TAG: "Cancer"

Finding a better way to track emerging cell therapies using MRIs


Technique might speed development of relevant therapies.

Cellular therapeutics – using intact cells to treat and cure disease – is a hugely promising new approach in medicine, but it is hindered by the inability of doctors and scientists to effectively track the movements, destination and persistence of these cells in patients without resorting to invasive procedures, like tissue sampling.

In a paper published Sept. 17 in the online journal Magnetic Resonance in Medicine, researchers at the UC San Diego School of Medicine, University of Pittsburgh and elsewhere describe the first human tests of using a perfluorocarbon (PFC) tracer in combination with non-invasive magnetic resonance imaging (MRI) to track therapeutic immune cells injected into patients with colorectal cancer.

“Initially, we see this technique used for clinical trials that involve tests of new cell therapies,” said first author Eric T. Ahrens, Ph.D., professor in the Department of Radiology at UC San Diego. “Clinical development of cell therapies can be accelerated by providing feedback regarding cell motility, optimal delivery routes, individual therapeutic doses and engraftment success.”

Currently, there is no accepted way to image cells in the human body that covers a broad range of cell types and diseases. Earlier techniques have used metal ion-based vascular MRI contrast agents and radioisotopes. The former have proven difficult to differentiate in vivo; the latter raise concerns about radiation toxicity and do not provide the anatomical detail available with MRIs.

“This is the first human PFC cell tracking agent, which is a new way to do MRI cell tracking,” said Ahrens. “It’s the first example of a clinical MRI agent designed specifically for cell tracking.”

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Education matters when it comes to treating prostate cancer


UCLA study finds ‘decisional conflict’ could negatively impact quality of care.

They say knowledge is power, and a new UCLA study has shown this is definitely the case when it comes to men making the best decisions about how to treat their prostate cancer.

UCLA researchers found that men who aren’t well educated about their disease have a much more difficult time making treatment decisions. That challenge, called “decisional conflict,” could negatively impact the quality of their care and their long-term outcomes.

The study should serve as a wake-up call for physicians, who can use the findings to target men less likely to know a lot about their prostate cancer. Doctors can educate patients prior to their appointments so they’re more comfortable making treatment decisions, said the study’s first author Dr. Alan Kaplan, a resident physician in the UCLA Department of Urology.

“For prostate cancer, there is no one right answer when it comes to treatment. It comes down to the right answer for each specific patient, and that is heavily dependent on their own personal preferences,” Kaplan said. “Men in general, and specifically economically disadvantaged men, have a hard time deciding what their preferences are, how they feel about any possible complications and what the future after treatment might be like. If you don’t know anything about your disease, you’ll have a really tough time making a decision.”

The findings from the one-year study appear were published online by the peer-reviewed journal Cancer.

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Drug targeting leukemia cells enters clinical trial


Antibody developed at UC San Diego.

Researchers at the UC San Diego School of Medicine have launched a phase one human clinical trial to assess the safety and efficacy of a new monoclonal antibody for patients with chronic lymphocytic leukemia (CLL), the most common form of blood cancer in adults.

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

Because ROR1 is not expressed by normal adult cells, scientists believe it is a biomarker of cancer cells in general and cancer stem cells in particular. Because it appears to drive tumor growth and disease spread, they believe it also presents an excellent target for anti-cancer therapy.

Developed at UC San Diego Moores Cancer Center by Thomas Kipps, M.D., Ph.D., who holds the Evelyn and Edwin Tasch Chair in Cancer Research, and colleagues, the antibody is called cirmtuzumab (also known as UC-961). In previous animal studies, Kipps’ team reported that ROR1 is singularly expressed on CLL and also on a variety of different cancers, including cancers of the breast, pancreas, colon, lung and ovary. In mouse models of CLL, ROR1 acts as an accelerant when combined with another oncogene to produce a faster-growing, more aggressive cancer.

Cirmtuzumab was developed under the auspices of the California Institute for Regenerative Medicine’s HALT leukemia grant awarded to Dennis Carson, M.D., principal investigator, and Catriona Jamieson, M.D., Ph.D., co-principal investigator to develop six distinct therapies against cancer stem cells. Kipps led one of the six projects and generated antibodies against ROR1, leading to the cirmtuzumab trial in patients with CLL.

“The primary goal of this phase one clinical trial is to evaluate whether cirmtuzumab is a safe and well-tolerated cancer stem cell-targeted agent in patients with CLL,” said Jamieson, chief of the Division of Regenerative Medicine, associate professor of medicine, director of stem cell research at UC San Diego Moores Cancer Center, deputy director of the Sanford Stem Cell Clinical Center and a principal investigator of the cirmtuzumab clinical trial.

Michael Choi, M.D., assistant clinical professor of medicine and co-principal investigator of the clinical trial said, “The trial will involve patients with relapsed or refractory CLL, who will receive an intravenous infusion every 14 days at Moores, followed by regular monitoring and clinic visits to assess efficacy and identify and manage any adverse effects. Initial treatment is planned for two months.”

To learn more about eligibility for this clinical trial, call Reilly L. Kidwell at (858) 534-4801 or Samuel Zhang at (858) 534-8127.

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Cancer and immune system: A double-edged sword


Findings have importance for desigining clinical trials with drugs that target immune system.

During cancer development, tumor cells decorate their surfaces with sugar compounds called glycans that are different from those found on normal, healthy cells. In today’s (Sept. 15) online early edition of the Proceedings of the National Academy of Sciences (PNAS), researchers at the UC San Diego School of Medicine report that sialic acids at the tips of these cancer cell glycans are capable of engaging with immune system cells and changing the latter’s response to the tumor – for good and bad.

“These cell surface glycans can promote or inhibit cancer progression, depending upon the stage of the disease,” said principal investigator Ajit Varki, M.D., Distinguished Professor of Medicine and Cellular and Molecular Medicine. “Our findings underscore the complexity of cancer and the consequent challenges in conquering it. The immune system may be a double-edged sword in cancer, tumor-promoting or tumor-inhibiting, depending upon circumstances.”

Specifically, the researchers found that receptors called siglecs on subsets of neutrophils and macrophages (two types of immune cell) can bind to sialic acids on the surface of tumor cells. Depending upon the stage of cancer and the tumor model used, the scientists reported that interaction between immune cell siglecs and tumor cell sialic acids produced opposite outcomes.

“During initial stages of growth, cancer cells appear to protect themselves from extermination by neutrophils by engaging siglecs via sialic acid-capped glycans,” said Varki, who is also a faculty member of the UC San Diego Moores Cancer Center. “But once the tumor was established, further growth was inhibited by engagement of siglecs on macrophages.”

The findings follow upon research by Varki and colleagues published earlier this year in PNAS that showed anti-tumor antibodies also behave contrarily. Low concentrations of antibodies can support cancer growth, but higher concentrations may inhibit it.

“The fact that the immune system can exert a promoting or inhibiting effect on cancer progression, depending on the situation and stage of disease, has importance for designing clinical trials with drugs that target the immune system,” said first author Heinz Läubli, M.D., Ph.D.

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Targeted leukemia treatment shows promise


UC Davis develops unique treatment approach.

Noriko Satake, UC Davis

Noriko Satake, UC Davis pediatric oncologist and researcher, has demonstrated in laboratory studies that a new, targeted treatment for leukemia is effective.

Satake’s research was published Sept. 9 in the British Journal of Haematology.

“We identified a novel molecular target that is important for the growth of precursor B-cell acute lymphoblastic leukemia (ALL), the most common cancer in children,” Satake said. “We developed a unique treatment approach using a drug that blocks the target molecule and kills leukemia cells, a nanoparticle vehicle that carries the drug, and an antibody driver that delivers the nanocomplexes (drug-loaded nanoparticles) to leukemia cells.

“We showed great efficacy of these new drug nanocomplexes on a cell line and on primary leukemia samples,” she added. “We also demonstrated that they had minimal toxicities on normal blood cells.”

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SF celebrates 3 new hospitals with stars, lights and action


UCSF Hard Hat Walk, Lights On Festival draw thousands to Mission Bay.

San Francisco’s Mission Bay district became a melting pot of celebrities, civic dignitaries, community members and assorted creatures of unknown species with dazzling outfits and daring dance moves, as the city marked the upcoming opening of the new UCSF Medical Center.

Thousands joined in Saturday’s revelry, starting with the 5K Hard Hat Walk along the waterfront and through the Mission Bay neighborhood and ending with the Lights On Festival in the public plaza outside the medical center complex. The event culminated in a multicolor light show illuminating the windows of the three hospitals opening on Feb. 1, 2015: UCSF Benioff Children’s Hospital San Francisco, UCSF Bakar Cancer Hospital and UCSF Betty Irene Moore Women’s Hospital.

Donors and attendees of the celebration raised more than $525,000 for the new hospitals, exceeding the fundraising goal of $500,000.

Kicking off the Hard Hat Walk, UCSF Medical Center CEO Mark Laret paid tribute to the construction crew, staff and fundraisers. He urged the crowds to remind themselves that with “every step you take, think about a child whose life is going to be saved in that hospital and a mom who’s going to have an easier birth because of innovations here.”

There was plenty of levity to offset the serious moments.

A number of teams assembled for the walk dressed in fun costumes. UCSF Chief Information Officer Joe Bengfort nixed the sweats in favor of Luke Skywalker duds to lead his team, the Jedi Masters, which raised close to $12,000. The UCSF Cancer Crusaders donned superhero masks and capes; the Children’s Emergency Department team all wore rainbow tutus; and Remembering Maggie McDonald – one of the top patient fundraising teams – sported yellow hard hats in tribute to 19-year-old Maggie, a longtime patient of UCSF Benioff Children’s Hospital San Francisco who passed away earlier this year.

At the festival, families enjoyed pastries, tacos and other tasty treats from top local restaurants, while children got their faces painted, participated in wall art, played bungee run and danced to Vocal Rush, a teen a cappella group from the Oakland School for the Arts. Other participants decompressed with chair messages or a snuggle with a friendly possum from the San Francisco Zoo’s Zoomobile.

Adding razzle-dazzle to the event were Jesse Tyler Ferguson, star of the ABC television show “Modern Family,” Olympic champion figure skater Kristi Yamaguchi and San Francisco Giants home run king Barry Bonds, a longtime friend and supporter of UCSF Benioff Children’s Hospital San Francisco (“my brother from another mother,” according to Ferguson).

The midafternoon sun had segued into an early evening chill by the time celebrated singer and Bay Area native Michael Franti took the stage. But the audience warmed up dancing to his hits, “I’m Alive” and “Say Hey.”

At his invitation, a group of patients joined him on stage. The new hospitals were very personal to him, Franti explained, because his 15-year-old son had been a long-term patient at UCSF Benioff Children’s Hospital San Francisco. The audience nodded in unison, knowing the hospitals will play a key role in their health and that of their loved ones for generations to come.

David Chiu, president of the San Francisco Board of Supervisors, said it best when he addressed the crowd: “This is a moment in time so special for San Francisco.”

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FDA approves new melanoma drug


The drug is a ‘game changer,’ says UCLA’s Dr. Antoni Ribas, the study’s principal investigator.

UCLA's Dr. Antoni Ribas (right) with Tom Stutz, whose health improved dramatically after treatment with the newly approved drug.

The U.S. Food and Drug Administration today (Sept.4) approved a new immunotherapy drug to treat advanced melanoma, signaling a paradigm shift in the way the deadly skin cancer is treated.

The drug, Keytruda, was tested on more than 600 patients who had melanoma that had spread throughout their bodies. Because so many of the patients in the early testing showed significant long-lasting responses, the study was continued and the FDA granted the drug “breakthrough therapy” status, allowing it to be fast-tracked for approval.

The largest phase one study in the history of oncology, the research was conducted at UCLA and 11 other sites in the U.S., Europe and Australia.

Keytruda, formerly known as MK-3475, is an antibody that targets a protein called PD-1 that is expressed by immune cells. The protein puts the immune system’s brakes on, keeping its T cells from recognizing and attacking cancer cells, said Dr. Antoni Ribas, the study’s principal investigator and a professor of medicine in the division of hematology–oncology at the David Geffen School of Medicine at UCLA.

For many years, when using immunotherapy to fight cancer, doctors’ strategy has been to bolster the immune system so it could kill the cancer cells. But the approach had limited success because PD-1 prevented the immune system from becoming active enough to attack the cancer. Keytruda, in effect, cuts the brake lines, freeing up the immune system to attack the cancer.

“This drug is a game changer, a very significant advance in the treatment of melanoma,” said Ribas, who also is a researcher at UCLA’s Jonsson Comprehensive Cancer Center. “For patients who have not responded to prior therapies, this drug now provides a very real chance to shrink their tumors and the hope of a lasting response to treatment.”

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UCSF doctor receives leadership award from National Cancer Institute


Will support Katie Kelley’s efforts related to gastrointestinal cancer.

Katie Kelley, UC San Francisco

Katie Kelley, M.D., a gastrointestinal oncologist at UC San Francisco, has received the 2014 Cancer Clinical Investigator Team Leadership Award from the National Cancer Institute (NCI). This highly competitive category was open to members at certified cancer centers only. The award, a $100,000 supplement to the Cancer Center Support Grant over a two-year period, will support Kelley’s effort related to her clinical leadership roles.

Her clinical research focus lies in the design and conduct of clinical trials of novel targeted agents and combination therapies in hepatocellular carcinoma (HCC) and cancers of the biliary tract.

Her translational research efforts have already enriched the research environment within UCSF. Specifically, Kelley has taken the lead role in addressing the critical need to better understand the complex tumor biology and identify therapeutic targets in hepatobiliary cancers at UCSF.

Kelley began her training and experience in clinical research during the research phase of her fellowship in hematology/oncology at UCSF in 2007 when she joined the Gastrointestinal Oncology Group. As a fellow, Kelley completed the UCSF Clinical and Translational Science Institute (CTSI) course, “Training in Clinical Research” in 2008 and received extensive informal training from mentors in GI Oncology, including Alan Venook, M.D.; Margaret Tempero, M.D.; Emily Bergsland, M.D.; and Andrew Ko, M.D.

With support from this award, Kelley will continue her leadership roles and participation in institutional and multisite trials at the Helen Diller Family Comprehensive Cancer Center (HDFCCC) and will apply her training, education and leadership skills to the leadership of the Clinical Research Support Office as its director.

Kelley’s long-term goal is to build upon her training and experience in translational clinical research, multidisciplinary collaborations, and experience as an executive officer for a National Clinical Trial Network to build a program in hepatobiliary cancers at UCSF as well as to contribute substantively to the design and conduct of clinical research across the HDFCCC. Former HDFCCC recipients include Ko, who received the award in 2012.

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Researchers ID enzyme that controls spread of breast cancer


UC San Diego findings offer hope for treatment.

A tumor with reduced levels of enzyme UBC13 (top) and a control tumor (bottom) that has spread to the lungs.

Researchers at the UC San Diego School of Medicine have identified an enzyme that controls the spread of breast cancer. The findings, reported in the current issue of PNAS, offer hope for the leading cause of breast cancer mortality worldwide. An estimated 40,000 women in America will die of breast cancer in 2014, according to the American Cancer Society.

“The take-home message of the study is that we have found a way to target breast cancer metastasis through a pathway regulated by an enzyme,” said lead author Xuefeng Wu, Ph.D., a postdoctoral researcher at UC San Diego.

The enzyme, called UBC13, was found to be present in breast cancer cells at two to three times the levels of normal healthy cells. Although the enzyme’s role in regulating normal cell growth and healthy immune system function is well-documented, the study is among the first to show a link to the spread of breast cancer.

Specifically, Wu and colleagues with the UC San Diego Moores Cancer Center found that the enzyme regulates cancer cells’ ability to transmit signals that stimulate cell growth and survival by regulating the activity of a protein called p38 which when “knocked down” prevents metastasis. Of clinical note, the researchers said a compound that inhibits the activation of p38 is already being tested for treatment of rheumatoid arthritis.

In their experiments, scientists took human breast cancer cell lines and used a lentivirus to silence the expression of both the UBC13 and p38 proteins. These altered cancer cells were then injected into the mammary tissues of mice.  Although the primary tumors grew in these mice, their cancers did not spread.

“Primary tumors are not normally lethal,” Wu said. “The real danger is cancer cells that have successfully left the primary site, escaped through the blood vessels and invaded new organs. It may be only a few cells that escape, but they are aggressive. Our study shows we may be able to block these cells and save lives.”

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New hospital will embrace next frontier of cancer treatment


UCSF Bakar Cancer Hospital opening Feb. 1.

The 70-bed UCSF Bakar Cancer Hospital will open Feb. 1.

When urologist Peter Carroll, M.D., M.P.H., did his residency at UCSF 30 years ago, cancer was “a word that was whispered,” a knowledgeable patient was someone who just followed doctor’s orders and oftentimes a diagnosis wasn’t made until disease was advanced.

That’s all changed with the introduction of routine use of imaging and other screening practices, in which, for example, an asymptomatic small kidney cancer might be spotted in a patient with suspected gallstones, said Carroll, interim director and head of the prostate cancer program at UCSF Helen Diller Family Comprehensive Cancer Center and associate dean of the UCSF School of Medicine.

Other pivotal advances include the development of new classes of treatments that has meant some cancers could be successfully managed as a chronic disease; and the advent of the Internet and social media providing patients with a wide window into information about their condition and prospective treatments.

“We’re witnessing a sea change in the way we respond to cancer. We’ve found that surveillance rather than treatment might be the best strategy for some low-grade cancers, while using novel therapy or combinations of treatments might offer the best chance for long-term survival for patients with some advanced cancers,” he said.

Carroll said clinicians are also learning that “treatment isn’t just determined by grade, staging, size of tumor, or even its site of origin and what it looks like under a microscope in some cases.”

“Advances in molecular biology, genomics and related technologies have led to a greater understanding of cancer at the molecular level,” he noted. “If we identify the genetic and molecular variations in each patient’s cancer cells, we can tailor treatments that target the molecular underpinnings of each patient’s disease.”

Embodying this evolution in cancer management is the new 70-bed UCSF Bakar Cancer Hospital, opening Feb. 1, 2015, at Mission Bay. It will be right down the street from the UCSF Helen Diller Family Cancer Research Building, dedicated to uncovering the basic biological mechanisms of cancer.

“It will be the ‘Emerald City’ emerging from the fog in a location surrounded by dozens of biotech companies, which will promote a synergy facilitating the bench-to-bedside process of developing innovative treatments like precision medicine,” said Carroll.

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How California measures up in fight against cancer


Ahead of other states in some areas, behind in smoking-related policies.

UC Davis' Elisa Tong (left) , Elizabeth David (right) and Lori Bremner from ACS CAN give a media briefing on ACS CAN's 2014 cancer progress report.

In a media briefing at the UC Davis Comprehensive Cancer Center today (Aug. 21), the American Cancer Society Cancer Action Network (ACS CAN) released How Do You Measure Up?, an annual report that scores each state on how they are doing in the fight against cancer.

The 2014 report shows California is ahead of other states in breast and cervical cancer screening programs, protecting young people from tanning devices and broadening Medicare eligibility. The Golden State, however, is falling far behind in smoking-related policies, which are crucial to preventing deaths from certain cancers.

“Tobacco-related cancers continue to lead to the vast majority of cancer deaths we see in the state,” said Elizabeth David, thoracic and cancer surgeon at UC Davis. “We know that 85 percent of lung cancers are caused by cigarette smoking. This year, about 16,000 people in California will be diagnosed with lung cancer and about 35 Californians will die each day from the disease.”

Smoking also increases the risk of many other cancers such as head and neck, esophageal, pancreatic, uterine, cervical, ovarian, kidney, bladder, stomach, colorectal and leukemias, she said.

Lori Bremner, board member with the ACS CAN and 37-year leukemia survivor, said California is failing in comprehensive tobacco control, which should include increasing the price of all tobacco products, implementing comprehensive smoke-free policies and fully funding and sustaining state-wide tobacco-prevention cessation programs.

“Evidence clearly shows that raising tobacco prices through taxes encourages users to quit or cut down and, most importantly, it prevents kids from ever starting,” Bremner said. “California is woefully underfunded in tobacco-prevention programs compared to what’s recommended by the U.S. Centers for Disease Control and Prevention.”

Elisa Tong, an associate professor of internal medicine who conducts research on tobacco control, said California has more than 4 million smokers, which cost the state $9 billion a year in health care expenses.

“In Sacramento, we actually have the highest smoking prevalence rate among California’s urban areas,” said Tong, who said smoke-free policies are crucial for cancer prevention and to help people quit smoking.

“We can address tobacco-cessation at a patient level, but with comprehensive smoke-free policies, we can address the whole environment the patient lives in,” she added.

In 2014, it is estimated that more than 1.6 million people in the United States will be diagnosed with cancer and more than 580,000 people will die from the disease. In California this year, an estimated 155,920 will be diagnosed with cancer and a predicted 153 people will perish daily from the disease.

To view the complete How Do You Measure Up? report, visit www.acscan.org.

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Nanoparticles show promise for cancer treatment, possible HIV cure


UCLA-led team engineers vault nanoparticles to create novel drug delivery system.

A multidisciplinary team of scientists from UCLA and Stanford University has used a naturally occurring nanoparticle called a vault to create a novel drug delivery system that could lead to advances in the treatment of cancer and HIV.

The research team was led by Dr. Leonard Rome, associate director of UCLA’s California NanoSystems Institute, and Dr. Jerome Zack, co-director of the UCLA AIDS Institute, both of whom are also members of UCLA’s Jonsson Comprehensive Cancer Center. Co-first authors on the study were Daniel Buehler, a UCLA postdoctoral researcher and Matthew Marsden, adjunct assistant professor in the department of medicine and a member of the AIDS Institute.

Their findings could lead to cancer treatments that are more effective with smaller doses and to therapies that could potentially eradicate the HIV virus.

The paper is the cover story of the Aug. 26 print edition of the journal ACSNano, and it was recently published online.

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