Now, a recently completed study conducted collaboratively by Dr. Joseph Guttenplan, a Professor of Basic Science & Craniofacial Biology at the NYU College of Dentistry, and Dr. Karam El-Bayoumy, a Professor of Biochemistry and Molecular Biology at Penn State University College of Medicine and Associate Director of Basic Research at the Penn State Cancer Institute, has shown that a powerful carcinogen in tobacco smoke can be used for oral cancer research in experimental animals, thus providing a new, more relevant research model with which to understand the initiation, progression, and, ultimately, the prevention of oral cancer. The two-year study was sponsored by the National Institute of Dental and Craniofacial Research, part of the NIH.

In a presentation on April 19 at the 2010 annual meeting of the American Association for Cancer Research (AACR) in Washington, DC, Dr. Guttenplan said the findings could ultimately facilitate research aimed at identifying new approaches to oral cancer prevention.

Oral cancer is a devastating disease that can severely and permanently compromise one’s ability to eat, drink, talk, and even kiss. In the United States, about 100 new cases of oral cancer occur each day, and approximately 7,000 people die annually from the disease. Worldwide, over 640,000 new cases of oral cancer occur annually. In addition to tobacco use, alcohol use and exposure to the HPV-16 virus (human papilloma virus version 16) are the leading causes of oral cancer.

The study described in Dr. Guttenplan’s presentation examined the impact of injecting low, medium, and high doses of dibenzo[a,l]pyrene, a powerful carcinogen in tobacco, into the mouths of 104 mice. The researchers examined 24 of the mice for mutagenesis and 80 for carcinogenesis. After 38 weeks, all of the mice in the high-dose mutagenesis group developed excessive numbers of mutations in their oral tissue, and within one year, 31% of the high-dose carcinogenesis group displayed large tumors in their mouths.

“As a result of this study,” said Dr. Guttenplan, “we now have a model that is significantly better than past models which relied on synthetic carcinogens. “We plan to use this new model in future studies to examine potential agents for cancer prevention.”

The research team analysed randomised controlled trials of people with Type 1 and Type 2 diabetes who had also been diagnosed with periodontal disease. The team looked at 690 papers and included seven studies in the review that fulfilled pre-specified criteria for inclusion.

Their findings suggest that the treatment of periodontal disease can reduce blood sugar levels in Type 2 diabetes, although there was not enough available evidence to support the same benefit for those with Type 1 diabetes.

Current belief is that, when bacteria infect the mouth and cause inflammation, the resulting chemical changes reduce the effectiveness of insulin produced in the body, thus making it more difficult for diabetics to control their blood sugar.

The findings are key because many patients and health care professionals do not necessarily make the association between the treatment of gum disease and the control of blood sugar levels. The study suggests that the effective treatment of gum disease could have a positive impact on diabetic patients, especially those with Type 2 diabetes, because it good blood sugar control contributes to lowering the risk of serious complications linked to the condition, such as eye problems and heart disease.

Terry Simpson, lead author at the Edinburgh Dental Institute, said: “It would be wise to advise patients of the relationship between treating periodontal disease and the possibility of lowering their blood sugar levels. Additionally, an oral health assessment should be recommended as part of their routine diabetes management.”

David Moles, Professor of Oral Health Research and Director of Postgraduate Education and Research at the Peninsula Dental School, added: “In this study we have helped confirm a link between the effective treatment of gum disease and lower blood sugar levels in those with Type 2 diabetes. Now what are required are larger randomised trials to further study dental treatment and its long term outcomes for those with diabetes, including the possibility of marrying dental care for diabetics with wider diabetes support and treatment networks and closer collaboration between doctors and dentists.”

Type 1 diabetes is the type of diabetes that typically develops in children and young adults. In Type 1 diabetes the body stops making insulin and the blood glucose level goes very high. Treatment to control the blood glucose level is with insulin injections and a healthy diet. Other treatments aim to reduce the risk of complications and include reducing blood pressure if it is high, and to lead a healthy lifestyle.

Type 2 diabetes occurs mainly in people aged over 40, although it is affecting a growing number of younger people. The ‘first-line’ treatment is diet, weight control and physical activity. If the blood glucose level remains high despite these measures, then tablets to reduce the blood glucose level are usually advised. Insulin injections are needed in some cases. Other treatments include reducing blood pressure if it is high, lowering high cholesterol levels and also other measures to reduce the risk of complications.

By Sandra Shagat February 16, 2010 Category: Health Sciences, Research

Physicians and scientists agree: If we cannot entirely prevent cancer, the next best thing is to find it earlier to augment the chances of a successful fight.

The good news is that there may soon be a new weapon in the battle against the so-called “worst” cancer — cancer of the pancreas. A multidisciplinary group of investigators from the UCLA School of Dentistry, the David Geffen School of Medicine at UCLA, the UCLA School of Public Health and UCLA’s Jonsson Comprehensive Cancer Center has demonstrated the usefulness of salivary diagnostics in the effort to find and fight the disease.

Their results, published by the journal Gastroenterology, are available online at http://dx.doi.org/10.1053/j.gastro.2009.11.010.

Pancreatic ductal adenocarcinoma, the most common type of cancer of the pancreas, is also the most lethal of all cancers, with a mortality rate that is approximately the same as the rate of incidence. The American Cancer Society reports that more than 42,000 people in the United States received a diagnosis of pancreatic cancer in 2009, and the disease caused more than 35,000 deaths. Pancreatic cancer is the fourth leading cause of cancer death in this country. For both men and women, the lifetime risk of developing pancreatic cancer is about one in 72.

A “silent killer,” pancreatic cancer produces its typical symptoms — abdominal pain and jaundice — only in the advanced stage of the disease, making it difficult to fight. Fewer than 5 percent of those diagnosed with the disease live for five years, and full remission is very rare, according to the World Health Organization.

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The study, led by Dr. Shiela Strauss, Associate Professor of Nursing and Co-Director of the Statistics and Data Management Core for NYU’s Colleges of Dentistry and Nursing, examined data from 2,923 adult participants in the 2003-2004 National Health and Nutrition Examination Survey who had not been diagnosed with diabetes. The survey, conducted by the National Center for Health Statistics of the Centers for Disease Control and Prevention, was designed to assess the health and nutritional status of adults and children in the United States.

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According to the scientists, these results suggest the structure of these so-called oxirane, or epoxy, molecules can be further refined in the laboratory to produce a safe, non-shrinking resin matrix, the chemical backbone of a composite filling.  “There has been a need in restorative dentistry for a safe, non-shrinking composite matrix,” said Dr. David Eick, a scientist at the University of Missouri at Kansas City and lead author on the study.  “These results mark a small, but important, research step toward meeting this need.”

Dental composites are the white, resin-based fillings that have become a mainstay of restorative dentistry.  In 1999 alone, the American Dental Association estimated that over 85 million composite fillings were placed in the United States, ranking them as the number one dental restorative in the country.

Despite the aesthetic advantages of tooth-colored composites over amalgam, many dentists say they remain hesitant to place these fillings in decayed back teeth, where the mechanical stresses of chewing are greatest.

They say the problem is composite fillings, which are typically inserted into cavities as a viscous-plastic gel, shrink by about three percent as they polymerize  and harden in the tooth.  Though three percent might seem trivial, composites are sealed tightly on all four sides of the tooth’s inner surface.  As the composite shrinks, it can pull away from the seal, creating an constant stress that may eventually crack the tooth or open a seam for bacteria to cause secondary caries.

To eliminate the problem, scientists say they need to improve the chemistry of the composite’s matrix backbone, the main source of the shrinkage.  One hope is to develop a suitable synthetic molecule, or monomer, that polymerizes without losing volume as it forms chemical bonds with other monomers.

According to Eick, a strong candidate is oxirane, which polymerizes cationically.  That is, its monomers open their aromatic rings and expand to form chemical bonds.  Current composites that are based on free-radical chemistry, in which their rings contract during bond formation, resulting in a slight loss of volume.

“The typical polymerization stress for most current composites is in the neighborhood of 20 megapascals,” said Eick, referring to a standard unit measure of stress.  “The oxiranes by themselves are maybe 8 megapascals and, when other expanding monomers are added to the oxirane, the measure is down to less than one.  So, we are getting very close to having a zero stress polymer.

To reach this point, however, has been no stroll through Kansas City’s Country Club Plaza.  Given the many issues that arise in designing synthetic materials, Eick and colleagues have assembled an interdisciplinary research team, which, according to Eick, “brings a synergistic scientific focus” to the project.  Included on the research team are material scientists, computer scientists, toxicologists, synthesis chemists, and important industry collaborators.

“The  team starts out by modeling a variety of molecules on the computer that we think might expand and which appear to have a biocompatible structure,” said Eick.  “Biocompatibility is a huge issue - as it is in the development of all dental materials - because residual monomers could leach from the composite into the body.  For this reason, the toxicologists run these molecules through a range of initial biocompatiblily tests that ultimately leave us with only the most viable molecules.

“These molecules are then given to the synthesis chemists,” continued Eick.  “Because the molecules are extremely large, it can really be a horrendous synthesis job to produce some of these materials.  For the easiest molecules, it can take three to six months just to synthesize them.”

Following this strategy, Eick and colleagues first reported in 1999 that  oxirane monomers, blended with polyol, had superior biocompatibility profiles compared to oxirane alone and two other oxirane mixtures.  Polyol, a generic term for polymers with a large number of hydroxyl groups, serves as a so-called “carrier” resin, helping to cross link the matrix network and modify its chemical properties.

The following year, the group published its prototype of a light-initiated, oxirane-polyol composite.  It consisted of an oxirane (UVR-6105); a polyol (pTHF-250); about 75 percent quartz/fumed silica filler, the inorganic bulk material that adds strength to the matrix; and a cationic photo-initiator and sensitizer system, which, when exposed to UV light, generates an acid that catalyzes the polymerization process.

Now, in this month’s issue of Dental Materials, Eick et al. report on the initial biocompatibilty and physical strength of three experimental oxirane-polyol composites.  Each composite contained the same chemical components as the previously reported prototype, with one exception.  The third composite had the low-viscosity acrylate, Ebecryl 1830, added to increase the degree of polymerization.

After a battery of laboratory tests, the scientists found that the first two composites - 4016E and 4016G - had acceptable compressive strengths, a gauge of their potential durability in the mouth, that were comparable to their earlier oxirane/polyol prototype.  These composites also were shown to be non-cytotoxic in standard cell culture assays.

However, the third composite, known as 4016GB, which included Ebecryl 1830, did not fare as well.  It scored poorly in compressive strength, indicating it likely lacks the necessary structural durability for long-term placement in the mouth.  It also was found to be mildly cytotoxic in the cell assays.

Based on their positive results with 4016E and 4016G, the scientists concluded that “suitable oxirane/polyol formulations can be designed and optimized to serve as matrix resins . . . with acceptable mechanical properties and good biocompatibility profiles.”  Studies are ongoing to further refine these and other oxirane/polyol composites for eventual clinical evaluation.

Published in the July 2002 issue of Dental Materials, the paper is titled, “In vitro biocompatibility of oxirane/polyol dental composites with promising physical properties.”  The authors are:  J.D. Eick, E.L. Kostoryz, S.M. Rozzi, D.W. Jacobs, JD Oxman, C.C. Chappelow, A.G. Glaros, and D.M. Yourtee.  The research was funded by the National Institute of Dental and Craniofacial Research and 3M Company.

via July 1, 2002 - Scientists Report New Resin Matrix Passes Initial Tests.

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