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.

HPV Prevalence and Predictive Biomarkers for Oropharyngeal Squamous Cell Carcinoma in Mexican Patients.

BACKGROUND: Worldwide prevalence of Oropharyngeal Squamous Cell Carcinoma (OPSCC) has increased, affecting mostly young males. OPSCC associated with Human Papillomavirus (HPV) infection exhibits particular characteristics in terms of response to treatment, hence HPV has been proposed as a prognostic factor. The impact of HPV positivity and associated biomarkers on OPSCC in the Mexican population has not been addressed. Therefore, the analysis of OPSCC prognostic markers in the Mexican population is necessary. METHODS: Retrolective study in Mexican OPSCC patients, where HPV prevalence, p16 and EGFR levels were assessed using INNO-LiPA and immunohistochemistry. RESULTS: We found an HPV prevalence of 57.6% in OPSCC cases treated at a reference center in Mexico. HPV and p16 positivity, as well as EGFR, associate with better outcomes in OPSCC patients, and they also promote reduced death risk. Notably, HPV presence and p16 positivity showed a significant association with disease-free survival (DFS), with a HR of 0.15 (p = 0.006) and a HR of 0.17 (p = 0.012), respectively, indicating a possible role as predictive biomarkers in Mexican OPSCC patients. CONCLUSIONS: Our results reflect the clinical utility of p16 analysis to improve overall survival (OS) and to predict recurrence in oropharyngeal cancer. These results position p16 and HPV as predictive biomarkers for OPSCC.

High prevalent human papillomavirus infections of the oral cavity of asymptomatic HIV-positive men.

BACKGROUND: Incidence of anal and oral infections with Human Papillomavirus (HPV) is increasing, particularly among Human Immunodeficiency Virus-positive (HIV+) men. HPV type 16 has exhibited the highest incidence and only limited data is available on other prevalent types, variants of HPV16, as well as associated factors. We were interested in identifying prevalent HPV types, variants of type 16, as well as factors associated with HPV16 infections in the oral cavity of HIV+ men who have sex with men (MSM). METHODS: A cross-sectional study of oral cavity samples from HIV+ MSM, that in a previous study were identified as positive for HPV16 in the anal canal. Cells from the oral cavity (102 samples, paired with 102 from the anal canal of same patient) were used to extract DNA and detect HPV infections using INNO-LiPA HPV Genotyping Extra II, and PCR. From these, 80 samples (paired, 40 anal and 40 oral) were used to identify variants of type 16 by sequencing. Statistical differences were estimated by the X2 test, and p values equal to or less than 0.05 were considered significant. SPSS ver. Twenty-four statistical software (IBM Corp) was used. RESULTS: We found a high prevalence of High-Risk HPV (HR-HPV) and Low-Risk HPV (LR-HPV). Patients were positive in the oral cavity for HR types; 16, 39 and 18 (80.4, 61.8 and 52.9% respectively) and LR types 11 and 6 (53.9 and 34.3% respectively). Surprisingly, only European variants of type 16 were found in the oral cavity, although American Asian (22.5%) and African (2.5%) variants were identified in the anal canal. The analysis showed that CD4 counts could be the most important risk factor associated with HR-HPV infections in the oral cavity, anal canal or both anatomical regions. The risk of infection of the oral cavity with type 18 increased in men diagnosed with HIV for more than 6 years. CONCLUSIONS: Prevalence of both HR and LR HPV's in the oral cavity of Mexican HIV+ MSM is very high. The fact that only European variants of HPV16 were found in the oral cavity suggest a possible tropism not previously described.

Luteolin inhibits lipopolysaccharide actions on human gingival fibroblasts.

Periodontal disease comprises a group of infections that lead to inflammation of the gingiva, periodontal tissue destruction, and in severe cases is accompanied by alveolar bone loss with tooth exfoliation. Actinobacillus actinomycetemcomitans is a Gram-negative microorganism, which possesses and produces lipopolysaccharide (LPS) molecules that play a key role in disease development. Human gingival fibroblasts are the major constituents of gingival connective tissue and may interact directly with bacteria and bacterial products including LPS. Flavonoids possess antioxidant and anti-inflammatory properties that reduce inflammatory molecule expression in macrophages and monocytes. In this study, we evaluated the ability of diverse flavonoids to regulate nitric oxide production of LPS-stimulated human gingival fibroblasts, and studied the effect of luteolin on diminish phosphorylation in mitogen-activated protein kinase (MAPK) family members as well as in protein kinase B (Akt), nuclear factor kappa B (NF-kappaB) activation, inducible nitric oxide synthase (NOS) expression, and nitric oxide (NO) synthesis. We also found that pretreatment with three flavonoids, including quercetin, genistein, and luteolin, blocked nitric oxide synthesis in a dose-dependent fashion. Luteolin exerted the strongest blocking action on expression of this inflammatory mediator. Luteolin pretreatment attenuated LPS-induced extracellular signal-regulated kinase, p38, and Akt phosphorylation. LPS treatment of human gingival fibroblasts resulted in NF-kappaB translocation. Cell pretreatment with luteolin abolished LPS effects on NF-kappaB translocation. In addition, luteolin treatment blocked LPS-induced cellular proliferation inhibition without affecting genetic material integrity. We concluded that luteolin interferes with LPS signaling pathways, reducing activation of several mitogen-activated protein kinase family members, and inhibits inflammatory mediator expression.

Actinobacillus actinomycetemcomitans lipopolysaccharide stimulates the phosphorylation of p44 and p42 MAP kinases through CD14 and TLR-4 receptor activation in human gingival fibroblasts.

Tyrosine phosphorylation is an early step in lipopolysaccharide (LPS) stimulated monocytes and macrophages that appears to play a key role in signal transduction. We have demonstrated that LPS purified from Actinobacillus actinomycetemcomitans also increases protein tyrosine phosphorylation in human gingival fibroblasts (HGF). This effect was elicited rapidly after LPS stimulation at concentrations that stimulate anti-bacterial responses in human gingival fibroblasts. Two main proteins, with an apparent molecular weight of 44 and 42 kDa, were phosphorylated after LPS stimulation of the human gingival fibroblasts. The phosphorylation was detected after 5 to 15 min and reached the maximum at 30 min of treatment. The increase in tyrosine phosphorylation was apparent following stimulation with LPS at 10 ng/ml and the response was dose dependent up to 10 microg/ml. Pretreatment with the tyrosine kinase inhibitors, herbimycin A and genistein inhibited the LPS-stimulated phosphorylation of p44 and p42 MAP kinases in a dose dependent manner. Pretreatment of human gingival fibroblasts with antibodies anti-CD14 or anti-TLR-4 but not anti-TLR-2 inhibited the LPS-induced tyrosine phosphorylation of p44 and p42. Additionally, LPS-induced p44 and p42 phosphorylation was inhibited by polymyxin treatment. These findings demonstrate that LPS from A. actinomycetemcomintans increases rapidly p44 and p42 phosphorylation (ERK 1 and ERK 2, respectively) in human gingival fibroblasts. Our data also suggest that CD14 and TLR-4 receptors are involved in the LPS effects in human gingival fibroblasts.

Role of p38 in nitric oxide synthase and cyclooxygenase expression, and nitric oxide and PGE2 synthesis in human gingival fibroblasts stimulated with lipopolysaccharides.

Periodontal disease, a gingival inflammatory disease caused by gram-negative bacteria, is the main cause of tooth loss. Lipopolysaccharides (LPS) present in bacterial cell walls induce human gingival fibroblasts' production of pro-inflammatory cytotoxins such as IL-1beta and TNFalpha. The goal of this study was to determine p38 role in the expression of inducible nitric oxide synthase enzyme (i-NOS) and cyclooxygenase (COX-2), as well as in PGE(2) and nitric oxide synthesis in human gingival fibroblasts challenged with LPS. We found that lipopolysaccharides induced a rapid and significant increase in p38 phosphorylation. After interruption of p38 transduction pathway by pre-treatment with inhibitor SB203580, no response to stimulation with LPS was observed; i-NOS expression and nitric oxide synthesis was completely blocked. However, p38 inhibition only partially blocked COX-2 expression and PGE2 synthesis. We conclude that p38 is critically involved in i-NOS induction, and that it participates in COX-2 expression and in PGE2 synthesis.