LRP5, SLC6A3, and SOX10 Expression in Conventional Ameloblastoma.

Cell proliferation and invasion are characteristic of many tumors, including ameloblastoma, and are important features to target in possible future therapeutic applications. OBJECTIVE: The objective of this study was the identification of key genes and inhibitory drugs related to the cell proliferation and invasion of ameloblastoma using bioinformatic analysis. METHODS: The H10KA_07_38 gene profile database was analyzed by Rstudio and ShinyGO Gene Ontology enrichment. String, Cytoscape-MCODE, and Kaplan-Meier plots were generated, which were subsequently validated by RT-qPCR relative expression and immunoexpression analyses. To propose specific inhibitory drugs, a bioinformatic search using Drug Gene Budger and DrugBank was performed. RESULTS: A total of 204 significantly upregulated genes were identified. Gene ontology enrichment analysis identified four pathways related to cell proliferation and cell invasion. A total of 37 genes were involved in these pathways, and 11 genes showed an MCODE score of ≥0.4; however, only SLC6A3, SOX10, and LRP5 were negatively associated with overall survival (HR = 1.49 (p = 0.0072), HR = 1.55 (p = 0.0018), and HR = 1.38 (p = 0.025), respectively). The RT-qPCR results confirmed the significant differences in expression, with overexpression of >2 for SLC6A3 and SOX10. The immunoexpression analysis indicated positive LRP5 and SLC6A3 expression. The inhibitory drugs bioinformatically obtained for the above three genes were parthenolide and vorinostat. CONCLUSIONS: We identify LRP5, SLC6A3, and SOX10 as potentially important genes related to cell proliferation and invasion in the pathogenesis of ameloblastomas, along with both parthenolide and vorinostat as inhibitory drugs that could be further investigated for the development of novel therapeutic approaches against ameloblastoma.

Efficacy of Antineoplastic Nanocarriers on 3D Oral Cancer Spheroids.

BACKGROUND/AIM: Cancer is a leading cause of death worldwide. Conventional treatments as surgery, chemotherapy, radiotherapy, and combined therapies are commonly used. However, these therapies have several limitations and side effects. To address these issues, innovative research is being conducted on nanocarriers (NCs) functionalized with antineoplastic agents. These NCs aim to overcome limitations and improve patients' lives. However, before they can be used clinically, these NCs are primarily assessed on a lab scale to determine their efficacy. MATERIALS AND METHODS: A primary cell culture was established from a lymphoblastic neoplasm in the maxilla. After characterization, the cells were cultured in 2D to evaluate the dose-effect of nanoparticles (NPs), such as Zinc oxide (ZnO) and Magnesium oxide (MgO), as well as those of free drugs of 5-fluorouracil (5-FU) and cisplatin (Cis). Based on the results, a 3D spheroid culture was used for further study. Finally, the spheroids were histologically processed for immuno-morphological observation. RESULTS: To evaluate spheroid cell viability, we conducted an MTT assay. Treatment of cell spheroids with ZnONPs, 5-FU, and NPs conjugated with antitumor agents such as 5-FU-ZnO and Cis-ZnO decreased cell viability by >25%, >60% and >10% and <20% at a concentration of 0.06, 0.015 and 0.015 & 0.03 mg/ml, respectively. CONCLUSION: Nanoparticles conjugated with antitumor agents showed promising antineoplastic effects on both 2D and 3D cell cultures. However, the efficacy of the nanoparticles varied between the different models. This highlights the importance of selecting appropriate in vitro culture models for the evaluation of biomedical agents.

Análisis inmunohistoquímico de MMP-1, MMP-2 y MMP-9 en ameloblastoma convencional / Immunohistochemical analysis of MMP-1, MMP-2, MMP-9 in conventional ameloblastoma

Introducción: las metaloproteinasas son enzimas que participan en la remodelación tisular y su función se relaciona con procesos fisiológicos y patológicos, como la invasión y la metástasis. El ameloblastoma convencional (AMC) es una neoplasia epitelial benigna odontogénica intraósea caracterizada por una progresión lenta y localmente invasiva, cuyo crecimiento se ha vinculado con el recambio ósea y la remodelación de la matriz extracelular. El objetivo del presente trabajo fue determinar la presencia inmunohistoquímica de MMP-1, MMP-2 y MMP-9 en el AMC. Material y métodos: se realizó un estudio piloto observacional analítico utilizando cinco muestras de AMC. Los especímenes fueron recolectados aleatoriamente del archivo del Departamento de Patología Oral y Maxilofacial, de la Escuela Nacional de Estudios Superiores (ENES) Unidad León, UNAM. Como grupo control se emplearon dos especímenes de folículo dental, obtenido de pacientes con indicación de su extracción por motivos ortodóncicos. Se realizó la técnica de inmunohistoquímica por peroxidasa, recolectando el nivel y proporción de inmunoexpresión de manera semicuantitativa. Resultados: cuatro pacientes fueron de género masculino y uno femenino, la edad promedio fue de 40.6 ± 14.9 años. Todas las muestras fueron obtenidas de la región mandibular posterior. Se observaron dos especímenes con patrón folicular y tres con plexiforme. Las MMP-2 y MMP-9 se detectaron sólo en uno de los cinco especímenes y únicamente en el parénquima de la lesión, con una proporción de 100%. Conclusión: según nuestro análisis inmunohistoquímico, las MMP-2 y MMP-9 son las metaloproteinasas que presentaron expresión positiva dentro de la patogénesis del AMC comparado a la MMP-1; no obstante, es necesario realizar este tipo de estudios en una población mayor (AU)

Introduction: metalloproteinases are enzymes involved in tissue remodeling and their function is related to physiological and pathological processes, such as invasion and metastasis. These enzymes are capable of degrading components of the extracellular matrix, which may promote tumor progression. Conventional ameloblastoma (CA) is described as a benign intraosseous epithelial odontogenic neoplasm characterized by a slow and locally invasive progression, whose growth has been linked to bone turnover and extracellular matrix remodeling. The aim of the present work was to determine the immunohistochemical presence of MMP-1, MMP-2 and MMP-9 in CA. Material and methods: an analytical observational pilot study was performed using 5 CA, randomly collected from the archive of the Department of Oral and Maxillofacial Pathology, Escuela Nacional de Estudios Superiores (ENES) Unidad León, UNAM. The control group used were two dental follicle samples, obtained from patients with extraction indication for orthodontic treatment. The peroxidase immunohistochemistry assay was performed, collecting semiquantitatively level and proportion of immunoexpression. Results: four patients were male and one female, the average age was 40.6 ± 14.9 years. All specimens were obtained from the posterior mandibular region. Two specimens were observed with follicular pattern and three with plexiform pattern. MMP-2 and MMP-9 were detected only in one of the five specimens, with presence in the parenchyma of the lesion, with a proportion of 100% of the cell analyzed. Conclusion: according to our immunohistochemical analysis, MMP-2 and MMP-9 are the metalloproteinases that presented positive expression within the pathogenesis of CA compared to MMP-1; however, it is necessary to perform this type of studies in a larger population (AU)

[Cancer stem cells in oral squamous cell carcinoma. Literature review]. / Células troncales cancerígenas en carcinoma oral de células escamosas. Revisión de la literatura.

Objective: To perform a literature review on oral squamous cell carcinoma, the presence of cancer stem cells; their association with the course of the disease and therapeutic applications. Methods: : A search was performed in the PubMed database by entering the following algorithm: ((((neoplastic stem cells [MeSH Terms ]) OR (Cancer stem cells [Text Word ])) AND (Squamous Cell Carcinoma of Head and Neck [MeSH Terms])) AND (Oral squamous cell carcinoma [Text Word ]), to find articles in english published between 2012 and 2022. The PRISMA diagram was used to identify and select the articles. Results: A result of 49 articles was obtained; of which 27 were chosen according to the title and abstract in their association with the topic. In addition, 8 additional articles suggested by their relationship with the information previously searched were included. In total, 35 articles were evaluated. There has been found that tumoral cells in squamous oral carcinoma are heterogeneous since they include cancer stem cells wich possess characteristics of stem and neoplasic cells; which possess characteristics of stem cells as well as neoplastic cells; they have been associated with disease progression, recurrence, and metastasis and have been considered to be a key mechanism of therapy failure. Conclusions: The expression of stem cell markers in oral squamous cell carcinomas has been demonstrated and has contributed to their identification in oral squamous cell carcinomas and has been implicated in the behavior of cancer cells. New therapeutic measures aimed at eliminating cancer stem cells have been proposed and developed.

Microarray and bioinformatic analysis of conventional ameloblastoma: an observational analysis

Abstract Ameloblastoma is a highly aggressive odontogenic tumor, and its pathogenesis is associated with many participating genes. Objective We aimed to identify and validate new critical genes of conventional ameloblastoma using microarray and bioinformatics analysis. Methodology Gene expression microarray and bioinformatic analysis were performed using CHIP H10KA and DAVID software for enrichment. Protein-protein interactions (PPI) were visualized using STRING-Cytoscape with MCODE plugin, followed by Kaplan-Meier and GEPIA analyses that were used for the candidate's postulation. RT-qPCR and IHC assays were performed to validate the bioinformatic approach. Results 376 upregulated genes were identified. PPI analysis revealed 14 genes that were validated by Kaplan-Meier and GEPIA resulting in PDGFA and IL2RA as candidate genes. The RT-qPCR analysis confirmed their intense expression. Immunohistochemistry analysis showed that PDGFA expression is parenchyma located. Conclusion With bioinformatics methods, we can identify upregulated genes in conventional ameloblastoma, and with RT-qPCR and immunoexpression analysis validate that PDGFA could be a more specific and localized therapeutic target.

Lesión granulomatosa en encía insertada-metástasis de carcinoma renal de células claras. Presentación de caso / Granulomatous Lesion in Inserted Gum-Metastasis of Renal Clear Cell Carcinoma. Case Presentation

Resumen: A nivel mundial el carcinoma renal constituye el 3% de todas las formas de cáncer en el cuerpo humano. Su comportamiento biológico es variable dependiendo de la biología de cada individuo; tiende a realizar metástasis a sitios contiguos como glándulas suprarrenales, hígado, pulmón, hueso, ganglios linfáticos sin embargo la presentación a distancia en cavidad bucal es poco frecuente más aún en encía insertada. Las lesiones granulomatosas del periodonto incluyen granulomas piógenos, granulomas de células gigantes entre otros. El objetivo principal de este caso clínico es describir las características clínicas e histopatológicas de las metástasis a cavidad bucal como lesiones granulomatosas. Se presenta el caso de una paciente femenina de 60 años de edad con antecedente de carcinoma renal de células papilares en riñón derecho tratado mediante nefrectomía en el año 2017, en el año 2019 presenta metástasis a pulmón izquierdo y a cavidad bucal. En la actualidad se encuentra bajo protocolo de tratamiento para metástasis de células claras renales.

Abstract: Worldwide, renal carcinoma constitutes 3% of all forms of cancer in the human body. Its biological behavior is variable depending on the biology of each individual; it tends to metastasize to contiguous sites such as adrenal glands, liver, lung, bone, lymph nodes, however, remote presentation in the oral cavity is less frequent, even in inserted gums. Granulomatous lesions of the periodontium include pyogenic granulomas, giant cell granulomas among others. The main objective of this clinical case is to describe the clinical and histopathological characteristics of oral cavity metastases as granulomatous lesions. The case of a 60-year-old female patient with a history of renal cell papillary carcinoma in the right kidney treated by nephrectomy in 2017 is presented, in 2019 she presented metastases to the left lung and oral cavity. It is currently under treatment protocol for renal clear cell metastases.

Expresión génica de receptores ECA2 en cavidad bucal y glándulas salivales y su papel en la infección por SARS CoV2. Revisión de la literatura / Gene Expression of ECA2 Receptors in the Oral Cavity and Salivary Glands and Its Role in SARS CoV2 Infection. Literature Review

Resumen Los receptores ECA2 presentan una expresión génica importante en las células escamosas de la lengua y glándulas salivales, mecanismo que es conveniente para la inoculación de SARS CoV2 toda vez que busca hacer el complejo de ensamblaje mediante su glicoproteína o proteína espiga hacia el receptor ECA2 de la mucosa bucal. Una vez inoculado y favorecido por las proteasas es la llave que permite la entrada del virión en la célula huésped para su posterior replicación, aumento de carga viral y potencial desaminación e infección; los estomatólogos deben estar alerta de los mecanismos de infección en cavidad bucal para protección propia y de los pacientes que son atendidos por este personal de salud.

Abstract ECA2 receptors have an important gene expression in the squamous cells of the tongue and salivary glands, a mechanism that is convenient for the inoculation of SARS CoV2 since it seeks to make the assembly complex through its glycoprotein or spike protein towards the ECA2 receptor of the oral mucosa. Once inoculated and favored by proteases, it is the key that allows the entry of the virion into the host cell for its subsequent replication, increase of viral load and potential deamination and infection; dental professionals must be alert to the mechanisms of infection in the oral cavity for their own protection and that of the patients who are treated by this health personnel.

SARS-CoV-2 Modelo de Inoculación en la Cavidad Oral. Revisión de la Literatura / SARS-CoV-2 Model of Inoculation in the Oral Cavity. Literature Review

RESUMEN: El virus SARS-CoV-2 ingresa al organismo de un individuo susceptible a través de la cavidad oral, nasal o de la mucosa conjuntival; busca ensamblarse por medio de su glicoproteína de superficie o espiga con los receptores de la enzima convertidora de angiotensina 2 que en boca los encontramos con mayor expresión en las células escamosas que recubren el epitelio lingual y las glándulas salivales, una vez que ingresa por medio de la activación de proteasas ingresa a la célula huésped para denudar su RNA viral, a diferencia de otros virus no necesita ir hasta el núcleo de tal forma que en el citoplasma inicia su replicación y utiliza los ribosomas del huésped para formar una gran cantidad de proteínas virales tanto estructurales como accesorias que le permita formar nuevos viriones potencialmente infecciosos; los estomatólogos deben tomar en cuenta esta vía de infección y extremar las medidas para disminuir su carga viral local en la cavidad oral y las barreras físicas de protección para el operador, el paciente y la ergonomía del consultorio.

ABSTRACT: SARS-CoV-2 virus enters the body of a susceptible individual through oral, nasal or conjunctival mucosa, seeking to bind to the spike glycoprotein surface through angiotensin-converting enzyme 2 receptors. These are found in the mouth with a higher expression in oral squamous cells that cover the lingual epithelium and salivary glands. Once proteolytic activation begins, it enters the host cell to denudate its viral RNA. In contrast with other viruses, it does not require nucleus access, and therefore replicates in the cytoplasm using the host's ribosomes to produce great amounts of both structural and accessory viral proteins. Since this generates new and potentially infectious virions, dentists must consider this route of infection and take extreme measures to decrease their viral load in the oral cavity. Physical protection barriers for the operator, the patient and the health and safety of the work place are critical in these cases.

Mucocele de glándulas de Blandin Nuhn. Caso inusual y revisión de la literatura / Mucocele da glândula Blandin Nuhn. Caso incomum e revisão da literatura / Mucocele of Blandin Nuhn glands. Unusual case and review of the literature

El mucocele asociado a las glándulas de Blandin Nuhn es un fenómeno de extravasación mucosa que ocurre en las glándulas salivales localizadas en la superficie ventral anterior de la lengua, son de tipo mixto, no encapsuladas, que forman parte del complejo de glándulas salivales menores de cavidad bucal. Objetivo: Se presenta el caso clínico de un paciente masculino que cursa la segunda década de vida con características clínicas peculiares de un mucocele de Blandin Nuhn. Caso clínico: Adolescente masculino de 14 años de edad presenta aumento de volumen localizado en superficie ventral de lengua, forma cilíndrica, de 3 meses de evolución y asintomático. Se realiza biopsia excisional para estudio histopatológico, el cual reporta fenómeno de extravasación mucosa y se establece la correlación clínico histopatológica. Conclusiones: Se debe fundamentar un diagnóstico correcto para proporcionar un tratamiento oportuno y evitar complicaciones en el paciente que afecten su calidad de vida.

Mucoceles of the glands of BlandinNuhn consist in a mucus extravasation phenomenon that occurs in the salivary glands located in the anterior ventral surface of the tongue. They are mixed, not encapsulated, and part of the complex of minor salivary glands of the oral cavity. Objective: This paper presents the clinical case of a male patient in his second decade of life with peculiar clinical characteristics of a mucocele of the glands of Blandin-Nuhn. Clinical case: A 14-year-old male adolescent has an increase in volume located on the ventral surface of the tongue, of cylindrical shape, with three months of evolution and is asymptomatic. An excisional biopsy is performed for histopathological study, which reports mucosal extravasation phenomenon and a histopathological clinical correlation is established. Conclusions: A correct diagnosis should have a solid foundation in order to provide timely treatment and avoid complications for the patient that may affect quality of life

A mucocele associada às glândulas de Blandin Nuhn é um fenômeno de extravasamento de mucosa que ocorre nas glândulas salivares localizadas na superfície ventral anterior da língua, do tipo misto, não encapsuladas, que fazem parte do complexo de glândulas salivares menores da cavidade oral. Objetivo: É apresentado o caso clínico de um paciente do sexo masculino na segunda década de vida com características clínicas peculiares de uma mucocele de Blandin Nuhn. Caso clínico: Adolescente de 14 anos apresenta aumento de volume localizado na superfície ventral da língua, formato cilíndrico, evolução de 3 meses e assintomático. A biópsia excisional é realizada para estudo histopatológico, que relata o fenômeno do extravasamento da mucosa e a correlação clínica histopatológica é estabelecida. Conclusões: Um diagnóstico correto deve ser baseado para fornecer tratamento oportuno e evitar complicações no paciente que afetem sua qualidade de vida

[Oral lichen planus. Case report and literature review]. / Liquen plano bucal. Reporte de un caso y revisión de la literatura.

BACKGROUND: Oral lichen planus is a chronic inflammatory skin disease of autoimmune nature, with infiltration of T lymphocytes that destroy the basal stratum, which causes white striae, erosions, ulcers and breaks in epithelial continuity. CASE REPORT: 54-year-old woman with multiple reticular and erosive lesions in the region of the buccal mucosa and lateral borders of the tongue, as well as desquamative gingivitis. Treatment with mometasone was started thrice daily for 20 days and intermittently with miconazole gel to prevent iatrogenic mycosis by the corticosteroid. The patient was examined at 20 days, after which 80 % improvement of the lesions that had central ulcerations was observed, which allowed the ingestion of food and fluids without pain and improved the quality of life. CONCLUSIONS: In autoimmune diseases, clinical-histopathological correlation is important for a definitive diagnosis to be established. Clinical follow-up of these patients should be carried out in the long term, in order to achieve remission of the lesions, control of the disease and avoid future complications.

Antecedentes: El liquen plano bucal es una enfermedad dermatológica inflamatoria crónica de base autoinmune, con infiltración de linfocitos T que destruyen el estrato basal, lo que ocasiona estrías blancas, erosiones, úlceras y diluciones epiteliales de continuidad. Reporte de caso: Mujer de 54 años con múltiples lesiones reticulares y erosivas en región de la mucosa yugal y bordes laterales de la lengua, así como gingivitis descamativa. Se inició tratamiento con mometasona tres veces al día por 20 días e intermitentemente con miconazol en gel, para prevenir micosis iatrogénica por el corticosteroide. La paciente fue revisada a los 20 días, al cabo de los cuales se observó mejoría de 80 % de las lesiones con ulceraciones centrales, lo que permitió la ingesta de alimentos y líquidos sin dolor y mejoró la calidad de vida. Conclusiones: En las enfermedades autoinmunes es importante la correlación clínico-histopatológica para establecer el diagnóstico definitivo. El seguimiento clínico de estos pacientes se debe realizar a largo plazo, para lograr la remisión de las lesiones, control de la enfermedad y evitar futuras complicaciones.

Estandarización en la observación y clasificación de lesiones epiteliales premalignas y malignas / Standardization in the observation and classification of premalignant and malignant epithelial lesions

Los criterios histológicos para determinar el grado de displasia, la clasificación de Broders y el frente de invasión tumoral (FIT) son parámetros subjetivos no cuantificables que pueden indicar el grado de evolución de displasias y carcinomas. Un factor importante a considerar durante la valoración histológica, es la variabilidad del diagnóstico entre patólogos. El objetivo es estandarizar los criterios y determinar la variabilidad intra e inter observador en el diagnóstico de displasias y COCE. Se seleccionaron y estandarizaron los criterios morfológicos para el diagnóstico y se revisaron los casos seleccionados aleatoriamente por tres patólogos bucales (30 displasias y 30 carcinomas) del Laboratorio de Patología Clínica y Experimental de la DEPeI de la FO, UNAM. Cada patólogo analizó y registró los parámetros establecidos para displasia, COCE y FIT en 2 ocasiones. Se aplicó el test Kappa para valorar la concordancia intra e inter observador. El Observador 1 v/s el 2 obtuvo una concordancia para COCE de 0,75 y en displasias de 0,60 e intraobservador de 0,90. El observador 2 v/s el 3 presentó una concordancia para COCE de 0,75 y en displasias de 0,59 e intraobservador de 0,91. El Observador 3 Vs el 1 tuvo una concordancia para COCE de 0,77, y en displasias de 0,59 e intraobservador de 0,92. La concordancia intraobservador e interobservador en COCE fue de buena a excelente, pero en displasias fue aceptable confirmando que su evaluación presenta mayor grado de dificultad. Con una adecuada estandarización se puede obtener una buena concordancia entre patólogos.

In the histological criteria for determining the degree of dysplasia, the Broders classification and the front of tumor invasion (FTI) are unquantifiable subjective parameters that may indicate the degree of development of carcinomas. An important factor to consider during the histological evaluation is the variability in the diagnosis of pathologists. The objective to standardize criteria and determine the intra and inter-observer variability in the diagnosis of dysplasias and OSCC. We selected and standardized morphological criteria for the diagnosis, and the cases were reviewed randomly by three oral pathologists (30 dysplasias and 30 carcinomas) from the Laboratory of Clinical and Experimental Pathology of the FO DEPeI, UNAM. Each pathologist analyzed and recorded the parameters for dysplasia and OSCC FIT on two occasions. Kappa test was applied to assess intra and inter-observer agreement. Observer 1 v/s 2 match for OSCC was 0.75, 0.60 for dysplasias and intra observer 0.90. Observer 2 v/s 3 presented a concordance of 0.75 for OSCC, 0.59 for dysplasias and intra-observer 0.91. Observer 3 v/s observer 1 for OSCC was 0.77, 0.59 for dysplasias and intra-observer 0.92. Intra observer and inter-observer concordance in OSCC were good or excellent, but in dysplasia was acceptable, confirming that its assessment showed the greatest difficulty with proper standardization we can obtain a better consensus between pathologists.