Gastric cancer(GC)remains among the most common cancers worldwide with a high mortality-to-incidence ratio.Accumulated evidence suggests that long noncoding RNAs(lncRNAs)are involved in gastric carcinogenesis.These tr...Gastric cancer(GC)remains among the most common cancers worldwide with a high mortality-to-incidence ratio.Accumulated evidence suggests that long noncoding RNAs(lncRNAs)are involved in gastric carcinogenesis.These transcripts are longer than 200 nucleotides and modulate gene expression at multiple molecular levels,inducing or inhibiting biological processes and diseases.Metastasis-associated lung adenocarcinoma transcript 1(MALAT1)is one of the best-studied lncRNAs with comprehensive actions contributing to cancer progression.This lncRNA regulates gene expression at the transcriptional and posttranscriptional levels through interactions with microRNAs and proteins.In the present review,we discussed the molecular mechanism of MALAT1 and summarized the current knowledge of its expression in GC.Moreover,we highlighted the potential use of MALAT1 as a biomarker,including liquid biopsy.展开更多
Type 1 gastric neuroendocrine tumors (gNETs) are usually small lesions, restricted to mucosal and sub-mucosal layers of corpus and fundus, with low aggressive behavior, for the majority of cases. Nevertheless, some ...Type 1 gastric neuroendocrine tumors (gNETs) are usually small lesions, restricted to mucosal and sub-mucosal layers of corpus and fundus, with low aggressive behavior, for the majority of cases. Nevertheless, some cases present aggressive behavior. The increasing incidence of gNETs brings together a new relevant problem: how to identify potentially aggressive type I gNETs. The challenging problem seems to be finding out signs or features able to predict potentially aggressive cases, allowing a tailored approach, since the involved societies dedicated to provide guidelines for management of these neoplasms apparently failed in producing staging systems able to accurately predict prognosis of these tumors. Additionally, it is also important to try to find out explanations for increasing incidence, as well as to identify potential targets aiming to reach better control of this neoplasia. Here, we discuss potential pathways implicated in aggressive behavior, as well as new strategies to improve clinical management of these tumors.展开更多
AIM: To characterize APC gene mutations and correlate them with patient phenotypes in individuals diagnosed with familial adenomatous polyposis(FAP) in northern Brazil. METHODS: A total of 15 individuals diagnosed wit...AIM: To characterize APC gene mutations and correlate them with patient phenotypes in individuals diagnosed with familial adenomatous polyposis(FAP) in northern Brazil. METHODS: A total of 15 individuals diagnosed with FAP from 5 different families from the north of Brazil were analyzed in this study. In addition to patients with histopathological diagnosis of FAP,family members who had not developed the disease were also tested in order to identify mutations and for possible genetic counseling. All analyzed patients or their guardians signed a consent form approved by the Research Ethics Committee of the Jo?o de Barros Barreto University Hospital(Belem,Brazil). DNA extracted from the peripheral blood of a member of each of the affected families was subjected to direct sequencing. The proband of each family was sequenced to identify germline mutations using the Ion Torrent platform. To validate the detected mutations,Sanger sequencing was also performed. The samples from all patients were also tested for the identification of mutations by real-time quantitative polymerase chain reaction using the amplification refractory mutation system. RESULTS: Through interviews with relatives and a search of medical records,it was possible to construct genograms for three of the five families included in the study. All 15 patients from the five families with FAP exhibited mutations in the APC gene,and all mutations were detected in exon 15 of the APC gene. In addition to the patients with a histological diagnosis of FAP,family members without disease symptoms showed the mutation in the APC gene. In the present study,we detected two of the three most frequent germline mutations in the literature: the mutation at codon 1309 and the mutation at codon 1061. The presence of c.3956 del C mutation was found in all families from this study,and suggests that this mutation was introduced in the population of the State of Pará through ancestor immigration(i.e.,a de novo mutation that arose in one member belonging to this state from Brazil). CONCLUSION: Regardless of its origin,the c.3956 del C mutation is a strong candidate biomarker of this hereditary cancer syndrome in families of northern Brazil.展开更多
Alterations in epigenetic control of gene expression play an important role in many diseases, including gastric cancer. Many studies have identified a large number of upregulated oncogenic mi RNAs and downregulated tu...Alterations in epigenetic control of gene expression play an important role in many diseases, including gastric cancer. Many studies have identified a large number of upregulated oncogenic mi RNAs and downregulated tumour-suppressor mi RNAs in this type of cancer. In this review, we provide an overview of the role of mi RNAs, pointing to their potential to be useful as diagnostic and/or prognostic biomarkers in gastric cancer. Moreover, we discuss the influence of polymorphisms and epigenetic modifications on mi RNA activity.展开更多
Gastric adenocarcinoma(GC)is one of the most heterogeneous cancers,posing challenges to wide applications of the discoveries when compared to other cancers.Nevertheless,the benefits of research in the fight against GC...Gastric adenocarcinoma(GC)is one of the most heterogeneous cancers,posing challenges to wide applications of the discoveries when compared to other cancers.Nevertheless,the benefits of research in the fight against GC are extraordinary,and even taking in mind the immense complexity of this disease,optimism is a great message to take home.Recent advances in GC research will pave the way for GC effective control,helping to save lives,together with permitting sustainable real-life support for those needing complex and high-expense interventions.展开更多
The search for cancer biomarkers is frequently based on comparisons between tumors and adjacent-to-tumor samples. However, even after histological confirmation of been free of cancer cells, these adjacent-to-tumor sam...The search for cancer biomarkers is frequently based on comparisons between tumors and adjacent-to-tumor samples. However, even after histological confirmation of been free of cancer cells, these adjacent-to-tumor samples might harbor molecular alterations which are not sufficient to cause them to look like cancer, but can differentiate these cells from normal cells. When comparing them, potential biomarkers are missed, and mainly the opportunity of finding initial aberrations presents in both tumors and adjacent samples, but not in true normal samples from non-cancer patients, resulting in misinterpretations about the carcinogenic process. Nevertheless, collecting adjacent-to-tumor samples brings trumps to be explored. The addition of samples from non-cancer patients opens an opportunity to increase the finds of the molecular cascade of events in the carcinogenic process. Differences between normal samples and adjacent samples might represent the first steps of the carcinogenic process. Adding samples of non-cancer patients to the analysis of molecular alterations relevant to the carcinogenic process opens a new window of opporttmides to the discovery of cancer biomarkers and molecular targets.展开更多
文摘Gastric cancer(GC)remains among the most common cancers worldwide with a high mortality-to-incidence ratio.Accumulated evidence suggests that long noncoding RNAs(lncRNAs)are involved in gastric carcinogenesis.These transcripts are longer than 200 nucleotides and modulate gene expression at multiple molecular levels,inducing or inhibiting biological processes and diseases.Metastasis-associated lung adenocarcinoma transcript 1(MALAT1)is one of the best-studied lncRNAs with comprehensive actions contributing to cancer progression.This lncRNA regulates gene expression at the transcriptional and posttranscriptional levels through interactions with microRNAs and proteins.In the present review,we discussed the molecular mechanism of MALAT1 and summarized the current knowledge of its expression in GC.Moreover,we highlighted the potential use of MALAT1 as a biomarker,including liquid biopsy.
文摘Type 1 gastric neuroendocrine tumors (gNETs) are usually small lesions, restricted to mucosal and sub-mucosal layers of corpus and fundus, with low aggressive behavior, for the majority of cases. Nevertheless, some cases present aggressive behavior. The increasing incidence of gNETs brings together a new relevant problem: how to identify potentially aggressive type I gNETs. The challenging problem seems to be finding out signs or features able to predict potentially aggressive cases, allowing a tailored approach, since the involved societies dedicated to provide guidelines for management of these neoplasms apparently failed in producing staging systems able to accurately predict prognosis of these tumors. Additionally, it is also important to try to find out explanations for increasing incidence, as well as to identify potential targets aiming to reach better control of this neoplasia. Here, we discuss potential pathways implicated in aggressive behavior, as well as new strategies to improve clinical management of these tumors.
基金Supported by Grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico(www.cnpq.br),No.401976/2010-6 and No.305220/2013-6(to Burbano RR)Coordenacao de Aperfeicoamento de Pessoal de Nível Superior(www.capes.gov.br),No.PNPD 2810/2011(to Moreira-Nunes CA)
文摘AIM: To characterize APC gene mutations and correlate them with patient phenotypes in individuals diagnosed with familial adenomatous polyposis(FAP) in northern Brazil. METHODS: A total of 15 individuals diagnosed with FAP from 5 different families from the north of Brazil were analyzed in this study. In addition to patients with histopathological diagnosis of FAP,family members who had not developed the disease were also tested in order to identify mutations and for possible genetic counseling. All analyzed patients or their guardians signed a consent form approved by the Research Ethics Committee of the Jo?o de Barros Barreto University Hospital(Belem,Brazil). DNA extracted from the peripheral blood of a member of each of the affected families was subjected to direct sequencing. The proband of each family was sequenced to identify germline mutations using the Ion Torrent platform. To validate the detected mutations,Sanger sequencing was also performed. The samples from all patients were also tested for the identification of mutations by real-time quantitative polymerase chain reaction using the amplification refractory mutation system. RESULTS: Through interviews with relatives and a search of medical records,it was possible to construct genograms for three of the five families included in the study. All 15 patients from the five families with FAP exhibited mutations in the APC gene,and all mutations were detected in exon 15 of the APC gene. In addition to the patients with a histological diagnosis of FAP,family members without disease symptoms showed the mutation in the APC gene. In the present study,we detected two of the three most frequent germline mutations in the literature: the mutation at codon 1309 and the mutation at codon 1061. The presence of c.3956 del C mutation was found in all families from this study,and suggests that this mutation was introduced in the population of the State of Pará through ancestor immigration(i.e.,a de novo mutation that arose in one member belonging to this state from Brazil). CONCLUSION: Regardless of its origin,the c.3956 del C mutation is a strong candidate biomarker of this hereditary cancer syndrome in families of northern Brazil.
基金Supported by Fundacao de Amparoà Pesquisa do Estado de Sao Paulothe Conselho Nacional de Desenvolvimento Científico e Tecnológicoand the Coordenacao de Aperfei?ooamento de Pessoal de Nível Superior
文摘Alterations in epigenetic control of gene expression play an important role in many diseases, including gastric cancer. Many studies have identified a large number of upregulated oncogenic mi RNAs and downregulated tumour-suppressor mi RNAs in this type of cancer. In this review, we provide an overview of the role of mi RNAs, pointing to their potential to be useful as diagnostic and/or prognostic biomarkers in gastric cancer. Moreover, we discuss the influence of polymorphisms and epigenetic modifications on mi RNA activity.
文摘Gastric adenocarcinoma(GC)is one of the most heterogeneous cancers,posing challenges to wide applications of the discoveries when compared to other cancers.Nevertheless,the benefits of research in the fight against GC are extraordinary,and even taking in mind the immense complexity of this disease,optimism is a great message to take home.Recent advances in GC research will pave the way for GC effective control,helping to save lives,together with permitting sustainable real-life support for those needing complex and high-expense interventions.
基金National Counsel of Technological and Scientific Development and Coordination for Enhancement of Higher Education Personnel for fellowship support
文摘The search for cancer biomarkers is frequently based on comparisons between tumors and adjacent-to-tumor samples. However, even after histological confirmation of been free of cancer cells, these adjacent-to-tumor samples might harbor molecular alterations which are not sufficient to cause them to look like cancer, but can differentiate these cells from normal cells. When comparing them, potential biomarkers are missed, and mainly the opportunity of finding initial aberrations presents in both tumors and adjacent samples, but not in true normal samples from non-cancer patients, resulting in misinterpretations about the carcinogenic process. Nevertheless, collecting adjacent-to-tumor samples brings trumps to be explored. The addition of samples from non-cancer patients opens an opportunity to increase the finds of the molecular cascade of events in the carcinogenic process. Differences between normal samples and adjacent samples might represent the first steps of the carcinogenic process. Adding samples of non-cancer patients to the analysis of molecular alterations relevant to the carcinogenic process opens a new window of opporttmides to the discovery of cancer biomarkers and molecular targets.