Author: Brianna Deane

 

FINDINGS:

 

IMPACT:
Human squamous cell carcinoma is highly invasive and frequently spreads to cervical lymph nodes. Understanding the molecular and epigenetic mechanisms that control the metastasis of squamous cell carcinoma in humans will help scientists develop new therapies for treating cancer.  

 

AUTHORS:

FUNDING:
This work was supported in part by grants from the National Institute of Dental and Craniofacial Research of the National Institutes of Health and the Shapiro Family Charitable Foundation.

JOURNAL:
Wang’s new research is published in Science Signaling — a peer-reviewed scientific journal published by the American Association for the Advancement of Science.

Recently, doctors have begun to categorize breast cancers into four main groups according to the genetic makeup of the cancer cells. Which category a cancer falls into generally determines the best method of treatment.

 

But cancers in one of the four groups — called “basal-like” or “triple-negative” breast cancer (TNBC) — have been particularly tricky to treat because they usually don’t respond to the “receptor-targeted” treatments that are often effective in treating other types of breast cancer. TNBC tends to be more aggressive than the other types and more likely to recur, and can also have a higher mortality rate.

 

Fortunately, better drug therapies may be on the horizon. UCLA researchers and collaborators led by Dean Ho, a professor at the UCLA School of Dentistry and co-director of the school’s Jane and Jerry Weintraub Center for Reconstructive Biotechnology, have developed a potentially more effective treatment for TNBC that uses nanoscale, diamond-like particles called nanodiamonds.

 

Nanodiamonds are between 4 and 6 nanometers in diameter and are shaped like tiny soccer balls. Byproducts of conventional mining and refining operations, the particles can form clusters following drug binding and have the ability to precisely deliver cancer drugs to tumors, significantly improving the drugs’ desired effect. In the UCLA study, the nanodiamond delivery system has been able to home in on tumor masses in mice with triple negative breast cancer.

 

Findings from the study are published online April 15 in the peer-reviewed journal Advanced Materials.

 

“This study demonstrates the versatility of the nanodiamond as a targeted drug-delivery agent to a tumor site,” said Ho, who is also a member of the California NanoSystems Institute at UCLA, UCLA’s Jonsson Comprehensive Cancer Center and the UCLA Department of Bioengineering. “The agent we’ve developed reduces the toxic side effects that are associated with treatment and mediates significant reductions in tumor size.”

 

The team combined several important cancer-fighting components on the nanodiamond surface, including Epirubicin, a highly toxic but widely used chemotherapy drug that is often administered in combination with other cancer drugs. The new compound was then bound to a cell-membrane material coated with antibodies that were targeted toward the epidermal growth factor receptor, which is highly concentrated on the surfaces of TNBC cells. The resulting agent is a drug-delivery system called a nanodiamond-lipid hybrid compound, or NDLP.

 

When tested on mice, the agent was shown to notably decrease tumor growth and eliminate the devastating side effects of cancer treatment.

 

Because of its toxicity, Epirubicin, when administered alone can cause serious side effects, such as heart failure and reduced white blood cell count, and it has been linked to an increased risk for leukemia. In the study, all of the mice that were given Epirubicin alone died well before the completion of the study. But all the mice given Epirubicin through the targeted NDLPs survived the treatment, and some of the tumors even regressed until they were no longer visible.

 

“Triple-negative breast cancer is often very aggressive and hard to treat, making aggressive chemotherapy a requirement,” said Dr. Edward K. Chow, co-first author of the study and an assistant professor at the Cancer Science Institute of Singapore. “The targeting and therapeutic efficiency of the nanodiamond-lipid agents were quite remarkable. The simultaneous tumor regression and improved drug tolerance are promising indicators for the continued development of the nanodiamonds toward clinical translation.”

 

The research team is now studying the efficacy and safety of the NDLPs in larger animals. Additional research objectives include determining whether nanodiamonds can enhance the tolerance of a wide spectrum of highly toxic drug compounds, which may improve current treatment options and outcomes. These discoveries will serve as precursors for human trials, the researchers said.

 

“The nanodiamond-lipid hybrid developed in this study is a modular platform,” said Laura Moore, a graduate student in Ho’s laboratory and a co-first author of the study. “Therefore, we can easily bind a wide spectrum of targeting antibodies and drug compounds to address several diseases.”

 

Dr. No-Hee Park, dean of the UCLA School of Dentistry, noted that the research will provide a foundation for future clinical applications.

 

“This pioneering study conducted by Dean Ho and his team provides a better understanding of the capabilities of the nanodiamond material to address several diseases,” Park said. “Their work is of paramount importance.”

 

Other authors of the study were Professor Eiji Osawa of the NanoCarbon Research Institute in Nagano, Japan, and Professor J. Michael Bishop of UC San Francisco. Laura Moore is currently at Northwestern University.

 

The study was supported by the National Cancer Institute, the National Science Foundation, the Wallace H. Coulter Foundation, the V Foundation for Cancer Research, the Society for Laboratory Automation and Screening, the George Williams Hooper Foundation, the American Cancer Society, Beckman Coulter, the European Commission, the Cancer Science Institute of Singapore, and the Singapore Ministry of Education Academic Research Fund.

 

The UCLA School of Dentistry is dedicated to improving the oral and systemic health of the people of California, the nation and the world through its teaching, research, patient care and public service initiatives. The School of Dentistry provides education and training programs that develop leaders in dental education, research, the profession and the community. The School of Dentistry also conducts research programs that generate new knowledge, promote oral health and investigate the cause, prevention, diagnosis and treatment of oral disease in an individualized disease-prevention and management model; and delivers patient-centered oral health care to the community and the state.

 

For more news, visit the UCLA Newsroom and follow us on Twitter.

The UCLA School of Dentistry has been awarded funding of more than $11 million from the Los Angeles–based child advocacy and grant-making organization First 5 LA to expand access to dental care in Los Angeles.

 

The funds will establish the UCLA–First 5 LA Children’s Dental Care Program (CDCP), which will support the delivery of care to children, from birth to age 5, and pregnant women over the next five years. The program will be especially beneficial to those in underserved communities, who are at high risk for dental disease, school officials said.

 

This new award comes on the heels of the $9.23 million that First 5 LA awarded to the dental school last year, bringing the total amount the school has received from the organization to nearly $21 million over the past 12 months.

 

“Our goal, over the next five years, is to develop an integrated health-care delivery system that will provide quality, ongoing dental care to underserved young children and pregnant women in Los Angeles communities,” said Dr. James J. Crall, project director of the CDCP. “We hope the Children’s Dental Care Program will serve as a prototype for transforming the oral health care system for young children throughout Los Angeles County and beyond.”

 

As part of the new program, UCLA faculty members hope to gain a better understanding of the barriers that limit the use of dental care services by underserved groups in order to initiate improvements in care.

“While focusing on dental care for young children, the program is also targeting pregnant women in an effort to provide them with the information and education they need to be able to provide a more positive and healthier approach to oral health for their developing children,” Crall said.

 

The program will roll out four major strategies over the next five years to increase access to oral heath care and improve the quality of care for young children and pregnant women: 

“This is a major investment by First 5 LA in Los Angeles County’s oral health care delivery system,” said No-Hee Park, dean of the UCLA School of Dentistry. “This funding will impact the oral health of tens of thousands of people for the foreseeable future. Greater access to quality oral health care must be addressed. Developing these improved delivery systems in our underserved communities is the best place to start.”

 

Crall, the CDCP project director, is a professor and chair of the division of public health and community dentistry at the UCLA School of Dentistry, a member of the UCLA Center for Healthier Children, Families and Communities, and project director for the UCLA–First 5 LA 21st-Century Dental Homes Project.

 

First 5 LA oversees the Los Angeles County allocation of funds from Proposition 10, which added a 50-cent tax on tobacco products sold in California. Funds raised help pay for health care, education and child development programs for children from the prenatal stage to age 5 and their families. First 5 LA’s mission is to increase the number of young children who are physically and emotionally healthy, safe and ready to learn.

 

The UCLA School of Dentistry is dedicated to improving the oral health of the people of California, the nation and the world through its teaching, research, patient care and public service initiatives. The School provides education and training programs that develop leaders in dental education, research, the profession and the community; conducts research programs that generate new knowledge, promote oral health and investigate the cause, prevention, diagnosis and treatment of oral disease in an individualized disease-prevention and management model; and delivers patient-centered oral health care to the community and the state.

 

For more news, visit the UCLA Newsroom and follow us on Twitter.

Philanthropists Dr. Mick Dragoo and his wife, Mary, have pledged a landmark gift of $5 million to the UCLA School of Dentistry to establish the UCLA Mick and Mary Dragoo Periodontal and Implant Clinical Research and Patient Care Center.

The Dragoo’s gift, the largest single donation from an individual or couple the dental school has ever received, will create a leading site for clinical research, patient care and education in periodontology and implantology — specialized areas of dentistry related to tooth-supporting structures and tooth replacement.

 

The new Dragoo Periodontal and Implant Center will be a place for world-renowned faculty to conduct independently funded clinical research to advance scientific knowledge in periodontal and implant dentistry. Researchers from the school will translate their findings into meaningful treatment protocols and will disseminate their research through publications, educational programs and the Internet to advance the state of patient care worldwide.

 

“With Dr. and Mrs. Dragoo’s extremely generous gift, our hope is to advance the standard of patient care, as well as influence decisions made by dentists and patients alike,” said Dr. No-Hee Park, dean of the UCLA School of Dentistry. “The Dragoo Center helps us further achieve our mission, which is to improve the oral health of the people of the world. I cannot thank the Dragoos enough for their support.”

 

Directing the Dragoo Periodontal and Implant Center will be Dr. Perry Klokkevold, an associate professor, acting chair and director of the residency program in the section of periodontics at the UCLA School of Dentistry. Klokkevold has more than 20 years of experience in education, administration and clinical practice in periodontics and implantology.

 

“We searched the country for the perfect place and director to execute our vision,” said Mick Dragoo. “Our search led us to the UCLA School of Dentistry, and we are thrilled that Dean No-Hee Park has appointed Dr. Klokkevold as the director of our new center.”

 

“I am fully committed, honored and inspired to have the opportunity to direct the Dragoo Periodontal and Implant Center,” Klokkevold said. “I share the Dragoo’s vision and goals of improving patient care worldwide through independently funded clinical research.”

 

Mick and Mary Dragoo are new donors to the UCLA family and the School of Dentistry. Dr. Dragoo is a well-known periodontist who has written and published numerous books and clinical articles. He has lectured extensively throughout the world and has been involved in independent clinical research on periodontology and implantology for nearly 40 years; he is considered an expert in these fields. He and Mary also own and operate Belle Marie Winery in Escondido, Calif., where Mick is the wine-maker.

 

The UCLA School of Dentistry is dedicated to improving the oral and systemic health of the people of California, the nation and the world through its teaching, research, patient care and public service initiatives. The School of Dentistry provides education and training programs that develop leaders in dental education, research, the profession and the community. The School of Dentistry also conducts research programs that generate new knowledge, promote oral health and investigate the cause, prevention, diagnosis and treatment of oral disease in an individualized disease-prevention and management model; and delivers patient-centered oral health care to the community and the state.

 

For more news, visit the UCLA Newsroom and follow us on Twitter.

 

Scientists from the UCLA School of Dentistry have been at the vanguard of research on human saliva in recent years, leading the way in the dynamic, emerging field of salivary diagnostics, which seeks to catalog the biological makeup of saliva to help screen for and detect both oral and systemic diseases.

 

Now, the Journal of the American Dental Association, a leading publication for dental professionals, has published a special supplement to its October issue in which Dr. David Wong, the school’s associate dean of research, outlines the state of the science of salivary diagnostics, highlighting advances made by researchers at UCLA and other institutions and charting a path for future research and clinical applications.

 

In the article, Wong’s research findings show that saliva is made up of complex sets of molecules — including genes, proteins, DNA and RNA — that help paint a picture of an individual’s biology. The study of the biological molecules in saliva is known as “salivaomics.” Findings show that by studying the “omics” in saliva — such as genomics, transcriptomics and proteomics — scientists can develop tests composed of many molecular measurements; the findings are then interpreted by a computational model to produce a clinically actionable result.

 

Through collaborative work with scientists at other institutions, UCLA researchers have developed several informatics and statistical tools to help interpret biomarkers in saliva; these biomarkers can then be used for early detection of disease, treatment monitoring, recurrence prediction and other translational assessments.

 

Research done at the UCLA School of Dentistry has shown that saliva, as a medium for health screening is just as useful as blood and other bodily fluids and has vast potential for the early detection of cancers, autoimmune diseases, diabetes and other disorders.

The ability to conveniently and inexpensively capture saliva samples in a clinical setting for diagnostic purposes would be a huge step forward for health care providers in the detection, treatment and prediction of recurrence of life-threatening diseases. Wong expects that future research in salivaomics will eventually translate into practical medical applications that will be administered in dentists’ and doctors’ offices.

 

And because it has been shown that 20 percent more Americans visit their dentists more regularly than their physicians, there will be substantial opportunities for dentists to engage in primary health care by taking saliva samples from their patients and, based on the medical findings of those samples, developing individualized treatment plans.

Dr. David Wong, a professor of oral biology and medicine who holds the Felix and Mildred Yip Endowed Chair in Dentistry at the UCLA School of Dentistry, is available for interviews.

 

JOURNAL:
Wong’s work appears in a special supplement to the October issue of the Journal of the American Dental Association. The full article can be read here.

FUNDING:
Wong’s research has been funded by the National Institute of Dental and Craniofacial Research and the National Cancer Institute.

Each year, more than a million Americans are at-risk of developing serious mental health problems after experiencing a terrifying event or serious physical injury. Once manifested, these psychiatric illnesses, such as post-traumatic stress disorder and depression, can be extremely crippling and difficult to treat and are a leading cause of disability in civilian, military and minority populations.

 

Recognizing these emerging disorders early on provides health care professionals the best opportunity for preventive interventions.

 

Now, a team of researchers, led by Dr. Vivek Shetty, a professor at the UCLA School of Dentistry, has received a $3.8 million research grant to develop a salivary-biomarker approach for identifying individuals at future risk of developing post-traumatic stress disorder and depression following a traumatic event.

 

Co-funded by the National Institute of Dental and Craniofacial Research and the National Institutes of Health’s Office of Behavioral and Social Sciences Research, the study seeks to develop a panel of salivary stress biomarkers that will allow early recognition of emerging mental health disorders and permit preemptive psychological care.

 

“Current assessment strategies rely on subjective reports of symptoms by trauma survivors,” Shetty said. “The symptom-based nature of psychological assessments presents significant challenges for trauma-care specialists attempting to differentiate between temporary distress and the early stages of mental health illnesses.

 

“Moreover,” he added, “the time and resource constraints of the acute-care setting do not allow for the structured screening required for psychological assessments. If successful, our salivary stress biomarker panel will allow the development of practical decision-aid tools to complement subjective clinical evaluation and allow timely referrals of ‘at-risk’ individuals.”

 

For the new five-year study, Shetty and his colleagues will repeatedly conduct psychological assessments and obtain corresponding saliva samples over a six-month period among a group of 600 individuals who have recently experienced a serious physical injury or sexual assault.

 

The team will use sophisticated analytical techniques to determine the levels of the individual salivary biomarkers at different points over the six months and to compare the biomarker patterns of individuals who subsequently develop PTSD and/or depression with those who do not.

 

The association of the biomarkers with mental disease would be used to develop mathematical models that utilize early stress biomarker levels to predict later development of traumatic psychopathology.

 

“Utilizing easily accessible saliva for evaluating stress reactions would allow front-line care providers to become more involved and proactive in the management of post-traumatic stress disorders, moving the focus away from treatment of unmanageable, late-stage conditions toward early identification and targeted interventions of vulnerable individuals,” said Shetty.

“Enabling health care providers to objectively and readily assess the risk for future psychological problems will set the stage for integrated post-trauma care that provides for essential and tailored mental health interventions in trauma care centers, as well as timely referrals for psychological after-care.”

 

The current research study builds on and complements Shetty’s ongoing development of mobile devices for point-of-care assessment and management of post-traumatic stress disorders using salivary diagnostics — a program funded through NIH’s Transdisciplinary Gene and Environment Initiative.

 

“Beyond the civilian population, post-traumatic mental health disorders are a significant problem for our military,” said Dr. No-Hee Park, dean of the School of Dentistry. “The scope of the mental health problem is increasingly manifest as thousands of soldiers are coming back from Iraq and Afghanistan. This grant allows Dr. Shetty to focus the skills and abilities of his team to help solve a very serious problem with advanced technology in the cutting-edge area of salivary diagnostics. I am hopeful that the results of this research will inform mental health efforts not only in civilian populations but also in military settings.

 

“Faculty from the UCLA School of Dentistry,” Park added, “have been at the forefront of the emerging field of salivary diagnostics in recent years, conducting groundbreaking research on the use of saliva as a diagnostic tool for the detection of oral cancer, early-stage pancreatic cancer, Sjogren’s syndrome and a variety of other maladies.”

 

 

For more news, visit the UCLA Newsroom and follow us on Twitter.