Melbourne Dental School - Research Publications

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    Systemic Anti-Inflammatory Agents in the Prevention of Chemoradiation-Induced Mucositis: A Review of Randomised Controlled Trials
    Mohammed, AI ; Fedoruk, L ; Fisher, N ; Liu, AX ; Khanna, S ; Naylor, K ; Gong, Z ; Celentano, A ; Alrashdan, MS ; Cirillo, N (MDPI AG, 2024)
    Mucositis is a pathological condition characterised by inflammation and ulceration of the mucous membranes lining the alimentary canal, particularly in the mouth (oral mucositis) and the gastrointestinal tract. It is a common side effect of cancer treatments, including chemotherapy and radiotherapy, and it is sometimes responsible for treatment interruptions. Preventing mucositis throughout the alimentary tract is therefore crucial. However, current interventions mainly target either oral or gastrointestinal side effects. This review aimed to investigate the use of systemically administered anti-inflammatory agents to prevent mucositis in cancer patients undergoing cancer treatment. PubMed, Ovid, Scopus, Web of Science, WHO ICTRP and ClinicalTrials.gov were screened to identify eligible randomised controlled trials (RCTs). The published literature on anti-inflammatory agents provides mixed evidence regarding the degree of efficacy in preventing/reducing the severity of mucositis in most anticancer treatments; however, sample size continued to be a significant limitation, alongside others discussed. Our review yielded a list of several anti-inflammatory agents that exhibit potential mucositis-preventive effects in cancer patients undergoing cancer treatment, which can be used to inform clinical practice.
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    Eosinophils in Oral Disease: A Narrative Review
    Al-Azzawi, HMA ; Paolini, R ; Cirillo, N ; O'Reilly, LA ; Mormile, I ; Moore, C ; Yap, T ; Celentano, A (MDPI, 2024-04)
    The prevalence of diseases characterised by eosinophilia is on the rise, emphasising the importance of understanding the role of eosinophils in these conditions. Eosinophils are a subset of granulocytes that contribute to the body's defence against bacterial, viral, and parasitic infections, but they are also implicated in haemostatic processes, including immunoregulation and allergic reactions. They contain cytoplasmic granules which can be selectively mobilised and secrete specific proteins, including chemokines, cytokines, enzymes, extracellular matrix, and growth factors. There are multiple biological and emerging functions of these specialised immune cells, including cancer surveillance, tissue remodelling and development. Several oral diseases, including oral cancer, are associated with either tissue or blood eosinophilia; however, their exact mechanism of action in the pathogenesis of these diseases remains unclear. This review presents a comprehensive synopsis of the most recent literature for both clinicians and scientists in relation to eosinophils and oral diseases and reveals a significant knowledge gap in this area of research.
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    The global distribution of special needs dentistry across dental school curricula
    Scepanovic, T ; Mati, S ; Ming, ALC ; Yeo, PYS ; Nguyen, D ; Aria, M ; D'aniello, L ; Fung, D ; Muriithi, E ; Mamgain, A ; Zihao, W ; Zeng, JH ; Nichols, A ; McCullough, M ; Lim, MAW ; Wylie, M ; Yap, T ; Paolini, R ; Celentano, A (Wiley, 2024-02-22)
    INTRODUCTION: Special needs dentistry (SND) is an emerging dental specialty, with ongoing developments in education and clinical practice focused towards the tailored management of individuals with special needs (SN). Patients with SN have a higher prevalence of oral diseases and unmet dental needs compared to the general population. Although inadequate training and experience in managing patients with SN has been highlighted as a significant barrier to accessing care, there is limited data about the extent of SND teaching at the entry-to-practice or higher levels. METHODS: This work is the first to map SND curricula globally, across 180 countries and 1265 dental schools. RESULTS: Although 74.62% of dental schools were found in developing economies, the distribution of programs that reported SND in their courses was highly skewed towards developed countries. In terms of advanced degrees, beyond basic entry-to-practice training, the USA delivered 60% of the SND programs, followed by Canada (15.56%), UK (13.33%), and Australia (8.89%). The term SND appeared in 33.95% of entry-to-practice level program curricula and was less commonly used in transitioning economies. Only 112 SND-specialized practitioners enter the workforce globally each year from developed economies, and all but three advanced degrees are found in G7 countries. CONCLUSION: By exploring the impact of economic status on its distribution, this paper highlighted the lack of SND representation in dental curricula, especially amongst programs in transitioning or developing economies. Education of both general dentists and specialists is critical as a collaborative effort is needed to manage the growing population of patients with SN.
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    Oral tongue squamous cell carcinoma diagnosis from tissue metabolic profiling
    Wang, S ; Li, K ; Zhao, T ; Sun, Y ; Zeng, T ; Wu, Y ; Ding, L ; Huang, X ; Celentano, A ; Yang, X ; Hu, Q ; Ni, Y (WILEY, 2024-05)
    OBJECTIVE: Disease metabolomes have been studied for identifying diagnostic and predictive biomarkers of pathology. Oral tongue squamous cell carcinoma (OTSCC) is one of the most prevalent subtypes of head and neck squamous cell carcinoma, yet the profile and diagnostic value of its tissue metabolite are unclear. SUBJECTS AND METHODS: Tumor tissue samples and matched normal mucosal tissue samples were collected from 40 OTSCC patients. Untargeted metabolic analysis by liquid chromatography-mass spectrometry/mass spectrometry, in positive and negative ion modes, was used to identify dysregulated metabolites in OTSCC. Further, utilizing LASSO regression and receiver operating characteristic analyses, biomarker metabolites were selected and validated, and a diagnostic model was established. RESULTS: One hundred and ninety metabolites were detected. The OTSCC had a total of 89 dysregulated metabolites, of which 73 were elevated. A diagnostic panel of nine metabolites was subsequently created that could accurately identify OTSCC with 100% sensitivity of 100%, 100% specificity and an AUC of 1.00. CONCLUSIONS: This study identified distinct metabolic characteristics of OTSCC and established a diagnostic model. Our research also contributes to the investigation of the pathogenesis of OTSCC.
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    Where will the next 3 years lead us?
    Celentano, A (WILEY, 2024-01)
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    Sociodemographic profiles and career motivations of Australian dental students
    Tran, H ; Ahmed, F ; Yousuf, M ; Chan, G ; Mariño, R ; Wylie, M ; Paolini, R ; Canfora, F ; McCullough, M ; Celentano, A (Nihon University School of Dentistry, 2024-01-16)
    PURPOSE: Prior studies explored factors influencing dental study choice, but shifts from BDSc to DDS degrees in some countries impact demographics and motivations, potentially affecting the dental workforce. The aim of this study was to establish Australian DDS and BOH students' sociodemographics and career motivations. METHODS: Questionnaires conducted in mid-2019 assessed sociodemographic profiles and career motivations. Statistical analysis utilized descriptive statistics and Fisher's exact test. RESULTS: The overall response rate was 71.3%. DDS students had an average age of 25.2 years, while BOH students averaged 21.5 years. Most BOH (80.7%) and DDS students (52.0%) were female. They were mainly single, local, Australian citizens from metropolitan areas. Self-motivation ranked highest, particularly for DDS students (P < 0.05). Significant motivators included healthcare occupation, helping others, interesting career, and flexible hours (P < 0.05). DDS students were more motivated by flexible hours and independence (P < 0.05), while females emphasized a healthcare profession (P = 0.003). International students were motivated by being their own boss (P = 0.003), and private school graduates valued lifestyle within the profession (P = 0.049). CONCLUSION: Despite sociodemographic changes, the main motivations for studying dentistry remain consistent. DDS students prioritized lifestyle factors such as time and remuneration over BOH students.
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    The effect of clinical interventions on the oral health-related quality of life in older adults
    Ky, J ; Scepanovic, T ; Senthilvadevel, N ; Mati, S ; Ming, A ; Ng, M ; Nguyen, D ; Yeo, P ; Zhao, T ; Paolini, R ; Lim, M ; Celentano, A (WILEY, 2022-12)
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    Transcriptional regulation of glucose transporters in human oral squamous cell carcinoma cells
    Paolini, R ; Moore, C ; Matthyssen, T ; Cirillo, N ; McCullough, M ; Farah, CS ; Botha, H ; Yap, T ; Celentano, A (WILEY, 2022-09)
    The increased glucose uptake observed in cancer cells is mediated by glucose transporters (GLUTs), a class of transmembrane proteins that facilitate the transport of glucose and other substrates across the plasma membrane. Despite the important role of glucose in the pathophysiology of oral squamous cell carcinoma (OSCC), there is very limited data regarding the expression of GLUTs in normal or malignant cells from the oral mucosa. We analysed the messenger RNA (mRNA) expression of all 14 GLUTs in two OSCC (H357/H400) and one non-malignant oral keratinocyte (OKF6) cell line using a quantitative polymerase chain reaction. GLUT expression was evaluated at baseline and after treatment with two specific GLUT inhibitors, namely, BAY876 (GLUT1) and WZB117 (GLUT1, GLUT3 and GLUT4). Here, we show that GLUT1, GLUT3, GLUT4, GLUT5, GLUT6, GLUT8, GLUT12 and GLUT13 transcripts were measurably expressed in all cell lines while GLUT2, GLUT7, GLUT9, GLUT11 and GLUT14 were not expressed. GLUT10 was only found in H357. In the presence of BAY876 and WZB117, OSCC cells exhibited significant alterations in the transcriptional profile of GLUTs. In particular, we observed distinct proliferation-dependent changes of mRNAs to GLUT1, GLUT3, GLUT4, GLUT5 and GLUT6 in response to selective GLUT inhibitors. In summary, we documented for the first time the expression of GLUT5, GLUT6 and GLUT12 in normal and malignant oral keratinocytes. Whilst regulation of GLUT transcripts was cell line and inhibitor specific, GLUT3 was consistently upregulated in actively proliferating OSCC cell lines, but not in OKF6, regardless of the inhibitor used, suggesting that modulation of this transporter may act as one of the primary compensation mechanisms for OSCC cells upon inhibition of glucose uptake.
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    Characterization of a novel dual murine model of chemotherapy-induced oral and intestinal mucositis
    Mohammed, AI ; Celentano, A ; Paolini, R ; Low, JT ; McCullough, MJ ; O' Reilly, LA ; Cirillo, N (NATURE PORTFOLIO, 2023-01-25)
    Oral and intestinal mucositis are debilitating inflammatory diseases observed in cancer patients undergoing chemo-radiotherapy. These are devastating clinical conditions which often lead to treatment disruption affecting underlying malignancy management. Although alimentary tract mucositis involves the entire gastrointestinal tract, oral and intestinal mucositis are often studied independently utilizing distinct organ-specific pre-clinical models. This approach has however hindered the development of potentially effective whole-patient treatment strategies. We now characterize a murine model of alimentary tract mucositis using 5-Fluorouracil (5-FU). Mice were given 5-FU intravenously (50 mg/kg) or saline every 48 h for 2 weeks. Post initial injection, mice were monitored clinically for weight loss and diarrhea. The incidence and extent of oral mucositis was assessed macroscopically. Microscopical and histomorphometric analyses of the tongue and intestinal tissues were conducted at 3 interim time points during the experimental period. Repeated 5-FU treatment caused severe oral and intestinal atrophy, including morphological damage, accompanied by body weight loss and mild to moderate diarrhea in up to 77.8% of mice. Oral mucositis was clinically evident throughout the observation period in 88.98% of mice. Toluidine blue staining of the tongue revealed that the ulcer size peaked at day-14. In summary, we have developed a model reproducing the clinical and histologic features of both oral and intestinal mucositis, which may represent a useful in vivo pre-clinical model for the study of chemotherapy-induced alimentary tract mucositis and the development of preventative therapies.