Melbourne Dental School - Research Publications
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ItemMolecular diagnostics in oral cancer and oral potentially malignant disorders-A clinician's guide(WILEY, 2020-01)Current risk stratification of individuals for the development of oral squamous cell carcinoma (OSCC), including those with oral potentially malignant disorders (OPMD), remains based on clinical detection of visibly abnormal mucosa and tissue biopsy with histological assessment for the presence of OSCC or oral epithelial dysplasia (OED). In OPMD, the presence of OED remains the only prognostic tool used in standard care for the development of future OSCC, despite its ample limitations. There is assured potential that the analysis of the genome, transcripts and proteome can provide insight into what is occurring at a cellular level preceding the appearance of clinically observable change. The landscape of the role of the genome and its transcriptome on the development of OSCC and relationships with OPMDs are immense with exploration occurring on several fronts. For clinicians involved in the diagnosis and care of patients with OSCC and OPMD, understanding of commonly used molecular diagnostic techniques is imperative to gain useful insight from the expanding literature investigating the development of OSCC and the relationship with the clinical presentations which encompass OPMDs. Here we present an introduction to molecular diagnostic methods used in the study of OSCC and OPMD.
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ItemGroup pain education is as effective as individual education in patients with chronic temporomandibular disorders(WILEY, 2020-07)BACKGROUND: Temporomandibular disorders (TMD) are recognised as the most common chronic orofacial pain condition, with prevalence figures ranging from 3% to 12%. Patients referred to tertiary orofacial pain clinics for the management of TMD often experience delays in receiving treatment. The objective of the present study was to assess a group treatment programme to deliver effective earlier intervention for patients with chronic TMD. METHODS: Forty-two patients with TMD seen at the Oral Medicine Clinic, Royal Dental Hospital of Melbourne, were administered baseline validated pain questionnaires: the Graded Chronic Pain Scale and Pain Catastrophising Scale. Twenty patients subsequently received education about basic neurophysiology of pain, TMD and relaxation techniques in either a group setting or in a one-on-one session and were followed longitudinally. Administration of pain questionnaires was repeated at 4-6 weeks post-intervention. RESULTS: No evidence of difference in levels of anxiety, somatic symptoms or catastrophising was found between patients who received either group or individual intervention. Both were effective at reducing pain intensity and levels of disability. Individual intervention resulted in a greater reduction in rumination. CONCLUSION: Patients with TMD can receive effective reduction of TMD-related pain and catastrophising from either group or individual education regarding neurophysiology of pain, TMD and relaxation techniques. Group education should accelerate time to commencement of care in large referral-based settings.
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ItemA review of drugs that contribute to bleeding risk in general dental practice(WILEY, 2020-06)The risk of postoperative bleeding is a daily concern for many general dental practitioners. A thorough medical and medication history must be taken to consider all risk factors, particularly drugs, that contribute to bleeding risk. While the risk from drugs such as aspirin, warfarin and clopidogrel are well known, the extent to which new antiplatelet agents and direct oral anticoagulants affect bleeding risk is less well understood. In addition, there are drugs other than antithrombotics, such as antidepressants and complementary medicines that also impair haemostasis. The aim of this paper is to provide dentists with an updated overview of the drugs commonly encountered in general dental practice that can contribute to a patient's postoperative bleeding risk.
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ItemDistinct phenolic, alkaloid and antioxidant profile in betel quids from four regions of Indonesia(NATURE PORTFOLIO, 2020-10-01)Betel quid (BQ) is a chewing mixed package that mainly contains areca nut (AN), betel leaf (Leaf) or betel stem inflorescence (SI), and slaked lime, and is consumed with or without tobacco BQ chewing is common in South East Asia and has been strongly associated with malignant and potentially malignant diseases of the oral cavity. Alkaloids such as arecoline are often accounted for the carcinogenic potential of BQ, however the chemical composition of BQ has not been studied in detail. In the current study, we investigated the total phenolic content (TPC), antioxidant activity (by mean of ferric reducing antioxidant power, FRAP), radical scavenging activity (DPPH test), polyphenolic profile and arecoline content in different components of BQ, namely AN, Leaf or SI, Husk, and blended BQ (BQ mix, containing AN, Leaf or SI and slaked lime). Samples were imported from 4 major regions of Indonesia, namely: Banda Aceh (BA), North Sumatra (NS), West Kalimantan (WK) and West Papua (WP). The highest TPC, FRAP, and DPPH values were detected in AN samples compared to other BQ components, while samples from WP region were of higher values compared to the other regions. High performance liquid chromatography-Mass Spectrometry (LC-MS) analysis showed that Husk contains the widest range of polyphenols, including hydroxybenzoic acids, hydroxycinnamic acids, flavanols, flavonols and stilbenes. Catechin and epicatechin were the main polyphenols detected in BQ, and they were present at the highest concentrations in WP-AN sample. Arecoline was detected in all AN and BQ mix samples and was significantly correlated with catechin and epicatechin, and significantly negatively correlated with p-hydroxybenzoic acid. Notably, arecoline concentration changed significantly when AN was blended in BQ mixtures. The current study is the first to extensively characterise the chemical composition of BQ and provides insight for a better understanding of the interactions of BQ alkaloids and phenolics in the development of oral submucous fibrosis and oral cancer.
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ItemNo Preview AvailableThe role of Candida albicans candidalysin ECE1 gene in oral carcinogenesis(WILEY, 2020-10)Oral squamous cell carcinoma is associated with many known risk factors including tobacco smoking, chronic alcoholism, poor oral hygiene, unhealthy dietary habits and microbial infection. Previous studies have highlighted Candida albicans host tissue infection as a risk factor in the initiation and progression of oral cancer. C albicans invasion induces several cancerous hallmarks, such as activation of proto-oncogenes, induction of DNA damage and overexpression of inflammatory signalling pathways. However, the molecular mechanisms behind these responses remain unclear. A recently discovered fungal toxin peptide, candidalysin, has been reported as an essential molecule in epithelial damage and host recognition of C albicans infection. Candidalysin has a clear role in inflammasome activation and induction of cell damage. Several inflammatory molecules such as IL-6, IL-17, NLRP3 and GM-CSF have been linked to carcinogenesis. Candidalysin is encoded by the ECE1 gene, which has been linked to virulence factors of C albicans such as adhesion, biofilm formation and filamentation properties. This review discusses the recent epidemiological burden of oral cancer and highlights the significance of the ECE1 gene and the ECE1 protein breakdown product, candidalysin in oral malignancy. The immunological and molecular mechanisms behind oral malignancy induced by inflammation and the role of the toxic fungal peptide candidalysin in oral carcinogenesis are explored. With increasing evidence associating C albicans with oral carcinoma, identifying the possible fungal pathogenicity factors including the role of candidalysin can assist in efforts to understand the link between C albicans infection and carcinogenesis, and pave the way for research into therapeutic potentials.
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ItemKava constituents exert selective anticancer effects in oral squamous cell carcinoma cells in vitro(NATURE PORTFOLIO, 2020-09-28)Kava is a beverage made from the ground roots of the plant Piper Methysticum. Active compounds of Kava have previously been demonstrated to exert an antiproliferative effect through cell cycle arrest and promotion of apoptosis. Our aim was to investigate the in vitro effects of the main constituents derived from Kava on oral squamous cell carcinoma (OSCC) activity. Gas chromatography mass spectrometry (GCMS) was used to characterise the main constituents of two Kava preparations. Cell proliferation was assessed in two human OSCC cell lines (H400 and BICR56) and in normal oral keratinocytes (OKF6) treated with the identified Kava constituents, namely Flavokawain A (FKA), Flavokawain B (FKB), yangonin, kavain and methysticin using an MTS in vitro assay. Cell migration at 16 h was assessed using a Transwell migration assay. Cell invasion was measured at 22 h using a Matrigel assay. Cell adhesion was assessed at 90 min with a Cytoselect Adhesion assay. The two Kava preparations contained substantially different concentrations of the main chemical constituents. Treatment of malignant and normal oral keratinocyte cell lines with three of the identified constituents, 10 μg/ml FKA, 2.5 μg/ml FKB and 10 μg/ml yangonin, showed a significant reduction in cell proliferation in both H400 and BICR56 cancer cell lines but not in normal OKF6 cells. Remarkably, the same Kava constituents induced a significant reduction of OSCC cell migration and invasion. We have demonstrated, for the first time, that Kava constituents, FKA, FKB and yangonin have potential anticancer effects on OSCC. This highlights an avenue for further research of Kava constituents in the development of future cancer therapies to prevent and treat OSCC.
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ItemMeasuring Antibiotic Stewardship Programmes and Initiatives: An Umbrella Review in Primary Care Medicine and a Systematic Review of Dentistry(MDPI, 2020-09)Antibiotic stewardship aims to tackle the global problem of drug-resistant infections by promoting the responsible use of antibiotics. Most antibiotics are prescribed in primary care and widespread overprescribing has been reported, including 80% in dentistry. This review aimed to identify outcomes measured in studies evaluating antibiotic stewardship across primary healthcare. An umbrella review was undertaken across medicine and a systematic review in dentistry. Systematic searches of Ovid Medline, Ovid Embase and Web of Science were undertaken. Two authors independently selected and quality assessed the included studies (using Critical Appraisal Skills Programme for the umbrella review and Quality Assessment Tool for Studies with Diverse Designs for the systematic review). Metrics used to evaluate antibiotic stewardship programmes and interventions were extracted and categorized. Comparisons between medical and dental settings were made. Searches identified 2355 medical and 2704 dental studies. After screening and quality assessment, ten and five studies, respectively, were included. Three outcomes were identified across both medical and dental studies: All focused on antibiotic usage. Four more outcomes were found only in medical studies: these measured patient outcomes, such as adverse effects. To evaluate antibiotic stewardship programmes and interventions across primary healthcare settings, measures of antibiotic use and patient outcomes are recommended.
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ItemExtracellular Vesicles in Oral Squamous Cell Carcinoma and Oral Potentially Malignant Disorders: A Systematic Review(MDPI, 2020-02)Extracellular vesicles (EVs) are secreted from most cell types and utilized in a complex network of near and distant cell-to-cell communication. Insight into this complex nanoscopic interaction in the development, progression and treatment of oral squamous cell carcinoma (OSCC) and precancerous oral mucosal disorders, termed oral potentially malignant disorders (OPMDs), remains of interest. In this review, we comprehensively present the current state of knowledge of EVs in OSCC and OPMDs. A systematic literature search strategy was developed and updated to December 17, 2019. Fifty-five articles were identified addressing EVs in OSCC and OPMDs with all but two articles published from 2015, highlighting the novelty of this research area. Themes included the impact of OSCC-derived EVs on phenotypic changes, lymph-angiogenesis, stromal immune response, mechanisms of therapeutic resistance as well as utility of EVs for drug delivery in OSCC and OPMD. Interest and progress of knowledge of EVs in OSCC and OPMD has been expanding on several fronts. The oral cavity presents a unique and accessible microenvironment for nanoparticle study that could present important models for other solid tumours.
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ItemDental opioid prescribing rates after the up-scheduling of codeine in Australia(NATURE PORTFOLIO, 2020-05-21)The misuse of pharmaceutical opioids is a major public health issue. In Australia, codeine was re-scheduled on 1 February 2018 to restrict access; it is now only available on prescription. The aim of this study was to measure the change in dental opioid prescriptions, one year before and after the codeine re-scheduling in Australia and to assess dental prescribing rates of opioids for 2018 by population and by clinician. Data was extracted for dental opioids for the year immediately prior and after the codeine up-schedule (1 February 2017-31 January 2019) from the publicly-available national prescription database (Pharmaceutical Benefits Scheme). Descriptive statistics, T-tests and odds ratios were used to identify significant prescribing differences. Codeine, codeine/paracetamol, oxycodone and tramadol use increased significantly the year after the codeine restriction than the previous year (13.8-101.1%). Australian dentists prescribed 8.6 prescriptions/1,000 population in 2018, with codeine/paracetamol accounting for most prescriptions (96%). The significant increase in opioid prescribing highlights that Australian dentists may be contributing to the misuse of pharmaceutical opioids. Educational efforts should be targeted at the appropriate use of opioids and patient selection. Dentists should be added to the prescription monitoring system SafeScript so they can make informed decisions for patients who are potentially misusing opioids.