Gene mutations play critically important role in acute myeloid leukemia — a promising development for new treatments.

Neil Shah and Catherine Smith, UC San Francisco

The key to treating one of the most common types of human leukemia may lie within mutations in a gene called FLT3, according to new research led by physician-scientists at the UC San Francisco Helen Diller Family Comprehensive Cancer Center.

Published this week in the journal Nature, the work validates certain activating mutations in the FLT3 gene as targets for acute myeloid leukemia therapy — a critically important finding for developing drugs.

“These mutations are critically important for the survival of leukemia cells that harbor them,” said Neil Shah, M.D., Ph.D., who led the research, and is co-leader of the Hematopoietic Malignancies Program at the Helen Diller Family Comprehensive Cancer Center at UCSF and the Edward S. Ageno Distinguished Professor of Hematology/Oncology. “Our results also identify drug-resistant mutations in FLT3 that represent high-value targets for future drug development, and will hopefully rekindle interest in developing potent FLT3 inhibitors for the treatment of acute myeloid leukemia.”

The new work also suggests why a handful of older drugs developed to treat acute myeloid leukemia by targeting FTL3 have previously failed in clinical trials. The problem with these drugs was not lack of precision but of power — they were aimed at the right target needed to stop the cancer, but most likely did not hit this target hard enough.

Patients in the future may be better served by therapies that involve combinations of multiple, more potent drugs that can suppress all drug-resistant forms of FLT3, said Shah, whose lab is working to identify such compounds and bring them to the clinic as quickly as possible.

A common and deadly form of cancer

Acute myeloid leukemia occurs when the precursors of our own blood cells become corrupted by mutations in their DNA. The mutant precursors then fail to produce several critical components of blood: white cells, which fight infections; red cells, which carry the blood’s oxygen supply; and platelets, which clog vessels when they are cut and help minimize blood loss.

Instead, the mutant precursors give rise to leukemia cells, which accumulate in the bone marrow and bloodstream, crowding out the healthy blood components, and commonly lead to life-threatening infections, anemia and bleeding.

Over the last several decades, the five-year survival for acute myeloid leukemia has not improved, even as better diagnostic tests, imaging techniques and treatments have driven down mortality for other forms of cancer. According to the National Cancer Institute, 1 in 256 Americans will be diagnosed with acute myeloid leukemia in their lifetime and today nearly four out of five people with the disease die within five years of their diagnosis.

The goal of therapy is to eliminate cancerous cells altogether from the bone marrow, and the discovery several years ago that many people with acute myeloid leukemia have activating mutations in the FTL3 gene, coupled with the relationship of these mutations to poor prognosis, led scientists to speculate that targeting this mutated gene might be an effective way to fight the cancer — but only if the gene was critically important for the survival of leukemia cells.

Several drugs were tested in the clinic, but failed to put the disease into deep remission. The cause for these failures came down to one of two possible reasons: either the FTL3 gene mutations were not central “drivers” critical for cancer to develop and leukemia cells to survive, or the drugs themselves could not achieve the necessary degree of inhibition of FLT3.

The new work by Shah and his colleagues demonstrates the latter. They worked with eight leukemia patients who participated in a clinical trial involving a compound known as AC220, the first clinically-active FLT3 inhibitor. All eight relapsed after first achieving deep remissions with AC220.

In collaboration with Pacific Biosciences, a Menlo Park company, a new sequencing technology was adapted to more sensitively and precisely detect drug-resistant mutations. The team showed that in all eight cases, one or more of these mutations evolved at the time AC220-resistant disease developed.

They are now searching for compounds that can specifically target these mutated, AC220-resistant forms of FTL3, and have identified several promising candidates, one of which is currently being evaluated in a clinical trial at UCSF by Catherine Smith, M.D., who works in Shah’s laboratory and is the first author of the article.

The article, “Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia” by Catherine C. Smith, Qi Wang, Chen-Shan Chin, Sara Salerno, Lauren E. Damon, Mark J. Levis, Alexander E. Perl, Kevin J. Travers, Susana Wang, Jeremy P. Hunt, Patrick P. Zarrinkar, Eric E. Schadt, Andrew Kasarskis, John Kuriyan and Neil P. Shah is published in Nature on April 15.

This work was funded by grants from the Leukemia and Lymphoma Society, the Doris Duke Charitable Foundation, and the National Cancer Institute, one of the National Institutes of Health. Additional support was provided by Art and Alison Kern and the Edward S. Ageno family.

In addition to UCSF, authors of this study are affiliated with UC Berkeley, Pacific Biosciences, Mount Sinai School of Medicine, Johns Hopkins University, the University of Pennsylvania and Ambit Biosciences in San Diego.

Scott Lippman will join UC San Diego from University of Texas MD Anderson Cancer Center.

Scott Lippman

Scott M. Lippman, M.D., chair of Thoracic/Head and Neck Medical Oncology at The University of Texas (UT) MD Anderson Cancer Center, has accepted the position of director of Moores Cancer Center at the University of California, San Diego, beginning May 1.

UC San Diego Moores Cancer Center, home to nearly 350 medical and radiation oncologists, cancer surgeons, and researchers, is one of only 41 National Cancer Institute (NCI)-designated comprehensive cancer centers in the country.  It is part of UC San Diego Health System, the San Diego region’s only academic health system.

“As the new director, Lippman will implement strong initiatives for ramping up the research-driven cancer therapy and prevention programs and clinical trials of the Moores Cancer Center,” said David A. Brenner, M.D., vice chancellor for health sciences and dean of the School of Medicine at UC San Diego. “His ultimate goal, and ours, is to facilitate the translation of novel discoveries from our world-class laboratories into personalized therapies. I am confident that under Dr. Lippman’s leadership, research at Moores Cancer Center will benefit our patients and change standards of care for decades to come.”

Lippman currently holds the Charles A. LeMaistre Distinguished Chair in Thoracic Oncology and is professor of Cancer Medicine and Cancer Prevention at MD Anderson. Lippman graduated from Johns Hopkins University School of Medicine, did his internship and residency training at Johns Hopkins Hospital and Harbor-UCLA Medical Center, and had hematology/medical oncology training at Stanford University and the University of Arizona. He is triple board-certified in internal medicine, hematology and medical oncology.

Lippman’s major fields of research are translational/molecular studies of cancer risk, molecular-targeted drug development and personalized therapy, with a long-standing record of funding from the NCI in these research areas, including recently as principal investigator of two program project (P01) grants and a Specialized Program of Research Excellence (SPORE). He is also leader of the Lung Cancer Program of the MD Anderson Cancer Center Support Grant and is co-investigator on the American Association for Cancer Research (AACR) Stand Up to Cancer (SU2C) project involving molecular studies of lung cancer.

Lippman will bring to UC San Diego Health Sciences more than 25 years of experience as principal investigator of translational research involving investigator-initiated clinical trials. He has participated in the national leadership of clinical/translational research planning and development within the NCI Cooperative Group setting and currently sits on the National Institutes of Health (NIH) Clinical Trials/Translational Research Advisory Committee. He has served on several cancer center external advisory boards and major-trial steering committees, and has played a leadership role in major AACR and American Society of Clinical Oncology (ASCO) committees and programs.

In addition to extensive research and academic administrative responsibilities, Lippman plans to maintain an active clinical practice, including the accrual of new patients to clinical research protocols.  As a clinician, he is well-respected by his peers, with recognition in every major “Top Doctor” listing including recently in the U.S. News Top Doctors.

Author of more than 300 publications in high-impact journals, including The New England Journal of Medicine, JAMA, PNAS, and The Lancet, and chapters in major medical textbooks, Lippman has received many awards, among them the ASCO-American Cancer Society Award, AACR Cancer Research and Prevention Foundation Award, and the ASCO Statesman Award, and he is an elected member of the prestigious Association of American Physicians.

His extensive record of extramural service includes serving on the Food and Drug Administration Oncologic Drugs Advisory Committee, NIH Clinical Oncology Study Section, and NIH Chemo/Dietary Prevention study section, which he currently chairs. He has served on the editorial boards of several top-tier, peer-reviewed journals, including Cancer Research, Journal of the National Cancer Institute, and Journal of Clinical Oncology, and is editor-in-chief of the AACR journal Cancer Prevention Research. He also has chaired major scientific meetings including AACR and Keystone meetings and has given keynote lectures at major international scientific meetings.

UC’s Tobacco-Related Disease Research Program is studying the health risks.

The stale smell of cigarette smoke moves many a traveler to request a smoke-free hotel room. Who wants to smell someone else’s bad habit? But the lingering odor may be telling us something else — something more troubling.

Research funded by the UC-run Tobacco-Related Disease Research Program (TRDRP) shows that long after smoke has cleared from a room, toxic pollutants from cigarette smoke adhere to bedspreads, carpets, clothing — even furniture, walls, ventilation systems and hallways of hotels that allow smoking. Similar toxicants cling to surfaces in rental cars driven by smokers.

Byproducts of cigarette burning produces potent carcinogens when they combine with common indoor compounds. Many can remain in rooms for months.

“In the 1950s, we found that smoking could kill you; then research in the ’80s and ’90s, showed that secondhand smoke is dangerous,” said Georg Matt, a psychology professor of at San Diego State University who focuses on policies to protect nonsmokers.

“The potential health risks of what we call thirdhand smoke are only now being studied. This is a new frontier.”

Matt is a member of the Cancer Prevention and Control Program at UC San Diego and an investigator in a new thirdhand smoke research effort by the TRDRP.

The TRDRP funded the research consortium in 2011 to bring together experts in a range of fields, from toxicology and chemistry to behavioral and policy research, in order to determine the scope of thirdhand smoke risk and help develop policies to protect people where needed. Consortium researchers presented their findings on thirdhand smoke at the “Linking Tobacco Control Research and Practice for a Healthier California” conference — held April 10-12 in Sacramento. The conference was sponsored by TRDRP and the state’s Tobacco Control Program.

“We don’t yet know the degree of risk, but we are already finding that indoor smoking leaves a nearly indelible imprint,” Matt said. “We need to find out what risk this pollution poses.”

Risks to infants and toddlers are of particular concern to consortium scientists. Young children crawl on rugs and carpets and often put their hands in their mouths. They have more contact with pollutants that cling to surfaces in the home.

An infant’s developing brain is very susceptible to low levels of toxins, and immature immune systems are particularly vulnerable to persistent pollutants. Researchers suspect that children with respiratory diseases like asthma are likely to be at highest risk.

“This is a newly emerging concern, but one we think is very important to study,” said Anwer Mujeeb, program officer for TRDRP’s thirdhand smoke research effort. “We are leading the way in research to learn how these pollutants form, how long they remain and how they interact. Of course, it’s critical to determine at what concentrations they pose a threat to health.”

TRDRP is funded by California state cigarette taxes and managed by UC. The program launched the thirdhand smoke research consortium with $3.35 million to support a range of investigations.

“We’re very fortunate to have in California scientists who are already making an impact in tobacco research,” said Mujeeb. The research goes hand in hand with efforts to reduce the number of people who take up smoking in the first place.”

Matt and his colleagues in the THS consortium have shown that about 90 percent of nicotine from cigarette smoke remains on indoor surfaces long after the butt is in the ashtray. Their new research shows how much nicotine nonsmokers pick up on their hands from furniture and bedding in hotel rooms where cigarettes have been smoked. Cotinine, a byproduct of nicotine metabolism, shows up in the urine of these nonsmokers after a single night in the hotel room.

“Secondhand smoke is a mixture of more than 4,000 compounds, including some 50 carcinogens, plus irritants and teratogens (substances that can cause developmental or birth defects). But the potential dangers don’t end with direct exposure to smoke,” Matt said.

In effect, the smoke never really clears.

Consortium research brings together scientists and policy scholars at UC campuses, the Lawrence Berkeley National Laboratory (LBNL) and other sites in and out of the state. Experts vet research proposals, and studies are selected to answer the many unknowns in this new field and integrate findings from different areas of expertise.

Hugo Destaillats and colleagues at LBNL, UCSF and Portland State University have recently found that in just three hours, cigarette smoke and a common indoor home compound known as nitrous acid combine to form a carcinogen at levels 10 times higher than normal. Unvented gas appliances and car engines commonly emit nitrous acid. (See video at top of this page for more about research at LBNL and UCSF.)

The carcinogen formed by the smoke residue and nitrous acid may persist on surfaces in the home long after the cigarette is extinguished, exposing residents any time they are home, Destaillats said.

“Smoking a cigarette can last maybe 10 minutes,” he said. “But the pollutants remain for hours.”

Destaillats is a staff scientist in the Indoor Environment Group of the Environmental Energy Technologies division at Lawrence Berkeley National Laboratories (LBNL) and a professor at Arizona State University. The new research has been published in the Proceedings of the National Academy of Sciences.

“Tackling thirdhand smoke is tough because it’s pushing the technological sensitivity of measurements of pollutants,” said UCSF scientist Neal Benowitz, an authority on nicotine metabolism and principal investigator of the TRDRP thirdhand smoke consortium.

The only way to make solid ressarch progress, he said, is to look at it from many angles: developing biomarkers to measure levels of pollutants, assessing their persistence in the indoor environment and determining how much they are absorbed by the body.

“The effort requires many skills, like environmental chemistry, toxicology, pharmacology and the ability to track and measure the pollutants over time,” said Benowitz, who is vice chair of the UCSF’s Department of Biopharmaceutical Sciences and co-leader of the Center for Tobacco Control Research and Education at UCSF. He is also the leader of the Tobacco Control Program of the UCSF Comprehensive Cancer Center.

“I think the state of California is very forward thinking to try to pursue this question. If anyone has the expertise to make real progress, it’s this talented, multi-discipline research group,” Benowitz said.

The thirdhand smoke trail may well lead to changes in attitudes about smoking and to decisions to give up the habit or not ever start it, Matt said.

“Afterall, there would be no third or secondhand smoke without ‘firsthand’ smoking,” he said.

One positive sign he’s found is an uptick in the number of people demanding smoke-free used cars, rental cars, apartments and hotel rooms.

A 2008 study found that used nonsmoker cars were offered for sale at a considerably higher price than their published value and above comparable smoker cars.

“These findings suggest that community preferences are affecting the value of smoke-free cars,” Matt said. “That’s how norms change. And as we close more research and policy loopholes, we’ll have more ammunition to cut down smoking and save lives.”

Scan offers early assessment of chemotherapy’s effectiveness on soft-tissue sarcomas.

Fritz Eiber, UCLA

Researchers from UCLA‘s Jonsson Comprehensive Cancer Center have found that by administering a PET scan to individuals with soft-tissue sarcomas after just a single cycle of neoadjuvant chemotherapy, they can predict increased survival in these patients.

Prior research by this multidisciplinary team of physician-scientists had shown that a combined PET/CT scan using a glucose uptake probe called FDG allowed them to determine the pathologic response of patients’ tumors after the first dose of chemotherapy drugs. They then wondered if the patients who showed a significant PET response after the first round of chemotherapy also were surviving longer.

“We did find that patients who experienced an early PET response to treatment had significantly increased survival,” said the study’s senior author, Dr. Fritz Eilber, an associate professor of surgical oncology and director of the Jonsson Cancer Center’s sarcoma program. “This is vital because patients want to know if the drugs are working and what that says about their ultimate outcome.”

The study was published Sunday (April 1) in Clinical Cancer Research, a peer-reviewed journal of the American Association of Cancer Research.

In the study, 39 patients with soft-tissue sarcoma underwent a PET scan to measure their tumor’s metabolism, or how much glucose was being taken up by the tumor, prior to getting chemotherapy. The patients were given another PET scan after the first round of chemotherapy.

Those whose tumors demonstrated a 25 percent or more decrease in metabolic activity — a response considered “significant” — were later determined to have significantly increased survival rates, compared with patients who had less than a 25 percent decrease, Eilber said.

“It’s an important finding because we can now identify whether patients are getting the right chemotherapy very quickly,” Eilber said. “Patients don’t want to have to wait until the cancer recurs or they die to find out whether their chemotherapy worked or not.”

Going forward, Eilber and his team are working to design new molecular imaging tools that may tell them even more about a patient’s cancer beyond the conventional FDG probe.

“Just looking at the size of the tumor is not good enough anymore,” Eilber said. “We want to image what’s happening within the tumor in real time.”

The study was funded by the In vivo Cellular and Molecular Imaging Center at UCLA’s Jonsson Comprehensive Cancer Center and the U.S. Department of Energy.

“This study suggests that PET allows survival predictions after the initial cycle of neoadjuvant chemotherapy and might therefore potentially serve as an early end-point biomarker,” the study states. “Such information cannot be derived from CT scanning based on serial tumor-size measurements. The ability to assess treatment response early during the course of therapy can potentially guide management decisions. Treatment could be switched from neoadjuvant chemotherapy to immediate surgery in non-responding patients, while it would be continued in responders. Such risk adapted therapy could reduce treatment associated morbidity and costs.”

UCLA’s Jonsson Comprehensive Cancer Center has more than 240 researchers and clinicians engaged in disease research, prevention, detection, control, treatment and education. One of the nation’s largest comprehensive cancer centers, the Jonsson Center is dedicated to promoting research and translating basic science into leading-edge clinical studies. In July 2011, the center was named among the top 10 cancer centers nationwide by U.S. News & World Report, a ranking it has held for 11 of the last 12 years.

Study compares robotic and traditional surgery outcomes for bladder cancer in a variety of hospital settings across the country.

Jim Hu, UCLA

With technological advancements opening the door to less invasive medical procedures, robotic-assisted surgery is becoming increasingly popular, despite being more expensive than traditional surgery. Robotic-assisted surgical removal of the bladder due to cancer is a new approach to the traditional “open” — or more invasive — operation called a radical cystectomy.

Bladder cancer is the fourth most commonly diagnosed cancer in men, and the American Cancer Society estimates that 73,500 people will be diagnosed with bladder cancer in 2012. A third of those will require a radical cystectomy.

During a robotic procedure, the surgeon sits behind a console several feet from the patient and uses joysticks and foot peddles to control a robot; the robot holds and manipulates small surgical tools, which are inserted through tiny key-hole incisions in the patient’s body.

Previously noted benefits of robotic surgery include smaller incisions and less trauma for the patient. In addition, surgeons have a better three-dimensional view and more freedom of wrist movement, and the procedure eliminates hand tremors, making tasks like suturing easier.

But since the robotic surgery field is fairly new, only now are larger, more comprehensive studies being published that compare hospital and patient outcomes of traditional open surgeries to robot-assisted procedures.

A new study currently online in the journal European Urology has found that compared to open surgery for bladder cancer, robotic surgery results in fewer deaths and in-patient complications and reduces the need for intravenous nutrition after the procedure. The procedure, however, is more costly.

“While we expected to see greater expenses associated with the robotic procedure for bladder cancer, we were surprised to see the significant reduction in deaths and complications, particularly this early in its adoption,” said the study’s senior author, Dr. Jim Hu, director of minimally invasive surgery in the urology department at the David Geffen School of Medicine at UCLA.

Hu noted that previous reports of outcomes from robotic-assisted surgery have come from single medical centers and have not included direct comparisons to traditional surgery.

“This is one of the first national population-based studies comparing robotic and traditional surgery outcomes for bladder cancer,” Hu said. It is also one of the first studies to compare the procedures in a variety of hospital settings across the country.

In conducting the research, Hu, along with colleagues at Harvard Medical School and Georgetown University Hospital, used the U.S. Nationwide Inpatient Sample, a national government database of hospital in-patient information that includes data from 1,050 hospitals in 44 states.

The researchers used information from 2009, the most recent date for which data were available on radical cystectomy for bladder cancer at the time the study was conducted. The team looked at 1,444 traditional open surgeries and 224 robotic-assisted laparoscopic procedures. They found that robotic-assisted surgeries accounted for 13 percent of all radical cystectomies in 2009.

Using statistical analysis, Hu and his colleagues compared hospital-level information, including in-patient deaths, complications, length of hospital stays and costs for the two procedures.

One of the most striking findings the team reported was that one in 100 patients receiving open radical cystectomy (2.5 percent) died during hospitalization, but there were no in-hospital deaths for patients who underwent robotic-assisted cystectomy.

The researchers also found that patients who underwent robotic-assisted laparoscopic surgery experienced fewer in-patient complications than those who had the traditional open procedure (49.1 percent vs. 63.8 percent).

After the robotic procedure, patients also had less need of parenteral nutrition than their open-surgery counterparts (6.4 percent vs. 13.3); parenteral nutrition is provided intravenously if there is delayed recovery of bowel function.

The researchers found no difference in the length of hospital stays between the two procedures, with patients who underwent both types of surgery spending approximately eight days in the hospital.

Total costs for the robotic procedure, however, were significantly higher — more than $3,000 higher than traditional open surgery. The researchers said this may be due to longer operation times and greater use of disposable instruments with the robot. Hu also noted that the study didn’t factor in expenses for robot acquisition and maintenance, so the costs may be even higher.

In addition, women were less likely to undergo a robotic procedure, possibly due to gender-based differences in anatomy that make robotic procedures more difficult, the researchers said. Bladder cancer is rarer in women — men are three times more likely to be diagnosed with the disease.

The researchers found that 95.7 percent of the robotic procedures — compared with 73.9 percent of traditional procedures — were performed at teaching hospitals.

The majority of both types of patients (76.8 percent for the robotic procedure and 67 percent for the open procedure) had key lymph nodes removed during their operations, in keeping with a national practice guideline related to reducing disease recurrence and improving survival. Still, roughly a quarter of robotic-procedure patients and a third of open-procedure patients did not undergo lymph node removal, indicating that both procedures could improve in this area.

Hu noted that while the surgeon plays the most important role in bladder cancer surgery outcomes, better tools may help the surgeon achieve improved outcomes. Just as newer tennis rackets made of synthetic fibers cost more but allow greater precision and power than the wooden rackets of 40 years ago, robotic surgery for bladder cancer has certain advantages over the traditional open approach.

“The history of most technology demonstrates that as more innovations and advances occur over time, the costs may be reduced,” Hu said. “We hope that our study will add to the growing base of outcomes information in the robotics field.”

Hu said the next stage of research will involve expanding the study to follow patients beyond the hospital. The team will also look more closely at the severity of surgical complications, assess tumor characteristics and include other factors that may play a role in outcomes.

The researchers suggest that interested patients ask their doctors if they are candidates for robotic-assisted bladder cancer surgery and make sure to obtain second opinions to gauge the confidence, training and experience of the surgeons.

The study was funded by the American Urological Association Foundation and the U.S. Department of Defense.

Additional study authors included Dr. Hua-yin Yu and Dr. Adam S. Kibel, Division of Urology, Brigham and Women’s Hospital, Harvard Medical School, Boston; Nathanael D. Hevelone and Stuart R. Lipsitz, Center for Surgery and Public Health, Brigham and Women’s Hospital, Harvard Medical School, Boston; Dr. Keith J. Kowalczyk, Department of Urology, Georgetown University Hospital, Washington, D.C.; Dr. Paul L. Nguyen, Department of Radiation Oncology, Lank Center for Genitourinary Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston; and Dr. Toni K. Choueiri, Department of Medicine, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston.

Elected president of the American Association of Cancer Research.

Frank McCormick, UC San Francisco

Frank McCormick, Ph.D., FRS, director of the Helen Diller Family Comprehensive Cancer Center at UC San Francisco, was elected president of the 35,000-member American Association of Cancer Research (AACR), the world’s largest organization of its kind dedicated to prevent and cure cancer through research, education, communication and collaboration.

His term began at the group’s annual meeting, which takes place — fittingly enough — at Chicago’s McCormick Place and runs through April 4. It’s the world’s biggest meeting for cancer researchers.

McCormick was vice president of research for Cetus Corp. in the 1980s — still the early days of biotech — and in 1992 he founded Onyx Pharmaceuticals, where his pioneering research led to the development of a treatment for kidney and liver cancer. In 1996, McCormick was made a fellow of the Royal Society. He joined the faculty at UCSF in 1997.

In an interview, McCormick discusses his views on progress to date in the battle against cancer, and shares his vision for what’s ahead.

Read the interview and sidebar about UCSF’s top discoveries in the war on cancer

Dollars donated by California tax filers support innovative research to fight breast cancer, tobacco-related diseases.

Research can be slow and purposely deliberate. Investigating cancer can take many years to gather data, prove hypotheses, develop treatments and find cures.

But while many scientists tackle that important work, UC-run programs — funded by donations from California taxpayers — are making sure that cancer research involves and informs the community, especially groups vulnerable to a hard-hitting disease that won’t quickly go away.

Yearly contributions from tax filers — many in modest dollar amounts — benefit the UC-administered Tobacco-Related Disease Research Program (TRDRP) and the California Breast Cancer Research Program (CBCRP).

Line 413 for tobacco-related cancer awareness, prevention

Last year, more than 31,000 people checked line 413 at the end of their state income tax forms and donated an average of nearly $14 to the California Cancer Research Fund. Those contributions now fund a statewide project to deliver culturally-sensitive cancer awareness and prevention information to groups that are constantly bombarded by tobacco industry marketing. The project was conceived and is administered by UC’s Tobacco-Related Disease Research Program.

“Many people are still shocked to hear that tobacco-related illnesses and cancer are the No.1 killer of African Americans,” said Carol McGruder, who is co-chair of the African American Tobacco Control Leadership Council (AATCLC), a researcher and San Francisco activist fighting the pervasive effects of tobacco in the community.

She notes that while smoking in California has plummeted to under 12 percent — the second lowest rate in the nation only to Utah — the rate among African Americans may be as high as 30 percent, according to some community-based studies. McGruder also points out that billboards for tobacco products are placed in African American communities at a rate four to five times greater than in white neighborhoods, and products such as menthol cigarettes are targeted specifically at African Americans, especially young people.

McGruder is part of a collaborative project, Alliance for Data dissemination to achieve Equity for Priority Populations on Tobacco (ADEPT). ADEPT is one of many projects funded by the Tobacco Related Disease Research Program, which administers a variety of innovative research grants in biomedical science, addiction, policy, regulatory and environmental science and health disparities in California, ADEPT is funded exclusively and solely from the cancer research fund from taxpayers’ line 413 contributions.

The LGBT community is another that suffers from high rates of smoking — more than double the general population, and lesbians smoke at a rate triple of that of all women, according to studies. “Tobacco is one of the leading preventable causes of death among LGBTs, if not the leading cause,” said Naphtali Offen, a UCSF research associate and co-founder of the Coalition of Lavender Americans on Smoking and Health (CLASH), an ADEPT partner.

Offen’s research at UCSF has documented how the tobacco industry has targeted LGBTs since the early 1990s with ads in gay media glamorizing smoking and sponsorship of events, especially those that provided AIDS and health-related services to the community. CLASH has worked to undo ties between the tobacco industry and LGBT community leaders and event organizers. And now that it is part of the tax-funded collaborative, it will expand its efforts as one of California’s leading resources for smoking cessation support, provider training and multifaceted education around LGBT tobacco use.

Other community partners in ADEPT will address tobacco-related health disparities including cancer disparities and reach out to American Indian/Alaskan natives, Asian Americans, native Hawaiians and Pacific Islanders, Hispanics and Latinos and low socioeconomic status populations.

While each partner will develop culture-specific programs and materials aimed at their groups, all will learn from each other about effective means of delivering cancer and health awareness information, whether its via social media, ads in ethnic newspapers or neighborhood forums, said Rod Lew, principal investigator for ADEPT and executive director of the Asian Partners for Empowerment, Advocacy and Leadership.

A key part of the effort will be training community and tobacco control leaders throughout the state to disseminate key health and research information to these various populations, said Lew.

Line 405 for breast cancer

Donations from line 405 of the state tax forms have funded nearly $10 million in research grants aimed at identifying environmental factors that may cause breast cancer, developing therapies to block the cancer from spreading, exploring natural products that may thwart the disease, and improving support networks to help patients and families navigate a sometimes daunting health care system.

CBCRP is renowned not only for its innovative research, but also for engaging community organizations in its studies. One project funded by 405 tax check-off contributions teamed researchers and the Asian Health Services in Oakland to look at breast cancer risks in nail salon workers, mostly Vietnamese women, who are overly exposed to chemicals in the polish and products that they breathe and touch. (See above video).

“I’m impressed by CBCRP’s research strategy  that requires a balanced partnership between researchers and community representatives so that the community can see the direct benefits of the research sooner than later,” said Thu Quach, a scientist at the Cancer Prevention Institute of California and a leader in the study of nail salon workers.

Research guides policymakers, too

Advocates and researchers in the ADEPT collaborative extend their education efforts beyond their communities. The African American Tobacco Control Leadership Council, for example, has been urging the FDA to ban menthol-flavored cigarettes. The group has presented research to the FDA’s Tobacco Products Scientific Advisory Committee showing that as many as 80 percent of African American smokers use menthol cigarettes and those cigarettes tend to hook youth into the unhealthy habit.

Other ADEPT groups have targeted cigarillos, little cigars whose popularity and sales have increased in recent years. The product is not regulated by the FDA and not subject to the same taxes as cigarettes.

On the breast cancer side, research results of the check-off-funded nail salon worker study have helped inform public policy, said Quach. This includes reintroduction of the Federal Safe Cosmetic Act of 2011 to ban toxic compounds, require premarket safety testing and provide greater regulatory authority to the FDA to oversee cosmetic manufacturers.

Some CBCRP and state tax check-off studies are designed specifically to inform policymakers. Joy Melnikow, a family and community medicine professor and director of the Center for Healthcare Policy and Research at UC Davis, received a grant last year to analyze a tool that policymakers and others can use to consider impacts of various options on future health program benefits and costs. Such a tool — a user-friendly computer interface — is important as breast cancer screening and health programs for underserved women in California are faced with increasing need for services and shrinking budgets.

“While this project is specific to a breast cancer screening program for underserved women in California, if it is successful, a similar approach could be used for other breast cancer screening programs and policy decisions,” said Melnikow. “We hope that policy decisions informed by evidence will lead to better outcomes for women.

“The California Breast Cancer Research Program, funded through tax check-off contributions, supports our project and other research, all of which have as their ultimate goal better care and outcomes for women with breast cancer,” she said.

UC Berkeley Wellness Letter: Other tests may be just as good, encourage more to be tested.

Screening for colorectal cancer — that is, cancers of the colon (large intestine) and rectum — is a proven lifesaver. This is partly due to the fact that this is one cancer which screening can actually prevent, since it can lead to the detection and removal of polyps, some of which may progress to cancer.

So why are anywhere from one-third to one-half of Americans over 50 not getting the recommended tests for colorectal cancer? One reason this screening rate lags behind those for some other cancers may be an overemphasis on colonoscopy as the screening test of choice in this country.

For years many experts, organizations and media spokespeople (such as Katie Couric) have promoted colonoscopy as the best colorectal screening test. As a result, it has become the most frequently used screening test for colorectal cancer in the U.S. Most doctors today do not even discuss alternatives with their patients.

Offering only colonoscopies discourages some people from getting tested, since they may dread the bowel-cleansing prep (clear liquid diet, strong laxatives and high fluid intake), are scared or embarrassed about the procedure itself, worry about potential complications and/or can’t afford its high price. Medicare and private insurance cover colonoscopy (and other screening tests), but that leaves out uninsured people, who are only half as likely to be screened for colorectal cancer as the insured.

Colonoscopy is a good test, though not perfect. You should know your other screening options as well. “Much more screening will be carried out if primary-care providers and the American public are not made to feel that screening tests other than colonoscopy are ineffective,” says Dr. James Allison, professor emeritus of medicine at the University of California, San Francisco, and a leading expert on colorectal cancer screening.

Colonoscopy: strengths and weaknesses

Colonoscopy examines the colon via a flexible scope that transmits the images to a video screen while the patient is sedated. The claim that it is the best screening option has been based on assumptions and expectations about what it can do — allow a doctor to examine the entire colon and rectum and remove polyps during the procedure. But colonoscopy’s superiority has never been proven in randomized controlled trials (the “gold standard”) comparing its effectiveness to other tests.

Other kinds of studies have suggested that colonoscopy (typically done every ten years if no cancer or polyps are found) doesn’t save more lives than sigmoidoscopy, which examines only the lower part of the colon and is usually done every five years. In some studies, sigmoidoscopy was combined with stool tests (see below). Two large randomized controlled studies comparing colonoscopy with stool tests are underway, but results won’t be available for years.

[Editor’s note: In February, shortly after this article went to press, a major study on colonoscopy was published in the New England Journal of Medicine. It confirmed that colonoscopy, by detecting and removing polyps, can prevent cancer and save lives. In fact, it cut the death rate from the disease by half. But the study was not a randomized controlled study, did not look at colonoscopy as a screening test for the general public, and didn’t compare it to stool tests or sigmoidoscopy. It included only people with polyps, some of which were detected by these other tests.]

One problem with colonoscopy is that it’s less effective in detecting polyps and cancer in the right side of the colon (the upper portion, including the ascending colon and cecum) than the left side. This is because many polyps and cancers in the right side are flat, pale and difficult to identify and remove completely. Also, bowel cleansing may be less complete in the right side of the colon, making detection more difficult there.

Other factors can also reduce colonoscopy’s accuracy. For instance, it tends to be less accurate when done comparatively quickly, by less experienced doctors (typically those who are not gastroenterologists) and/or when patients don’t prep adequately to empty the colon.

In addition, though colorectal cancer starts in certain adenomas and other polyps, the vast majority of polyps detected and removed (including most ademonas) are harmless. It’s estimated that 30 to 50 percent of Americans over 50 have or will develop adenomas, and that between 1 and 10 percent of these polyps will progress to cancer in 5 to 10 years.

Finally, colonoscopy poses a small — but not insignificant — risk of serious complications such as bleeding or colon perforation.

Sigmoidoscopy has some advantages over colonoscopy. It costs only a fraction as much, is quicker and can be done well by primary care doctors. The prep is simpler, and sedation is usually not needed. But it too misses some cancers, especially since it can’t examine the upper portion of the colon. And if suspicious polyps are found, you’ll need a colonoscopy to remove them and check the upper colon.

Starting with stool

Not too long ago, annual stool tests were the primary way to screen for colorectal cancer in the U.S. In most countries they still are. Called fecal occult blood tests (FOBT), they detect hidden (“occult”) blood in stool, a possible sign of colorectal cancer. Your doctor gives you a kit to take home; you then provide one to three stool samples to be analyzed, depending on the type of FOBT. You’ll be referred for a colonoscopy if blood is detected.

The standard stool tests are called guaiac tests, named for the compound used on the test cards. The early versions have increasingly been replaced by more sensitive guaiac tests. However, they still often produce false-positive results because of blood that comes from something besides polyps or cancer; certain foods or medications (even vitamin C) can also throw off the results. And they miss some advanced polyps and cancers, especially those that don’t bleed or do so intermittently. That’s why screening should be done every year — repeated testing provides multiple opportunities to identify advanced polyps before they become malignant and early cancers before they become life-threatening.

A 2010 review paper in Gastroenterology concluded that annual highly sensitive FOBT is indeed effective at identifying colon cancer and reducing deaths from it. Because it is inexpensive, more people can afford FOBT, so it may save more lives than colonoscopy, according to some analyses. But FOBT is most effective only if people are compliant—take the test annually and do the follow-up tests when necessary.

A more advanced form of FOBT is the fecal immunochemical test (FIT), which is superior in several ways. For one thing, it requires only one stool sample. It is more accurate than standard FOBT because it identifies antigens in blood that may be in the stool, and it can’t be thrown off by food or medication. And it only detects blood originating in the colon or rectum. What’s more, the processing and reading of the test can be automated for quality assurance. Used primarily in Europe, Australia, Japan and Israel, FIT is being used more and more in the U.S., even though it is more expensive than standard stool tests.

Wellness Letter’s advice

Everybody age 50 to 75 should be screened for colorectal cancer, whichever test they use. People at high risk — notably those with a family history, a known genetic risk, inflammatory bowel disease or certain other disorders — should start earlier.

Discuss the screening options with your doctor. Colonoscopy is not the only test — which is fortunate, since there aren’t enough skilled practitioners to screen all eligible people. Nor is it necessarily the best. All the tests have strengths and weaknesses, which you and your doctor need to weigh. Here are the options:

• Colonoscopy every 10 years, unless polyps have been found or you are at high risk, in which case more frequent testing will be needed. Despite that standard guideline, many people, especially those over 65, have colonoscopies repeated in less than seven years, even though there is no clear reason for them to repeat the exam that soon, according to a study in the Archives of Internal Medicine last year.

• Sigmoidoscopy every five years, along with stool tests (preferably FIT) every three years.

• Annual stool tests. Ask your doctor about FIT, or at least make sure you’re getting a highly sensitive FOBT.

• People at elevated risk or with a history of polyps and/or colon cancer should have colonoscopies — and perhaps FIT during the intervals.

Your doctor should consider your personal preferences. For instance, some people want to steer clear of colonoscopy because of its prep, invasiveness and/or cost. Others prefer colonoscopy because it usually needs to be done only once a decade rather than every year like stool tests, and it allows for the removal of polyps, if present. (It’s worth noting that some colon-cleansing preps and regimens are easier and still effective — we’ll discuss this in an upcoming issue.)

You can stop being screened after 75 if you’ve always had normal results and have no symptoms, and all screening should stop after age 85, according to federal guidelines. With increasing age, the benefits of screening decline, while the risks from sigmoidoscopy and especially colonoscopy increase.

Related:
View an accompany editorial

UC Merced professor discovers that tobacco smoke activates an enzyme that causes cancer cells to spread to other parts of body.

Henry Jay Forman, UC Merced

Cigarette smoke not only can cause cancer, but it’s also responsible for the spread of it, according to research by UC Merced biochemistry professor Henry Jay Forman.

Forman discovered tobacco smoke activates an enzyme — called Src — that causes cancer cells to spread to other parts of the body. The study will appear in the April 15 edition of Free Radical Biology and Medicine.

Cigarette smoke is the major cause of lung cancer, Forman said, but nearly half of lung cancer patients remain active smokers. Nonetheless, researchers haven’t understood how cigarette smoke causes cancer to metastasize.

The lab was also able to prevent cigarette smoke from activating the enzyme by introducing an antioxidant. Forman’s discovery could prove useful in the fight against cancer, as it creates more understanding on how it spreads and how antioxidants can help combat this.

Forman will present his findings on April 21 at the Experimental Biology 2012 conference in San Diego.

Forman co-authored the paper with a professor from the University of Padova in Italy. Forman served as a visiting professor during the summer while also conducting research.

In another paper, recently published in the Journal of Biological Chemistry, Forman collaborated with investigators at USC who are experts in looking at how cells maintain themselves using proteasome, which degrades old and damaged proteins. When cells are under oxidative stress, the proteasomes work faster to remove damaged proteins.

However, the lab discovered the signal used to increase a cell’s defenses doesn’t happen in old age, causing cells to die and turn malignant. The findings offer more insight into age-related problems, such as Alzheimer’s disease. Both studies were supported by the National Institutes of Health.

Forman will continue his research this summer, focusing on three projects: understanding how differences in the expression of a particular enzyme increases human susceptibility to air pollution; studying how people with sickle cell trait may have a sickle cell crisis when doing severe exercise; and studying how cigarette smoke activates an enzyme that regulates changes in lung cancer cells that promote metastasis. The three projects are funded by the National Institutes of Health.

Yoga, qigong and other forms of healing complement standard care at UCSF’s Osher Center.

Breast cancer survivor Helen Robillard closes her eyes as she gently rotates her arms clockwise. Her movements are measured and deliberate; her breathing slow and purposeful.

She studies qigong (pronounced “chee-gung”), an ancient Chinese practice of aligning breath, movement and awareness for healing and exercise, including through this class at the UC San Francisco Osher Center for Integrative Medicine.

“It’s a very relaxing class, so you really learn to slow down,” Robillard says during a break. “It allows me to focus on my movements, where my hands are, where my feet are and it’s stress reduction.”

Diagnosed with breast cancer in the summer of 2009, Robillard added qigong and other integrative medicine classes at Osher to the standard recovery regimen after several rounds of chemotherapy sapped her strength.

“I’m building little muscles in my legs that help in my balance,” she says. “I can close my eyes at points and be off somewhere else. I can focus and be aware of my movements. It adds to my awareness of how I can relax when I’m stressed.”

That focus and relaxation are key aspects of integrative medicine.

“This kind of program allows you to exercise in a comfortable, soft, not strenuous way, and will allow almost anybody to participate,” said Joseph Acquah, O.M.D., a licensed acupuncturist at the Osher Center. “It’s very soft; it’s gentle. It’s calming. You get to use your mind and body at the same time and there’s a focus which is always good for health.”

Emergence of integrative medicine

The term “integrative medicine” didn’t exactly roll off people’s tongues when UCSF established the Osher Center for Integrative Medicine in 1997. UCSF Chancellor emeritus Haile Debas, M.D., then dean of the UCSF School of Medicine, with support from the Bernard Osher Foundation created a center that would test the effectiveness of complementary medicine through research, as well incorporate the best of these strategies into professional education and patient care.

Margaret Chesney and Donald Abrams, UC San Francisco

“Integrative medicine combines conventional medicine with evidence-based practices from other healing traditions, including meditation, acupuncture and optimal nutrition,” said Margaret Chesney, Ph.D., director of the Osher Center. “Integrative medicine practitioners work in partnership with patients to encourage personalized care plans and lifestyle changes to promote health.”

UCSF’s Osher Center for Integrative Medicine combines conventional medicine with evidence-based practices from other healing traditions, including meditation, yoga, tai chi and qigong. This approach has become a popular way for cancer survivors and others who are recovering from debilitating illnesses to regain strength and balance after chemotherapy and surgery. Others benefit from stress-reduction programs like laughter yoga. See slideshow.

Donald Abrams, M.D., a UCSF oncologist, has been providing integrative medicine consultation to people living with cancer at the Osher Center since 2004.

“Integrative medicine can reduce significant burden on our health care system,” he said. “And perhaps if we focus more on integrative interventions, prevention and wellness, we may be able to fix our health care system.”

Integrative medicine takes a “patient-centered” approach, meaning health care providers personalize care based on the patient’s physical, emotional, mental, social, spiritual and environmental influences. Their goal is to integrate many different approaches to treatment and prevention, increasing the options available to medical professionals — and to patients.

“At the Osher Center, integrative oncologists work with the UCSF cancer center oncologists and the cancer patient to design an integrative approach that will combine the best state-of-the-art cancer care with complementary approaches such as acupuncture for comprehensive patient-centered care,” Chesney said.

Patients at the Osher Center say the approach is working.

“There’s a lot of trauma associated with cancer and it was important for me to find a place where I felt supported,” said Diane McCarney, another qigong participant who is both diabetic and a breast cancer survivor. “I found in a very short amount of time, just going to those gentle, easy classes, I was able to get much stronger and quicker, and I started to feel better once I started moving again.”

“People need to start thinking differently about health and this is the way to do it,” added Robillard. “It’s hard to put on your gym clothes and go to a class. But once you do it, it’s energizing and the support you get from other people is great. You know you’re not alone. It energizes me and makes me feel normal again rather than like a sick person. I would definitely recommend it.”

As patients catch on, Abrams is hopeful integrative medicine becomes a key component in treating cancer patients.

“I hope people become aware that integrative medicine is here to stay,” Abrams said. “It’s shown to be successful in treating some of the more difficult conditions that are plaguing people.”

UCLA findings may help lead to new treatments for infectious disease, cancer.

Dendritic cell in a tuberculoid leprosy lesion

UCLA researchers have pinpointed a new mechanism that potently activates T cells, the group of white blood cells that plays a major role in fighting infections.

The team specifically studied how dendritic cells, immune cells located at the site of an infection, become more specialized to fight the leprosy pathogen known as Mycobacterium leprae. Dendritic cells, like scouts in the field of a military operation, deliver key information about an invading pathogen that helps activate the T cells in launching a more effective attack.

The research was published online Sunday (March 25) in the journal Nature Medicine.

It was previously known that dendritic cells were important for a strong immune response and that the number of dendritic cells at an infection site positively correlated with a robust reaction. However, until now it was poorly understood how dendritic cells become more specialized to address specific types of infections.

The researchers found that a protein called NOD2 triggers a cell-signaling molecule known as interleukin-32, which induces general immune cells called monocytes to become specialized, information-carrying dendritic cells.

“This is the first time that this potent infection-fighting pathway with dendritic cells has been identified and demonstrated to be important in fighting human disease,” said the study’s first author, Mirjam Schenk, a postdoctoral scholar in the division of dermatology at the David Geffen School of Medicine at UCLA.

In conducting the study, the scientists used monocytes taken from the blood of both healthy donors and leprosy patients and incubated the cells with the pathogen M. Leprae or specific parts of the mycobacteria known to trigger NOD2 and TLR2, both of which are associated with immune system activation.

The researchers wanted to investigate how these proteins might trigger mechanisms that “turn on” different immune receptors that recognize specific parts of the microbe in an infection. The NOD2 interleukin-32 pathway was the most effective and caused the monocytes to develop into dendritic cells that carry critical information about the pathogen to the T cells.

The team studied the gene-expression profiles of the protein-triggered pathways and also examined how the monocytes of leprosy patients responded to NOD2. They found that NOD2 worked to induce moncytes to become dendritic cells in tuberloid leprosy, a milder infection that is more easily contained. The NOD2 pathway was inhibited and could not be activated in lepromatous leprosy, which is more serious and causes widespread infection throughout the body.

“We were surprised to find the high potency of the dendritic cells in triggering certain specific T cell responses, which may be useful in developing new therapeutic strategies for infectious diseases and cancer,” said senior investigator Dr. Robert Modlin, UCLA’s Klein Professor of Dermatology and chief of dermatology at the Geffen School of Medicine.

Leprosy, one of the world’s oldest known diseases, is a chronic infectious disease that affects the skin, the peripheral nerves, the upper respiratory tract and the eyes and can lead to disfigurement of the hands, face and feet. In 2008, approximately 249,000 new cases of leprosy were reported worldwide, according to the World Health Organization.

Modlin said leprosy is a good model for studying immune mechanisms in host defense since it presents as a clinical spectrum that correlates with the level and type of immune response of the pathogen.

In the next stage of research, the scientists will attempt to further understand how to manipulate the innate immune system to induce a potent immune response in human infections, and possibly for cancer immunotherapy as well.

The study was funded by the NIH’s National Institute of Allergy and Infectious Diseases and National Institute of Arthritis and Musculoskeletal and Skin Diseases. (Grant numbers: RO1s AI022553, AR040312 and AI047868.)

Additional study authors included Stephan R. Krutzik, Peter A. Sieling, Delphine J. Lee, Rosane M.B. Teles and Maria Teresa Ochoa from the dermatology division in the department of medicine at the David Geffen School of Medicine at UCLA; Evangelia Komisopoulou and Thomas G. Graeber from UCLA’s Crump Institute for Molecular Imaging, Institute for Molecular Medicine, Jonsson Comprehensive Cancer Center, California NanoSystems Institute, and department of molecular and medical pharmacology; Euzenir N. Sarno from the department of mycobacteriosis at the Oswaldo Cruz Foundation in Rio de Janeiro, Brazil; Thomas H. Rea from the department of dermatology at the University of Southern California School of Medicine; Soohyun Kim from the department of biomedical science and technology at Konkuk University in Seoul, South Korea; and Genhong Cheng from the department of microbiology, immunology and molecular genetics at the David Geffen School of Medicine at UCLA.

Tests in flatworms provide a potential strategy for preventing the growth of cancer cells.

Harshani Peiris, UC Merced

A flatworm known for its ability to regenerate cells is shedding more light on how cancer could be treated and how regenerative medicine could better target diseases, according to researchers at the University of California, Merced.

In research published online in the Journal of Cell Science, biology professor Néstor Oviedo has shown that signaling by a protein called Target of Rapamycin (TOR) — found in humans and most other mammals — is crucial for planaria’s unique tissue regeneration. Disabling the protein prevents the flatworm’s regrowth, a sign that disabling it in abnormal cells could prevent the growth of a cancer.

“It’s a new model in which we can study stem cell behavior by manipulating the signaling pathways,” Oviedo said.

Researchers have recognized that the TOR protein plays a role in cancer, aging and degenerative diseases, but they haven’t figured out how it works.

Oviedo’s lab is approaching this question using tiny flatworms known as planaria. Long relegated as a scientific oddity, the planarian is now among the species that could be crucial in understanding the role of stem cells. The worm’s ability to repair itself is unparalleled, and its secrets could help combat cancer and degenerative diseases.

For this study, Oviedo’s lab disabled the TOR protein in planaria and then amputated parts of the flatworm. Under typical circumstances, the organism would be able to repair itself.

But researchers discovered the planaria’s stem cells recognized they needed to regrow tissue but were unable to regenerate it in the correct place and instead formed tissues in abnormal places. This kind of regeneration hasn’t been reported before. Additionally, the planaria with the disabled protein were unable to grow, even if nutrients were available.

In addition to stopping cancer, understanding TOR and its role in regulation could lead to the development of medicines to encourage tissue regeneration and to fight degenerative diseases, such as Alzheimer’s.

Graduate student Harshani Peiris, who was the lead author on the paper, said the planaria gives researchers the ability to look at the reactions of an entire organism, rather than just looking at cells in a Petri dish.

“We have a cutting-edge look into what’s happening at the system level,” Peiris said.

The research was funded by a grant from the UC Cancer Research Coordinating Committee.

The paper’s co-authors include undergraduate students Daniel Ramirez and Devon Davidian, professor Marcos Garcia-Ojeda, and staff members Elyze Ozamoto and Frank Weckerle.