TAG: "Cancer"

Lifestyle changes may lengthen telomeres, a measure of cell aging


Diet, meditation, exercise can help key element of immune cell aging, UCSF scientists report.

A small pilot study shows for the first time that changes in diet, exercise, stress management and social support may result in longer telomeres, the parts of chromosomes that affect aging.

It is the first controlled trial to show that any intervention might lengthen telomeres over time.

The study will be published online today (Sept. 16) in The Lancet Oncology.

The study was conducted by scientists at UC San Francisco and the Preventive Medicine Research Institute, a nonprofit public research institute in Sausalito that investigates the effect of diet and lifestyle choices on health and disease. The researchers say they hope the results will inspire larger trials to test the validity of the findings.

“Our genes, and our telomeres, are not necessarily our fate,” said lead author Dean Ornish, M.D., UCSF clinical professor of medicine, and founder and president of the Preventive Medicine Research Institute.

“So often people think ‘Oh, I have bad genes, there’s nothing I can do about it,’” Ornish said. “But these findings indicate that telomeres may lengthen to the degree that people change how they live. Research indicates that longer telomeres are associated with fewer illnesses and longer life.”

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Cost-effectiveness analysis applied to state breast cancer screening program


UC Davis study conducted in response to recent government funding cutbacks.

Joy Melinkow, UC Davis

Joy Melinkow, UC Davis

When public health budgets are constrained, mammography screening should begin later and occur less frequently, a cost-effectiveness analysis for California’s Every Woman Counts (EWC) program concludes.

As outlined in a paper published in Value in Health, the analysis focused on several policy questions, including the effect on EWC program costs and outcomes of starting screening at age 50 years instead of 40 and of screening every two years instead of every year. The study was conducted in response to recent government funding cutbacks.

“This was not a clinical recommendation, but rather was intended to help a public health program use its resources to the greatest effectiveness,” said lead author Joy Melnikow, director of the UC Davis Center for Healthcare Policy and Research.

EWC, administered through the California Department of Public Health Cancer Detection Section, is one of the largest of 68 Centers for Disease Control and Prevention-funded programs across the country. It reimburses providers at Medi-Cal rates (Medi-Cal is the California version of Medicaid) for screening and diagnostic services for breast and cervical cancers. It provides services to women who are not eligible for Medi-Cal, who otherwise lack coverage for breast and cervical cancer screening, and whose income is less than 200 percent of the federal poverty threshold.

The study, conducted by UC Davis and EWC researchers, was based on a sophisticated microsimulation model that projected outcomes based on existing program data. It found that starting mammography screening biennially at age 50 was strongly supported by the model results, given that program funding did not allow screening of the full population of eligible women beginning at age 40.

“Because breast cancer incidence goes up with age, using program funds to screen all eligible women over age 50 will have a greater impact on reducing breast cancer deaths,” said Melnikow.  “The goal was to advise a public health program in a timeframe that could be helpful, given that cost-effectiveness analysis typically takes a long time to conduct — often too long to be of use in a quickly changing policy environment.”

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‘Wildly heterogeneous genes’


New approach subtypes cancers by shared genetic effects.

Trey Ideker, UC San Diego

Trey Ideker, UC San Diego

Cancer tumors almost never share the exact same genetic mutations, a fact that has confounded scientific efforts to better categorize cancer types and develop more targeted, effective treatments.

In a paper published in the Sept. 15 advanced online edition of Nature Methods, researchers at UC San Diego propose a new approach called network-based stratification (NBS), which identifies cancer subtypes not by the singular mutations of individual patients, but by how those mutations affect shared genetic networks or systems.

“Subtyping is the most basic step toward the goal of personalized medicine,” said principal investigator Trey Ideker, Ph.D., division chief of genetics in the UC San Diego School of Medicine and a professor in the departments of medicine and bioengineering at UC San Diego. “Based on patient data, patients are placed into subtypes with associated treatments. For example, one subtype of cancer is known to respond well to drug A, but not drug B. Without subtyping, every patient looks the same by definition, and you have no idea how to treat them differently.”

Recent advances in knowledge and technology have made it easier (and less expensive) to sequence individual genomes, especially in the treatment of cancer, which is fundamentally a disease of genes.

But genes are “wildly heterogeneous,” said Ideker. It is in combination, influenced by other factors, that mutated genes cause diseases like cancer. Every patient’s cancer is genetically unique, which can affect the efficacy and outcomes of clinical treatment.

“When you look at patients’ data at the level of genes, everybody looks different,” said Ideker. “But when you look at impacted biological networks and systems, groupings do appear. No genes are mutated in exactly the same place, but the mutations do appear in the same genetic pathways.”

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Nanodiamonds used to deliver chemotherapy drugs into brain tumors


Method found to have greater cancer-killing efficiency than existing treatments.

These images show the retention of doxorubicin and ND-DOX in brain tissue, with light microscopic images (upper rows) and fluorescence images detecting fluorescence generated from doxorubicin (lower rows). The images show the distribution of unmodified doxorubicin and ND-DOX after convection-enhanced delivery (CED) at 6, 16, 24 and 72 hours.

These images show the retention of doxorubicin and ND-DOX in brain tissue, with light microscopic images (upper rows) and fluorescence images detecting fluorescence generated from doxorubicin (lower rows). The images show the distribution of unmodified doxorubicin and ND-DOX after convection-enhanced delivery (CED) at 6, 16, 24 and 72 hours.

Researchers at UCLA’s Jonsson Comprehensive Cancer Center have developed an innovative drug-delivery system in which tiny particles called nanodiamonds are used to carry chemotherapy drugs directly into brain tumors. The new method was found to result in greater cancer-killing efficiency and fewer harmful side effects than existing treatments.

The research, published in the advance online issue of the peer-reviewed journal Nanomedicine: Nanotechnology, Biology and Medicine, was a collaboration between Dean Ho of the UCLA School of Dentistry and colleagues from the Lurie Children’s Hospital of Chicago and Northwestern University’s Feinberg School of Medicine. Ho co-directs UCLA Dentistry’s Weintraub Center for Reconstructive Biotechnology and is a professor in the division of oral biology and medicine, the division of advanced prosthodontics, and the department of bioengineering.

Glioblastoma is the most common and lethal type of brain tumor. Despite treatment with surgery, radiation and chemotherapy, the median survival time for glioblastoma patients is less than one-and-a-half years. The tumors are notoriously difficult to treat, in part because chemotherapy drugs injected alone often are unable to penetrate the system of protective blood vessels that surround the brain, known as the blood–brain barrier. And those drugs that do cross the barrier do not stay concentrated in the tumor tissue long enough to be effective.

The drug doxorubicin, a common chemotherapy agent, has shown promise in a broad range of cancers, and it has served as model drug for the treatment brain tumors when injected directly into the tumor. Ho’s team originally developed a strategy for strongly attaching doxorubicin molecules to nanodiamond surfaces, creating a combined substance called ND–DOX.

Nanodiamonds are carbon-based particles roughly 4 to 5 nanometers in diamter that can carry a broad range of drug compounds. And while tumor-cell proteins are able to eject most anticancer drugs that are injected into the cell before those drugs have time to work, they can’t get rid of the nanodiamonds. Thus, drug–nanodiamond combinations remain in the cells much longer without affecting the tissue surrounding the tumor.

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UC Davis established endowed chair for clinical cancer research


Lung cancer expert Karen Kelly appointed to post.

Karen Kelly, UC Davis

Karen Kelly, UC Davis

Karen Kelly, associate director for clinical research at the UC Davis Comprehensive Cancer Center, is the recipient of the university’s first endowed chair in cancer clinical research.

The Tegley & Harmon Endowed Chair is named in honor of Elizabeth Erica Harmon, who passed away at age 30, and her cousin, Jennifer Rene Harmon Tegley, who died at age 18, just one year after being diagnosed with a very aggressive throat cancer.

The Harmon family made a $765,000 gift to create the endowed chair to support the work of Kelly, who managed Jennifer’s end-of-life care and is building the cancer center’s phase one clinical trial program. The Harmon family gift was matched with funds from the UC Davis Health System’s Dean’s Catalyst Fund.

“With so many important advances in genomics and drug development, this is an exciting time to be engaged in cancer research,” Kelly said. “As the university’s first cancer clinical research chair, I am honored to lead our comprehensive cancer center team in bringing these innovative new treatments to patients.”

A private appreciation reception will be held tonight at the cancer center in honor of the Harmon family. UC Davis Chancellor Linda Katehi will address the group about the importance of the investment in cancer clinical research at a time of great promise and need for discovery.

The Tegley & Harmon Endowed Chair was the university’s 150th. Its establishment was celebrated in April at the annual UC Davis Endowed Chairs and Professorships gala.

The Harmon family also has contributed to the cancer center directly; in 2012 the family made a $1 million gift to support the cancer center expansion project. In recognition, the center’s lobby area was named the Jennifer Rene Harmon Tegley and Elizabeth Erica Harmon Pavillion.

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Swallowing exercises help head, neck cancer patients receiving radiation


Study finds swallow preservation exercises appear to maintain patient’s ability to swallow.

Marilene Wang, UCLA

Marilene Wang, UCLA

A study at UCLA’s Jonsson Comprehensive Cancer Center has found that head and neck cancer patients receiving radiation as part of their treatment were less likely to need a feeding tube or suffer unwanted side effects such as worsening of diet or narrowing of the throat passage if they performed a set of prescribed swallowing exercises — called a “swallow preservation protocol” — during therapy.

The study, conducted from 2007 to 2012, was led by Dr. Marilene Wang, a member of the Jonsson Cancer Center and professor-in-residence in the department of head and neck surgery at UCLA’s David Geffen School of Medicine. The study was published online by the journal Otolaryngology–Head and Neck Surgery, and will appear later in the journal’s print edition.

Surgery and radiation have been the traditional treatments for head and neck cancer, but with the advent of improved and targeted chemotherapy, many types of this disease are treated with chemotherapy and radiation, (chemoradiation) in the hope of preserving the tissue and structure. But, even when tissue and structure are preserved, patients do not always retain their ability to swallow naturally and normally.

Most patients who receive chemoradiation have significant side effects during treatment and for a long time after recovery. Difficulty swallowing (dysphagia) is one of the most common unwanted side effects of radiation and chemoradiation, and is one of the main predictors of diminished quality of life for the patient after treatment.

Wang’s study was designed to evaluate the swallow preservation protocol, in which patients had swallow therapy before, during and after radiation treatment. The protocol’s effectiveness was measured by patients’ continued ability to swallow and how that affected their diets, whether they needed a feeding tube, and whether they developed narrowing of the throat (stenosis). The same attributes were also measured for a group of patients who were not compliant with the protocol.

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UC awarded $21M in stem cell grants


Diseases targeted include prostate cancer, autism, ALS and AIDS/HIV.

Alysson Muotri, UC San DIego

Alysson Muotri, UC San DIego

The University of California and its affiliates received seven grants totaling more than $21 million in the latest round of funding from the state’s stem cell agency.

Prostate cancer, autism, ALS and AIDS/HIV are among the diseases targeted by the California Institute for Regenerative Medicine, whose governing board awarded a total of more than $40 million in funding for this round.

Overall, CIRM’s governing board has awarded more than $1.8 billion in stem cell grants, with half of the total going to the University of California or UC-affiliated institutions.

CIRM Early Translation Awards IV:

  • UC Irvine: $4.3 million: Magdalene Seiler
  • UCLA: $13 million: Donald Kohn, Gerald Lipshutz, Robert Reiter, Jerome Zack
  • UC San Diego: $1.8 million: Alysson Muotri
  • UCSF-affiliated J. David Gladstone Institutes: $2.3 million: Steven Finkbeiner

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Thyroid cancer biopsy guidelines should be simplified, researchers say


UCSF study calls for new standards to reduce unnecessary procedures.

Scanning thyroidA team led by UC San Francisco researchers has called for simplified guidelines on when to biopsy thyroid nodules for cancer, which they say would result in fewer unnecessary biopsies.

Their recommendation, based on a retrospective study published online this week in JAMA Internal Medicine, is to biopsy patients only when imaging reveals a thyroid nodule with microcalcifications – tiny flecks of calcium – or one that is more than two centimeters in diameter and completely solid. Any other findings represent too low a risk to require biopsy or continued surveillance for cancer, the scientists concluded.

More than 98 percent of detected nodules in the study were benign, not malignant cancers.

“Compared with other existing guidelines, many of which are complicated to apply, following these simple, evidence-based guidelines would substantially decrease the number of unnecessary thyroid biopsies in the United States,” said lead author Rebecca Smith-Bindman, M.D., a UCSF School of Medicine professor with the Department of Radiology and Biomedical Imaging and the Department of Epidemiology and Biostatistics. “Right now, we’re doing far too many thyroid biopsies in patients who are really at very low risk of having thyroid cancer,” she said.

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Innovation profile: Rebecca Smith-Bindman

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Disabling enzyme reduces tumor growth, cripples cancer cells, study finds


UC Berkeley research sheds new light on importance of lipids in development of cancer.

Illustration of an aggressive cancer cell. (Image by O’Reilly Science Art)

Illustration of an aggressive cancer cell.

Knocking out a single enzyme dramatically cripples the ability of aggressive cancer cells to spread and grow tumors, offering a promising new target in the development of cancer treatments, according to a new study by researchers at the University of California, Berkeley.

The paper, published today (Aug. 26), in the journal Proceedings of the National Academy of Sciences, sheds new light on the importance of lipids, a group of molecules that includes fatty acids and cholesterol, in the development of cancer.

Researchers have long known that cancer cells metabolize lipids differently than normal cells. Levels of ether lipids – a class of lipids that are harder to break down – are particularly elevated in highly malignant tumors, although the nature of that correlation has been unclear for decades.

“Cancer cells make and use a lot of fat and lipids, and that makes sense because cancer cells divide and proliferate at an accelerated rate, and to do that, they need lipids, which make up the membranes of the cell,” said study principal investigator Daniel Nomura, assistant professor in UC Berkeley’s Department of Nutritional Sciences and Toxicology. “Lipids have a variety of uses for cellular structure, but what we’re showing with our study is that lipids can also send signals that fuel cancer growth.”

In the study, Nomura and his team tested the effects of reducing ether lipids on human skin cancer cells and primary breast tumors. They targeted an enzyme, alkylglycerone phosphate synthase, or AGPS, known to be critical to the formation of ether lipids.

The researchers first confirmed that AGPS expression increased when normal cells turned cancerous. They then found that inactivating AGPS substantially reduced the aggressiveness of the cancer cells.

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Scientists take fight against prostate cancer from lab to clinic


UCLA’s efforts have made a life-saving difference for countless patients and their families.

Jean deKernion, UCLA

Jean deKernion, UCLA

The awarding of $11.6 million in federal funding from the National Cancer Institute (NCI) to enable a multidisciplinary group of UCLA scientists to continue their important prostate cancer research is just the latest in a string of “big hits” for the team.

“To get something like this funded now is really something,” said Dr. Jean deKernion, professor emeritus who pioneered prostate cancer research at UCLA two decades ago and was one of the first principal investigators when UCLA’s Specialized Program of Research Excellence (SPORE) site in prostate cancer  started in 2001.

This award marks the third round of NCI funding for the SPORE group, which is comprised of UCLA scientists, clinicians, oncologists, radiologists, pathologists and imaging specialists. Together, they’ve turned UCLA into one of the nation’s pre-eminent research engines for advances in the prevention, diagnosis and treatment of prostate cancer and made a life-saving difference in the lives of countless patients and their families.

“This renewal of the UCLA prostate SPORE is indicative of the world-class research we have on this campus,” said Dr. James Economou, UCLA vice chancellor for research and professor of microbiology, immunology and molecular genetics; molecular and medical pharmacology; and surgical oncology.

Roughly one in six men will be diagnosed with prostate cancer, making it the second most common cancer in men. It is estimated that 238,000 new cases of prostate cancer will be diagnosed in the United States this year, and about 30,000 men will die from the disease.

The SPORE program has been key in advancing preventative care and developing diagnostic tools and therapies.

“UCLA’s world-class research in prostate cancer, joined with over 15 years of faculty entrepreneurial initiative and technology transfer efforts, are bringing life-saving technology to the clinic and the marketplace,” said Emily Loughran, director of licensing in UCLA’s Office of Intellectual Property and Industry Sponsored Research. “It is truly gratifying to see a lot of hard work come to fruition.”

In June, Johnson & Johnson, a manufacturer of multinational medical devices and pharmaceutical and consumer packaged goods, struck a $1 billion deal with Aragon Pharmaceuticals Inc., a UCLA start-up and leader in developing drugs that fight hormone-driven cancers, to acquire the rights to a UCLA-developed androgen receptor antagonist program. This program includes ARN-509, a second-generation androgen receptor-signaling inhibitor designed and synthesized in 2006 by a UCLA team headed by former SPORE investigator Dr. Charles Sawyers, who worked at the Jonsson Comprehensive Cancer Center for nearly 18 years, and Dr. Michael Jung, a professor of chemistry and biochemistry. This compound is currently being evaluated in multiple Phase II trials in men with castration-resistant prostate cancer.

In addition, the UCLA-created prostate cancer drug Xtandi, a new anti-androgen treatment that can prolong life for men who have failed hormone and chemotherapies, received approval from the U.S. Food and Drug Administration in 2012. Xtandi, which was also developed by Sawyers and Jung and later licensed to California’s Medivation Inc., inhibits the androgen receptor (AR), the engine of prostate cancer progression, at three distinct points in the signaling pathway. In its Phase III clinical study, Xtandi increased median survival by 4.8 months in men with the chemotherapy-resistant disease, providing a 37 percent reduction in the risk of death compared to placebo.

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Sugar helps scientists find, assess prostate tumors


New GE technology enables UCSF researchers to safely detect tumors in real time.

Prostate cancer scanA natural form of sugar could offer a new, noninvasive way to precisely image tumors and potentially see whether cancer medication is effective, by means of a new imaging technology developed at UC San Francisco in collaboration with GE Healthcare.

The technology uses a compound called pyruvate, which is created when glucose breaks down in the body and which normally supplies energy to cells. In cancer, however, pyruvate is more frequently converted to a different compound, known as lactate.

Previous animal studies showed that scientists could track the levels of pyruvate as it is converted to lactate via magnetic resonance imaging (MRI), by using a technology called hyperpolarization and injecting the hyperpolarized pyruvate into the body. The amount of lactate produced and rate of conversion enabled researchers to precisely detect the limits of a mouse’s tumor, identify which cancers were most aggressive and track early biochemical changes as tumors responded to medication, long before physical changes occurred.

Now, a 31-patient study performed by scientists at UCSF and their collaborators at GE Healthcare has shown that the technology is safe in humans and effectively detects tumors in patients with prostate cancer.

Findings appeared online in the Aug. 14 issue of Science Translational Medicine.

While this first-in-human study was designed to identify a safe dosage and verify effectiveness, it lays the groundwork for using the technology to diagnose a variety of cancers and track treatment noninvasively, without conducting repeated biopsies.

“We now have a safe dose for patients – that was our primary goal,” said Sarah J. Nelson, Ph.D., a UCSF professor of radiology and director of the Surbeck Laboratory of Advanced Imaging at UCSF, who was lead author on the study and led a diverse team on this project.

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Clinical trial evaluates new minimally invasive rectal cancer surgery


UC San Diego team is first in U.S. to integrate two novel minimally invasive techniques to treat rectal cancer.

Elisabeth McLemore, UC San Diego

Elisabeth McLemore, UC San Diego

Surgeons at the UC San Diego School of Medicine are evaluating a new, combined surgery technique to remove cancerous tumors from the rectum. The hybrid technique uses the body’s natural opening to remove malignancies and diseased tissue while also performing reconstruction. UC San Diego Health System’s surgical team is the first in the United States – in a clinical trial setting – to integrate two novel minimally invasive techniques to treat rectal cancer.

“By operating through the rectum, and with one small abdominal incision, we are able to perform an effective operation to remove the cancer, and to visualize and identify pelvic structures that are vital to normal bladder and sexual function,” said Elisabeth McLemore, M.D., colorectal surgeon at UC San Diego Health System and principal investigator of the study. “With this advanced approach, we reduce the number of incisions from six to one. This can result in less blood loss, less pain and a shorter hospital stay for the patient.”

Santiago Horgan, UC San Diego

Santiago Horgan, UC San Diego

This clinical trial surgery combines a technique called natural orifice translumenal endoscopic surgery (NOTES) with laparoscopic total mesorectal excision (TME), a form of rectal surgery. The NOTES technique allows the surgeons to operate through the rectum to remove tumors and TME ensures that a section of normal tissue around the tumor is also safely removed to reduce the chance of cancer recurrence.

“This study is evaluating both the safety and efficacy of the surgery, as well as pain levels, cosmetic outcomes, operative costs and logistical outcomes,” said Santiago Horgan, M.D., chief of minimally invasive surgery at UC San Diego Health System and director of the UC San Diego Center for the Future of Surgery. “Our goal is to expand the range of minimally invasive techniques that can be performed for patients with any form of digestive cancer.”

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