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Epidemiology and Clinical Features of Mycobacterium avium Complex Pulmonary Disease in a Brazilian Amazon Cohort

Advances in Microbiology 2024年第6期14卷 287-302页

作者： Jose Tadeu Colares Monteiro Adriana Rodrigues Barretto Ruan Seguin Azevedo Quaresma Bianca Miranda Gouveia Ismari Perini Furlaneto Victória Menezes da Costa Yan Corrêa Rodrigues Layana Rufino Ribeiro Ricardo J. de Paula Souza e Guimarães Alex Brito Souza Ana Roberta Fusco da Costa Karla Valéria Batista Lima joao de barros barreto university hospital Federal University of Par Belm Brazil Center for Biological and Health Sciences Ph.D. Program in Parasitic Biology in the Amazon Region (PPGBPA) State University of Par (UEPA) Belm Brazil department of Medicine Centro Universitrio do Par CESUPA Belm Brazil Bacteriology and Mycology Section Evandro Chagas Institute (SABMI/IEC) Ministry of Health Ananindeua Brazil Geoprocessing Laboratory Evandro Chagas Institute/SVSA/MS Ananineua Brazil

The incidence of Mycobacterium avium complex pulmonary disease (MACPD) has been globally increasing. The present study aims to provide a comprehensive analysis of clinical characteristics and treatment response among patients in the Amazon region of Brazil and conduct a retrospective cohort study at a prominent referral hospital in the State of Par, Brazil, from 2012 to 2020. The M. avium group represented 58.9% of cases, followed by M. intracellulare (35.7%), M. colombiense (3.6%), and M. chimaera (1.8%). The majority of patients (73.2%) were female and with an average age of 63 years. Primary clinical manifestations included persistent cough and sputum production. The Charlson comorbidity index (CCI) averaged 2.47, with 36.3% of patients having a CCI score equal to higher than 3. Notably, over 70% of patients had received treatment for pulmonary tuberculosis before initiating treatment for MAC infection. The fibrocavitary radiologic form was the most prevalent (55.4%), frequently exhibiting a bilateral distribution (53.6%). Antimicrobial susceptibility revealed a significant prevalence of MAC resistance to drugs in the therapeutic regimen. despite this, most of the patients experienced clinical improvement (50%). In conclusion, this study highlights a higher prevalence of MAC infections among middle-aged women, with a history of pulmonary tuberculosis treatment and presenting the fibrocavitary radiological form was predominant.

关键词： MACDP Nontuberculous Mycobacteria Mycobacterium avium Lung Disease

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Helicobacter pylori in dental plaque and stomach of patients from Northern Brazil

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World Journal of Gastroenterology 2010年第24期16卷 3033-3039页

作者： Mnica Baraúna Assumpo Luisa Caricio Martins Hivana Patricia Melo Barbosa Katarine Antonia dos Santos Barile Sintia Silva de Almeida Paulo Pimentel Assumpo Tereza Cristina de Oliveira Corvelo Endoscopy department Joo de Barros Barreto University Hospital Immunopathology Laboratory Nucleus of Tropical Medicine Federal University of Pará Immunogenetics Laboratory Federal University of Pará Paulo Pimentel Assumpo Surgery Department Joo de Bar-ros Barreto University Hospital

AIM: To establish whether virulence factor genes vacA and cagA are present in Helicobacter pylori (H. pylori) retrieved from gastric mucosa and dental plaque in pa-tients with dyspepsia. METHODS: Cumulative dental plaque specimens and gastric biopsies were submitted to histological exami-nation, rapid urease test and polymerase chain reac-tion (PCR) assays to detect the presence of cagA and vacA polymorphisms.RESULTS: detection of H. pylori from dental plaque and gastric biopsy samples was greater by PCR com-pared to histological examination and the rapid ure-ase test. DNA from H. pylori was detected in 96% of gastric mucosa samples and in 72% of dental plaque samples. Sixty-three (89%) of 71 dental plaque sam-ples that were H. pylori-positive also exhibited identical vacA and cagA genotypes in gastric mucosa. The most common genotype was vacAs1bm1 and cagA positive, either in dental plaque or gastric mucosa. These viru-lent H. pylori isolates were involved in the severity of clinical outcome.CONCLUSION: These pathogenic strains were found simultaneously in dental plaque and gastric mucosa, which suggests that gastric infection is correlated with the presence of H. pylori in the mouth.

关键词： Helicobacter pylori Gastric mucosa dental plaque cagA vacA

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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 lines.METHODS 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 analysis.RESULTS 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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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 cancers.The incidence and mortality rates are quite similar.The main reason for the high mortality is diagnosis at advanced stages of disease,when treatment options are poor.One 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 biopsies.Hereditary gastric cancer(HGC)syndromes,though representing a sizeable group to monitor for prevention or,at least,for early diagnosis,are apparently extremely rare.The 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 diagnosis.In 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

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Interleukin-1 and TNF-α polymorphisms and Helicobacter pylori in a Brazilian Amazon population

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World Journal of Gastroenterology 2009年第12期15卷 1465-1471页

作者： Hivana Patricia Melo Barbosa Luisa Caricio Martins Sidney Emanuel Batista dos Santos Samia demachki Mnica Baraúna Assumpo Charliana Damasceno Arago Tereza Cristina de Oliveira Corvelo Laboratory of Immunogenetics Federal University of Pará66075-110BelémBrazil Nucleus of Tropical Medicine Federal University of Pará66055-240BelémBrazil Laboratory of Human and Medical Genetics Federal University of Pará66075-110BelémBrazil department of Pathology Joo de Barros Barreto Universitary HospitalFederal University of Pará66073-000BelémBrazil department of Endoscopy Joo de Barros Barreto Universitary HospitalFederal University of Pará66073-000BelémBrazil

AIM:To study the association between Interleukin-1(IL-1)and tumor necrosis factor(TNF)-αpolymorphisms,infection by Helicobacter pylori(H pylori)and the development of gastrointestinal diseases.METHODS:Genomic DNA was extracted from the peripheral blood of 177 patients with various gastrointestinal diseases and from 100 healthy volunteers.The polymorphisms in IL-1βand TNF-αgenes were analyzed using the polymerase chain reactionrestriction fragment length polymorphism method(PCRRFLP)and those from IL-1RN with PCR.The presence of infection due to H pylori and the presence of the CagA toxin were detected by serology.The histopathological parameters in the gastric biopsies of the patients were according to the Sydney classification.RESULTS:A comparison of the frequencies of the different polymorphisms studied among the patients and the control group demonstrated that the allele IL1RN*2 was more frequent among patients with gastric ulcers and adenocarcinoma.Carriers of the allele ILRN*2 and those with reactive serology for anti-CagA IgG had a greater risk of developing peptic ulcer and gastric adenocarcinoma,as well as a higher degree of inflammation and neutrophilic activity in the gastric mucosa.CONCLUSION:Our results indicate a positive association between IL-1RN gene polymorphism and infection by positive H pylori CagA strains and the development of gastric ulcers and adenocarcinoma.

关键词：白细胞介素1 多态性分析法肿瘤坏死因子幽门螺杆菌 PCRRFLP 幽门螺旋杆菌组织病理学参数 RN基因多态性

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Clinical implication of 14-3-3 epsilon expression in gastric cancer

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World Journal of Gastroenterology 2012年第13期18卷 1531-1537页

作者： Mariana Ferreira Leal Danielle Queiroz Calcagno Smia demachki Paulo Pimentel Assumpo Roger Chammas Rommel Rodríguez Burbano Marília de Arruda Cardoso Smith Genetics Division Department of Morphology and GeneticFederal University of So PauloSo Paulo 04023-900Brazil Pathology Service Joo de Barros Barreto University HospitalFederal University of ParáBelém 60673-000Brazil Surgery Service Joo de Barros Barreto University HospitalFederal University of ParáBelém 60673-000Brazil Laboratory of Experimental Oncology School of MedicineUniversity of So PauloSo Paulo 01246-903Brazil Human Cytogenetics Laboratory Institute of Biological SciencesFederal University of ParáBelém 66073-000Brazil

AIM:To evaluate for the first time the protein and mRNA expression of 14-3-3εin gastric carcinogenesis.METHODS:14-3-3εprotein expression was determined by western blotting,and mRNA expression was examined by real-time quantitative RT-PCR in gastric tumors and their matched non-neoplastic gastric tissue samples.RESULTS:Authors observed a significant reduction of 14-3-3εprotein expression in gastric cancer(GC)samples compared to their matched non-neoplastic tissue.Reduced levels of 14-3-3εwere also associated with diffuse-type GC and early-onset of this pathology.Our data suggest that reduced 14-3-3εmay have a role in gastric carcinogenesis process.CONCLUSION:Our results reveal that the reduced 14-3-3εexpression in GC and investigation of 14-3-3ε interaction partners may help to elucidate the carcino-genesis process.

关键词：胃癌临床意义 14-3-3蛋白 RT-PCR检测 mRNA表达量表肿瘤组织气相色谱仪

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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

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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

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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

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Association between Helicobacterpylori, Epstein-Barr virus, human papillomavirus and gastric adenocarcinomas

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World Journal of Gastroenterology 2018年第43期24卷 4928-4938页

作者： Carolina Rosal Teixeira de Souza Marcelli Carolini Alves Almeida Andre Salim Khayat Emerson Lucena da Silva Paulo Cardoso Soares Luiz Claudio Chaves Rommel Mario Rodriguez Burbano Laboratory of Human Cytogenetics Institute of Biological Sciences Federal University of Para Belem Para 66075-110 Brazil Oncology Research Center Federal University of Para Joao deBarros Barreto University Hospital Belem Para 66073-000Brazil Ophir Loyola hospital Belem Para 66060-281 Brazil

AIM To correlate Helicobacter pylori(H. pylori), Epstein-Barr virus(EBV) and human papillomavirus(HPV) with gastric cancer(GC) cases in Pará State, Brazil.METHODS Tissue samples were obtained from 302 gastric adenocarcinomas. A rapid urease test was used to detect the presence of H. pylori, and the presence of the cagA gene in the HP-positive samples was confirmed by PCR. An RNA in situ hybridization test designed to complement Eber1 RNA was used to detect the presence of EBV in the samples, and the L1 region of HPV was detected using nested PCR. Positive HPV samples were genotyped and analyzed for E6 and E7 viral gene expression. Infections were also correlated with the clinical and pathological characteristics of the patients.RESULTS The majority of the 302 samples analyzed were obtained from men(65%) aged 55 years or older(67%) and were classified as the intestinal subtype(55%). All three pathogens were found in the samples analyzed in the present study(H. pylori : 87%, EBV: 20%, HPV: 3%). Overall, 78% of the H. pylori-positive(H. pylori+) samples were cag A +(H. pylori-cag A+), and there was an association between the cytotoxic product of this gene and EBV. Coinfections of H. pylori-cagA+ and EBV were correlated with the most advanced tumor stages. Although only 20% of the tumors were positive for EBV, infection with this virus was associated with distant metastasis. Only the HPV 16 and 18 strains were found in the samples, although no expression of the E6 and E7 oncoproteins was detected. The fundus of the stomach was the region least affected by the pathogens.CONCLUSION HPV was not involved in gastric tumorigenesis. Prophylactic and therapeutic measures against H. pylori and EBV may prevent the development of GC, especially the more aggressive forms.

关键词：乳头状瘤病毒协会腺癌胃区域检测测试设计 HPV EBV

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