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Background: Oropharyngeal Neisseria gonorrhoeae (NG) infections are common, increasing, and have a higher treatment failure compared with other infection sites. Due to antimicrobial resistance, NG has become a global public health threat as available treatments remain scarce. Little is known about where NG colonizes in the oral mucosa and therefore, where antibiotics need to be distributed to cure infection. A recent review also highlighted the lack of oral cell models available for investigating NG infection. We recently started creating an in-vitro co-culture model for NG strains with human oral epithelial cells to understand patterns of NG growth in the mouth and examine antibiotic uptake by oral cell types supporting NG growth. Methods: NG strains were grown on Chocolate agar with IsoVitaleX and in modified Fastidious broth media in optimised conditions. NG colonies were assessed using a colony counter (Scan1200, Interscience technology). In a 2D model, NG were cocultured with 4 human oral keratinocyte cell lines isolated from different anatomical subsites of the oral cavity. Intra- and extra-cellular NG was quantified, and intracellular spatial distribution was assessed with confocal microscopy and immunocytochemistry. Invasion into 3D spheroids was characterised with penetration depth assessed via histological analysis (haematoxylin and eosin staining) and immunocytochemistry with images taken on a Zeiss Axioscan7 slide scanner or LSM800 confocal microscope. Real time invasion into spheroids was imaged using a MuviCyte live-cell imaging system. Lastly, host cell viability in response to NG infection was also assessed. Results: We created the first-of-its-kind in-vitro model for NG oral infection demonstrating that it is possible to co-culture NG with oral derived cells. NG survives and infects oral cells in an in vitro setting in both 2D and 3D models. Different strains of NG infected oral cells to significantly different degrees. Conclusion: Our presented model can be used to explore the interactions of NG with oral tissues and to investigate current and new therapeutics against oropharyngeal gonorrhoea. [ABSTRACT FROM AUTHOR]

The article discusses the appointment of a new Editor-in-Chief for the Journal of Oral Pathology & Medicine (JOPM). The new editor reflects on the previous editor's tenure and aims to uphold and build upon the high standards set. The new editor plans to introduce changes such as an editorial dedicated to the journal's history, unveiling the profiles of the editorial board members, expanding and diversifying the board, implementing a rigorous statistical review process, and addressing gender imbalance within the board. The editor also plans to optimize workflow and systems to improve efficiency. The appointment is for a 3-year term, during which the editor aims to earn the community's trust and preserve the journal's integrity. [Extracted from the article]

Objective: To systematically review retrospective studies examining prognostic potentials of candidate biomarkers to stratify malignant progression of oral leukoplakia (OL) and proliferative verrucous leukoplakia (PVL). Materials and Methods: A systematic literature search of PubMed, EMBASE, Evidence‐Based Medicine and Web of Science databases targeted literature published through 29 March 2018. Inter‐rater agreement was ascertained during title, abstract and full‐text reviews. Eligibility evaluation and data abstraction from eligible studies were guided by predefined PICO questions and bias assessment by the Quality in Prognosis Studies tool. Reporting followed Preferred Reporting Items for Systematic Review and Meta‐Analysis criteria. Biomarkers were stratified based on cancer hallmarks. Results: Eligible studies (n = 54/3,415) evaluated 109 unique biomarkers in tissue specimens from 2,762 cases (2,713 OL, 49 PVL). No biomarker achieved benchmarks for clinical application to detect malignant transformation. Inter‐rater reliability was high, but 65% of included studies had high "Study Confounding" bias risk. Conclusion: There was no evidence to support translation of candidate biomarkers predictive of malignant transformation of OL and PVL. Systematically designed, large, optimally controlled, collaborative, prospective and longitudinal studies with a priori‐specified methods to identify, recruit, prospectively follow and test for malignant transformation are needed to enhance feasibility of prognostic biomarkers predicting malignant OL or PVL transformation. [ABSTRACT FROM AUTHOR]

Background: Matrix metalloproteinases (MMPs) play a crucial role in the malignant phenotype of cancer cells. In particular, active levels of MMP2 in cancer cells have been associated with invasion and metastasis through the degradation of basement membrane extracellular matrix proteins. However, little is known about the role of this potential biomarker in oral cancer. Our aim was to investigate the effect of MMP2 inhibition on OSCC activity in vitro, as well as to assess MMP2 dysregulation in oral cancer samples.Methods: Human OSCC cell lines H357 and H400 were tested with the selective MMP2 inhibitor ARP101 and the MMP2 neutralising monoclonal antibody MA5-13590 to assess cell proliferation in vitro using MTS assay. Cell migration at 12/24 h was assessed using a Transwell migration assay. Cell invasion was assessed at 24 h using a Corning Matrigel invasion assay. MMP2 expression was assessed in 208 tissue samples (related to 60 OSCC cases and nine normal control) using tissue microarray (TMA) and further analysed via TCGA.Results: Both ARP101 and MA5-13590 monoclonal antibody reduced cell proliferation in both the cell lines tested. Treatment with 4μg/mL of MMP2 monoclonal antibody showed a significant decrease in cell migration at 24 hours. The administration of ARP101 and monoclonal antibody to H357 and H400 cell lines induced a drastic reduction in cell invasion at 24 h compared to the control. In patients, TCGA analysis demonstrated that oral cancer tissues express significantly higher levels of MMP2 mRNA compared to normal oral tissues. Further, IHC analysis on TMA showed significant difference in MMP2 protein expression between low and high histopathological grade OSCC.Conclusions: We have demonstrated, for the first time, that MMP2 inhibition affects oral cancer cells ability to survive, migrate and invade in vitro. Differences between MMP2 expression in normal and malignant tissues varied. Further research on the role of MMP2 in OSCC and novel mechanisms to inhibit MMP2-dependent pathways should be encouraged. [ABSTRACT FROM AUTHOR]

The article presents a study which examined the effects of the nuclear factor of kappa B (NF-kB1) and c-Rel subunit loss in the oral carcinogen 4-nitroquinoloine-1 oxide (4-NQO) model of oral squamous cell carcinoma (OSCC). Topics include the risk factors of OSCC like pro-inflammatory agents and carcinogens such as alcohol and tobacco, as well as the use of mice in the study.

Tumour progression allows for aberrant angiogenesis. Consequently, cancer‐associated thrombosis is a prevalent complication that is coupled with poor prognosis. Anticoagulants have therefore been prescribed with chemotherapeutic agents to target potential thrombo‐embolic risk. A systematic review was carried out to summarise existing evidence on the interactions between anticoagulants and oral cancer. This treatment paradigm has demonstrated beneficial results in some oncology patients, thus associating anticoagulants with anticancer effects. Increasing prevalence of oral cancer presents a need to source alternative therapeutic means to prevent disease progression, and thus the use of anticoagulants in these patients may provide an avenue for this to occur. The paucity of evidence regarding the interactions between oral squamous cell carcinoma and anticoagulants emphasises the urgency with which further research should be conducted. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Synthetic corticosteroids are routinely administered during the treatment of several diseases, including malignancies. However, recent evidence suggests that corticosteroids may have tumor‐promoting effects, particularly in epithelial neoplasms. Our aim was to assess the role of the recently characterized cancer‐associated glucocorticoid (GC) system in the resistance to chemotherapy of oral malignant keratinocytes. Human malignant oral keratinocyte cell lines H314/H357/H400/BICR16/BICR56 were tested with: two chemotherapeutic agents, doxorubicin (DOXO) and 5‐fluorouracil (5‐FU), as well as hydrocortisone (HC), adrenocorticotropic hormone (ACTH), 5‐pregnen‐3‐beta‐ol‐20‐one‐16‐alfa‐carbonitrile (PCN), and two glucose uptake inhibitors, Fasentin and WZB. Both DOXO and 5‐FU induced apoptosis in a dose‐dependent and time‐dependent manner. HC administration (100 nM) reduced the effectiveness of both chemotherapeutic agents to a variable extent in all 5 oral squamous cell carcinoma cell lines. ACTH also reduced the effectiveness of DOXO on 2 cell lines tested (H357 and BICR56). The glucose uptake inhibitors Fasentin and WZB were able to partially block the increased resistance to the cytotoxic drugs induced by HC. In summary, we have demonstrated, for the first time, the importance of cortisol on oral cancer cells ability to proliferate and combat the effectiveness of chemotherapeutic agents. This effect appears to be glucose dependent. Synthetic corticosteroids are routinely administered during the treatment of several diseases, including malignancies. However, recent evidence suggests that corticosteroids may have tumor‐promoting effects, particularly in epithelial neoplasms. We have demonstrated, for the first time, the importance of cortisol on oral cancer cells ability to proliferate and combat the effectiveness of chemotherapeutic agents. [ABSTRACT FROM AUTHOR]