TAG: "Cancer"

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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Jacobses’ latest gift to aid cancer care

$1M contribution to support UC San Diego Center for Personalized Cancer Therapy.

Irwin and Joan Jacobs

Irwin and Joan Jacobs

A leadership gift of $1 million from San Diego philanthropists Joan and Irwin Jacobs will help UC San Diego Moores Cancer Center change how cancer is treated by supporting the Center for Personalized Cancer Therapy, a newly established center headed by Razelle Kurzrock, M.D. The UC San Diego Moores Cancer Center is one of just 41 National Cancer Institute-designated comprehensive cancer centers in the United States, and the only one in the San Diego region.

“Thanks to the generosity of Joan and Irwin Jacobs, UC San Diego will strengthen our leading role in the future of cancer research,” said Chancellor Pradeep K. Khosla. “We are grateful for the Jacobses’ longstanding commitment to improving the lives of San Diegans, and for their confidence in UC San Diego’s ability to positively impact this critical area of health care.”

The $1 million contribution by the Jacobses is the most recent in a series of gifts from the local philanthropists that are helping to shape the impact of research at UC San Diego. In 2010, the couple pledged $75 million to help fund the state-of-the art Jacobs Medical Center, scheduled to open on the university’s East Campus in La Jolla in 2016. In 2003, they committed $110 million — the largest gift in the history of the university — to the Jacobs School of Engineering. They also have made significant charitable gifts to numerous scholarship and fellowship programs, the School of Medicine, the Division of Arts and Humanities, the School of International Relations and Pacific Studies, the Stuart Collection, and the Rady School of Management, where they are recognized as founding donors.

Irwin Jacobs was a founding faculty member of UC San Diego, serving as a professor of electrical and computer engineering from 1966 to 1972. Jacobs is founding chairman and CEO emeritus of Qualcomm Inc., a San Diego-based Fortune 500 company. Both he and his wife, Joan, have been dedicated advisers as well as donors to the university, and each has served as board members of the UC San Diego Foundation. Joan was a co-founder of the Friends of the International Center and the Friends of the Stuart Collection, as well as a long-term board member of the La Jolla Playhouse.

Razelle Kurzrock, UC San Diego

Razelle Kurzrock, UC San Diego

“Over the past months, Joan and I became increasingly excited as we learned more about successes in translational work in personalized medicine that Dr. Kurzrock had achieved at M.D. Anderson and her plans for the new UC San Diego Center for Personalized Cancer Therapy,” said Irwin Jacobs. “We agreed it was important to help ensure that this new center move ahead rapidly, with research and support of clinical trials in an area that could have such positive results on cancer patients from around the world. We look forward to following the activities closely.”

Kurzrock, a renowned oncologist and professor of medicine who was recruited to UC San Diego last November, is known for developing one of the largest and best phase 1 clinical trials programs in the nation while at the University of Texas M.D. Anderson Cancer Center. A central theme of that program was the personalized medicine strategy, an approach utilizing advanced molecular technologies to match patients with targeted cancer treatments.

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Nonsurgical oncology specialists conduct nearly half of sarcoma surgeries

Patients whose sarcomas aren’t diagnosed until after surgery often require second operation.

Robert Canter, UC Davis

Robert Canter, UC Davis

Orthopedic oncologists and surgical oncologists, who have been trained in the complex procedures required to remove sarcomas located deep in the muscles and other soft tissues of the limbs, conducted only 52 percent of these operations at 85 academic medical centers during a three-year period, according to an analysis of national data by UC Davis researchers that is published online today in the Journal of Surgical Oncology.

The remaining 48 percent of these sarcoma surgeries were conducted by general surgeons, plastic surgeons and orthopedic surgeons, whose post-medical degree fellowship training did not emphasize the multi-disciplinary evaluation and surgical management of sarcomas and other cancers located deep in the soft tissue of the arms and legs, said Robert J. Canter, associate professor of surgery at UC Davis and first author of the journal article.

The UC Davis study is the first to examine the overall frequency and distribution nationwide of the different surgical specialists who remove sarcomas and other deep-seated tumors in the soft tissue of patients’ limbs.

“Our findings may have significant implications for the quality of care provided to patients who undergo surgery to resect, or remove, sarcomas in the deep soft tissue of the limbs,” said Canter, a surgical oncologist.

Canter explained that only orthopedic oncologists and surgical oncologists, but not general surgeons, plastic surgeons and orthopedic surgeons, have been trained in how to remove sarcomas from muscles and other soft tissue without leaving behind cancerous cells that could trigger another tumor. Studies have shown that achieving tumor-free margins improves the long-term survival of cancer patients.

Patients whose sarcomas are not diagnosed until after the surgery often require a second operation to remove remaining cancer cells, Canter said. A repeat operation puts the patient at risk again for surgical complications, he noted.

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Vitamin C helps control gene activity in stem cells

UCSF-led research could lead to improved treatments for cancer, in vitro fertilization.

Miguel Ramalho-Santos, UC San Francisco

Vitamin C affects whether genes are switched on or off inside mouse stem cells, suggesting that it could may play a fundamental role in helping to guide normal development in mice, humans and other animals, a team led by UC San Francisco researchers has discovered.

The researchers found that vitamin C assists enzymes that play a crucial role in releasing the brakes that keep certain genes from becoming activated in the embryo soon after fertilization, when egg and sperm fuse.

The discovery might eventually lead to the use of vitamin C to improve results of in vitro fertilization, in which early embryos now are typically grown without the vitamin. It also could help treat cancer, in which tumor cells abnormally engage or release these brakes on gene activation.

The researchers’ study was published June 30 in the journal Nature.

In the near term, stem cell scientists may begin incorporating vitamin C more systematically into their procedures for growing the most healthy and useful stem cells, according to UCSF stem cell scientist Miguel Ramalho-Santos, Ph.D., who led the study. In fact, the unanticipated discovery emerged from an effort to compare different formulations of the growth medium, a kind of nutrient broth used to grow mouse embryonic stem cells in the lab.

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Aspirin may fight cancer by slowing DNA damage

Study of patients with pre-cancerous conditions probed NSAID effects on mutation rate.

Aspirin is known to lower risk for some cancers, and a new study led by a UC San Francisco scientist points to a possible explanation, with the discovery that aspirin slows the accumulation of DNA mutations in abnormal cells in at least one pre-cancerous condition.

“Aspirin and other non-steroidal anti-inflammatory drugs, which are commonly available and cost-effective medications, may exert cancer-preventing effects by lowering mutation rates,” said Carlo Maley, Ph.D., a member of the UCSF Helen Diller Family Comprehensive Cancer Center, and an expert on how cancers evolve in the body over time.

In the study, published June 13 in the online journal PLOS Genetics, Maley – working with gastroenterologist and geneticist Brian Reid, M.D., Ph.D., of the Fred Hutchinson Cancer Research Center – analyzed biopsy samples from 13 patients with a pre-cancerous condition called Barrett’s esophagus who were tracked for six to 19 years. In an “observational crossover” study design, some patients started out taking daily aspirin for several years, and then stopped, while others started taking aspirin for the first time during observation. The goal was to track the rate of mutations in tissues sampled at different times.

The researchers found that biopsies taken while patients were on an aspirin regimen had on average accumulated new mutations about 10 times more slowly than biopsies obtained during years when patients were not taking aspirin.

“This is the first study to measure genome-wide mutation rates of a pre-malignant tissue within patients for more than a decade, and the first to evaluate how aspirin affects those rates,” Maley said.

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Standing up to bone cancer

Athletic mom credits her fully functioning right shoulder to UC Irvine Health.

Lan Zentil was a poster girl for healthy living. The 38-year-old filled her spare time with rock climbing, tennis and stand-up paddle boarding in the surf that laps her hometown of Laguna Beach. In between, she kept watch over a husband, two young children and a thriving real estate business.

Then one day about a year ago, she sat in a chair, leaned back and felt a hard lump in her right shoulder. “It felt like a pingpong ball under my skin,” Zentil says.

After seeing three doctors, one of whom told Zentil the lump “was nothing,” she arrived in the office of Dr. Bang H. Hoang, director of the UC Irvine Health Multidisciplinary Sarcoma Center and associate professor of orthopaedic surgery. The “nothing” lump turned out to be a chondrosarcoma, a rare type of bone cancer diagnosed in fewer than 500 Americans a year.

Hoang, a nationally recognized expert in sarcomas, told Zentil and her husband, Tony, that surgery to remove the mass could leave her with limited use of the shoulder — especially tough news for someone with Zentil’s energetic interests. He would do his best, Hoang said gently, before introducing them to other specialists on staff.

“We walked out of there with our heads spinning,” Zentil recalls. “But it felt so good to know there was such a network of research and information,” a center where experts collaborated and were versed in the latest advancements. We felt this is where we were supposed to be.”

Now recovered with a fully functional right shoulder, Zentil is once again rock climbing, paddle boarding and playing tennis. She is awed by the fact that she found a world-class specialist for her rare cancer right in Orange County.

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Major grant funds researchers using big data to predict cancer outcomes

UC Santa Cruz bioinformatics experts awarded $3.5M NIH grant.

Joshua Stuart, UC Santa Cruz

Despite some successes, predicting cancer outcomes based on the molecular signatures in cancer cells remains a major challenge. A new effort, funded by the National Cancer Institute and led by researchers at the University of California, Santa Cruz, aims to clear several key roadblocks that have stymied progress in this field.

The $3.5 million project will use the latest in “big data” technology to bridge the gap between the petabytes of raw genomic data in centralized repositories like UCSC’s Cancer Genomics Hub (CGHub) and the higher levels of interpretive information that can lead to clinically useful predictions, such as which drugs are most effective against tumors with certain mutations. Project leader Joshua Stuart, an associate professor of biomolecular engineering at UCSC’s Baskin School of Engineering, compares the raw genomic data to the binary code running on a computer.

“Your Web browser doesn’t understand zeros and ones. There are layers and layers of software programs between that and what you see on a Web page. We need to do the same thing for DNA sequences to reach the higher levels of interpretation needed for scientific discovery,” Stuart said.

Stuart’s group will build a separate database, called the Biomedical Evidence Graph (BMEG), for storing and analyzing interpretive information derived from the raw sequence data stored in the CGHub. Like Facebook’s social graph, the BMEG will use a graph database structure designed for lightning-fast access to complex, interconnected datasets.

“Our analyses can reveal connections between different tumor samples based on their molecular profiles, and the natural way to represent that in a database is with the graph structures used for Facebook and other social networks,” Stuart said.

A UCSC team led by bioinformatics expert and BMEG co-investigator David Haussler established CGHub in 2012 to manage data from the Cancer Genome Atlas (TCGA) consortium and other NIH cancer genomics research programs. Because CGHub holds genome sequences from thousands of individual patients, access is strictly controlled and limited to researchers approved by NIH. But the BMEG will hold higher-level data derived from analyses of the raw genome sequences and will not require the same level of security restrictions.

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New alternative to surgery lets doctors remove suspicious polyps

Minimally invasive procedure keeps colon intact.

James Yoo, UCLA

Millions of people each year have polyps successfully removed during colonoscopies. But when a suspicious polyp is bigger than a marble or in a hard-to-reach location, patients are referred for surgery to remove a portion of their colon — even if doctors aren’t sure whether the polyp is cancerous or not.

Since only 15 percent of all polyps turn out to be malignant, many patients are unnecessarily subjected to the risks of this major surgery. Now there is an alternative.

A UCLA team of surgeons and gastroenterologists has been performing a new, minimally invasive procedure to remove large and hard-to-reach polyps while keeping the colon intact. The procedure, which combines two minimally invasive techniques, has currently been performed at only a handful of medical centers in the United States.

In the June issue of the journal Surgical Endoscopy, the UCLA researchers present their experiences using the new technique — known as CELS, for combination endoscopy and laparoscopy surgery — and offer the first comparison of the new technique and standard surgery.

“The CELS approach combines the best of minimally invasive techniques and may prove to be a viable option for select patients,” said senior author Dr. James Yoo, an assistant professor of surgery and chief of the colon and rectal surgery program for the UCLA Health System and the David Geffen School of Medicine at UCLA.

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Study IDs protein essential for normal heart function

Protein being studied to fight cancer; may cause toxicity in cardiac cells.

Asa Gustafsson, UC San Diego

A study by researchers at Skaggs School of Pharmacy and Pharmaceutical Sciences and the Department of Pharmacology at UC San Diego, shows that a protein called MCL-1, which promotes cell survival, is essential for normal heart function.

Their study, published in the June 15 online issue of the journal Genes & Development, found that deletion of the gene encoding MCL-1 in adult mouse hearts led to rapid heart failure within two weeks, and death within a month.

MCL-1 (myeloid cell leukemia-1) is an anti-apoptotic protein, meaning that it prevents or delays the death of a cell. It is also a member of the BCL-2 family of proteins that regulate mitochondria – the cell’s power producers – and cell death. Aberrant expression of anti-apoptotic BCL-2 family members is one of the defining features of cancer cells, and is strongly associated with resistance to current therapies. Thus, these proteins are currently major targets in the development of new therapies for patients with cancer.

But, while MCL-1 is up regulated in a number of human cancers, contributing to the overgrowth of cancer cells, it is found at high levels in normal heart tissue. Additionally, the researchers found that autophagy – a process which deals with mitochondrial maintenance and is normally induced by myocardial stress – was impaired in mice with MCL-1 deficient hearts.

In summary, the study demonstrated that the loss of MCL-1 led to rapid dysfunction of mitochondria, impaired autophagy and heart failure, even in the absence of cardiac stress.

“Cardiac injury, such as a heart attack, causes levels of MCL-1 to drop in the heart, and this process may increase cardiac cell death,” said Åsa B. Gustafsson, Ph.D., an associate professor at UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences. “Therefore, preserving normal levels of this protein in cardiac tissue could reduce damage after a heart attack and prevent progression to heart failure.”

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Developmental protein plays role in spread of cancer

Protein is called Receptor-tyrosine-kinase-like Orphan Receptor 1 or ROR1.

Metastasized human breast cancer cells (magnified 400 times, stained brown) in lymph nodes.

A protein used by embryo cells during early development, and recently found in many different types of cancer, apparently serves as a switch regulating the spread of cancer, known as metastasis, report researchers at the UC San Diego School of Medicine and UC San Diego Moores Cancer Center in the June 15 issue of the journal Cancer Research.

Metastasis is responsible for 90 percent of cancer-related deaths. More than 575,000 Americans die of cancer each year, the second leading cause of death in the United States after cardiovascular disease.

The scientists, led by principal investigator Thomas Kipps, M.D., Ph.D., Evelyn and Edwin Tasch Chair in Cancer Research at UC San Diego, discovered an association between the protein, called Receptor-tyrosine-kinase-like Orphan Receptor 1 or ROR1, and the epithelial-mesenchymal transition (EMT), a process that occurs during embryogenesis when cells migrate and then grow into new organs during early development.

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Hormone therapy for endometrial cancer targets connective tissue

Progesterone treatment eliminates tumor cells by binding to receptors in connective tissue.

Sanaz Memarzadeh, UCLA

The female hormone progesterone has been used for several decades as a therapy for endometrial cancer, which starts in the lining of the uterus. Yet scientists didn’t understand the mechanisms behind the therapy or its site of action.

Now, a new a study from the G.O. Discovery Lab team at UCLA and UCLA collaborators shows that progesterone, rather than directly targeting tumors, eliminates tumor cells indirectly by binding to progesterone receptors in connective tissue cells (stroma) in the tumors’ microenvironment.

Like breast and prostate tumors, endometrial cancer is regulated by hormones. But unlike therapies for those cancers, in which drugs block hormone signaling, progesterone therapy actually stimulates its hormone receptor, the researchers found.

While doctors know that a certain subsets of patients will benefit from progesterone treatment, prescribing the therapy is like shooting in the dark because it’s unclear in advance which women will respond and which may have resistant tumors, according to the study’s senior author, Dr. Sanaz Memarzadeh, an assistant professor of obstetrics and gynecology and director of the G.O. Discovery Lab at UCLA. Therefore, while progesterone can be effective as a therapy in endometrial cancer, its use is not widely embraced in clinical practice, she said.

“When viewing tumors under the microscope, clinicians often focus on the cancer cells and neglect the supporting stroma in the microenvironment,” said Memarzadeh, who also is a researcher at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA and UCLA’s Jonsson Comprehensive Cancer Center. “In this study, we found that all of the progesterone anti-tumor effects are in fact mediated through the stroma, even though it makes up a minor fraction of the tumor. I believe these exciting findings are going to surprise the clinical community and change the way people look at patterns of hormone-receptor expression in endometrial tumors.”

The results of the three-year study, done using a specially developed laboratory model created by Memarzadeh’s team that closely mimics human endometrial cancer, appear in the early online edition of Cancer Research, a peer-reviewed journal of the American Association for Cancer Research.

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Supreme Court rules that human genes can’t be patented

UCSF geneticist led charge to challenge company’s monopoly of cancer genetic test.

Robert Nussbaum, UC San Francisco

The scientific community at UC San Francisco is reacting positively to the Supreme Court’s unanimous ruling on Thursday that human genes cannot be patented.

Most agree that the ruling reduces barriers to genetic testing and enables scientists to further genetic research and share data aimed ultimately at preventing and curing disease.

“This is great news for patient care,” says Beth Crawford, M.S., a genetic counselor and director of genetic counseling for the Cancer Risk Program at the UCSF Helen Diller Family Comprehensive Cancer Center. “It will provide patients with greater access to genetic testing and will decrease the cost over time for the tests. Across the board, genetic medicine will move forward to advance scientific and clinical research.”

Adds Julie Mak, M.S., also a genetic counselor for the Cancer Risk Program, “Our community is enormously excited to learn that the Supreme Court of the United States has ruled against the patenting of human genes. We agree that this is appropriate, as genes are naturally occurring and not the creation of any individual or company.”

Until now, if a woman in the United States wanted to get tested to see whether she carried a potentially deadly mutation for two breast cancer genes – BRCA1 and BRCA2 – she had to go through a company that had found the precise location of the genes and patented its discovery.

The company, Utah-based Myriad Genetics Inc., was sued over its claim of patents relating to BRCA1 and BRCA2, whose mutations are linked to increased hereditary risk for breast and ovarian cancer.

Myriad Genetics angered many in the genetic research community by guarding tightly the results of the thousands of tests that have been performed since Myriad launched the BRACAnalysis test in 1996, and with those, critical data on which mutations are significant for people of diverse backgrounds. Those critics include UCSF geneticist Robert Nussbaum, M.D., who argued that the genetic information should be in the public domain to help advance scientific discovery.

Nussbaum, chief of the Division of Genomic Medicine at UCSF, started a grass-roots project, Sharing Clinical Reports, to make the vast amount of data gleaned from Myriad available to the research community.

“My real focus is on delivering medical care,” Nussbaum, who was in clinic Thursday and unavailable to comment, told KQED’s “On the Media” in an interview last month. “Suppose every radiology department in the country took X-rays, interpreted their results and kept it private to themselves. … How much progress would have been made in interpreting CAT scans or MRI scans under that circumstance? I see that as very analogous.”

The Supreme Court on Thursday ruled that “naturally occurring DNA segment is a product of nature and not patent eligible merely because it has been isolated,” Justice Clarence Thomas wrote in the majority opinion.

The ruling is seen as somewhat of a split decision since all nine justices said while the naturally occurring, isolated biological material itself is not patentable, a synthetic version of the gene material may be patented.

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Related link:
UC Santa Cruz: Gene patent decision called step forward for open research




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