Mayo Clinic researchers along with collaborators from Life Technologies are reporting on the application of a new approach for sequencing RNA to study cancer tumors. Their findings from a proof-of-principle study on oral carcinomas appear in the current issue of PLoS One, the online science journal.
To explore the advantages of massively parallel sequencing of genomic transcripts (RNA), the researchers used a novel, strand-specific sequencing method using matched tumors and normal tissues of three patients with the specific cancer. They also analyzed the genomic DNA from one of the tumor-normal pairs which revealed numerous chromosomal regions of gain and loss in the tumor sample.
The key finding of this work was that alterations in gene expression which can arise from a variety of genomic alterations frequently are driven by losses or gains in large chromosomal regions during tumor development.
In addition to the specific tumor findings, this study also demonstrated the value of this RNA sequencing (RNA-Seq) method. It will allow researchers to measure strand-specific expression across the entire sample's transcriptome. This technology reveals far more detail about genome-wide transcription than traditional microarrays.
"This method allows us to investigate genetic changes at a level that we were never able to see before," says David Smith, Ph.D., Mayo Clinic genomics researcher and corresponding author of the study. "This provides us with much more information about alterations during cancer development that could reveal important therapeutic targets. We can more completely understand the relationship between an individual's genome and the alterations to that which result in disease.
This is a huge step in speed, detail and diagnostic power for the field of individualized medicine. This transforms how we are going to study cancer -- and how we're going to practice medicine -- in the very near future."
The urgency of this condition points to the need for more efficient technologies and methods. Head and neck cancers are the sixth most prevalent carcinomas in the world. Advanced stage oral and throat cancers have a five-year survival rate of only 50 percent in the United States. Information provided by these and continued studies will help to better characterize the molecular basis of cancer development. That information can hopefully define better therapeutic strategies for treating an individual's specific cancer.
Tuesday, February 23, 2010
SIBLING proteins may predict oral cancer
IMAGE: Dr. Kalu Ogbureke is an oral and maxillofacial pathologist in the MCG School of Dentistry.
The presence of certain proteins in premalignant oral lesions may predict oral cancer development, Medical College of Georgia researchers said.
SIBLINGs, or Small Integrin-Binding Ligand N-linked Glycoproteins, are a family of five proteins that help mineralize bone but can also spread cancer. SIBLINGs have been found in cancers including breast, lung, colon and prostate.
"Several years ago we discovered that three SIBLINGs—osteopontin, bone sialoprotein and dentin sialophosphoprotein—were expressed at significantly high levels in oral cancers," said Dr. Kalu Ogbureke, an oral and maxillofacial pathologist in the MCG School of Dentistry. "Following that discovery, we began to research the potential role of SIBLINGs in oral lesions before they become invasive cancers."
The study, published online this week in the journal Cancer, examined 60 archived surgical biopsies of precancerous lesions sent to MCG for diagnosis and the patients' subsequent health information. Eighty-seven percent of the biopsies were positive for at least one SIBLING protein—which the researchers discovered can be good or bad, depending on the protein. For instance, they found that the protein, dentin sialophosphoprotein, increases oral cancer risk fourfold, while bone sialoprotein significantly decreases the risk.
"The proteins could be used as biomarkers to predict [the potential of a lesion to become cancerous]," said Dr. Ogbureke, the study's lead author. "That is very significant, because we would then be in a position to modify treatment for the individual patient's need in the near future."
Precancerous oral lesions, which can develop in the cheek, tongue, gums and floor and roof of the mouth, are risk factors for oral squamous cell carcinoma, which accounts for over 95 percent of all oral and pharyngeal cancers. Oral cancer, the sixth most common cancer in the world, kills about 8,000 Americans annually, Dr. Ogbureke said.
Treatment has been stymied up to this point because of clinicians' inability to predict which lesions will become cancerous. Surgery is standard for oral cancer, but treatment methods vary for precancerous lesions.
"When we treat these lesions now, there's an implied risk of under- or over-treating patients," Dr. Ogbureke said. "For example, should the entire lesion be surgically removed before we know its potential to become cancer, or should we wait and see if it becomes cancer before intervening?"
Further complicating the matter is that the severity of dysplasia, or abnormal cell growth, in a lesion can be totally unrelated to cancer risk. Some mild dysplasias can turn cancerous quickly while certain severe dysplasias can remain harmless indefinitely. The protein findings, which help eliminate the guesswork in such cases, "are fundamental," Dr. Ogbureke said. "If we're able to recognize these lesions early and biopsy them to determine their SIBLING profile, then oral cancer could be preventable and treatable very early."
Dr. Ogbureke's next step is to design a multi-center study that incorporates oral cancer risk factors, such as smoking and alcohol consumption, to further investigate their relationship with SIBLING protein expression.
Comments by American Dental Association
*
On the Pew Center on the States’ report
‘The Cost of Delay: State Dental Policies Fail One in Five Children’
President Dr. Ron Tankersley:
“We welcome the Pew organization to our longstanding fight to improve the lives of American children by helping more of them enjoy the good oral health that too many of them now lack. Pew’s presenting its information in the form of a report card makes it easy for anyone to understand that too many kids in too many states are suffering. And we face huge challenges in changing that.
“Even in states to which Pew awarded an A, countless children lack access to dental care and suffer as a consequence. These children are just like your children. Except these children can’t eat or sleep properly, can’t pay attention in school, can’t even smile, because of untreated dental disease.
“We don’t agree with everything in the report. But certainly, it highlights some of the major policy areas that the American Dental Association and state dental societies have advocated for years—things like increased Medicaid funding, school sealant programs and community water fluoridation. It also highlights the urgent need for reliable routine data collection so that policies are well-informed and kids are not left suffering.
“The report does omit some policy areas that we believe are equally important to improving children’s access to care. For instance, some states have innovative programs—like student loan forgiveness and tax incentives—to help dentists establish practices in underserved areas or practice in community health centers. And when it comes to fixing Medicaid, money is a huge issue, but it isn’t the only issue. Patients and parents need oral health education to help them take care of themselves and their families to prevent disease. Many of them need additional services, like transportation, in order to be able to get to dental appointments. If Medicaid did a better job of these things, treatment costs would decrease, because we would be preventing more disease and treating less.
“The ADA and state dental societies have a long history as the nation’s leading advocates for oral health. ADA members donated some $2.16 billion in free care to disadvantaged children and adults, both as individuals and through such programs as Give Kids A Smile and Missions of Mercy, in 2007 alone. . But we’re the first to admit that we can’t do this alone, and charity is no substitute for an effective, equitable oral health delivery system. We’re grateful for assistance from the Pew Center and others who are willing to lend a hand in what undoubtedly will remain a long, tough fight.”
On the Pew Center on the States’ report
‘The Cost of Delay: State Dental Policies Fail One in Five Children’
President Dr. Ron Tankersley:
“We welcome the Pew organization to our longstanding fight to improve the lives of American children by helping more of them enjoy the good oral health that too many of them now lack. Pew’s presenting its information in the form of a report card makes it easy for anyone to understand that too many kids in too many states are suffering. And we face huge challenges in changing that.
“Even in states to which Pew awarded an A, countless children lack access to dental care and suffer as a consequence. These children are just like your children. Except these children can’t eat or sleep properly, can’t pay attention in school, can’t even smile, because of untreated dental disease.
“We don’t agree with everything in the report. But certainly, it highlights some of the major policy areas that the American Dental Association and state dental societies have advocated for years—things like increased Medicaid funding, school sealant programs and community water fluoridation. It also highlights the urgent need for reliable routine data collection so that policies are well-informed and kids are not left suffering.
“The report does omit some policy areas that we believe are equally important to improving children’s access to care. For instance, some states have innovative programs—like student loan forgiveness and tax incentives—to help dentists establish practices in underserved areas or practice in community health centers. And when it comes to fixing Medicaid, money is a huge issue, but it isn’t the only issue. Patients and parents need oral health education to help them take care of themselves and their families to prevent disease. Many of them need additional services, like transportation, in order to be able to get to dental appointments. If Medicaid did a better job of these things, treatment costs would decrease, because we would be preventing more disease and treating less.
“The ADA and state dental societies have a long history as the nation’s leading advocates for oral health. ADA members donated some $2.16 billion in free care to disadvantaged children and adults, both as individuals and through such programs as Give Kids A Smile and Missions of Mercy, in 2007 alone. . But we’re the first to admit that we can’t do this alone, and charity is no substitute for an effective, equitable oral health delivery system. We’re grateful for assistance from the Pew Center and others who are willing to lend a hand in what undoubtedly will remain a long, tough fight.”
Majority of States Fail to Ensure Proper Dental Health & Access to Care for Children
An estimated one in five children in America go without dental care each year and two thirds of states do not have effective policies in place to ensure proper dental health and access to care, according to a report by the Pew Center on the States.
The Cost of Delay: State Dental Policies Fail One in Five Children, released with support from the W.K. Kellogg Foundation and the DentaQuest Foundation, grades each state's policy responses to the urgent challenges in dental health among America's low-income children. February is National Children's Dental Health Month.
"Millions of children go without dental care each year but the good news is, it's fixable," said Shelly Gehshan, director of the Pew Children's Dental Campaign. "By enacting a handful of effective policies, states can help eliminate the long-term health and economic consequences of untreated dental problems among kids. Several states are leading the way—but all states can and must do more to ensure access to dental care for the 17 million children left out of the system."
Pew scored all 50 states and the District of Columbia, using an A-F scale, on whether and how well they are employing eight proven policy solutions to ensure dental health and access to care for children. These policies fall into four categories: cost-effective ways to help prevent problems from occurring in the first place; Medicaid improvements that enable and motivate more dentists to treat disadvantaged children; new workforce models that expand the number of qualified dental providers; and gathering data to gauge progress and improve performance.
Only six states merited "A" grades: Connecticut, Iowa, Maryland, New Mexico, Rhode Island and South Carolina. These states met at least six of the eight policy benchmarks and had policies in place that met or exceeded the national performance standards. These high grades do not mean that all people in the state have access to quality dental care services. Severe access problems still exist in states that received "A" grades, but these states have policies in place needed to improve dental care.
Nine states received a grade of "B": Alaska, Colorado, Idaho, Illinois, Maine, New Hampshire, Ohio, Texas and Washington. Twenty states received a grade of "C" because they met four or fewer of the eight policy benchmarks. Six states and the District of Columbia earned a "D" grade: Alabama, Indiana, Mississippi, Montana, Nevada and Utah. Nine states earned an "F," meeting only one or two policy benchmarks: Arkansas, Delaware, Florida, New Jersey, Hawaii, Louisiana, Pennsylvania, West Virginia and Wyoming. No state met all eight targets. New Jersey ranked lowest in the nation, meeting only one benchmark.
There are many solutions that can be achieved at relatively little cost and the return on investment for children and taxpayers will be significant. Americans are expected to spend $106 billion on dental care in 2010. This includes many expensive restorative treatments – from fillings to root canals – that could have been mitigated or avoided altogether with earlier, easier and less expensive ways of ensuring adequate dental care when they were children.
The Pew report highlights four proven solutions that can improve both the dental health of children and their access to care:
• Sealants: Protective coatings applied to the teeth by a dentist or hygienist cost one third as much as filling a cavity and have been shown to prevent 60 percent of cavities. School-based programs are the most cost-effective strategy for providing sealants to disadvantaged children, yet this strategy is vastly underutilized.
• Community water fluoridation: Identified by the Centers for Disease Control and Prevention (CDC) as one of 10 great public health achievements of the 20th Century, fluoridated water counteracts tooth decay and strengthens teeth. Fluoride occurs naturally in water, but the level varies within states and across the country. In addition to being the most far-reaching preventive measure states can enact, fluoridation also offers an unmatched return on investment, saving $38 in dental treatment costs for every dollar spent. About 30 percent of the population on community water systems does not yet receive fluoridated water.
• Medicaid improvements: Making minor changes to this federal program can enable and motivate more dentists to treat low-income children. Only 38 percent of Medicaid-eligible children received dental care in 2007, largely because too few dentists are willing to treat them. The number of children receiving dental services more than doubled over just four years in several states that have increased Medicaid reimbursement rates.
• More dental providers: New professionals, similar to nurse practitioners in the medical field, can expand the number of qualified dental providers who can fill the unmet needs of children. A growing number of states are exploring new models that increase the involvement of physicians, hygienists, and new types of dental professionals.
DentaQuest Foundation
The DentaQuest Foundation is committed to optimal oral health for all Americans through its support of prevention and access to affordable oral health care, and through partnerships with philanthropies, policy makers and community leaders.
The Cost of Delay: State Dental Policies Fail One in Five Children, released with support from the W.K. Kellogg Foundation and the DentaQuest Foundation, grades each state's policy responses to the urgent challenges in dental health among America's low-income children. February is National Children's Dental Health Month.
"Millions of children go without dental care each year but the good news is, it's fixable," said Shelly Gehshan, director of the Pew Children's Dental Campaign. "By enacting a handful of effective policies, states can help eliminate the long-term health and economic consequences of untreated dental problems among kids. Several states are leading the way—but all states can and must do more to ensure access to dental care for the 17 million children left out of the system."
Pew scored all 50 states and the District of Columbia, using an A-F scale, on whether and how well they are employing eight proven policy solutions to ensure dental health and access to care for children. These policies fall into four categories: cost-effective ways to help prevent problems from occurring in the first place; Medicaid improvements that enable and motivate more dentists to treat disadvantaged children; new workforce models that expand the number of qualified dental providers; and gathering data to gauge progress and improve performance.
Only six states merited "A" grades: Connecticut, Iowa, Maryland, New Mexico, Rhode Island and South Carolina. These states met at least six of the eight policy benchmarks and had policies in place that met or exceeded the national performance standards. These high grades do not mean that all people in the state have access to quality dental care services. Severe access problems still exist in states that received "A" grades, but these states have policies in place needed to improve dental care.
Nine states received a grade of "B": Alaska, Colorado, Idaho, Illinois, Maine, New Hampshire, Ohio, Texas and Washington. Twenty states received a grade of "C" because they met four or fewer of the eight policy benchmarks. Six states and the District of Columbia earned a "D" grade: Alabama, Indiana, Mississippi, Montana, Nevada and Utah. Nine states earned an "F," meeting only one or two policy benchmarks: Arkansas, Delaware, Florida, New Jersey, Hawaii, Louisiana, Pennsylvania, West Virginia and Wyoming. No state met all eight targets. New Jersey ranked lowest in the nation, meeting only one benchmark.
There are many solutions that can be achieved at relatively little cost and the return on investment for children and taxpayers will be significant. Americans are expected to spend $106 billion on dental care in 2010. This includes many expensive restorative treatments – from fillings to root canals – that could have been mitigated or avoided altogether with earlier, easier and less expensive ways of ensuring adequate dental care when they were children.
The Pew report highlights four proven solutions that can improve both the dental health of children and their access to care:
• Sealants: Protective coatings applied to the teeth by a dentist or hygienist cost one third as much as filling a cavity and have been shown to prevent 60 percent of cavities. School-based programs are the most cost-effective strategy for providing sealants to disadvantaged children, yet this strategy is vastly underutilized.
• Community water fluoridation: Identified by the Centers for Disease Control and Prevention (CDC) as one of 10 great public health achievements of the 20th Century, fluoridated water counteracts tooth decay and strengthens teeth. Fluoride occurs naturally in water, but the level varies within states and across the country. In addition to being the most far-reaching preventive measure states can enact, fluoridation also offers an unmatched return on investment, saving $38 in dental treatment costs for every dollar spent. About 30 percent of the population on community water systems does not yet receive fluoridated water.
• Medicaid improvements: Making minor changes to this federal program can enable and motivate more dentists to treat low-income children. Only 38 percent of Medicaid-eligible children received dental care in 2007, largely because too few dentists are willing to treat them. The number of children receiving dental services more than doubled over just four years in several states that have increased Medicaid reimbursement rates.
• More dental providers: New professionals, similar to nurse practitioners in the medical field, can expand the number of qualified dental providers who can fill the unmet needs of children. A growing number of states are exploring new models that increase the involvement of physicians, hygienists, and new types of dental professionals.
DentaQuest Foundation
The DentaQuest Foundation is committed to optimal oral health for all Americans through its support of prevention and access to affordable oral health care, and through partnerships with philanthropies, policy makers and community leaders.
Saturday, February 13, 2010
Psychosocial Problems Are Common in Children With Dental Fear
Children and adolescents with severe dental fear often come from families with a turbulent background. It is also more common that they have had counselling contact with a psychologist. These are the conclusions of research carried out at the Sahlgrenska Academy at the University of Gothenburg, Sweden.
Annika Gustafsson, specialist in child dentistry, has studied children and adolescents of school age who have received specialist dental care because they develop many cavities and also suffer from severe dental fear. "I wanted to investigate how children and adolescents with dental behaviour management problems who received specialist dental care differed from patients of the same age within ordinary dental care. I also wanted to discover why they cancel appointments and fail to attend appointments more often," says Annika Gustafsson.
Just over 250 children and adolescents with dental behaviour management problems and their parents have completed questionnaires describing their family situation and everyday life. Their answers have been compared with answers from the same number of patients within ordinary dental care. "The children and adolescents with dental behaviour management problems suffered significantly more from dental fear, and they lived in families with lower social class and poor economy. Most often, they lived in single-parent families, they had fewer leisure activities and more psychosocial problems than patients within ordinary dental care," says Annika Gustafsson.
Their parents, in turn, stated that they also suffered from severe dental fear and had greater problems with anxiety and worry than parents of children and adolescents within ordinary dental care. "I believe that it has a negative effect on a child or adolescent if their parent does not want to go to the dentist with them due to the parent's own fear," says Annika Gustafsson, who has compared the number of cancelled appointments and appointments that they failed to attend for the children and adolescents with dental fear and for those in ordinary dental care. "Children and adolescents that avoided dental appointments had had contact with a psychologist or counsellor four times as often," says Annika Gustafsson.
She believes that it is important that these patients are met with respect and understanding within the dental care system. "We must also become better at discovering at an early age which children and adolescents need help and support. We should collaborate more closely with the social services," says Annika Gustafsson.
Dental fear
About 5% of Sweden's population suffer from severe dental fear. The very thought of dental care produces severe anxiety in these patients. The fear may have been caused by frightening experiences of dental care during childhood. Fortunately, many types of help are available, including medication for anxiety, nitrous oxide gas, hypnosis and -- in severe cases -- anaesthesia.
Annika Gustafsson, specialist in child dentistry, has studied children and adolescents of school age who have received specialist dental care because they develop many cavities and also suffer from severe dental fear. "I wanted to investigate how children and adolescents with dental behaviour management problems who received specialist dental care differed from patients of the same age within ordinary dental care. I also wanted to discover why they cancel appointments and fail to attend appointments more often," says Annika Gustafsson.
Just over 250 children and adolescents with dental behaviour management problems and their parents have completed questionnaires describing their family situation and everyday life. Their answers have been compared with answers from the same number of patients within ordinary dental care. "The children and adolescents with dental behaviour management problems suffered significantly more from dental fear, and they lived in families with lower social class and poor economy. Most often, they lived in single-parent families, they had fewer leisure activities and more psychosocial problems than patients within ordinary dental care," says Annika Gustafsson.
Their parents, in turn, stated that they also suffered from severe dental fear and had greater problems with anxiety and worry than parents of children and adolescents within ordinary dental care. "I believe that it has a negative effect on a child or adolescent if their parent does not want to go to the dentist with them due to the parent's own fear," says Annika Gustafsson, who has compared the number of cancelled appointments and appointments that they failed to attend for the children and adolescents with dental fear and for those in ordinary dental care. "Children and adolescents that avoided dental appointments had had contact with a psychologist or counsellor four times as often," says Annika Gustafsson.
She believes that it is important that these patients are met with respect and understanding within the dental care system. "We must also become better at discovering at an early age which children and adolescents need help and support. We should collaborate more closely with the social services," says Annika Gustafsson.
Dental fear
About 5% of Sweden's population suffer from severe dental fear. The very thought of dental care produces severe anxiety in these patients. The fear may have been caused by frightening experiences of dental care during childhood. Fortunately, many types of help are available, including medication for anxiety, nitrous oxide gas, hypnosis and -- in severe cases -- anaesthesia.
Subscribe to:
Posts (Atom)