Medical center is first in U.S. to use MarginProbe during lumpectomies.

Dr. Alice Police using MarginProbe to analyze a breast cancer tumor. UC Irvine Medical Center is the first in the U.S. to use the device, which reduces the need for additional surgery to remove cancerous tissue.

Any breast cancer surgeon who regularly performs lumpectomies confronts the question “Did I get it all?” Thirty to 60 percent of the time in the U.S., the answer is “no,” requiring the patient to undergo a second surgery to remove the remaining tumor.

Surgeons at UC Irvine Medical Center are the first in the country to use a device that reduces by half the need to reoperate and cut out breast cancer cells missed during an initial lumpectomy. The MarginProbe System lets the surgeon immediately assess whether cancer cells remain on the margins of excised tissue. Currently, patients have to wait days for a pathologist to determine this.

“All of my patients know someone who has had to go back into surgery because their doctor didn’t get the entire tumor out,” said UC Irvine Health surgical oncologist Dr. Alice Police. “The ability to check tissue in the operating room is a game changer in surgery for early-stage breast cancer.”

The goal in a lumpectomy is to completely remove the cancer while preserving as much normal breast tissue as possible. If a pathologist finds cancer cells on the edges of the tissue taken out, surgeons must assume the lumpectomy didn’t get the entire tumor.

The Food and Drug Administration approved MarginProbe in December 2012, and UC Irvine Medical Center is the first hospital in the U.S. to employ the system, according to manufacturer Dune Medical Devices.

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New class of molecules may be key emerging “enhancer therapy.”

Christopher Glass, UC San Diego

In a pair of distinct but complementary papers, researchers at the UC San Diego School of Medicine and colleagues illuminate the functional importance of a relatively new class of RNA molecules. The work, published online this week in the journal Nature, suggests modulation of “enhancer-directed RNAs” or “eRNAs” could provide a new way to alter gene expression in living cells, perhaps affecting the development or pathology of many diseases.

Enhancers are sequences in the genome that act to boost or “enhance” the activity or expression of nearby genes. They “often behave in a cell-specific manner and play an important role in establishing a cell’s identity and functional potential,” said Christopher Glass, M.D., Ph.D., a professor in the department of Medicine and Cellular and Molecular Medicine at UC San Diego and principal investigator of one of the papers.

Although enhancers have been recognized for more than 25 years, scientists have labored to fully flesh out the breadth and complexity of what enhancers do and how they do it. In 2010, it was discovered that enhancers directed expression of RNA on a broad scale in neurons and macrophages, a type of immune system cell. Dubbed eRNAs, they were different from other classes of nuclear non-coding RNAs, and raised new questions about their potential roles in the functions of enhancers. The two Nature papers attempt to answer some of these questions.

Michael Rosenfeld, UC San Diego

In the first, principal investigator Glass and colleagues investigated a pair of related transcriptional repressors called Rev-Erb-alpha and Rev-Erb-beta (proteins with important roles in regulating the circadian rhythm in many cell types) in mouse macrophages. Using genome-wide approaches, they found that the Rev-Erb proteins repressed gene expression in macrophages primarily by binding to enhancers. Collaboration with researchers at the Salk Institute for Biological Studies revealed that the repressive function of Rev-Erbs was highly correlated with their ability to repress the production of eRNAs.

In the second paper, principal investigator Michael G. Rosenfeld, M.D., a professor in the UC San Diego Department of Medicine and Howard Hughes Medical Institute investigator, and colleagues looked at estrogen receptor binding in human breast cancer cells – and its impact on enhancer transcription.  In contrast to the repressive functions of Rev-Erbs, estrogen receptors (ERs) activate gene expression; but, like Rev-Erbs, they primarily function by also binding to enhancers. ER binding was shown to be associated with increases in enhancer-directed eRNAs in the vicinity of estrogen-induced genes, and to exert roles on activation of coding target genes.

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Preliminary tests show very manageable side effects for treating patients with skin cancer.

Antoni Ribas, UCLA

Researchers from UCLA’s Jonsson Comprehensive Cancer Center report that a new drug in preliminary tests has shown promising results with very manageable side effects for treating patients with melanoma, the deadliest form of skin cancer.

The results were presented at the 2013 meeting of the American Society of Clinical Oncology today (June 2) in Chicago by Dr. Antoni Ribas, professor of medicine in the UCLA division of hematology-oncology, who led the research. Following Ribas’ presentation, the study was published online ahead of press in the New England Journal of Medicine.

The results are from the first clinical trial of the drug lambrolizumab (MK3475), which was discovered and developed by Merck. Researchers analyzed 135 patients with advanced metastatic melanoma who were divided into three groups with different treatment regimens.

Overall, 38 percent of patients taking lambrolizumab saw confirmed improvement of their cancer across all dose levels. Of those taking the lowest dose of lambrolizumab, 25 percent showed improvement, while 52 percent of those who received the highest dose improved. The rate of any tumor response across all patients was 77 percent. Researchers have not yet determined the average duration of response to the drug, because only five patients who had initial responses were taken off the study after their cancers got worse. To date, the longest response has been over one year.

Side effects with lambrolizumab are usually mild and easily managed. These include fatigue, fever, skin rash, loss of skin color and muscle weakness. Thirteen percent of patients had side effects that were more severe, including inflammation of the lung or kidney, and thyroid problems.

“This study is showing the highest rate of durable melanoma responses of any drug we have tested thus far for melanoma, and it is doing it without serious side effects in the great majority of patients,” Ribas said.

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Findings may provide a new set of targets for oncogene-specific drug development.

Glioblastoma multiforme

An international team of researchers – led by principal investigator Paul S. Mischel, M.D., a member of the Ludwig Institute for Cancer Research and professor in the Department of Pathology at the UC San Diego School of Medicine – has found that a singular gene mutation helps brain cancer cells to not just survive, but grow tumors rapidly by altering the splicing of genes that control cellular metabolism.

The findings are published online in the journal Cell Metabolism.

Mischel, who heads the Ludwig Institute’s molecular pathology laboratory based at UC San Diego, and colleagues focused upon a process called alternative splicing, in which a single gene encodes for multiple proteins by including or excluding different, specific regions of DNA.

Alternative splicing is a tightly regulated and normal activity in healthy cells. For Mischel and colleagues in Los Angeles, Ohio and Japan, the question was whether mutations of a gene called EGFRvIII caused differential alternative splicing in glioblastoma multiformes (GBMs), the most common and aggressive type of malignant brain tumor. Median survival after GBM diagnosis is just 15 months with standard-of care radiation and chemotherapy. Without treatment, it is less than five months.

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UC San Diego scientists develop new tumor visualization strategy.

Scientists at the University of California, San Diego, have designed tiny spherical particles to float easily through the bloodstream after injection, then assemble into a durable scaffold within diseased tissue. An enzyme produced by a specific type of tumor can trigger the transformation of the spheres into netlike structures that accumulate at the site of a cancer, the team reports in the journal Advanced Materials this week.

Targeting treatments specifically to cancerous or other diseased cells depends on some means of accumulating high levels of a drug or other therapeutic agent at the specific site and keeping it there. Most efforts so far depend on matching a piece of the drug-delivering molecule to specific receptors on the surface of the target cell.

Inspiration for this new strategy came from biological systems that use shape to alter the ability of something to lock in place or slip away and escape, said Nathan Gianneschi, a professor of chemistry and biochemistry, who led the project.

“We wanted to come up with a new approach,” Gianneschi said. “Specifically, we wanted to design switchable materials that we could inject in one shape and have them change to another between the blood and tumors.”

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16-year-old Davis High School student recipient of Blue and White Foundation grant.

Primo and Matthew Lara

What started as a dinner-table conversation between a teen and his father has become a bonafide cancer research study for Matthew Lara, a Davis High School sophomore and the son of UC Davis Comprehensive Cancer Center medical oncologist and researcher Primo (Lucky) Lara Jr.

Matthew, 16, will put on a suit and present his findings on non-small-cell lung cancer during a poster session in Chicago on Saturday at the annual meeting of American Society of Clinical Oncology (ASCO), a 30,000-member cancer research organization.

Matthew’s poster, entitled “Predictors of survival for younger patients less than 50 years of age with non-small cell lung cancer (NSCLC): a California Cancer Registry analysis,” describes his findings that younger people with lung cancer tend to have better survival rates than older patients with lung cancer. His poster represents the largest analysis of age-related survival in lung cancer ever conducted. The work was based on data from the California Cancer Registry, a massive, statewide repository for demographic and epidemiological cancer case data.

Primo Lara also will present research at ASCO on Saturday. His study — unrelated to Matthew’s work — analyzed survival variables associated with small cell lung cancer patients who had previously been treated with platinum-containing chemotherapy.

Matthew’s project was born at the dinner table.

“We were talking about lung cancer, and I asked my dad if young people get lung cancer and if they do better than older people,” said Matthew. “My Dad said, ‘Well, you can certainly try to find the answer to that yourself!’ So we did.”

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Method could facilitate at-home urine tests.

Reginald Penner, UC Irvine

Early screening for prostate cancer could become as easy for men as personal pregnancy testing is for women, thanks to UC Irvine research published today (May 22) in the Journal of the American Chemical Society.

After more than a decade of work, UC Irvine chemists have created a way to clearly identify clinically usable markers for prostate cancer in urine, meaning that the disease could be detected far sooner, with greater accuracy and at dramatically lower cost. The same technology could potentially be used for bladder and multiple myeloma cancers, which also shed identifiable markers in urine.

“Our goal is a device the size of a home pregnancy test priced around $10. You would buy it at the drugstore or the grocery store and test yourself,” said the study’s corresponding author, Reginald Penner, UC Irvine Chancellor’s Professor of chemistry. “We’re on the verge of a very important breakthrough in a new era of personal health management.”

About 240,000 men in the U.S. are diagnosed with prostate cancer each year, and 29,000 are expected to die of it in 2013. But current, widely utilized testing does not always catch the disease in its early stages, often yields false positives and can lead to unnecessary, risky treatments.

A recent report concluded that the prostate-specific antigen, or PSA, test can be more harmful than beneficial, although it remains important for detecting recurring prostate cancer. The UC Irvine researchers used a different biomarker, PSMA, and plan to test others to pinpoint if a cancer is growing aggressively or not.

“A big problem is that the approach used now does not catch cancer soon enough,” said co-author Gregory Weiss, a UC Irvine biochemist. “We want this to be a disruptive technology that will change how we save lives and that will bring down health care costs drastically.”

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Older patients should carefully consider options.

Timothy Daskivich, UCLA

Older prostate cancer patients with other underlying health conditions should think twice before committing to surgery or radiation therapy for their cancer, according to a multicenter study led by researchers from the UCLA Department of Urology.

The study reports 14-year survival outcomes for 3,000 men diagnosed with prostate cancer between 1994 and 1995. The results suggest that older patients with low- or intermediate-risk prostate cancer who have at least three underlying health problems, or co-morbidities, are much more likely to die of something other than their cancer.

“For men with low-to-intermediate–risk disease, prostate cancer is an indolent disease that doesn’t pose a major risk to survival,” said the study’s first author, Dr. Timothy Daskivich, a UCLA Robert Wood Johnson fellow. “The take-home point from this study is that older men with multiple underlying health problems should carefully consider whether they should treat these tumors aggressively, because that treatment comes with a price.”

Aggressive treatments for prostate cancer, including surgery, external radiation and radioactive seed implants, can result in major side effects, including erectile dysfunction, urinary incontinence and bowel problems. Also, the survival advantage afforded by these treatments does not develop until approximately eight to 10 years after treatment.

In many cases, Daskivich said, either “watchful waiting” or active surveillance — monitoring the patient’s cancer very closely with regular biopsies and intervening with surgery or radiation if the disease progresses — is better than hitting the disease with everything in the treatment arsenal.

The study appears May 21 in the early online issue of the peer-reviewed journal Annals of Internal Medicine.

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UC San Diego experts answer questions about breast cancer.

Sarah Blair, UC San Diego

It’s not surprising that Angelina Jolie’s announcement that she had preventive double mastectomy is big news. You can read about it here, here, here and here – among myriad places.

The fact remains, though, that Jolie’s dilemma and decision is far from novel. It’s one faced by many women, almost all without the glare or notice of media.

With that in mind, we reprise a pair of Q&As posed to breast cancer experts at UC San Diego: Teresa Helsten, M.D., assistant clinical professor in the School of Medicine’s Division of Hematology-Oncology at Moores Cancer Center and Sarah Blair, M.D., associate professor of surgery at Moores Cancer Center.

Read Q&A

Related link:
UC Santa Barbara scholar Laury Oaks addresses issue of whether prophylactic mastectomy is a universal key to breast cancer prevention

Seventh annual event will feature new stand-up paddleboard (SUP) competition.

UC San Diego Moores Cancer Center will host the 7th annual Survivor Beach on Sunday, June 2. The event, which has become a La Jolla tradition, will feature a stand-up paddleboard (SUP) competition, beach festival with food trucks and more. Hundreds of community members will gather for the morning event in solidarity in the fight against cancer.

Last year, more than 300 people attended Survivor Beach, which honors those who have fought cancer, as well as the family, friends and caregivers of those with cancer. New to the event this year will be open and elite stand-up paddleboard races, as well as SUP clinics. Survivor Beach also will feature a brief program with comments from a cancer survivor sharing his inspirational story. The following beach festival will include a dance performance by Heali’i’s Polynesian Revue and a live DJ. Participants can also line their surfboards along the sea wall on the beach in front of Scripps Institution of Oceanography as a visual display of their support in the quest to conquer cancer.

For the sixth year in a row, Survivor Beach is sponsored by biotechnology company Genentech, which discovers, develops, manufactures and commercializes medicines to treat patients with serious or life-threatening medical conditions, including cancer.

“Set along the gorgeous coastline of La Jolla, Survivor Beach demonstrates the power and strength that results from coming together to fight cancer,” said Alex Panici, chair of the 7th annual Survivor Beach. “This year, Survivor Beach offers added fun with stand-up paddleboard events for everyone from the most elite to the newest paddlers.”

The event precedes the annual Luau and Longboard Invitational in August, which will raise funds for research, patient care, and outreach and educational programs at UC San Diego Moores Cancer Center, the region’s only National Cancer Institute-Comprehensive Cancer Center.

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UC Davis event targets Asian-American adults.

A UC Davis medical student prepares to draw blood for hepatitis screening test.

Asian Americans and adult children of foreign-born Asian Americans are invited to a free hepatitis B screening event Sunday (May 19) at the UC Davis Comprehensive Cancer Center.

The event, from 10 a.m. to 2 p.m., is being held in recognition of Asian Pacific Islander Heritage Month and National Hepatitis Testing Day. It is funded with a federal grant aimed at boosting hepatitis B screening and preventing liver cancer in the Asian-American community.

“Our goal is to screen 1,000 foreign-born or children of foreign-born Asian Americans who are 18 years of age or older, and who are from areas where hepatitis B is endemic,” said Julie Dang, a community health program supervisor at the UC Davis Comprehensive Cancer Center and study program manager.

One of every 10 Asian Pacific Islanders has hepatitis, and most do not know they have been infected because often there are no symptoms. Untreated, hepatitis B virus can lead to liver cancer. Nearly 80 percent of liver cancer cases in Asian Americans can be directly traced to the Hepatitis B virus infection.

Screening participants who test negative and need vaccination will be put on a waiting list and contacted when vaccines become available.  All participants will receive a phone call and a result letter regarding their status.

“Individuals who test positive will receive individual counseling sessions to help them understand their status and get referrals for  care,” said Dang.

Additional event offerings will include risk-factor screenings (hepatitis C, diabetes and blood pressure), health education and light refreshments. All participants will receive a $10 Walmart gift card for their contribution to the study.

The event is co-sponsored by the Asian American Network for Cancer Awareness, Research and Training (AANCART), a national organization that is headquartered at the cancer center

The UC Davis Comprehensive Cancer Center is at 4501 X St. in Sacramento. To RSVP for the event, please contact Tina Fung at (916) 734-5371, or email her at tina.fung@ucdmc.ucdavis.edu.

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Cancers physically alter cells in the lymphatic system to promote the spread of disease.

Researchers at the UC San Diego School of Medicine and UC San Diego Moores Cancer Center report that cancers physically alter cells in the lymphatic system – a network of vessels that transports and stores immune cells throughout the body – to promote the spread of disease, a process called metastasis.

The findings are published in this week’s online early edition of the Proceedings of the National Academy of Sciences.

Roughly 90 percent of all cancer deaths are due to metastasis – the disease spreading from the original tumor site to multiple, distant tissues and finally overwhelming the patient’s body. Lymph vessels are often the path of transmission, with circulating tumor cells lodging in the lymph nodes – organs distributed throughout the body that act as immune system garrisons and traps for pathogens and foreign particles.

The researchers, led by principal investigator Judith A. Varner, Ph.D., professor of medicine at UC San Diego Moores Cancer Center, found that a protein growth factor expressed by tumors called VEGF-C activates a receptor called integrin α4β1 on lymphatic vessels in lymph node tissues, making them more attractive and sticky to metastatic tumor cells.

“One of the most significant features of this work is that it highlights the way that tumors can have long-range effects on other parts of the body, which can then impact tumor metastasis or growth,” said Varner.

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