Possible markers for earlier diagnosis of aggressive tongue cancer

Squamous cell carcinoma of the tongue, also known as oral tongue cancer, is an aggressive form of cancer that generally affects older people. Patients with the disease often find it difficult to eat, swallow food, or speak. Reasons for its generally poor prognosis include late detection, before pain usually starts and only when physical symptoms such as lesions are present, and a propensity for spreading to other sites in the body.

But in a potential harbinger of hope for arriving at an earlier diagnosis and treatment, in a new study published in Oncotarget, a team of researchers from Case Western Reserve University School of Medicine, Cleveland Clinic, and University Hospitals Cleveland Medical Center has found that bacterial diversity and richness, and fungal richness, are significantly reduced in tumor tissue compared to their matched non-tumor tissues.

This raises the prospect that certain bacteria and fungi, in sufficient amounts and in possibly interactive ways, may play a part in the development of oral tongue cancer. (Previous research has shown that bacteria can spur gastric and colorectal cancer and that bacterial/fungal interplay can contribute to or exacerbate Crohn's disease.)

"Our findings mean that it may be possible to perform precautionary testing in patients at high-risk for oral tongue cancer," said the study's co-senior author Mahmoud A. Ghannoum, PhD, professor in the Department of Dermatology at Case Western Reserve School of Medicine and University Hospitals Cleveland Medical Center. "If the patterns that we found are present in people who are not yet showing signs of lesions, we could begin treatment early, offering the possibility of better patient outcomes."

Oral tongue cancer, which arises in the anterior two-thirds [front] of the tongue, has been rapidly increasing and is now the second most common malignancy in the oral cavity. While human papillomavirus causes nearly ninety percent of base-of-tongue tumors [back], HPV is rarely found (only 2.3 percent) in oral tongue cancer. The causes of oral tongue cancer are unclear, but genetic mutations probably play a role, while smoking and chewing of tobacco, alcohol use, and poor dental hygiene are correlated with the development of this type of cancer.

"Poor oral hygiene has long been associated with oral cancers, suggesting that oral bacteriome (bacterial community) and mycobiome (fungal community) could play a role," said co-senior author Charis Eng, MD, PhD, professor and vice chairman of the Department of Genetics and Genome Sciences at Case Western Reserve School of Medicine and Hardis Chair of the Genomic Medicine Institute at the Cleveland Clinic.

While the bacteriome is increasingly recognized as playing an active role in health, the role of the mycobiome has been much less studied, and never before in the case of oral tongue cancer. In the new study, the researchers extracted tissue DNA from 39 paired tumor and adjacent normal tissues from patients with the cancer. Analyses showed that Firmicutes was the most abundant bacterial phylum, and was significantly increased in tumor compared to non-tumor tissue, 48 percent vs. 40 percent, respectively.

In total, the abundance of 22 bacterial and seven fungal genera [types] was significantly different between the tumor and adjacent normal tissue, including Streptococcus, which was significantly increased in the tumor group (34 percent vs. 22 percent in normal tissue.)

"Studies are starting to emerge demonstrating interactions between bacteria and fungi in the formation of disease," said Ghannoum. "Thus, additional research is needed aimed at understanding how these two communities influence or are influenced in disease settings such as oral tongue cancer."

New dental material resists plaque and kills microbes

                     

IMAGE: Biofilms composed of Streptococcus mutans--a common cause of tooth decay--were much easier to remove when grown on a newly developed dental material (right image), which has an antimicrobial agent within... view more 

Credit: University of Pennsylvania

Dentists rely on composite materials to perform restorative procedures, such as filling cavities. Yet these materials, like tooth enamel, can be vulnerable to the growth of plaque, the sticky biofilm that leads to tooth decay.
In a new study, researchers from the University of Pennsylvania evaluated a new dental material tethered with an antimicrobial compound that can not only kill bacteria but can also resist biofilm growth. In addition, unlike some drug-infused materials, it is effective with minimal toxicity to the surrounding tissue, as it contains a low dose of the antimicrobial agent that kills only the bacteria that come in contact with it.
"Dental biomaterials such as these," said Geelsu Hwang, research assistant professor in Penn's School of Dental Medicine, "need to achieve two goals: first, they should kill pathogenic microbes effectively, and, second, they need to withstand severe mechanical stress, as happens when we bite and chew. Many products need large amounts of anti-microbial agents to maximize killing efficacy, which can weaken the mechanical properties and be toxic to tissues, but we showed that this material has outstanding mechanical properties and long-lasting antibiofilm activities without cytotoxicity."
Hwang collaborated on the study, which was published in the journal ACS Applied Materials and Interfaces, with Penn Dental Medicine professor Hyun (Michel) Koo and Bernard Koltisko and Xiaoming Jin of Dentsply Sirona.
The newly developed material is comprised of a resin embedded with the antibacterial agent imidazolium. Unlike some traditional biomaterials, which slowly release a drug, this material is non-leachable, thereby only killing microbes that touch it.
"This can reduce the likelihood of antimicrobial resistance," Hwang said.
Hwang and colleagues put the material through its paces, testing its ability to kill microbes, to prevent growth of biofilms and to withstand mechanical stress.
Their results showed it to be effective in killing bacterial cells on contact, severely disrupting the ability of biofilms to grow on its surface. Only negligible amounts of biofilm matrix, the glue that holds clusters of bacteria together, were able to accumulate on the experimental material, in contrast to a control composite material, which showed a steady accumulation of sticky biofilm matrix over time.
Then, the team assessed how much shear force was required to remove the biofilm on the experimental material. While the smallest force removed almost all the biofilm from the experimental material, even a force four times as strong was incapable of removing the biofilm from the control composite material.
"The force equivalent to taking a drink of water could easily remove the biofilm from this material," Hwang said.
Hwang, who has an engineering background, has welcomed the opportunity to apply his unique expertise to problems in the dental field. Looking ahead, he looks forward to further opportunities to develop and test innovative products to preserve and restore oral health.

Jawbone loss predates rheumatoid arthritis

                     

IMAGE: In the above x-ray image, the white dotted line indicate the normal jawbone level at a molar site in the lower jaw. The individual has periodontitis and has therefore lost... view more 

Credit: Pernilla Lundberg and Solbritt Rantapää-Dahlqvist

Jawbone loss caused by periodontitis predates the onset of rheumatoid arthritis. This according to research from Umeå University in Sweden presented in the journal Arthritis & Rheumatology. The research also shows a causal relationship between jawbone loss and elevated levels of the bone resorption inducing molecule RANKL in the blood.
Jawbone loss caused by inflammation is characteristic to both periodontitis - a disease leading to tooth loss - and rheumatoid arthritis. Despite differences in what causes the inflammation in periodontitis or rheumatoid arthritis, it has now been established that there is a correlation between the two.
"For example, it's known that individuals with rheumatoid arthritis to a great extent show symptoms of tooth loss than individuals with healthy joints. It's also been known that treatments aimed at periodontitis also ease symptoms from joints in individuals with rheumatoid arthritis. What's not been proven so far, however, is a causal relationship between the two," says Pernilla Lundberg, senior lecturer at the Department of Odontology at Umeå University, and one of the researchers behind the study.
In a collaboration, Pernilla Lundberg and Solbritt Rantapää-Dahlqvist, who is a researcher at the Department of Public Health and Clinical Medicine at Umeå University, have analysed the prevalence of jawbone loss in dental x-rays of individuals with rheumatoid arthritis. The X-rays were performed before arthritis symptoms had developed, and were compared with X-rays from matching controls. All participants in the study had on numerous occasions donated blood to the Medical Biobank Northern Sweden Health and Disease Study. Dental X-rays had been retrieved from the treating dentists.
The results, now presented in the journal Arthritis & Rheumatology, show for the first time that the individuals who later develop rheumatoid arthritis to a greater degree show signs of jawbone loss. Individuals with rheumatoid arthritis also to a greater extent develop jawbone loss over time. Among the individuals who later developed rheumatoid arthritis, the greatest degree of bone loss was detected in individuals who also showed elevated levels of the bone resorption inducing molecule RANKL in the blood.
"As far as we know, no one has previously been able to show that individuals who later develop rheumatoid arthritis have a higher degree of jawbone loss before showing any symptoms of arthritis," says Solbritt Rantapää-Dahlqvist.
"Our results indicate a causal relationship between periodontitis and rheumatoid arthritis. Nevertheless, further clinical studies and studies on basic mechanisms are needed in order to prove the existence of a causal relationship with certainty."