TAG: "Cancer"

Reducing unnecessary, high-dose CT scans could cut associated cancers


Risk in children could be reduced by 62 percent, UC Davis-led study finds.

Diana Miglioretti, UC Davis

A study examining trends in X-ray computed tomography (CT) use in children in the United States has found that reducing unnecessary scans and lowering the doses for the highest-dose scans could lower the overall lifetime risk of future imaging-related cancers by 62 percent. The research by a UC Davis Health System scientist is published online today (June 10) in JAMA Pediatrics. It is accompanied by a journal editorial.

The 4 million CT scans of the most commonly imaged organs conducted in children each year could result in approximately 4,870 future cancers, the study found. Reducing the highest 25 percent of radiation doses could prevent 2,090 — or 43 percent — of these future cancers. By also eliminating unnecessary imaging, 3,020 — or 62 percent — of cancers could be prevented, said Diana Miglioretti, lead study author and Dean’s Professor in Biostatistics in the Department of Public Health Sciences at UC Davis Health System.

“There are potential harms from CT, meaning that there is a cancer risk, albeit very small in individual children, so it’s important to reduce this risk in two ways,” said Miglioretti, who is a member of the UC Davis Comprehensive Cancer Center. “The first is to only do a CT when it’s medically necessary, and use alternative imaging when possible. The second is to dose CT appropriately for children.”

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Free skin cancer screening draws hundreds on sunny San Francisco day


UCSF hosts event at Castro Mission Health Center.

Thomas Busse receives a free skin cancer screening from UCSF's Rupa Pugashetti at the Castro Mission Health Center in San Francisco on June 1.

The blazing Saturday sun may have been an appropriate reminder for people to think about getting screened for skin cancer.

The turnout at the free screening, held this year at the Castro Mission Health Center on June 1, made it one of the most successful – nearly 250 people were examined, up from 170 the previous year, according to Patrick Unemori, M.D., a resident with the UCSF Department of Dermatology, which hosted the event.

Of those who were screened, UCSF dermatologists made 85 case referrals, including 22 possible cases of melanoma – the most dangerous form of skin cancer – and 23 possible cases of non-melanoma skin cancer, Unemori said.

People who came to the skin cancer screening also were given an opportunity to learn more about proper sun protection through presentations by medical students, and they were sent home with samples of sunscreen and other skin protectants.

Skin cancer is the most common form of cancer, with more than 3 million skin cancers diagnosed annually in some 2 million people in the United States. One in five Americans will develop skin cancer in their lifetime, but many cases can be easily treated if detected early.

Anyone can develop skin cancer, regardless of skin color or general health. Melanoma is the most common form of cancer for young adults 25 to 29 years old.

The UCSF Department of Dermatology has hosted a free skin cancer screening each year at locations around San Francisco, with volunteer participation from UCSF Medical Center and San Francisco General Hospital and Trauma Center. This year, nearly 40 faculty, residents, staff and medical students gave their time to make the screening a success.

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Bladder cancer recurrence, mortality could decline with better treatment compliance


UCLA study is first to examine the burden of the disease on the population.

Karim Chamie, UCLA

Researchers at UCLA’s Jonsson Comprehensive Cancer Center led by Dr. Karim Chamie have found that more intense surveillance and treatment of bladder cancer in the first two years after diagnosis could reduce the number of patients whose cancer returns after treatment and lower the disease’s death rate. The study was published online ahead of press today (June 4) in the journal Cancer.

Based on the team’s previous research showing underutilization of care for patients with bladder cancer, this study is the first to examine the burden of the disease on the population. To date no one had examined the morbidity of recurrence of the disease in the U.S.

Chamie, assistant professor-in-residence in the UCLA department of urology, and his colleagues found that nearly three quarters of patients with high-grade, non–muscle-invasive bladder cancer suffered a return of the disease within 10 years. In 33 percent of patients, the cancer progressed to a more advanced form requiring removal of the bladder, radiation therapy or systemic chemotherapy. And in an additional 41 percent, the cancer recurred without further spread of the disease.

“Even though 80 percent of bladder cancer patients don’t die of their disease within five years, most patients will either die of other causes or bladder cancer, require aggressive treatment — removal of the bladder, radiation and/or chemotherapy — or have a recurrence of the disease,” Chamie said. “This study highlights the need to comply with treatment guidelines to prevent recurrences by instilling anticancer agents inside the bladder and following patients more closely within the first two years of diagnosis.”

The study was based on a nationwide sample of Medicare beneficiaries who had high-grade, non–muscle-invasive bladder cancer. “We have Level I evidence that demonstrates that a single instillation of chemotherapy into the bladder can minimize recurrences, and that six instillations can minimize recurrence and progression,” Chamie said. “Efforts should be increased to offer patients intravesical therapy with the goal of minimizing the burden of this disease.”

The researchers also found that the burden of bladder cancer on the population is very high, and that the elderly, women and African-American patients had a higher likelihood of dying of bladder cancer than younger patients, men and white patients, respectively.

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Onyx Pharmaceuticals, UCSF announce Oncology Innovation Alliance


Strategic alliance focused on advancing drug discovery and development.

Jeffrey Bluestone, UC San Francisco

Onyx Pharmaceuticals Inc. (Nasdaq: ONXX) and the UC San Francisco Helen Diller Family Comprehensive Cancer Center today (June 3) announced the formation of the Oncology Innovation Alliance (OIA), a public-private partnership focusing on the discovery and development of novel therapies and their potential role in treating various types of hematologic cancers and solid tumors.

“This collaboration will leverage expertise across UCSF and Onyx to further our collective understanding of cancer and hopefully translate scientific research rapidly from the laboratory to the clinic and, ultimately, to patients,” said Pablo J. Cagnoni, M.D., executive vice president, global research & development and technical operations at Onyx Pharmaceuticals. “The UCSF Helen Diller Family Comprehensive Cancer Center is a recognized leader in oncology research and patient care, and Onyx is committed to forming strategic alliances that encourage innovation and the advancement of new treatments for patients.”

The alliance aims to transform cancer care by harnessing the expertise in fundamental science and medicine at both UCSF and Onyx to address the full continuum of that care, from prediction and diagnosis to new therapies and post-treatment monitoring, to identify opportunities to improve the patient experience and outcomes.

The partnership will focus on drug discovery and development, and seeks to advance the broader scope of patient care while contributing to the biological understanding of hematologic malignancies and solid tumors, discovering novel drug targets, identifying potential biomarkers to support patient selection and implementing innovative clinical development approaches.

“UCSF and Onyx share a vision of transforming care for patients with cancer, so we can precisely diagnose, treat and possibly even prevent cancer from occurring,” said Jeffrey Bluestone, Ph.D., executive vice chancellor and provost at UCSF. “Our goal is to create an umbrella partnership that enables us to work together to better understand the cascade of events within a cell that leads to disease, and find innovative ways to use that knowledge to diagnose and treat patients far more precisely than we can today.”

A joint steering committee comprised of representatives from Onyx and UCSF will provide oversight of the alliance. The term of the agreement extends for three years. Financial terms of the collaboration were not disclosed.

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New technology makes breast cancer surgery more precise at UC Irvine


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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Enhancer RNAs alter gene expression


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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New drug shows promise for treating advanced melanoma


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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Oncogene mutation hijacks splicing process to promote growth and survival


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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Shape-shifting nanoparticles offer cancer insight


UC San Diego scientists develop new tumor visualization strategy.

Scientists at the University of California, San DiegoShapeshifting nanoparticles, 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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Father and teen son to present their respective cancer research at ASCO


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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Chemists devise cheap, accurate way to detect prostate cancer


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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No-treatment approach may be best choice for older prostate cancer patients


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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