The Protective Role of Cranberries and Blueberries in Oral Cancer.

BACKGROUND: Oral cancer has a high prevalence worldwide, and this disease is caused by genetic, immunological, and environmental factors. The main risk factors associated with oral cancer are smoking and alcohol. RESULTS: There are various strategies to reduce risk factors, including prevention programs as well as the consumption of an adequate diet that includes phytochemical compounds derived from cranberries (Vaccinium macrocarpon A.) and blueberries (Vaccinium corymbosum L.); these compounds exhibit antitumor properties. RESULTS: The main outcome of this review is as follows: the properties of phytochemicals derived from cranberries were evaluated for protection against risk factors associated with oral cancer. CONCLUSIONS: The secondary metabolites of cranberries promote biological effects that provide protection against smoking and alcoholism. An alternative for the prevention of oral cancer can be the consumption of these cranberries and blueberries.

The role of p21-activated kinase 4 in the progression of oral squamous cell carcinoma by targeting PI3K-AKT signaling pathway.

BACKGROUND: Oral squamous carcinoma (OSCC), the most common head and neck malignancy, has a strong propensity for malignant proliferation and metastasis, which will decrease the survival of patients. P21-activated kinase 4 (PAK4), a classical serine/threonine protein kinase with multiple cellular functions, has an essential role in cancer cell migration and invasion. Here, we elucidated the function and possible molecular mechanisms of the effect of PAK4 on the biological behaviors of OSCC. METHODS: The expression of genes and protein was detected by real-time PCR and western blotting. We used oral squamous carcinoma cell lines, Tca8117, Cal 27, SCC 4, and SCC 9 for validation of our cell function data. Flow cytometry, 3D cultures, and clone formation assay were used to detect proliferation of cells. RNA sequencing and bioinformatic analysis was performed to determine the potential function of PAK4. RESULTS: Immunohistochemistry, western blotting and real-time PCR demonstrated that PAK4 expression was up-regulated in OSCC tissues. Overexpression of PAK4 promoted the proliferation, migration and invasion of OSCC cell lines. RNA sequencing (RNA-seq) for the transcriptome-wide analysis of differential gene expression followed by bioinformatic analysis was performed to determine the potential function of PAK4. Based on the KEGG enrichment analysis and GO analysis of differential expression genes (DEGs) we found that PAK4 promotes the cell-cycle machinery, which associated with 44 regulated genes, thereby promoting cancer cell differentiation. CONCLUSIONS: This study demonstrates that the PAK4 regulates the biological behaviors of OSCC by PI3K-AKT signaling pathway, and these findings might provide a novel strategy for OSCC treatment.

Cociente ganglionar como factor pronóstico de recurrencia tumoral en pacientes con carcinoma escamoso de cavidad oral.

BACKGROUND: The lymph node ratio (LNR) is a recent tool, but its predictive value for recurrence is uncertain. OBJECTIVE: To evaluate LNR as a prognostic factor for disease-free survival (DFS) in patients with oral squamous cell carcinoma. METHOD: Retrospective observational study. Patients with oral squamous cell carcinoma undergoing resection and lymph node dissection. Chi squared, Kaplan-Meier, log rank and Cox regression tests were run; bilateral p ≤ 0.05 determined statistical significance. RESULTS: 88 patients were included, 45% (n = 40) men and 54% (n = 48) women, mean age of 60.42 (± 14.28) years. Main tumor location in tongue (75%); 61% in clinical stage I-III and 39% in clinical stage IV. Population was divided into LNR < 0.06 (58%) and LNR ≥ 0.06 (42%). The median DFS was not reached for both groups (p = 0.018). Predictors of DFS were the LNR (p = 0.024; hazard ratio [HR]: 2.20; confidence interval of 95% [95% CI]: 1.11-4.39) and the clinical stage (p = 0.004; HR: 1.76; 95% CI: 1.19-2.59). In the multivariate analysis, predictors were not maintained (p = 0.227 and 0.191, respectively). CONCLUSIONS: Significant differences were observed in the DFS analysis, however, they were not predictive of local recurrence in the multivariate analysis.

ANTECEDENTES: El cociente ganglionar (LNR) es una herramienta reciente, pero su valor predictivo de recurrencia es incierto. OBJETIVO: Evaluar el LNR como factor pronóstico de supervivencia libre de enfermedad (SLE) en pacientes con carcinoma oral de células escamosas. MÉTODO: Estudio retrospectivo observacional. Pacientes con carcinoma oral de células escamosas sometidos a resección y disección ganglionar. Se aplicaroon las pruebas de ji al cuadrado, Kaplan-Meier, log rank y regresión de Cox; se consideró estadísticamente significativo p ≤ 0.05 bilateral. RESULTADOS: Fueron incluidos 88 pacientes, el 45% (n = 40) hombres y el 54% (n = 48) mujeres, con una edad media de 60.42 (± 14.28) años. La principal localización tumoral fue la lengua (75%); el 61% en etapa I-III y el 39% en etapa IV. Se dividió en LNR < 0.06 (58%) y LNR ≥ 0.06 (42%). La mediana de SLE no fue alcanzada para ambos grupos (p = 0.018). Resultaron predictores de SLE el LNR (p = 0.024; hazard ratio [HR]: 2.20; intervalo de confianza del 95% [IC95%]: 1.11-4.39) y la etapa clínica (p = 0.004; HR: 1.76; IC95%: 1.19-2.59). En el análisis multivariado no se mantuvieron predictores (p = 0.227 y p = 0.191, respectivamente). CONCLUSIONES: Se observaron diferencias significativas en el análisis de SLE, pero no se mantuvieron como predictoras de recurrencia local en el análisis multivariado.

Photobiomodulation is associated with a decrease in cell viability and migration in oral squamous cell carcinoma.

The treatment of squamous cell carcinoma (SCC) involves surgery, chemotherapy, and/or radiotherapy, which can cause mucositis (inflammation of the oral mucosa that causes considerable pain and can compromise the continuity of oncological treatment). Photobiomodulation (PBM) has been successfully used in the treatment of mucositis, but doubts arise regarding the use of laser for areas in which tumor cells may remain. In this study, the effect of PBM on the viability, mitochondrial activity, proliferation, apoptosis, and migration of cells derived from oral SCC was evaluated. SCC9 cells were irradiated with laser (660 and 780 nm, using 11 dosimetric parameters) and submitted to mitochondrial and caspase 3 activity tests after 1 and 3 days. Based on the results, cell viability (neutral red assay), proliferation (BrdU assay), and migration (scratch-wound assay) were evaluated using only the dosimetric parameters recommended for mucositis. Non-irradiated cells served as the control. The experiments were performed in triplicate. The 11 parameters diminished mitochondrial activity and induced tumor cell apoptosis. Using the parameters recommended for mucositis, irradiation with 780 nm (70 mW, 4 J/cm2) proved to be the safest and led to a reduction in cell viability, the induction of apoptosis, and a reduction in the migration capacity of the tumor cells.

Expresión de Podoplanina en Mucosa Oral Normal, Displasia Epitelial Oral y Carcinoma Oral de Células Escamosas / Immunoexpression of Podoplanin in Normal Oral Mucosa, Epithelial Displasia and Oral Squamous Cell Carcinoma

RESUMEN: Evaluar la inmunoexpresión de podoplanina (PDPN) en el epitelio y vasos linfáticos en muestras de mucosa oral normal (MON), displasia epitelial oral (DEO) y carcinoma espinocelular oral (CECO). Estudio descriptivo de serie de casos. La muestra estuvo constituida por 19 casos de MON, 18 de DEO y 19 de CECO. Se consideraron positivas aquellas células con tinción de membrana y/o citoplasmático. Para la evaluación de PDPN epitelial se realizó un análisis semicuantitativo a través del producto entre la intensidad y porcentaje de células teñidas (immunoreactive score- IRS), mientras que para la evaluación de los vasos linfáticos, se determinó la densidad media vascular (DMV) a partir del promedio de la densidad linfática en tres campos ópticos por muestra. El mayor valor de IRS se observó en el grupo de CECO, seguido por DEO y el menor valor fue en el grupo de MON, con diferencias estadísticamente significativas al comparar CECO/DEO (p= 0,0200) y CECO/MON (p= 0,0078). Al comparar los valores de DMV según diagnóstico, se obtuvo que estos fueron bastante similares y no presentaron diferencias significativas entre sí (p= 0,4273). Finalmente, se analizó la relación entre los valores de IRS de podoplanina epitelial y la densidad media vascular de los linfáticos, a través del test de independencia de Spearman, el cual determinó que no hay un grado de asociación entre ambas variables (p= 0,2056). Conclusión: el IRS epitelial aumenta su valor al comparar muestras de MON, DEO y CECO. No existen diferencias significativas, en las muestras estudiadas, entre los valores de DMV linfática. No existe relación entre la expresión de PDPN epitelial y DMV linfática en muestras de DEO y CECO.

ABSTRACT: The objective of this study was to evaluate the expression of Podoplanin (PDPN) in epithelium and lymphatic vessels in normal oral mucosa (NOM), oral epithelial displasia (OED) and oral squamous cell carcinoma (OSCC). A descriptive case study was carried out. Nineteen histological samples diagnosed with NOM, 18 diagnosed with OED and 19 with OSCC. Immunopositive cells for PDPN were those that presented membrane and/or cytoplasmic staining. A semi-quantitative analysis of the stained sections was made according to the immunoreactive score (IRS) for the extension and intensity of epithelial cells, while the evaluation of lymphangiogenesis was made through the calculation of the mean vascular density (MVD). The results indicated the higher IRS value was in OSCC followed by OED and lowest in NOM, with significant differences between OSCC/OED (p= 0.0200) and OSCC/NOM (p= 0.0078). No differences in MVD were found between the studied samples (p= 0.4273). Finally, the correlation between the value of epithelial IRS and MVD was analyzed through Spearman Independence test, which determined there was no statistically significant relationship between the studied variables (p= 0.2056). In conclusion, epithelial IRS value is greater in OSCC samples than OED and NOM. There was no statistically significant difference in lymphatic MVD in the studied samples. There is no correlation between the epithelial PDPN expression and lymphatic MVD in OSCC and OED samples.