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Sobral L.M.,University of Sao Paulo | Mercante A.M.C.,Hospital Heliopolis | Xavier F.C.A.,Federal University of Bahia | Guimaraes D.M.,University of Sao Paulo | And 9 more authors.
PLoS ONE | Year: 2012

The prediction of tumor behavior for patients with oral carcinomas remains a challenge for clinicians. The presence of lymph node metastasis is the most important prognostic factor but it is limited in predicting local relapse or survival. This highlights the need for identifying biomarkers that may effectively contribute to prediction of recurrence and tumor spread. In this study, we used one- and two-dimensional gel electrophoresis, mass spectrometry and immunodetection methods to analyze protein expression in oral squamous cell carcinomas. Using a refinement for classifying oral carcinomas in regard to prognosis, we analyzed small but lymph node metastasis-positive versus large, lymph node metastasis-negative tumors in order to contribute to the molecular characterization of subgroups with risk of dissemination. Specific protein patterns favoring metastasis were observed in the "more-aggressive" group defined by the present study. This group displayed upregulation of proteins involved in migration, adhesion, angiogenesis, cell cycle regulation, anti-apoptosis and epithelial to mesenchymal transition, whereas the "less-aggressive" group was engaged in keratinocyte differentiation, epidermis development, inflammation and immune response. Besides the identification of several proteins not yet described as deregulated in oral carcinomas, the present study demonstrated for the first time the role of cofilin-1 in modulating cell invasion in oral carcinomas. © 2012 Polachini et al.


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 | Year: 2011

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.


Hoff P.M.,University of Sao Paulo | Hoff P.M.,Hospital Sirio Libanes | Hochhaus A.,Universitatsklinikum Jena | Pestalozzi B.C.,University of Zürich | And 12 more authors.
Journal of Clinical Oncology | Year: 2012

Purpose: Cediranib is a highly potent inhibitor of vascular endothelial growth factor (VEGF) signaling with activity against all three VEGF receptors. HORIZON II [Cediranib (AZD2171, RECENTIN) in Addition to Chemotherapy Versus Placebo Plus Chemotherapy in Patients With Untreated Metastatic Colorectal Cancer] assessed infusional fluorouracil, leucovorin, and oxaliplatin/ capecitabine and oxaliplatin (FOLFOX/CAPOX) with or without cediranib in patients with previously untreated metastatic colorectal cancer (mCRC). Patients and Methods: Eligible patients were initially randomly assigned 1:1:1 to receive cediranib (20 or 30 mg per day) or placebo plus FOLFOX/CAPOX. In an early analysis of this and two other cediranib studies (HORIZON I [Cediranib Plus FOLFOX6 Versus Bevacizumab Plus FOLFOX6 in Patients With Previously Treated Metastatic Colorectal Cancer] and HORIZON III [Cediranib Plus FOLFOX6 Versus Bevacizumab Plus FOLFOX6 in Patients With Untreated Metastatic Colorectal Cancer]), the 20-mg dose met the predefined criteria for continuation. Subsequent patients were randomly assigned 2:1 to the cediranib 20 mg or placebo arms. Progression-free survival (PFS) and overall survival (OS) were coprimary end points. Results: In all, 860 patients received cediranib 20 mg (n = 502) or placebo (n = 358). The addition of cediranib to FOLFOX/CAPOX resulted in PFS prolongation (hazard ratio [HR], 0.84; 95% CI, 0.73 to 0.98; P = .0121; median PFS, 8.6 months for cediranib v 8.3 months for placebo) but had no impact on OS (HR, 0.94; 95% CI, 0.79 to 1.12; P = .5707; median OS, 19.7 months for cediranib v 18.9 months for placebo). There were no significant differences in the secondary end points of objective response rate, duration of response, or liver resection rate. Median chemotherapy dose-intensity was decreased by approximately 10% in patients treated with cediranib. Adverse events (AEs) associated with cediranib were manageable. Conclusion: Addition of cediranib 20 mg to FOLFOX/CAPOX resulted in a modest PFS prolongation, but no significant difference in OS. The cediranib AE profile was consistent with those from previous studies. Because of the lack of improvement in OS, cediranib plus an oxaliplatin-based regimen cannot be recommended as a treatment for patients with mCRC. © 2012 by American Society of Clinical Oncology.


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 | Year: 2011

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.


Boing A.F.,Federal University of Santa Catarina | Antunes J.L.F.,Federal University of Santa Catarina | Antunes J.L.F.,University of Sao Paulo | de Carvalho M.B.,Hospital Heliopolis | And 6 more authors.
Journal of Epidemiology and Community Health | Year: 2011

Background A higher burden of head and neck cancer has been reported to affect deprived populations. This study assessed the association between socioeconomic status and head and neck cancer, aiming to explore how this association is related to differences of tobacco and alcohol consumption across socioeconomic strata. Methods We conducted a case-control study in São Paulo, Brazil (1998e2006), including 1017 incident cases of oral, pharyngeal and laryngeal cancer, and 951 sexand age-matched controls. Education and occupation were distal determinants in the hierarchical approach; cumulative exposure to tobacco and alcohol were proximal risk factors. Outcomes of the hierarchical model were compared with fully adjusted ORs. Results Individuals with lower education (OR 2.27; 95% CI 1.61 to 3.19) and those performing manual labour (OR 1.55; 95% CI 1.26 to 1.92) had a higher risk of disease. However, 54% of the association with lower education and 45% of the association with manual labour were explained by proximal lifestyle exposures, and socioeconomic status remained significantly associated with disease when adjusted for smoking and alcohol consumption.


PubMed | Instituto Do Cancer Arnaldo Vieira Of Carvalho, University of Brasilia and University of Sao Paulo
Type: Journal Article | Journal: International archives of otorhinolaryngology | Year: 2015

IntroductionSchwannoma of the olfactory groove is an extremely rare tumor that can share a differential diagnosis with meningioma or neuroblastoma. ObjectivesThe authors present a case of giant schwannoma involving the anterior cranial fossa and ethmoid sinuses. Case ReportThe 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 8.04.33.7 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. ConclusionSchwannomas 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.


Naime F.F.,Instituto Paulista Of Cancerologia | Naime F.F.,Conjunto Hospitalar do Mandaqui | Naime F.F.,Instituto Do Cancer Arnaldo Vieira Of Carvalho | Fakhouri F.,Conjunto Hospitalar do Mandaqui | And 2 more authors.
Rare Tumors | Year: 2012

Multicentric Castleman's disease (MCD) is a rare lymphoproliferative disorder. It is found with higher frequency in patients with HIV infection, with systemic symptoms and poor prognosis. We present the case of a 32-year old man with HIV disease, Kaposi's sarcoma, lymphadenopathy, fever and hemolytic anemia. A diagnosis of Castleman's disease is confirmed through biopsy and treatment is often based only on published case reports. Systemic treatments for MCD have included chemotherapy, anti-herpes virus, highly active antiretroviral therapy and, more recently, monoclonal antibodies against both IL6 and CD20. © F.F. Naime et al., 2012 Licensee PAGEPress, Italy.


PubMed | Instituto Do Cancer Arnaldo Vieira Of Carvalho
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016

7355 Background: Lung cancer is a common disease in elderly patients. However, age alone is a very uncertain prognostic criteria for outcome and tolerance to treatment. Despite some meta-analysis have shown that performance status is a better criteria for treatment decision, elderly patients were poorly represented.We analyzed data from 82 patients aged 80 or older with NSCLC admitted at our institution from august 1998 to july 2003. Thirty-eight patients (46,3%) received any chemotherapy regimen.Average age was 82 years. Most patients (73,2%) were men, 90.2% were ECOG PS 2 or less, 67 patients (81.7%) were clinical stage IIIB or IV and the most common histologic type was squamous-cell carcinoma. Median survival for all patients was 13.4 weeks. Patients that received chemotherapy had a significantly longer median survival compared to those that did not, 28.3 versus 8 weeks, respectively. Thirty patients (79%) from the chemo treated group received Carboplatin AUC 4 day 1 plus Vinorelbine 25 mg/m


PubMed | Instituto Do Cancer Arnaldo Vieira Of Carvalho
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016

17125 Background: Small cell lung cancer (SCLC) is an aggressive disease characterized by rapid growth and early metastasis. Actually, the treatment of choice for advanced SCLC is cisplatin combined with etoposide. For these patients 9 to 12 months are the expected survival, overall response is 61%-78 % and complete response rate is 10%-14%. Despite of these results 5 years overall survival is less than 5% justifying the search for more effective treatment scheme.Fourteen patients were analyzed between January and October 2005. They received Cisplatin 80 mg/mPatients received 2-6 cycles (median = 3.78 ); KPS was 50%-90% (median 80%); median age 57 yrs (range 21-75). Thirteen patients had objective response (92.8%), 4 complete response (28.6%) and 9 partial response (64.3%). Non-hematological grade (G) 3-4 toxicity consisted of nausea and vomiting (28.6%); anorexia (42.8%); neurotoxicity (14.5%). Only one patient (7.1%) had neutropenia G3 and another subject (7.1%) had thrombocytopenia G3. There were no febrile neutropenia cases.Although a large study should be performed to confirm these results, PGV association shows promising activity in SCLC patients. Toxicity profile was very favorable too. [Table: see text] No significant financial relationships to disclose.


PubMed | Instituto Do Cancer Arnaldo Vieira Of Carvalho
Type: Clinical Trial, Phase III | Journal: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer | Year: 2011

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.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(2)) or docetaxel (75 mg/m(2)). 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.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.The favorable benefit-to-risk profile of pemetrexed/carboplatin suggests that pemetrexed/carboplatin is an appropriate first-line treatment option for chemonave patients with advanced, nonsquamous non-small cell lung cancer.

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