TAG: "Cancer"

Health food store product shows promise for treating prostate cancer


Mushroom-supplemented soybean extract could extend life expectancy in advanced cases.

Paramita Ghosh, UC Davis

Paramita Ghosh, UC Davis

A natural, nontoxic product called genistein-combined polysaccharide, or GCP, which is commercially available in health stores, could help lengthen the life expectancy of certain prostate cancer patients, UC Davis researchers have found.

Men with prostate cancer that has spread to other parts of the body, known as metastatic cancer, and who have had their testosterone lowered with drug therapy are most likely to benefit. The study, recently published in the journal Endocrine-Related Cancer, was conducted in prostate cancer cells and in mice.

Lowering of testosterone, also known as androgen-deprivation therapy, has long been the standard of care for patients with metastatic prostate cancer, but life expectancies vary widely for those who undergo this treatment. Testosterone is an androgen, the generic term for any compound that stimulates or controls development and maintenance of male characteristics by binding to androgen receptors.

The current findings hold promise for GCP therapy as a way to extend life expectancy of patients with low response to androgen-deprivation therapy.

Paramita Ghosh, an associate professor in the UC Davis School of Medicine, led the pre-clinical study with a team that included UC Davis Comprehensive Cancer Center Director Ralph de Vere White, a UC Davis distinguished professor of urology. Ruth Vinall in the UC Davis Department of Urology and Clifford Tepper in the UC Davis Department of Biochemistry and Molecular Medicine directed the studies in mice; Ghosh’s laboratory conducted the cell studies.

The research focused on GCP, a proprietary extract cultured from soybeans and shiitake mushrooms and marketed by Amino-Up of Sapporo, Japan. Researchers found that the combination of the compounds genistein and daidzein, both present in GCP, helps block a key mechanism used by prostate cancer cells to survive in the face of testosterone deprivation.

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Check the box, fund cancer research


Funding UC cancer research programs is as easy as checking a box on state tax return form.

Californians can file their taxes and, at the same time, join the fight against cancer.

It’s simple. On your state income tax return form, check line 405 and/or 413. Contributions — and none is too small — go to the California Breast Cancer Research Fund (line 405) and the California Cancer Research Fund (line 413).

Both funds are administered by two UC programs that are renowned not only for innovative research, but also for working with health care and community advocates in targeting the issues and needs of cancer patients and families, especially the underserved.

Last year, the two funds received a combined $873,000. Contributions from 2012 tax filers averaged about $14.

That money goes a long way, supporting researchers across the state as they investigate new ways to prevent, detect, treat and cure cancer. (See box for links to examples of funded research.) Next year, an estimated 144,800 Californians will be diagnosed with cancer and 55,415 will die of the disease, according to the American Cancer Society and the California Department of Public Health.

The UC Tobacco-Related Disease Research Program (TRDRP) has administered the California Cancer Research Fund (line 413) since the fund’s inception in 2009.

“Cancer is a challenging disease to treat,” said Bart Aoki, director of TRDRP. “The problem is compounded by pronounced disparities in the incidence and mortality.”

Funds from the tax checkoff are directed toward research on diagnosis and treatment of all cancers, as well as to dissemination of timely information about cancer prevention and early diagnosis to disproportionately impacted communities, he said.

“The generous contributions Californians make to the California Breast Cancer Research Fund [line 405] enable us to support research in new areas that otherwise would not be explored,” said Marion Kavanaugh-Lynch, director of the UC California Breast Cancer Research Program (CBCRP).

Over the years, the state’s tax checkoff has funded nearly $10 million in research grants awarded throughout California by CBCRP.

These are aimed at developing tests to detect breast cancer, identifying environmental factors that may cause the disease, exploring innovative therapies to thwart the cancer and improving support networks to help patients and families navigate a sometimes daunting health care system.

And to support this research, many tax filers don’t even need to write a check (if they’re getting a refund). They may simply check line 405 and/or 413 on their tax form.

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Golden retriever study suggests neutering affects dog health


Study of 759 dogs finds a doubling of hip dysplasia among males neutered before age 1.

Neutering, and the age at which a dog is neutered, may affect the animal’s risk for developing certain cancers and joint diseases, according to a new study of golden retrievers by a team of researchers at the University of California, Davis.

The study, which examined the health records of 759 golden retrievers, found a surprising doubling of hip dysplasia among male dogs neutered before one year of age. This and other results will be published today (Feb. 13) in the online scientific journal PLOS ONE.

“The study results indicate that dog owners and service-dog trainers should carefully consider when to have their male or female dogs neutered,” said lead investigator Benjamin Hart, a distinguished professor emeritus in the UC Davis School of Veterinary Medicine.

“It is important to remember, however, that because different dog breeds have different vulnerabilities to various diseases, the effects of early and late neutering also may vary from breed to breed,” he said.

While results of the new study are revealing, Hart said the relationship between neutering and disease-risk remains a complex issue. For example, the increased incidence of joint diseases among early-neutered dogs is likely a combination of the effect of neutering on the young dog’s growth plates as well as the increase in weight on the joints that is commonly seen in neutered dogs.

Dog owners in the United States are overwhelmingly choosing to neuter their dogs, in large part to prevent pet overpopulation or avoid unwanted behaviors. In the U.S., surgical neutering — known as spaying in females — is usually done when the dog is less than 1 year old.

In Europe, however, neutering is generally avoided by owners and trainers and not promoted by animal health authorities, Hart said.

During the past decade, some studies have indicated that neutering can have several adverse health effects for certain dog breeds. Those studies examined individual diseases using data drawn from one breed or pooled from several breeds.

Against that backdrop, Hart and colleagues launched their study, using a single hospital database. The study was designed to examine the effects of neutering on the risks of several diseases in the same breed, distinguishing between males and females and between early or late neutering and non-neutering.

The researchers chose to focus on the golden retriever because it is one of the most popular breeds in the U.S. and Europe and is vulnerable to various cancers and joint disorders. The breed also is favored for work as a service dog.

The research team reviewed the records of female and male golden retrievers, ranging in age from 1 to 8 years, that had been examined at UC Davis’ William R. Pritchard Veterinary Medical Teaching Hospital for two joint disorders and three cancers: hip dysplasia, cranial cruciate ligament tear, lymphosarcoma, hemangiosarcoma and mast cell tumor. The dogs were classified as intact (not neutered), neutered early (before 12 months age), or neutered late (at or after 12 months age).

Joint disorders and cancers are of particular interest because neutering removes the male dog’s testes and the female’s ovaries, interrupting production of certain hormones that play key roles in important body processes such as closure of bone growth plates, and regulation of the estrous cycle in female dogs.

The study revealed that, for all five diseases analyzed, the disease rates were significantly higher in both males and females that were neutered either early or late compared with intact (non-neutered) dogs.

Specifically, early neutering was associated with an increase in the occurrence of hip dysplasia, cranial cruciate ligament tear and lymphosarcoma in males and of cranial cruciate ligament tear in females. Late neutering was associated with the subsequent occurrence of mast cell tumors and hemangiosarcoma in females.

In most areas, the findings of this study were consistent with earlier studies, suggesting similar increases in disease risks. The new study, however, was the first to specifically report an increased risk of late neutering for mast cell tumors and hemangiosarcoma.

Furthermore, the new study showed a surprising 100 percent increase, or doubling, of the incidence of hip dysplasia among early-neutered males. Earlier studies had reported a 17 percent increase among all neutered dogs compared to all non-neutered dogs, indicating the importance of the new study in making gender and age-of-neutering comparisons.

Other researchers on this UC Davis study were: Gretel Torres de la Riva, Thomas Farver and Lynette Hart, School of Veterinary Medicine; Anita Oberbauer, Department of Animal Science; Locksley Messam, Department of Public Health Sciences; and Neil Willits, Department of Statistics.

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UCSF researchers pinpoint stem cell survival strategy


Autophagy key to blood and immune system health, but may increase cancer risk.

Leukemia cells

Leukemia cells

Stem cells of the aging bone marrow recycle their own molecules to survive and keep replenishing the blood and immune systems as the body ages, researchers at UC San Francisco have discovered.

The recycling process, known as autophagy, or self-eating, involves reusing molecules and the chemical energy obtained from these molecules to withstand the killing effect of metabolic stress that intensifies as the body ages.

The discovery, reported online Feb. 6 in the journal Nature, showed that autophagy allows stem cells to avoid the alternative response to stress, which is programmed cellular suicide, in which cells that aren’t up to snuff kill themselves for the greater good.

While this trick of autophagy may help delay the onset of anemia, immune-system failure and other maladies that occur with age, as a survival strategy it is a bit of a compromise, said the senior author of the study, Emmanuelle Passegué, Ph.D., of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF.

Autophagy might increase cancer risk, she said, by allowing old stem cells to survive despite having accumulated risky mutations over a lifetime.

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New details on the molecular machinery of cancer


Berkeley Lab researchers resolve EGFR activation mystery.

Jay Groves, Berkeley Lab

Jay Groves, Berkeley Lab

Researchers with Lawrence Berkeley National Laboratory and UC Berkeley have provided important new details into the activation of the epidermal growth factor receptor (EGFR), a cell surface protein that has been strongly linked to a large number of cancers and is a major target of cancer therapies.

“The more we understand about EGFR and the complex molecular machinery involved in the growth and proliferation of cells, the closer we will be to developing new and more effective ways to cure and treat the many different forms of cancer,” says chemist Jay Groves, one of the leaders of this research. “Through a tour-de-force of quantitative biology techniques that included cutting edge time-resolved fluorescence spectroscopy in living cells, Nuclear Magnetic Resonance, and computational modeling, we’ve determined definitively how EGFR becomes activated through to its epidermal growth factor (EGF) ligand.”

Groves, who holds joint appointments with Berkeley Lab’s Physical Biosciences Division and UC Berkeley’s Chemistry Department and is also a Howard Hughes Medical Institute (HHMI) investigator, is one of two corresponding authors of a paper in the journal Cell that describes this research. The paper is titled “Conformational Coupling across the Plasma Membrane in Activation of the EGF Receptor.” The other corresponding author is John Kuriyan, who also holds joint appointments with Berkeley Lab, UC Berkeley and HHMI.

In high school biology classes we learn that genes contain coded instructions that are translated into the assembly of specific proteins. Many proteins, however, must be activated by post-translational processes such as autophosphorylation, the addition of phosphate. Protein activation can impact many important cellular processes including proliferation, differentiation and migration. Cancer is essentially a case of these cellular functions gone wild, often the result of problems with the EGFR. However, despite its well-established links to cancer, EGFR activation has only been partially understood.

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New details on the molecular machinery of cancer


Berkeley Lab researchers resolve EGFR activation mystery.

Jay Groves, Berkeley Lab

Researchers with Lawrence Berkeley National Laboratory and the UC Berkeley have provided important new details into the activation of the epidermal growth factor receptor (EGFR), a cell surface protein that has been strongly linked to a large number of cancers and is a major target of cancer therapies.

“The more we understand about EGFR and the complex molecular machinery involved in the growth and proliferation of cells, the closer we will be to developing new and more effective ways to cure and treat the many different forms of cancer,” says chemist Jay Groves, one of the leaders of this research. “Through a tour-de-force of quantitative biology techniques that included cutting edge time-resolved fluorescence spectroscopy in living cells, Nuclear Magnetic Resonance, and computational modeling, we’ve determined definitively how EGFR becomes activated through to its epidermal growth factor (EGF) ligand.”

Groves, who holds joint appointments with Berkeley Lab’s Physical Biosciences Division and UC Berkeley’s Chemistry Department, and is also a Howard Hughes Medical Institute (HHMI) investigator is one of two corresponding authors of a paper in the journal Cell that describes this research. The paper is titled “Conformational Coupling across the Plasma Membrane in Activation of the EGF Receptor.” The other corresponding author is John Kuriyan, who also holds joint appointments with Berkeley Lab, UC Berkeley and HHMI.

In high school biology classes we learn that genes contain coded instructions that are translated into the assembly of specific proteins. Many proteins, however, must be activated by post-translational processes such as autophosphorylation, the addition of phosphate. Protein activation can impact many important cellular processes including proliferation, differentiation and migration. Cancer is essentially a case of these cellular functions gone wild, often the result of problems with the EGFR. However, despite its well-established links to cancer, EGFR activation has only been partially understood.

“As a member of the large class of cell surface receptors known as receptor tyrosine kinases, EGFR features a ligand-binding domain on its extracellular side and a kinase domain on its intracellular side,” Groves says. “The text-book explanation for EGFR activation is that the binding of EGFR’s ligand, EGF, to its extracellular side induces dimerization of the receptor, which in turn brings together the kinase domains on the intracellular sides of the dimer, allowing them to phosphorylate one another.”

Groves says while the picture is accurate, it is an oversimplification of the mechanics behind the process because isolated intracellular kinase domains in solution can be active on their own at relatively low concentration without EGF ligand-induced dimerization. Dimerization is the combining of two identical molecules into a single compound molecule.

Measuring autophosphorylation as a function of EGFR surface density in cells, Groves, Kuriyan and their colleagues found that structural coupling between the EGFR transmembrane helix and extracellular juxtamembrane modules in addition to EGF ligand-engagement is required for EGFR activation. This structural coupling permits dimerization to take place in the presence of the EGF ligand.

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Breakfast with Champions to benefit prostate cancer research


UC San Diego event Feb. 22 will feature Pro Football Hall of Famers.

Breakfast with Champions logoThe University of California, San Diego, will host its first-ever fundraiser for prostate cancer research, “Breakfast with Champions,” on Friday, Feb. 22, at the La Jolla Country Club. The event will feature Pro Football Hall of Famers and prostate cancer survivors Mike Haynes and Deacon Jones, who will discuss their experiences as champions, both on and off the field. The public is invited; all proceeds from the event will benefit prostate cancer research at the UC San Diego School of Medicine.

Prostate cancer is one of the most common forms of cancer among men in the United States, just second to non-melanoma skin cancer. According to the American Cancer Society’s estimates for 2013, roughly 1 in 6 men will be diagnosed with the disease.

“We have developed a world-class program for prostate cancer patients at the UC San Diego Moores Cancer Center with the goal of better serving the families in our community,” said Christopher Kane, M.D., chief of the Division of Urology at UC San Diego’s School of Medicine. “The most important goal is to provide compassionate and excellent care, from meticulous surgery to technologically advanced radiation therapy and the most experienced care for men with high risk and advanced disease.”

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New strategies pinpoint breast cancer risk, spare many from agony


State tax checkoff helps fund cancer research.

With the help of donations from state tax filers, the California Breast Cancer Research Program funds innovative research. Studies have led to simple tests that guide treatment by distinguishing non-invasive forms of the cancer from aggressive types.

Every year, a small lump in the breast or a suspect speck on a mammogram leads 40,000 women in the U.S. to a diagnosis of the most common form of non-invasive cancer.

The condition — ductal carcinoma in situ, or DCIS — is most often harmless. The pre-cancer cells are usually confined to breast milk ducts and lie dormant, posing no threat. But 15 percent of DCIS cases give rise to invasive cancer and, until now, oncologists had no way to tell one from the other.

As a result, women with DCIS have had two basic options: Wait and hope that the condition won’t advance to an aggressive cancer, or choose to treat it now as a potential life threat.

The second choice leads to a full or partial mastectomy, often followed by radiotherapy or hormone treatment. Whatever the decision, it comes with heightened anxiety. And those who choose treatment face pain, discomfort and often high medical costs — all for a condition that only leads to cancer about one time out of five.

In 2007, after 10 years of research, a team of UCSF scientists developed the first simple test that may spare about half of the women diagnosed with DCIS from aggressive treatment. The test looks for telltale proteins, or biomarkers, in breast tissue that indicate that the breast cells are responding abnormally to stress.

“For the first time, we identified the patients who have the lowest risk and the group at highest risk of developing invasive cancer,” says Thea Tlsty, Ph.D., a UCSF professor of pathology whose basic cancer research underlies the success. She and her colleague, Karla Kerlikowske, M.D., professor of medicine, are advancing this biomarker strategy to large clinical trials in several sites within the U.S and abroad.

“This would not have been possible without combining our expertise in both basic and clinical research,” Tlsty said.

With support from the UC’s California Breast Cancer Research Program and the state’s tax checkoff, which allows tax filers to donate to cancer research, the two scientists are working to extend the current biomarker signature to parse those at higher risk for metastasis. They hope to more precisely distinguish within this higher-risk group which women will need aggressive treatment and which may worry less.

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Biennial mammograms sufficient for older women?


Research shows same benefit as yearly test, with fewer false positive results.

Nurse Assisting Patient Undergoing MammogramAmong older women, getting a mammogram every two years was just as beneficial as getting a mammogram annually, and led to significantly fewer false positive results, according to a study led by UC San Francisco.

The national study of more than 140,000 women between the ages of 66 and 89 appeared online today (Feb. 5) in the Journal of the National Cancer Institute.

“Screening every other year, as opposed to every year, does not increase the probability of late-stage breast cancer in older women,” said lead author Dejana Braithwaite, Ph.D., a UCSF assistant professor of epidemiology and biostatistics. “Moreover, the presence of other illnesses such as diabetes or heart disease made no difference in the ratio of benefit to harm.”

From 1999 to 2006, data were collected on 2,993 older women with breast cancer and 137,949 women without breast cancer – “the largest available screening mammography data set in the United States,” according to Braithwaite. The data were obtained from five Breast Cancer Surveillance Consortium (BCSC) mammography registries in Washington, California, North Carolina, New Hampshire and Vermont.

The researchers found no difference in rates of late-stage breast cancer between women screened annually and women screened biennially.

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New radiation oncology device reduces treatment times, increases safety


New multi-leaf collimator is accurate to within .01 millimeters.

Stanley Benedict, UC Davis

With radiation oncology treatments, the goal is to hit the tumor with as much ionizing X-ray energy as possible, while sparing adjacent, healthy tissue. The UC Davis Comprehensive Cancer Center has taken a major step toward that goal as one of the first sites in North America to install a sophisticated new multi-leaf collimator (MLC) system on its medical linear accelerators.

The MLC system precisely focuses high-energy, megavoltage X-ray beams that increase doses to tumors and minimize doses nearby. The 160-leaf collimator also allows radiation oncologists to customize the therapeutic beams to conform to a tumor’s shape and size. For patients, the highly conformal treatments mean fewer side effects and less time on the treatment table.

With its increased leaf speed and advanced reliability and monitoring of leaf position, the new system will be used to treat a wide variety of diseases, including prostate, breast and lung cancers, as well as for highly specialized treatments such as stereotactic body radiosurgery.

“This system is safe, reliable, accurate and fast,” said Stanley Benedict, chief of clinical physics in the UC Davis Department of Radiation Oncology. “It’s great technology for our patients.”

The collimator is the latest weapon in the NCI-designated cancer center’s treatment options. The system complements other sophisticated radiation oncology technologies already established at UC Davis, such as Gamma Knife radiosurgery, image-guided radiotherapy and high-dose-rate brachytherapy, which pinpoint tumors and avoid healthy tissue.

Multi-leaf collimators act like high-tech lenses, focusing radiation beams and conforming them to the shape of an individual’s unique tumor. With its 160 tungsten leaves and larger field size (40 centimeters by 40 centimeters), the new device can precisely target tumors both large and tiny. This versatility is particularly helpful when treating head and neck and other complicated tumors surrounded by normal tissue.

The new device is accurate to within .01 millimeters, allowing oncologists to conform treatments to tumors with the utmost precision.

In addition to the MLC, a new software package precisely controls the leaves to ensure that the beam aligns tightly to the target. The software also can move individual leaves as quickly as 6 cm per second. The collimator’s high speed is ideal for radiation dose control and for arc-based treatments, in which a linear accelerator gantry rotates around the patient while simultaneously conforming to the tumor from different angles and continuously shaping the radiation beam.

“This is a very safe system,” said Richard Valicenti, chair of the Department of Radiation Oncology. “And because it’s so fast, we can reduce individual treatment times from between 25 and 50 percent.”

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‘Psychic cells’


Scientists discover cells can communicate through physical barriers.

Keith Norris, UCLA

Scientists at UCLA and Charles R. Drew University of Medicine and Science have discovered a possible method by which cancer cells and dying cells communicate with nearby normal nerve cells without being physically connected to them.

Dr. Keith Norris, senior author of the research and assistant dean for clinical and translational science at the David Geffen School of Medicine at UCLA, said the study contributes to the understanding of cell communication, which until now was known to take place only through direct contact or direct stimulation of receptors in the cells of molecules known as ligands or in hormones, signaling factors, nerves and other pathways.

It now appears, the researchers say, that cells may be able to effectively communicate through physical barriers. Their study appears in the January issue of the peer-reviewed American Journal of Translational Research.

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New target for cancer treatment


UC Irvine research reveals promising binding site on mutant p53 protein.

Molecular dynamics simulation of the p53 protein

Molecular dynamics simulation of the p53 protein

UC Irvine biologists, chemists and computer scientists have identified an elusive pocket on the surface of the p53 protein that can be targeted by cancer-fighting drugs. The finding heralds a new treatment approach, as mutant forms of this protein are implicated in nearly 40 percent of diagnosed cases of cancer, which kills more than half a million Americans each year.

In an open-source study published online this week in the journal Nature Communications, the UC Irvine researchers describe how they employed a computational method to capture the various shapes of the p53 protein. In its regular form, p53 helps repair damaged DNA in cells or triggers cell death if the damage is too great; it has been called the “guardian of the genome.”

Mutant p53, however, does not function properly, allowing the cancer cells it normally would target to slip through control mechanisms and proliferate. For this reason, the protein is a key target of research on cancer therapeutics.

Within cells, p53 proteins undulate constantly, much like a seaweed bed in the ocean, making binding sites for potential drug compounds difficult to locate. But through a computational method called molecular dynamics, the UC Irvine team created a computer simulation of these physical movements and identified an elusive binding pocket that’s open only 5 percent of the time.

After using a computer to screen a library of 2,298 small molecules, the researchers selected the 45 most promising to undergo biological assays. Among these 45 compounds, they found one, called stictic acid, that fits into the protein pocket and triggers tumor-suppressing abilities in mutant p53s.

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