Oral cancer prediction by noninvasive genetic screening

Oral squamous cell carcinomas (OSCCs) develop in genetically altered epithelium in the mucosal lining, also coined as fields, which are mostly not visible but occasionally present as white oral leukoplakia (OL) lesions. We developed a noninvasive genetic assay using next-generation sequencing (NGS) on brushed cells to detect the presence of genetically altered fields, including those that are not macroscopically visible. The assay demonstrated high accuracy in OL patients when brush samples were compared with biopsies as gold standard. In a cohort of Fanconi anemia patients, detection of mutations in prospectively collected oral brushes predicted oral cancer also when visible abnormalities were absent. We further provide insight in the molecular landscape of OL with frequent changes of TP53, FAT1 and NOTCH1. NGS analysis of noninvasively collected samples offers a highly accurate method to detect genetically altered fields in the oral cavity, and predicts development of OSCC in high-risk individuals. Noninvasive genetic screening can be employed to screen high-risk populations for cancer and precancer, map the extension of OL lesions beyond what is visible, map the oral cavity for precancerous changes even when visible abnormalities are absent, test accuracy of promising imaging modalities, monitor interventions and determine genetic progression as well as the natural history of the disease in the human patient.     

What is the Potential Interplay between Microbiome and Tumor Microenvironment in Oral Squamous Cell Carcinomas?

Oral cancer, with an around 50% mortality rate, is one of the most common malignancies world-wide. It is often detected in advanced or terminal stage and has a poor prognosis, although substantial progress in cancer management. Microbiome has become an increasingly recognized factor that may contribute to the cancerous development. Oral microbiological population comprising more than 700 bacterial species, varies since saliva and different habitats of oral cavity. A shift of composition of oral microbiome from usual condition to functional inflammation to pathological state has been discovered amongst patients with premalignant disorders and oral carcinoma, with evidence suggesting the tumor microenvironment (TME) could strongly exacerbate the influence of oral microorganisms. The complex interactions taking place in either cancer formation or progression have been evaluated in several publications, however given their results’ heterogeneity, a review is needed to correctly untangle the potential correlation in this group of pro-carcinogenesis. In this review, we briefly summarize our current knowledge of the role of oral microbiome, focusing on its potential crosstalk with TME in oral squamous cell carcinomas (OSCC) more precisely, and pave the way for manipulating oral microbiome to deal with OSCC in the future.     

Diabetic foot ulcers: A devastating complication of diabetes mellitus continues non-stop in spite of new medical treatment modalities

Diabetic foot ulcer is a devastating complication of diabetes mellitus and significant cause of mortality and morbidity all over the world and can be complex and costly. The development of foot ulcer in a diabetic patient has been estimated to be 19%-34% through their lifetime. The pathophysiology of diabetic foot ulcer consist of neuropathy, trauma and, in many patients, additional peripheral arterial disease. In particular, diabetic neuropathy leads to foot deformity, callus formation, and insensitivity to trauma or pressure. The standard algorithms in diabetic foot ulcer management include assessing the ulcer grade classification, surgical debridement, dressing to facilitate wound healing, off-loading, vascular assessment (status and presence of a chance for interventional vascular correction), and infection and glycemic control. Although especially surgical procedures are sometimes inevitable, they are poor predictive factors for the prognosis of diabetic foot ulcer. Different novel treatment modalities such as nonsurgical debridement agents, oxygen therapies, and negative pressure wound therapy, topical drugs, cellular bioproducts, human growth factors, energy-based therapies, and systematic therapies have been available for patients with diabetic foot ulcer. However, it is uncertain whether they are effective in terms of promoting wound healing related with a limited number of randomized controlled trials. This review aims at evaluating diabetic foot ulcer with regard to all aspects. We will also focus on conventional and novel adjunctive therapy in diabetic foot management.     

The bioavailability of ingested 26Al-labelled aluminium and aluminium compounds in the rat

The fractional uptake of ingested aluminium and aluminium compounds (aluminium citrate, aluminium nitrate, aluminium chloride, aluminium sulphate, aluminium hydroxide, aluminium oxide, aluminium metal, powdered aluminium pot electrolyte, acidic sodium aluminium phosphate (SALP), basic sodium aluminium phosphate (Kasal), sodium aluminium silicate and FD&C red 40 aluminium lake) from the gastro-intestinal tract of adult female rats was measured. This was determined by comparing retained body burden of ²⁶Al at seven days post-admistration of an i.v. injection of ²⁶Al-labelled aluminium citrate with that retained following the gastric admistration of ²⁶Al-labelled test compounds as either solutions or suspended solid. The calculated percentage uptake of ²⁶Al for all the aluminium solutions was similar: aluminium citrate 0.08%, aluminium chloride 0.05%, aluminium nitrate 0.05% and aluminium sulphate 0.21%. The uptake of ²⁶Al administered as insoluble particulates was lower: 0.03% for aluminium hydroxide; 0.02% for aluminium oxide; 0.04% for powdered pot electrolyte; 0.12% for sodium aluminium silicate; and 0.09% for FD&C red 40 aluminium lake. For aluminium metal, SALP and Kasal the amount of ²⁶Al present in the rats was insufficient to determine uptake and was less than 0.03%. The results produced for aluminium citrate, aluminium hydroxide and aluminium sulphate are close to those published for man.