Pro-and Anti-inflammatory Biomarkers as Potential Prognosis Markers in Oral Squamous Cell Carcinoma

ABSTRACT: The most widely used method to classify prognostic factors in cancers today is TNM. However, Oral Squamous Cell Carcinoma (OSCC) often demonstrates different behaviors in relation to aggressiveness and therapeutic response at the same TNM stage. So, in such cases biomarkers can be used to identify the biological diversity of these tumors more reliably, leading to better therapeutic strategies and disease management. The presence of inflammatory immune cells in the tumor microenvironment can have pro or antitumor effects and the investigation of the expression of inflammatory markers in OSSC can be usefulto design immunotherapeutic interventions. The Transforming Growth Factor alpha is a potent stimulator of cell migration that acts on cell proliferation, invasion and metastasis of cancer, as well as immune suppression and angiogenesis. Inflammatory cytokines, such as Interferon-gamma, mediate macrophage differentiation. Macrophages are an important component of the OSCC microenvironment. The greater amount of tumor-associated macrophages, especially the M2 phenotype, may be associated with a more aggressive biological behavior of the OSCC and, consequently, with reduced survival.

RESUMEN: El método más utilizado para clasificar los factores de pronóstico en los cánceres en la actualidad es TNM. Sin embargo, el carcinoma oral de células escamosas (COCE) a menudo muestra diferentes comportamientos en relación con la agresividad y la respuesta terapéutica en la misma etapa TNM. Entonces, en tales casos, los biomarcadores pueden usarse para identificar la diversidad biológica de estos tumores de manera más confiable, lo que lleva a mejores estrategias terapéuticas y manejo de la enfermedad. La presencia de células inmunes inflamatorias en el microambiente tumoral puede tener efectos pro o antitumorales y la investigación de la expresión de marcadores inflamatorios en COCE puede ser útil para diseñar intervenciones inmunoterapéuticas. El factor de crecimiento transformante α es un potente estimulador de la migración celular que actúa sobre la proliferación celular, la invasión y metástasis del cáncer, así como la inmunosupresión y la angiogénesis. Las citocinas inflamatorias, como el IFN-γ, median en la diferenciación de macrófagos. Los macrófagos son un componente importante del microambiente COCE. La mayor cantidad de macrófagos asociados a tumores, especialmente el fenotipo M2, puede estar asociada a un comportamiento biológico más agresivo del COCE y, en consecuencia, a una menor supervivencia.

DHEA and frontal fibrosing alopecia: molecular and physiopathological mechanisms

Abstract The transforming growth factor-beta 1 (TGFβ1) promotes fibrosis, differentiating epithelial cells and quiescent fibroblasts into myofibroblasts and increasing expression of extracellular matrix. Recent investigations have shown that PPAR (peroxisome proliferator-activated receptor*) is a negative regulator of fibrotic events induced by TGFβ1. Dehydroepiandrosterone (DHEA) is an immunomodulatory hormone essential for PPAR functions, and is reduced in some processes characterized by fibrosis. Although scarring alopecia characteristically develops in the female biological period in which occurs decreased production of DHEA, there are no data in the literature relating its reduction to fibrogenic process of this condition. This article aims to review the fibrogenic activity of TGFβ1, its control by PPAR and its relation with DHEA in the frontal fibrosing alopecia.

Salivary transforming growth factor alpha in patients with Sjögren's syndrome and reflux laryngitis.

INTRODUCTION: Saliva plays a key role in the homeostasis of the digestive tract, through its inorganic components and its protein growth factors. Sjögren's syndrome patients have a higher prevalence of gastroesophageal reflux disease and laryngopharyngeal reflux. Decreased salivary transforming growth factor alpha levels were observed in dyspeptic patients, but there have been no studies in patients with Sjögren's syndrome and laryngopharyngeal reflux. OBJECTIVE: To compare the salivary transforming growth factor alpha levels of patients with Sjögren's syndrome and laryngopharyngeal reflux to those of healthy controls. METHODS: This is a prospective controlled study. Twelve patients with Sjögren's syndrome and laryngopharyngeal reflux and 11 controls were prospectively evaluated. Spontaneous and stimulated saliva samples were obtained to establish salivary transforming growth factor alpha concentrations. RESULTS: The salivary transforming growth factor alpha levels of patients were significantly higher than those of healthy controls. Five patients with laryngopharyngeal reflux also had erosive esophagitis; their salivary transforming growth factor alpha levels were comparable to controls. CONCLUSION: Salivary transforming growth factor alpha level was significantly higher in patients with Sjögren's syndrome and laryngopharyngeal reflux when compared to the control group.

Salivary transforming growth factor alpha in patients with Sjögren's syndrome and reflux laryngitis / Estudo da concentração salivar do fator transformador de crescimento alfa em indivíduos com Sindrome de Sjögren e refluxo laringofaríngeo

Introduction: Saliva plays a key role in the homeostasis of the digestive tract, through its inorganic components and its protein growth factors. Sjögren's syndrome patients have a higher prevalence of gastroesophageal reflux disease and laryngopharyngeal reflux. Decreased salivary transforming growth factor alpha levels were observed in dyspeptic patients, but there have been no studies in patients with Sjögren's syndrome and laryngopharyngeal reflux. Objective: To compare the salivary transforming growth factor alpha levels of patients with Sjögren's syndrome and laryngopharyngeal reflux to those of healthy controls. Methods: This is a prospective controlled study. Twelve patients with Sjögren's syndrome and laryngopharyngeal reflux and 11 controls were prospectively evaluated. Spontaneous and stimulated saliva samples were obtained to establish salivary transforming growth factor alpha concentrations. Results: The salivary transforming growth factor alpha levels of patients were significantly higher than those of healthy controls. Five patients with laryngopharyngeal reflux also had erosive esophagitis; their salivary transforming growth factor alpha levels were comparable to controls. Conclusion: Salivary transforming growth factor alpha level was significantly higher in patients with Sjögren's syndrome and laryngopharyngeal reflux when compared to the control group. .

Introdução: A saliva exerce influência primordial na homeostase do sistema digestório, pelos seus componentes inorgânicos e pelos fatores de crescimento. Indivíduos com sindrome de Sjögren (SS) apresentam maior incidência da doença do refluxo gastroesofágico (DRGE) e do refluxo laringofaríngeo (RLF). Concentrações salivares diminuídas do fator transformador de crescimento alfa (TGF-α) foram observadas em doentes dispépticos, porém não há estudos em populações com SS e RLF. Objetivo: Comparar concentrações salivares do TGF-α; de indivíduos com SS e RLF a de controles saudáveis. Método: Trata-se de um estudo prospectivo controlado. Doze pacientes com SS e RLF e 11 indivíduos controles saudáveis tiveram amostras salivares espontâneas e estimuladas coletadas para estabelecer concentração de TGF-α. Resultados: A concentração salivar de TGF-α; foi estatisticamente maior no grupo estudo para ambas amostras. Este aumento foi confirmado nos sete indivíduos do grupo estudo que não apresentavam esofagite erosiva quando comparados ao grupo controle, porém não houve diferença estatística da concentração de TGF-α; entre pacientes do grupo estudo que apresentava mesofagite erosiva em comparação ao grupo controle. Conclusão: A concentração salivar de TGF-α; foi estatisticamente maior no grupo de indivíduos com SS e RLF, sem esofagite erosiva. .

Bone remodeling at microscrew interface near extraction site in the beagle dog mandible-histologic and immunohistochemical analyses

Extraction is often used as part of orthodontic therapy, and good control of anchorage is a key step after extraction. Although microscrews can be implanted close to the extraction site in order to achieve orthodontic support, the efficiency of bone remodeling at the implant-bone interface near the extraction region is dubious. OBJECTIVE: The purpose of this study was to investigate bone remodeling of the bone-microscrew interface near the tooth extraction site, in the absence of loading. MATERIAL AND METHODS: Third and fourth premolars were extracted from the mandibles of beagle dogs, followed by placement of test microscrews near the extraction sites. Control microscrews were placed further away from the extraction site. All samples were collected after 1, 3, 8, or 12 weeks of healing following extraction. The bone remodeling process at the interface was evaluated using histologic and immunohistochemical analyses. RESULTS: Initially, a large number of inflammatory cells were aggregated at the interface. The expression levels of core binding factor (Cbfa1), osteocalcin (OC) and transforming growth factor beta (TGF-β) were inconspicuous in both groups, whereas tumor necrosis factor alpha (TNF-α) was strongly expressed, especially in the test groups (P<0.05). Subsequently, the expression levels of Cbfa1, OC and TGF-β were found to increase significantly, and active osteogenesis was observed. CONCLUSIONS: During week 1, inflammatory reaction is a major concern at the bone-microscrew interface near the extraction site. However, with healing, the influence of extraction on the remodeling of bone surrounding the microscrews decreases, thus facilitating successful treatment. .