, hopes that by investigating genetic factors with a particular focus on those genes known to contribute to human height, he can decipher key elements about the underlying biology of osteosarcoma initiation.

“Alex’s Lemonade Stand Foundation has a rich history of funding high-impact pediatric oncology research,” said Walsh, assistant professor in residence of neurological surgery and epidemiology and biostatistics in the UCSF Department of Neurological Surgery. “I am excited to join the ranks of previous award recipients and I look forward to using the funding to investigate osteosarcoma etiology. Children who are tall for their age are at greatly increased risk to develop osteosarcoma, a malignant bone cancer.”

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Is life in America hazardous to immigrants’ health?


Over time, the health status of immigrant groups tends to decline.

By Dan Gordon, UCLA

America is a nation of immigrants drawn from all parts of the world by the promise of freedom and a good life. But a substantial body of evidence suggests that for the newly arrived, life in the United States can be hazardous to their well-being.

When they get here, immigrants are on average healthier than their native-born American counterparts. But the longer they stay, the worse they fare on measures such as heart disease, hypertension, diabetes and mental health.

Faculty at the UCLA Fielding School of Public Health are working on identifying factors contributing to the declining health status of immigrant groups that’s occurring over time and through the generations.

Part of it has to do with an unfamiliarity with U.S. society and its complicated health care system. Many immigrants lack health insurance. But Marjorie Kagawa-Singer, a professor at the Fielding School who focuses on the delivery of care that appropriately considers a patient’s culture, notes that it’s more than just cost.

“If someone is new to this country, doesn’t speak the language and has to learn to navigate our system, it’s like plopping us in the middle of Siberia and expecting us to figure out what we need,” she said.

For example, many immigrants across the educational and cultural spectrum hold beliefs about disease and how the body works that diverge from the biomedical model practiced in the U.S., Kagawa-Singer added, and many health care practitioners are uneducated on those differences.

“When you have problems in both health literacy among patients and cultural competence among practitioners, you get this ‘perfect storm’ of people who will not be able to utilize the health care system even when it’s offered,” said Kagawa-Singer.

Since 2000, Kagawa-Singer has headed the Los Angeles site of the Asian American Network for Cancer Awareness, Research and Training, the first federally funded cancer prevention and control research initiative focusing on Asian Americans. In lectures and short courses on cultural competence, Kagawa-Singer advises health professionals to demonstrate their trustworthiness and compassion.

“It’s not the health problem you’re treating, it’s the person,” she said. “When patients recognize you’re making the effort and respecting their dignity, they’re going to be much more forgiving and willing to teach and learn.” The challenge, she noted, is that the U.S. health care system is designed for short encounters, despite the fact that it may take longer to get to know and understand patients from different backgrounds.

Adopting the American diet

Public health experts have postulated that immigrants decline in health as they assimilate and adopt the health habits of their new communities — including high-fat diets and processed foods, along with reduced physical activity. To some extent, though, that equation has changed with globalization of the food supply, said May C. Wang, a Fielding School professor who focuses on early childhood obesity.

“Most low-income countries now have access to the processed foods we’ve been eating for the past few decades,” Wang noted. But even when immigrants’ tastes are similar to those of non-immigrants, immigrants with minimal financial means face considerable challenges to eating well. “Education alone doesn’t work in a community that doesn’t have the ability to access healthy food,” Wang said. “And in the very poorest communities, trying to change the environment by placing healthier foods where people live, work and go to school is challenging.”

The problem is compounded for immigrant groups, she explained, because they tend to have fewer social ties, are constricted by language barriers and often lack the know-how to pursue resources that could help them.

Wang works closely with the Public Health Foundation Enterprises Women, Infants, and Children (WIC) Program, the largest local WIC agency in the country. It serves 300,000-plus families a year, the vast majority of them non-English-speaking immigrants. The overall childhood obesity rate has plateaued or declined in the U.S. in recent years, Wang noted, but the obesity rate among the mostly immigrant Latino children remains substantially higher than for other groups. Among the low-income, preschool-aged Latino children enrolled in L.A. County’s WIC program in 2011, nearly 22 percent were obese.

To better understand the impact of various strategies to improve diet and reduce early childhood obesity, said Wang, “We are examining the social and physical environments in which immigrants live and how these affect their ability to put into practice nutrition knowledge they acquire from participation in the WIC program.”

The work aligns with the University of California Global Food Initiative, which seeks to harness the resources of all 10 UC campuses to address a critical issue of our time: How to sustainably and nutritiously feed a world population expected to reach eight billion by 2025.

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Bitter food but good medicine from cucumbers


UC Davis research could have applications in treating cancer, developing other food crops.

High-tech genomics and traditional Chinese medicine come together as researchers identify the genes responsible for the intense bitter taste of wild cucumbers. Taming this bitterness made cucumber, pumpkin and their relatives into popular foods, but the same compounds also have potential to treat cancer and diabetes.

“You don’t eat wild cucumber, unless you want to use it as a purgative,” said William Lucas, professor of plant biology at the University of California, Davis, and co-author on the paper published Nov. 28 in the journal Science.

That bitter flavor in wild cucurbits — the family that includes cucumber, pumpkin, melon, watermelon and squash — is due to compounds called cucurbitacins. The bitter taste protects wild plants against predators.

The fruit and leaves of wild cucurbits have been used in Indian and Chinese medicine for thousands of years, as emetics and purgatives and to treat liver disease. More recently, researchers have shown that cucurbitacins can kill or suppress growth of cancer cells.

Bitterness is known to be controlled by two genetic traits, “Bi” which confers bitterness on the whole plant, and “Bt,” which leads to bitter fruit. In the new work, Lucas, Sanwen Huang at the Chinese Academy of Agricultural Sciences and colleagues employed the latest in DNA sequencing technology to identify the exact changes in DNA associated with bitterness.

They also tasted a great many cucumbers. “Luckily this is an easy trait to test for,” Lucas said. “You just chomp on a cucumber leaf of fruit and your tongue gives you the readout!”

They were able to identify nine genes involved in making cucurbitacin and show that the trait can be traced to two transcription factors that switch on these nine genes, in either leaves or the fruit, to produce cucurbitacin.

The new research shows how domestication tweaked cucumber genetics to make the fruit more edible. Understanding that process might open up approaches to developing other food crops based on plants that are naturally either inedible or poor in nutrition, Lucas said.

It could also make it much easier to produce cucurbitacins in large enough quantities to use in clinical trials and potentially in medicine, Lucas said. For example the anti-malarial drug artemisinin, originally derived from traditional Chinese medicine, is now being produced either as a precursor molecule in yeast or through synthetic biology systems.

Other collaborators on the study included researchers at the Institute of Vegetables and Flowers, Beijing; Agricultural Genomics Institute, Shenzhen, China; Nanjing Agricultural University, Nanjing; Hunan Agricultural University, Changsha; Institute of Botany, Chinese Academy of Sciences, Beijing; Hunan Academy of Agricultural Sciences, Changsha; Wuhan University, Wuhan; Institute of Microbiology, Chinese Academy of Sciences, Beijing; Nihon University, Tokyo, Japan; and Wageningen University, Wageningen, The Netherlands.

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Scientists discover why some patients respond to a life-saving melanoma drug


UCLA findings will help physicians determine the best treatment for patients.

UCLA Jonsson Comprehensive Cancer Center members Dr. Paul Tumeh and Dr. Antoni Ribas

By Reggie Kumar, UCLA

UCLA researchers have pioneered a new methodology to predict why some patients battling advanced melanoma respond well and others do not to the new breakthrough drug pembrolizumab.

The study, led by UCLA Jonsson Comprehensive Cancer Center members Dr. Paul Tumeh and Dr. Antoni Ribas, primary investigator of pembrolizumab, is the first of its kind since the U.S.Food and Drug Administration approved its use under the name Keytruda in September, and it could lead the way for more effective use of the drug in patients with melanoma and other cancers.

A protein known as PD-1 puts the immune system’s brakes on, preventing T cells from attacking cancer cells. Pembrolizumab removes the brake lines, freeing up the immune system to kill cancer cells.

“We’ve had amazing clinical success treating patients battling advanced melanoma with pembrolizumab. The challenge is that it only works in approximately 30 percent of patients with melanoma,” said Tumeh, lead author of the study and UCLA assistant professor of dermatology. “To address this challenge, we developed an approach that can select for patients who are likely to respond to this therapeutic class.”

During the two-year study, Tumeh and Ribas analyzed 46 patients with advanced melanoma who were treated with pembrolizumab and who underwent tumor biopsies before and during treatment. They analyzed the biopsies and classified them according to whether the patient responded or not to pembrolizumab. In collaboration with Dr. David Elashoff, UCLA Jonsson Comprehensive Cancer Center member and adjunct professor of medicine, the information allowed them to develop an algorithm that could predict the likelihood of treatment success or failure.

“Our job was to figure out why some patients are predisposed to respond and others are not,” said Ribas, professor of hematology and oncology in the department of medicine. “Now with these results researchers can develop better drug combinations that are more effective, less costly and with fewer side effects.”

Fifteen additional tumor samples were obtained from patients given pembrolizumab in Paris, without Ribas’ team knowing what the clinical outcomes were. After applying their predictive algorithm Tumeh correctly predicted what would happen in 13 out of the 15 patient cases.

Keytruda was the first PD-1 immunotherapy drug approved by the FDA and there are eight others currently in clinical development. Ribas and Tumeh’s findings will help scientists and clinicians develop and correctly prescribe the best treatment for patients with melanoma and other cancers.

“The next big step is to classify the different types of patients who do not respond to pembrolizumab so we can develop drugs that can modulate the tumors in a way that makes them responsive to pembrolizumab,” said Tumeh.

The findings are reported online today (Nov. 26) ahead of print in the journal Nature.

This research was supported by Stand Up to Cancer and the National Institute of Health. Additional funding was provided by the UCLA Jonsson Comprehensive Cancer Center through philanthropy and other sources.

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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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