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dos Santos M.,Federal University of Espirito Santo | dos Santos M.,Laboratorio Of Biologia Molecular Do Hospital Heliopolis | da Cunha Mercante A.M.,Anatomia Patologica do Hospital Heliopolis | Nunes F.D.,University of Sao Paulo | And 11 more authors.
Molecular Biology Reports

Human N-myc downstream-regulated gene 1 (NDRG1) is a metastasis suppressor gene with several potential functions, including cell differentiation, cell cycle regulation and response to hormones, nickel and stress. The purpose of this study was to investigate the immunoexpression of NDRG1 in oral and oropharyngeal squamous cell carcinomas searching for its role in the clinical course of these tumors. We investigated immunohistochemical expression of NDRG1 protein in 412 tissue microarray cores of tumor samples from 103 patients with oral and oropharyngeal squamous cell carcinomas and in 110 paraffin-embedded surgical margin sections. The results showed NDRG1 up-regulation in 101/103 (98.1 %) tumor samples, but no expression in any normal tissue sample. Western blot assays confirmed the immunohistochemical findings, suggesting that lower levels of NDRG1 are associated with a high mortality rate. NDRG1 overexpression was related to long-term specific survival (HR = 0.38; p = 0.009), whereas the presence of lymph-node metastasis showed the opposite association with survival (HR = 2.45; p = 0.013). Our findings reinforce the idea that NDRG1 plays a metastasis suppressor role in oral and oropharyngeal squamous cell carcinomas and may be a useful marker for these tumors. © 2012 Springer Science+Business Media B.V. Source

Biazevic M.G.H.,University of Sao Paulo | Toporcov T.N.,University of Sao Paulo | Antunes J.L.F.,University of Sao Paulo | Rotundo L.D.B.,University of Sao Paulo | And 4 more authors.
Nutrition and Cancer

We examined the association between coffee consumption and oral cancer in a hospital-based case-control study comprising 143 patients with oral and oropharyngeal squamous cell carcinoma attended at 3 major hospitals in Sao Paulo, Brazil, and 240 controls without cancer, recruited from outpatient units of the same hospitals and matched with cases by sex and age. Associations were assessed by multivariate logistic regression conditioned on sociodemographic and behavioral characteristics. Tobacco smoking, alcohol drinking, and higher intake of bacon and deep-fried foods were directly related to disease; the inverse was observed to family income and salad intake. Coffee consumption and tobacco smoking were partially correlated (Spearman correlation coefficient 0.14 among cases, 0.31 among controls). When adjusted for all covariates, a cumulative coffee consumption higher than 18.0 daily liters x year during lifetime was indicated to be protective against disease (adjusted odds ratio 0.39, 95% confidence interval 0.16-0.94, P = 0.037). This observation may have pharmacological implications for clinical medication of these cancers and is relevant to programs aimed at reducing the burden of disease. Copyright © 2011, Taylor & Francis Group, LLC. Source

Nascimento L.A.,University of Sao Paulo | Settanni F.A.P.,University of Sao Paulo | Filho J.F.D.G.,Instituto Do Cancer Arnaldo Vieira Of Carvalho | Sanchez I.N.D.,University of Sao Paulo | And 2 more authors.
International Archives of Otorhinolaryngology

Introduction Schwannoma of the olfactory groove is an extremely rare tumor that can share a differential diagnosis with meningioma or neuroblastoma. Objectives The authors present a case of giant schwannoma involving the anterior cranial fossa and ethmoid sinuses. Case Report The patient presented with a 30-month history of left nasal obstruction, anosmia, and sporadic ipsilateral bleeding. Computed tomography of the paranasal sinuses revealed expansive lesion on the left nasal cavity extending to nasopharynx up to ethmoid and sphenoid sinuses bilaterally with intraorbital and parasellar extension to the skull base. Magnetic resonance imaging scan confirmed the expansive tumor without dural penetration. Biopsy revealed no evidence of malignancy and probable neural cell. Bifrontal craniotomy was performed combined with lateral rhinotomy (Weber-Ferguson approach), and the lesion was totally removed. The tumor measured 8.0-×-4.3-×-3.7 cm and microscopically appeared as a schwannoma composed of interwoven bundles of elongated cells (Antoni A regions) mixed with less cellular regions (Antoni B). Immunohistochemical study stained intensively for vimentin and S-100. Conclusion Schwannomas of the olfactory groove are extremely rare, and the findings of origin of this tumor is still uncertain but recent studies point most probably to the meningeal branches of trigeminal nerve or anterior ethmoidal nerves. Copyright © 2015 by Thieme Publicações Ltd. Source

Lopez R.V.M.,University of Sao Paulo | Zago M.A.,University of Sao Paulo | Eluf-Neto J.,University of Sao Paulo | Curado M.P.,Hospital Araujo Jorge | And 12 more authors.
Brazilian Journal of Medical and Biological Research

The association of education, tobacco smoking, alcohol consumption, and interleukin-2 (IL-2 +114 and -384) and -6 (IL-6 -174) DNA polymorphisms with head and neck squamous cell carcinoma (HNSCC) was investigated in a cohort study of 445 subjects. IL-2 and IL-6 genotypes were determined by real-time PCR. Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (95%CI) of disease-specific survival according to anatomical sites of the head and neck. Mean age was 56 years and most patients were males (87.6%). Subjects with 5 or more years of schooling had better survival in larynx cancer. Smoking had no effect on HNSCC survival, but alcohol consumption had a statistically significant effect on larynx cancer. IL-2 gene +114 G/T (HR = 0.52; 95%CI = 0.15-1.81) and T/T (HR = 0.22; 95%CI = 0.02-3.19) genotypes were associated with better survival in hypopharynx cancer. IL-2 +114 G/T was a predictor of poor survival in oral cavity/oropharynx cancer and larynx cancer (HR = 1.32; 95%CI = 0.61-2.85). IL-2 -384 G/T was associated with better survival in oral cavity/oropharynx cancer (HR = 0.80; 95%CI = 0.45-1.42) and hypopharynx cancer (HR = 0.68; 95%CI = 0.21-2.20), but an inverse relationship was observed for larynx cancer. IL-6 -174 G/C was associated with better survival in hypopharynx cancer (HR = 0.68; 95%CI = 0.26-1.78) and larynx cancer (HR = 0.93; 95%CI = 0.42-2.07), and C/C reduced mortality in larynx cancer. In general, our results are similar to previous reports on the value of education, smoking, alcohol consumption, and IL-2 and IL-6 genetic polymorphisms for the prognosis of HNSCC, but the risks due to these variables are small and estimates imprecise. Source

Rodrigues-Pereira J.,Instituto Do Cancer Arnaldo Vieira Of Carvalho | Kim J.-H.,Yonsei University | Magallanes M.,Military Hospital of Mexico | Lee D.H.,University of Ulsan | And 6 more authors.
Journal of Thoracic Oncology

Introduction: This study compared survival without toxicity in patients with advanced, nonsquamous non-small cell lung cancer who were treated with first-line pemetrexed/carboplatin or docetaxel/carboplatin. Methods: This multicenter, open-label, parallel-group, phase 3 trial comprised patients randomized (1:1) to pemetrexed/carboplatin (n = 128) or docetaxel/carboplatin (n = 132). Patients received treatment on day 1 of each 21-day cycle (maximum of six cycles). Treatment included carboplatin (area under the curve = 5 mg/ml × min) and pemetrexed (500 mg/m) or docetaxel (75 mg/m). The primary outcome measure, survival without treatment-emergent grade 3/4 toxicity, was defined as the time from randomization to the first treatment-emergent grade 3/4 adverse event or death and was analyzed using a log-rank test. The analysis population included 106 patients in the pemetrexed/carboplatin (Pem/Carb) group and 105 patients in the docetaxel/carboplatin (Doc/Carb) group. Results: Survival without treatment-emergent grade 3/4 toxicity was significantly longer in the Pem/Carb versus the Doc/Carb group (log-rank p < 0.001; median survival without treatment-emergent grade 3/4 toxicity: 3.2 versus 0.7 months; adjusted hazard ratio = 0.45 [95% confidence interval: 0.34-0.61]). Overall survival was similar in the Pem/Carb versus the Doc/Carb group (log-rank p = 0.934; median survival: 14.9 versus 14.7 months; adjusted hazard ratio = 0.93 [95% confidence interval: 0.66-1.32]). Compared with the Doc/Carb group, fewer patients in the Pem/Carb group experienced grade 3/4 drug-related, treatment-emergent neutropenia, leukopenia, or febrile neutropenia, and more patients experienced anemia and thrombocytopenia. There were three study drug-related deaths during treatment in each group. Conclusions: The favorable benefit-to-risk profile of pemetrexed/carboplatin suggests that pemetrexed/carboplatin is an appropriate first-line treatment option for chemonaïve patients with advanced, nonsquamous non-small cell lung cancer. Copyright © 2011 by the International Association for the Study of Lung Cancer. Source

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