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Insights into gastric neuroendocrine tumors burden

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Chinese Journal of Cancer Research 2017年第2期29卷 137-143页

作者： Taíssa Maíra Thomaz Araújo Williams Fernandes Barra André Salim Khayat paulo pimentel de assumpcao Oncology Research Center Federal University of paráPara 66073-005Brazil

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.

关键词： gNETs gastrin receptor epidemiology

Metastasis-associated lung adenocarcinoma transcript 1 molecular mechanisms in gastric cancer progression

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World Journal of Gastrointestinal Oncology 2023年第9期15卷 1520-1530页

作者： Daniel Mateus de Oliveira Batista Jessica Manoelli Costa da Silva Carolina de Oliveira Gigek Marilia de Arruda Cardoso Smith paulo pimentel de assumpcao Danielle Queiroz Calcagno Nucleo de Pesquisas em Oncologia Universidade Federal do ParaBelem 66073-000ParaBrazil departamento de Patologia Universidade Federal de São PauloSao Paulo 04023-062São PauloBrazil Disciplina de Genetica Departamento de Morfologia e GeneticaUniversidade Federal de São PauloSão Paulo 04023-900Sao PauloBrazil

Gastric cancer(GC)remains among the most common cancers worldwide with a high mortality-to-incidence *** evidence suggests that long noncoding RNAs(lncRNAs)are involved in gastric *** transcripts are longer than 200 nucleotides and modulate gene expression at multiple molecular levels,inducing or inhibiting biological processes and ***-associated lung adenocarcinoma transcript 1(MALAT1)is one of the best-studied lncRNAs with comprehensive actions contributing to cancer *** lncRNA regulates gene expression at the transcriptional and posttranscriptional levels through interactions with microRNAs and *** the present review,we discussed the molecular mechanism of MALAT1 and summarized the current knowledge of its expression in ***,we highlighted the potential use of MALAT1 as a biomarker,including liquid biopsy.

关键词： Long noncoding RNA Gastric carcinogenesis Transcriptional levels Posttranscriptional levels Prognostic biomarker Liquid biopsy

Traps and trumps from adjacent-to-tumor samples in gastric cancer research

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Chinese Journal of Cancer Research 2018年第5期30卷 564-567页

作者： paulo pimentel de assumpcao Andre Salim Khayat Taissa Maira Thomaz Araujo Williams Fernandes Barra Geraldo Ishak Mine Maria Pereira Cruz Ramos Sidney Emanuel Batista dos Santos Andrea Kely Campos Ribeiro dos Santos Samia demachki Paula Barauna de assumpcao Danielle Queiroz Calcagno Ney Pereira Carneiro dos Santos Monica Barauna de assumpcao Fabiano Cordeiro Moreira Andre Mauricio Ribeiro dos Santos Carolina Barauna de assumpcao Gregory Joseph Riggins Rommel Mario Rodriguez Burbano Oncology Research Center Federal University of Para Belem 66075-110 Brazil PhD Program in Genetics and Molecular Biology Federal University of Para Belem 66075-110 Brazil Gastrointestinal Endoscopy Service Joao de Barros Barreto University Hospital Belem 66073-000 Brazil department of Surgical Oncology Oswaldo Cruz Germany Hospital Sao Paulo 01327-001 Brazil department of Neurosurgery Johns Hopkins University Baltimore 21287 USA Laboratory of Molecular Biology Ophir Loyola Hospital Belem 66060-281 Brazil

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.

关键词： Adjacent-to-tumor trumps traps

Presence of c.3956del C mutation in familial adenomatous polyposis patients from Brazil

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World Journal of Gastroenterology 2015年第31期21卷 9413-9419页

作者： Caroline Aquino Moreira-Nunes Diego di Felipe ávila Alcantara Sérgio Figueiredo Lima-Júnior Sandro Roberto de Araújo Cavalléro Juan Antonio Rey Giovanny Reboucas Pinto paulo pimentel de assumpcao Rommel Rodriguez Burbano Biological Science Institute Federal University of Pará Nucleus of Research in Oncology Federal University of Pará Molecular Neuro-oncogenetics Laboratory Research Unit-Unidad de InvestigaciónHospital Universitario La Paz Genetics and Molecular Biology Laboratory Federal University of Piaui

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

关键词： Familial adenomatous polyposis APC Torrent sequencing Colorectal cancer

Role of mi RNAs and their potential to be useful as diagnostic and prognostic biomarkers in gastric cancer

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World Journal of Gastroenterology 2016年第35期22卷 7951-7962页

作者： Kelly Cristina da Silva Oliveira Taíssa Maíra Thomaz Araújo Camila Inagaki Albuquerque Gabriela Alcantara Barata Carolina Oliveira Gigek Mariana Ferreira Leal Fernanda Wisnieski Fernando Augusto Rodrigues Mello Junior André Salim Khayat paulo pimentel de assumpcao Rommel Mário Rodriguez Burbano Marília Cardoso Smith Danielle Queiroz Calcagno Núcleo de Pesquisas em Oncologia Universidade Federal do Pará Hospital Universitário Joao de Barros Barreto Disciplina de Genética Departamento de Morfologia e Genética Universidade Federal de Sao Paulo Laboratório de Citogenética Humana Instituto de Ciências Biológicas Universidade Federal do Pará

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.

关键词： Gastric cancer Epigenetic Diagnostic biomarkers miRNAs Prognostic biomarkers

Hereditary gastric cancer:Three rules to reduce missed diagnoses

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World Journal of Gastroenterology 2020年第13期26卷 1382-1393页

作者： Paula assumpcao Taíssa Araújo André Khayat Geraldo Ishak Sidney Santos Williams Barra Joao Felipe Acioli Benedito Rossi paulo assumpcao Programa de Pós-Graduacao em Genética e Biologia Molecular Universidade Federal do ParáBelém 66075-110Brazil Núcleo de Pesquisas em Oncologia Universidade Federal do ParáBelém 66073-000Brazil Hospital Universitário Joao de Barros Barreto Universidade Federal do ParáBelém 66073-000Brazil Centro de Oncologia e Aconselhamento Genético Hospital Sírio LibanêsSao Paulo 01308-050Brazil

Gastric cancer remains one of the most lethal *** incidence and mortality rates are quite *** main reason for the high mortality is diagnosis at advanced stages of disease,when treatment options are *** of the supposed strategies to overcome late-stage diagnosis is identifying people at high risk with the aim of establishing rigorous clinical control,including routine endoscopy and *** gastric cancer(HGC)syndromes,though representing a sizeable group to monitor for prevention or,at least,for early diagnosis,are apparently extremely *** low rate of HGC diagnosis might be related to the low rates of suspicion,insufficient familiarity about clinical diagnosis criteria,and the supposed conditional necessity of a molecular *** this review,we will discuss simple measures to increase HGC diagnosis by applying three rules that might provide an opportunity for precision care to benefit the families affected by this disease.

关键词： Hereditary gastric cancer Rules Diagnosis

Identification of IL11RA and MELK amplification in gastric cancer by comprehensive genomic profiling of gastric cancer cell lines

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World Journal of Gastroenterology 2016年第43期22卷 9506-9514页

作者： Danielle Queiroz Calcagno Sylvia Santomi Takeno Carolina Oliveira Gigek Mariana Ferreira Leal Fernanda Wisnieski Elizabeth Suchi Chen Taíssa Maíra Thomaz Araújo Eleonidas Moura Lima Maria Isabel Melaragno Samia demachki paulo pimentel assumpcao Rommel Rodriguez Burbano Marília Cardoso Smith Disciplina de Genética Departamento de Morfologia e GenéticaUniversidade Federal de Sao Paulo Núcleo de Pesquisas em Oncologia Hospital Universitário Joao de Barros Barreto departamento de Biologia Molecular Universidade Federal da Paraíba Disciplina de Gastroenterologia Cirúrgica Universidade Federal de Sao Paulo departamento de Ortopedia e Traumatologia Universidade Federal de Sao Paulo

AIM To identify common copy number alterations on gastric cancer cell *** Four gastric cancer cell lines(ACP02, ACP03, AGP01 and PG100) underwent chromosomal comparative genome hybridization and array comparative genome hybridization. We also confirmed the results by fluorescence in situ hybridization analysis using the bacterial artificial chromosome clone and quantitative real time PCR *** The amplification of 9p13.3 was detected in all cell lines by both methodologies. An increase in the copy number of 9p13.3 was also confirmed by fluorescence in situ hybridization analysis. Moreover, the interleukin 11 receptor alpha(IL11RA) and maternal embryonic leucine zipper kinase(MELK) genes, which are present in the 9p13.3 amplicon, revealed gains of the MELK gene in all the cell lines studied. Additionally, a gain in the copy number of IL11 RA and MELK was observed in 19.1%(13/68) and 55.9%(38/68) of primary gastric adenocarcinoma samples, respectively. CONCLUSION The characterization of a small gain region at 9p13.3 in gastric cancer cell lines and primary gastric adenocarcinoma samples has revealed MELK as a candidate target gene that is possibly related to the development of gastric cancer.

关键词： IL11RA Gastric cancer Genomic profiling MELK 9p13.3

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巴西构造应力场的遗传有限单元法反演

地球物理学报 2000年第2期43卷 166-174页

作者：石耀霖 Marcelo assumpcao 中国科学技术大学研究生院北京100039 Institute of Astronomy and Geophysics University of Sao Paulobrazil01065

基于观测的主应力方位资料，应用遗传有限单元法对巴西及邻区边界位移和板内力源进行了反演，确认了前人的研究结果：板块边界作用是控制区域应力场的主要因素，山脉和海岸地形造成的扩展力是控制应力场的一个重要因素．同时显示了板块... 详细信息

基于观测的主应力方位资料，应用遗传有限单元法对巴西及邻区边界位移和板内力源进行了反演，确认了前人的研究结果：板块边界作用是控制区域应力场的主要因素，山脉和海岸地形造成的扩展力是控制应力场的一个重要因素．同时显示了板块在垂直载荷下的弯曲对局部水平应力场造成相当的影响．反演结果也表明，除了过去公认的东西向挤压作用外，巴西还受到相当明显的南北向构造作用．它的存在与最近ＧＰＳ资料的分析是一致的．研究还表明遗传有限单元法是偏微分方程反演问题求解的一种有效方法．

关键词：构造应力场地球物理反演问题巴西遗传有限元

Interrelationship between chromosome 8 aneuploidy,C-MYC amplification and increased expression in individuals from northern Brazil with gastric adenocarcinoma

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World Journal of Gastroenterology 2006年第38期12卷 6207-6211页

作者： Danielle Queiroz Calcagno Mariana Ferreira Leal Aline Damaceno Seabra Andre Salim Khayat Elizabeth Suchi Chen Samia demachki paulo pimentel assumpcao Mario Henrique Girao Faria Silvia Helena Barem Rabenhorst Márcia Valéria Pitombeira Ferreira Marília de Arruda Cardoso Smith Rommel Rodríguez Burbano Human Cytogenetics and Toxicological Genetics Laboratory Department of BiologyCenter of Biological SciencesFederal University of ParáBelémPABrazil Genetics Division department of Morphology Federal University of Sao PauloSao PauloSPBrazil department of Pathology and Surgery Service Federal University of ParáBelémPABrazil Joao de Barros Barreto University Hospital Federal University of ParáBelémPABrazil Molecular Genetics Laboratory department of Pathology Medical SchoolFederal University of CearáFortalezaCEBrazil

AIM: To investigate chromosome 8 numerical aberra- tions, C-MYC oncogene alterations and its expression in gastric cancer and to correlate these findings with histo- pathological characteristics of gastric tumors. METHODS: Specimens were collected surgically from seven patients with gastric adenocarcinomas. Immu- nostaining for C-MYC and dual-color fluorescence in situ hybridization (FISH) for C-MYC gene and chromosome 8 centromere were performed. RESULTS: All the cases showed chromosome 8 aneu- ploidy and C-MYC amplification, in both the diffuse and intestinal histopathological types of Lauren. No significant difference (P denocarcinomas. C-MYC high amplification, like homogeneously stained regions (HSRs) and double minutes (DMs), was observed only in the intestinal-type. Structural rearrangement of C-MYC, like translocation, was observed only in the diffuse type. Regarding C-MYC gene, a significant difference (P < 0.05) was observed between the two histological types. The C-MYC protein was expressed in all the studied cases. In the intestinal- type the C-MYC immunoreactivity was localized only in the nucleus and in the diffuse type in the nucleus and cytoplasm. CONCLUSION: Distinct patterns of alterations between intestinal and diffuse types of gastric tumors support the hypothesis that these types follow different genetic path- ways.

关键词： Chromosome 8 aneuploidy C-MYC amplification Immunostaining Gastric adenocarcinoma