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Hematolymphoid neoplasms originating in the periapical region of a tooth are rare occurrences. Their signs, symptoms, and radiographic findings can also mimic lesions of endodontic origin. History-taking and clinical examination provide clues to determine the possibility of a non-endodontic lesion, although the definitive diagnosis can only be rendered based on histologic examination. In our case series, we present four cases of hematolymphoid neoplasms that radiographically mimicked endodontic lesions. All the cases initially underwent endodontic treatment, but the lesions failed to resolve. In one case, the clinician suspected a diagnosis of lymphoma based on the patient's history. In the other cases, the clinicians' impression was that the lesions originated from endodontic issues. We present two cases of diffuse large B-cell lymphoma, a case of a plasma cell neoplasm, and a case of Langerhans cell histiocytosis, along with a literature review of three entities when found in the oral cavity as well as review of hematolymphoid neoplasm mimicking endodontic lesion previously reported in literature.
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BACKGROUND: In oral squamous cell carcinoma (OSCC), the tumor-node-metastasis (TNM) staging system is a significant factor that influences prognosis and treatment decisions for OSCC patients. Unfortunately, TNM staging does not consistently predict patient prognosis and patients with identical clinicopathological characteristics may have vastly different survival outcomes. Host immunity plays an important role in tumor progression but is not included in the TNM staging system. Tumor-infiltrating lymphocytes (TILs) are part of the host immune response that recognizes tumor cells; and the presence of TILs has emerged as potential candidates for prognostic markers for many types of cancers. The present study aims to determine the association of T cell-specific markers (CD3, CD4, CD8, and FOXP3) with clinicopathological characteristics and survival outcomes in OSCC patients. The prognostic value of CD3, CD4, and CD8 will also be evaluated based on tumor stage. METHODS: Tissue microarrays were constructed containing 231 OSCC cases and analyzed by immunohistochemical staining for the expression of CD3, CD4, CD8, and FOXP3. The expression scores for each marker were correlated with clinicopathological parameters and survival outcomes. The prognostic impact of CD3, CD4 and CD8 were further analyzed based on tumor stage (early or advanced). RESULTS: CD3, CD4, and CD8 were found to be significantly associated with both overall survival and progression-free survival using univariate analysis. However, none of these markers were found to independently predict the survival outcomes of OSCC using multivariate analysis. Only conventional factors such as nodal status, tumor differentiation and perineural invasion (PNI) were independent predictors of survival outcomes, with nodal status being the strongest independent predictor. Additionally, low CD4 (but not CD3 or CD8) expression was found to identify early-stage OSCC patients with exceptionally poor prognosis which was similar to that of advanced staged OSCC patients. CONCLUSIONS: TIL markers such as CD3, CD4, CD8, and FOXP3 can predict the survival outcomes of OSCC patients, but do not serve as independent prognostic markers as found with conventional factors (i.e. nodal status, tumor differentiation and PNI). CD4 expression may assist with risk stratification in early-stage OSCC patients which may influence treatment planning and decision making for early-stage OSCC patients.
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Carcinoma de Células Escamosas , Linfócitos do Interstício Tumoral , Neoplasias Bucais , Estadiamento de Neoplasias , Humanos , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Neoplasias Bucais/patologia , Neoplasias Bucais/imunologia , Neoplasias Bucais/mortalidade , Masculino , Feminino , Prognóstico , Pessoa de Meia-Idade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/mortalidade , Idoso , Fatores de Transcrição Forkhead/metabolismo , Adulto , Biomarcadores Tumorais/metabolismo , Idoso de 80 Anos ou mais , Complexo CD3/metabolismoRESUMO
MicroRNA (miR)-200c suppresses the initiation and progression of oral squamous cell carcinoma (OSCC), the most prevalent head and neck cancer with high recurrence, metastasis, and mortality rates. However, miR-200c -based gene therapy to inhibit OSCC growth and metastasis has yet to be reported. To develop an miR-based gene therapy to improve the outcomes of OSCC treatment, this study investigates the feasibility of plasmid DNA encoding miR-200c delivered via non-viral CaCO 3 -based nanoparticles to inhibit OSCC tumor growth. CaCO 3 -based nanoparticles with various ratios of CaCO 3 and protamine sulfate (PS) were utilized to transfect pDNA encoding miR-200c into OSCC cells and the efficiency of these nanoparticles was evaluated. The proliferation, migration, and associated oncogene production, as well as in vivo tumor growth for OSCC cells overexpressing miR-200c were also quantified. It was observed that, while CaCO 3 -based nanoparticles improve transfection efficiencies of pDNA miR-200c , the ratio of CaCO 3 to PS significantly influences the transfection efficiency. Overexpression of miR-200c significantly reduced proliferation, migration, and oncogene expression of OSCC cells, as well as the tumor size of cell line-derived xenografts (CDX) in mice. In addition, a local administration of pDNA miR-200c using CaCO 3 delivery significantly enhanced miR-200c transfection and suppressed tumor growth of CDX in mice. These results strongly indicate that the nanocomplexes of CaCO 3 /pDNA miR-200c may potentially be used to reduce oral cancer recurrence and metastasis and improve clinical outcomes in OSCC treatment. (227 words).
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INTRODUCTION: Radiographic findings in periradicular areas are repeatedly associated with infected root canal systems. Although non-odontogenic lesions in teeth are reported to be low, they often mimic periapical pathoses, and consequently, histopathologic examinations after surgical revisions are nurtured. METHODS: Biopsies submitted to the College of Dentistry between 2003 and 2021 were reviewed. Clinicopathologic characteristics were collected, including age, sex, medical history, location, sensibility tests, and clinic impressions from each specimen. Histopathologic diagnosis and gross description were also part of our database. RESULTS: A total of 72,055 pathology reports were reviewed, of which 10,031 lesions (13.9%) met the criterion of being intraosseous lesions at the periradicular area. Among those 10,031 lesions, 7.94% (n = 796) were of non-endodontic origin, 7153 were documented as non-vital, and 2.36% (n = 169) of these non-vital teeth were diagnosed with a non-endodontic origin. A total of 5707 lesions were obtained from surgeries within the periapical tissues, primarily performed by endodontists (94.02%). Non-endodontic lesions were reported in 1.09% of the cases. Odontogenic keratocyst was the most common non-endodontic diagnosis, followed by nasopalatine duct cyst and benign fibro-osseous lesion, respectively. CONCLUSIONS: Pathologic findings of the periradicular tissues are not always from endodontic origin. The probability of encountering non-endodontic lesions is almost 8%. Even in clinically reported teeth with pulp necrosis, 1%-3% of biopsies were confirmed as non-endodontic lesions.
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Background: Epidermal growth factor receptor (EGFR) is well known as a general prognostic biomarker for head and neck tumors, however the specific prognostic value of EGFR in oral squamous cell carcinoma (OSCC) is controversial. Recently, the presence of tumor-infiltrating T cells has been associated with significant survival advantages in a variety of disease sites. The present study will determine if the inclusion of T cell specific markers (CD3, CD4 and CD8) would enhance the prognostic value of EGFR in OSCCs. Methods: Tissue microarrays containing 146 OSCC cases were analyzed for EGFR, CD3, CD4 and CD8 expression using immunohistochemical staining. EGFR and T cell expression scores were correlated with clinicopathological parameters and survival outcomes. Results: Results showed that EGFR expression had no impact on overall survival (OS), but EGFR-positive (EGFR+) OSCC patients demonstrated significantly worse progression free survival (PFS) compared to EGFR-negative (EGFR-) patients. Patients with CD3, CD4 and CD8-positive tumors had significantly better OS compared to CD3, CD4 and CD8-negative patients respectively, but no impact on PFS. Combined EGFR+/CD3+ expression was associated with cases with no nodal involvement and significantly more favorable OS compared to EGFR+/CD3- expression. CD3 expression had no impact on OS or PFS in EGFR- patients. Combinations of EGFR/CD8 and EGFR/CD4 expression showed no significant differences in OS or PFS among the expression groups. Conclusion: Altogether these results suggest that the expression of CD3+ tumor-infiltrating T cells can enhance the prognostic value of EGFR expression and warrants further investigation as prognostic biomarkers for OSCC.
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Human ß-defensin 3 (HBD3) is an antimicrobial peptide up-regulated in the oral tissues of individuals with head and neck squamous cell carcinomas (HNSCC) and oral squamous cell carcinomas (SCC) and present in high concentrations in their saliva. In this study, we determined if HBD3 contributes to HNSCC pathogenesis by inducing programmed death-ligand 1 (PD-L1) expression on HNSCC cell lines. For this, SCC cell lines SCC4, SCC15, SCC19, SCC25, and SCC99 (5.0 × 104 viable cells) were used. Cells were incubated with IFNγ (0.6 µM) and HBD3 (0.2, 2.0, or 20.0 µM) for 24 h. Cells alone served as controls. Cells were then treated with anti-human APC-CD274 (PD-L1) and Live/Dead Fixable Green Dead Cell Stain. Cells treated with an isotype antibody and cells alone served as controls. All cell suspensions were analyzed in a LSR II Violet Flow Cytometer. Cytometric data was analyzed using FlowJo software. Treatment with IFNγ (0.6 µM) increased the number of cells expressing PD-L1 (p < 0.05) with respect to controls. Treatment with HBD3 (20.0 µM) also increased the number of cells expressing PD-L1 (p < 0.05) with respect to controls. However, treatment with IFNγ (0.6 µM) was not significantly different from treatment with HBD3 (20.0 µM) and the numbers of cells expressing PD-L1 were similar (p = 1). Thus, HBD3 increases the number of cells expressing PD-L1. This is a novel concept, but the role HBD3 contributes to HNSCC pathogenesis by inducing PD-L1 expression in tumors will have to be determined.
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Individual computational models of single myeloid, lymphoid, epithelial, and cancer cells were created and combined into multi-cell computational models and used to predict the collective chemokine, cytokine, and cellular biomarker profiles often seen in inflamed or cancerous tissues. Predicted chemokine and cytokine output profiles from multi-cell computational models of gingival epithelial keratinocytes (GE KER), dendritic cells (DC), and helper T lymphocytes (HTL) exposed to lipopolysaccharide (LPS) or synthetic triacylated lipopeptide (Pam3CSK4) as well as multi-cell computational models of multiple myeloma (MM) and DC were validated using the observed chemokine and cytokine responses from the same cell type combinations grown in laboratory multi-cell cultures with accuracy. Predicted and observed chemokine and cytokine responses of GE KER + DC + HTL exposed to LPS and Pam3CSK4 matched 75% (15/20, p = 0.02069) and 80% (16/20, P = 0.005909), respectively. Multi-cell computational models became 'personalized' when cell line-specific genomic data were included into simulations, again validated with the same cell lines grown in laboratory multi-cell cultures. Here, predicted and observed chemokine and cytokine responses of MM cells lines MM.1S and U266B1 matched 75% (3/4) and MM.1S and U266B1 inhibition of DC marker expression in co-culture matched 100% (6/6). Multi-cell computational models have the potential to identify approaches altering the predicted disease-associated output profiles, particularly as high throughput screening tools for anti-inflammatory or immuno-oncology treatments of inflamed multi-cellular tissues and the tumor microenvironment.
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Células Dendríticas/metabolismo , Epitélio/patologia , Gengiva/patologia , Inflamação/imunologia , Queratinócitos/metabolismo , Mieloma Múltiplo/metabolismo , Neoplasias/imunologia , Biomarcadores/metabolismo , Linhagem Celular Tumoral , Biologia Computacional , Simulação por Computador , Citocinas/metabolismo , Células Dendríticas/patologia , Ensaios de Triagem em Larga Escala , Humanos , Inflamação/diagnóstico , Queratinócitos/patologia , Mieloma Múltiplo/patologia , Neoplasias/diagnóstico , PrognósticoRESUMO
BACKGROUND: Biomarkers like programmed death ligand-1 (PDL1) have become a focal point for immunotherapeutic checkpoint inhibition in head and neck squamous cell carcinoma (HNSCC). However, it's only part of the total immunosuppressive biomarker profile of HNSCC cells. Matrix metalloproteinases (MMPs) are enzymes that break down the basement membrane allowing cancer cells to metastasize and play an important role in the tumor microenvironment. MMPs can also activate certain cytokines, growth factors, and chemokines post-translationally. The objective of this study was to determine MMP and biomarker profiles of seven different HNSCC cell lines. METHODS: Authenticated cell lines were grown in minimal media at 1×106 viable cells/mL and incubated at 37 °C. After 24 hrs supernatants were collected, and adhering cells were lysed. Multiplex immunoassays were used to determine MMP1, MMP7, MMP9, IL-6, VEGFA, IL-1α, TNF-α, GM-CSF, IL-1RA, and IL-8 concentrations in supernatants. ELISAs were used to determine PDL1, CD47, FASL, and IDO concentrations in cell lysates. A one-way ANOVA was fit to examine log-transformed concentrations of biomarkers between seven HNSCC cell lines, and pairwise group comparisons were conducted using post- hoc Tukey's honest significance test (α=0.05). RESULTS: Significant differences (P<0.05) in MMP and biomarker concentrations were found between the seven HNSCC cell lines. For example, MMP9 was highest in SCC25 and UM-SCC99, MMP7 was highest in SCC25 and UM-SCC19, and MMP1 was highest in SCC25. CONCLUSIONS: These results suggest different patients' HNSCC cells can express distinct profiles of select biomarkers and MMPs, which could be due to metastatic stage of the cancer, primary tumor site, type of tissue the tumor originated from, or genomic differences between patients. MMP and biomarker expression profiles should be considered when choosing cell lines for future studies. The results support the reason for personalized medicine and the need to further investigate how it can be used to treat HNSCC.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Extranodal de Células T-NK/diagnóstico por imagem , Linfoma Extranodal de Células T-NK/tratamento farmacológico , Neoplasias Maxilares/diagnóstico por imagem , Neoplasias Maxilares/tratamento farmacológico , Neoplasias de Tecidos Moles/diagnóstico por imagem , Neoplasias de Tecidos Moles/tratamento farmacológico , Biomarcadores Tumorais/sangue , Meios de Contraste , DNA de Neoplasias/sangue , Diagnóstico Diferencial , Humanos , Biópsia Guiada por Imagem , Imuno-Histoquímica , Linfoma Extranodal de Células T-NK/virologia , Masculino , Neoplasias Maxilares/virologia , Pessoa de Meia-Idade , Invasividade Neoplásica , Reação em Cadeia da Polimerase , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Radiografia Panorâmica , Neoplasias de Tecidos Moles/virologiaRESUMO
Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy. The submandibular gland is rarely involved, about less than 10% of all other major salivary glands. We report a case of a 49-year-old female who presented with a mass on the left side of the floor of the mouth. She was complaining of neck pain for the last 2-3 days and had noticed the mass growing in size and becoming tender to palpation. There was no exacerbation of pain during eating, drinking, or opening of mouth. A multidetector CT scan was made. The radiographic examination revealed a mostly well-defined hypodense area suggestive of mucocele (ranula), which was thought to be corroborated by the clinical findings. The treatment of choice was the complete excision of the mucocele and the left submandibular salivary gland. The histopathological examination surprisingly revealed a low-grade MEC. No further treatment was recommended; however, a follow up was scheduled in 4 months. This atypical location of MEC in the floor of the mouth simulated the clinical and radiographic features of a mucocele. This case highlights the value and importance of using all the available diagnostic tools and modalities for optimal patient management, as the histopathological analysis played an important role to confirm the diagnosis.
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Carcinoma Mucoepidermoide/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias das Glândulas Salivares/diagnóstico por imagem , Biópsia por Agulha Fina , Carcinoma Mucoepidermoide/patologia , Carcinoma Mucoepidermoide/cirurgia , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Rânula/diagnóstico por imagem , Neoplasias das Glândulas Salivares/patologia , Neoplasias das Glândulas Salivares/cirurgiaRESUMO
OBJECTIVES: Programmed death-ligand 1 (PD-L1) expression is correlated with objective response rates to PD-1 and PD-L1 immunotherapies. However, both immunotherapies have only demonstrated 12%-24.8% objective response rates in patients with head and neck squamous cell carcinoma (HNSCC), demonstrating a need for a more accurate method to identify those who will respond before their therapy. Immunohistochemistry to detect PD-L1 reactivity in tumors can be challenging, and additional methods are needed to predict and confirm PD-L1 expression. Here, we hypothesized that HNSCC tumor cell genomics influences cell signaling and downstream effects on immunosuppressive biomarkers and that these profiles can predict patient clinical responses. STUDY DESIGN: We identified deleterious gene mutations in SCC4, SCC15, and SCC25 and created cell line-specific predictive computational simulation models. The expression of 24 immunosuppressive biomarkers were then predicted and used to sort cell lines into those that would respond to PD-L1 immunotherapy and those that would not. RESULTS: SCC15 and SCC25 were identified as cell lines that would respond to PD-L1 immunotherapy treatment and SCC4 was identified as a cell line that would not likely respond to PD-L1 immunotherapy treatment. CONCLUSIONS: This approach, when applied to HNSCC cells, has the ability to predict PD-L1 expression and predict PD-1- or PD-L1-targeted treatment responses in these patients.
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Antígeno B7-H1/genética , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/imunologia , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/imunologia , Biologia Computacional , Regulação Neoplásica da Expressão Gênica , Genômica , Humanos , Imuno-Histoquímica , Imunoterapia , Mutação , Transdução de Sinais , Carcinoma de Células Escamosas de Cabeça e Pescoço , Pesquisa Translacional Biomédica , Células Tumorais CultivadasRESUMO
PURPOSE: Interaction of the programmed death-1 (PD-1) co-receptor on T cells with the programmed death-ligand 1 (PD-L1) on tumor cells can lead to immunosuppression, a key event in the pathogenesis of many tumors. Thus, determining the amount of PD-L1 in tumors by immunohistochemistry (IHC) is important as both a diagnostic aid and a clinical predictor of immunotherapy treatment success. Because IHC reactivity can vary, we developed computational simulation models to accurately predict PD-L1 expression as a complementary assay to affirm IHC reactivity. METHODS: Multiple myeloma (MM) and oral squamous cell carcinoma (SCC) cell lines were modeled as examples of our approach. Non-transformed cell models were first simulated to establish non-tumorigenic control baselines. Cell line genomic aberration profiles, from next-generation sequencing (NGS) information for MM.1S, U266B1, SCC4, SCC15, and SCC25 cell lines, were introduced into the workflow to create cancer cell line-specific simulation models. Percentage changes of PD-L1 expression with respect to control baselines were determined and verified against observed PD-L1 expression by ELISA, IHC, and flow cytometry on the same cells grown in culture. RESULT: The observed PD-L1 expression matched the predicted PD-L1 expression for MM.1S, U266B1, SCC4, SCC15, and SCC25 cell lines and clearly demonstrated that cell genomics play an integral role by influencing cell signaling and downstream effects on PD-L1 expression. CONCLUSION: This concept can easily be extended to cancer patient cells where an accurate method to predict PD-L1 expression would affirm IHC results and improve its potential as a biomarker and a clinical predictor of treatment success.
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Antígeno B7-H1/metabolismo , Carcinoma de Células Escamosas/genética , Neoplasias Bucais/genética , Mieloma Múltiplo/genética , Adulto , Carcinoma de Células Escamosas/patologia , Simulação por Computador , Humanos , Pessoa de Meia-Idade , Modelos Biológicos , Simulação de Dinâmica Molecular , Neoplasias Bucais/patologia , Mieloma Múltiplo/patologiaRESUMO
The aim of this study was to compare the immunoexpression of epithelial mucins (MUCs) in salivary duct cysts, papillary cystadenomas, and mucoepidermoid carcinomas and to evaluate if any of these markers could be useful for differentiating between mucoepidermoid carcinoma and papillary cystadenoma. We also sought to validate the p63 expression pattern found to differentiate between mucoepidermoid carcinoma and papillary cystadenoma. Immunoexpression of MUC1, MUC2, MUC4, MUC7, and p63 was studied and quantified in 22 mucoepidermoid carcinomas, 12 papillary cystadenomas, and 3 salivary duct cysts. The immunohistochemical evaluation was collectively performed by 3 oral pathologists. Scores and trends in proportions were assessed using the nonparametric Wilcoxon-Mann-Whitney rank sum test. Mucoepidermoid carcinomas, papillary cystadenomas, and salivary duct cysts demonstrated variable MUC expression patterns. All tumors were positive for p63 immunoexpression with p63 labeling in salivary duct cysts and papillary cystadenomas (15/15) limited to the basal layers of the cystic spaces, whereas in mucoepidermoid carcinomas (22/22) the p63 labeling extended throughout the suprabasal layers (p < 0.001). This study adds more confirmatory data to validate that the reactivity pattern of p63 protein can be used in distinguishing between papillary cystadenoma and low-grade mucoepidermoid carcinoma. Although positive reactivity in a tumor with MUC1 and MUC4 was inconclusive, negative reactivity suggests the diagnosis of a benign PC or SDC.
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Biomarcadores Tumorais/análise , Carcinoma Mucoepidermoide/diagnóstico , Cistadenoma Papilar/diagnóstico , Proteínas de Membrana/biossíntese , Mucinas/biossíntese , Neoplasias das Glândulas Salivares/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Masculino , Proteínas de Membrana/análise , Pessoa de Meia-Idade , Mucinas/análiseRESUMO
OBJECTIVES: To retrospectively study the prevalence of perineural invasion (PNI) in cases of mucoepidermoid carcinoma (MEC). The study evaluated if previously assessed PNI would be increased by re-review of the original hematoxylin and eosin-stained (H&E) slides and also review of slides reacted immunohistochemically with S100 to enhance nerve visualization and whether this is associated with clinical outcome. STUDY DESIGN: Thirty-one cases were reviewed for PNI with H&E-stained slides as well as S-100-reacted slides. These results were compared with the original pathology report's PNI status when available (13 of 31). Subject demographic characteristics and clinical outcome were collected from electronic medical records. RESULTS: PNI was identified in 23% (3 of 13) of tumors in the original reports, 13% (4 of 31) of the authors' re-review of the slides, and 29% (9 of 31) by immunohistochemical assessment for S100. PNI and larger-diameter nerve involvement were significantly associated with death at 5-year follow-up. CONCLUSIONS: Immunohistochemical assessment for S100 improves the accuracy of PNI determination. PNI is a significant factor in the survival outcome of cases of MEC.
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Carcinoma Mucoepidermoide/patologia , Imuno-Histoquímica , Invasividade Neoplásica/patologia , Neoplasias das Glândulas Salivares/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Mucoepidermoide/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias das Glândulas Salivares/terapiaRESUMO
Long-chain bases, found in the oral cavity, have potent antimicrobial activity against oral pathogens. In an article associated with this dataset, Poulson and colleagues determined the cytotoxicities of long-chain bases (sphingosine, dihydrosphingosine, and phytosphingosine) for human oral gingival epithelial (GE) keratinocytes, oral gingival fibroblasts (GF), dendritic cells (DC), and squamous cell carcinoma (SCC) cell lines [1]. Poulson and colleagues found that GE keratinocytes were more resistant to long-chain bases as compared to GF, DC, and SCC cell lines [1]. In this study, we assess the susceptibility of DC to lower concentrations of long chain bases. 0.2-10.0 µM long-chain bases and GML were not cytotoxic to DC; 40.0-80.0 µM long-chain bases, but not GML, were cytotoxic for DC; and 80.0 µM long-chain bases were cytotoxic to DC and induced cellular damage and death in less than 20 mins. Overall, the LD50 of long-chain bases for GE keratinocytes, GF, and DC were considerably higher than their minimal inhibitory concentrations for oral pathogens, a finding important to pursuing their future potential in treating periodontal and oral infections.
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Long-chain bases are present in the oral cavity. Previously we determined that sphingosine, dihydrosphingosine, and phytosphingosine have potent antimicrobial activity against oral pathogens. Here, we determined the cytotoxicities of long-chain bases for oral cells, an important step in considering their potential as antimicrobial agents for oral infections. This information would clearly help in establishing prophylactic or therapeutic doses. To assess this, human oral gingival epithelial (GE) keratinocytes, oral gingival fibroblasts (GF), and dendritic cells (DC) were exposed to 10.0-640.0 µM long-chain bases and glycerol monolaurate (GML). The effects of long-chain bases on cell metabolism (conversion of resazurin to resorufin), membrane permeability (uptake of propidium iodide or SYTOX-Green), release of cellular contents (LDH), and cell morphology (confocal microscopy) were all determined. GE keratinocytes were more resistant to long-chain bases as compared to GF and DC, which were more susceptible. For DC, 0.2-10.0 µM long-chain bases and GML were not cytotoxic; 40.0-80.0 µM long-chain bases, but not GML, were cytotoxic; and 80.0 µM long-chain bases induced cellular damage and death in less than 20 min. The LD50 of long-chain bases for GE keratinocytes, GF, and DC were considerably higher than their minimal inhibitory concentrations for oral pathogens, a finding important to pursuing their future potential in treating periodontal and oral infections.
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Células Dendríticas/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Gengiva/citologia , Queratinócitos/efeitos dos fármacos , Esfingosina/análogos & derivados , Esfingosina/toxicidade , Anti-Infecciosos/toxicidade , Diferenciação Celular/efeitos dos fármacos , Permeabilidade da Membrana Celular/efeitos dos fármacos , Células Cultivadas , Células Dendríticas/metabolismo , Fibroblastos/metabolismo , Gengiva/efeitos dos fármacos , Humanos , Queratinócitos/metabolismo , Dose Letal Mediana , Saliva/químicaRESUMO
Zoonotic anatrichosomiasis in a mother and daughter is reported. Both presented with a 10-week history of multiple painful oral ulcers. Biopsy specimens revealed the presence of small, coiled trichuroid nematodes with distinctive morphological features, including stichocytes and paired bacillary bands. This represents an unusual infection by a zoonotic Anatrichosoma species.