Letícia Martins Lamarão

Fundação Hemopa

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Rommel Mário Rodríguez Burbano

Universidade Federal do Pará

Caroline Aquino Moreira-Nunes

Universidade Federal do Ceará

Paulo Pimentel de Assumpção

Universidade Federal do Pará

Jersey Heitor da Silva Maués

Universidade Estadual de Campinas (UNICAMP)

Maurício Koury Palmeira

Fundação Hemopa

Giovanny R. Pinto

Universidade Federal do Delta do Parnaíba

Raquel Carvalho Montenegro

Universidade Federal do Ceará

Maria Salete Maciel de Lima

Fundação Hemopa

Juan A. Rey

Industrial University of Santander

Renata Bezerra Hermes de Castro

Fundação Hemopa

Cooperative Institutions

Universidade Federal do Pará

Instituto Evandro Chagas

Fundação Hemopa

Foundation Center

Ministério da Saúde

Universidade do Estado do Pará

Ministério da Saúde

Universidade da Amazônia

Universidade Federal de São Paulo

Secretaria da Saúde

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Genetic screening analysis of patients with hereditary diffuse gastric cancer from northern and northeastern Brazil

Hereditary Cancer in Clinical Practice (2014)

Caroline Aquino Moreira-Nunes Mariceli Baia Leão Barros Bárbara do Nascimento Borges Raquel Carvalho Montenegro Letícia Martins Lamarão

Hereditary diffuse gastric cancer (HDGC) is a hereditary autosomal inherited syndrome associated with CDH1 germline mutations. In Brazil, gastrointestinal tumors are among the most prevalent tumor types and constitute a serious public health problem, especially in the northern and northeastern regions. This study aimed to investigate germline mutations, methylation pattern and genomic rearrangements in the CDH1 gene and quantitative changes in the DNA of HDGC patients in northern and northeastern Brazil.Twenty-seven DNA samples from the members of four families affected by HDGC were analyzed using array comparative genomic hybridization (aCGH), DNA sequencing and methylation pattern.No evidence of gain and loss events or any rearrangements were found in any of the samples tested using aCGH. No promoter region hypermethylation was observed either. Two of the four families presented different types of germline mutations. The 185G > T and 1018A > G germline mutations detected in this study have been described in Asian and European families, respectively. The ancestors of the two families carrying these mutations had originated from those continents.This is the first study to evaluate CDH1 gene germline mutations in Brazilian families with HDGC. In our study, 50% of the families showed no CDH1 gene alterations, and it is possible that in regions with a high incidence of gastric cancer, such as northern and northeastern Brazil, environmental factors might have induced the different genetic alterations analyzed in this study.

CDH1

Comparative genomic hybridization

Human genetics

genomic DNA

10.1186/1897-4287-12-18

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Citations (24)

RT-PCR for confirmation of echovirus 30 isolated in Belém, Brazil

The Brazilian Journal of Infectious Diseases (2007)

Maria de Lourdes Contente Gomes Lauze Lee Alves Ferreira Rodrigo Henryque Gomes Letícia Martins Lamarão Edna da Silveira

Echovirus (Echo) 30 or human enterovirus B is the most frequent enterovirus associated with meningitis cases. Epidemics and outbreaks of this disease caused by Echo 30 have occurred in several countries. In Brazil, Echo 30 has been isolated from sporadic cases and outbreaks that occurred mainly in the south and southeast regions. We used RT-PCR to examine Echo 30 isolates from meningitis cases detected from March 2002 to December 2003 in Belém, state of Pará, in northern Brazil. The patients were attended in a Basic Health Unit (State Health Secretary of Pará), where cerebrospinal fluid (CSF) was collected and stored in liquid nitrogen. Weekly visits were made by technicians from Evandro Chagas Institute to the health unit and samples were stored at -70 degrees C in the laboratory until use. HEp-2 and RD cell lines were used for viral isolation and neutralization with specific antisera for viral identification. RNA extraction was made using Trizol reagent. The RT-PCR was made in one step, and the total mixture (50 microL) was composed of: RNA, reaction buffer, dNTP, primers, Rnase inhibitor, reverse transcriptase, Taq polymerase and water. The products were visualized in agarose gel stained with ethidium bromide, visualized under UV light. Among the 279 CSF samples examined, 30 (10.7%) were EV positive, 29 being Echo 30 and one was Cox B. Nineteen Echo 30 were examined with RT-PCR; 18 tested positive (762 and 494 base pairs). The use of this technique permitted viral identification in less time than usual, which benefits the patient and is of importance for public-health interventions.

Echovirus

Trizol

Aseptic meningitis

Ethidium bromide

10.1590/s1413-86702007000400006

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Gastric Cancer Cell Lines Have DifferentMYC-Regulated Expression Patterns but Share a Common Core of Altered Genes

Canadian Journal of Gastroenterology and Hepatology (2018)

Jersey Heitor da Silva Maués Helem Ferreira Ribeiro Giovanny R. Pinto Luana de Oliveira Lopes Letícia Martins Lamarão

MYC is an oncogene responsible for excessive cell growth in cancer, enabling transcriptional activation of genes involved in cell cycle regulation, metabolism, and apoptosis, and is usually overexpressed in gastric cancer (GC). By using siRNA and Next-Generation Sequencing (NGS), we identified MYC -regulated differentially expressed Genes (DEGs) in three Brazilian gastric cancer cell lines representing the histological subtypes of GC (diffuse, intestinal, and metastasis). The DEGs were picked using Sailfish software, followed by Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis using KEGG. We found 11 significantly enriched gene sets by using enrichment score (ES), False Discovery Rate (FDR), and nominal P-values. We identified a total of 5.471 DEGs with correlation over (80%). In diffuse-type and in metastatic GC cell lines, MYC -silencing caused DEGs downregulation, while the intestinal-type GC cells presented overall DEGs upregulation after MYC siRNA depletion. We were able to detect 11 significant gene sets when comparing our samples to the hallmark collection of gene expression, enriched mostly for the following hallmarks: proliferation, pathway, signaling, metabolic, and DNA damage response. When we analyzed our DEGs considering KEGG metabolic pathways, we found 12 common branches covering a wide range of biological functions, and three of them were common to all three cell lines: ubiquitin-mediated proteolysis, ribosomes, and system and epithelial cell signaling in Helicobacter pylori infection. The GC cell lines used in this study share 14 MYC- regulated genes, but their gene expression profile is different for each histological subtype of GC. Our results present a computational analysis of MYC -related signatures in GC, and we present evidence that GC cell lines representing distinct histological subtypes of this disease have different MYC -regulated expression profiles but share a common core of altered genes. This is an important step towards the understanding of MYC ’s role in gastric carcinogenesis and an indication of probable new drug targets in stomach cancer.

Expression (computer science)

10.1155/2018/5804376

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Citations (14)

Quantitative difference of oral pathogen between individuals with gastric cancer and individuals without cancer

Oncotarget (2021)

Gyselle Ribeiro de Carvalho Oliveira Carla de Castro Sant’ Anna Letícia Martins Lamarão Adriana Costa Guimarães Carlos Alberto Machado da Rocha

// Gyselle Ribeiro de Carvalho Oliveira 1 , Carla de Castro Sant' Anna 2 , 3 , Letícia Martins Lamarão 4 , Adriana Costa Guimarães 5 , Carlos Machado da Rocha 5 , Marcelo de Oliveira Bahia 6 , Carolina Rosal de Souza 6 , Danielle Queiroz Calcagno 2 , Paulo Pimentel de Assumpção 2 and Rommel Rodriguez Burbano 2 , 3 , 6 1 School of Dentistry, Federal University of Pará, Belém, Pará, Brazil 2 High Complexity Oncology Unit, Federal University of Pará, Rua dos Mundurucus, Hospital Universitário João de Barros Barreto, 2º piso da UNACOM, Belém, Pará, Brazil 3 Ophir Loyola Hospital, Av. Gov Magalhães Barata, Belem, Pará, Brazil 4 Foundation Center for Hemotherapy and Hematology, Travessa Padre Eutíquio, Belém, Pará, Brazil 5 Federal Institute of Pará, Belém, Pará, Brazil 6 Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil Correspondence to: Carla de Castro Sant' Anna, email: santannacarla@yahoo.com.br Keywords: periodontal disease; microbiome; gastric cancer; oral pathogens Received: December 08, 2020 Accepted: July 13, 2021 Published: August 17, 2021 Copyright: © 2021 Oliveira et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT The loss of teeth and lack of oral hygiene have been associated with the risk of developing gastric cancer (GC) in several populations evidenced in epidemiological studies. In this study, we quantitatively compared the proportion of oral pathogens in individuals with gastric cancer and individuals without cancer in a referral hospital in the city of Belém, Brazil. This study evaluated 192 patients with GC and 192 patients without cancer. Periodontal clinical examination was performed, and all individuals were submitted to the collection of salivary and dental biofilms. When comparing the median periodontal indexes in the gastric and cancer-free groups, it was statistically significant ( p < 0.001) in the gastric cancer group compared to the probing depth of the periodontal pocket. Levels of bacterial DNA were observed in saliva and dental plaque, with a statistically significant difference ( p < 0.001) between individuals with cancer and without neoplasia in all the bacteria surveyed. Significant relationships ( p < 0.001) between biological agents and GC have been found in bacterial species that cause high rates of periodontal pathology and caries. The results suggest a different quantitative association in the presence of oral pathogens between individuals without cancer and patients with GC. As noted, it cannot be said that the bacteria present in the oral cavity increase the risk of gastric cancer or are aggravating factors of the disease. However, it is worth mentioning that, as it is part of the digestive system, the lack of care for the oral cavity can negatively affect the treatment of patients with gastric cancer.

10.18632/oncotarget.28034

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Citations (4)

Prevalence of Dengue Virus, Chikungunya and Zika Infection in Blood Donors of Northern of Brazil

Research Square (Research Square) (2021)

Letícia Martins Lamarão Angelita Silva Miranda Corrêa Renata Bezerra Hermes de Castro Carlos Eduardo de Melo Amaral Patrícia Danin Jordão Monteiro

Abstract We identified the prevalence of infection by the Dengue virus, Chikungunya and Zika in blood donors in epidemic and non-epidemic periods in the State of Pará, in Northern Brazil, we classify the donors (symptomatic or asymptomatic) and the possibility of this screening being carried out in a sample pool.

Zika Virus

Chikungunya fever

Asymptomatic carrier

10.21203/rs.3.rs-600092/v2

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Citations (0)

Prevalence, incidence and residual risk of transfusion-transmitted HBV infection before and after the implementation of HBV-NAT in northern Brazil

PLoS ONE (2018)

Angelita Silva de Miranda Corrêa Letícia Martins Lamarão Priscilla Cristina Moura Vieira Renata Bezerra Hermes de Castro Núbia Caroline Costa de Almeida

Nucleic acid testing (NAT) for virus detection during blood screening has helped to prevent transfusion-transmitted infections worldwide. In northern Brazil, NAT was implemented in 2012 for HIV and HCV and more recently, in January 2015, the screening for HBV was included and currently used concomitant with serological tests (HBsAg and anti-HBc). This study aims to evaluate the prevalence and the incidence of HBV infection among voluntary blood donors at ten regional blood centers of HEMOPA Foundation in Pará state and to compare the residual risk of transfusion-transmitted HBV infection before and after the Brazilian HBV-NAT implementation.The prevalence (restricted to first time donors- FT) and seroconversion rate (restricted to repeat donors- RP) of HBV were calculated based on rates of confirmed positive samples. Residual risk was based on the incidence and window period (WP) model described by Schreiber and coauthors. Logistic and Poisson regression were used in the statistical analysis by SPSS v20.0. A p value <0.05 was considered statistically significant.HBV prevalence in the periods before and after the implementation of HBV-NAT were 247 and 251 per 100,000 donations, respectively. Seroconversion rates were 114 and 122 per 100,000 donations in the two periods, respectively. The residual risk (RR) for HBV decreased significantly in the posterior period to the HBV-NAT implementation, when compared to RR before implementation, with a reduction of 1:144,92 to 1:294,11 donations (p <0,001).The RR to HBV decreased after the implementation of HBV-NAT, increasing significantly the transfusional security in the North region of Brazil at HEMOPA Foundation.

Seroconversion

Residual risk

Nat

Window period

10.1371/journal.pone.0208414

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Citations (11)

Human pegivirus (HPgV, GBV-C) RNA prevalence, genome characterization and association with HIV coinfection among volunteer blood donors from a public hemotherapy service in Northern Brazil.

Research Square (Research Square) (2020)

Aniel de Sarom Negrão Silva Clayton Silva Rafael Ribeiro Barata Pedro Silva Patrícia Danin Jordão Monteiro

Abstract BackgroundHuman pegivirus (HPgV) - formerly known as GBV-C - is a member of the Flaviviridae family and belongs to the species Pegivirus C. It is a non-pathogenic virus and is transmitted among humans mainly through the exposure to contaminated blood and is often associated with human immunodeficiency virus (HIV) infection. This study aimed to determine the prevalence of HPgV viremia, its association with HIV and clinical epidemiological factors, as well as the full-length sequencing and genome characterization of HPgV recovered from blood donors of the HEMOPA Foundation in Belém-PA-BrazilMethodsPlasma samples were obtained from 459 donors, tested for the presence of HPgV RNA by the RT-qPCR. From these, a total of 26 RT-qPCR positive samples were submitted to the NGS sequencing approach in order to obtain the full genome + . Genome characterization and phylogenetic analysis were conducted.ResultsThe prevalence of HPgV was 12.42%. We observed the highest prevalences among donors aged between 18 to 30 years old (16.5%), with brown skin color (13.2%) and men (15.8%). The newly diagnosed HIV-1 prevalence was 26.67%. The genotype 2 (2A and 2B) was identified. No data on viral load value was found to corroborate the protective effect of HPgV on HIV evolution.ConclusionsThis study provided information regarding the HPgV infection among blood donors from HEMOPA Foundation. Furthermore, we genetically characterized the HPgV circulating strains and described by the first time the genotype 2 genomes in the Brazilian Amazon region.

GB virus C

10.21203/rs.3.rs-21410/v1

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Citations (1)

Expression of hsa-miR-9 and MYC Copy Number Variation in Hereditary Diffuse Gastric Cancer

Anticancer Research (2017)

Kelly Cristina da Silva Oliveira Amanda Braga Bona FERNANDA JARDIM DA SILVA Thayanne Macedo Pinheiro Diego Di Felipe Ávila Alcântara

Approximately, 15-50% of families affected by hereditary diffuse gastric cancer (HDGC) exhibit CDH1 germline mutations. CDH1 gene encodes E-cadherin, protein essential to the cell-cell contact of gastric epithelium. Studies have shown that hsa-miR-9 participates in this protein downregulation. Moreover, MYC is responsible for the transcription of hsa-miR-9-3. In the present study, hsa-miR-9 expression and MYC copy number variation were investigated to elucidate the hsa-miR-9 role in HDGC.Tumor samples were obtained from nine individuals with HDGC history belonging to four Brazilian families. Then, relative quantification of hsa-miR-9 expression and MYC gene copy number variation analysis were performed by real-time PCR.In all the samples, an overexpression of hsa-miR-9 and an increased MYC copy number (≥3 copies) were observed.hsa-miR-9 acts as an oncomiR in HDGC. In addition, we suggest that hsa-miR-9 acts as second event in individuals with HDGC carrying CDH1 gene germinline mutations.

CDH1

10.21873/anticanres.11579

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Citations (5)

Prevalence and clinical features of respiratory syncytial virus in children hospitalized for community-acquired pneumonia in northern Brazil

BMC Infectious Diseases (2012)

Letícia Martins Lamarão Francisco Lúzio de Paula Ramos Wyller Alencar de Mello Mirleide Cordeiro dos Santos Luana Soares Barbagelata

Abstract Background Childhood pneumonia and bronchiolitis is a leading cause of illness and death in young children worldwide with Respiratory Syncytial Virus (RSV) as the main viral cause. RSV has been associated with annual respiratory disease outbreaks and bacterial co-infection has also been reported. This study is the first RSV epidemiological study in young children hospitalized with community-acquired pneumonia (CAP) in Belém city, Pará (Northern Brazil). Methods With the objective of determining the prevalence of RSV infection and evaluating the patients’ clinical and epidemiological features, we conducted a prospective study across eight hospitals from November 2006 to October 2007. In this study, 1,050 nasopharyngeal aspirate samples were obtained from hospitalized children up to the age of three years with CAP, and tested for RSV antigen by direct immunofluorescence assay and by Reverse Transcription Polymerase Chain Reaction (RT-PCR) for RSV Group identification. Results RSV infection was detected in 243 (23.1%) children. The mean age of the RSV-positive group was lower than the RSV-negative group (12.1 months vs 15.5 months, p <0.001) whereas gender distribution was similar. The RSV-positive group showed lower means of C-reactive protein (CRP) in comparison to the RSV-negative group (15.3 vs 24.0 mg/dL, p <0.05). Radiological findings showed that 54.2% of RSV-positive group and 50.3% of RSV-negative group had interstitial infiltrate. Bacterial infection was identified predominantly in the RSV-positive group (10% vs 4.5%, p<0.05). Rhinorrhea and nasal obstruction were predominantly observed in the RSV-positive group. A co-circulation of RSV Groups A and B was identified, with a predominance of Group B (209/227). Multivariate analysis revealed that age under 1 year ( p <0.015), CRP levels under 48 mg/dL ( p <0.001) and bacterial co-infection ( p <0.032) were independently associated with the presence of RSV and, in the analyze of symptoms, nasal obstruction were independently associated with RSV-positive group ( p <0.001). Conclusion The present study highlights the relevance of RSV infection in hospitalized cases of CAP in our region; our findings warrant the conduct of further investigations which can help design strategies for controlling the disease.

Medical microbiology

10.1186/1471-2334-12-119

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Citations (49)

First isolation of enterovirus 71 (EV-71) from Northern Brazil

The Brazilian Journal of Infectious Diseases (2003)

Letícia Martins Lamarão Ana Maria T. R. Maciel Maria de Lourdes Contente Gomes

Enterovirus 71 (EV-71) has been associated to cases of neurological disease in many countries including Brazil. This virus has now been reported from three of the five Brazilian regions. Our study relates the findings concerning to the first isolate of this virus in Northern region of Brazil. A 15-month old female patient, from the rural zone of the municipality of Santana do Araguaia in southern Pará state was admitted at the hospital with acute, flaccid, asymmetric and ascending motor deficiency, located in the right lower limb. Stools samples from this child were inoculated in RD cells and was isolated an EV-71. We plan to sequence our strain and compare it to other isolates in Brazil. Differences at the molecular level can explain why EV-71 strains circulating in other continents, such as Asia, appear to be more virulent.

Enterovirus 71

Acute flaccid paralysis

Strain (injury)

Isolation

10.1590/s1413-86702003000400009

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Citations (3)