TAG: "Cancer"

New brain cancer treatment may be more effective, less toxic

Results of UCSF clinical trial may change standard of care for primary CNS lymphoma.

James Rubenstein, UC San Francisco

A phase two clinical trial testing a new protocol for treating a relatively rare form of brain cancer, primary CNS lymphoma, may change the standard of care for this disease, according to doctors at UC San Francisco who led the research.

Described this week in the Journal of Clinical Oncology, the trial involved 44 patients who were given a combination of high-dose chemotherapy with immune therapy, rather than the standard combination of chemotherapy with a technique known as whole-brain radiotherapy.

The new treatment approach was significantly less toxic because it avoided whole-brain radiotherapy, which at high doses can kill brain cells and lead to a progressive deterioration of the function of the nervous system in patients. Many patients die from the toxicity of the radiation as opposed to the cancer itself.

The new treatment also seemed to work better, with the majority of patients on the trial still alive with a follow-up of nearly five years, researchers found.

The lymphoma-free survival of patients with this form of brain cancer was doubled compared to the lymphoma-free survival in previous multicenter U.S. cooperative-group-sponsored clinical trials involving brain radiotherapy, said UCSF oncologist James Rubenstein, M.D., Ph.D., associate professor of medicine, who led the study.

In addition, unlike previous treatments for primary CNS lymphoma, the new approach was equally effective in older patients – those over 60 – as it was in younger patients. This is particularly significant given that the incidence of this type of brain tumor appears to be increasing in patients 65 and older.

Rubenstein is a member of the UCSF Helen Diller Family Comprehensive Cancer Center, which is one of the country’s leading research and clinical care centers, and is the only comprehensive cancer center in the San Francisco Bay Area.

The work raises the possibility of taking a “personalized medicine” approach to guiding treatment for this form of cancer because the researchers identified a biomarker – a gene called BCL6 – which could predict the outcome of treatment depending on how much of the gene was present in the tumor.

A randomized clinical trial, which will test the effectiveness of the new therapeutic approach in a larger patient population, is now enrolling at UCSF and at other medical centers in the United States.

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Inaugural cancer research fellows class includes 11 from UC

AACR honors distinguished scientists.

Shinya Yamanaka, UC San Francisco

Eleven University of California scientists, including five Nobel laureates, are being inducted into the prestigious inaugural class of fellows of the American Association for Cancer Research Academy.

The new academy has been created to recognize individuals who have made exceptional contributions to cancer or to cancer-related biomedical science. Membership in the new academy is the most prestigious honor bestowed by the American Association for Cancer Research (AACR), the world’s oldest and largest scientific organization focused on preventing and curing cancer.

Also, the association will recognize UCLA’s Roger Lo, M.D., Ph.D.,  with the 33rd Annual AACR Award for Outstanding Achievement in Cancer Research at its annual meeting. Lo is an assistant professor in the department of medicine, division of dermatology at the David Geffen School of Medicine at UCLA, with a joint appointment in the department of medical and molecular pharmacology, and a member of the Signal Transduction and Therapeutic Program at UCLA’s Jonsson Comprehensive Cancer Center.

The inaugural class of 106 AACR Academy members who will be inducted today (April 5) include:

UC Irvine

  • Irwin Rose, Ph.D., Nobel laureate, distinguished professor emeritus of physiology and biophysics


  • Dennis Slamon, M.D., Ph.D., director of clinical/translational research, director of the Revlon/UCLA Women’s Cancer Research Program at Jonsson Comprehensive Cancer Center, professor of medicine, chief of the division of hematology/oncology and executive vice chair for research for UCLA’s Department of Medicine

UC San Diego

  • Webster Cavenee, Ph.D., director of the Ludwig Institute for Cancer Research and distinguished professor
  • Napoleone Ferrara, M.D., distinguished professor of pathology and senior deputy director for basic sciences at Moores Cancer Center
  • Roger Tsien, Ph.D., Nobel laureate, professor of pharmacology, chemistry and biochemistry

UC San Francisco

  • J. Michael Bishop, M.D., Nobel laureate and chancellor emeritus of UCSF;
  • Elizabeth Blackburn, Ph.D., Nobel laureate and UCSF professor of biochemistry and biophysics;
  • Yuet Wai Kan, M.D., UCSF professor of hematology;
  • Frank McCormick, Ph.D., director of the Helen Diller Family Comprehensive Cancer Center, and associate dean of the UCSF School of Medicine;
  • Shinya Yamanaka, M.D., Ph.D., Nobel laureate, UCSF professor of anatomy and senior investigator at the Gladstone Institute of Cardiovascular Disease.

Lawrence Berkeley National Laboratory

  • Mina Bissell, Ph.D., distinguished scientist, life sciences division

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Symposium highlights breast cancer research advances

Event will be May 17-18 in Costa Mesa.

The California Breast Cancer Research Program will host a symposium to discuss the latest studies and key national issues affecting research on the disease on May 17 and 18 in Costa Mesa.

Scientists, advocates, health care providers, policymakers and community members will share recent advances in breast cancer prevention, detection, treatment and survivorship research and look ahead to new research directions.

The symposium, “From Research to Action: Two Decades of Change,” commemorates 20 years of work by the California Breast Cancer Research Program (CBCRP), which is administered by the University of California Office of the President on behalf of the state of California. Since its establishment in 1993 by the state Legislature, the CBCRP has been hailed for its innovative research and for involving advocates and community members in charting research strategies.

“The symposium is an opportunity for people who are affected by breast cancer to meet with the experts who are working on ways to halt the disease,” said Mhel Kavanaugh-Lynch, M.D., M.P.H., director of the CBCRP. “Among the goals is to give everyone a good understanding of the interactions between research and policy, how each drives the other, and the implications for future breast cancer research, prevention and care.”

Symposium highlights include:

  • Sessions on the environmental impacts on breast cancer risk, including discussion of a recent federal report, “Breast Cancer and the Environment: Prioritizing Prevention,” which outlines a new path for future research. A panel to discuss the impact of the report on communities will include division directors of the National Institute of Environmental Health Sciences and the National Cancer Institute.
  • A program on the “Role of Research in Setting Breast Cancer Policy.” Panelists will discuss how laws on genetic patents and privacy and health care reform will shape team research, patient recruitment and health care in the years ahead.
  • “Breast Cancer 101,” a workshop on the fundamentals of breast cancer basic science and clinical outcomes for symposium attendees who do not have a background in scientific research.

In addition to some of the top breast cancer researchers in the state, keynote speakers will be:

  • Susan Love, M.D., president of the Dr. Susan Love Research Foundation, whose address is titled “Pushing the Envelope: 20 Years of Pioneering Breast Cancer Research in California.”
  • Dennis Slamon, M.D., Ph.D, director of UCLA Clinical/Translational Research and the Revlon/UCLA Women’s Cancer Research Program at the JonssonComprehensive Cancer Center. Slamon and his colleagues conducted the laboratory and clinical research that led to the development of the breast cancer drug Herceptin.

The symposium will take place at the Hilton Orange County/Costa Mesa. The registration fee is $25, and the deadline to register is April 26. To register go to: http://cbcrp.org/symposium/registration2013/choose.asp

For more information about the symposium, visit: http://cbcrp.org/symposium

About the California Breast Cancer Research Program

The mission of the California Breast Cancer Research Program (CBCRP) is to eliminate breast cancer by leading innovation in research, communication and collaboration in the California scientific and lay communities.

Created by the state Legislature in 1993, the CBCRP is the largest state-funded breast cancer research program in the nation and is administered by the University of California Office of the President. To date, the CBCRP has awarded 939 grants to 107 scientific institutions and community entities, totaling more than $230 million for research in California to prevent, treat and cure breast cancer. Grants from the CBCRP fill gaps not traditionally funded by other research programs to jump-start new areas of investigation that push the boundaries of research and foster new collaborations.

The CBCRP is funded through the voluntary tax check-off program on personal income tax form 540, a portion of the state tobacco tax and individual contributions. For more information, visit cabreastcancer.org.

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Dietary fish oils show promise against cancer

Fatty acid metabolite can slow tumor growth in mice.

Guodong Zhang, UC Davis

Guodong Zhang, UC Davis

A team of UC Davis scientists has found that a product resulting from a metabolized omega-3 fatty acid helps combat cancer by cutting off the supply of oxygen and nutrients that fuel tumor growth and spread of the disease.

The scientists report their discovery in the Proceedings of the National Academy of Sciences (PNAS). The groundbreaking study was a collaboration among multiple UC Davis laboratories and Harvard University.

The metabolite is epoxy docosapentaenoic acid (EDP), an endogenous compound produced by the human body from the omega-3 fatty acid named docosahexaenoic acid (DHA), which is found in fish oil and breast milk. In animal studies, the UC Davis scientists found that EDP inhibits angiogenesis, the formation of new blood vessels in the body.

Tumors grow and spread by hijacking the normal biological process of angiogenesis, which plays a role in wound repair as well in growth and development. The UC Davis researchers determined that by inhibiting angiogenesis, EDP reduces the growth and spread (metastasis) of tumors in mice. The research provides the first scientific evidence about EDP’s potent anti-cancer, anti-metastatic effects.

EDP works by a different mechanism than many current anti-cancer drugs that block angiogenesis.

“Our investigation opens up a new understanding of the pathways by which omega-3 fatty acids exert their biologic effects,” said Guodong Zhang, the lead author of the article and a postdoctoral researcher in the laboratory of Bruce Hammock in the Department of Entomology and the UC Davis Comprehensive Cancer Center.

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How genes turn on and off

New insights could enhance our understanding of human development, cancer therapies and autism.

Janine LaSalle, UC Davis

Janine LaSalle, UC Davis

Researchers at UC Davis and the University of British Columbia have shed new light on methylation, a critical process that helps control how genes are expressed. Working with placentas, the team discovered that 37 percent of the placental genome has regions of lower methylation, called partially methylated domains (PMDs), in which gene expression is turned off. This differs from most human tissues, in which 70 percent of the genome is highly methylated.

While PMDs have been identified in cell lines, this is the first time they have been found in regular human tissue. In addition to enhancing our understanding of epigenetics, this work could influence cancer research and help illuminate how environmental toxins affect fetal development. The paper was published online this week in the Proceedings of the National Academy of Sciences (PNAS).

Since it was unraveled more than ten years ago, the human genome has been the focus of both popular interest and intense scientific focus. But the genome doesn’t act alone; there are many factors that influence whether genes are turned on or off. One of these is an epigenetic process called methylation, in which a group of carbon and hydrogen atoms (a methyl group) attaches to DNA, adjusting how genes are expressed.

“I like to think of epigenetics as a layer on top of your genetic code,” said senior author Janine LaSalle, professor of medical microbiology and immunology. “It’s not the DNA sequence but it layers on top of that — and methylation is the first layer. Those layers provide a lot of information to the cells on where and when to turn on the genes.”

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Kidney-sparing surgery underutilized for those who need it most

National treatment trends raise concerns about rise of kidney removals.

Ithaar Derweesh, UC San Diego

Ithaar Derweesh, UC San Diego

Researchers at the UC San Diego School of Medicine have released study results that show national treatment trends in the surgical management of patients with kidney disease.

The study found that partial and complete kidney removal (total nephrectomy) and energy-based techniques to destroy tumors are all on the rise. Surprisingly, the patients most in need of kidney-sparing surgery are still more likely to undergo total nephrectomy. The findings recently published online in BJU International.

“While the overall proportion of patients receiving kidney preserving treatments for localized kidney tumors continues to grow, the most significant, and perhaps unsettling finding was that patients with kidney insufficiency still undergo complete kidney removal – even though kidney preserving treatment may be indicated,” said senior author Ithaar Derweesh, M.D., urologic oncologist at UC San Diego Moores Cancer Center.

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Monoclonal antibody targets, kills leukemia cells

Findings represent potential new therapy for treating patients with blood cancer.

Chronic lymphocytic leukemia cells

Researchers at the UC San Diego Moores Cancer Center have identified a humanized monoclonal antibody that targets and directly kills chronic lymphocytic leukemia (CLL) cells.

The findings, published in the online early edition of the Proceedings of the National Academy of Sciences today (March 25) represent a potential new therapy for treating at least some patients with CLL, the most common type of blood cancer in the United States.

CLL cells express high levels of a cell-surface glycoprotein receptor called CD44.  Principal investigator Thomas Kipps, M.D., Ph.D., Evelyn and Edwin Tasch Chair in Cancer Research, and colleagues identified a monoclonal antibody called RG7356 that specifically targeted CD44 and was directly toxic to cancer cells, but had little effect on normal B cells.

Moreover, they found RG7356 induced CLL cells that expressed the protein ZAP-70 to undergo apoptosis or programmed cell death. Roughly half of CLL patients have leukemia cells that express ZAP-70.  Such patients typically have a more aggressive form of the disease than patients with CLL cells that do not express that specific protein.

Previous research by Kipps and others has shown that CLL cells routinely undergo spontaneous or drug-induced cell death when removed from the body and cultured in the laboratory. They found that CLL cells receive survival signals from surrounding non-tumor cells that are present in the lymph nodes and bone marrow of patients with CLL. One of these survival signals appears to be transmitted through CD44. However, when CD44 is bound by the RG7356 monoclonal antibody, it seems to instead convey a death signal to the leukemia cell.

“By targeting CD44, it may be possible to kill CLL cells regardless of whether there are sufficient numbers of so-called ‘effector cells,’ which ordinarily are required by other monoclonal antibodies to kill tumor cells,” said Kipps. “We plan to initiate clinical trials using this humanized anti-CD44 monoclonal antibody in the not-too-distant future.”

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Research on immune-cell therapy could strengthen promising cancer treatment

UCLA, Caltech researchers successfully monitor change in genetically modified T cells.

James Heath, UCLA

A new study of genetically modified immune cells by scientists from UCLA and the California Institute of Technology could help improve a promising treatment for melanoma, an often fatal form of skin cancer.

The research, which appears today (March 21) in the advance online edition of the journal Cancer Discovery, was led by James Heath, a member of UCLA’s Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research and UCLA’s Jonsson Comprehensive Cancer Center. Heath is a professor of molecular and medical pharmacology at UCLA and also holds the Elizabeth W. Gilloon Chair in Chemistry at Caltech.

The melanoma treatment uses T cells — immune cells that play a major role in fighting infection — taken from patients with melanoma. The cells are then genetically modified in the laboratory so that when they are reintroduced into a patient’s bloodstream, they specifically attack melanoma tumors. In early clinical trials, this treatment was shown to shrink tumors dramatically in many patients, but the positive effects were often short-lived.

The UCLA and Caltech researchers found that after the engineered T cells were returned to patients, their efficacy faded within two to three weeks. Surprisingly, however, once the engineered cells were no longer effective, a new group of non-engineered T cells arose that had a similar tumor-killing effect that lasted even longer, the scientists discovered.

Using newly developed nanotechnology chips to perform multidimensional and multiplexed immune-monitoring assays, the researchers were able to examine at high resolution single engineered T cells taken at different times from patients undergoing the therapy, each of whom had a different level of response to the treatment.

“The engineered T cells did not recover their tumor-killing effect,” Heath said, “but after one month, another group of T cells appeared that did have tumor-killing effects for another 90 days. Those were not the genetically engineered T cells, and they appeared to be a byproduct of a process called ‘antigen spreading’ by the original engineered cells. After 90 days, those cells lost their tumor-killing ability as well.”

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Imaging agent enables better cancer detection

Dye developed at UC San Diego finds, stages cancers more accurately.

Anne Wallace, UC San Diego

Anne Wallace, UC San Diego

Researchers at the UC San Diego School of Medicine have shown that a new imaging dye, designed and developed at UC San Diego Moores Cancer Center, is an effective agent in detecting and mapping cancers that have reached the lymph nodes. The radioactive dye called Technetium Tc-99m tilmanocept, successfully identified cancerous lymph nodes and did a better job of marking cancers than the current standard dye. Results of the phase three clinical trial published online Tuesday in the Annals of Surgical Oncology.

“Tilmanocept is a novel engineered radiopharmaceutical specifically designed for sentinel lymph node detection,” said David R. Vera, Ph.D., the drug’s inventor, who is a professor in the UCSD Department of Radiology. “The molecule, developed at UC San Diego School of Medicine, offers surgeons a new tool to accurately detect and stage melanoma and breast cancers while in the operating room.”

On March 13, tilmanocept received U.S. Food and Drug Administration approval.

After a cancer diagnosis, surgeons want to be sure that the disease has not spread to a patient’s lymph nodes, especially the sentinel nodes that may be the first place that a cancer reaches. The lymphatic system is a network of vessels and ducts that carry disease-fighting cells throughout the body, but can also act as a way for cancer cells to access the bloodstream.  By surgically removing and examining the sentinel nodes that drain a tumor, doctors can better determine if a cancer has spread.

“Tilmanocept advances the molecular targeting in breast cancer. It’s the first agent that is binding to a lymph node because it is a lymph node that plays an important role in metastasis,” said Anne Wallace, M.D., professor of surgery, UC San Diego School of Medicine and principal investigator of the study.  “Tilmanocept’s ability to identify more cancer containing nodes will lead to better post-operative care for patients, especially those patients who had more than one positive sentinel node.”

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Awards guide promising early-stage research toward patient benefit

UCSF’s Clinical and Translational Science institute funds Catalyst Awards.

Mary Nakamura, UC San Francisco

An innovative project to develop a potential therapy to treat a wide range of cancers has won a major UC San Francisco award that aims to drive promising early-stage research through the complex process of translating ideas into patient benefit.

The Catalyst Awards, which combine funding with customized expert feedback and advice, announced winners for its fall 2012 cycle. Funded by UCSF’s Clinical and Translational Science Institute (CTSI), the awards focus on the development of four areas: therapeutics, diagnostics, devices and now also digital health.

This cycle’s top, $100,000 award went to Mary Nakamura, M.D., an associate professor in residence in the UCSF School of Medicine. Funding for her proposal – “A Recombinant Fusion Protein that redirects VEGF to actively kill cancer cells: R1FasL” – will support additional research to test the efficacy and safety of using an artificial protein, known as R1FasL, in cancer treatment.

“I think [the Catalyst Award program] creates a target for people who have innovative ideas to help move their work forward. That just hasn’t existed in academia before,” said Keith Yamamoto, Ph.D., vice chancellor for research at UCSF and one of several UCSF leaders on hand for presentations by the 20 Catalyst Award finalists.

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UC Davis research advances efforts to prevent dangerous blood clots

Study will help physicians calculate risk of post-surgical venous thromboembolisms.

Robert Canter, UC Davis

New research from the UC Davis Comprehensive Cancer Center, published in the Journal of Surgical Research, may help clinicians determine which patients are at highest risk for post-surgical blood clots in the legs or lungs.

A team led by Robert Canter, UC Davis associate professor of surgery, studied the medical histories of more than 470,000 surgical patients to determine which factors increased their risk of blood clots, also called venous thromboembolism (VTE). The team then created a nomogram, a type of calculator, which can help clinicians predict an individual’s 30-day VTE risk. The results could change clinical practice by providing a more rational approach to preventing dangerous blood clots.

Blood clots are a critical safety and quality challenge for hospitals around the nation. While they can be prevented by administering blood thinners, such as heparin, these measures increase the risk of bleeding. To complicate matters, clinicians have had no way of determining which patients are at higher risk for blood clots, forcing them to adopt a one-size-fits-all approach to prevention.

“The standard preventive measure is heparin,” said Canter. “However, there are many questions surrounding its use: What type of heparin should be administered? What dosage? Should we give it to patients before or after surgery? By identifying patients who are at higher risk for VTE, we attempt to answer many of these questions and help to personalize treatment.”

Blood clots of the legs or lungs are a serious surgical complication, which can cause shortness of breath, longer hospital stays and, in rare cases, death. Successful treatment often requires patients to take the blood thinner Coumadin for three to six months after discharge.

The researchers combed through the American College of Surgeons National Surgical Quality Improvement (ACS-NSQIP) database to identify 471,000 patients who underwent abdominal or thoracic surgeries between 2005 and 2010. Their goal was to identify VTE events within 30 days of surgery, both in the hospital and after discharge (VTEDC). VTE includes deep vein thrombosis (clots in the legs) or pulmonary embolism (clots in the lungs).

The team considered many patient factors: age, body mass index (BMI), gender, race, pre-existing conditions, medical history, smoking and others. The group also factored in different approaches to surgery—abdominal, thoracic, laparoscopic, etc. — as well as the specific procedure type such as gastrointestinal, hernia, bariatric, splenectomy or lung. They also looked at post-operative complications, as these could affect both the length of stay and blood clot prevention efforts.

“There are a multitude of factors that go into whether a patient is at risk for VTE, as well as how to prevent it,” said Canter. “Prior to this study, no one had ever looked at so many of these factors so comprehensively.”

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Innovation Profile: Greg Maynard: Stopping blood clots, saving lives

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UC medical centers honored for oncology programs

Four UC med centers among 100 singled out by Becker’s Hospital Review.

UC Davis Medical Center buildingMedical centers at UC Davis, UCLA, UC San Diego and UC San Francisco have been named among “100 Hospitals and Health Systems with Great Oncology Programs” by Becker’s Hospital Review, a national publication geared to hospital and health system leaders.

The Becker’s Hospital Review editorial team selected the hospitals based on clinical accolades, quality care and contributions to the field of oncology. The ranking recognizes hospitals that are “on the cutting edge of cancer treatment, prevention and research,” according to the publication.

The editorial board considers the ratings of reputable health-care resources including U.S. News & World Report, the National Cancer Institute, the American College of Surgeons and other credentialing organizations when making selections.

“Each organization has demonstrated a focus on patient-centered cancer care and emphasis on continual innovation in treatments and services,” according to the publication’s press release. “Many of these organizations also have a place in the history of cancer prevention and research, as they‘ve driven groundbreaking discoveries and made clinical milestones.”

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