RESUMEN
Oral squamous cell carcinomas (OSCCs) can arise from potentially malignant disorders, such as leukoplakia. The immune system plays an important role recognizing tumour precursor cells. However, due to immuno-editing mechanisms cancer cells are able to escape immune system surveillance. OBJECTIVE: To evaluate the profile of dendritic (Langerhans and plasmacytoid) and T cells in OSCC and oral epithelial dysplasia (OED) and correlate these findings with clinical data. MATERIALS AND METHODS: Fifty cases of OSCC and 48 of OED were immunostained for CD1a and CD83 dendritic Langerhans cells (DLC), CD303 plasmacytoid dendritic cells (pDC) and CD8 followed by quantitative analysis. RESULTS: Analysis revealed a significant decrease in the number of mature CD83 DLC in OSCC compared with OED. CD303 positivity was significantly increased in the OSCC group when compared to OED. CD8-positive lymphocytes were significantly decreased in OSCC compared with OED lesions. No statistical correlation was found with clinical data. CONCLUSION: The number of mature dendritic cells (DC) was decreased in OSCC compared with OED lesions suggesting that either these cells might have migrated to lymph nodes to present the tumour antigens and activate the immune system or cytokines secreted by the tumour microenvironment are inhibiting the adequate maturation of DLC. The numbers of pDC were significantly increased in the OSCC group compared with the OED group. This suggests they may play an important role in the defence against tumours although it is not clear whether this is promoting or inhibiting malignant progression.
Asunto(s)
Carcinoma in Situ/inmunología , Carcinoma de Células Escamosas/inmunología , Células Dendríticas , Monitorización Inmunológica , Neoplasias de la Boca/inmunología , Boca/inmunología , Boca/patología , Linfocitos T , Adulto , Carcinoma in Situ/patología , Carcinoma de Células Escamosas/patología , Epitelio/inmunología , Epitelio/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/patología , Estudios RetrospectivosRESUMEN
The aim of this study was to evaluate NF-kB during 5-fluorouracil (FU)-induced oral mucositis and ascertain whether photobiomodulation (PBM), as a preventive and/or therapeutic modality, influences this transcription factor. Ninety-six male golden Syrian hamsters were allocated into four groups: control (no treatment); PBM therapeutic, PBM preventive, and PBM combined. Animals received an injection of 5-FU on days 0 and 2. On days 3 and 4, the buccal mucosa was scratched. Irradiation was carried out using a 660-nm, 40-mW diode laser at 6 J/cm(2) during 6 s/point, 0.24 J/point, for a total dose of 1.44 J/day of application. Animals were euthanized on days 0, 5, 10, and 15 (n=6). Buccal mucosa was removed for protein quantification by Western blot. Clinical analysis revealed that PBM groups exhibited less mucositis than controls on day 10. Control animals exhibited lower levels of NF-kB during mucositis development and healing. The preventive and combined protocols were associated with higher NF-kB levels at day 5; however, the therapeutic group had higher levels at days 10 and 15. These findings suggest that the preventive and/or therapeutic PBM protocols reduced the severity of oral mucositis by activating the NF-kB pathway.
Asunto(s)
Antimetabolitos Antineoplásicos/administración & dosificación , Fluorouracilo/administración & dosificación , FN-kappa B/metabolismo , Fototerapia/métodos , Estomatitis/tratamiento farmacológico , Estomatitis/metabolismo , Estomatitis/terapia , Animales , Western Blotting , Cricetinae , Esquema de Medicación , Terapia por Láser/métodos , Rayos Láser , Masculino , Mesocricetus , Multimerización de Proteína , Cicatrización de HeridasRESUMEN
Keratinocytes play a central role in wound healing by responding to tissue injury through the activation of cellular proliferation and migration. Current clinical evidence suggests that the laser phototherapy (LPT) accelerates wound healing in a variety of oral diseases; however, the molecular mechanisms involved in response to LPT are not fully understood. Oral keratinocytes (NOK-SI) maintained under nutritional-deficit culture medium (2% fetal bovine serum) were irradiated with InGaAlP laser (660 nm; 40 mW; 0.04 cm2 spot size) in punctual and contact modes. The energy densities used were 4 and 20 J/cm2 corresponding to 4 and 20 s of exposure times and 0.16 and 0.8 J of energy per point, respectively. Three sessions of irradiations were applied with 6-h intervals. Further, the impact of LPT over cellular migration, proliferation, and activation of the mammalian target of rapamycin (mTOR) pathway, known to play a major role in epithelial migration and wound healing, was analyzed. Compared with control cells, the LPT-treated cells showed accelerated cellular migration without any changes in proliferation. Furthermore, LPT resulted in an increase in the phospho-S6 ribosomal protein, indicating activation of the mTOR signaling pathway. Collectively, these findings suggest that the LPT activates mTOR signaling pathway, promotes epithelial cell migration, and accelerates healing of oral mucosa.
Asunto(s)
Movimiento Celular/efectos de la radiación , Queratinocitos/efectos de la radiación , Terapia por Luz de Baja Intensidad/métodos , Transducción de Señal/efectos de la radiación , Serina-Treonina Quinasas TOR/metabolismo , Actinas/metabolismo , Análisis de Varianza , Proliferación Celular/efectos de la radiación , Supervivencia Celular/efectos de la radiación , Humanos , Queratinocitos/citología , Mucosa Bucal/citología , PolimerizacionRESUMEN
OBJECTIVE: To assess cytogenetic abnormalities through quantification of micronuclei, broken eggs, and karyorrhexis, in cells from normal oral mucosa of individuals exposed to carcinogens (alcohol and tobacco) and adjacent to leukoplakias and squamous cell carcinomas. STUDY DESIGN: The sample was composed of 40 subjects aged > 30 years, divided into four groups: control, alcohol/tobacco, leukoplakia, and squamous cell carcinoma. For control and alcohol/tobacco groups, cells were collected from lower lip, tongue border, and floor of the mouth. For leukoplakia and squamous cell carcinoma groups, mucosa contralateral and adjacent to the lesions were analyzed. Cytologic smears were stained with the Feulgen reaction. A blind observer analyzed 1,000 cells per slide to quantify micronuclei, broken eggs, and karyorrhexis. RESULTS: The leukoplakia group showed an increased number of micronuclei compared to controls (p = 0.0016) and the alcohol/tobacco group (p = 0.0048) and also increased broken eggs compared to the alcohol/tobacco group (p = 0.0172). Similarly, the carcinoma group presented more micronuclei compared to controls (p = 0.0462) and more broken eggs compared to the alcohol/tobacco group (p = 0.0104). CONCLUSION: The assessment of cytogenetic abnormalities micronuclei and broken eggs may be useful for monitoring individuals exposed to risk factors for developing oral cancer.