TAG: "Cancer"

Researchers discover leukemia’s role in inhibiting immune cell development


Study highlights cross-country collaboration between UCSF, Harvard that led to discovery.

Emmanuelle Passegué (right) speaks with a colleague in her lab at UCSF's Parnassus campus.

Emmanuelle Passegué (right) speaks with a colleague in her lab at UCSF's Parnassus campus.

UC San Francisco’s Emmanuelle Passegué, Ph.D., an expert on how the blood system arises during development, recently led a study in which researchers discovered how leukemia, a blood cancer, can gain a stronghold in bone marrow and inhibit the development of normal immune cells.

Passague, a researcher with the UCSF Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, and colleagues – including long-term collaborator Amy Wagers, Ph.D., a professor at Harvard University’s Department of Stem Cell and Regenerative Biology – found that leukemia cells cause other nearby cells to abnormally deposit collagen and inflammatory proteins, leading to fibrosis – or scarring – of the bone marrow cavity.

“They remodel the microenvironment so that it is basically callous, kicking the normal stem cells out of the bone marrow and encouraging the production of even more leukemic cells,” Passegué says.

While Passegué’s discoveries are fundamental, they also point to new strategies for fighting cancer.

Read more about the study and the cross-country collaboration of Passegué and Wagers in the Harvard Gazette.

Learn more about Passegué’s work on her laboratory website.

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Clinical trial advances gene therapy with precise drug delivery


Southern California’s first real-time MRI-guided gene therapy for brain cancer.

Neurosurgeons at the UC San Diego School of Medicine and UC San Diego Moores Cancer Center are among the first in the world to utilize real-time magnetic resonance imaging (MRI) guidance for delivery of gene therapy as a potential treatment for brain tumors. Using MRI navigational technology, neurosurgeons can inject Toca 511 (vocimagene amiretrorepvec), a novel investigational gene therapy, directly into a brain malignancy. This new approach offers a precise way to deliver a therapeutic virus designed to make the tumor susceptible to cancer-killing drugs.

“With chemotherapy, just about every human cell is exposed to the drug’s potential side-effects. By using the direct injection approach, we believe we can limit the presence of the active drug to just the brain tumor and nowhere else in the body,” said Clark Chen, M.D., Ph.D., chief of stereotactic and radiosurgery and vice chairman of neurosurgery at UC San Diego Health System. “With MRI, we can see the tumor light up in real time during drug infusion. The rest of the brain remains unaffected so the risk of the procedure is minimized.”

Toca 511 is a retrovirus engineered to selectively replicate in cancer cells, such as glioblastomas. Toca 511 produces an enzyme that converts an anti-fungal drug, flucytosine (5-FC), into the anti-cancer drug 5-fluorouracil (5-FU).  After the injection of Toca 511, the patients are treated with an investigational extended-release oral formulation of 5-FC called Toca FC. Cancer cell killing takes place when 5-FC comes into contact with cells infected with Toca 511.

“Inevitably, almost all glioblastoma patients fail currently available therapy.  The challenge, in part, is knowing if current drugs are actually penetrating the tumor. This MRI-guided approach will help us deliver this drug into the tumor directly to see if the drug is working,” said Santosh Kesari, M.D., Ph.D., principal investigator and director of neuro-oncology at Moores Cancer Center.  “This approach may lead to new treatment options for patients battling several other types of brain cancers.”

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Therapy could treat breast cancer that’s spread to brain


Researchers at UCLA successfully combine cellular and gene therapies.

Noriyuki Kasahara, UCLA

Noriyuki Kasahara, UCLA

Researchers at UCLA‘s Jonsson Comprehensive Cancer Center have successfully combined cellular therapy and gene therapy in a mouse-model system to develop a viable treatment strategy for breast cancer that has spread to a patient’s brain.

The research, led by Carol Kruse, a professor of neurosurgery and member of the Jonsson Cancer Center and the UCLA Brain Research Institute, was published Aug. 1 in the journal Clinical Cancer Research.

Breast cancer is the most common form of cancer in women, and metastasis is a major cause of health deterioration and death from the disease. Managing metastasis is difficult for several reasons: The circulatory network known as the blood–brain barrier prevents many anti-cancer drugs from reaching areas of the brain to which cancer has spread, and metastases have a tendency to spring up in multiple brain locations simultaneously, making current treatments such as radiation challenging.

Cellular therapy is a type of immunotherapy that uses T cells, the foot soldiers of the immune system, that have been sensitized in the laboratory to kill breast cancer cells. These sensitized T cells are injected into the parts of the brain to which cancer has spread. The research shows that the T cells can move through tissue and recognize and directly kill the tumor cells.

With the gene therapy, genetically modified cancer cells are killed by a drug called 5-flurocytosine (5-FC). To get the gene into the cancer cells, the researchers first insert it into a virus that can infect the tumor cells. After the virus has infected the cells, non-toxic 5-FC is given to the patient. Tumor cells infected by the virus convert the non-toxic drug to a toxic form that kills the cancer cells. Dr. Noriyuki Kasahara, a professor in the department of medicine at UCLA, developed the gene therapy method in his laboratory.

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Non-invasive test could improve colon cancer screening rates


Study explores best ways to reach uninsured patients.

Samir Gupta, UC San Diego

Organized mailing campaigns could substantially increase colorectal cancer screening among uninsured patients, a study published in the Aug. 5 online edition of JAMA Internal Medicine reveals. The research also suggests that a non-invasive colorectal screening approach, such as a fecal immunochemical test (FIT) might be more effective in promoting participation in potentially life-saving colon cancer screening among underserved populations than a colonoscopy, a more expensive and invasive procedure.

The study was led by Samir Gupta, M.D., M.S.C.S., an associate professor of clinical medicine and gastroenterologist at the UC San Diego School of Medicine and Veterans Affairs San Diego Healthcare System, and conducted by UT Southwestern’s Division of Digestive and Liver Diseases, Simmons Cancer Center, and the Moncrief Cancer Institute, in close collaboration with John Peter Smith (JPS) Hospital in Fort Worth, Texas.

As part of the study, uninsured patients not up-to-date with screening between the ages of 54 to 64 years and cared for by a safety-net health system were sent mailed invitations to use and return a no-cost FIT, or encouraged to undergo a colonoscopy through a mailed invitation to schedule one at no cost. In addition, both groups received telephone follow-up to promote test completion.

The study showed that FIT participation tripled, and colonoscopy participation doubled in the study sample of nearly 6,000 patients, when compared to usual care strategy for colorectal screenings. According to Gupta, the difference was much bigger than expected, and the findings could have health policy implications.

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Immune system molecule promotes tumor resistance to anti-angiogenic therapy


Discovery could improve efficacy of anti-cancer drugs.

Napoleone Ferrara, UC San Diego

Napoleone Ferrara, UC San Diego

A team of scientists, led by Napoleone Ferrara, M.D., has shown for the first time that a signaling protein involved in inflammation also promotes tumor resistance to anti-angiogenic therapy.

The findings by Ferrara – professor of pathology at the UC San Diego School of Medicine and senior deputy director for basic science at the UC San Diego Moores Cancer Center – and colleagues at Genentech, a biotechnology firm based in South San Francisco, are published in the Aug. 4 advance online publication of the journal Nature Medicine.

Angiogenesis is a physiological process in which new blood vessels form from existing vessels. It is fundamental to early development and wound healing, but some cancer tumors exploit angiogenesis to promote blood vessel growth and fuel a tumor’s transition from a benign to a malignant state.

In the late 1980s, Ferrara led efforts to identify a key gene (VEGF) involved in angiogenesis and subsequent development of the first drugs to block VEGF-mediated growth in a variety of cancers, among them lung, kidney, brain and colorectal. Researchers discovered, however, that similar to other therapies, VEGF-targeting drugs may lose effectiveness as tumors develop resistance, allowing cancers to recur.

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Discovery could improve liver transplant success


Natural substance found in blood vessels stimulates organ and tissue regeneration.

Bruce Hammock, UC Davis

Bruce Hammock, UC Davis

Researchers from multiple institutions, including UC Davis and Harvard Medical School, have discovered a novel and natural means that could increase the success of human liver transplants and speed the recovery of both the patient and the donor.

The study is especially significant because of the desperate shortage of livers among thousands of very ill patients, said lead researcher Dipak Panigrahy of Harvard Medical School, in work published online in the July 29 edition of Proceedings of the National Academy of Sciences (PNAS).

According to the American Liver Foundation website, 1,848 patients died in 2005 while waiting for a donated liver to become available. “Currently, about 17,000 adults and children have been medically approved for liver transplants and are waiting for donated livers to become available. The waiting list grows every year.”

The researchers found that a natural substance in blood vessels stimulates organ and tissue regeneration.

“The endothelium of blood vessels generate the lipid mediators called epoxyeicosatrienoic acids or EETs,” explained Panigrahy, assistant professor of pathology at Harvard Medical School and the Center of Vascular Biology Research at the Beth Israel Deaconess Medical Center, Boston. “EETs stimulate blood vessel formation, and organ regeneration is dependent on blood vessel formation. However, the role of EETs in organ regeneration is unknown. Our research shows that EETs stimulate organ and tissue regeneration.”

The 28-member discovered that “systemic administration of EETs significantly increased liver and lung regeneration by 23 percent to 46 percent when compared to control mice post partial liver resection,” Panigrahy said.

“This can be very useful in transplant both for the donor and the recipient in getting full function back with liver transplant,” said researcher and co-author Bruce Hammock, a distinguished professor of entomology with a joint appointment at the UC Davis Comprehensive Cancer Center.

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Secondhand smoke in bars and restaurants means higher asthma, cancer risk


UC Berkeley/LBNL study finds risks well above the acceptable level.

People having lunch in outdoor restaurant, MilanIn the first study to evaluate the health risks of exposure to secondhand smoke for patrons of restaurants and bars, researchers have found that the risks are well above the acceptable level. The study assessed the risk for lung cancer and heart disease deaths among both patrons and servers and also for asthma initiation — the first study to do so — among servers.

Lawrence Berkeley National Laboratory scientists Lara Gundel and Michael Apte contributed to the study, which was led by Ruiling Liu and Katharine Hammond from UC Berkeley’s School of Public Health. The results were published in the journal Tobacco Control in a paper titled, “Assessment of risk for asthma initiation and cancer and heart disease deaths among patrons and servers due to secondhand smoke exposure in restaurants and bars.”

Taking exposure data from 65 restaurants and bars in Minnesota over an eight-month period in 2007, the researchers found that the lifetime excess risk of lung cancer death was 18 in a million for patrons visiting only nonsmoking sections and 80 in a million for patrons in the smoking section. For servers, the lifetime excess risk was 802 in a million for lung cancer death.

Extrapolating to the entire country, the researchers estimate that the lifetime excess risk for the general nonsmoking population due to exposure to secondhand smoke in restaurants and bars would result in 214 additional lung cancer deaths and 3,001 additional heart disease deaths per year.

“One in a million is significant,” said Gundel. “You can’t control people smoking, but to support tobacco-free policies we need to know how to protect people.”

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Major changes urged for cancer screening, treatment


Scientific panel recommends new personalized strategies to reduce cancer overtreatment.

Woman having mammogramTo address the growing problem of people being overdiagnosed and overtreated for cancer, a group of scientists convened by the National Cancer Institute and chaired by a UC San Francisco breast cancer expert is proposing a major update of the way the nation approaches diseases now classified as “cancer.”

The “Viewpoint” article will be published online today (July 29) in the Journal of the American Medical Association.  

Laura Esserman, UC San Francisco

Laura Esserman, UC San Francisco

When cancer screening programs were widely initiated three decades ago, medical knowledge of the disease was more simplistic. The intent was to detect cancer at its earliest stages to reduce illness and mortality, but in fact early diagnosis has not led to a proportional decline in serious disease and death, the scientists write in the JAMA commentary.

Instead, screening programs are identifying not only malignant cancers, but also slow-growing, low-risk lesions, and sweeping them into the same treatment process. As a result, patients are being diagnosed and treated for forms of cancer that might never actually harm them – a phenomenon that’s been termed overdiagnosis, which translates to “too much medicine.”

Now, with the advancement of scientific understanding of the biology of cancer, the authors say it is time for significant changes in practice and policy.

“By recognizing that cancer is not one disease, but a number of different diseases, we can individualize our treatment based on biology and avoid overtreatment,” said panel chair Laura J. Esserman, M.D., M.B.A., director of the Carol Franc Buck Breast Care Center at the UCSF Helen Diller Family Comprehensive Cancer Center.

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Luau and Longboard Invitational celebrates 20th anniversary


Surf-themed event has raised nearly $6M to fund cancer research at UC San Diego.

Surf legends show off their boards at the Luau and Longboard Invitational.

Surf legends show off their boards at the Luau and Longboard Invitational.

A surfer and San Diego resident at the time, Kary Mullis won the Nobel Prize in Chemistry in 1993 for his invention of the polymerase chain reaction, considered one of the monumental scientific techniques of the 20th century. That year, Mullis also became the founding honorary chair of the Luau and Longboard Invitational, a fundraising event for the UC San Diego Moores Cancer Center that unites two passions common in San Diego: surfing and science. Two decades later, Mullis returns to the event as the 2013 recipient of the Rell Sunn Award, which will be presented at the 20th Annual Luau and Longboard Invitational on Sunday, Aug. 18.

“The Luau and Longboard Invitational is a tradition truly unique to San Diego,” said UC San Diego Chancellor Pradeep K. Khosla. “It combines two of our region’s greatest strengths — our location and life sciences industry — to advance cancer research for the well-being of our community and society at large.”

Now in its 20th year, the annual event has raised nearly $6 million to advance research at UC San Diego Moores Cancer Center, which is the only one of its kind in San Diego and Imperial counties to hold a National Cancer Center Institute designation as a Comprehensive Cancer Center, and one of just 41 such centers in the United States. Most recently, UC San Diego Health System was ranked among the nation’s best in U.S. News and World Report’s 2013-2014 America’s Best Hospitals issue, taking the number one spot in the San Diego metropolitan area as well as national rankings in 10 specialties — including cancer.

“The support shown by the local community and businesses each year at the Luau and Longboard Invitational is truly incredible,” said Moores Cancer Center director Scott Lippman, M.D. “Their generous donations help us to achieve our mission of translating promising scientific discoveries into new and better options for the care of our patients.”

The fundraiser opens with a surfing competition followed by a luau celebration, which includes the presentation of the Rell Sunn “Queen of Makaha” Award. The award was established in memory of Rell Sunn, a Hawaiian surfer and longtime Luau and Longboard Invitational supporter who lost her battle with breast cancer. Each year, the event volunteer committee selects an honoree who has displayed a strong will, unselfishness and compassion in the battle against cancer. Past recipients have included Nobel laureate and UC San Diego professor Roger Tsien; National Medal of Science recipient and UC San Diego alumnus J. Craig Venter; and former director of Moores Cancer Center Dennis Carson, who discovered and developed a drug — now marketed as Leustatin — that effectively treats hairy cell leukemia, once considered deadly.

The surfing competition is free for viewing; a ticket to the luau fundraiser is $150. For more information about sponsorship opportunities, team entries, tickets and event activities, call (858) 246-1230, or visit the event website at www.longboardluau.org. More information on UC San Diego Moores Cancer Center can be found at www.cancer.ucsd.edu.

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Mice teeth provide insights into stem cells


Stem cell discovery furthers research on cell-based therapy and cancer.

Stem cellsStem cell researchers at UC San Francisco have found a key role for a protein called BMI1 that may help scientists direct the development of tissues to replace damaged organs in the human body.

“Scientists have known that BMI1 is a central control switch within the adult stem cells of many tissues, including the brain, blood, lung and mammary gland,” said Ophir Klein, M.D., Ph.D., who directs the Craniofacial and Mesenchymal Biology (CMB) program and serves as chair of the Division of Craniofacial Anomalies at UCSF. “BMI1 also is a cancer-causing gene that becomes reactivated in cancer cells.”

Klein’s research group now has shown that BMI1 plays another role in ensuring that the process of development unfolds normally.

The hallmarks of all stem cells are that they are immature, they keep dividing to replenish their numbers almost indefinitely, and they generate new specialized cells to function in the tissues in which they reside – a process called cell differentiation.

Pushed in one direction, the BMI1 switch enables normal stem cells to divide and renew their own numbers. Thrown in the other direction, it keeps cell proliferation in check. But now, Klein’s research team has shown that BMI1 also keeps this stock of stem cells from spinning off daughter cells that mature into the wrong type of specialized cell in the wrong place.

The new discovery suggests that manipulating BMI1, along with other regulatory molecules, might one day be among the steps included in molecular recipes to turn specialized cell development on and off to create new cell-based treatments for tissues lost to injury, disease or aging, Klein said.

The dual role of BMI1 also is intriguing to think about in pathological settings, such as cancer, Klein said. Growing evidence suggests that many cancers are driven by abnormally behaving adult stem cells or by cells that have abnormally acquired stem cell-like properties. If these cancerous cells could be made to become specialized cells rather than stem cells when they divide, it might slow tumor growth, some cancer researchers believe. Inactivating BMI1 in cancer stem cells might be one strategy, Klein suggested.

The study by Klein’s research team is published in the July issue of Nature Cell Biology, and was conducted on adult stem cells found in the large incisors of mice.

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Deadliest cancers may respond to new drug treatment strategy


UCSF discovery may provide novel solution for patients.

Prostate gland adenocarcinoma

Prostate gland adenocarcinoma

UC San Francisco researchers have found a way to knock down cancers caused by a tumor-driving protein called “myc,” paving the way for patients with myc-driven cancers to enroll in clinical trials for experimental treatments.

Myc acts somewhat like a master switch within cells to foster uncontrolled growth. Until now, it has been impossible to target with drugs.

The discovery of an unexpected biochemical link within tumor cells should lead to clinical trials for experimental drug treatments that indirectly target myc and that already are being evaluated in human studies, the researchers said.

UCSF Helen Diller Family Comprehensive Cancer Center scientists led by Davide Ruggero, Ph.D., and Kevan Shokat, Ph.D., used one such drug to stop tumor growth in a mouse model of myc-driven lymphoma and multiple myeloma types of blood cancer.

Their study is published online in Proceedings of the National Academy of Sciences (PNAS).

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UCLA researchers find link between intestinal bacteria and white blood cell cancer


Study is first to show relationship between intestinal microbiota and onset of lymphoma.

Robert Schiestl, UCLA

Robert Schiestl, UCLA

Researchers from UCLA’s Jonsson Comprehensive Cancer Center have discovered that specific types of bacteria that live in the gut are major contributors to lymphoma, a cancer of the white blood cells.

Published online ahead of press today (July 15) in the journal Cancer Research, the study was led by Robert Schiestl, member of the Jonsson Cancer Center and professor of pathology and laboratory medicine, environmental health sciences, and radiation oncology.

In rodents, intestinal bacteria influence obesity, intestinal inflammation and certain types of epithelial cancers. (Epithelial cancers affect the coverings of the stomach, liver or colon.) However, little is known about the identity of the bacterial species that promote the growth of, or protect the body from, cancer — or about their effect on lymphoma.

Up to 1,000 different species of bacteria (intestinal microbiota) live in the human gut. Intestinal microbiota number 100 trillion cells; over 90 percent of the cells in the body are bacteria. The composition of each person’s microbiome — the body’s bacterial make-up — is very different, due to the types of bacteria people ingest early in their lives, as well as the effects of diet and lifestyle.

Schiestl’s group wanted to determine whether differences in peoples’ microbiomes affect their risk for lymphoma, and whether changing the bacteria can reduce this risk. They studied mice with ataxia-telangiectasia (A-T), a genetic disease that in humans and mice is associated with a high rate of B-cell lymphoma. They discovered that, of mice with A-T, those with certain microbial species lived much longer than those with other bacteria before developing lymphoma, and had less of the gene damage (genotoxicity) that causes lymphoma.

“This study is the first to show a relationship between intestinal microbiota and the onset of lymphoma,” Schiestl said. “Given that intestinal microbiota is a potentially modifiable trait, these results hold considerable promise for intervention of B-cell lymphoma and other diseases.”

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