Friday, March 15, 2019

How a common oral bacteria makes colon cancer more deadly

Findings may help predict aggressive colon cancer and identify new treatment targets

This article is alarming because it is identifying a second periodontal pathogen in connection to systemic health. Up to this point one bacteria that is found in aggressive forms of periodontal disease has been indicated in systemic disease, p. Gingivalis. These links to systemic health should be a huge wake up call to anyone with oral disease. If you suspect you or a loved one may have periodontal disease you could be saving a life by having it treated.

COLUMBIA UNIVERSITY IRVING MEDICAL CENTER

NEW YORK, NY (March 4, 2019)--Researchers at the Columbia University College of Dental Medicine have determined how F. nucleatum -- a common oral bacteria often implicated in tooth decay -- accelerates the growth of colon cancer. The study was published online in the journal EMBO Reports.
Why it matters
The findings could make it easier to identify and treat more aggressive colon cancers. It also helps explain why some cases advance far more quickly than others, thanks to the same bacteria found in dental plaque.
Background
Colon cancer is the second leading cause of cancer death in the U.S. Researchers have long known that the disease is caused by genetic mutations that typically accumulate over the course of a decade. "Mutations are just part of the story," says study leader Yiping W. Han, PhD, professor of microbial sciences at Columbia University's College of Dental Medicine and Vagelos College of Physicians & Surgeons. "Other factors, including microbes, can also play a role."
Scientists have also demonstrated that about a third of colorectal cancers are associated with a common oral bacterium called F. nucleatum. Those cases are often the most aggressive, but nobody knew why. In a prior study, Han's research team discovered that the bacterium makes a molecule called FadA adhesin, triggering a signaling pathway in colon cells that has been implicated in several cancers. They also found that FadA adhesin only stimulates the growth of cancerous cells, not healthy cells. "We needed to find out why F. nucleatum only seemed to interact with the cancerous cells," says Han.
What the study found
In the current study, the researchers found in cell cultures that noncancerous colon cells lack a protein, called Annexin A1, which stimulates cancer growth. They then confirmed both in vitro and later in mice that disabling Annexin A1 prevented F. nucleatum from binding to the cancer cells, slowing their growth.
The researchers also discovered that F. nucleatum increases production of Annexin A1, attracting more of the bacteria. "We identified a positive feedback loop that worsens the cancer's progression," says. Han. "We propose a two-hit model, where genetic mutations are the first hit. F. nucleatum serves as the second hit, accelerating the cancer signaling pathway and speeding tumor growth."
Clinical implications
The researchers then looked at an RNA-sequencing dataset, available through the National Center for Biotechnology Information of 466 patients with primary colon cancer. Patients with increased Annexin A1 expression had a worse prognosis, regardless of the cancer grade and stage, age, or sex.
Next steps
The researchers are currently looking for ways to develop Annexin A1 as a biomarker for more aggressive cancers and as a potential target for developing new treatments for colon and other types of cancer.
More details
Yiping Han, PhD, is a professor of microbial sciences in dental medicine at the Columbia University College of Dental Medicine and of microbiology and immunology at Columbia University Vagelos College of Physicians & Surgeons.
The study is titled, "Fusobacterium nucleatum promotes colorectal cancer by inducing Wnt/ß-catenin modulator Annexin A1."
The other contributors are Mara Roxana Rubinstein (Columbia), Jung Eun Baik (Columbia), Stephen M. Lagana (Columbia), Richard P. Han (The Horace Mann School, Bronx, NY), William J. Raab (Columbia), Debashis Sahoo (University of California San Diego, San Diego, CA), Piero Dalerba (Columbia), and Timothy C. Wang (Columbia).
The study was funded by grants from the National Institutes of Health (RO1CA192111, RO1DE014924, RO1DE023332, and P30 CA013696). Dr. Dalerba receives royalties and/or stocks from OncoMed Pharmaceuticals Inc., Quanticel Pharmaceuticals Inc. (now a fully owned subsidiary of Celgene) and Forty Seven Inc. as a coinventor of several patents and patent applications. The other authors declare no financial or other conflicts of interest.
About Columbia University College of Dental Medicine
Columbia University College of Dental Medicine (CDM), one of the nation's first dental schools, educates general dentists and specialists to practice dentistry as the oral health specialty of medicine. CDM provides comprehensive, precision care to over 30,000 patients each year through more than 130,000 visits, making CDM the largest source of oral healthcare to underserved upper Manhattan communities. A centerpiece of the school's offerings is the Center for Precision Dental Medicine, a clinic that will personalize care and education through big data and first-of-its-kind technology. Other programs bring oral healthcare to local schools, seniors, and community centers. For more information, visit dental.columbia.edu
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About Columbia University Irving Medical Center
Columbia University Irving Medical Center provides international leadership in basic, preclinical, and clinical research; medical and health sciences education; and patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the Vagelos College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Columbia University Irving Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest faculty medical practices in the Northeast. For more information, visit cuimc.columbia.edu or columbiadoctors.org.
Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

Friday, March 1, 2019

DENTAL DISEASE RESPONSIBLE FOR OVERALL HEALTH?

We continue to see more information streaming into the public area on the subject of  oral disease and it's  causative links to disease of the body. With this in mind, we'd like to share this following article from Medical News Today.

The unexpected dangers of gum disease

  Published
                Fact checked by Gianna D'Emilio
In this Spotlight, we will cover some of the surprising links between gum disease and disparate health issues.

Gums and the brain

Although spatially the gums are near the brain, one wouldn't normally associate dental complaints with neurological conditions.
Alzheimer's and P. gingivalis linked
However, some studies have found a link between periodontal disease and tooth loss and cognitive function. One study looking at cognitive performance followed 597 men for up to 32 years. The authors conclude:
"Risk of cognitive decline in older men increases as more teeth are lost. Periodontal disease and caries, major reasons for tooth loss, are also related to cognitive decline."
Researchers have also linked periodontal disease with an increased buildup of beta-amyloid in the brain — the neurological hallmark of Alzheimer's.Other experiments have produced evidence that one type of bacteria commonly found in cases of periodontitis — Porphyromonas gingivalis — can be found in the brains of individuals with Alzheimer's.
Following on from that discovery, in a more recent study, researchers showed that P. gingivalisinfection boosts the production of beta-amyloid in the brain.
In this study, the researchers paid particular attention to an enzyme produced by P. gingivalis called gingipain. They found that this protease was toxic to tau, another protein that plays a pivotal role in Alzheimer's.
It is worth noting that other researchers have concluded that beta-amyloid is produced in response to a pathogen. The way we view Alzheimer's is slowly changing.
In the future, scientists hope that targeting gingipain enzymes might help stop neurodegeneration in some people with Alzheimer's disease. They have already designed a gingipain inhibitor, which they are testing in humans.

The researchers hope that it will "slow or prevent further neurodegeneration and accumulation of pathology in [Alzheimer's disease] patients."

The heart of the matter

Although not everyone with heart disease has gum disease, and not everyone with gum disease has heart disease, there does appear to be a correlation.
Links between gum disease and the heart
Of course, individuals who smoke or drink large quantities of alcohol are more likely to have both oral and cardiovascular issues, but there appears to be more to the relationship than shared risk factors alone.
Whether gum disease is an independent risk factor for heart disease is still being discussed, but there are some theories as to how the two might be related.
Some think that the link could involve inflammation. Primarily, inflammation is a response to irritants or pathogens; it is a protective mechanism. However, if it continues for an extended period, it can damage tissues and organs.
It is possible that inflammation in the gums sets off a cascade that, ultimately, sparks inflammation in the cardiovascular system.
Alternatively, the link between heart and gum diseases may be due to bacteria.
Bacteria in the gums can enter the blood supply and be propelled to distant destinations, including the heart, where they can cause inflammation and damage. As evidence that this possible, researchers have shown that P. gingivalis is the most commonly found bacterial species in the coronary artery.
Cancer risk increase

Once again, gum disease and cancer do not, on the surface, appear to have much in common.
A study published in 2008 investigated tooth loss and cancer in 48,375 men. The authors concluded that there was, indeed, a link between gum disease and cancer. They write:

    "Periodontal disease was associated with a small, but significant, increase in overall cancer risk."
Another, more recent, study involving more than 68,000 adults found a strong association between gum disease and overall cancer risk; the link was also significant between gum disease and pancreatic cancer.
Why might this be the case? A paper published in Nature goes some way toward an explanation.
The researchers found that an enzyme produced by a type of bacteria commonly associated with gum disease — Treponema denticola — commonly appears in certain tumors of the gastrointestinal system.
The enzyme, known as T. denticola chymotrypsin-like proteinase, helps the bacteria invade tissue in gum disease. The researchers found that it also activated other enzymes that promote cancer cells as they advance into healthy tissue.

Erectile dysfunction

Gum disease could lead to trouble in the bedroom
An estimated 50 percent of men over the age of 40 experience erectile dysfunction. It is a complex condition that can result from both psychological and physiological factors.
Some well-known risk factors include smoking tobacco, drinking alcohol, and hypertension. According to some scientists, periodontal disease might also increase the risk of erectile dysfunction.
For instance, the authors of a literature review published in 2016 identify an association between erectile dysfunction and chronic periodontitis.
In fact, they suggest "that physicians should refer patients with [erectile dysfunction] to oral healthcare providers for a comprehensive oral evaluation and treatment."

Although sexual dysfunction and gum health seem worlds apart, there are a number of potential ways in which they could influence each other.
Once again, inflammation might be the culprit. As mentioned earlier, inflammation in one part of the body — the mouth, in this instance — can spread via chemical messengers in the blood and impact other regions.
Erectile dysfunction is often due to malfunctioning blood vessels; specifically, the smooth muscles lining the walls of blood vessels lose their ability to relax. This is referred to as endothelial dysfunction, and it prevents vasodilation in the penis and, consequently, erections.
A so-called proinflammatory state may promote endothelial dysfunction and, therefore, increase the risk of erectile dysfunction.

However, the link has not been definitively proven. The authors of a review published in 2016 concluded that, although this link seems likely, more large-scale studies are needed.

Gums and lungs

Of course, the mouth is a shared gateway to the gums and the lungs, making a link between gum and lung diseases less surprising than some of the others that we have encountered.
A study published in February 2019 investigated the records of 1,380 men. The authors found a significant relationship between chronic periodontitis and a reduction in respiratory function.
This link remained significant, even after controlling for confounding variables, such as smoking.
Once again, inflammation may be the link between the two conditions. If the tubes in the lungs that carry air are inflamed, they become narrower and air flow is restricted.
Aside from the probable role of inflammation, bacteria present in the mouth might also be breathed into the lungs. Once in the lungs, the bacteria could trigger infections that directly lead to inflammation.
A recent meta-analysis investigated potential links between gum disease and lung cancer. The authors concluded that "patients with periodontal disease are at increased risk of developing lung cancer."
In their paper, they outline some potential ways in which gum disease might increase lung cancer risk. For instance, breathing in bacteria, such as P. gingivalis, from the mouth could cause infections.
Similarly, enzymes produced during the course of gum disease might pass into the lungs. Once there, they could help pathogens take root and colonize the lung tissue.

These changes spark inflammation; over the long term, inflammation causes changes in cells that raise the likelihood of cancer developing.

The take-home message

One could read this article as a worrying collection of conditions made all the more likely to occur, courtesy of gum disease.
If we adopt the opposite approach, though, the take-home message could be much more positive: Good dental hygiene may reduce our risk of developing a range of serious health problems.
As the authors of the lung cancer analysis, mentioned above, write, "periodontal disease is a preventable and treatable disease." Managing it at an early stage might reduce the risks of a multitude of ills.

Friday, February 15, 2019

TO VAPE OR NOT TO VAPE: HOW VAPING AFFECTS HEALING

E-cigarette Vaping Impacts Wound Healing 


A new study shows that e-cigarette vaping negatively affects skin wound healing, causing damage similar to that of traditional cigarette smoking. 

Researchers, led by a team from Boston Medical Center (BMC), found exposure to both e-cigarette vaping and traditional cigarettes in experimental models resulted in increased tissue death, which delays wound healing. 

In the study published in JAMA Facial Plastic Surgery, researchers exposed experimental models to one of the following: traditional cigarettes, electronic cigarettes or no cigarettes. They checked serum cotinine levels, a biomarker for exposure to tobacco smoke, in both positive control and experimental groups to ensure that comparable nicotine exposure was achieved in both those groups. Researchers then created skin flaps, which were grafted back on each of the models from which they were created, and then monitored the grafts daily for viability and wound healing. After two weeks, a statistically increased rate of tissue death was found on grafted flaps in groups exposed to either e-cigarettes or traditional cigarettes, according to the study.

“Based on our findings, e-cigarettes are not a safe alternative to traditional cigarettes as it relates to timely wound healing,” says Jeffrey Spiegel, MD, chief of facial plastic surgery at BMC and the study’s corresponding author. “Providers and patients need to understand the risks of both types of smoking so that they can make the best decision to keep the patient as safe as possible before and after surgery.” 

Read more of this study in JAMA Facial Plastic Surgery (2018); doi:10.1001/ jamafacial.2018.1179.

Friday, January 11, 2019

TO ADD FLUORIDE OR NOT?

The controversy over fluoridation is a HOT issue. Here is the most recent information from the ADA about public water supply fluoridation.

ADA News Logo

Study reaffirms efficacy of water fluoridation in preventing decay

January 07, 2019
By Michelle Manchir
Kids with Medicaid in Juneau with no access to optimally fluoridated water had more dental caries-related procedures than youth who grew up before the Alaskan capital ceased its fluoridation program, according to research published in December in BMC Oral Health.

For the study, "Consequences of Community Water Fluoridation Cessation for Medicaid-eligible Children and Adolescents in Juneau, Alaska," public health researchers analyzed Medicaid dental claims records of about 1,900 0- to 18-year-old patients in Juneau's main ZIP code. They compared claims from a year in which the city water was fluoridated at an optimal level for tooth decay, 2003, and from 2012, five years after the city ended its fluoridation program.

Researchers found that "by taking the fluoride out of the water supply, the trade-off for that is children are going to experience one additional caries procedure per year at a ballpark of $300 more per child," said Jennifer Meyer, lead author of the article and an assistant professor of allied health at the University of Alaska, in an NPR article about the research.

Furthermore, children born after community water fluoridation cessation in Juneau underwent the most dental caries procedures and incurred the highest caries treatment costs on average, according to the study.

"These results expand our understanding of caries epidemiology under community water fluoridation cessation conditions and reaffirm that optimal community water fluoridation exposure prevents dental decay," the authors concluded. "These findings can offer fiscal estimates of the cost burden associated with (community water fluoridation) cessation policies and help decision-makers advance oral health, prevent dental caries, and promote equity in oral health outcomes."

To read the full article, visit bmcoralhealth.biomedcentral.com and search for the article title.

The ADA has endorsed since 1950 the fluoridation of community water supplies as safe, effective and necessary in preventing tooth decay.

For more information or resources about fluoridation, visit ADA.org/fluoride.

Friday, November 2, 2018

Oral Cancer and HPV

In our efforts to provide the highest standard of care our team routinely attends continuing education courses.  Our hygienists recently attended an update in Oral Cancer. The presentation was given by the surgeons from Washington University School of Medicine, Department of Head and Neck Surgical Oncology. Dr. Jose P. Zevallos, the Division Chief  started the morning with  an update on oropharyngeal cancer.

Dr. Zevallos recounted the rise in orophoharyngeal cancer began to be noticed in the 1980's and 1990's. It wasn't until the early 2000's it was discovered that this rise in cancer was being caused by  HPV (Human papillomavirus). The scary thing about this cancer is that it's demographic is across all age ranges, in smokers and non-smokers, with an increase noted in all races. Another troubling thing about HPV related cancers is that it has a 30 year legacy period between infection and onset of cancer. The infection generally occurs in the patients 20's and then lays dormant until the 50's to 60's. People with autoimmune diseases or people taking immunosuppressants are at a higher risk for developing HPV related cancers.

Another issue associated with HPV oropharyngeal cancers is our lack of ability to reliably screen for them. There are some saliva tests for oral HPV infection, however there is a high rate of false positives with these tests. This is because 2-8% of the population will have the infection but only a tiny percent of those get cancer. Once a tumor is present there will be very high levels of HPV in the saliva. The current saliva tests do not screen for the levels of HPV present in the saliva. Secondly, these tumors form deep in the base of the tonsillar crypt and the base of the tongue, making them very hard to see in a visual oral exam.

The Gardisil vaccine now cover 9 of the high risk forms of HPV. This vaccine is our best chance at preventing cancers. However, much of the population is still at risk for developing an HPV related cancer of the head, neck and mouth. This is why it is critical to have regular dental checkups and ensure your provider is competently evaluating your oral and oropharyngeal cavities for any early signs of cancer.




Possible signs and symptoms of oral cavity and oropharyngeal cancers include:
  • A sore in the mouth that doesn't heal (the most common symptom)
  • Pain in the mouth that doesn’t go away (also very common)
  • A lump or thickening in the cheek
  • A white or red patch on the gums, tongue, tonsil, or lining of the mouth
  • A sore throat or a feeling that something is caught in the throat that doesn’t go away
  • Trouble chewing or swallowing
  • Trouble moving the jaw or tongue
  • Numbness of the tongue or other area of the mouth
  • Swelling of the jaw that causes dentures to fit poorly or become uncomfortable
  • Loosening of the teeth or pain around the teeth or jaw
  • Voice changes
  • A lump or mass in the neck
  • Weight loss
  • Constant bad breath
Many of these signs and symptoms can also be caused by things other than cancer, or even by other cancers. Still, it's very important to see a doctor or dentist if any of these conditions lasts more than 2 weeks so that the cause can be found and treated, if needed.

Friday, October 12, 2018

Oral Bacteria Use Your Bloodstream As Highway To Your Body

PERIODONTAL PATHOGENS AREN'T JUST IN YOUR MOUTH



The concept of sterile blood no longer exists. Bacteremia occurs when pathogens enter the bloodstream. Many microbes simply enter the bloodstream transiently. They are shed from the primary biofilm found in the mouth by chewing or routine dental hygiene at home.
Higher concentrations of pathogens enter the blood by invasive dental procedures, including mechanical debridement, extractions, and endodontic procedures. It requires only 60 seconds for a pathogen to travel anywhere in the body as a result of an invasive dental procedure. 
Bacteremia results in “seeding” bacteria at potentially new systemic locations. These new sites are typically under stress and have become susceptible to invasion. 
Translocation is a pathogen’s arrival at a new systemic site from its point of origin. New biofilms or microbiomes of pathogens emerge at sites where these species are not normally found. The impact of these pathogens is the same wherever they colonize: cellular destruction.
Co-Occurrence
In the past several years, much evidence has shown a prevalence of periodontal pathogens in arterial biofilms and microbiomes. Recently, the term “co-occurrence” has become relevant as it describes the existence of two similar biofilms in the same patient at the same time.
study published in February 2017 found that a large group of patients who had both the symptoms of periodontitis and of heart disease had a similar profile of periodontal high-risk pathogens at the two independent locations. For three pathogens, the co-occurrence was at the 95% confidence level. Eight other pathogens were simply determined to have a very high incidence of correlation. 
In a dental practice, a simple salivary test can be performed to determine the specific bacteria that are present in the mouth, understanding that the very same bacteria that are found in high concentrations in the mouth also are found on the lining of the patient’s arterial walls.
The goal of periodontal therapy should be to eliminate the bacterial etiology. Successful periodontal therapy must include antimicrobials and or antibiotics specific to the pathogens present in a given individual’s oral bacterial flora or biofilm. 
If periodontal therapy is only delivered with a local focus, what will become of the already translocated and in-place biofilms and pathogens in hosts who are medically or genetically compromised and incapable of mounting an effective immune response? Does a systemic disease warrant a systemic response? These questions need to be considered when periodontal therapy is warranted.
Looking at periodontal disease as a bacterial infection that travels throughout the body is much different than looking at periodontal disease as a localized bacterial infection of the oral cavity only. Systemic mitigation of pathogens requires a total body wellness approach. Periodontal disease treatment must be considered a part of the preventive armamentarium for chronic disease management in the human body, which is a complex ecosystem. 
This article excerpted from:
Dentistry Today
08 Oct 2018  Traci Warner, RDH  Today's Dental News

Friday, October 5, 2018

New Research: Smoking Can Damage Your Tooth's Nerve


Smoker's have been cautioned about lung disease, gum disease and other deleterious affects of smoking, but a new study has shown that smoking can affect the pulp (nerve and blood supply inside your tooth) of your tooth.
Researchers at the Case Western Reserve University School of Dental Medicine found that smoking weakens the ability for pulp in teeth to fight illness and disease.
In other words, smokers have fewer defense mechanisms on the inside of their teeth.
"That might explain why smokers have poorer endodontic(root canal treatment) outcomes and delayed healing than non-smokers," said Anita Aminoshariae, associate professor of endodontics and director of predoctoral endodontics. "Imagine TNF-? and hBD-2 are among the soldiers in a last line of defense fortifying a castle. Smoking kills these soldiers before they even have a chance at mounting a solid defense."
The results of the study were published in the Journal of Endodontics.
Aminoshariae said that, previously, there was little research into the endodontic effects of smoking -- the inside of teeth. Smokers had worse outcomes than nonsmokers, with greater chances of developing gum disease and nearly two times more likely to require a root canal.
This new preliminary research set out to explain the possible contributing factors.
Thirty-two smokers and 37 nonsmokers with endodontic pulpitis -- more commonly known as dental-tissue inflammation -- were included in the study.
"We began with a look at the dental pulp of smokers compared with nonsmokers," she said. "We hypothesized that the natural defenses would be reduced in smokers; we didn't expect them to have them completely depleted."
One interesting find, Aminoshariae noted, was that for two patients who quit smoking, those defenses returned.
Joining Aminoshariae in the study were former students Caroline Ghattas Ayoub and Mohammed Bakkar; faculty members Tracey Bonfield, Catherine Demko, Thomas A. Montagnese and Andre K. Mickel; and research Santosh Ghosh -- all from the School of Dental Medicine.

Case Western Reserve University. (2018, September 26). Dental research shows that smoking weakens immune systems. ScienceDaily. Retrieved October 5, 2018 from www.sciencedaily.com/releases/2018/09/180926110940.htm