Parotideomasseteric fascia flap is an effective management for prevention of postoperative salivary collection arising from radical surgery of oral cancer.

Salivary collection (SC) following surgery for oral cancer represents an underreported and unrecognized complication. Our study aimed to evaluate the efficacy of parotideomasseteric fascia flap (PFF) in preventing postoperative SC, comparing its effectiveness with other conventional methods. Between November 2019 and January 2023, 221 patients diagnosed with oral squamous cell carcinoma (OSCC) undergoing wide tumor ablation and neck dissection at Xiangya Hospital were included in the study. Patients were randomly allocated into four groups based on different intraoperative techniques to assess the preventive efficacy of PFF against SC. The incidence of SC in the PFF group was only 5.9%, which was significantly lower than the other three groups (p < 0.05). Among the 221 patients, the highest SC incidence occurred in buccal cancer cases (19.6%). However, in the PFF group, the incidence was not significantly different (9.5%; p > 0.05). Univariate analysis revealed a higher SC incidence associated with advanced clinical T stage (p = 0.02), N(+) stage (p = 0.01), low average serum albumin (SA) level (p = 0.00), and a large parotid wound (p = 0.00). In multivariate analysis, only average SA (p = 0.01; odds ratio [OR] 4.104; 95% CI 0.921-11.746) emerged as the most prevalent factor predisposing to SC. The utilization of PFF demonstrated a notable reduction in the incidence of postoperative SC, establishing it as a safe, effective, and convenient method for patients undergoing radical ablation for OSCC.

Characteristics and clinical significance of tertiary lymphoid structures in OSCC.

OBJECTIVES: This study aimed to investigate the characteristics of tertiary lymphoid structures (TLSs) in oral squamous cell carcinoma (OSCC) and their association with clinical and pathological features. MATERIALS AND METHODS: 12 TLS-related chemokines in TCGA database were analyzed to investigate the TLSs in OSCC. The density, maturity, and location of TLSs in a large cohort of 189 OSCC patients (114 of which had clinical and prognostic information) were assessed. And the significance between TLSs and clinicopathologic characteristics was analyzed. RESULTS: Bioinformatics and analysis showed that TLSs were associated with better clinical outcomes in OSCC. Histological staining and analysis showed that the overall survival rate of the high-density group (71/112, 63.4%) was significantly higher (p < 0.0001) than that of the low-density group (41/112, 36.6%), and the high-density group had fewer lymph node metastases (50.0%/68.3%, p = 0.021). And TLSs were divided into 4 types according to the maturity and location. Different types of TLSs are associated with prognosis (OS, p < 0.0001), clinical features (T stage, p = 0.028; degree of differentiation, p = 0.043), and precancerous lesion types (OSF, p = 0.049) of OSCC patients. CONCLUSION: TLSs were closely associated with better OSCC prognosis, and a more systematic classification may better guide the formulation of further treatment options.

The Potential MicroRNA Diagnostic Biomarkers in Oral Squamous Cell Carcinoma of the Tongue.

Oral squamous cell carcinoma (OSCC) of the tongue is a common type of head and neck malignancy with a poor prognosis, underscoring the urgency for early detection. MicroRNAs (miRNAs) have remarkable stability and are easily measurable. Thus, miRNAs may be a promising biomarker candidate among biomarkers in cancer diagnosis. Biomarkers have the potential to facilitate personalized medicine approaches by guiding treatment decisions and optimizing therapy regimens for individual patients. Utilizing data from The Cancer Genome Atlas, we identified 13 differentially expressed upregulated miRNAs in OSCC of the tongue. Differentially expressed miRNAs were analyzed by enrichment analysis to reveal underlying biological processes, pathways, or functions. Furthermore, we identified miRNAs associated with the progression of OSCC of the tongue, utilizing receiver operating characteristic analysis to evaluate their potential as diagnostic biomarkers. A total of 13 upregulated miRNAs were identified as differentially expressed in OSCC of the tongue. Five of these miRNAs had high diagnostic power. In particular, miR-196b has the potential to serve as one of the most effective diagnostic biomarkers. Then, functional enrichment analysis for the target gene of miR-196b was performed, and a protein-protein interaction network was constructed. This study assessed an effective approach for identifying miRNAs as early diagnostic markers for OSCC of the tongue.

Analysis of methylation-driven genes for predicting the prognosis of patients with oral squamous cell carcinoma.

Background: Oral squamous cell carcinoma (OSCC) is a highly aggressive malignancy that is characterized by early distant metastasis and poor prognosis. DNA methylation plays an important role in the etiology and pathogenesis of OSCC. This study aimed to identify methylation-driven genes through bioinformatics analysis as potential biomarkers for early diagnosis and prognostic assessment of OSCC. Methods: Methylation data, RNA sequencing (RNA-seq) data and clinical prognosis information of OSCC patients were retrieved from The Cancer Genome Atlas (TCGA) database. The R packages MethylMix were employed to analyze the correlation between methylation status and corresponding gene expression in tumor and normal tissues to obtain methylation-driven genes. Univariate Cox regression analysis was developed to further screen methylation-driven genes associated with the prognosis of OSCC patients. Subsequently, multivariate Cox regression analysis was utilized to construct a linear prognostic risk prediction model. Furthermore, a combined survival analysis integrating methylation and gene expression was performed to investigate the prognostic value. Results: A total of 374 differentially expressed methylation-driven genes were identified. Seven methylation-driven genes (BST2, KRT15, ZNF134, NT5E, GSTA7P, NAPRT, and GOLPH3L) were found to be significantly associated with patient prognosis. Additionally, four methylation-driven genes (BST2, KRT15, ZNF134 and NAPRT) were used to construct a linear prognostic risk prediction model for OSCC patients. Furthermore, a combined Kaplan-Meier survival analysis revealed that three methylation-driven genes (ZKSCAN7, MFF, ZNF134) alone can be used as independent prognostic markers or drug targets. Conclusions: Our findings facilitate a better understanding of molecular mechanisms of OSCC and provide potential biomarkers of early diagnosis, precision treatment and prognosis evaluation.

ETS1-mediated Regulation of SOAT1 Enhances the Malignant Phenotype of Oral Squamous Cell Carcinoma and Induces Tumor-associated Macrophages M2-like Polarization.

Oral squamous cell carcinoma (OSCC) is an aggressive cancer that poses a substantial threat to human life and quality of life globally. Lipid metabolism reprogramming significantly influences tumor development, affecting not only tumor cells but also tumor-associated macrophages (TAMs) infiltration. SOAT1, a critical enzyme in lipid metabolism, holds high prognostic value in various cancers. This study revealed that SOAT1 is highly expressed in OSCC tissues and positively correlated with M2 TAMs infiltration. Increased SOAT1 expression enhanced the capabilities of cell proliferation, tumor sphere formation, migration, and invasion in OSCC cells, upregulated the SREBP1-regulated adipogenic pathway, activated the PI3K/AKT/mTOR pathway and promoted M2-like polarization of TAMs, thereby contributing to OSCC growth both in vitro and in vivo. Additionally, we explored the upstream transcription factors that regulate SOAT1 and discovered that ETS1 positively regulates SOAT1 expression levels. Knockdown of ETS1 effectively inhibited the malignant phenotype of OSCC cells, whereas restoring SOAT1 expression significantly mitigated this suppression. Based on these findings, we suggest that SOAT1 is regulated by ETS1 and plays a pivotal role in the development of OSCC by facilitating lipid metabolism and M2-like polarization of TAMs. We propose that SOAT1 is a promising target for OSCC therapy with tremendous potential.

Hsa_circRNA_101036 aggravates hypoxic-induced endoplasmic reticulum stress via the miR-21-3p/TMTC1 axis in oral squamous cell carcinoma.

Objective: Circular RNAs (circRNAs) have been identified as potential biomarkers and therapeutic targets for various types of cancer, including Oral squamous cell carcinoma (OSCC). Hsa_circRNA_101036 was found to function as a cancer suppressor gene in OSCC; however, the underlying regulatory mechanism remains unclear. We investigated the role of hsa_circRNA_101036 in OSCC development and progression and explored its potential as a therapeutic target. Methods: We performed a bioinformatics analysis and used experimental approaches to investigate the regulatory mechanism of hsa_circRNA_101036. The database StarBase v.2.0 was used to predict potential target-miRNAs of hsa_circRNA_101036. The levels of hsa_circRNA_101036, miR-21-3p, and TMTC2 expression in samples of OSCC cancer tissue (n = 15) and adjacent tissue (n = 15) were determined. We also examined the effects of hsa_circRNA_101036 overexpression on OSCC cell lines by using cell viability, migration, and invasion assays. The proportions of apoptotic cells and the reactive oxygen species (ROS) levels were analyzed by flow cytometry. We also investigated how hsa_circRNA_101036 overexpression affected the levels of miR-21-3p and TMTC2, and endoplasmic reticulum (ER) stress in OSCC cells. Results: The levels of hsa_circRNA_101036 and TMTC2 expression were significantly lower, while miR-21-3p expression was higher in tumor tissues and OSCC cells when compared to adjacent tissues and normal oral fibroblasts, respectively. The levels of HIF-1α and miR-21-3p expression were significantly increased under conditions of hypoxia, while the levels of hsa_circRNA_101036 and TMTC2 were decreased. The expression levels of proteins associated with ER stress, the proportions of apoptotic cells, and the levels of ROS were all increased by hypoxia stimulation. In addition, overexpression of hsa_circRNA_101036, but not mutant hsa_circRNA_101036, was found to enhance the effect of hypoxia on HSC3 and OECM-1 cells. Hsa_circRNA_101036 overexpression suppressed tumor growth and induced ER stress. Finally, knockdown of miR-21-3p had the same effect as overexpression of hsa_circRNA_101036. Conclusion: Our findings suggest that hsa_circRNA_101036 plays a critical role in the development and progression of OSCC. Overexpression of hsa_circRNA_101036 aggravated ER stress, and increased cell apoptosis and ROS production in OSCC under hypoxic conditions. Hsa_circRNA_101036 up-regulated TMTC2 expression by sponging miR-21-3p in OSCC.

Efficacy of Cisplatin-CXCR4 Antagonist Combination Therapy in Oral Cancer.

Cisplatin is a platinum-based compound that is widely used for treating inoperable oral squamous cell carcinoma (OSCC) in Japan; however, resistance to cisplatin presents a challenge and innovative approaches are required. We aimed to investigate the therapeutic potential of targeting the chemokine receptor CXCR4, which is involved in angiogenesis and tumor progression, using the CXCR4 inhibitor AMD3100, in combination with cisplatin. AMD3100 induced necrosis and bleeding in OSCC xenografts by inhibiting angiogenesis. We investigated the combined ability of AMD3100 plus cisplatin to enhance the antitumor effect in cisplatin-resistant OSCC. An MTS assay identified HSC-2 cells as cisplatin-resistant cells in vitro. Mice treated with the cisplatin-AMD combination exhibited the most significant reduction in tumor volume, accompanied by extensive hemorrhage and necrosis. Histological examination indicated thin and short tumor vessels in the AMD and cisplatin-AMD groups. These results indicated that cisplatin and AMD3100 had synergistic antitumor effects, highlighting their potential for vascular therapy of refractory OSCC. Antitumor vascular therapy using cisplatin combined with a CXCR4 inhibitor provides a novel strategy for addressing cisplatin-resistant OSCC.

Oral and oropharyngeal NUT carcinoma: a multicentre screening study of poorly differentiated oral cancer.

BACKGROUND AND AIMS: Nuclear protein testis (NUT) carcinoma (NC) is a rare and highly aggressive tumour characterised by chromosomal rearrangement of the nuclear protein testis family member 1 (NUTM1) gene, also known as the NUT gene. NC occurs mainly in the head and neck, mediastinum and lung. In general, primary NC in the oral cavity is extremely rare and reported sporadically. METHODS: A total of 111 formalin-fixed and paraffin-embedded specimens of poorly differentiated oral and oropharyngeal tumours were collected from 10 hospitals. NUT protein IHC staining was performed on these samples, and fluorescence in-situ hybridisation (FISH) and RNA sequencing detection were further carried out for NUT IHC-positive cases. RESULTS: The expression of NUT protein in tumour cells was detected in five cases (five of 111, 4.5%). The tumours in these cases were located in the oral floor, lip, base of the tongue, gingiva and hard palate. FISH detection results showed BRD4::NUT rearrangement in three patients and a non-BRD4::NUT rearrangement pattern in two patients. RNA sequencing results confirmed BRD4::NUT rearrangement in two cases. CONCLUSIONS: To our knowledge, this is the first and largest retrospective study of oral NC, and we found that NC is easily misdiagnosed as poorly differentiated oral squamous cell carcinoma (SCC) or poorly differentiated carcinoma. The morphology and immunophenotype of four NC cases were similar to SCC, and abrupt keratinisation was observed in three cases. Therefore, it is necessary to detect NUT protein for NC screening in oral malignant tumours with these morphologies, especially for young patients who are more likely to be misdiagnosed with other types of cancer.

A 5-ALA mediated photodynamic therapy increases natural killer cytotoxicity against oral squamous cell carcinoma cell lines.

Oral squamous cell carcinoma (OSCC) constitutes over 90% of oral cancers, known for its aggressiveness and poor prognosis. Photodynamic therapy (PDT) has emerged as a promising adjuvant therapy and is linked to immunogenic cell death, activating innate and adaptive anti-tumor responses. Natural Killer (NK) cells, key players in malignant cell elimination, have not been extensively studied in PDT. This study evaluates whether PDT increases OSCC cell lines' susceptibility to NK cell cytotoxicity. PDT, using 5-aminolevulinic acid (5-ALA) and LED irradiation, was applied to Ca1 and Luc4 cell lines. Results showed a dose-dependent viability decrease post-PDT. Gene expression analysis revealed upregulation of NK cell-activating ligands (ULBP1-4, MICA/B) and decreased MHC class I expression in Ca1, suggesting increased NK cell susceptibility. Enhanced NK cell cytotoxicity was confirmed in Ca1 but not in Luc4 cells. These findings indicate that PDT may enhance NK cell-mediated cytotoxicity in OSCC, offering potential for improved treatment strategies.

Oncological Outcome of Node-Positive Oral Squamous Cell Carcinomas Treated With Selective and Comprehensive Neck Dissection.

Selective neck dissection (SND) is the treatment of choice in patients with oral squamous cell carcinomas (OSCCs) and clinically node-negative necks (cN0). The treatment of patients with positive-staged necks (cN+) includes SND as well as comprehensive neck dissection (CND). The clear benefit of one or the other remains under debate. We aim to address this lack of clarity by analysing patients with OSCC staged with clinically node-positive necks, treated with either CND or SND using a level-by-level approach. This retrospective study included patients diagnosed with OSCC with clinically (cN+) and pathologically (pN+) positive cervical lymph nodes (LNs) with clear neck level categorization during the years 2010-2019. In total, 74 patients were analysed. Cox regression analysis found no significance for the type of ND being an independent risk factor, neither for overall survival (OS) nor for disease-free survival (DFS). Regional recurrence of CND cases (5.77%) was comparable to SND cases (9.09%). For OS, extracapsular spread (ECS) and male sex were identified as independent risk factors with poorer outcome. pT-stage and ECS were found to be independent risk factors for DFS. The results of this study suggest that both CND and SND may be viable treatment options for certain patients with OSCC pN+.

Effect and mechanism of resveratrol on ferroptosis mediated by p53/SLC7A11 in oral squamous cell carcinoma.

OBJECTIVE: Resveratrol (Res) is a natural phytoestrogen with antitumor activity. This study sought to investigate the role of Res in ferroptosis in oral squamous cell carcinoma (OSCC). METHODS: Normal human oral keratinocyte (HOK)/oral OSCC (CAL-27/SCC-9) cell lines were treated with different doses of Res. Res toxicity was determined by MTT assay, with half maximal inhibitory concentration values of Res on CAL-27 and SCC-9 cells calculated. Cell viability/colony formation efficiency/migration/invasion/cycle were assessed by CCK-8/colony formation assay/transwell assay/flow cytometry. The expression of p53 protein in the nucleus and cytoplasm, glutathione peroxidase 4 (GPX4) expression, and SLC7A11 messenger RNA (mRNA) and protein expression levels were determined by Western blot and RT-qPCR. Fe2+ content, reactive oxygen species (ROS) level, reduced glutathione (GSH), and lactate dehydrogenase (LDH) release were assessed. RESULTS: Medium- to low-dose Res had no toxic effect on HOK cells, while high-dose Res markedly reduced HOK cell viability. Res significantly suppressed the viability of OSCC cells (CAL-27 and SCC-9). Res inhibited OSCC cell colony formation/migration/invasion, and induced G1 phase arrest. Res caused the translocation of p53 protein to the nucleus, obviously increased Fe2+ content, ROS level and LDH release, decreased GSH content and GPX4 protein expression, and induced ferroptosis. Down-regulation of p53 partially reversed the inhibitory effects of Res on CAL-27 cell malignant behaviors. Res inhibited SLC7A11 transcription by promoting p53 entry into the nucleus. SLC7A11 overexpression negated the the regulatory effects of p53 knockout on the role of Res in OSCC cell malignant behaviors and ferroptosis. CONCLUSION: Res accelerated ferroptosis and inhibited malignant behaviors in OSCC cells by regulating p53/SLC7A11.

TUSC3, p53 and p21 genetic association with development of oral submucous fibrosis and oral squamous cell carcinoma among addictive tobacco chewers of Pakistan.

BACKGROUND: This study delves into the intricate landscape of oral cancer, a global concern with a high incidence in Asian countries. We focus on oral squamous cell carcinoma (OSCC), primarily driven by the consumption of betel nut and its derivatives. OSCC often arises from premalignant lesions like oral submucous fibrosis (OSF). In Pakistan, OSCC is prevalent among men due to various addictive substances, including smokeless tobacco and chewing materials. Mutations in tumor suppressor genes, such as TP53 and p21, play crucial roles in this malignancy's development. We also explore the involvement of TUSC3 gene deletion in OSCC and OSF. METHODS: In this study we investigated demographics, TUSC3 gene expression, deletion analysis, and TP53 and p21 genetic alterations in OSCC and OSF patients (blood and tissue of 50 samples in each condition) who had tobacco derivates usage history. The association analysis was carried out mainly through PCR based genotyping. RESULTS: The study's patient cohort (OSCC and OSF) displayed a wide age range from 13 to 65 years (Mean = 32.96 years). Both conditions were more prevalent in males, with a male-female ratio of approximately 2.5:1. Chewing habits analysis revealed high frequencies of gutka use in both OSF and OSCC patients. TUSC3 expression analysis in OSCC cell lines indicated significant downregulation. Genotyping showed no TUSC3 deletion in OSF cases, but a deletion rate of over 22% in OSCC tissue samples. Analysis supported a significant association of TUSC3 deletion with OSCC development but not with OSF. Polymorphism in p53 exon 4 and p21 (rs1801270) were significantly associated with both OSCC and OSF, adding to their pathogenesis. Our findings further revealed a strong correlation between TUSC3 deletion and the excessive use of tobacco and related products, shedding light on the genetic underpinnings of OSCC development. CONCLUSIONS: Notably, our study provides a crucial insight into genetic aspects underlying OSCC and OSF in response of addictive consumption of areca nut, betel quid, and tobacco derivatives. A significant association between TUSC3 deletion and OSCC development, along with polymorphisms in TP53 and p21, underscores the importance of further research into the molecular mechanisms driving oral cancer progression for improved diagnosis and treatment outcomes.

Nanocatalytic NO gas therapy against orthotopic oral squamous cell carcinoma by single iron atomic nanocatalysts.

Oral squamous cell carcinoma (OSCC) has been being one of the most malignant carcinomas featuring high metastatic and recurrence rates. The current OSCC treatment modalities in clinics severely deteriorate the quality of life of patients due to the impaired oral and maxillofacial functions. In the present work, we have engineered the single-atom Fe nanocatalysts (SAF NCs) with a NO donor (S-nitrosothiol, SNO) via surface modification to achieve synergistic nanocatalytic NO gas therapy against orthotopic OSCC. Upon near-infrared laser irradiation, the photonic hyperthermia could effectively augment the heterogeneous Fenton catalytic activity, meanwhile trigger the thermal decomposition of the engineered NO donor, thus producing toxic hydroxyl radicals (•OH) and antitumor therapeutic NO gas at tumor lesion simultaneously, and consequently inducing the apoptotic cell death of tumors via mitochondrial apoptosis pathway. This therapeutic paradigm presents an effective local OSCC therapeutics in a synergistic manner based on the nanocatalytic NO gas therapy, providing a promising antitumor modality with high biocompatibility.

In this work, we have engineered the NIR-triggered NO liberating donor module RSNO onto single-atom Fe nanocatalysts for synergized nanocatalytic therapy and NO gas therapy against orthotopic OSCC with high therapeutic selectivity, efficacy and biocompatibility.

[Retracted] Galectin­3 blockade suppresses the growth of cetuximab­resistant human oral squamous cell carcinoma.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the colony formation assay data shown in Fig. 4C on p. 6 were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes, which had already been published. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 24: 685, 2021; DOI: 10.3892/mmr.2021.12325].

Traversing the Terrain: Potential Pitfalls within the AJCC 8th Edition Staging System for Lip and Oral Cavity Cancers.

In 1977, the American Joint Committee on Cancer (AJCC) introduced the inaugural Cancer Staging Manual, which implemented the T (tumor extent), N (regional lymph node status), and M (presence or absence of distant metastasis) staging system. This systematic approach aimed to convey the extent of disease across various cancer types, providing clinicians with a practical framework to plan treatment strategies, predict prognosis, and assess outcomes. The AJCC 8th edition, effective from January 1, 2018, continues this tradition. However, certain shortcomings persist in the AJCC 8th edition, as identified through clinical experience. Specifically, challenges arise in accurately assessing depth of invasion in unique histological variants of oral squamous cell carcinoma (e.g., Oral verrucous carcinoma, Carcinoma cuniculatum, and Papillary squamous cell carcinoma) and minor salivary gland tumors. Additionally, discrepancies exist in the perception of bone invasion patterns and in reporting practices. There is also a need for staging guidelines for malignant odontogenic tumors and multifocal tumors of the oral cavity, supplemented by diagrammatic representations. Lastly, there is a call for comprehensive staging criteria for carcinomas of the ear, external auditory canal, and temporal bone. We advocate for the inclusion of these considerations in future editions of the AJCC Cancer Staging Manual.

JARID2, a novel regulatory factor, promotes cell proliferation, migration, and invasion in oral squamous cell carcinoma.

BACKGROUND: Accurate regulation of gene expression is crucial for normal development and function of cells. The prognostic significance and potential carcinogenic mechanisms of the related gene JARID2 in OSCC are not yet clear, but existing research has indicated a significant association between the two. METHODS AND MATERIALS: The relationship between the expression of the JARID2 gene in tumor samples of OSCC patients and clinical pathological factors was analyzed using immunohistochemistry experiments and RT-qPCR analysis. Based on the clinical pathological data of patients, bioinformatics analysis was conducted using public databases to determine the function of JARID2 in OSCC. Knockdown OSCC cell lines were constructed, and the impact of JARID2 on the biological behavior of OSCC cell lines was assessed through CCK-8, wound healing assay, and transwell analysis. RESULTS: Immunohistochemistry experiments confirmed the correlation between JARID2 and the prognosis of OSCC patients, while RT-qPCR experiments demonstrated its expression levels in tissue and cells. CKK-8 experiments, wound healing assays, and Transwell experiments indicated that knocking down JARID2 had a negative impact on the proliferation, invasion, and migration of OSCC cells. Bioinformatics analysis results showed that the expression of JARID2 in OSCC is closely associated with patient gene co-expression, gene function enrichment, immune infiltration, and drug sensitivity. CONCLUSION: Our study indicates that JARID2 is a novel prognostic biomarker and potential therapeutic target for OSCC.

Integrating lipid metabolite analysis with MRI-based transformer and radiomics for early and late stage prediction of oral squamous cell carcinoma.

BACKGROUND: Oral Squamous Cell Carcinoma (OSCC) presents significant diagnostic challenges in its early and late stages. This study aims to utilize preoperative MRI and biochemical indicators of OSCC patients to predict the stage of tumors. METHODS: This study involved 198 patients from two medical centers. A detailed analysis of contrast-enhanced T1-weighted (ceT1W) and T2-weighted (T2W) MRI were conducted, integrating these with biochemical indicators for a comprehensive evaluation. Initially, 42 clinical biochemical indicators were selected for consideration. Through univariate analysis and multivariate analysis, only those indicators with p-values less than 0.05 were retained for model development. To extract imaging features, machine learning algorithms in conjunction with Vision Transformer (ViT) techniques were utilized. These features were integrated with biochemical indicators for predictive modeling. The performance of model was evaluated using the Receiver Operating Characteristic (ROC) curve. RESULTS: After rigorously screening biochemical indicators, four key markers were selected for the model: cholesterol, triglyceride, very low-density lipoprotein cholesterol and chloride. The model, developed using radiomics and deep learning for feature extraction from ceT1W and T2W images, showed a lower Area Under the Curve (AUC) of 0.85 in the validation cohort when using these imaging modalities alone. However, integrating these biochemical indicators improved the model's performance, increasing the validation cohort AUC to 0.87. CONCLUSION: In this study, the performance of the model significantly improved following multimodal fusion, outperforming the single-modality approach. CLINICAL RELEVANCE STATEMENT: This integration of radiomics, ViT models, and lipid metabolite analysis, presents a promising non-invasive technique for predicting the staging of OSCC.

TCF12 induces ferroptosis by suppressing OTUB1-mediated SLC7A11 deubiquitination to promote cisplatin sensitivity in oral squamous cell carcinoma.

Chemotherapy resistance is a major obstacle to effective cancer treatment, and promotion of ferroptosis can suppress cisplatin resistance in tumor cells. TCF12 plays a suppressive role in oral squamous cell carcinoma (OSCC), but whether it participates in the regulation of cisplatin resistance by modulating ferroptosis remains unclear. Here, we found that TCF12 expression was decreased in OSCC cells compared with normal oral cells, and it was reduced in cisplatin (DDP)-resistant OSCC cells compared with parental cells. Moreover, overexpression of TCF12 sensitized DDP-resistant cells to DDP by promoting ferroptosis. Intriguingly, silencing TCF12 reversed the promotion effect of the ferroptosis activator RSL3 on ferroptosis and DDP sensitivity, and overexpressing TCF12 antagonized the effect of the ferroptosis inhibitor liproxstatin-1 on ferroptosis and DDP resistance. Mechanically, TCF12 promoted ubiquitination of SLC7A11 and decreased SLC7A11 protein stability through transcriptional repression of OTUB1, thereby facilitating ferroptosis. Consistently, SLC7A11 overexpression neutralized the promotion effect of TCF12 on ferroptosis and DDP sensitivity. Additionally, upregulation of TCF12 hindered the growth of mouse OSCC xenografts and enhanced the DDP sensitivity of xenografts by inducing ferroptosis. In conclusion, TCF12 enhanced DDP sensitivity in OSCC cells by promoting ferroptosis, which was achieved through modulating SLC7A11 expression via transcriptional regulation of OTUB1.

Formulation of 1% α-mangostin in orabase gel induces apoptosis in oral squamous cell carcinoma.

BACKGROUND: Plant-derived compounds have chemopreventive properties to be used as alternative medicine. Pericarp of Mangosteen (Garcinia mangostana Linn.), a tropical fruit in Southeast Asia contains a phytochemical α-mangostin (α-MG) that demonstrates potent anticancer effects against various types of cancer. α-MG has been reported to be the most effective agent in human cancer cell lines. The objectives of this study were to develop oral gel formulations containing α-MG and determine their (1) anticancer activity, (2) anti-HPV-16 and antimicrobial activities, (3) nitric oxide (NO) inhibitory activity, and (4) wound healing effect. METHODS: Formulations of oral gel containing α-MG were developed. Anticancer activity on SCC-25 was assessed. Apoptotic induction was determined using flow cytometry technique. Antiviral activity against HPV-16 pseudovirus and antimicrobial activity against S. mutans, P. gingivalis and C. albicans were investigated. NO inhibition was carried out. Fibroblast cell migration was determined by in vitro scratch assay. RESULTS: The formulation of 1% α-MG in orabase gel demonstrated anticancer activity by promoting apoptosis in SCC-25. The induction of apoptotic activity was dose dependent with pronounced effect in late apoptosis. The formulation appeared to reduce cell viability of oral keratinocytes (OKC). At CC50 it showed an inhibition against HPV-16 pseudovirus infection. The formulation had no antimicrobial activity against S. mutans, P. gingivalis and C. albicans. No significant NO inhibitory activity and wound healing effects were found. CONCLUSIONS: 1% α-MG in orabase gel exhibited anticancer activity by inducing apoptosis although low level of cytotoxicity observed in OKC was present. The appropriate carrier for novel nano-particles targeting cancer cells should be further investigated.

Novel vaccination strategies based on optimal stimulation of CD4+ T helper cells for the treatment of oral squamous cell carcinoma.

Oral Squamous Cell Carcinoma (OSCC) is the most common malignant tumor of the oral cavity. Despite recent advances in the field of oral cancer therapy, including the introduction of immunotherapeutic approaches, the 5-year survival rate remains steadily assessed around 50%. Thus, there is an urgent need for new therapeutic strategies. After the characterization of the immune phenotype of three human OSCC cell lines (CAL-27, SCC-25, and SCC-4) and one mouse OSCC cell line (MOC2) showing their similarities to resected patient tumors, we explored for the first time an experimental preclinical model of therapeutic vaccination with mouse OSCC MOC2 cell line stably expressing MHC class II antigens after CIITA gene transfection (MOC2-CIITA). Mice injected with MOC2-CIITA reject or strongly retard tumor growth; more importantly, vaccinated animals that fully reject MOC2-CIITA tumors display anti-tumor immunological memory protective against challenge with parental MOC2 tumor cells. Further experiments of adoptive cell transfer or in vivo cell depletion show that both CD4+ and CD8+ T lymphocytes prove fundamental in tumor rejection. This unprecedented approach for oral cancer opens the way for possible future translation of novel immunotherapeutic strategies to the human setting for the treatment of this tumor.