Comprehensive insights into the understanding of hypoxia in ameloblastoma

Hypoxia is characterized by a disparity between supply and demand of oxygen. The association between hypoxia and head and neck tumors is a topic of significant interest. Tumors frequently encounter areas with inadequate oxygen supply, resulting in a hypoxic microenvironment. Ameloblastoma is one of the most common benign odontogenic tumors of the maxillofacial region. It is a slow-growing but locally invasive tumor with a high recurrence rate. The literature has demonstrated the correlation between hypoxia and ameloblastoma, revealing a discernible link between the heightened expression of hypoxic markers in low oxygen conditions. This association is intricately tied to the tumoral potential for invasion, progression, and malignant transformation. Hypoxia profoundly influences the molecular and cellular landscape within ameloblastic lesions. The present review sheds light on the mechanisms, implications, and emerging perspectives in understanding this intriguing association to clarify the dynamic relationship between hypoxia and ameloblastoma

IL-1/IL-1R Signaling in head and neck cancer

Decades ago, the study of cancer biology was mainly focused on the tumor itself, paying little attention to the tumor microenvironment (TME). Currently, it is well recognized that the TME plays a vital role in cancer development and progression, with emerging treatment strategies focusing on different components of the TME, including tumoral cells, blood vessels, fibroblasts, senescent cells, inflammatory cells, inflammatory factors, among others. There is a well-accepted relationship between chronic inflammation and cancer development. Interleukin-1 (IL-1), a potent pro-inflammatory cytokine commonly found at tumor sites, is considered one of the most important inflammatory factors in cancer, and has been related with carcinogenesis, tumor growth and metastasis. Increasing evidence has linked development of head and neck squamous cell carcinoma (HNSCC) with chronic inflammation, and particularly, with IL-1 signaling. This review focuses on the most important members of the IL-1 family, with emphasis on how their aberrant expression can promote HNSCC development and metastasis, highlighting possible clinical applications

Genomic and transcriptomic analysis of ameloblastoma reveals distinct molecularly aggressive phenotypes.

Ameloblastoma (AM) is a benign but locally infiltrative epithelial odontogenic neoplasm of the jawbones that may reach grotesque proportions and be highly recurrent if inadequately removed. The BRAFV600E mutation has been demonstrated as key molecular event in its development, nevertheless, there are many queries about its aetiopathogenesis that are yet to be answered. In this study, we aimed to integrate results from whole-exome sequencing (WES) and RNA-sequencing in AM samples to identify novel candidate genes that may be relevant to its pathogenesis. Thirteen-matched tumors were subjected to WES and RNAseq, respectively, to detect gene mutations and gene expression profile, along to the presence of gene fusions. Mutations were validated with sanger sequencing, whereas transcriptome results were validated with qPCR. Results from both molecular techniques were merged in order to identify novel candidate genes, that were biological validated with immunohistochemistry. BRAFV600E mutation was present in 62% of the analyzed cases, and each AM presented at least two or three mutations affecting cancer-driver genes. RNAseq showed different molecular subgroups associated with an aggressive and cancer-related phenotype (epithelial-mesenchymal transition-EMT and KRAS gene sets). No gene fusions were detected among the cases. CDH11 and TGM2, novel genes associated with EMT in AM, were selected and validated in tissue. Both WES and RNAseq results showed gene alterations related to proliferation, cell differentiation, and metabolic processes. These results show that AM share many of the hallmarks of cancer secondary to the presence of oncogenic mutations or activation of oncogenic signaling pathways

Hypoxia-inducible factor-1α at the invasive tumor front in oral squamous cell carcinoma.

BACKGROUND Hypoxia in oral cancer promotes tumoral invasion by inducing epithelial-mesenchymal transition, leading to aggressive tumor progression. AIM To characterize the expression of hypoxia-inducible factor 1-alpha (HIF-1α) at the invasive tumor front (ITF) in comparison to tumor islands (TI) in oral squamous cell carcinoma (OSCC) and to explore its relationship with E-cadherin and Vimentin expression. METHODS Thirty-eight cases of OSCC and five cases of normal oral mucosa (NOM) were included in this study. The ITF was identified based on the region and immune expression of AE1/AE3. Immunohistochemistry was performed to assess the expression of HIF-1α, Vimentin, and E-cadherin. The immunostaining was analyzed using an immunoreactive score, and the results were illustrated using immunofluorescence. RESULTS HIF-1α expression was significantly higher in the TI region compared to the ITF region (P = 0.0134). Additionally, a significant difference was observed between TI and NOM (P = 0.0115). In the ITF regions, HIF-1α expression showed a significant correlation with Vimentin expression, with higher levels of HIF-1α associated with increased Vimentin expression (P = 0.017). CONCLUSION Based on the results of this study, HIF-1α appears to play a distinct role in OSCC tumor progression, underscoring the importance of exploring hypoxia-driven changes in cellular phenotype at the ITF of OSCC. Further research is needed to better understand their impact on OSCC prognosis.Comisión Sectorial de Investigación Científica (CSIC - Grupo de investigación 88180); Agencia Nacional de Investigación e Innovación/Sistema Nacional de Investigadores (ANII/SNI); Programa de Desarrollo de las Ciencias Básicas (PEDECIBA), Uruguay

Análisis inmunohistoquímico de p53 y Ki67 en carcinomas espinocelulares bien diferenciados y carcinomas verrucosos de la mucosa oral

Tesis (Magíster en Odontología, Especialización en Patología, Diagnóstico y Medicina Oral)El estudio de la patogénesis molecular del cáncer oral puede ayudar a buscar marcadores moleculares que pudiesen predecir el comportamiento clínico de un tumor (1 ). Recientes avances en biología celular han elucidado mecanismos precisos de sistemas de regulación del ciclo celular, y han mostrado que la proliferación celular no regulada es una característica común de muchos cánceres. El ciclo celular está regulado no sólo por varias ciclinas, complejos de cinasas dependientes de ciclinas (Cdk) e inhibidores de COK, como p16, p15 y p21 , sino que también por genes supresores de tumores. como pRb y p53, y otras proteínas asociadas al ciclo celular (2). Además, existen otro tipo de proteínas, denominadas proteínas de proliferación celular, como Ki-67, PCNA, que están estrictamente relacionadas con la división celular, y se han visto fuertemente vinculadas en el desarrollo de algunos cánceres (3). Un buen entendimiento de la carcinogénesis oral es importante para el establecimiento de nuevas estrategias de tratamiento. Actualmente se están realizando más estudios para medir la expresión de distintas proteínas relacionadas con la inhibición y estimulación del ciclo celular en carcinomas espinocelulares orales, aunque son escasos en carcinomas verrucosos orales, por lo que queda todavía mucho por clarificar

Senescent Cells in Cancer: Wanted or Unwanted Citizens

Over recent decades, the field of cellular senescence has attracted considerable attention due to its association with aging, the development of age-related diseases and cancer. Senescent cells are unable to proliferate, as the pathways responsible for initiating the cell cycle are irreversibly inhibited. Nevertheless, senescent cells accumulate in tissues and develop a pro-inflammatory secretome, known as the senescence-associated secretory phenotype (SASP), which can have serious deleterious effects if not properly regulated. There is increasing evidence suggesting senescent cells contribute to different stages of carcinogenesis in different anatomical sites, mainly due to the paracrine effects of the SASP. Thus, a new therapeutic field, known as senotherapeutics, has developed. In this review, we aim to discuss the molecular mechanisms underlying the senescence response and its relationship with cancer development, focusing on the link between senescence-related inflammation and cancer. We will also discuss different approaches to target senescent cells that might be of use for cancer treatment

Estudio de prevalencia de lesiones orales asociadas a infecciones de transmisión sexual de origen viral

Tesis (Magister Odontología)Las infecciones de transmisión sexual (ITS) han sido históricamente un problema de salud frecuente. Estas infecciones son causadas por diferentes tipos de microorganismos que se transmiten a menudo, si no en todos los casos, de persona a persona a través del contacto sexual (18, 23). Las ITS causan una morbilidad importante y contribuyen grandemente a incrementar los gastos de salud pública. El riesgo de adquirir una ITS es alto en áreas urbanas, en estratos socioeconómicos bajos, en personas jóvenes, trabajadoras sexuales y sus clientes, personas con múltiples parejas sexuales, hombres homosexuales y en asociación con el uso de drogas ilícitas (37). Hoy en día los clínicos reconocen un aumento en las infecciones de transmisión sexual. El incremento de éstas, refleja en parte, los cambios de actitud en la conducta sexual. Un incremento en la prevalencia de la actividad orogenital puede esperarse que sea acompañado del correspondiente incremento en las manifestaciones orofaríngeas de las ITS, y los clínicos tienen un rol crítico en la prevención, diagnóstico y tratamiento de tales condiciones (35). Algunas ITS, como el VIH, dan sus primeros signos clínicos dentro de la boca (2,6). Es por esto, que es crucial para el odontólogo general estar en conocimiento del amplio espectro clínico que pueden adoptar estas enfermedades cuando se manifiestan en el sistema estomatognático, para establecer así, un diagnóstico adecuado de forma temprana y mejorar el pronóstico y calidad de vida de nuestros pacientes (18, 23)

Inflammatory Mediators in Oral Cancer: Pathogenic Mechanisms and Diagnostic Potential

Approximately 15% of cancers are attributable to the inflammatory process, and growing evidence supports an association between oral squamous cell carcinoma (OSCC) and chronic inflammation. Different oral inflammatory conditions, such as oral lichen planus (OLP), submucous fibrosis, and oral discoid lupus, are all predisposing for the development of OSCC. The microenvironment of these conditions contains various transcription factors and inflammatory mediators with the ability to induce proliferation, epithelial-to-mesenchymal transition (EMT), and invasion of genetically predisposed lesions, thereby promoting tumor development. In this review, we will focus on the main inflammatory molecules and transcription factors activated in OSCC, with emphasis on their translational potential.</jats:p