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Schrago C.G.,Federal University of Rio de Janeiro | Menezes A.N.,Instituto Nacional do Cancer | Moreira M.A.M.,Instituto Nacional do Cancer | Seuanez H.N.,Federal University of Rio de Janeiro | Seuanez H.N.,Instituto Nacional do Cancer
PLoS ONE | Year: 2012

The evolution of Neotropical Primates (NP) is permeated by factors associated with the pattern of diversification and the biogeography of the major lineages. These questions can be better understood by providing a robust estimate of the chronological scenario of NP evolution, a reason why molecular dating methods have been widely applied. One aspect of especial interest is the timing of diversification of the major NP lineages (pitheciids, atelids and cebids), which may have resulted from rapid episodes of adaptive radiation, a question that requires NP divergence time estimates with accurate statistical certainty. In this study, we evaluated the primate timescale focused on the age of nodes of NP radiation. We investigated the performance of complete primate mitochondrial genomes as traditional molecular markers of primate evolution and further including original mitochondrial data from the endangered muriqui, Brachyteles arachnoides (Accession No. JX262672). Comparisons of the age estimates at NP nodes based on mitochondrial genomes with those obtained from a nuclear supermatrix showed similar degrees of uncertainty. Further molecular data and more informative calibration priors are required for a more precise understanding of the early NP diversification. © 2012 Schrago et al.

Panis C.,Instituto Nacional do Cancer | Panis C.,State University Londrina | Pizzatti L.,Instituto Nacional do Cancer | Herrera A.C.,State University Londrina | And 3 more authors.
Cancer Letters | Year: 2013

This study evaluated the plasmatic proteomic profile of breast cancer patients in the early (ED) and advanced (AD) stages, employing high-throughput proteomics. We identified 92 differentially expressed proteins in ED and 73 proteins in AD patients. Gelsolin, lumican, clusterin, SALL4 and PMS2, as well hTERT, TNF-α and GRHL3 were chosen for further investigation. ED presented augmented expression of GRHL3 and reduced circulating TNF-α with high expression of GRHL3 in tumors. AD displayed high TNF-α and a significant expression of PMS2 in tumors. These findings suggest processes enrolling stem cell division in ED, with TNF-α signaling and DNA mismatch repair in the advanced stage. © 2012.

Boldrini E.,Hospital do Cancer do Barretos | Peres S.V.,Hospital do Cancer do Barretos | Morini S.,Hospital do Cancer do Barretos | De Camargo B.,Instituto Nacional do Cancer
Journal of Pediatric Hematology/Oncology | Year: 2010

Background: Metastasis is an important prognostic factor among patients with osteosarcoma. It has been reported that ezrin is important in enabling metastasis and that CD44 expression leads to functional increases in ezrin activation. Objective: The aim of this study was to correlate ezrin and CD44 expression with prognosis. Samples and Methods: Patients with a diagnosis of osteosarcoma who had been treated at Hospital de Cancer de Barretos, Barretos, SP, Brazil, between 2000 and 2005 were selected from the Hospital Tumor Registry. Fifty-two patients and, among these, 34 surgical biopsy specimens of osteosarcoma before chemotherapy were reviewed by the Pathology Department. Ezrin and CD44H protein expression was evaluated using immunohistochemistry on the initial biopsy for these 34 samples. Results: Most patients (76%) were ezrin-positive in cytoplasm and membrane (38.2%); 58.9% presented high-intensity staining and 50.0% had high scores. Half of the patients were CD44H-positive, predominantly in cytoplasm (38.2%); 20.6% presented staining in more than 50% of the cells. None of the markers showed associations with any of the clinicopathologic variables studied. Among the ezrin-positive patients, the 5-year survival rate was 12.8%, whereas it was 41.7% among ezrin-negative patients (P = 0.121). The interaction between ezrin and poor histologic response among nonmetastatic patients showed an association with relapse-free 5-year survival of 100% versus 12.7% (P=0.042). The overall survival rates for CD44-positive and negative patients were similar (21.5% and 25.3%, respectively) (P=0.676). Conclusions: Neither CD44H nor ezrin immunoexpression could predict the prognosis for patients with osteosarcoma in our small sample. Copyright © 2010 by Lippincott Williams & Wilkins.

De Camargo B.,Instituto Nacional Of Cancer | De Oliveira Santos M.,Instituto Nacional do Cancer | Rebelo M.S.,Instituto Nacional do Cancer | De Souza Reis R.,Instituto Nacional do Cancer | And 3 more authors.
International Journal of Cancer | Year: 2010

The Brazilian Population-Based Cancer Registry (PBCR) was started in 1967; today there are 20 PBCRs in Brazil. We report the first descriptive analysis of the incidence of childhood cancer based on data from 14 PBCRs, corresponding to 15% of the child and adolescent population in Brazil. Data were obtained from registry databases, including information on population coverage and data quality indicators. The International Classification of Childhood Cancer was used. Age-adjusted rates were calculated by world population. Incidence by cancer registry, age, sex, and cancer type were calculated per 1,000,000 children. Age-adjusted rates per 1,000,000 children/adolescents ranged from 92 to 220 among the 14 PBCRs. The principal groups of cancers were leukemia, lymphoma and central nervous tumors. The median incidence rate of childhood cancer in the 14 PBCRs was 154.3 per million; children 1-4 years of age had the highest incidence rates. The Brazilian PBCRs provide important information about pediatric cancer incidence in an emerging country. The observed incidence rates of childhood leukemia were similar to previous reported rates, and the age-specific incidence rates of retinoblastoma (0-4 years of age) were higher than those for developed countries. These data can be used as baseline incidence rates of childhood and adolescent cancer in Brazil in future epidemiological studies. © 2009 UICC.

Suarez-Kurtz G.,Instituto Nacional Do Cancer | Pena S.D.,Federal University of Minas Gerais | Hutz M.H.,Federal University of Rio Grande do Sul
Pharmacogenomics | Year: 2012

Background: New drug applications submitted to regulatory agencies in developing countries rarely include data from local clinical trials. We used the FST statistics to explore the pharmacogenomic diversity of the Brazilian population and its potential implications in drug regulatory assessment and decisions. Methods: The FST analyses were based on data for 44 polymorphisms in 12 pharmacogenes among 1034 healthy Brazilians, recruited in four different geographical regions and self-identified as branco (white) pardo (brown) or preto (black). Each region/color group comprised 83-89 individuals. The Utah residents of northern and western European ancestry and Yoruba people from Nigeria, Africa, cohorts of the HapMap project were used as proxies of the European and sub-Saharan African ancestral roots of Brazilians, respectively. Results: Allele-specific FST values for the overall Brazilian cohort revealed low genetic divergence between white and brown (F ST = 0.005 ± 0.006, mean ± standard deviation), white and black (0.013 ± 0.017) and brown and black (0.004 ± 0.005) individuals. However, the distribution of FST values for white vs brown (p < 0.0001, analysis of variance) and white vs black (p < 0.0001) differed significantly across the geographical regions. Considerably larger pharmacogenomic divergence was observed between black Brazilians and Yoruba people from Nigeria, Africa (FST = 0.028 ± 0.035) compared to white Brazilians vs Utah residents of northern and western European ancestry (0.007 ± 0.010). Conclusion: The present FST analyses highlight the challenge faced by Brazilian regulatory agencies when assessing the relevance to Brazilians of pharmacogenomic data derived from foreign populations, with distinct biogeographical ancestries. This challenge is compounded by the heterogeneity of the Brazilian population with respect to the frequency distribution of pharmacogenomic polymorphisms across color categories and geographical regions. © 2012 Future Medicine Ltd.

Suarez-Kurtz G.,Instituto Nacional Do Cancer | Paula D.P.,Federal Rural University of Rio de Janeiro | Struchiner C.J.,Programa de Computacao Cientifica
Pharmacogenomics | Year: 2014

The heterogeneous Brazilian population, with European, African and Amerindian ancestral roots is a model case for exploring the impact of population admixture on the frequency distribution of polymorphisms in pharmacogenes, and the design and interpretation of pharmacogenomics trials. Examples drawn from studies carried out by researchers of the Brazilian pharmacogenomics network, support the following conclusions: the distribution of polymorphisms varies across geographical regions and self-reported 'race/color categories, and is best modeled as continuous functions of individual proportions of European and African ancestry; the differential frequency of polymorphisms impacts the calculations of sample sizes required for adequate statistical power in clinical trials performed in different segments of the Brazilian population; and extrapolation of pharmacogenomics data from well-defined ethnic groups to Brazilians is plagued with uncertainty. Data for warfarin and tacrolimus are reviewed to highlight the advantages and challenges of performing pharmacogenomic trials in Brazilians. © 2014 Future Medicine Ltd.

The study aimed to reflect, based on the theoretical framework of Max Scheler, about the ethical dilemmas experienced by nurses in the ICU, and about the values that guide their actions and decisions,. This is qualitative research, and ten ICU nurses have been interviewed at a university hospital. It was identified the experience of ethical dilemmas related to the terminality related to the limits of intervention and use of material resources, as well as the issue of blood transfusion in case of religious restrictions. The values identified were: respect, dignity of the patient, scientific knowledge, humility, passion for the profession and love of God. The theory of values is an important tool for nursing because it allows the approach of an ethics of humanizing praxis, especially in situations of ethical dilemmas.

Vasconcellos-Silva P.R.,Instituto Nacional do Cancer | Griep R.H.,Escola Nacional de Saude Publica Sergio Arouca Fiocruz | De Souza M.C.,Coordenacao de Prevencao e Vigilancia
Ciencia e Saude Coletiva | Year: 2015

Internet search patterns associated with “windows” of collective interest have been increasingly investigated in the field of public health. This article sets out to identify search patterns relating to the quest for information on skin protection after the perception of excessive exposure to UV radiation - the so-called “summer effect” as it is commonly referred to in Brazil. To calculate the number of hits on the Brazilian National Cancer Institute website - a renowned source of information resources on prevention - log analyzer software was used to measure the volume of hits on specific content pages. The pages on skin protection and self-examination (pages of interest) were monitored over a 48-month period. It was seen that, although the monthly average of hits on pages of interest revealed statistically significant annual growth, the results for the analysis of variance showed no significant differences between the number of hits in the summer compared with other months (p = 0.7491). In short, the perception of intense exposure to the summer sun did not encourage further interest to search for information on prevention. © 2015, Associacao Brasileira de Pos - Graduacao em Saude Coletiva. All rights reserved.

The epidermal growth factor receptor (EGFR) is differently expressed in breast cancer, and its presence may favor cancer progression. We hypothesized that two EGFR functional polymorphisms, a (CA)n repeat in intron 1, and a single nucleotide polymorphism, R497K, may affect EGFR expression and breast cancer clinical profile. The study population consisted of 508 Brazilian women with unilateral breast cancer, and no distant metastases. Patients were genotyped for the (CA)n and R497K polymorphisms, and the associations between (CA)n polymorphism and EGFR transcript levels (n = 129), or between either polymorphism and histopathological features (n = 505) were evaluated. The REMARK criteria of tumor marker evaluation were followed. (CA)n lengths ranged from 14 to 24 repeats, comprehending 11 alleles and 37 genotypes. The most frequent allele was (CA)16 (0.43; 95% CI = 0.40-0.46), which was set as the cut-off length to define the Short allele. Variant (CA)n genotypes had no significant effect in tumoral EGFR mRNA levels, but patients with two (CA)n Long alleles showed lower chances of being negative for progesterone receptor (ORadjusted = 0.42; 95% CI = 0.19-0.91). The evaluation of R497K polymorphism indicated a frequency of 0.21 (95% CI = 0.19 - 0.24) for the variant (Lys) allele. Patients with variant R497K genotypes presented lower proportion of worse lymph node status (pN2 or pN3) when compared to the reference genotype Arg/Arg (ORadjusted = 0.32; 95% CI = 0.17-0.59), which resulted in lower tumor staging (ORadjusted = 0.34; 95% CI = 0.19-0.63), and lower estimated recurrence risk (OR = 0.50; 95% CI = 0.30-0.81). The combined presence of both EGFR polymorphisms (Lys allele of R497K and Long/Long (CA)n) resulted in lower TNM status (ORadjusted = 0.22; 95% CI = 0.07-0.75) and lower ERR (OR = 0.25; 95% CI = 0.09-0.71). When tumors were stratified according to biological classification, the favorable effects of variant EGFR polymorphisms were preserved for luminal A tumors, but not for other subtypes. The data suggest that the presence of the variant forms of EGFR polymorphisms may lead to better prognosis in breast cancer, especially in patients with luminal A tumors.

Panis C.,Instituto Nacional do Cancer | Pizzatti L.,Instituto Nacional do Cancer | Abdelhay E.,Instituto Nacional do Cancer
Current Proteomics | Year: 2013

Although proteomics is a very recently developed science, important advances have already occurred in this field. There is growing interest in the scientific community for using this technology as a high-throughput innovative strategy for biomarker discovery in the field of cancer research. However, certain challenges must be overcome before reaching this goal. The basis for discovering reliable biomarkers is rooted in technical and biological parameters. The main biological limit is outlining tumor heterogeneity, while methodological issues include appropriate study designs, the use of sensitive technologies for screening, and the employment of confident strategies for data validation. This review focuses on the major questions related to the strengths and limitations of the development of cancer biomarkers by pro-teomic-based studies. © 2013 Bentham Science Publishers.

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