Mast Cell Infiltration and Subtype Promote Malignant Transformation of Oral Precancer and Progression of Oral Cancer.

The role of mast cell (MC), a common myeloid-derived immune cell, in the development of oral squamous cell carcinoma (OSCC) is unclear. The aim of this study was to investigate MC infiltration in oral precancer and oral cancer. The evaluation of immune cell infiltration and its association with prognosis in OSCC used RNA sequencing and multiple public datasets. Multiplex immunofluorescence was used to explore the infiltration of MC in the microenvironment of OSCC and oral precancer and the interaction with CD8+ cells. The role of MC in OSCC progression was verified by in vivo experiments. The resting MC infiltration was mainly present in oral precancer, whereas activated MC infiltration was significantly higher in OSCC. Activated MC was associated with malignant transformation of oral precancer and poor prognosis of OSCC. In vivo studies showed that MC promoted the growth of OSCC. The infiltration of activated MC was negatively correlated with the infiltration of CD8+ T cells. The subtype of MC containing tryptase without chymase (MCT) was significantly higher in OSCC compared with oral precancer and was associated with poor survival. Furthermore, spatial distance analysis revealed a greater distance between MCT and CD8+ cells, which was also linked to poor prognosis in OSCC. Cox regression analysis showed that MCT could be a potential diagnostic and prognostic biomarker. This study provides new insights into the role of MC in the immune microenvironment of OSCC. It might enhance the immunotherapeutic efficacy of OSCC by developing targeted therapies against MC. SIGNIFICANCE: In this study, we investigated the role of mast cells (MC) in oral precancer and oral cancer and demonstrated that MCs are involved in oral cancer progression and may serve as a potential diagnostic and prognostic marker. It might improve the immunotherapeutic efficacy through developing targeted therapies against MCs.

Determination of Volatile Halogenated Hydrocarbons in Drinking and Environmental Waters by Headspace Gas Chromatography.

Volatile halogenated hydrocarbons (VHHs) are annually produced and released into the environment, posing a threat to public health. In this study, a simple, rapid, sensitive and automated method based on headspace and gas chromatography (GC) with electron-capture detection was described for the determination of VHHs in different concentration levels in water samples. The proposed headspace GC method was initially optimized, and the optimum experimental conditions found were 10-mL water sample containing 20% w/v sodium chloride placed in a 20-mL vial and stirred at 60°C for 35 min, and then 14 VHHs were well separated on DB-35 MS capillary column with a split ratio of 12.5: 1. The limits of detection were in the low µg/L level, ranging between 0.01 and 0.6 µg/L. Finally optimized method was applied for determination 14 VHHs in drinking and environmental waters. The total mean concentrations of VHHs were 34.962, 26.183, 3.228 and 647.344 µg/L in tap water, purified water with 1-year-old filter element, seawater and effluents, respectively. However, no VHHs was detected in purified water with a new filter element. The main composition is different among different water matrix, which may be attributed to their different sources.

The prevalence, diagnostic accuracy and genotype-phenotype correlation of GNAS mutations in fibrous dysplasia: a meta-analysis.

Background: There is inconsistent evidence regarding the accuracy of GNAS mutations identification for the diagnosis of FD/MAS. This study was performed to estimate the prevalence and diagnostic accuracy of GNAS mutations detection and to preliminarily investigate the genotype-phenotype correlation in FD patients. Methods: Five electronic databases were searched from 1995 to 2024 using search terms related to GNAS and fibrous dysplasia. Observational studies of FD patients undergoing GNAS mutation detection in FD were included. Results: A total of 878 FD patients were included. The pooled prevalence of GNAS mutations in FD based on the random effects model was 74% (95% CI = 64%-83%). Regarding diagnostic accuracy, a sensitivity of 0.83 (95% CI, 0.65-0.96), specificity of 0.99 (95% CI, 0.98-1.00) and the area under the receiver operating characteristic curve of 98.38% were found. Additionally, meta-analysis and Fisher's test showed the GNAS mutation types were significantly associated with FD types (OR = 3.51, 95% CI = 1.05 to 11.72; p < 0.05). Conclusion: A high detection rate of GNAS mutations occurred in FD, and its detection is reliable for diagnosing FD. Additionally, GNAS mutation type was types were significantly associated with FD type. Systematic Review Registration: Identifier CRD42024553469.

CT-based radiomics analysis of different machine learning models for differentiating gnathic fibrous dysplasia and ossifying fibroma.

OBJECTIVE: In this study, our aim was to develop and validate the effectiveness of diverse radiomic models for distinguishing between gnathic fibrous dysplasia (FD) and ossifying fibroma (OF) before surgery. MATERIALS AND METHODS: We enrolled 220 patients with confirmed FD or OF. We extracted radiomic features from nonenhanced CT images. Following dimensionality reduction and feature selection, we constructed radiomic models using logistic regression, support vector machine, random forest, light gradient boosting machine, and eXtreme gradient boosting. We then identified the best radiomic model using receiver operating characteristic (ROC) curve analysis. After combining radiomics features with clinical features, we developed a comprehensive model. ROC curve and decision curve analysis (DCA) demonstrated the models' robustness and clinical value. RESULTS: We extracted 1834 radiomic features from CT images, reduced them to eight valuable features, and achieved high predictive efficiency, with area under curves (AUC) exceeding 0.95 for all the models. Ultimately, our combined model, which integrates radiomic and clinical data, displayed superior discriminatory ability (AUC: training cohort 0.970; test cohort 0.967). DCA highlighted its optimal clinical efficacy. CONCLUSION: Our combined model effectively differentiates between FD and OF, offering a noninvasive and efficient approach to clinical decision-making.

Clinicopathological characteristics and diagnostic accuracy of BRAF mutations in ameloblastoma: A Bayesian network analysis.

OBJECTIVE: This Bayesian network meta-analysis was performed to analyze the associations between clinicopathological characteristics and BRAF mutations in ameloblastoma (AM) patients and to evaluate the diagnostic accuracy. MATERIALS AND METHODS: Four electronic databases were searched from 2010 to 2024. The search terms used were specific to BRAF and AM. Observational studies or randomized controlled trials were considered eligible. The incidence of BRAF mutation and corresponding clinicopathological features in AM patients were subjected to Bayesian network analyses and diagnostic accuracy evaluation. RESULTS: A total of 937 AM patients from 20 studies were included. The pooled prevalence of BRAF mutations in AM patients was 72%. According to the Bayesian network analysis, BRAF mutations are more likely to occur in younger (odds ratio [OR], 2.3; credible interval [CrI]: 1.2-4.5), mandible site (OR, 3.6; 95% CrI: 2.7-5.2), and unicystic (OR, 1.6; 95% CrI: 1.1-2.4) AM patients. Similarly, higher diagnostic accuracy was found in the younger, mandible, and unicystic AM groups. CONCLUSIONS: The incidence, risk, and diagnostic accuracy of BRAF mutation in AM were greater in younger patients, those with mandible involvement, and those with unicystic AM than in patients with other clinicopathological features. In addition, there was a strong concordance in the diagnostic accuracy between molecular tests and immunohistochemical analysis.

A prognostic model built on amino acid metabolism patterns in HPV-associated head and neck squamous cell carcinoma.

OBJECTIVES: To compare amino acid metabolism patterns between HPV-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC) patients and identify key genes for a prognostic model. DESIGN: Utilizing the Cancer Genome Atlas dataset, we analyzed amino acid metabolism genes, differentiated genes between HPV statuses, and selected key genes via LASSO regression for the prognostic model. The model's gene expression was verified through immunohistochemistry in clinical samples. Functional enrichment and CIBERSORTx analyses explored biological functions, molecular mechanisms, and immune cell correlations. The model's prognostic capability was assessed using nomograms, calibration, and decision curve analysis. RESULTS: We identified 1157 key genes associated with amino acid metabolism in HNSCC and HPV status. The prognostic model, featuring genes like IQCN, SLC22A1, SYT12, and TLX3, highlighted functions in development, metabolism, and pathways related to receptors and enzymes. It significantly correlated with immune cell infiltration and outperformed traditional staging in prognosis prediction, despite immunohistochemistry results showing limited clinical identification of HPV-related HNSCC. CONCLUSIONS: Distinct amino acid metabolism patterns differentiate HPV-positive from negative HNSCC patients, underscoring the prognostic model's utility in predicting outcomes and guiding therapeutic strategies.

PON3::LCN1 and HTN3::MSANTD3 Gene Fusions With NR4A3/NR4A2 Expression in Salivary Acinic Cell Carcinoma.

Acinic cell carcinoma of the salivary gland (AciCC) is a low-grade carcinoma characterized by the overexpression of the transcription factor nuclear receptor subfamily 4 group A member 3 (NR4A3). AciCC has been the subject of a few molecular research projects. This study delves into AciCC's molecular landscape to identify additional alterations and explore their clinical implications. RNA sequencing and immunohistochemical staining for markers NR4A3/NR4A2, DOG-1, S100, and mammaglobin were utilized on 41 AciCCs and 11 secretory carcinoma (SC) samples. NR4A3 was evident in 35 AciCCs, while the residual 6 were NR4A3-negative and NR4A2-positive; SC samples were consistently NR4A3-negative. A novel fusion, PON3 exon 1- LCN1 exon 5, was detected in 9/41 (21.9%) AciCCs, exhibiting a classical histologic pattern with serous cell components growing in solid sheets alongside the intercalated duct-like component. Clinical follow-up of 39 patients over a median of 59 months revealed diverse prognostic outcomes: 34 patients exhibited no disease evidence, whereas the remaining 5 experienced poorer prognosis, involving local recurrence, lymph node, and distant metastasis, and disease-associated death, 4 of which harbored the PON3::LCN1 fusion. In addition, the HTN3::MSANTD3 fusion was recurrently identified in 7/41 AciCC cases. SC patients lacked both fusions. Immunohistochemistry uncovered differential expression of DOG-1, S100, and mammaglobin across samples, providing nuanced insights into their roles in AciCC. This study accentuates PON3::LCN1 and HTN3::MSANTD3 fusions as recurrent molecular events in AciCC, offering potential diagnostic and prognostic utility and propelling further research into targeted therapeutic strategies.

Genomic alterations in oral multiple primary cancers.

Oral squamous cell carcinoma (OSCC) is the predominant type of oral cancer, while some patients may develop oral multiple primary cancers (MPCs) with unclear etiology. This study aimed to investigate the clinicopathological characteristics and genomic alterations of oral MPCs. Clinicopathological data from patients with oral single primary carcinoma (SPC, n = 202) and oral MPCs (n = 34) were collected and compared. Copy number alteration (CNA) analysis was conducted to identify chromosomal-instability differences among oral MPCs, recurrent OSCC cases, and OSCC patients with lymph node metastasis. Whole-exome sequencing was employed to identify potential unique gene mutations in oral MPCs patients. Additionally, CNA and phylogenetic tree analyses were used to gain preliminary insights into the molecular characteristics of different primary tumors within individual patients. Our findings revealed that, in contrast to oral SPC, females predominated the oral MPCs (70.59%), while smoking and alcohol use were not frequent in MPCs. Moreover, long-term survival outcomes were poorer in oral MPCs. From a CNA perspective, no significant differences were observed between oral MPCs patients and those with recurrence and lymph node metastasis. In addition to commonly mutated genes such as CASP8, TP53 and MUC16, in oral MPCs we also detected relatively rare mutations, such as HS3ST6 and RFPL4A. Furthermore, this study also demonstrated that most MPCs patients exhibited similarities in certain genomic regions within individuals, and distinct differences of the similarity degree were observed between synchronous and metachronous oral MPCs.

Digital pathology-based artificial intelligence models for differential diagnosis and prognosis of sporadic odontogenic keratocysts.

Odontogenic keratocyst (OKC) is a common jaw cyst with a high recurrence rate. OKC combined with basal cell carcinoma as well as skeletal and other developmental abnormalities is thought to be associated with Gorlin syndrome. Moreover, OKC needs to be differentiated from orthokeratinized odontogenic cyst and other jaw cysts. Because of the different prognosis, differential diagnosis of several cysts can contribute to clinical management. We collected 519 cases, comprising a total of 2 157 hematoxylin and eosin-stained images, to develop digital pathology-based artificial intelligence (AI) models for the diagnosis and prognosis of OKC. The Inception_v3 neural network was utilized to train and test models developed from patch-level images. Finally, whole slide image-level AI models were developed by integrating deep learning-generated pathology features with several machine learning algorithms. The AI models showed great performance in the diagnosis (AUC = 0.935, 95% CI: 0.898-0.973) and prognosis (AUC = 0.840, 95%CI: 0.751-0.930) of OKC. The advantages of multiple slides model for integrating of histopathological information are demonstrated through a comparison with the single slide model. Furthermore, the study investigates the correlation between AI features generated by deep learning and pathological findings, highlighting the interpretative potential of AI models in the pathology. Here, we have developed the robust diagnostic and prognostic models for OKC. The AI model that is based on digital pathology shows promise potential for applications in odontogenic diseases of the jaw.

Correlation between gene polymorphism and adverse reactions of high-dose methotrexate in osteosarcoma patients: a systematic review and meta-analysis.

OBJECTIVE: We aimed to provide a reference based on evidence for an individualized clinical medication of high-dose methotrexate (HD-MTX) in osteosarcoma patients by evaluating the effect of gene polymorphism on adverse reactions of HD-MTX usage. METHODS: Several databases were combed for research on the association between gene polymorphisms and adverse reactions to HD-MTX up to January 2023. A meta-analysis and/or descriptive analysis on the incidence of HD-MTX-related adverse reactions were conducted by using clinical studies meeting inclusion criteria. RESULTS: Twelve studies involving 889 patients were included. There were 8, 6, 5, and 4 studies related to MTHFR C677T, MTHFR A1298C, RFC1 G80A, and MDR1 C3435T polymorphisms, respectively. The results of the meta-analysis showed that the MTHFR C677T polymorphism was associated with G3-4 hepatotoxicity, G3-4 nephrotoxicity, G3-4 gastrointestinal toxicity, and G3-4 mucositis under the recessive genetic model (MM vs. Mm/mm). Limited research showed that MTHFR C677T was associated with G3-4 nephrotoxicity in the allelic genetic model (M vs. m). MTHFR A1298C polymorphism was associated with a decreased risk of adverse reactions to HD-MTX usage, without statistical significance. This review's descriptive analysis showed no significant correlation between the RFC1 G80A, and MDR1 C3435T polymorphism and adverse reactions of HD-MTX. CONCLUSION: The MTHFR C677T mutation may enhance the risk of HD-MTX adverse reactions in osteosarcoma patients. Existing studies have not found a significant correlation between the MTHFR A1298C, RFC1 G80A, and MDR1 C3435T polymorphism and adverse reactions caused by HD-MTX. Lastly, this conclusion was limited because of few studies.

Colloid Pattern of Salivary Mucinous Adenocarcinomas With Recurrent BRAF V600E Mutations.

The relationship between various patterns of mucin-producing salivary adenocarcinomas, including invasive salivary adenocarcinomas with mucinous differentiation, such as colloid and papillary carcinomas, remains unclear. Herein, we aimed to describe the clinicopathologic characteristics, immunophenotypes, molecular underpinnings, and clinical behavior of salivary mucinous adenocarcinomas (MA) to clarify their classification. We described a broad series of colloid and papillary patterns of MAs, indicating that papillary pattern presented papillary cystic proliferation of mucinous columnar cells as salivary intraductal papillary mucinous neoplasms with recurrent AKT1 E17K mutations, whereas colloid adenocarcinomas containing large mucinous pools or lakes around the malignant epithelial nests or islands harbored BRAF V600E mutations with worse prognosis. Typical morphologic structures, CK7(+), CK20(-), CDX2(-), p63(-), p40(-), MAML2 fluorescence in situ hybridization (-), AR(-), TTF-1(-), S100(-), mammaglobin(-), or S100/mammaglobin(+) with ETV6 fluorescence in situ hybridization (-) immunophenotype, and recurrent AKT1 E17K or BRAF V600E mutations may be defined. To our knowledge, this small series represents the first genetic study on a typical colloid pattern of MA, and our study with the spectrum documentation for MA in clinicopathologic characteristics, histologic and immunophenotypes, molecular features, and clinical behavior will allow for a better understanding of these rare but distinctive tumors.

Combined RNAi of CTTN and FGF2 Modulates Cell Migration, Invasion and G1/S Transition of Hepatocellular Carcinoma through Ras/ERK Signaling Pathway.

BACKGROUND: Most patients with hepatocellular carcinoma (HCC) die of rapid progression and distant metastasis. Gene therapy represents a promising choice for HCC treatment, but the effective targeted methods are still limited. OBJECTIVE: CTTN/cortactin plays a key role in actin polymerization and regulates cytoskeleton remodeling. However, the interaction network of CTTN in HCC is not well understood. METHODS: siRNA was designed for CTTN silencing and Affymetrix GeneChip sequencing was used to obtain the gene profile after CTTN knockdown in the HCC cell line SMMC-7721. Potential interacting genes of CTTN were identified using qRT-PCR. The inhibition on HCC by combined RNA interference (RNAi) of CTTN and fibroblast growth factor 2 (FGF2) was detected. RESULTS: A total of 1,717 significantly altered genes were screened out and 12 potential interacting genes of CTTN were identified. The interaction of CTTN and FGF2 was validated and combined RNAi of CTTN and FGF2 achieved a synergistic effect, leading to better inhibition of HCC cell migration, invasion and G1/S transition than single knockdown of CTTN or FGF2. Mechanistically, combined RNAi of CTTN and FGF2 modulated the Ras/ERK signaling pathway. In addition, the EMT epithelial marker E-cadherin was upregulated while the mesenchymal marker Vimentin and cell cycle protein Cyclin D1 were downregulated after combined RNAi of CTTN and FGF2. Additionally, qRT-PCR and immunohistochemical staining showed that both CTTN and FGF2 were highly expressed in metastatic HCC tissues. CONCLUSION: Combined RNAi of CTTN and FGF2 may be a novel and promising intervention strategy for HCC invasion and metastasis.

Architectural and cytological features of epithelial dysplasia associated with transformation risk.

OBJECTIVES: This study explored associations between histological features of dysplasia and malignant transformation, as well as genomic copy number alterations. MATERIALS AND METHODS: Overall, 201 samples were collected from patients of oral leukoplakia. The associations of dysplastic features with malignant transformation and copy number alterations were investigated by Cox proportional hazards regression analysis and the Mann-Whitney U-test. RESULTS: Eight individual histological features, such as irregular epithelial stratification (p = 0.001), mitoses high in epithelium (p = 0.033), extension of changes along minor gland ducts (p < 0.001), etc., were associated with greater risk of malignant transformation. A model including histological features and age showed good performance for predicting malignant transformation (area under receiver operating characteristic curve: 0.806). Irregular epithelial stratification (p = 0.007), abnormal nuclear shape (p = 0.005), abnormal cell size (p = 0.004), etc. were associated with greater genomic instability. CONCLUSIONS: A Cox proportional hazards model using eight histological features and patient age reliably predicted the malignant potential of oral epithelial dysplasia. Identification of these histological features closely related to malignant transformation may aid the management of oral potentially malignant disorders and early detection of oral squamous cell carcinoma.

Head and neck carcinoma in children: A clinicopathological study of 42 cases.

Background/purpose: Cancer is an important part of the global burden of childhood diseases. Head and neck carcinoma in children is rare and related research is limited. This study aimed to investigate the clinicopathological features of childhood head and neck carcinoma. Materials and methods: Forty-two cases of childhood head and neck carcinoma treated in our institution were reviewed and analyzed. Results: Median age overall was 11 years. Twenty-three patients (54.8%) were male and 19 (45.2%) were female. Parotid gland location was most common (54.8%). Mucoepidermoid carcinoma and squamous cell carcinoma were the most common histological types (57.1% and 11.9%, respectively). Two patients had a history of bone marrow transplantation and two had a history of odontogenic keratocyst. The recurrence rate after treatment was 8.6%. Conclusion: Early diagnosis and treatment and close follow-up of childhood head and neck carcinoma are warranted to prevent recurrence and improve clinical outcome.

Biomarkers of malignant transformation in oral leukoplakia: from bench to bedside. / å£è ”ç™½æ–‘ç™Œå˜ç”Ÿç‰©æ ‡å¿—ç‰©ï¼š ä»ŽåŸºç¡€ç§‘ç ”åˆ°ä¸´åºŠåº”ç”¨.

Oral leukoplakia is a common precursor lesion of oral squamous cell carcinoma, which indicates a high potential of malignancy. The malignant transformation of oral leukoplakia seriously affects patient survival and quality of life; however, it is difficult to identify oral leukoplakia patients who will develop carcinoma because no biomarker exists to predict malignant transformation for effective clinical management. As a major problem in the field of head and neck pathologies, it is imperative to identify biomarkers of malignant transformation in oral leukoplakia. In this review, we discuss the potential biomarkers of malignant transformation reported in the literature and explore the translational probabilities from bench to bedside. Although no single biomarker has yet been applied in the clinical setting, profiling for genomic instability might be a promising adjunct.

Isolation of Cells with Morphological and Spatial Information from Oral Submucous Fibrosis Samples by Laser Capture Microdissection.

Oral submucous fibrosis (OSF) is a common type of potentially malignant disorder in the oral cavity. The atrophy of epithelium and fibrosis of the lamina propria and the submucosa are often found on histopathological slides. Epithelial dysplasia, epithelial atrophy, and senescent fibroblasts have been proposed to be associated with the malignant transformation of OSF. However, because of the heterogeneity of potentially malignant oral disorders and oral squamous cell carcinoma, it is difficult to identify the specific molecular mechanisms of malignant transformation in OSF. Here, we present a method to obtain a small number of epithelial or mesenchymal cells carrying morphological data and spatial information by laser capture microdissection on formalin-fixed paraffin-embedded tissue slides. Using a microscope, we can precisely capture microscale (~500 cells) dysplastic or atrophic epithelial tissue and fibrotic subepithelial tissue. The extracted cells can be evaluated by genome or transcriptome sequencing to acquire genomic and transcriptomic data with morphological and spatial information. This approach removes the heterogeneity of bulk OSF tissue sequencing and the interference caused by cells in non-lesioned areas, allowing for precise spatial-omics analysis of OSF tissue.

PTCH/SMO gene mutations in odontogenic keratocysts and drug interventions.

BACKGROUND: Odontogenic keratocysts (OKCs) are odontogenic jaw lesions that cause destruction and dysfunction of the jawbone. OKCs can be sporadic or associated with nevoid basic cell carcinoma syndrome (NBCCS). However, the factors that initiate OKCs and the mechanism of cyst formation remain unclear. Here, we investigated the impact of PTCH1 and SMO mutations on disease progression, as well as the effects of sonic hedgehog (SHH) signaling pathway inhibitors GDC-0449 and GANT61 on OKC fibroblasts. METHODS: Eight sporadic OKC fibroblasts without gene mutations were used as the control, and six NBCCS-related fibroblasts were cultured in vitro. The effect of PTCH1 non-truncated mutation 3499G>A (p.G1167R) and SMO c.2081C>G (p.P694R) mutation on OKC fibroblast proliferation was examined by EdU assay. CCK8 and wound-healing assays detected the effects of OKC fibroblasts carrying PTCH1 c.3499G>A (p.G1167R) and SMO c.2081C>G (p.P694R) mutations on the proliferation and migration of HaCaT cells after co-culture. Quantitative real-time PCR detected the effects of GDC-0449 or GANT61 on the SHH signaling pathway in NBCCS-related OKCs with PTCH1 truncated mutations and PTCH1 c.3499G>A (p.G1167R) and/or SMO c.2081C>G (p.P694R) mutations. RESULTS: PTCH1 c.3499G>A (p.G1167R) and SMO c.2081C>G (p.P694R) promoted the proliferation of OKC fibroblasts. The proliferation and migration of HaCaT cells were affected by NBCCS-related OKC fibroblasts carrying PTCH1 c.3499G>A (p.G1167R) and SMO c.2081C>G (p.P694R) mutations. GDC-0449 significantly inhibited the SHH signaling pathway in NBCCS-related OKC fibroblasts with PTCH1 truncated mutations. An NBCCS-related OKC carrying PTCH1 c.3499G>A (p.G1167R) and SMO c.2081C>G (p.P694R) mutations were resistant to GDC-0449 but inhibited by GANT61. CONCLUSIONS: Genetic mutations in OKC fibroblasts may affect the biological behavior of epithelial and stromal cells and cause disease. GDC-0449 could be used to treat OKCs, especially NBCCS-related OKCs with PTCH1 truncated mutations. SMO c.2081C>G (p.P694R) may lead to resistance to GDC-0449; however, GANT61 may be used as an alternative inhibitor.

Adenoid Ameloblastoma Shares Clinicopathologic, Immunohistochemical, and Molecular Features With Dentinogenic Ghost Cell Tumor: A Comparative Analysis.

The updated classification of odontogenic tumors by the World Health Organization (WHO) has included adenoid ameloblastoma (AA) as a distinct entity. However, distinguishing between AA and dentinogenic ghost cell tumor (DGCT) can still be challenging due to their significant morphologic similarities. In this study, we aimed to compare the clinicopathologic, immunohistochemical, and molecular characteristics of AA and DGCT to aid in their differentiation and to shed light on their pathologic mechanisms. Thirteen cases of AA and 14 cases of DGCT (15 samples) were analyzed, along with 11 cases of adenomatoid odontogenic tumor (AOT) and 18 cases of conventional ameloblastoma (AM) for comparative purposes. The study found that AA and DGCT shared a similar long-term prognosis. Immunohistochemically, all cytokeratins detected, except CK8/18, were not statistically significant in differentiating AA and DGCT, while there was a statistically significant difference in the immunophenotype of CK7 and CK10/13 between AA and AM. Nuclear ß-catenin accumulation were detected in all cases of AA and DGCT, while AOTs and AMs exhibited cytoplasmic ß-catenin. Molecularly, CTNNB1 hotspot mutations were found in only 1 case of AA (1/13), but not found in the other 3 types of tumors. BRAF p.V600E mutation was positive in 2/13 (15%) AA, 1/15 (7%) DGCT, and 2/11 (18%) AOT cases. In comparison, conventional AM was positive for BRAF p.V600E mutation in 94% (17/18) of cases, while KRAS mutations were detected in 63% (7/11) of AOT cases. The study suggests that the so-called AA is a rare benign tumor that exhibits clinical, immunohistochemical, and molecular features similar to DGCTs. Based on these findings, AA should not be categorized as a standalone entity solely based on the presence of whorls/morules and cribriform/duct-like structures. Further studies are needed to investigate the pathologic mechanisms of these tumors and to identify potential therapeutic targets.

Molecular mechanisms underlying the epigallocatechin-3-gallate-mediated inhibition of oral squamous cell carcinogenesis.

OBJECTIVES: To reveal the mechanisms underlying the epigallocatechin-3-gallate (EGCG)-mediated inhibition of carcinogenesis and the related regulatory signaling pathways. DESIGN: The effect of EGCG on the proliferation of OSCC cells was examined. SuperPred, ChEMBL, Swiss TargetPrediction, DisGeNET, GeneCards, and National Center for Biotechnology Information databases were used to predict the EGCG target genes and oral leukoplakia (OL)-related, oral submucosal fibrosis (OSF)-related, and OSCC-related genes. The binding of EGCG to the target proteins was simulated using AutoDock and PyMOL. The Cancer Genome Atlas (TCGA) dataset was subjected to consensus clustering analysis to predict the downstream molecules associated with these targets, as well as their potential functions and pathways. RESULTS: EGCG significantly inhibited OSCC cell proliferation (p < 0.001). By comparing EGCG target genes with genes linked to oral potentially malignant disorder (OPMD) and OSCC, a total of eleven potential EGCG target genes were identified. Furthermore, EGCG has the capacity to bind to eleven proteins. Based on consensus clustering and enrichment analysis, it is suggested that EGCG may hinder the progression of cancer by altering the cell cycle and invasive properties in precancerous lesions of the oral cavity. Some possible strategies for modifying the cell cycle and invasive properties may include EGCG-mediated suppression of specific genes and proteins, which are associated with cancer development. CONCLUSIONS: This study investigated the molecular mechanisms and signaling pathways associated with the EGCG-induced suppression of OSCC. The identification of specific pharmacological targets of EGCG during carcinogenesis is crucial for the development of innovative combination therapies involving EGCG.

[Determination of polybrominated diphenyl ethers in marine sediments by composite chromatography column purification-gas chromatography-negative chemical ionization-mass spectrometry].

Polybrominated diphenyl ethers (PBDEs) are used as additive flame retardants. Because they lack the ability to form chemical bonds, PBDEs can easily enter the sediment environment. The accurate qualitative and quantitative analysis of PBDEs in sediments is of great importance for the accurate assessment of PBDE pollution in this environment. Sediments contain many impurities. Therefore, PBDEs in sediment should be purified before analysis to reduce the matrix effect. A method based on gas chromatography-negative chemical ionization-mass spectrometry (GC-NCI/MS) was developed to determine 13 PBDEs in marine sediment samples using a column packed with deactivated silica gel, acidified silica gel, Florisil, and anhydrous sodium sulfate. Sediment samples were extracted by ultrasonication with a mixed solvent of n-hexane-dichloromethane (3∶1, v/v). After two cycles of ultrasonic extraction, the extract was purified by a composite chromatographic column and eluted with n-hexane-dichloromethane (3∶1, v/v). Thirteen PBDEs were determined by GC-NCI/MS in selected-ion monitoring (SIM) mode. The effects of different fillers, eluents, and elution volumes on the purification of PBDEs in the composite column were compared and analyzed, and the GC-NCI/MS analysis conditions were optimized. Three different packing columns were used to purify the sample extract. The first column was packed with 3 g of deactivated silica, 6 g of acidic silica, 3 g of deactivated silica, 3 g of Florisil, and 6 g of anhydrous sodium sulfate; the second column was packed with 3 g of Florisil, 3 g of deactivated silica, 6 g of acidic silica, 3 g of deactivated silica, and 6 g of anhydrous sodium sulfate; and the third column was packed with 3 g of deactivated silica, 6 g of acidified silica, 3 g of deactivated silica, and 6 g of anhydrous sodium sulfate. Among these columns, that packed with 3 g of deactivated silica, 6 g of acidic silica, 3 g of deactivated silica, 3 g of Florisil, and 6 g of anhydrous sodium sulfate showed the best purification effect. The 13 PBDEs showed good linearity in the mass concentration range of 0.1-20 µg/L with correlation coefficients (r2) greater than 0.995 (decabromodiphenyl oxide (BDE-209), r2>0.99). The limits of quantification (S/N=10) was 0.002-0.126 µg/kg. The average recoveries of the 13 PBDEs at three spiked levels of 0.2, 1.0, and 4.0 µg/kg were 85.3%-101.3%, 84.8%-113.6%, and 86.3%-94.7% with relative standard deviations of 4.4%-14.0%, 0.4%-4.9%, and 1.9%-6.6%, respectively. These findings indicate that the method has high sensitivity and accuracy as well as good precision. Finally, the method was applied to the analysis and detection of PBDEs in actual marine sediment samples. The results revealed that the sediment samples contained different contents of the 13 PBDEs, and high detection rates were obtained for lower-brominated PBDE homologs. The detection rate of bis(4-bromophenyl) ether (BDE-15) was 100%, and the detected content of BDE-209 was as high as 60.49 µg/kg. These results demonstrate that the developed method is suitable for the accurate qualitative and quantitative analysis of PBDEs in marine sediment samples.