Mapping Conformational Changes in the Saliva Proteome Potentially Associated with Oral Cancer Aggressiveness.

Diverse proteomics-based strategies have been applied to saliva to quantitatively identify diagnostic and prognostic targets for oral cancer. Considering that these targets may be regulated by events that do not imply variation in protein abundance levels, we hypothesized that changes in protein conformation can be associated with diagnosis and prognosis, revealing biological processes and novel targets of clinical relevance. For this, we employed limited proteolysis-mass spectrometry in saliva samples to explore structural alterations, comparing the proteome of healthy control and oral squamous cell carcinoma (OSCC) patients with and without lymph node metastasis. Thirty-six proteins with potential structural rearrangements were associated with clinical patient features including transketolase and its interacting partners. Moreover, N-glycosylated peptides contribute to structural rearrangements of potential diagnostic and prognostic markers. Altogether, this approach utilizes saliva proteins to search for targets for diagnosing and prognosing oral cancer and can guide the discovery of potential regulated sites beyond protein-level abundance.

Oral streptococci S. anginosus and S. mitis induce distinct morphological, inflammatory, and metabolic signatures in macrophages.

Oral streptococci, key players in oral biofilm formation, are implicated in oral dysbiosis and various clinical conditions, including dental caries, gingivitis, periodontal disease, and oral cancer. Specifically, Streptococcus anginosus is associated with esophageal, gastric, and pharyngeal cancers, while Streptococcus mitis is linked to oral cancer. However, no study has investigated the mechanistic links between these Streptococcus species and cancer-related inflammatory responses. As an initial step, we probed the innate immune response triggered by S. anginosus and S. mitis in RAW264.7 macrophages. These bacteria exerted time- and dose-dependent effects on macrophage morphology without affecting cell viability. Compared with untreated macrophages, macrophages infected with S. anginosus exhibited a robust proinflammatory response characterized by significantly increased levels of inflammatory cytokines and mediators, including TNF, IL-6, IL-1ß, NOS2, and COX2, accompanied by enhanced NF-κB activation. In contrast, S. mitis-infected macrophages failed to elicit a robust inflammatory response. Seahorse Xfe96 analysis revealed an increased extracellular acidification rate in macrophages infected with S. anginosus compared with S. mitis. At the 24-h time point, the presence of S. anginosus led to reduced extracellular itaconate, while S. mitis triggered increased itaconate levels, highlighting distinct metabolic profiles in macrophages during infection in contrast to aconitate decarboxylase expression observed at the 6-h time point. This initial investigation highlights how S. anginosus and S. mitis, two Gram-positive bacteria from the same genus, can prompt distinct immune responses and metabolic shifts in macrophages during infection.IMPORTANCEThe surge in head and neck cancer cases among individuals devoid of typical risk factors such as Human Papilloma Virus (HPV) infection and tobacco and alcohol use sparks an argumentative discussion around the emerging role of oral microbiota as a novel risk factor in oral squamous cell carcinoma (OSCC). While substantial research has dissected the gut microbiome's influence on physiology, the oral microbiome, notably oral streptococci, has been underappreciated during mucosal immunopathogenesis. Streptococcus anginosus, a viridans streptococci group, has been linked to abscess formation and an elevated presence in esophageal cancer and OSCC. The current study aims to probe the innate immune response to S. anginosus compared with the early colonizer Streptococcus mitis as an important first step toward understanding the impact of distinct oral Streptococcus species on the host immune response, which is an understudied determinant of OSCC development and progression.

Targeted Phosphoproteomics of Human Saliva Extracellular Vesicles via Multiple Reaction Monitoring Cubed (MRM3).

Oral squamous cell carcinoma (OSCC) has become a global health problem due to its increasing incidence and high mortality rate. Early intervention through monitoring of the diagnostic biomarker levels during OSCC treatment is critical. Extracellular vesicles (EVs) are emerging surrogates in intercellular communication through transporting biomolecule cargo and have recently been identified as a potential source of biomarkers such as phosphoproteins for many diseases. Here, we developed a multiple reaction monitoring cubed (MRM3) method coupled with a novel sample preparation strategy, extracellular vesicles to phosphoproteins (EVTOP), to quantify phosphoproteins using a minimal amount of saliva (50 µL) samples from OSCC patients with high specificity and sensitivity. Our results established differential patterns in the phosphopeptide content of healthy, presurgery, and postsurgery OSCC patient groups. Notably, we discovered significantly increased salivary phosphorylated alpha-amylase (AMY) in the postsurgery group compared to the presurgery group. We hereby present the first targeted MS method with extremely high sensitivity for measuring endogenous phosphoproteins in human saliva EVs.

Shaping the future of oral cancer diagnosis: advances in salivary proteomics.

INTRODUCTION: Saliva has gained increasing attention in the quest for disease biomarkers. Because it is a biological fluid that can be collected is an easy, painless, and safe way, it has been increasingly studied for the identification of oral cancer biomarkers. This is particularly important because oral cancer is often diagnosed at late stages with a poor prognosis. AREAS COVERED: The review addresses the evolution of the experimental approaches used in salivary proteomics studies of oral cancer over the years and outlines advantages and pitfalls related to each one. In addition, examines the current landscape of oral cancer biomarker discovery and translation focusing on salivary proteomic studies. This discussion is based on an extensive literature search (PubMed, Scopus and Google Scholar). EXPERT OPINION: The introduction of mass spectrometry has revolutionized the study of salivary proteomics. In the future, the focus will be on refining existing methods and introducing powerful experimental techniques such as mass spectrometry with selected reaction monitoring, which, despite their effectiveness, are still underutilized due to their high cost. In addition, conducting studies with larger cohorts and establishing standardized protocols for salivary proteomics are key challenges that need to be addressed in the coming years.

Factors associated with recurrence in patients with oral cancer in Mongolia.

INTRODUCTION: In Mongolia, there has been limited research on the posttreatment survival rate, recurrence, and occurrence of oral cancer. The goal of this study is to investigate the risk factors that contribute to the recurrence of oral cancer to increase survival rates, facilitate early detection, and improve treatment accuracy. METHOD: A retrospective cohort method was used, with medical records from 173 patients diagnosed with squamous cell carcinoma of the mouth at the National Cancer Center of Mongolia's Department of Head and Neck Surgery, Radio, and Chemotherapy between 2012 and 2017. The Mongolian National University of Medical Sciences' Research Ethics Committee approved the project. RESULTS: The findings revealed that 109 cases (63.0%) were men and 64 (37.0%) were females, with a large proportion of patients (28.3%) falling between the ages of 61 and 70. Men had a 3.8 times higher risk of cancer recurrence than women (OR = 3.79, CI = 1.24-11.57). Furthermore, lymph node metastases and treatment were linked to oral cancer recurrence. CONCLUSION: This study offers light on the factors that influence the recurrence of oral cancer, giving useful insights for improving patient outcomes through early detection and proper treatment.

Association of DOK3 and infiltrated tumor-associated macrophages with risk for the prognosis of Porphyromonas gingivalis-infected oral cancer: a 12-year data analysis of 200 patients from a tertiary teaching hospital, Urumqi, China.

BACKGROUND: While there is an understanding of the association between the expression of Porphyromonas gingivalis (P. gingivalis) and prognosis of oral squamous cell carcinoma (OSCC), significance specially to address the relevance between different immunohistochemical intensities of P. gingivalis and tumor-associated macrophages (TAMs) in OSCC tissue and related clinicopathologic characteristics has not been well investigated. The present study aimed to investigate the pathological features related to M2-TAM in P. gingivalis-infected OSCC and ascertain its clinical relevance with patients' prognosis. METHODS: A prospective cohort study was designed to comparatively analyze 200 patients from June 2008 to June 2020. Bioinformatics analyses were implemented to identify DOK3 as a key molecule and to appraise immunocyte infiltration using Gene Expression Omnibus and The Cancer Genome Atlas databases. Immunohistochemical evaluation was performed to analyze the association between the expression levels of P. gingivalis, DOK3, and M2-TAM and clinicopathological variables using Fisher's exact test or Pearson's chi-square test. Cox analysis was used to calculate hazard ratios (HR) with corresponding 95% confidence interval (CI) for various clinicopathological features. The Kaplan-Meier approach and log-rank test were used to plot the survival curves. RESULTS: The expression level of P. gingivalis was positively associated with DOK3 and M2-TAMs expression level (P < 0.001). Parameters, including body mass index, clinical stage, recurrence, tumor differentiation, and P. gingivalis, DOK3, and M2-TAM immunoexpression levels, affected the prognosis of patients with OSCC (all P < 0.05). In addition, P. gingivalis (HR = 1.674, 95%CI 1.216-4.142, P = 0.012), DOK3 (HR = 1.881, 95%CI 1.433-3.457, P = 0.042), and M2-TAM (HR = 1.649, 95%CI 0.824-3.082, P = 0.034) were significantly associated with the 10-year cumulative survival rate. CONCLUSIONS: Elevated expression of P. gingivalis and DOK3 indicates M2-TAM infiltration and unfavorable prognosis of OSCC, and could be considered as three novel independent risk factors for predicting the prognosis of OSCC.

Recurrence of oral squamous cell carcinoma in surgically treated patients at Khartoum Teaching Dental Hospital retrospective cross-sectional study.

BACKGROUND: In terms of survival rate, recurrent oral squamous cell carcinoma (OSCC) after primary surgery is considered as a poor prognostic indicator. OBJECTIVE: This study aims to determine the incidence of OSCC recurrence among patients treated at Khartoum Teaching Dental Hospital (KTDH) and possible risk factors associated with it. METHODS: Records of 303 patients with a history of radical surgery were retrieved from the hospital's archives, and the histopathological records were retrieved from the archival specimens of Professor Ahmed Suleiman Oral Pathology Laboratory, Faculty of Dentistry, and University of Khartoum. RESULTS: Advanced stages of OSCC (III, IV) were associated with higher recurrence rates, and the poorly differentiated OSCC was the commonest recurrent type. CONCLUSION: The condition of the surgical margin is a significant predictor of OSCC recurrence and tumor stage. The tumor site, the type of surgical resection, and the tumor differentiation were also identified as significant factors influencing the recurrence of OSCC.

Survival analysis of Sudanese oral squamous cell carcinoma patients with field of cancerization.

BACKGROUND: The late presentation and diagnosis of OSCC account for the large number of patients with the advanced form of the disease. In Sudan, cases with delayed presentation, particularly those with risk factors such as Toombak dipping and alcohol consumption, frequently present with extensive lesions and a wide area of Field cancerization which characterized by the presence of genetic and epigenetic changes in histologically normal-appearing tissues, and have increased risk for recurrent and second primary tumors. This necessitates more aggressive treatment and is usually associated with poorer outcomes. The present study aims to investigate the survival of oral squamous cell carcinoma patients with a wide field of cancerization. METHODS: This prospective longitudinal study includes ninety-three oral cancer patients with extensive fields of cancerization who underwent surgical treatment at Khartoum Teaching Dental Hospital (KTDH) conducted from 2019 to 2023. These patients were regularly assessed for clinical changes such as recurrence, the development of second primary tumours, and overall survival over a period of one year. RESULTS: Out of the 93 patients, 57 (61.3%) were males, and 36 (38.7%) were females. The majority of the patients (82%) had stage IV tumours, and 62.3% had nodal metastasis. Twenty-eight (30%) patients developed recurrences, and 14 (15%) developed second primary tumours. The overall one-year survival rate was 89%, and all deceased patients passed away within 12 months. The survival rate for patients with different types of recurrences varied, with patients who had regional, local, and locoregional recurrences having survival rates of 87%, 74%, and 72%, respectively. Patients who did not experience a recurrence had a one-year survival rate of 92%. Patients who developed second primary tumours had an 86% survival rate. The survival rates for OSCC patients at stages III, IVa, and IVb were 90%, 90%, and 71%, respectively. CONCLUSION: In this study, 62% of patients had nodal metastasis, 30% developed recurrence, and 15% developed second primary tumours. The overall one-year survival rate was 89%, although the development of recurrences and second primary tumours had a negative impact on the survival rate.

Systemic and Local Administration of a Dual-siRNA Complex Efficiently Inhibits Tumor Growth and Bone Invasion in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) accounts for nearly 90% of oral and oropharyngeal cancer cases and is characterized by high mortality and poor prognosis. RNA-based gene therapies have been developed as an emerging option for cancer treatment, but it has not been widely explored in OSCC. In this work, we developed an efficient siRNA cationic micelle DOTAP-mPEG-PCL (DMP) by self-assembling the cationic lipid DOTAP and monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) polymer. We tested the characteristics and transformation efficiency of this micelle and combined DMP with siRNA targeting STAT3 and TGF-ß to evaluate the antitumor effect and bone invasion interfering in vitro and in vivo. The average size of the DMP was 28.27 ± 1.62 nm with an average zeta potential of 54.60 ± 0.29 mV. The DMP/siRNA complex showed high delivery efficiency, with rates of 97.47 ± 0.42% for HSC-3. In vitro, the DMP/siSTAT3 complex exhibited an obvious cell growth inhibition effect detected by MTT assay (an average cell viability of 25.1%) and clonogenic assay (an average inhibition rate of 51.9%). Besides, the supernatant from HSC-3 transfected by DMP/siTGF-ß complexes was found to interfere with osteoclast differentiation in vitro. Irrespective of local or systemic administration, DMP/siSTAT3+siTGF-ß showed antitumor effects and bone invasion inhibition in the OSCC mice mandibular invasion model according to tumor volume assays and Micro-CT scanning. The complex constructed by DMP cationic micelles and siSTAT3+siTGF-ß represents a potential RNA-based gene therapy delivery system for OSCC.

Extracellular vesicles from Aggregatibacter actinomycetemcomitans exhibit potential antitumorigenic effects in oral cancer: a comparative in vitro study.

Aggregatibacter actinomycetemcomitans is an opportunistic Gram-negative periodontopathogen strongly associated with periodontitis and infective endocarditis. Recent evidence suggests that periodontopathogens can influence the initiation and progression of oral squamous cell carcinoma (OSCC). Herein we aimed to investigate the effect of A. actinomycetemcomitans-derived extracellular vesicles (EVs) on OSCC cell behavior compared with EVs from periodontopathogens known to associate with carcinogenesis. EVs were isolated from: A. actinomycetemcomitans and its mutant strains lacking the cytolethal distending toxin (CDT) or lipopolysaccharide (LPS) O-antigen; Porphyromonas gingivalis; Fusobacterium nucleatum; and Parvimonas micra. The effect of EVs on primary and metastatic OSCC cells was assessed using cell proliferation, apoptosis, migration, invasion, and tubulogenesis assays. A. actinomycetemcomitans-derived EVs reduced the metastatic cancer cell proliferation, invasion, tubulogenesis, and increased apoptosis, mostly in CDT- and LPS O-antigen-dependent manner. EVs from F. nucleatum impaired the metastatic cancer cell proliferation and induced the apoptosis rates in all OSCC cell lines. EVs enhanced cancer cell migration regardless of bacterial species. In sum, this is the first study demonstrating the influence of A. actinomycetemcomitans-derived EVs on oral cancer in comparison with other periodontopathogens. Our findings revealed a potential antitumorigenic effect of these EVs on metastatic OSCC cells, which warrants further in vivo investigations.

Porphyromonas gingivalis promotes the progression of oral squamous cell carcinoma by stimulating the release of neutrophil extracellular traps in the tumor immune microenvironment.

BACKGROUND: The aim of this study was to investigate the impact of Porphyromonas gingivalis (P. gingivalis) on the progression of oral squamous cell carcinoma (OSCC) through neutrophil extracellular traps (NETs) in the tumor immune microenvironment. METHODS: The expression of NETs-related markers was identified through immunohistochemistry, immunofluorescence, and Western blotting in different clinical stages of OSCC samples. The relationship between NETs-related markers and clinicopathological characteristics in 180 samples was analyzed using immunohistochemistry data. Furthermore, the ability to predict the prognosis of OSCC patients was determined by ROC curve analysis and survival analysis. The effect of P. gingivalis on the release of NETs was identified through immunofluorescence and immunohistochemistry, both in vitro and in vivo. CAL27 and SCC25 cell lines were subjected to NETs stimulation to elucidate the influence of NETs on various cellular processes, including cell proliferation, migration, invasion, and metastasis in vitro. Furthermore, the impact of NETs on the growth and metastatic potential of OSCC was assessed using in vivo models involving tumor-bearing mice and tumor metastasis mouse models. RESULTS: Immunochemistry analysis revealed a significant correlation between the NETs-related markers and clinical stage, living status as well as TN stage. P. gingivalis has demonstrated its ability to effectively induce the release of NETs both in vivo and in vitro. NETs have the potential to facilitate cell migration, invasion, and colony formation. Moreover, in vivo experiments have demonstrated that NETs play a pivotal role in promoting tumor metastasis. CONCLUSION: High expression of NETs-related markers demonstrates a strong correlation with the progression of OSCC. Inhibition of the NETs release process stimulated by P. gingivalis and targeted NETs could potentially open up a novel avenue in the field of immunotherapy for patients afflicted with OSCC.

Does the use of intraoperative frozen section of bone marrow from the cut end of the mandible help assess the adequacy of bone margins following mandibulectomy for oral cancer?

BACKGROUND: The adequacy of the cut end of the mandible following a segmental mandibulectomy done for oral cancer intraoperatively is at times assessed using a frozen section (FS) of the bone marrow (BM) at the cut ends. The study aimed to assess its utility to guide the intraoperative decision on the adequacy of bony margins. MATERIALS AND METHODS: All patients with oral squamous cell carcinoma (OSCC) who underwent segmental mandibulectomy from January 2012 to December 2021 at our institute and for whom intraoperative FS of BM was utilized were included. We analyzed the sensitivity, specificity, and positive and negative predictive value (PPV, NPV) of this in predicting positive bone margins. RESULTS: A total of 457 patients were included in the study. The majority of the cases were per premium cases (n = 372, 81.4%). The median age of the cohort was 52 years (range: 22-80 years). Most patients had T4 disease (n = 406, 88.8%). On FS, BM was positive in only 18 patients (3.9%) for whom the bone margin was revised. BM biopsy report in the final histopathology was positive in 12 patients (2.2%). The sensitivity, specificity PPV, and NPV were 52.3%, 98.65%, 64.7%, and 97.7% respectively. No factors predicting BM positivity on FS could be identified in this cohort. CONCLUSIONS: The BM FS was positive in only a small percentage of patients, and it helped in reducing the bone margin positivity rate from 3.9% to 2.2% only. Hence the intraoperative BM FS seems to have limited utility as seen from our study.

Oral cavity squamous cell carcinomas in zoo-managed Goeldi's monkeys (Callimico goeldii).

BACKGROUND: Oral cavity squamous cell carcinomas (OCSCCs) are relatively common in multiple non-human primate species but are poorly documented in Goeldi's monkeys. METHODS: Four Goeldi's monkeys with OCSCC, from three zoological collections, underwent necropsy with cytology, histopathology, immunohistochemistry, and pan-herpesvirus PCR analysis. RESULTS: All animals were euthanised and exhibited poor-to-emaciated body condition. Three OCSCCs arose from the maxillary oral mucosa and a single OCSCC was primarily mandibular, with bone invasion evident in three cases. Histologically, one OCSCC in situ was diagnosed, whilst the rest were typically invasive OCSCCs. Neoplastic cells were immunopositive for pancytokeratin and E-cadherin. All examined cases were negative for regional lymph node (RLN) and/or distant metastases, cyclooxygenase-2 (COX-2) immunoexpression, and panherpesvirus PCR expression. CONCLUSIONS: OCSCCs in Goeldi's monkeys may be deeply invasive, but not readily metastatic. No herpesvirus-association or COX-2 expression was evident; the latter suggesting that NSAIDs are unlikely to be a viable chemotherapeutic treatment.

The role of periodontitis in cancer development, with a focus on oral cancers.

Periodontitis is a severe gum infection that begins as gingivitis and can lead to gum recession, bone loss, and tooth loss if left untreated. It is primarily caused by bacterial infection, which triggers inflammation and the formation of periodontal pockets. Notably, periodontitis is associated with systemic health issues and has been linked to heart disease, diabetes, respiratory diseases, adverse pregnancy outcomes, and cancers. Accordingly, the presence of chronic inflammation and immune system dysregulation in individuals with periodontitis significantly contributes to the initiation and progression of various cancers, particularly oral cancers. These processes promote genetic mutations, impair DNA repair mechanisms, and create a tumor-supportive environment. Moreover, the bacteria associated with periodontitis produce harmful byproducts and toxins that directly damage the DNA within oral cells, exacerbating cancer development. In addition, chronic inflammation not only stimulates cell proliferation but also inhibits apoptosis, causes DNA damage, and triggers the release of pro-inflammatory cytokines. Collectively, these factors play a crucial role in the progression of cancer in individuals affected by periodontitis. Further, specific viral and bacterial agents, such as hepatitis B and C viruses, human papillomavirus (HPV), Helicobacter pylori (H. pylori), and Porphyromonas gingivalis, contribute to cancer development through distinct mechanisms. Bacterial infections have systemic implications for cancer development, while viral infections provoke immune and inflammatory responses that can lead to genetic mutations. This review will elucidate the link between periodontitis and cancers, particularly oral cancers, exploring their underlying mechanisms to provide insights for future research and treatment advancements.

Marine-derived κ-carrageenan-coated zinc oxide nanoparticles for targeted drug delivery and apoptosis induction in oral cancer.

BACKGROUND: Kappaphycus alvarezii, a marine red algae species, has gained significant attention in recent years due to its versatile bioactive compounds. Among these, κ-carrageenan (CR), a sulfated polysaccharide, exhibits remarkable antimicrobial properties. This study emphasizes the synergism attained by functionalizing zinc oxide nanoparticles (ZnO NPs) with CR, thereby enhancing its antimicrobial efficacy and target specificity against dental pathogens. METHODS: In this study, we synthesized ZnO-CR NPs and characterized them using SEM, FTIR, and XRD techniques to authenticate their composition and structural attributes. Moreover, our investigation revealed that ZnO-CR NPs possess better free radical scavenging capabilities, as evidenced by their effective activity in the DPPH and ABTS assay. RESULTS: The antimicrobial properties of ZnO-CR NPs were systematically assessed using a zone of inhibition assay against dental pathogens of S. aureus, S. mutans, E. faecalis, and C. albicans, demonstrating their substantial inhibitory effects at a minimal concentration of 50 µg/mL. We elucidated the interaction between CR and the receptors of dental pathogens to further understand their mechanism of action. The ZnO-CR NPs demonstrated a dose-dependent anticancer effect at concentrations of 5 µg/mL, 25 µg/mL, 50 µg/mL, and 100 µg/mL on KB cells, a type of Human Oral Epidermal Carcinoma. The mechanism by which ZnO-CA NPs induced apoptosis in KB cells was determined by observing an increase in the expression of the BCL-2, BAX, and P53 genes. CONCLUSION: Our findings unveil the promising potential of ZnO-CR NPs as a candidate with significant utility in dental applications. The demonstrated biocompatibility, potent antioxidant and antiapoptotic activity, along with impressive antimicrobial efficacy position these NPs as a valuable resource in the ongoing fight against dental pathogens and oral cancer.

Multifunctional curcumin mediated zinc oxide nanoparticle enhancing biofilm inhibition and targeting apoptotic specific pathway in oral squamous carcinoma cells.

BACKGROUND: Oral health remains a significant global concern with the prevalence of oral pathogens and the increasing incidence of oral cancer posing formidable challenges. Additionally, the emergence of antibiotic-resistant strains has complicated treatment strategies, emphasizing the urgent need for alternative therapeutic approaches. Recent research has explored the application of plant compounds mediated with nanotechnology in oral health, focusing on the antimicrobial and anticancer properties. METHODS: In this study, curcumin (Cu)-mediated zinc oxide nanoparticles (ZnO NPs) were synthesized and characterized using SEM, EDAX, UV spectroscopy, FTIR, and XRD to validate their composition and structural features. The antioxidant and antimicrobial activity of ZnO-CU NPs was investigated through DPPH, ABTS, and zone of inhibition assays. Apoptotic assays and gene expression analysis were performed in KB oral squamous carcinoma cells to identify their anticancer activity. RESULTS: ZnO-CU NPs showcased formidable antioxidant prowess in both DPPH and ABTS assays, signifying their potential as robust scavengers of free radicals. The determined minimal inhibitory concentration of 40 µg/mL against dental pathogens underscored the compelling antimicrobial attributes of ZnO-CU NPs. Furthermore, the interaction analysis revealed the superior binding affinity and intricate amino acid interactions of ZnO-CU NPs with receptors on dental pathogens. Moreover, in the realm of anticancer activity, ZnO-CU NPs exhibited a dose-dependent response against Human Oral Epidermal Carcinoma KB cells at concentrations of 10 µg/mL, 20 µg/mL, 40 µg/mL, and 80 µg/mL. Unraveling the intricate mechanism of apoptotic activity, ZnO-CU NPs orchestrated the upregulation of pivotal genes, including BCL2, BAX, and P53, within the KB cells. CONCLUSIONS: This multifaceted approach, addressing both antimicrobial and anticancer activity, positions ZnO-CU NPs as a compelling avenue for advancing oral health, offering a comprehensive strategy for tackling both oral infections and cancer.

The association between referral by specialists in oral diagnosis on survival rates of patients with oral cancer: A retrospective cohort study.

BACKGROUND: To assess the influence of diagnosis and referral provided by specialists in oral diagnosis on disease-free survival and overall survival of patients with oral cancer. METHODS: A cohort of 282 patients with oral cancer treated at a regional cancer hospital from 1998 to 2016 was analyzed retrospectively. The referral register of the patients was analyzed and assigned to two groups: (1) those referred by oral diagnosis specialists (n = 129), or (2) those referred by nonspecialized professionals (n = 153). The cancer treatment evolution was assessed from the patients' records, and the outcome was registered concerning cancer recurrence and death. Sociodemographic and clinicopathological variables were explored as predictors of disease-free survival and overall survival. RESULTS: Group 1 exhibited lower T stages and a reduced incidence of regional and distant metastases. Surgery was performed in 75.2% of cases in Group 1, while in Group 2, the rate was 60.8%. Advanced T stages and regional metastases reduced the feasibility of surgery. Higher TNM stages and tumor recurrence were associated with decreased disease-free survival, while surgical intervention was a protective factor. Higher TNM stage had a negative impact on the overall survival. CONCLUSION: Specialized oral diagnosis did not directly impact disease-free survival and overall survival and did not influence the indication of surgery in oral cancer; however, it was associated with the diagnosis of early tumors and better prognosis.

Clinicopathological features of myofibromas and myofibromatosis affecting the oral and maxillofacial region: A systematic review.

BACKGROUND: Myofibromas are rare benign neoplasms composed of myoid cells and myofibroblasts. This study aimed to systematically review case reports and a series of myofibromas (MF) and myofibromatosis (MFT) occurring in the oral and maxillofacial regions in order to describe their main clinicopathological features. METHODS: This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Electronic searches were conducted in 2023 in four databases: MEDLINE/PubMed, Web of Science, Scopus, and EMBASE. A manual search and a search in the grey literature were also conducted. The lesions were classified as MF or MFT according to their original report. RESULTS: A total of 169 cases were included in this systematic review. Men were slightly more affected, with a painless nodule. When occurring in soft tissue, MF usually developed in the gingiva (mean age:29.23 ± 21.93 years) and when it was intra-osseous, it occurred more frequently in the posterior mandible (mean age:14.33 ± 15.62 years). MFT occurred mainly in the mandible and was predominantly described as well-circumscribed masses of spindle cells organized in fascicles with a prominent vascular activity in a hemangiopericytoma-like pattern. The lesions were mainly positive for smooth muscle actin and vimentin immunomarkers. Surgical excision was the treatment of choice in the majority of cases and recurrence was observed in only three cases. CONCLUSION: MF and MFT affect more men, with an indolent clinical course. Intra-osseous tumors and MFT seem to occur more frequently in younger individuals. These lesions seem to have a good prognosis and low recurrence.

Tumor immune microenvironment in odontogenic carcinomas: Evaluation of the therapeutic potential of immune checkpoint blockade.

BACKGROUND: Despite recent advances in the use of immune checkpoint blockade (ICB) across various cancer types, its efficacy in odontogenic carcinomas remains unexplored. This study aims to investigate PD-L1 expression and the tumor immune microenvironment (TIME) in odontogenic carcinomas to determine the therapeutic potential of ICB and the significance of immune markers. METHODS: The expressions of PD-L1 and T cell markers (CD3, CD8, and FOXP3) were visualized by immunohistochemistry in 21 tissue samples of odontogenic carcinomas. Tumoral PD-L1 expression and the density and spatial distribution of T cell subsets were evaluated, from which TIME was determined. The associations of the variables with clinicopathological and prognostic factors were statistically analyzed. RESULTS: PD-L1 was positively expressed in 52.4% (11/21) of the cases studied. Among tumor types, ameloblastic carcinoma showed significantly higher PD-L1 expression (p = 0.016). TIME based on the intratumoral and stromal T cell distribution was immune-inflamed in 61.9% (13/21) and immune-excluded in 38.1% (8/21), with no immune-desert cases. PD-L1 expression was associated with the densities of all intratumoral T cell subsets (p = 0.03 for CD3, p = 0.03 for CD8, and p = 0.008 for FOXP3) but not with those of stromal T cells. High PD-L1 expression was associated with larger tumor size (p = 0.021), while the intratumoral CD8/CD3 ratio was inversely correlated with tumor size (p = 0.048). CONCLUSION: These findings indicate the involvement of adaptive immune resistance in a subset of odontogenic carcinomas and support the therapeutic potential of ICB in patients with these rare malignancies.

Clinicopathological characteristics of odontogenic carcinosarcoma: A systematic review.

BACKGROUND: The aim of the present systematic review was to summarize evidence on odontogenic carcinosarcoma, analyzing clinical, epidemiological, imaging, histopathological, immunohistochemical, therapeutic, and prognostic features of this tumor. MATERIALS AND METHODS: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Searches were performed in the Ovid MEDLINE (Wolters Kluwer), PubMed (National Library of Medicine), Web of Science (Thomson Reuters), Scopus (Elsevier), and LILACS (Latin American and Caribbean Center on Health Sciences Information) databases, without publication date or language restrictions. Case reports or case series of OCS reporting clinical, radiological, and histopathological data that confirmed the diagnosis were selected. The Joanna Briggs Institute-University of Adelaide tool was used for critical appraisal of the included articles. RESULTS: Odontogenic carcinosarcoma is a rare, aggressive tumor associated with high mortality; however, the metastasis rate is low. The tumor has a male predilection. The mean patient age is 40 years, but there is no predilection for age. The left posterior mandible is the most affected site, but no specific radiographic features have been reported. CONCLUSION: Given its rarity, dentists, oral-maxillofacial surgeons, and physicians need to be aware of odontogenic carcinosarcoma in order to increase the diagnostic potential, preventing delays in diagnosis and treatment and thus contributing to lower morbidity of the tumor.