ABSTRACT
BACKGROUND: This study aimed to evaluate sociodemographic and clinical factors influencing overall survival (OS) in patients with oral squamous cell carcinoma (OSCC). MATERIAL AND METHODS: Medical charts of 547 patients with OSCC from a public hospital in northeastern Brazil seen between 1999 and 2013 were evaluated. Survival analysis was performed using the Kaplan-Meier method. The influence of age, sex, ethnicity, clinical stage, anatomical location, type of treatment, and comorbidities on the patients' prognosis was evaluated. Cox proportional hazards regression model was used to identify independent prognostic factors. RESULTS: The 5-year OS was 39%. Multivariate analysis showed that age < 40 years (HR = 2.20; 95%CI: 1.02-4.72) and a single treatment modality (HR = 1.91; 95%CI: 1.37-2.67) were associated with a poor prognosis, while early clinical stage resulted in better outcomes (HR = 0.38; 95%CI: 0.25-0.58). CONCLUSIONS: OSCC patients in advanced clinical stages, diagnosed at a younger age, and submitted to a single therapeutic modality have a poorer prognosis.
Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Adult , Brazil , Carcinoma, Squamous Cell/therapy , Humans , Mouth Neoplasms/therapy , Prognosis , Retrospective Studies , Squamous Cell Carcinoma of Head and NeckABSTRACT
Benzofuroxan is an interesting ring system, which has shown a wide spectrum of biological responses against tumor cell lines. We investigated, herein, the antitumor effects of benzofuroxan derivatives (BFDs) in vitro and in a melanoma mouse model. Cytotoxic effects of twenty-two BFDs were determined by MIT assay. Effects of BFD-22 in apoptosis and cell proliferation were evaluated using Annexin V-FITC/PI and CFSE staining. In addition, the effects in the cell cycle were assessed. Flow cytometry, western blot, and fluorescence microscopy analysis were employed to investigate the apoptosis-related proteins and the BRAF signaling. Cell motility was also exploited through cell invasion and migration assays. Molecular docking approach was performed in order to verify the BFD-22 binding mode into the ATP catalytic site of BRAF kinase. Moreover, the BFD-22 antitumor effects were evaluated in a melanoma murine model using B16F10. BFD-22 was identified as a potential hit against melanoma cells. BFD-22 induced apoptosis and inhibited cell proliferation of B16F10 cells. BFD-22 has suppressed, indeed, the migratory and invasive behavior of B16F10 cells. Cyclin D1 and CDK4 expression were reduced leading to cell cycle arrest at G0/G1 phase. Of note, phosphorylation of BRAF at Ser338 was strongly down-regulated by BFD-22 in B16F10 cells. The accommodation/orientation into the binding site of BRAF was similar of BAY43-9006 (co-crystallized inhibitor of BRAF, sorafenib). Importantly, BFD-22 presented in vivo antimetastatic effects and showed better therapeutic efficacy than sorafenib and taxol. BFD-22 can be considered as a new lead compound and, then, can be helpful for the designing of novel drug candidates to treat melanoma. (C) 2016 Elsevier Inc. All rights reserved.
Subject(s)
Pharmacology , Medical Oncology , Allergy and ImmunologyABSTRACT
Background: Eugenol (EUG) is a major phenolic compound present in clove whose anti-cancer properties have been demonstrated previously. These anti-cancer properties may involves the modulation of different mechanisms, including alpha-estrogen receptor (alpha ER) in luminal breast cancer cells, COX-2 inhibition in melanoma cells or p53 and caspase-3 activation in colon cancer cells. Hypothesis: EUG promotes a burst in ROS production causing cell-cycle perturbations, mitochondria toxicity and clastogenesis triggering apoptosis in melanoma breast-and cervix-cancer cells in vitro. Methods: Morphological changes were evaluated through the light-and electronic-microscopy. Cell-cycle, ROS, PCNA and Apoptosis was detected by flow cytometry and clastogenicity was evaluated by Comet-assay. Results: The results obtained herein pointed out that EUG promotes, increasing ROS production leading to abrogation of G2/M of phase of cell-cycle, and consecutively, clastogenesis in vitro. In addition, EUG induces Proliferation Cell Nuclear Antigen (PCNA) downregulation and decreasing in mitochondria potential (Delta Psi m). Of note, a Bax up-regulation was also observed on cells treated with EUG. All of these findings cooperate in order to induce apoptosis in cancer cells. Conclusion: These promising results presented herein shed new light on the mechanisms of action of EUG suggesting a possible applicability of this phenylpropanoid as adjuvant in anti-cancer therapy. (C) 2016 Elsevier GmbH. All rights reserved.
